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Limb salvage after failed transmetatarsal amputation despite collateral only flow to the foot

by Jordan James Ernst, DPM, MS, FACPM1*; Dalton Ryba, DPM2

The Foot and Ankle Online Journal 13 (4): 5

Peripheral vascular disease is a common affliction in the diabetic patient, and its presence adds great complexity to limb salvage efforts. While many patients with critical limb ischemia may be relegated to a major amputation, especially in the setting of a failed minor amputation, worthwhile salvage efforts may be possible. We present a case of limb salvage by way of a Chopart’s amputation performed after a failed amputation at the transmetatarsal level. In this patient, pedal circulation was supplied only by collateral vessels, as occlusion affected all 3 major below-knee arteries. To our knowledge, limb salvage has not been previously described in this scenario. Given the favorable outcome presented in this piece, we hope to raise awareness of the potential for salvage in this patient population, and spur continuous research into the complex entity of peripheral vascular disease. Additionally, we present our operative and perioperative pearls as a resource for the limb salvage surgeon.

Keywords: angiosomes, PVD, CLI, revascularization, diabetic

ISSN 1941-6806
doi: 10.3827/faoj.2020.1304.0005

1 – Fellowship-Trained Foot and Ankle Surgeon, Texas Institute of Orthopedic Surgery and Sports Medicine, Grapevine, TX
2 – Foot and Ankle Surgeon, Lone Star Orthopaedic and Spine Specialists
* – Corresponding author: jordanj.ernst88@gmail.com


Limb salvage, the preservation of pedal structures in part or total to form a functional appendage, may be fraught with difficulties. This is particularly true regarding the comorbid diabetic host. Peripheral vascular disease, often a concomitant ailment in this particular patient population, can further complicate salvage efforts, if not render them futile. Revascularization prior to these undertakings is optimal to improve salvage success rates, though end-stage vascular disease may present a scenario where the below-knee vascular tree cannot be improved via open or endovascular methods. In this event, optimizing alternative routes of perfusion is paramount [1].

While vascular supply to the foot in patients with peripheral vascular disease is often characterized by the patency of native in-line vessels to the foot, situations may exist where the foot is supplied solely by collateral circulation. While the latter pattern of circulation may allow the intact pedal tissue to survive, the added circulatory demands of a superimposed ulceration or wound are likely to affect limb loss, as demands of tissue repair outweigh host perfusion. Three vessel occlusion to the lower extremity with recalcitrant ulceration with or without subsequent infection is a well-accepted indication for proximal amputation.

To our knowledge, limb salvage has not been described in a scenario of below-knee 3 vessel occlusion in the face of a non-healing intra-pedal amputation. In this report, we present a case of a limb-sparing Chopart’s amputation in a patient with collateral-only flow to the affected foot who had failed to heal a transmetatarsal amputation (TMA) necessitated by gangrene. Additionally, we present several peri-operative and operative pearls with respect to our soft tissue management that we contend contributed to the success of this endeavor.

Figure 1 Clinical photograph of patient upon initial presentation to the emergency department. Clinical photograph of worsening changes to the affected toe.

Case Study

We present a 74-year-old hispanic female with a past medical history of NIDDM with peripheral neuropathy, hyperlipidemia, hypertension and peripheral arterial disease who presented initially to the emergency department in February of 2017 with concern for worsening left 4th digit necrosis (Figure 1a). The patient admitted a one month history of hyperpigmentation to the respective area with an acute history of darkening to the toe. The patient was also complaining of a recent increase in claudication symptoms and malaise. On clinical exam, the patient had distal tuft necrosis to the left 4th digit extending from the proximal interphalangeal joint distally with associated peri-ulcerative edema and ischemic rubor proximally. The left posterior tibial and dorsalis pedis arteries were non-palpable. She was admitted to the hospital for vascular optimization. Duplex arterial doppler exam revealed occlusion of the right iliac, common femoral, posterior tibial and peroneal arteries, and stenosis of the left superficial femoral artery with peroneal occlusion and significant infrapopliteal disease with an ABI of 0.42. The patient ultimately underwent left superficial femoral artery angioplasty. Recanalization of the left pedal vascular tree was unsuccessful as the procedure revealed single vessel runoff to the anterior ankle via the anterior tibial artery which was then seen to be occluded at that level, leaving collateral only flow to the left foot. The patient was discharged with plans to await tissue demarcation in preparation for outpatient amputation. The patient returned to the emergency department for acute worsening gangrenous change to the affected toe (Figure 1b).

Figure 2 One week status post transmetatarsal amputation. At this point the incision is well coapted.

The patient had no acute signs of infection, however, the tissues appeared non-viable distally. Based on the recent vascular findings the discussion was had with the patient and her family that a proximal amputation may be imminent. Ultimately, the patient underwent a transmetatarsal amputation (Figure 2) despite understanding the multifactorial risk for a more proximal amputation. She was discharged postoperatively following a pathology report negative for osteomyelitis at the proximal metatarsal margins.

At initial follow up, the surgical incision had dehisced with a large area of lateral breakdown despite compliance with non-weight-bearing recommendations. In initial salvage efforts, the patient underwent serial debridements under local blockade as she had ischemic pain to the amputation site.

Figure 3 Wound breakdown to TMA site seen during 1st follow-up visit.

Figure 4 Persistence of lateral wound breakdown despite local wound care with serial debridements and HBO therapy.

Adjunctively we attempted negative pressure therapy as well as hyperbaric oxygen (HBO) treatments. The wound unfortunately persisted with predominantly fibrotic tissue and areas of deep probing to bone. While the wound remained stable and without infection, no improvements were noted in the wound’s size or characteristics (Figure 3). We discussed with the patient and family members at length the likelihood of a proximal amputation. The patient and family wished to avoid proximal amputation if at all possible. Considering her age and comorbid conditions, and likely deconditioning and increased cardiac demand with a proximal amputation, it was surmised that she would not likely obtain a prosthesis. We made no guarantees in success following a limb salvage attempt, but ultimately agreed to proceed with a Chopart’s amputation.

Operative Technique – Chopart’s Amputation

The patient was placed supine on the operative table, and the modified Chopart’s procedure was carried out under local anesthetic with monitored anesthesia care. No tourniquet was used so as not to provoke further damage to the tenuous vasculature, and to fully assess the intra-operative bleeding and viability of the tissues. After removing gross non-viable tissue and necrosis from the prior incision site distally, we began sharply elevating the dorsal flap proximally to the level of the Chopart’s joint as a full-thickness layer to preserve vascularity. To accommodate this, the medial and lateral portions of the incisions were extended proximally to apices just at the level of the Chopart’s joint.

No attempt was made to preserve tendon structures for later transfer. Gentle retraction was used to lift the flap and expose the naviculocuneiform joint. We sharply incised through the dorsal capsule, exposing the distal navicular cartilage. Sharp dissection was then carried laterally to disarticulate the calcaneocuboid joint in similar fashion. We then sectioned the disarticulated osseous structures from the plantar flap sharply, preserving a robust plantar flap. We then transected both dorsal and plantar flaps distally at increasingly proximal intervals until bleeding margins were obtained, after which the flaps were able to be opposed. Particular attention was paid in the retention of deep plantar structures within the plantar flap. Given the robustness of our plantar flap and intact deep vascularized structures, the plantar flap was extended distally and dorsally. The dorsal flap was revised to accommodate in-setting of the plantar tissues dorsally, leaving the dorsal subcutaneous and muscular layers intact along with the neurovascular bundle. This affected a “dual deep tissue” layer dorsally, which we felt would add to the healing potential of the flaps, especially along the dorsal closure. Despite the thickness of the flap dorsally, we were able to carefully approximate the skin overlying the flap with the more proximal dorsal skin using simple sutures of prolene. The proximal extension of the plantar flap is vividly appreciated in the clinical images as evidenced by the sharp demarcation of the pink plantar tissue with the darker anterior skin (Figure 4). No deep sutures were utilized so as to prevent occlusion of any remaining deep auxiliary vessels. Given that there were no signs of infection or deep abscess, the surgery was not staged, but rather closed primarily. The osseous structures were sent for procurement of a clean margin biopsy.

Figure 5 Healed Chopart’s amputation.

Post-operative course

The patient did experience an area of breakdown about the lateral incision which had appeared somewhat tenuous intra-operatively. She ultimately healed after 5 months of wound care which included debridements under local blockade in the office. Infection did not complicate the area of wound breakdown. She understood wound healing would be prolonged given her advanced peripheral vascular disease, and that she was still at risk for a proximal amputation which she continually expressed her desire to avoid. Hyperbaric oxygen therapy was used as an adjunct. She was fitted for a custom AFO shortly thereafter which she uses to ambulate with a gait assistive device both at home and in the community. The patient has denied experiencing any phantom, ischemic, or neuropathic pain at the limb. During this postoperative period she was able to reduce her hemoglobin A1C from 9.5 to 7.5% over a 2 month period with the assistance of family practitioner in adjusting her insulin regimen and by dietary modifications. Her sound limb has also remained ulceration free. She is now 7 months ulceration free, 1 year postoperatively.

Discussion

The ability to perform basic activities of daily living, ambulation, functional independence, or even simply to transfer or adjust position in bed after loss of the contralateral limb are among the goals sought to be attained by the amputee. Interestingly, ambulatory status may specifically confer a benefit to mortality after lower extremity amputation [2]. This rehabilitation demand is often unmet in the transtibial or transfemoral amputee. This is attributable to hurdles such as a delay in obtaining a prosthesis, slower postoperative convalescence, greater rehabilitation demands compared to a minor amputation, and an inability to use the prosthesis secondary to cognitive or physical limitations. Though the reamputation rate after minor amputations has been shown to be greater than after a major amputation such as a below-knee amputation (BKA) [3,4], they ultimately offer a greater chance of ambulation if successful [5], offering a much quicker rehabilitation process. Nearly one third of patients will not ambulate after a major amputation [6]. Furthermore, bipedal ambulation after a transtibial amputation for vascular disease is uncommon [6]. In addition to these biomechanical advantages of limb salvage, other advantages are compounded in the dysvascular patient. Pinzur [7], in his pioneering work, illustrated the near linear relationship between increasing metabolic demand and ascending amputation level. In amputees afflicted with peripheral vascular disease, metabolic reserve is greatly diminished, so much so that ambulating with an above knee amputation in this cohort demands maximum aerobic capacity. In other words, self-selected and maximum walking speeds are nearly identical. In this regard, a Chopart’s amputation may provide the select patient with a greater level of independence and improved overall outcomes as compared with a proximal amputation. With regards to quality of life, Wukich [8] has shown that amongst diabetic patients with foot ulcerations, major amputation is feared more than death, and the loss of a limb has been compared to the death of a spouse in terms of psychological impact [4].

Figure 6 Radiograph of healed modified Chopart’s amputation. With this technique, equal segments of bone remain anterior and posterior to the ankle.

It should be remembered that successful completion of the operation is only the beginning of the recovery process, especially in the amputee. Depression is especially common after major amputation [4].

In this instance, we chose to employ the Boffeli modified Chopart’s amputation [9]. He and his colleagues have described the numerous biomechanical derangements that ensue after the traditional method of a Chopart’s amputation; complete loss of the calcaneal inclination angle, maximal talar plantarflexion within the ankle mortise, and an overload of the lateral column. With preservation of the navicular as their modification describes, weight transfer is encouraged through the medial column by way of extended reach of the talar head, as there is now an equal amount of osseous structure both anterior and posterior to the ankle joint (Figure 5). One drawback this modification does not address is the violation of the extensor tendons, where concern for an equinus contracture remains. As long as the soft tissues are amenable, our practice is to simply elevate and preserve the dorsal tendons with their respective flap and allow adherence to plantar flap distally, as well as the surrounding tissues after closure. As evidenced by the supplementary video (Video), this has not only prevented equinus contracture in our patient, but has afforded her maintenance of active dorsiflexion. Additionally, maintenance of the extensors has combated the potential inversion deformity from retention of the posterior tibial tendon insertion, as her muscle inventory is equal and symmetric across the ankle.

Figure 7 Custom socket-type AFO which has allowed for bipedal ambulation. The device can be inserted into a shoe as well.

We feel this modification contributes to improved function and decreased susceptibility to wounds postoperatively.

Regarding the function in this particular patient, her family has reported that she is independently ambulatory in the home with a gait assistive device, and ambulates short distances in the community. Her prosthesis is a socket type partial foot ankle-foot orthosis. While a simple diabetic shoe with plastazote insert and toe filler may suffice for managing a foot after a transmetatarsal or Lisfranc amputation, a more extensive device is needed after a more proximal pedal amputation. These types of devices serve to protect the residuum of the foot from high pressures, restore lost foot length, and temper external moments caused by loading of the prosthetic foot [10]. The prosthesis manufactured for our patient incorporates an extensive carbon fiber shell that encompasses the leg and remnant foot, a so-called “above ankle” intervention (Figure 6). The shell provides a laminated foot socket which is bonded to the prosthetic forefoot consisting of complaint foam to redistribute the pressure of ambulation away from the residuum of the foot. The carbon fiber extends from the socket beneath the foam filler to form a foot plate the entire length of the prosthetic. Given the relatively small amount of surface area of the remnant foot over which to distribute the loading forces of gait, this stiff shell-type design allows loading forces to instead be distributed over a wide area, and prevent pistoning of the amputation site that would occur in a normal shoe [10,11]. Given the alteration in center of pressure excursion in persons with partial foot amputation [10], a stiff above ankle device is needed to allow the center of pressure to extend beyond the residual foot and be borne by the prosthetic, rather than the vulnerable amputation stump. The advantage of the Chopart’s amputation over a more proximal amputation in regards to postoperative ambulation are that the residual foot offers direct end-bearing with a full limb and a stable heel pad, permitting short distance brace free ambulation. [9,11] However, with the failure rate after Chopart’s amputation being reported at 60% over a 5 year period [12], clearly, an experienced prosthetist is invaluable in preserving the salvaged extremity. Most illustrative of this fact is the systematic review by Schade of 74 Chopart’s amputations where high-profile prosthetic devices were seen to maintain function of these residual limbs at a mean follow-up of 21.1 months [13].

While many surgeons generally advocate for transtibial amputation if a transmetatarsal amputation cannot be performed or has failed [6], we find this recommendation to be unfounded. In a review of 77 TMAs, 41 failed to heal. Of these failures, 32 were treated with 22 Chopart’s and 10 Lisfranc amputations, ultimately allowing salvage in 25 [14]. The authors do not further delineate the results between the Lisfranc and Chopart’s amputations, but we can clearly conclude that at least 15 of the salvaged limbs were salvaged with a Chopart’s amputation. Distal level amputees achieve proportionally higher functional dependence and social reintegration [15]. In the diabetic host, Stone and colleagues elucidated better function and a demonstrable survival advantage for patients undergoing proximal foot amputations than those undergoing BKA [14]. This has been illustrated in the patients’ case. Yet, preservation of function is not the only consideration concerning level of amputation. Often soft tissue healing potential, of which vascular supply is integral, is a barrier in maintaining the proximal foot. As the amount of perfusion decreases, the potential for salvage is concurrently reduced. Angiography is the diagnostic modality of choice in assessment of lower extremity perfusion. Yet, while angiography can define the specific perfusion pattern of the affected limb and provide a route of intervention, the predictability in healing potential after intervention is uncertain [16]. In our patient, the vascular service offered that she would not likely heal any amputation distal to the transtibial level, based on computed tomography angiography. Despite recommendations from vascular surgeons and interventionists, the foot and ankle surgeon is ultimately tasked with judiciously deciding a reasonable level of amputation that is not only functional and in line with the patient’s wishes, but that also has adequate perfusion.

Our case is a vivid illustration that a simple cutoff of vessel patency, angiosomal supply, or arterial brachial index does not exist when predicting amputation healing. In the endeavor of limb salvage in the vascularly compromised limb, the question is simply whether there is, or is not, enough perfusion to support tissue healing. Histologically, no overt differences between lower extremity arteriosclerosis between diabetic and non-diabetic individuals has been elucidated. Conversely, a more distal predilection of these obstructive changes has been observed in those with diabetes [17]. In this way, blockage of the metatarsal and digital arteries, coupled with blockade of the named vessels, may create an end-artery situation [18]. In this scenario, the amount of tissue dependent on a single artery may comprise nearly the entire foot. When this artery is compromised, the dependent tissue dies, as there is no replacement for its function. This scenario occurred in the patient’s sentinel event leading to a digital amputation. Thereafter, the tenuous perfusion that had allowed her limb to simply exist, was not apt to heal the insult of an amputation at the transmetatarsal level. Rather than relegating her to a below-knee amputation, a limb-sparing Chopart’s amputation was performed after careful consideration and discussion with the patient. At this level, it appears her collateral network had in fact developed sufficiently to provide adequate perfusion for soft tissue preservation.

We offer that in the face of end-stage vascular disease, that is, a situation where the pedal circulation cannot be surgically improved, a failed minor amputation does not necessarily mandate limb loss, even with no direct in-line flow to the foot. While a potentially more expedient cure in that of a proximal amputation is always discussed with the patient, a limb without emergent infection in this scenario can be, with appropriate clinical acumen, considered for salvage. Adherence to the tenants of limb salvage is paramount to allow the surgeon to decide if this is a reasonable goal. Assuming the resultant extremity would provide appropriate form and function, this may not only better align with the patient’s desires, but could provide a more metabolically sound solution, while concurrently allowing improved independence and mental health. These benefits must be tempered cautiously with the potential for failure, which could have the inverse effect on these desired goals. A prolonged course of attempted limb salvage with multiple levels of amputation failure and extended wound care could metabolically decondition the patient, exacerbate depression, and potentially affect a delay in return to function that could potentially be obtained with a prosthetic.

Keeping in mind limb salvage is more than merely preserving tissue, nearly any pedal structure can be expendable in the pursuit of a functional limb. Likewise, a named pedal artery is not an absolute exception. Of course, a certain amount of perfusion is necessary to allow salvage, but in some cases, in-line angiosomal flow is not mandatory.

In conclusion, in patients with poor or even collateral only flow to the foot, limb salvage may be possible. In those patients who are adequately informed about the potential for failure and major amputation, limb salvage may be entertained. This decision must be carefully made, weighing all available relevant patient characteristics, and crucially, with due consideration to the patient’s goals, desires, and tolerance for risk of failure.

References

  1. Murrant CL. Structural and functional limitations of the collateral circulation in peripheral artery disease. J Physiol (Lond) 586:5845, 2008.
  2. Wukich DK, Ahn J, Raspovic KM, Gottschalk FA, La Fontaine J, Lavery LA. Comparison of transtibial amputations in diabetic patients with and without end-stage renal disease. Foot Ankle Int 38:388–96, 2017.
  3. Thorud JC, Jupiter DC, Lorenzana J, Nguyen TT, Shibuya N. Reoperation and reamputation after transmetatarsal amputation: a systematic review and meta-analysis. J Foot Ankle Surg 55:1007-12, 2016.
  4. Zhang W, Abou-Zamzam A. Lower extremity amputation: General considerations. In: Cronewett JL, Johnston KW, editors. Rutherford’s vascular surgery, Philadelphia: Saunders Elsevier; 2010, p. 1792-97.
  5. Mandolfino T, Canciglia A, Salibra M, Ricciardello D, Cuticone G. Functional outcomes of transmetatarsal amputation in the diabetic foot: timing of revascularization, wound healing and ambulatory status. Updates Surg 68:401-5, 2016.
  6. Eidt JF, Kalapatapu VR. Lower extremity amputation: Techniques and results. In: Cronewett JL, Johnston KW, editors. Rutherford’s vascular surgery, Philadelphia: Saunders Elsevier; 2010, p. 1772-90.
  7. Pinzur MS, Gold J, Schwartz D, Gross N. Energy demands for walking in dysvascular amputees as related to the level of amputation. Orthopedics 15:1033-36, 1992.
  8. Wukich DK, Raspovic KM, Suder NC. Patients with diabetic foot disease fear major lower-extremity amputation more than death. Foot Ankle Spec 11:17-21, 2018.
  9. Boffeli TJ, Mahoney KJ. Chopart’s amputation for osteomyelitis of the midfoot. In: Boffeli TJ, editor. Osteomyelitis of the foot and ankle, medical and surgical management, Switzerland: Springer International; 2015, p. 283-96.
  10. Dillon MP. Partial foot amputation: Evidence for device use. Lower Extremity Review, https://lermagazine.com/article/partial-foot-amputation-evidence-for-device-use; 2010 [accessed 7 April 2019].
  11. Sage RA, Pinzur M, Stuck R, Napolitano C. Amputation and rehabilitation of the diabetic foot. In: Veves A, Giurini JM, Logerfo FW, editors. The diabetic foot. Contemporary diabetes, Totowa: Humana Press; 2006, p. 363-389.
  12. Brown ML, Tang W, Patel A, Baumhauer JF. Partial foot amputation in patients with diabetic foot ulcers. Foot Ankle Int 33:707-16, 2012.
  13. Schade VL, Roukis TS, Yan JL. Factors associated with successful Chopart amputation in patients with diabetes: a systematic review. Foot Ankle Spec 3:278-84, 2010
  14. Stone PA, Back MR, Armstrong PA, et al. Midfoot amputations expand limb salvage rates for diabetic foot infections. Ann Vasc Surg 19:805-11, 2005.
  15. Inderbitzi R. The long-term mobility and mortality of patients with peripheral arterial disease following bilateral amputation. Eur J Vasc Endovasc Surg 26:59-64, 2003.
  16. Toursarkissian B, Hagino RT, Khan K, Schoolfield J, Shireman PK, Harkless L. Healing of transmetatarsal amputation in the diabetic patient: is angiography predictive?. Ann Vasc Surgm 19:769-73, 2005
  17. Andros G, Lavery L. Diabetic Foot Ulcers. In: Cronewett JL, Johnston KW, editors. Rutherford’s vascular surgery, Philadelphia: Saunders Elsevier; 2010, p. 1735-46.
  18. O’neal LW. Surgical pathology of the foot and clinicopathologic correlations. In: Bowker JH, Pfiefer M, editors. The diabetic foot, Philadelphia: Mosby Elsevier; 2008, p. 367-86.

Limb salvage in Charcot deformity correction: A case series of 20 limbs

by Jordan James Ernst, DPM, MS, FACPM1*; Dalton Ryba, DPM2; Alan Garrett, DPM, FACFAS3

The Foot and Ankle Online Journal 13 (4): 4

Charcot arthropathy is a disabling complication of peripheral neuropathy, with progressive osseous destruction often necessitating operative intervention to prevent ulceration and even amputation. The prospect of a stable, plantigrade foot is one that is best sought through timely intervention. While a host of procedures and techniques for Charcot reconstruction have been described in the literature, no clear consensus has been reached on a superior method or modality, nor on what factors most significantly affect outcomes and complications. We present a case series of 18 patients (20 limbs) operatively treated at our institution and followed for an average of 3 years for Charcot deformity. Reconstructive efforts consisted of both internal and internal fixation, and combinations thereof. To date, 1 patient has received a below-knee amputation. At 3 years (range 12-50 months), 80% of our limbs have shown that our interventions have provided lasting correction and defense against future ulceration and other undue sequelae. Three limbs remain affected by ulceration. In total, 95% of limbs have avoided major amputation. Our results appear comparable with the available literature. While successful results are being achieved in this endeavor, many questions remain unanswered, awaiting higher levels of empirical evidence to aid in their resolution.

Keywords: diabetic foot, arthrodesis, reconstruction, external fixation, beaming, tibiotalocalcaneal fusion, arthropathy

ISSN 1941-6806
doi: 10.3827/faoj.2020.1304.0004

1 – Fellowship-Trained Foot and Ankle Surgeon, Texas Institute of Orthopedic Surgery and Sports Medicine, Grapevine, TX
2 – Foot and Ankle Surgeon, Lone Star Orthopaedic and Spine Specialists
3 – John Peter Smith Hospital, Foot and Ankle Surgery, Dept. of Orthopedics, Acclaim Bone and Joint Institute
* – Corresponding author: jordanj.ernst88@gmail.com


Charcot arthropathy, a potentially disabling complication of peripheral neuropathy, often demands surgical intervention due to the progressive nature of osseous destruction, which, when left unabated, may lead to deformity susceptible to ulceration, infection, and ultimately, amputation. Surgical intervention is often necessary to create a stable, plantigrade foot that is less prone to ulceration. While a host of procedures and techniques for Charcot reconstruction have been described in the literature, no clear consensus has been reached on a superior method or modality, nor has a deformity-specific correction algorithm been established.

In addition to procedural selection, operative timing with respect to stage of deformity has not been clearly defined. Despite this, failed conservative management, recalcitrant ulceration, continued pain secondary to residual bony deformity, and as a final effort to avoid amputation remain the primary surgical indications [1].

The insensate foot is one that is prone to recurrent, unperceived trauma. Continued ambulation, coupled with neuropathic joint relaxation and hypotonia, allows for progressive osseous destruction that compromises the pedal architecture. Loss of vasomotor tone, as a result of autonomic neuropathy, allows shunting within the Haversian system, increasing bone perfusion with subsequent demineralization and, eventually, osteopenia. The resultant abnormal bone is ill equipped to protect the vulnerable joints from the aforementioned neuropathic destruction and deformity. As each case of Charcot deformity is unique, largely due to patient physiology and pattern of destruction, direct comparison of fixation techniques and patient cohorts may not be feasible. Despite this lack of standardization, sound understanding of the principles of each surgical technique remains the mainstay of enabling a surgeon to devise a construct that will have the most effectual outcome.

The aim of our study was to review, at midterm follow up, the outcomes of 20 limbs post Charcot deformity correction. We deemed a successful outcome as a stable, ulceration free limb allowing for ambulation. A limb with remaining wound or ulceration, or one that underwent major amputation, was regarded as an unsuccessful outcome.

Case Series

From February 2010 to July 2017, 26 limbs in 24 patients were treated consecutively at our institution for Charcot deformity of the midfoot, rearfoot, and ankle, or combinations thereof, with at least 12 months of follow up available. Our institutional review board approved this retrospective case series. Of these patients, we excluded one patient who was treated at an outside institution between treatments at our institution, one patient who died due to unrelated causes, and 4 others who were lost to follow up as they had not been seen at our institution in over 1.5 years. Inclusion for operative reconstruction included recurrent ulceration despite conservative measures. We prefer to avoid surgical intervention in those with a closed soft tissue envelope though deformities that were deemed unbraceable and neuropathic fractures/dislocations that were complicated by Charcot destruction were also included. We did not elect to perform a reconstruction for any patient who would have clearly been better served with a proximal amputation. In deciding between conservative and surgical intervention, we carefully weighed the risks and benefits of each potential treatment including the location and magnitude of deformity, patient willingness and ability to comply with post-operative instructions, comorbid conditions, glycemic control, vascular status, family support, social issues, wound presence with or without concurrent infection, and others. Notably, reliance on casting/bracing to contain the deformity, skin breakdown, deep vein thrombosis, and contralateral Charcot development are of special concern in patients undergoing conservative approaches. In total, 20 limbs in 18 patients met our study criteria.

In some patients, after successful Charcot reconstruction at a given anatomic location, the patient later incurred a Charcot event at a separate site within the same extremity. In these instances, for calculating wound duration preoperatively and time in external fixation, the total time for all patients combined was divided by the total number of “Charcot events” (and thus reconstructions) rather than number of limbs. This was performed to avoid artificially higher average time intervals that would have been produced by attributing the pre-operative wound time and external fixation time for multiple surgeries to one limb. In total, 24 reconstructions were performed as 4 of the 20 limbs underwent surgical correction of a repeat Charcot event.

A complete review of the medical charts including radiographs were performed to gather the data for our study. In addition to demographic information, the following variables and parameters were recorded: the location(s) of the deformity, primary and adjunctive procedures performed, date of index and subsequent surgeries, presence of wound(s) and osteomyelitis, time to wound healing, wound duration prior to surgery, percentage of patients obtaining a Charcot Restraint Orthotic (CRO) walker post operatively, complications, comorbid conditions, tobacco use, Hg A1C%, prior pedal amputations, date of last follow up, and total follow up time.

Of the 20 limbs, 6 had Charcot deformity of the ankle (Brodsky 3A), 5 had deformity in the rearfoot/Chopart’s joint (Brodsky 2), 17 demonstrated abnormality at the midfoot/Lisfranc joint (Brodsky 1), and 1 patient developed a Charcot process to the calcaneal tuber (Brodsky 3B). Additionally, 5 of these patients presented with combined Brodsky 1 and 2 deformities.

Our patients, on average, were afflicted by 4.3 comorbid conditions. Diabetes was responsible for the neuropathic process in 14 patients, idiopathic causes in 2, spinal stenosis in 1, and Lupus in 1. Eight patients had a history of cardiac disease, 1 of CVA, 3 of COPD, 2 of chronic kidney disease (1 ESRD), 2 of psychiatric disorders, and 3 of hepatitis. Peripheral vascular disease affected 1 patient. Ten patients had a history of tobacco use. The average A1C value in those with diabetes preoperatively was 9.3%.

The average patient age was 55.7 years, there were 9 females and 9 males. Average BMI measured 34.6kg/m2.

Operative Procedures

All procedures were performed by the senior author. Two reconstructions were performed during the acute phase of the disease (Eichenholz I), and the remainder were performed during the inert phase (Eichenholz stage II/III), all after distal perfusion had been deemed appropriate.

The index procedures were performed at the location of existing deformity, with subsequent surgery (subsequent Charcot event) performed at the new location of deformity.

Seven patients underwent columnar beaming (example in Figure 4), one medial column plating and screw fixation, one medial double screw fusion, and one medial column screw fusion. All but one of these constructs was augmented with application of a static circular frame. Three underwent plantar midfoot planing with placement of external fixation alone.

One patient underwent bilateral beaming in a staged fashion. The other patient who underwent bilateral procedures was treated for a calcaneal avulsion fracture on the right side with fragment excision, achilles tendon reattachment via anchors, and flexor hallucis longus transfer. Contralaterally, he developed midfoot, and then, ankle deformity, treated sequentially with external fixation and planning and TTC fusion respectively.

Regarding the 5 tibiotalocalcaneal (TTC) fusions, 3 underwent intramedullary nailing. In one such case, nailing initially proved effective but was compromised by late infection. Limb salvage was achieved with the use of a titanium cage after temporization with an antibiotic nail (Figure 1). The other 2 patients underwent lateral TTC plate and screw fixation (Figure 3) constructs respectively, as prior hardware precluded intramedullary nailing. In 4/5 TTC fusions, a static circular frame was applied over the respective fusion construct. Two intramedullary nails were placed after arthroscopic ankle preparation. In these cases, there was not yet flagrant malalignment necessitating an open approach. With open approaches, we formally prepare the subtalar joint with our constructs. The necessity for this has been debated [2].

Two patients underwent medial Lisfranc fusion with external fixation utilizing olive wires and no additional hardware. These were performed for severe dislocations in the acute phase that threatened soft tissue integrity. No limbs underwent concomitant TTC fusion and midfoot bolting as we did not treat a patient with simultaneous deformity. However, 4 patients that received midfoot reconstruction subsequently underwent treatment for deformity at the ankle. An additional patient, who was treated for midfoot disease and then later developed ankle pathology, underwent a below-knee amputation (BKA) for concomitant ankle abscess and systemic sepsis (Figure 2).

The remaining patient underwent ankle fusion by way of external fixation alone given the attendant joint sepsis.

Cases of soft tissue infection were treated with thorough irrigation and debridement with appropriate antibiotic therapy. Osteomyelitis was treated with bone resection as necessary with infectious disease consultation to manage prolonged antibiotic therapy.

Results

Eighteen patients for a total of 20 limbs (2 patients with bilateral reconstructions) were operatively treated at our institution and followed for an average of 3 years for Charcot deformity. Given the 20% rate of a repeat Charcot reconstruction, 24 reconstructions were performed in total (4 repeat Charcot reconstructions for patients who developed ankle disease after midfoot surgery). To date, 1 patient has received a BKA. Overall, 80% of our limbs have obtained a successful outcome. Three limbs remain affected by ulceration, 2 of which had wounds preoperatively. In total 95% of limbs have been salvaged or remain salvageable.

With respect to primary midfoot/hindfoot reconstruction, there were 17 such cases. As mentioned, 5 developed subsequent disease of the ankle, with 3 out of 4 attempted ankle reconstructions obtaining salvage, and in the remaining patient salvage not attempted due to emergent infection (BKA). Of the remaining 12 primary midfoot/hindfoot reconstructions, 10 limbs were salvaged. One patient in this group underwent bilateral midfoot reconstructions in a staged fashion.

Figure 1 This patient incurred separate Charcot events at both the midfoot and then the ankle, approximately 3.5 years apart. Panels a, b show his presentation after his ankle Charcot event. He had been treated by our team with external fixation and planing after a failed midfoot fusion several years prior at another facility. His midfoot hardware was removed and the ankle addressed with TTC nail fusion (c,d), the tract of which can still be appreciated within the tibial medullary canal (k,l). The nail was removed due to a chronic non-union with superimposed late infection (e,f), and a titanium cage was placed (i,j) after temporary fixation with an antibiotic nail (g,h). At last follow-up, a pseudoarthrosis is appreciated about the titanium cage (k,l). Clinical view of patient (m,n,o): A stable, plantigrade foot is demonstrable, despite the pseudoarthrosis, which has been maintained with his CRO Walker. We see him periodically in the clinic for surveillance exams.

Figure 2 This patient underwent Charcot reconstruction of his midfoot during the acute phase of the destructive process, clinical photo in panel a. Deformity appeared isolated to the LisFranc complex but was grossly unstable as evidenced by the divergent pattern of dislocation seen on his ED radiographs (b,c). Given the tenuous soft tissue, we elected to utilize an external fixation only construct to reposition the gross malalignment of the midfoot via olive wires (d,e). The patient coalesced successfully in an acceptable position (f,g). He ambulated ulceration free for 4 months before presenting to the ED with an ankle abscess and in a septic state. No open wounds were present but soft tissue emphysema was seen on x-ray over an area of the medial ankle where an obvious abscess was present (h). An emergent bedside incision and drainage was performed in the ED (i) before he was taken to the operative theater for a guillotine BKA. It appears that when he presented in sepsis he was undergoing a Charcot process about the ankle (h). The relationship of the Charcot event to the abscess is unclear, although we have encountered Charcot flares complicated by abscess without open wounds previously. This example highlights that with Charcot correction, success is never absolute.

Figure 3 This patient was initially treated for a Charcot deformity with plantar planing and external fixation application for a midfoot prominence and resultant ulceration (a). After successfully healing his ulceration and removal of the external fixator, he presented back to the clinic a few months later with a gross varus deformity at the ankle, and lateral malleolar wound, after a period of admitted unprotected ambulation. Radiographs revealed a pathologic bimalleolar fracture and severe varus deformity of the ankle (b,c). As a broken half pin from his prior external fixator obstructed the tibial canal, he underwent TTC fusion via large diameter cannulated screws. The wound was excised through a lateral approach that entailed fibular takedown, subtalar and ankle joint preparation, and corrective cuts to the tibia and talus to realign the rearfoot and ankle to the leg. An external fixator was placed to extend the area of stability beyond the fusion sites (d,e). Radiographs at final follow-up reveal good osseous union to the ankle and subtalar joints with maintained deformity correction (f,g).

Figure 4 Example of medial column bolting. A midfoot Charcot process in the quiescent phase as demonstrated by the partial coalescence and lack of bony fragmentation (a,b). Note the plantar subluxation of the midfoot on the rearfoot, most demonstrable at the talonavicular joint (b). Significant osseous resorption is seen at the intermediate cuneiform which is displaced medially along with the medial column (a). Medial column bolting was utilized to restore stability and correct deformity. This was enhanced with the application of a static external fixator to extend fixation beyond the joint segments affected by the neuropathic process (c,d). Radiographs at final follow up reveal maintained correction (e,f). The joints were not formally prepared in this instance, though it has become our preferred technique to do so.

As stated, the 4 repeat Charcot reconstructions were patients who developed disease of the ankle after undergoing midfoot reconstruction. Three of these limbs were ultimately salvaged, with 1 afflicted with persisting ulceration. In total, of the 7 patients with ankle deformity, 5 were salvaged. These include the 3 that were successfully reconstructed subsequent to midfoot reconstruction and 2 primary ankle salvages. The 2 remaining patients were the patient relegated to BKA and the patient with failed ankle salvage after prior midfoot surgery.

In 1 patient, calcaneal avulsion repair with FHL transfer was performed successfully on one side with primary ankle salvage performed on the contralateral side at a later date (1 of 2 patients with primary ankle salvage).

In total, there were 20 primary limb reconstructions, 17 of the midfoot/hindfoot, 2 of the ankle, and 1 of the calcaneal tuber.

The average A1C value in those with diabetes preoperatively was 9.3%. The average A1C in those still with unsuccessful outcomes was 8.3%, while in those with successful outcomes averaged 9.7%. Four patients had a history of amputation within the forefoot. Total time in the external fixation device averaged 2.8 months. Twelve limbs (60%) had ulcerations preoperatively, 3 wounds were complicated by underlying osteomyelitis. At the time of frame removal, 10 of the wounds had healed. The other 2 patients with preoperative wounds have maintained their limbs but are still with wounds, 1 with prior osteomyelitis. Average wound time prior to surgery was 11.2 months. Pin tract infections occurred in 6 frames, wires broke in 2, one of which with concomitant infection that prompted premature frame removal. Other complications included 1 abscess formation, 1 case of non-pin tract cellulitis, 1 incision dehiscence, and 1 decubitus ulceration. Descriptive characteristics of the study population can be seen in Table 1.

Ulcer Free Limbs:

16 Limbs

15 Patients

Limbs with Ulceration/BKA:

4 Limbs

4 Patients

Total study population:

20 Limbs

18 Patients

Gender 6 M, 8 F 3 M, 1 F 9 M, 9 F
Age (years) 56.8 51.5 55.7
Follow – Up (months) 37.2 32.3 36.4
Laterality 9 R, 5 L 3 R, 1 L 12 R, 8 L
BMI (kg/m2) 35.2 32.3 34.6
Diabetes-related neuropathy (limbs) 12 3 15
A1C 9.7% 8.3% 9.3%
PVD 0 1 1
Comorbid Conditions (Avg #) 4.1 5 4.3
Tobacco Use 60% 50% 55.6%
Cardiac disease 6 3 8
ESRD 0 1 1
Number of pre-operative wounds and duration 10 Limbs

10.6 months

2 Limbs

14 months

12 Limbs

11.2 months

Osteomyelitis (limbs) 2 1 3
Time In External Fixation per Events (months) 2.8 2.9 2.8
Repeat Charcot Events

(Limbs)

3 2 5
Prior Forefoot Amputations (limbs) 2

1 ipsilateral

2

2 ipsilateral

4

3 ipsilateral

Location of Deformity
Ankle/Hindfoot 5 2 7
Midfoot/Hindfoot 13 4 17
Procedures Performed
TTC/TC/Ankle Fusion 5 1 6
Midfoot and Combined Midfoot/Rearfoot Fusions 7 3 10
Midfoot Fracture-Dislocation Correction with External Fixation Alone 1 1 2
Planing with ex-fix alone 5 0 5
Calcaneal Avulsion Repair 1 0 1

Table 1 Descriptive summary of patient population averages. *Note the number of patients with a salvaged limb and those with an unsalvaged limb do not equal the total number of patients as one patient had successful reconstruction on one side and failure of the contralateral extremity (both midfoot reconstructions).

Discussion

Limb salvage rates in patients undergoing Charcot reconstruction are reported with great variability in the literature. With any of these data points, it is important to consider that each surgeon has an individualized selection bias to their respective patient population. While certain indications for Charcot correction have been developed, each cohort is ultimately that surgeon’s unique population deemed appropriate for surgical intervention. As such, there is likely heterogeneity when comparing patient populations undergoing Charcot reconstruction. As previously mentioned, the choice to attempt reconstruction in a patient with Charcot deformity is multifaceted, and often difficult. Zgonis has described the choice between conservative measures and surgical intervention in Charcot patients as the “lesser of two evils” given the significant complications in each [3]. In addition to deciding between reconstruction and non-operative care, amputation is an alternative in many patients. Clearly, limb salvage should not be undertaken in those whose medical status or limited functional capacity would preclude them from ever realizing the benefits of limb salvage. In these patients, this choice can become complex however, as in some patients, the magnitude of the contribution of comorbid conditions versus the limb deformity itself, to lack of function, cannot be easily discerned. No patient in our series requested a below knee amputation, although all patients with Charcot joint disease are made aware from initial diagnosis that the limb is at risk for this outcome. As no patient with emergent infection underwent reconstruction, the procedures could be seen as elective.

Domek, et al., demonstrated that among diabetic patients undergoing elective surgery, the average A1C value of those with postoperative complications was 6.29%, compared with 6.11% for those who did not. Each 1% increase portended a 5% increase in complication risk [4]. Though A1C based risk stratification for diabetic patients undergoing elective procedures has been clearly illustrated, these guidelines are not necessarily best interpreted as concrete “cut off” points when deciding to offer a patient Charcot reconstruction, but rather as a valuable prognostic tool to be considered in the entirety of the clinical situation. Furthermore, bracing in the face of severe deformities is impractical. Ramanujam, et al., have shown that in a cohort of 116 patients with Charcot of the foot and/or ankle treated with external fixation, A1C was not associated with risk of amputation or mortality [5]. A1C Averaged 8.16% in their series, somewhat lower than our average. While not an ideal average, the surgeon must contemplate which scenario offers the best propensity for healing; a wound with an underlying structural abnormality in a patient with an A1C of 9%, or a wound without underlying prominence in that same patient. Those in our study with successful outcomes trended towards higher A1C values. Keeping this in mind, there are undoubtedly patients whose comorbid conditions lack a level of control so great that surgical reconstruction is doomed to failure. The diabetic host with ESRD is one such patient that is often cited as being ill-equipped to convalesce successfully after Charcot reconstruction, given the devastating effects of renal disease on bone metabolism [6] and the sheer mortality associated with the disease [7].

With respect to prior amputations, our results showed that half of those with an unsuccessful outcome had a history of prior forefoot amputation. A greater sample size could ascertain whether prior forefoot amputation is truly an independent risk factor for amputation, or rather a reflection of more severe disease processes in these patients.

Increased morbidity has been reported in Charcot reconstructions in the face of ulceration [5], and internal fixation is often avoided in these cases [8].

Regarding wound presence in our cohort, 10/12 (83.3%) patients with preoperative wounds obtained successful outcomes compared to the overall success rate of 80%. Of the 3 patients who remained with ulceration or wound at the end of our study period, 2 had wounds preoperatively.

In considering the success of our interventions, 80% of these patients ultimately achieved the goals of reconstruction, a plantigrade and functional extremity without a predilection for re-ulceration. In measuring the merit of our interventions however, we must also examine the effect of our interventions on those in whom reconstruction has not attained the desired outcome. One patient underwent major amputation as a result of infection not directly related to our intervention. In assessing the 3 patients in whom wound healing has not been achieved, 2 had wounds pre-operatively. The one postoperative wound developed from non-compliance from the patient wedging her external fixator around her wheelchair footrests to create a decubitus heel ulceration. No wounds were complicated with infection at last follow up. We feel that while 100% success has not been obtained, we have stayed true to the bioethic of non-maleficence or “Primum non nocere”. All 3 of these limbs remain salvageable, and a non-healing wound was never created by our surgical approach.

While the risk of contralateral Charcot after an initial event is well documented in the literature [3], less information has been assembled on the risk of a Charcot event within the same limb at a secondary location. In our series, 5 patients (25% of limbs) developed ankle Charcot deformity after having undergone treatment for breakdown at the midfoot level, comprising 5/17 of all patients treated for midfoot disease. One had been treated with bolting of the midfoot, 3 with external fixation alone, and 1 with plating. Of these 5 patients, 4 admitted to a period of non-compliance with their CRO walker, and 1 had declined CRO walker fitting and instead ambulated in a custom-made gauntlet AFO. On average, the Charcot events were separated by 2.3 years. Given our sample size, we cannot speculate on the potential risk for a repeat Charcot event within the same limb. Clearly, it would stand to reason that if one segment of the pedal framework is fused, the adjacent segments are placed under increased demand, and thus at increased risk for overload and collapse. To what extent this is true and the relationship between various anatomical zones remains to be seen [9]. Increased understanding of ipsilateral Charcot events could potentially affect future fixation methods. To our knowledge, the percentage of this occurrence has not been documented. Our rate of 25%, while seemingly high, does not have a reference standard for us to compare our outcomes. Perhaps our results are an aberration, or non-compliance was the culprit, or perhaps our follow up of 3 years was simply long enough to realize a potentially underreported sequela. The rate of contralateral Charcot has been reported to be approximately 25%, [10] matching our value for ipsilateral deformity. In our population, 2 patients were surgically treated for contralateral deformity, however more potentially had contralateral Charcot deformities that were treated conservatively, so we did not attempt to compare rates of contralateral versus ipsilateral Charcot in our own series. One of our patients with bilateral deformity at the midfoot level was treated successfully on one side, but remains with an ulceration on the contralateral extremity.

While we routinely obtained radiographs after Charcot reconstruction, we did not include rates of union in our series. LaFontaine has described the abnormal character and cellularity of this bone [11]. This type of bone not only demands more robust fixation, but also has suboptimal reparative capacity. At times, unconventional fixation is required, as in our TC fusion with a titanium cage. This method is touted to facilitate osseous formation through structural mechanics rather than through copious biologics. Via load transfer and its open architecture allowing for graft incorporation, the device is said to actively participate in the healing process [12]. In the absence of radiographic evidence of hardware failure or frank peri-implant fracture, we deem clinical union to be of greater importance in determining weight bearing progression in Charcot patients. Wiewiorsky, et al., elaborated that complete osseous union is not a definite prerequisite for stability [9]. All wound-free patients in our series were instructed to advance to weight bearing in a CRO walker once clinically stable. All but 3 of our wound free patients obtained a CRO walker device. At our institution, we routinely have patients fitted for a CRO walker in the post anesthesia unit after frame removal. Coordination of this effort preoperatively with the prosthetist is key to minimizing the patient’s time to obtaining the device, and therefore their risk of collapse. While waiting for their custom device to be manufactured, a fracture boot is utilized for weight bearing in a controlled environment such as the home or a rehabilitation facility.

With regard to fixation options, progress has been made to discern the general trends and outcomes with various fixation methods, but also to develop and refine techniques for improved success.

Dayton, et al., in their systematic review comparing internal and external fixation for Charcot deformity, presented general concepts of fixation methods [8]. They elaborate that internal fixation has a greater degree of comfortability, being a technique surgeons are most often more familiar with and perceive as being more straightforward. External fixation, while potentially more technically demanding, offers a less invasive approach that ultimately yields a platform for soft tissue preservation while allowing an adjustable design with a wide range of stability.

Their results elucidated several trends in fixation choice. They noted internal fixation tended to be the method of choice when ulceration or osteomyelitis were absent. In contrast, external fixation was most often employed when osteomyelitis or wounds were present. This method was also often staged to afford limb salvage and allowed for earlier weight bearing. Overall, the odds of success with internal fixation was 0.52 times as likely as with external fixation, despite the higher usage of external fixation in more complicated cases.

While internal and external fixation each have merits of their own [1,5] combining the two methods may provide a more favorable outcome [13,14]. Hagewald, et al., in a series of 22 patients with Charcot deformity without osteomyelitis, were able to attain a 91% incidence of short term (58 weeks) limb-salvage utilizing a combined approach. Flap closure was used for wound coverage in the 8 patients with ulcerations [14].

Lamm and colleagues obtained impressive results with a novel two-stage approach to midfoot Charcot deformity correction [15]. Their protocol first obtains correction through gradual distraction and realignment with a Taylor Spatial Frame. Prior to application, a percutaneous Gigli saw osteotomy is performed across the coalesced midfoot to allow for manipulation of the forefoot on a fixed hindfoot, utilizing wires affixed to the frame on either side of the osteotomized segment. This correction is successively maintained with a minimally invasive arthrodesis technique consisting of percutaneously inserted partially threaded, cannulated, intramedullary metatarsal screws after frame removal. The guidewires are used to stabilize the foot before the frame is removed.

All patients underwent Ilizarov external fixation, with additional internal fixation at the location(s) of deformity and bone resection as needed. The authors contend this approach may be especially beneficial in those patients with bone quality insufficient to rely solely on internal fixation, thus requiring stabilization away from the internal site of correction. While the results of dual fixation appear promising, a recent systematic review did not reveal any added benefit of combined fixation [16].

One of the tenants of the Charcot reconstruction “superconstruct” is to extend the area of fixation beyond the osseous segments affected by the neuropathic process [17]. In many of our constructs, a static circular fixator fulfilled this objective whether in isolation or combined with internal fixation. Combined fixation was utilized in 14/24 (58%) of our reconstructions.

In a review of the Charcot literature in the last 5 years, it would seem that the most common location of deformity undergoing operative intervention is that of the hindfoot and ankle [16]. There appears to be a reduced trend for surgical treatment of midfoot Charcot deformity. Lamm advocates primarily for non-operative care in Charcot deformities limited to affliction at the Lisfranc complex, given the inherent anatomic stability at this location [18]. In our current study, two patients with isolated Lisfranc deformity were treated surgically. The remaining patients with Lisfranc degeneration also had pathology at the more proximal midfoot and Chopart’s joints that warranted remedial alignment with fixation.

Our study had a number of limitations. The most notable methodological weakness is the retrospective nature of the design. Two authors were responsible for gathering, compiling, and analyzing data from the patient medical records. This could have inadvertently increased the potential for bias in our results. Additionally, this method is somewhat limited by the accuracy and quality of documentation. However, the patient records were thoroughly reviewed by each of the two reviewing authors independently, and a unified agreement was reached regarding any discrepancies. Given our sample size and the diversity of fixation methods and deformities, we could not set out to correlate various patient factors, types of fixation, and deformity level, to the obtained outcomes. The heterogeneity of Charcot deformity both in pattern of deformity and temporality of presentation, together with each unique host, render such undertakings of outcome based comparisons arduous, requiring a multitude of patients. Rather, we contend we have shown that in a high risk patient population affected by Charcot deformity, limb salvage efforts are effective and without undue sequelae. Indeed, high quality randomized controlled trials are not likely warranted or ethical [19]. The systematic review of Schneekloth appears to agree with this sentiment [16]. The authors report that while the overall quality of literature regarding this topic has improved greatly in recent years, evidence concerning the timing of treatment and the use of different fixation methods remains inconclusive. As a whole, they found that approximately 9% of patients undergoing Charcot reconstruction will undergo major amputation.

In summary, 80% of our limbs have obtained successful outcomes at a follow-up of 3 years, providing vivid examples of how Charcot deformity is amenable to, and even mandates a diverse surgical repertoire to obtain a stable, ulceration free limb. In this approach, the utility of external fixation cannot be understated given the increased propensity for limb salvage [8]. We theorize that this approach, together with more aggressive soft tissue coverage, will offer the highest potential for success. Further research may provide the surgeon with greater knowledge with which to temper their decisions rather than to develop an accepted protocol or gold standard of treatment [19]. Increased understanding of the risk for a secondary Charcot event after reconstruction may be a pivotal factor as well. Given these methods and findings, we hope to better arm the reconstructive surgeon for this formidable task. With ongoing treatment, patient recruitment, and analysis, we aspire to develop this work into one which can more clearly aid the limb salvage specialist in their decision making amongst a host of surgical options.

References

  1. Grant WP, Garcia-Lavin SE, Sabo RT, Tam HS, Jerlin E. A retrospective analysis of 50 consecutive Charcot diabetic salvage reconstructions. J Foot Ankle Surg 48:30-83, 2009
  2. Mulhern JL, Protzman NM, Levene MJ, et al. Is subtalar joint cartilage resection necessary for tibiotalocalcaneal arthrodesis via intramedullary nail? A multicenter evaluation. J Foot Ankle Surg 55:572-77, 2016.
  3. Zgonis T, Roukis TS, Lamm BM. Charcot foot and ankle reconstruction: current thinking and surgical approaches. Clin Podiatr Med Surg 24:505-17, 2007.
  4. Domek N, Dux K, Pinzur M, Weaver F, Rogers T. Association between hemoglobin A1c and surgical morbidity in elective foot and ankle surgery. J Foot Ankle Surg 55:939-43, 2016.
  5. Ramanujam CL, Han D, Zgonis T. Lower extremity amputation and mortality rates in the reconstructed diabetic Charcot foot and ankle with external fixation: data analysis of 116 patients. Foot Ankle Spec 9:113-26, 2016
  6. Miller PD. Chronic kidney disease and the skeleton. Bone Res 2:140-44, 2014.
  7. U.S. Renal Data System, USRDS 2013 Annual Data Report: Atlas of Chronic Kidney Disease and End-Stage Renal Disease in the United States, National Institutes of Health, National Institute of Diabetes and Digestive and Kidney Diseases, Bethesda, MD, 2013. Chapter Five: Mortality, Volume 2.
  8. Dayton P, Feilmeier M, Thompson M, Whitehouse P, Reimer RA. Comparison of complications for internal and external fixation for Charcot reconstruction: a systematic review. J Foot Ankle Surg 54:1072-75, 2015.
  9. Wiewiorski M, Yasui T, Miska M, Frigg A, Valderrabano V. Solid bolt fixation of the medial column in Charcot midfoot arthropathy. J Foot Ankle Surg 52:88-94, 2013
  10. Caputo GM, Ulbrecht J, Cavanagh PR, Juliano P. The Charcot foot in diabetes: six key points. Am Fam Physician 57:2705–10, 1998.
  11. La fontaine J, Shibuya N, Sampson HW, Valderrama P. Trabecular quality and cellular characteristics of normal, diabetic, and Charcot bone. J Foot Ankle Sur 50:648-53, 2011.
  12. Olivares-navarrete R, Hyzy SL, Slosar PJ, Schneider JM, Schwartz Z, Boyan BD. Implant materials generate different peri-implant inflammatory factors: poly-ether-ether-ketone promotes fibrosis and microtextured titanium promotes osteogenic factors. Spine 40:399-404, 2015.
  13. Capobianco CM, Ramanujam CL, Zgonis T. Charcot foot reconstruction with combined internal and external fixation: case report. J Orthopaedic Surg Res 11:5-7, 2010.
  14. Hegewald KW, Wilder ML, Chappell TM, Hutchinson BL. Combined internal and external fixation for diabetic Charcot reconstruction: A retrospective case series. J Foot Ankle Surg 55:619-27, 2016.
  15. Lamm BM, Gottlieb HD, Paley D. A two-stage percutaneous approach to charcot diabetic foot reconstruction. J Foot Ankle Surg. 49:517-22, 2010.
  16. Schneekloth BJ, Lowery NJ, Wukich DK. Charcot Neuroarthropathy in Patients With Diabetes: An updated systematic review of surgical management. J Foot Ankle Surg 55:586-90, 2016.
  17. Sammarco VJ. Superconstructs in the treatment of Charcot foot deformity: plantar plating, locked plating, and axial screw fixation. Foot Ankle Clin. 14:393-407, 2009.
  18. Lamm BM. Surgical reconstruction and stepwise approach to acute Charcot neuroarthropathy. In: Zgonis T, editor. Surgical reconstruction of the diabetic foot and ankle, Philadelphia: Wolters Kluwer; 2009, p. 223-29.
  19. Shazadeh Safavi P, Jupiter DC, Panchbhavi V. A systematic review of current surgical interventions for Charcot neuroarthropathy of the midfoot. J Foot Ankle Surg 56:1249-52, 2017.

A literature review exploring the use of botulinum toxin A injection therapy for chronic exertional compartment syndrome treatment

by Ebony Love DPM DABPM1, Michelle Garcia MS2, Ziad Labbad MD DPM CPed3

The Foot and Ankle Online Journal 13 (4): 3

Chronic exertional compartment syndrome (CECS) is a rare condition typically affecting runners. It has been speculated that the cause of CECS is due to a transient ischemia occurring during exercise compromising blood flow and leading to increased intramuscular pressure. The first line of treatment for patients is cessation of the aggravating activity which some individuals are less inclined to follow. If conservative treatment fails, the next option is a fasciotomy with a recurrence risk of 44.7%. A review of current literature on treatment options for CECS illustrates preliminary studies of the use of botulinum toxins A injection therapy. The use of botulinum toxin A as a non-surgical option for CECS has been theorized due to the analgesic properties and muscle hypotonia to improve blood flow. The objective of this review was to search the current literature on the use of botulinum toxin A as a treatment option for patients with CECS. A thorough search of the literature via PubMed concerning botulinum toxin as a treatment option for patients with CECS was completed. Botulinum toxin A injections demonstrate a statistically significant decrease in intramuscular pressure in the anterior and lateral compartments of the leg. A high correlation is noted in patients experiencing no exertional pain extending to fourteen months following the injections with no reported adverse effects. Patients were able to resume and continue pre-injections level of activity without any residual effects. Our goal was to investigate the current literature for non-surgical treatments for CECS. The effectiveness of this potential therapy both short term and long term are not fully understood as of yet, however future large prospective randomized controlled studies are needed.

Keywords: Chronic exertional compartment syndrome, botulinum toxin A

ISSN 1941-6806
doi: 10.3827/faoj.2020.1304.0003

1 – Clinical Associate Professor Temple University School of Podiatric Medicine, Medicine Department, Philadelphia, PA.
2 – Podiatric Student Temple University School of Podiatric Medicine
3 – Clinical Professor Temple University School of Podiatric Medicine, Biomechanics and Medicine Department
* – Corresponding author: elove@temple.edu


Chronic exertional compartment syndrome (CECS) is a rare condition typically affecting runners. It has been speculated that the cause of CECS is due to transient ischemia during exercise compromising blood flow and leading to increased intramuscular pressure in the lower extremities [1]. CECS is considered to be a clinical diagnosis. Patients often present with an intolerable dull, achy pain in their legs after running a consistent distance with no history of trauma. Neurological symptoms such as paraesthesia, numbness, and transient slap-foot are commonly seen clinically with patients with CECS [1]. The first line of treatment for patients is the cessation of the aggravating activity that some individuals are less inclined to follow or unable to follow due to occupational demand. If conservative treatment fails, the gold standard is a fasciotomy with a recurrence risk of 44.7% [1,3]. A review of current literature on treatment options for CECS illustrates preliminary studies of the use of botulinum toxins A injection therapy. The use of botulinum toxin A as a non-surgical option for CECS has been theorized due to the analgesic properties and muscle hypotonia to improve blood flow [2,3]. The objective of this review was to search the current literature on the use of botulinum toxin A as a treatment option for patients with CECS.

Methodology

A thorough search of the literature via PubMed concerning botulinum toxin A as a treatment option for patients with CECS was completed.

Results

Isner-Horobeti, et. al., performed a preliminary investigation on the effects of botulinum toxin A injections in the anterior and lateral compartments of the leg in patients diagnosed with CECS [3]. The intramuscular pressure (IMP), exertional pain, and muscle strength was monitored before and after injections. A total of 25 anterior leg compartments and 17 lateral compartments in 16 patients with CECS was studied. Specifically, IMP was measured before the injection and 3–9 months after injection.

The follow-up visit showed that there was a statistically significant decrease of IMP at one minute and five minute intervals following the cessation of running protocol in both the anterior and lateral compartments. The anterior and lateral compartments illustrated a reduction of 63% and 68% of IMP over the five-minute interval following cessation of activity, respectively. By five minutes following activity the anterior compartment was ≤20 mm Hg in 88% of patients and 93% of patients in the lateral compartment [3].

Over the course of the follow-up period, 94% of patients reported complete eradication of pain. Additionally, patients who presented with no pain were shown to have an increase in running performance of the protocol at follow-up visits. In regards to muscle strength, there was a noticeable loss of muscle grade in the tibialis anterior muscle at the one-month follow-up visit in 69% of subjects, with the minimum muscle grade 4/5 in 19% of subjects. Patients demonstrated no permanent functional loss despite decrease in muscle strength; muscle strength returned to normal in all patients at following visits. The authors concluded that reduction of IMP and pain could be due to muscle hypotonia leading to muscle atrophy and improved blood flow, however, the effects of botulinum toxin A are not yet fully understood [3].

Since the Isner-Horobeti initial article, there have been two additional case studies utilizing the Isner-Horobeti’s methodology to treat a twenty-year-old female recreational runner with a one-year history of CECS and a twenty-three-year-old male in the active military with a seven-year history of CECS [4,5].

In 2016, Baria and Sellon utilized the methodology of Isner-Horobeti (2013) to treat a twenty-year-old female recreational runner [4]. The patient’s symptoms were progressively worsening to the point that even walking provoked her pain with noted paresthesia bilaterally in her legs. The patient reported intense pain with running which resolved after ten minutes of rest with failed interventions with ice and heat. The patient was not interested in surgical interventions; thus an alternative approach was needed. Ultrasound and electrical stimulated guided botulinum toxin injections were performed in the tibialis anterior, extensor digitorum longus, extensor hallucis longus, fibularis longus, and fibularis brevis [4].

Following the botulinum toxin A injections, there was a time period of fourteen-month follow-ups. The patient reported decreased pain and no noted paresthesia with activity at one week following the injections. Pain relief continued through the 14-month period with no reported loss in muscle strength and no adverse effects. In this study, the authors measured muscle bulk and sonographic echotexture that illustrated within normal limits at the final fourteen-month visit indicating no loss in muscle mass. They concluded that chemically induced muscle atrophy from the botulinum toxin A injections was not the cause of the reduction in intramuscular pressure and further studies to investigate the pharmacological effects need to be investigated [4].

In 2019, a twenty-three-year-old male on active military duty presented with continuous, bilateral lower leg pain with exertional activity. Due to the worsening symptoms and failed conservative treatments [5]. The clinical presentation noted that after ten minutes of running there was paresthesia to the dorsum of the feet and tearing, burning pain to the anterior lower legs that lasted up to twenty minutes following cessation of activity despite the application of ice and heat. CECS was confirmed in this patient utilizing a Stryker intracompartmental pressure monitor device noted >30 mm Hg in the anterior and lateral compartments bilaterally following one minute of exercise [5].

Due to occupational physical demand, worsening symptoms, failed conservative treatments, and noted high risk of recurrence after a fasciotomy, the patient opted for botulinum A toxin injections therapy for treatment. Following the methodology of Isner-Horobeti, the patient underwent a series of botulinum A toxin injections in the anterior and lateral compartments of the lower leg bilaterally. The initial side effect reported at the patient’s one-week follow-up is initial soreness at injection sites and mild foot drop bilaterally. After the two-week follow-up, the patient denied any pain and soreness in the lower legs; after the 6 months follow up the mild foot drop previously noted bilaterally resolved and the patient reported eradication of pain and paresthesia with activity [5].

Discussion

Our goal was to investigate the current literature for non-surgical treatments for CECS. These case studies are preliminary first steps toward evaluating botulinum toxin A injections as a potential form of therapy. The results from these studies illustrated eradication of pain and paresthesia seen following the injections in patients with CECS. Most importantly, there was no permanent functional loss and no evidence of recurrence in patients which are associated risk factors with current surgical treatment options for CECS. Interestingly, the primary theory of the effects of botulinum toxin A injections in decreasing intramuscular pressure was not supported in following case studies after Isner-Horobeti et. al. initial study. Investigating the muscle bulk and sonographic echotexture of injected muscles noted unchanged following injection therapy suggesting an alternative theory to muscle hypotonia leading to establish blood flow from transient ischemia [4]. The effectiveness of this potential form of therapy both short term and long term are not fully understood as of yet, however, future larger prospective randomized controlled studies are needed.

Acknowledgments

The authors sincerely acknowledge the Temple University School of Podiatric Medicine, the Medicine Department, for their support.

References

  1. Vajapey S, Miller TL. Evaluation, diagnosis, and treatment of chronic exertional compartment syndrome: a review of current literature. The Physician and Sportsmedicine. 2017;45(4):391-398.
  2. Oskarsson E, Piehl Aulin K, Gustafsson B-E, Pettersson K. Improved intramuscular blood flow and normalized metabolism in lateral epicondylitis after botulinum toxin treatment. Scandinavian Journal of Medicine & Science in Sports. 2009;19(3):323-328.
  3. Isner-Horobeti M-E, Dufour SP, Blaes C, Lecocq J. Intramuscular pressure before and after botulinum toxin in chronic exertional compartment syndrome of the leg: a preliminary study. Am J Sports Med. 2013;41(11):2558-2566.
  4. Baria MR, Sellon JL. Botulinum toxin for chronic exertional compartment syndrome: a case report with 14 month follow-up. Clinical Journal of Sport Medicine. 2016;26(6):e111-e113.
  5. Hutto WM, Schroeder PB, Leggit JC. Botulinum toxin as a novel treatment for chronic exertional compartment syndrome in the U. S. Military. Military Medicine. 2019;184(5-6):e458-e461.

 

Overview of diabetic neuropathy and review of FDA-approved oral therapies

by Ebony Love DPM DABPM1*, Michelle Garcia MS2, Ziad Labbad MD DPM CPed3

The Foot and Ankle Online Journal 13 (4): 2

Diabetic neuropathy is the most common complication of uncontrolled and chronic diabetes. Neuropathy is the result when the somatosensory system is compromised leaving patients with irreversible nerve damage. The continuity of this neuropathic pain may lead to disorders such as insomnia, depression, and anxiety. The cause of neuropathic pain cannot be treated, and current treatment management focuses on treating the symptoms. A review of current literature on diabetic neuropathy and of FDA approved oral therapies is performed to provide an extensive overview in order to reduce and prevent the progression of this disease. The epidemiology of diabetic neuropathy can be characterized by its prevalence and risk factors. Symmetric polyneuropathy is the most common type of diabetic neuropathy accounting for about 75% of affected patients and is divided into classes depending on the types of sensory fibers involved. Small fiber neuropathy is associated with burning, prickling pain due to non-painful stimuli or an exaggerated response to painful stimuli. Large fiber affected neuropathy involves numbness, tingling without pain, and loss of protective sensation. Besides lifestyle intervention and glucose control the first line medication for diabetic neuropathy is gabapentin, pregabalin and duloxetine. This literature review guide is dedicated to the millions suffering from diabetic neuropathy. Neuropathic pain is a chronic disorder that can impair a patient’s quality of life. The results of this literature review demonstrate a need for long-term research with advancing technologies on new medications to understand their specific effects and risks to patients.

Keywords: diabetic neuropathy, gabapentin, duloxetine, cymbalta, FDA warning for gabapentinoids

ISSN 1941-6806
doi: 10.3827/faoj.2020.1304.0002

1 – Clinical Associate Professor Temple University School of Podiatric Medicine, Medicine Department , Philadelphia, PA.
2 – Podiatric Student Temple University School of Podiatric Medicine
3 – Clinical Professor Temple University School of Podiatric Medicine, Biomechanics and Medicine Department
* – Corresponding author: elove@temple.edu


Diabetic neuropathy is the most common complication of uncontrolled and chronic diabetes. Neuropathy is the result of a compromised somatosensory system leaving patients with irreversible nerve damage [1,2]. The progression of this neuropathic pain may lead to disorders such as insomnia, depression, anxiety, and impaired quality of life [1,2]. This common complication of diabetes is correlated to increase doctor visits and increase prescription of medication [2]. Currently, treatment management for diabetic neuropathic pain focuses on treating the symptoms due to the irreversible nerve damage [1,2].

Our goal was to provide an overview of diabetic neuropathy and oral treatment options including a recent update of the new FDA warnings on gabapentinoids.

Methodology

Thorough research of literature via PubMed concerning (i) the etiology of diabetic neuropathy; (ii) symptom presentation (iii) FDA approved oral medications for patients with neuropathic pain was reviewed.

Results

Epidemiology of Diabetic Neuropathy

The epidemiology of diabetic neuropathy can be characterized by its prevalence and risk factors such as lifestyle, comorbidities, and genetics. The prevalence of diabetes mellitus is 419 million adults worldwide (8.8% of the adult population), in which 50% of affected individuals will progress to develop polyneuropathy [3]. There is a high correlation of diabetic neuropathy in patients with obesity and increased waist circumference [3]. Clinical setting risks of diabetic neuropathy include comorbidities such as a high HbA1c, duration of diabetes disease, and poor glucose control [3]. For heredity causes, the opioid receptor gene (OPRM1) and sodium channel gene (SCN9A) showed significant association with diabetic neuropathy; it has been reported in one study that 56% of participants has reported a family member with diabetic neuropathy [3].

Signs and Symptoms of Diabetic Neuropathy

There are different types of diabetic neuropathy: symmetric polyneuropathy, autonomic neuropathy, and cardiovascular autonomic neuropathy [1,2]. Symmetric polyneuropathy is the most common type of diabetic neuropathy accounting for about 75% of affected patients [1]. The distribution of diabetic polyneuropathy includes a “stocking and glove” pattern because neuropathy typically affects the longest nerves of the body the most hence the feet, legs, hands, and forearms are the sites of the majority of symptoms [2]. Diabetic polyneuropathy is further divided into classes depending on the types of sensory fibers involved [1,2]. Small fiber neuropathy is associated with burning, prickling pain due to non-painful stimuli or an exaggerated response to painful stimuli. Clinical tests for small-fiber function include pinprick and temperature sensations [1]. Large fiber affected neuropathy involves numbness, tingling without pain, and loss of protective sensation. Due to the loss of protective sensations, large fiber affected neuropathy is associated as a high risk factor for foot ulcerations and amputations [1]. Clinical tests for large-fiber function include vibration perception with 128-Hz, proprioception, 10-g monofilament and ankle reflexes. Patients should be assessed for distal polyneuropathy starting at diagnosis of type 2 diabetes or five years after the diagnosis of type 1 diabetes with at least annual exams thereafter [1,2,3,4]. It is important to note that up to 50% of patients with diabetic neuropathy is asymptomatic which can put these individuals at greater risk for injuries to their feet that lack sensation [1]. Prevention and early detection is an important medical practice for diabetic care due to not being able to restore underlying nerve damage.

FDA Approved Oral Medications for Neuropathy Pain

Diabetic neuropathy is hard to treat due to the underlying irreversible nerve damage. At this time there is no medication capable of restoring the nerve damage caused by neuropathy. Current methods of treatment focus on treating the symptoms of diabetic neuropathy supporting “unconventional analgesics” medications including antiepileptics, Gabapentin and Pregabalin, and antidepressant, Duloxetine [1,4,5,6]. It is important to note that the amount of patients who actually receive worthwhile pain relief from any oral listed medication, greater than 50% of pain relief, only occur in about 10% to 25% of the affecting population [4].

Gabapentin acts to bind to α2-δ calcium channels in the central and peripheral nervous system to reduce excitability of nerve cells [4]. Evidence shows patient’s who experience relief of symptoms report at least 50% reduction in pain [1,4]. It is important to note that effective oral dose is at least 1200 mg and noted high correlation with reported successful dosing as high as 3600 mg per day [1,4]. Due to the necessary high doses for the drugs effectiveness to alleviate neuropathic pain there has been numerous reported withdrawal and side effects noted in Gabapentin than other approved oral medications for neuropathic pain [4]. Common side effects seen in patients taking Gabapentin include dizziness, drowsiness, gait disturbances, and hypoventilation; the incidence rates of patients taking this medication who experience these negative side effects ranges 1.1% to 19% of the time [4,8].

Pregabalin also binds to α2-δ calcium channels inhibitory to reduce excitability of nerve cells [6]. Evidence suggests that patients who experience relief of symptoms report 30%-50% improvement in pain [1,6]. The effective dose of Pregabalin is 300 mg or 600 mg per day orally [1,6]. The benefits of Pregabalin include faster onset of action and less necessary dose for effectiveness when compared to Gabapentin [1]. Similar to Gabapentin reported side effects include dizziness, drowsiness, and gait disturbances; specific side effects to Pregabalin include edema and weight gain [1,6].

Antidepressant Duloxetine binds to norepinephrine and selective serotonin reuptake inhibitors that influence the pain pathway [1,5,6]. Evidence supports the efficacy of Duloxetine for relieving neuropathic pain when compared to Pregabalin and Gabapentin [6]. Effective dose 60 mg and 120 mg everyday orally [1,5,6]. Side effects of Duloxetine include increased blood pressure and lower leg edema [6].

New FDA Warning on Gabapentinoids

Common side effects of gabapentinoids already noted publically is drowsiness and dizziness. However, with the current opioid epidemic there has been a growing concern regarding the overprescribing gabapentinoids for neuropathic pain relief [7]. Additionally, there has been evidence of drug abuse and withdrawal symptoms noted with chronic use [7,8]. Most recently, there has been a new FDA warning label on gabapentinoids due to case reports of respiratory distress in patients with respiratory issues, like COPD, combined with other opioid pain relievers, and combined with other central nervous depressants [9]. Medical professionals should reassess their reliance on first line use of gabapentinoids for treatment of neuropathic pain in patients with respiratory issues.

Discussion

Neuropathic pain is a chronic disorder that can impair a patient’s quality of life. Management of that pain should be addressed empathetically with a rational approach to manage the pain of neuropathy. The results of this literature review demonstrate a need for further research of the existing neuropathic pain medications to understand their specific effects and risks to patients. In closing, we should also continue to emphasize prevention of the progression of diabetic neuropathy with glucose control and lifestyle modifications.

Acknowledgments

The authors sincerely acknowledge the Temple University School of Podiatric Medicine, the Medicine Department, for their support.

References

  1. Pop-Busui R, Boulton AJM, Feldman EL, et al. Diabetic neuropathy: a position statement by the american diabetes association. Dia Care. 2017;40(1):136-154.
  2. Colloca L, Ludman T, Bouhassira D, et al. Neuropathic pain. Nat Rev Dis Primers. 2017;3(1):17002.
  3. Hébert HL, Veluchamy A, Torrance N, Smith BH. Risk factors for neuropathic pain in diabetes mellitus: PAIN. 2017;158(4):560-568.
  4. Wiffen PJ, Derry S, Bell RF, Rice ASC, Tölle TR, Phillips T, Moore RA. Gabapentin for chronic neuropathic pain in adults. Cochrane Database of Systematic Reviews 2017, Issue 6. Art. No.: CD007938..
  5. Raskin J, Pritchett YL, Wang F, et al. A double-blind, randomized multicenter trial comparing duloxetine with placebo in the management of diabetic peripheral neuropathic pain. Pain Med. 2005;6(5):346-356.
  6. Quilici S, Chancellor J, Löthgren M, et al. Meta-analysis of duloxetine vs. pregabalin and gabapentin in the treatment of diabetic peripheral neuropathic pain. BMC Neurol. 2009;9(1):6.
  7. Goodman CW, Brett AS. Gabapentin and pregabalin for pain — is increased prescribing a cause for concern? N Engl J Med. 2017;377(5):411-414.
  8. Quintero GC. Review about gabapentin misuse, interactions, contraindications and side effects. J Exp Pharmacol. 2017;9:13-21.
  9. Research C for DE and. FDA warns about serious breathing problems with seizure and nerve pain medicines gabapentin (Neurontin, gralise, horizant) and pregabalin (Lyrica, lyrica cr). FDA. Published online January 30, 2020. https://www.fda.gov/drugs/drug-safety-and-availability/fda-warns-about-serious-breathing-problems-seizure-and-nerve-pain-medicines-gabapentin-neurontin

Results of total ankle replacement in 71 patients with a follow-up period 6 month to 7 years

by Kirill S. Mikhaylov1*, Alexander Y. Kochish2, Aleksander A. Bulatov3, Evgeniy P. Sorokin

The Foot and Ankle Online Journal 13 (4): 1

The purpose of this study was to analyse the results of treatment in patients with arthritis of the ankle joint (AJ) based on analysis after surgery involving total ankle arthroplasty. We evaluated the efficiency of AJ replacement (71 patients). All patients were divided into two groups: prospective (6, 12 and 24 months) and retrospective (3, 5, and 7 years). The results were evaluated with the help of a visual analogue scale (VAS) and the 100-point AOFAS scale; we also performed X-ray examinations. With regard to AJ replacement, we identified a significant risk factor for the most frequent complication, which was aseptic instability of the implant components. Total ankle replacement (TAR) provides good or satisfactory treatment results in the vast majority of patients examined in the absence of complications: 100% on the VAS and 96% on the AOFAS scale after 2 years; 100% on both scales after 3 years; 92.3% on both scales after 5 years; and 85.7% on both scales after 7 years. At the same time, the dynamics of the various indicators studied were generally similar, but there were also some differences.

Keywords: ankle joint, arthrosis of the ankle joint, ankle arthroplasty, risk factors for poor treatment outcomes

ISSN 1941-6806
doi: 10.3827/faoj.2020.1304.0001

1 – PhD in Medical Sciences, Researcher, Vreden Russian Research Institute of Traumatology and Orthopaedics, St. Petersburg, Russia
2 – Professor, Vreden Russian Research Institute of Traumatology and Orthopaedics
3 – PhD in Medical Sciences, Vreden Russian Research Institute of Traumatology and Orthopaedics
4 – PhD in Medical Sciences, Researcher, Vreden Russian Research Institute of Traumatology and Orthopaedics
* – Corresponding author: web2@mail.ru


The improvement of methods of surgical treatment for patients with late stages of deforming arthrosis of the ankle joint (AJ) is one of the priority goals of modern traumatology and orthopaedics [1, 2]. Currently, patients with the specified pathology undergo two main types of surgery: the first is AJ arthrodesis, which has been used since the beginning of surgical orthopaedics, and the second is total ankle replacement (TAR), which has been used in clinical practice since the 1970s [3, 4] and quickly became an accepted method. According to the literature, both specified methods of surgical treatment have advantages and disadvantages and also show different results in the present day compared with the past. Therefore, the choice of one of these methods presents certain difficulties. Indications and contraindications for performing either of these surgeries are discussed in the following articles [5, 6, 7, 8, 9]. Surgeries of each type are quite often followed by complications and pathological states that substantially worsen the result of treatment in both the short- and long-term. In particular, after AJ fusion, patients often develop degenerate and dystrophic changes in joints of the middle part of the foot, and in addition, compensatory loads of the overlying large joints of the lower extremity lead to increased development of a pain syndrome [7].

Figure 1 a. Deformities of the bones forming the ankle joint in patients of the consequences of ankle joint injuries subgroup: a-radiographs of patient S, 53 years old, with the consequences of a fracture of the distal metaphysis of the tibia; b. X-ray of patient SH, 36 years old, with a consequence of fractures of both ankles.

Operations involving TAR increase the risk of future development of a number of pathological states, such as destruction of the established prosthesis designs, aseptic instability of their components and a deep periprosthesis infection [10, 11, 12]. Therefore, the introduction of TAR has been approached cautiously in clinical practice around the world. Indeed, according to the German register of operations, arthrodesis of the AJ is carried out approximately three times more often than its endoprosthesis replacement; the number of annually established endoprostheses of the AJ is about 1300 [13].

On the other hand, the relevant literature also has suggestions from some orthopaedists to greatly expand the indications for arthroplasty of the AJ [14, 15]. In particular, there are publications describing operations with the angles of varus or valgus deformations in this joint over 200 [16, 17, 18], at the site of tumoural damage of the tibia or talus [19], at defects of the talus [20] and also at the fracture of an earlier arthrodesis of the AJ [21, 22, 23]. The analysis of literature on this subject has convinced us that the comparative efficiency of ankle fusion and TAR operations, especially regarding long-term performance, and also risk factors for the development of a number of pathological states are insufficiently studied and need to be further investigated.

Materials and Methods

We performed an analysis of 71 patients who underwent TAR using three third-generation implants: Mobility (DePuy) 27, Hintegra (NewDeal) 37, and STAR (Waldemar Link) 7. The gender and age characteristics of patients are provided in Table 1 for comparison. Radiological examination showed that most patients had late-stage arthritis of the ankle and was based on the classification of Kellgren et al. [24]. It was found that 15 (21.1%) patients had stage II AJ arthrosis, 41 (57.8%) patients had stage III arthrosis, and 15 (21.1%) patients had stage IV arthrosis (Table 2).

It should be noted that pathological changes in the articular parts of the bones that form the AJ were found mainly in patients with the consequences of injuries to this joint. Thus, 10 (11.5%) patients had deformities of the distal metaphysis of the tibia after fractures (Figure 1 a) and 27 (51.9%) patients had ankle deformities (Figure 1 b), with 5 (9.6%) patients having significant deformities of the talus bone in this clinical subgroup. Among patients with AJ diseases that led to the development of deforming arthrosis, there were only two such observations: one patient (5.3%) with deformation of the distal metaphysis of the tibia and another (5.3%) with significant deformation of the talus bone.

For all patients, we carried out an objective and radiological inspection of the feet, including an X-ray analysis with the necessary projections, and patients also completed visual analogue scale (VAS) and American Orthopaedic Foot & Ankle Society (AOFAS) scores. Of note, all patients included in the research underwent surgery in the clinic by one team of surgeons in order to avoid differences in the result of treatment due to different operational techniques and equipment. It should be noted that, in general, all patients in the considered clinical group had VAS scores ranging from 6 to 10 and AOFAS scores ranging from 12 to 34, which corresponds to poor evaluation categories. In addition, they had pronounced restrictions on the amplitude of movement in the affected AJs (from 16° to 27°), which was significantly worse than normal indicators (on average 39±5°). All these changes are typical for the later stages of development of deforming ankle arthrosis (Table 3).

Average age (years) Sex Total
М F
48.1±4,2 29 (40.9%) 42 (59.1%) 71 (100%)

Table 1 Age and sex of patients of the first clinical group.

II III IV Total
n % n % n % n %
15 21.1 41 57.8 15 21.1 71 100

Table 2 Ankle arthrosis stages.

AOFAS VAS Movement amplitude
25.0±2.0 8.5±0.7 24.0±3.4°

Table 3 Preoperative clinical and functional indicators in patients.

Results

The most frequent reason for unsatisfactory treatment results from 6 months until 7 years after surgery was aseptic instability of components of the AJ. Therefore, special attention was paid in our work to the detection of significant risk factors of this emerging pathological state. We found that, in the prospective group of patients, radiological signs of instability of the established designs were observed 2 years after the surgery in 6 (19.4%) of 31 patients under clinical supervision. However, the presence of a severe pain syndrome and essential decrease in functionality, which necessitated carrying out a repeat operation (fusion), was reported only by one (3.2%) patient of the prospective group.

In the retrospective group from 3 to 7 years after treatment, radiological signs of instability of the components of the AJ were recorded for 16 (40%) of 40 observed patients. In addition, using VAS and AOFAS scores, patients with this complication had worse average values of these indicators (R<0.01) than other patients of the group. However, the revised procedures, including removal of unstable implants with subsequent biarticulate fusion of the ankle and subtalar joints were only carried out by interlocking intramedullary nails in 7 (43.8%) of 16 patients, as the other 9 patients preferred to keep the established endoprostheses. It should be particularly noted that these nine patients had only radiological signs of instability of the endoprosthetic components without essential migration of the bone bed, and they had a satisfactory functional result.

An example of a satisfactory functional result can be observed (Figure 2) 5 years after TAR with the presence of radiological signs of instability of the established construction. However, it is necessary to note that the patient did not demand a high functional load from the operated AJ.

Special attention in our research was paid to the detection of risk factors for developing aseptic instability of endoprostheses of the AJ. A search was carried out concerning two groups of factors noted in the relevant literature [4, 15, 17, 22, 25, 26, 27, 28]. The first group of risk factors included various deformations of the bones forming the AJ. The second group included the age of patients, related physical activity, and functional loads of the operated joints as significant factors. It should be noted that such analyses were carried out separately in the prospective group (31 patients) and in the retrospective group (40 patients). The results are presented in Tables 4 and 5.

The analysis showed that the risk of aseptic instability of the endoprosthetic components of the AJ during all periods of observation was clearly associated with previous fractures of the bones forming the joint. As can be seen, such fractures occurred in 5 of 6 patients with this pathological condition in the prospective group and in 13 of 16 patients in the retrospective group. In addition, we observed that the vast majority of these states (21 of 22 or 95.5%) occurred in patients under the age of 55 years. The proportion of patients with aseptic instability of the implant in the group of patients younger than 55 years was 34.4% (21 of 61) and only 10% (1 of 10) in the group of patients 55 years and older. It should also be noted that, in 19 (86.4%) of the 22 cases of aseptic instability of the endoprosthetic components, these patients performed activities involving high functional loads on the AJ in the postoperative period.

Analysis of the models installed as AJ implants in patients diagnosed with aseptic instability of the implant did not reveal any significant advantages for any one of the three used structures.

Figure 2 The result 5 years after total ankle replacement (left side) in a 42-year-old patient with the use of a Hintera implant (NewDeal). a) Radiological signs of instability of an endoprosthesis: the slight shift backwards of the tibial component and sagging of the talus component due to decreased height of the talus; b) Satisfactory functional result: 3 points on the VAS and 69 points on the AOFAS scale.

The third-generation implants studied implants had similar clinical effectiveness with respect to the development of the discussed pathological conditions. The analysis revealed the following significant risk factors of aseptic instability of the endoprosthetic components of the AJ: previous fractures of bones forming the joint, age of up to 55 years, and high functional load on the operated joints in the postoperative period.

Discussion

A comprehensive study of the results of ankle replacement of up to 7 years conducted in the prospective (31 people) and retrospective (40 people) subgroups of patients allowed us to make some generalizations presented in this section.

First of all, it was shown that operations with the AJ endoprosthesis in the absence of complications provided good or satisfactory treatment results in the vast majority of the examined patients: 100% on the VAS and 96% on the AOFAS scale after 2 years; 100% on both scales after 3 years; 92.3% on both scales after 5 years; and 85.7% after 7 years. At the same time, the dynamics of the various indicators studied were generally similar, but there were also some differences.

In particular, the severity of pain in the area of the operated joint, estimated by VAS, was minimal 2 years after the operation and gradually increased in the future, reaching a maximum by the 10-year follow-up. The functional capabilities of the AJs, determined on the AOFAS scale, reached the maximum average value 6 months after surgical treatment, remained at this level until 3 years, and then gradually decreased over the next 7 years of follow-up. Various indicators of gait biomechanics on the side of the operated joints gradually improved during the first 3 years after implantation of artificial AJs and then gradually deteriorated by the 7-year follow-up period. The amplitude of movements in the AJ (flexion/extension) increased after endoprosthesis on average only by 3–40° and reached the maximum average values, corresponding to about 75% of the norm, after 6 months. In the future, the volume of such movements gradually decreased and was an average of 46% of the norm 7 years after surgery.

However, it should be especially noted that, in the examined patients who did not show signs of aseptic instability of the established AJ components, the average values of almost all the studied parameters (except for the amplitude of movements) even 7 years after the performed operations were significantly better (P<0.05) than the corresponding preoperative values.

Anamnesis Age of patients, years Total
20–39 40–54
Change of a distal metaphysis of tibia 3 (50%) 3 (50%)
Fracture of ankle bones 1 (16,7%) 1 (16,7%)
Fracture of a collision bone 1 (16,7%) 1 (16,7%)
Deforming ankle joint arthrosis 1 (16,7%) 1 (16,7%)
Total 1 (16,7%) 5 (83,3%) 6 (100%)

Table 4 The anamnesis and age of patients who had aseptic instability of ankle joint endoprostheses 2 years after surgery.

Anamnesis Age of patients, years Total
20–39 40–54 55 and older
Change of a distal metaphysis of tibia 3 (18,8%) 3 (18,8%)
Fracture of ankle bones 2 (12,5%) 2 (12,5%) 4 (25%)
Fracture of a collision bone 6 (37,5%) 6 (37,5%)
Deforming ankle joint arthrosis 1 (6,3%) 1 (6,3%) 1(6,3%) 3 (18,7%)
Total 3 (18,8%) 12 (75%) 1(6,3%) 16 (100%)

Table 5 The anamnesis and age of patients who had aseptic instability of ankle joint endoprostheses from 3 to 7 years after surgery.

The above results of our research generally coincide with similar data in the literature. In particular, it is known that the analysis of the outcomes of the Hintegra (NewDeal) endoprosthesis in the period from 1 year to 5 years showed an increase in the AOFAS score on the average from 40.3 to 85.0 points [24]. Another publication presents the results of the Mobility (De Puy) endoprosthesis in 233 patients with an average follow-up period of 32.8 months [25]. It was noted that the function of the joints after the installation of this endoprosthesis improved on the AOFAS scale from an average of 48.2 to 84.1 points, and the pain syndrome on the VAS regressed from an average of 7.7 to 1.7 points. However, the volume of movement in the AJs that were operated on improved on average only by 2.1° (from 19.8° to 21.9°), which is quite consistent with the data we received.

A purposeful comparative analysis of our clinical data allowed us to conclude that, in the long-term postoperative period (3–7 years after the performed operations), there are no significant and reliable (P<0.05) differences in the values of clinical and functional indicators (according to the VAS and AOFAS scales) when using three different models of AJ implants: Hintegra (NewDeal), Mobility (De Puy) and STAR (Waldemar Link). Thus, it was shown that the third-generation implants studied have quite comparable clinical effectiveness in those patients who do not have aseptic loosening of the installed structures.

The analysis of models of installed AJ implants in patients with diagnosed aseptic instability of implants also did not reveal any significant advantage of any of the three designs used. However, in the prospective group, 2 years after surgery, instability of the Mobility (De Puy) endoprosthesis was observed in 3 (30%) of 10 cases, and a similar condition after installation of the Hintegra (New Deal) structure was recorded in 3 (14.3%) of 21 patients. Despite the revealed differences, in our opinion, these data are not enough to make a clear judgment about the advantages of one of these endoprosthetic models of over the other.

Our research has shown that aseptic instability of various components of AJ endoprostheses is a frequent unsatisfactory outcome of operations. In particular, it occurred in 6 (19.4%) of 31 patients of the prospective clinical subgroup by the 2-year follow-up period after surgical treatment. In the retrospective subgroup, 16 (40%) of 40 patients had this pathological condition in the long-term period (from 3 to 7 years) after surgical treatment. In our opinion, the proportion of patients with this condition in the retrospective clinical subgroup was so high, because patients with aseptic instability of implants purposefully went to the hospital, where they performed the primary implant of the AJ endoprosthesis. At the same time, patients with good clinical and functional results did not always agree to undergo additional examination in the long term after surgical treatment. It is likely that if the survey was not 40 patients, but all 116 patients operated on in RNIITO n.a. R. R. Vreden in 2003–2011, the proportion of patients with the discussed unsatisfactory outcomes would have been significantly lower.

The information we received generally coincided with those given by other researchers. Thus, according to various foreign authors, the percentage of patients with aseptic instability of AJ endoprosthetic components varies from 3% to 13.7% in the first 5 years after the surgery [26-27] and from 16% to 32% within 5 to 10 years after the surgery [28-29].

In a retrospective subgroup of our patients, the analysis of cases of aseptic instability of the components of the AJ endoprostheses showed that the largest number of them and, accordingly, the highest proportions of the number of examined patients were recorded within 3 years (5 cases or 17.2%) and 5 years (10 cases or 43.5%) after the performed operations. By the 7-year follow-up period, these indicators decreased (one case or 12.5%), and three patients examined after 10 years showed no signs of aseptic instability of the implants. In addition, it was noted that 3 years after the surgical treatment, X-rays of patients with the considered pathological condition showed signs of loosening only in the tibial components, and in later periods of observation (after 5 and 7 years), signs of instability of both the tibial and talus components were recorded. Thus, based on the data obtained, it can be assumed that usually the tibial components of endoprostheses are loosened first, and then, over time, instability also develops in the talus components of the implants.

It should be noted that the presence of radiographic signs of aseptic instability of AJ endoprosthesis, reducing the functionality of the operated joints (by AOFAS scale) and increasing pain intensity (by VAS), have significant individual differences. Therefore, patients with aseptic instability do not always agree to repeat the operation, which involves the removal of implants and arthrodesis of the AJ. In particular, such revision operations were performed only in 1 (16.7%) of 6 patients in the prospective subgroup and in 7 (43.8%) of 16 patients in the retrospective subgroup. Thus, most of our patients with aseptic instability of the components of the installed endoprosthesis preferred to keep the installed implants and refused arthrodesis of the AJ.

The facts described above indicate that X-ray signs of instability of AJ components do not always have pronounced clinical manifestations. In our opinion, this feature explains the large variation in the numbers of unsatisfactory results discussed in the publications of various authors. It should also be noted that our work took into account the X-ray signs of aseptic instability of the installed implants, which determined a fairly high percentage of patients with such negative results.

Special attention in our study was paid to determining the risk factors for the development of aseptic instability of AJ endoprostheses. The following factors were identified: technical errors in positioning the endoprosthetic components, the young age of patients (up to 55 years) and the associated high functional loads on the operated joints, as well as deformities of the tibial and talus bones that form the articular surfaces of the AJ that occurred as a result of previous injuries. Taking this into account, it is clear why the proportion of patients with the considered pathological condition was higher in the subgroup of patients with the consequences of ankle joint injuries (CAJI) than in the subgroup with diseases of this joint (DAJ). However, the analysis showed that the risk factor for developing this condition is not so much the presence of a history of AJ injuries as it is the existing deformities of the tibia and talus bones.

It should be noted that, according to the special literature, technical errors of implantation are considered an important cause of aseptic instability of AJ endoprostheses, which predetermine up to 15% of unsatisfactory results. Some authors noted that the positioning ratios of the tibial and talus components had a direct effect on the occurrence of pain and instability of implant components. Correct surgical technique and correct positioning of endoprosthetic components relative to the mechanical axis helped to increase the durability of the installed structures [30-32].

Some authors have developed their own classifications of the unsatisfactory results discussed. For example, Glazebrook and co-authors (2009) proposed dividing negative outcomes into high-value, moderate-value, and low-value outcomes. At the same time, infection in the area of surgical approach and aseptic instability of the prosthesis were highly significant; errors during implantation were moderately significant; and difficulties during the healing of postoperative wounds were insignificant. It should be noted that, due to the technical difficulties of installing AJ endoprostheses and ensuring good integration with bone tissue, the problem of aseptic instability of such implants has not yet been completely eliminated. It continues to be actual. The associated severe pain syndrome and reduced functionality are common causes of revision operations.

Also, it should be noted that there are publications in the special literature with indications of a direct link between the development of aseptic loosening of the AJ components and causes of pronounced deformities of the articular surfaces of the tibia and talus bones [33-34], as well as the young age and high physical activity of patients, which determine the increased functional workloads on the operated joints [35].

References

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  3. Stoyanov AV, Emelyanov VG, Pliev DG, et al. Ankle joint replacement (review). Traumatology and Orthopedics of Russia. 2011;(1):144–52. (In Russ.)
  4. Hintermann, B. Total ankle arthroplasty: history overview, current concepts and future perspectives. New York: Springer; 2005.
  5. Jordan RW, Chahal GS, Chapman A. Is end-stage ankle arthrosis best managed with total ankle replacement or arthrodesis? A systematic review. Adv Orthop. 2014;2014:986285.
  6. Koryshkov NA, Larionov SV, Murashova NA, et al. Anesthesia in surgeries of the foot and ankle (review). Traumatology and Orthopedics of Russia. 2012;(3):118–26. (In Russ.)
  7. Chou LB, Coughlin MT, Hansen S Jr, et al. Osteoarthritis of the ankle: the role of arthroplasty. J Am Acad Orthop Surg. 2008;16:249–59.
  8. Glazebrook MA, Arsenault K, Dunbar M. Evidence-based classification of complications in total ankle arthroplasty. Foot Ankle Int. 2009;30:945–9.
  9. Jiang JJ, Schipper ON, Whyte N, et al. Comparison of perioperative complications and hospitalization outcomes after ankle arthrodesis versus total ankle arthroplasty from 2002 to 2011. Foot Ankle Int. 2015;36:360–8.
  10. Borkosky SL, Mankovecky M, Prissel M, et al. Polyarticular sepsis originating from a prior total ankle replacement. Clin Podiatr Med Surg. 2013;30:97–100.
  11. Schipper ON, Haddad SL, Pytel P, et al. Histological analysis of early osteolysis in total ankle arthroplasty. Foot Ankle Int. 2017;38:351–9.
  12. Lee AY, Ha AS, Petscavage JM, et al. Total ankle arthroplasty: a radiographic outcome study. Am J Roentgenol. 2013;200:1310–6.
  13. Kostuj T, Preis M, Walther M, et al. German Total Ankle Replacement Register of the German Foot and Ankle Society (D. A. F.) – presentation of design and reliability of the data as well as first results. Z Orthop Unfall. 2014;152:446–54. (In German)
  14. Bibbo C. Controversies in total ankle replacement. Clin Podiatr Med Surg. 2013;30:21–34.
  15. Coetzee JC. Surgical strategies: lateral ligament reconstruction as part of the management of varus ankle deformity with ankle replacement. Foot Ankle Int. 2010;31:267–74.
  16. Schuberth JM, Christensen JC, Seidenstricker CL. Total ankle replacement with severe valgus deformity: technique and surgical strategy. J Foot Ankle Surg. 2017;56:618–27..
  17. Hobson SA, Karantana A, Dhar S. Total ankle replacement in patients with significant preoperative deformity of the hindfoot. J Bone Joint Surg Br. 2009;91:481–6.
  18. Reddy SC, Mann JA, Mann RA, et al. Correction of moderate to severe coronal plane deformity with the STAR ankle prosthesis. Foot Ankle Int. 2011;32:659–64. Erratum in: Foot Ankle Int. 2011 Sep;32(9):vi.
  19. Lampert C. Ankle joint prosthesis for bone defects. Orthopade. 2011;40:978–83. (In German).
  20. Mikhaylov KS, Emelyanov VG, Bulatov AA. Staged bilateral ankle arthroplasty for the treatment of patient with severe defect of the talus (case report). Traumatology and Orthopedics of Russia. 2013;(2):105–10. (In Russian)
  21. Atkinson HD, Daniels TR, Klejman S, et al. Pre- and postoperative gait analysis following conversion of tibiotalocalcaneal fusion to total ankle arthroplasty. Foot Ankle Int. 2010;31:927–32.
  22. Hintermann B, Barg A, Knupp M, et al. Conversion of painful ankle arthrodesis to total ankle arthroplasty. J Bone Joint Surg Am. 2009;91:850–8.
  23. Hintermann B, Barg A, Knupp M, et al. Conversion of painful ankle arthrodesis to total ankle arthroplasty. Surgical technique. J Bone Joint Surg Am. 2010;92 Suppl 1 Pt 1:55–66.
  24. Hintermann, B. The HINTEGRA ankle: short- and mid-term results. Orthopade. – 2006. – Bd. 35, H. 5. – S. 533-545.
  25. Rippstein, P.F. Total ankle replacement with use of a new three-component implant. J Bone Joint Surg. – 2011. – Vol. 93-A, N 15. – P. 1426-1435.
  26. Anderson, T. Uncemented STAR total ankle prostheses. Three to eight-year follow-up of fifty-one consecutive ankles. J Bone Joint Surg. – 2003. – Vol. 85-A. – P. 1321-1329.
  27. Barg, A. Total ankle replacement using HINTEGRA, an unconstrained, three-component system: surgical technique and pitfalls. Foot Ankle Clin. – 2012. – Vol. 17, N 4. – P. 607-635.
  28. Preyssas, P. Total ankle arthroplasty – three-component total ankle arthroplasty in western France: a radiographic study. Orthop Traumatol. Surg. Res. – 2012. – Vol. 98. – S. 31-40.
  29. Barg, A. HINTEGRA total ankle replacement: survivorship analysis in 684 patients. J Bone Joint Surg. Am. – 2013. – Vol. 95, N 13. – P.1175-1183.
  30. Bonasia, D.E. Total ankle replacement: why, when and how? Iowa Orthop. J. – 2010. – Vol. 30. – P. 119-130.
  31. Park, J.S. Total ankle arthroplasty. NYU Hosp. Jt. Dis. – 2011. – Vol. 69. – P. 27-35.
  32. Ng, S.Y. Total ankle replacement for rheumatoid arthritis of the ankle. Foot Ankle Clin. – 2012. – Vol. 17, N 4. – P. 555-564.
  33. Wood, P.L. Total ankle replacement: the results of 100 Mobility total ankle replacements. J Bone Joint Surg. – 2010. – Vol. 92-B, N 7. – P. 958-962.
  34. Weatherall, J.M. Post-traumatic ankle arthritis. Bull Hosp. Jt. – 2013. – Vol. 71, N 1. – P. 104-112.
  35. Winters, B.S. The use of allograft in joint-preserving surgery for ankle osteochondral lesions and osteoarthritis. Foot Ankle Clin. – 2013. – Vol. 18, N 3. – P. 529-542.

 

 

 

A systematic review of injectable corticosteroid for osteoarthritis of the first metatarsophalangeal joint

by Ian Reilly BSc, MSc, MCPod, FCPodS, FFPM RCPS(Glasg); Gillian Bromley BSc(Hons), MCPod; George Flanagan BSc(Hons), MCPod, FCPodS

The Foot and Ankle Online Journal 13 (3): 12

Intra-articular steroid injection is a common treatment modality for relief of pain and inflammation associated with degenerative joint disease. Use of injectable steroid preparations is widely accepted as safe and effective for the treatment of osteoarthritis of the 1st metatarsophalangeal joint. Despite the frequency of use, literature specific to pathology of the 1st metatarsophalangeal joint is sparse. The aim of this systematic review was to determine if good quality research exists to enable clinicians to adopt an evidenced based approach to corticosteroid injection of the 1st metatarsophalangeal joint. Despite the frequency of use, this review found no high quality studies that support the use of intra-articular corticosteroid injection of the 1st metatarsophalangeal joint in osteoarthritis.

Keywords: steroid injection, first metatarsophalangeal joint, osteoarthritis, hallux rigidus, systematic review

ISSN 1941-6806
doi: 10.3827/faoj.2020.1303.0012

1 – Department of Podiatric Surgery, Northamptonshire Healthcare Foundation NHS Trust, Danetre Hospital, Daventry, Northamptonshire, NN11 4DY. UK
* – Corresponding author: ianreilly@nhs.net


The use of injectable corticosteroid as part of a treatment strategy for painful joints is a common treatment modality. In degenerative disease the intended aim is to reduce the pain and inflammation associated with osteoarthritis (OA) as well as improve joint function [1]. The use of intra-articular (IA) corticosteroid injections (CSIs) for the treatment of OA is supported by guidelines provided by the United Kingdom (UK) National Institute for Health and Care Excellence (NICE) in patients who experience joint pain that is not adequately controlled by oral and/or topical options or where such treatment is contraindicated [2]. The basis for this guidance is largely derived from conclusions drawn from research into the efficacy of IA CSI’s at the knee and shoulder [3,4]: data from these studies has been extrapolated and applied to other synovial joints such as the first metatarsophalangeal joint (1st MPJ).

Osteoarthritis is the leading cause of disability in adults worldwide and results in significant morbidity [5]. Joints in the foot are often affected by this condition with the 1st MPJ being most commonly affected pedal joint [6]. Symptomatic 1st MPJ OA affects approximately 10% of the adult population and the prevalence increases with age – as do comorbidities amongst sufferers – with the result that reduced pharmacological treatment options available for pain relief in these patients [7]. Symptoms arising from OA are notoriously difficult to manage with oral analgesics alone: this ultimately results in a significant burden on primary care services [8]. This provides the niche for IA CSI, i.e. where other conservative treatment has failed, is contraindicated or where there is a desire or requirement to postpone the need for surgical intervention. Unmanaged foot pain is an independent risk factor for depression and falls in adults [9,10,11].

The authors are experienced injectors and are active in teaching CSI techniques to under- and postgraduate students. Anecdotally, we find that 80-90% of patients experience improvement following IA CSI for 1st MPJ OA but the extent and duration of that improvement varies. The variability in outcomes following CSI for 1st MPJ OA raises numerous questions: to what extent is pain reduced? Is joint function improved? Which patients are most likely to benefit from this treatment? What is the frequency with which corticosteroid should be administered and whether the use of ultrasound guided injections improves treatment outcomes [12,13,14]. Furthermore, there has been debate surrounding whether a steroid based solution, when combined with local analgesia, may even be chondrotoxic [15]. A Cochrane Review from 2010 [16] concerned with identifying optimal treatment modalities for 1st MPJ OA found low level evidence for physical therapy only. A systematic literature review was therefore undertaken (as part of a larger body of work being undertaken by the lead author) in order to identify randomized trials that had used IA CSI for OA of the 1st MPJ.

Methods

The research question is: is the use of corticosteroid injections for osteoarthritis of the first metatarsophalangeal joint in adults a safe and effective method of reducing pain and improving joint function?

In order to ensure a systematic review, minimize the risk of bias and provide transparency for replication of the process, a predetermined research methodology protocol was used, based on the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) checklist [17]. This was registered with PROSPERO. (Trial registration number: CRD42019135950. Available from: http://www.crd.york.ac.uk/PROSPERO/display_record.php?ID=CRD42019135950).

Selection criteria

Inclusion

Predetermined inclusion and exclusion criteria were used. Only systematic reviews, randomized controlled trials (RCTs), quasi randomized trials and controlled clinical trials were considered for inclusion as they form the hierarchy of evidence and are most likely to provide a robust evidence base suitable for informing clinical practice [18]. Those papers found were then screened for the following criteria:

  • Trials in which an IA CSI into the 1st MPJ used for the treatment of OA in adults,
  • Diagnosis and grading of OA in participants could be achieved via clinical examination and/ or via radiological means [19],
  • Any gender or ethnicity was considered.

In order to be able to determine the efficacy of treatment, trials were required to have provided quantitative or qualitative measures both pre- and post-intervention in order to be able to ascertain the mean differences relating to pain and/or joint function outcomes.

Exclusion

Trials in which intradermal, subcutaneous, intramuscular or extracapsular corticosteroid injections were performed were excluded, as were not trials that tested the efficacy of IA CSIs for conditions other than for OA, or tested CSIs at joints other than the 1st MPJ. Due to the high risk of bias, cohort and case studies, articles based on expert opinion, retrospective studies and narrative-based literature reviews were excluded [18].

Search strategy and data sources

To answer the research question a keyword search of six electronic databases (AMED, CINAHL, EMBASE, MEDLINE, PUBMED, and COCHRANE) up to February 2020 was undertaken by graduate research podiatrist (GB) to identify clinical trials that had tested the efficacy of IA CSI for the treatment of 1st MPJ OA.

AMED (1985 to 05.02.2020)

CINAHL (1982 to 05.02.2020)

EMBASE (1974 to 05.02.2020)

MEDLINE (1950 to 05.02.2020)

PUBMED (1966 to 05.02.2020)

COCHRANE (1966 to 05.02.2020)

No date or language restrictions were applied. Reference lists were reviewed, and key author searches were made to reduce the risk of any pertinent literature being missed. A list of keywords and results yielded are provided in Table 1.

# Database Search term Results
1 AMED (osteoarthritis).ti,ab 2945
2 AMED (hallux).ti,ab 1252
3 AMED (metatarsophalangeal).ti,ab 771
4 AMED (injection).ti,ab 2035
5 AMED (steroid).ti,ab 454
6 AMED (hallux limitus).ti,ab 62
7 AMED (hallux rigidus).ti,ab 178
8 AMED (1 AND 2) 35
9 AMED (1 AND 3) 37
10 AMED (6 OR 7 OR 8 OR 9) 272
11 AMED (4 AND 10) 5
23 CINAHL (osteoarthritis).ti,ab 21838
24 CINAHL (hallux).ti,ab 2033
25 CINAHL (metatarsophalangeal).ti,ab 1197
26 CINAHL (injection).ti,ab 43132
27 CINAHL (steroid).ti,ab 15241
28 CINAHL (hallux limitus).ti,ab 100
29 CINAHL (hallux rigidus).ti,ab 319
30 CINAHL (23 AND 24) 63
31 CINAHL (23 AND 25) 82
32 CINAHL (28 OR 29 OR 30 OR 31) 472
33 CINAHL (26 AND 32) 13
34 EMBASE (osteoarthritis).ti,ab 79498
35 EMBASE (hallux).ti,ab 5812
36 EMBASE (metatarsophalangeal).ti,ab 3924
37 EMBASE (injection).ti,ab 581417
38 EMBASE (steroid).ti,ab 163137
39 EMBASE (hallux limitus).ti,ab 153
40 EMBASE (hallux rigidus).ti,ab 664
41 EMBASE (34 AND 35) 183
42 EMBASE (34 AND 36) 258
43 EMBASE (39 OR 40 OR 41 OR 42) 1068
44 EMBASE (37 AND 43) 21
45 EMBASE (38 AND 43) 12
46 CINAHL (27 AND 32) 5
48 AMED (5 AND 10) 4
49 Medline (osteoarthritis).ti,ab 54837
50 Medline (hallux).ti,ab 4904
51 Medline (metatarsophalangeal).ti,ab 3209
52 Medline (injection).ti,ab 449653
53 Medline (steroid).ti,ab 125109
54 Medline (hallux limitus).ti,ab 139
55 Medline (hallux rigidus).ti,ab 586
56 Medline (49 AND 50) 137
57 Medline (49 AND 51) 189
58 Medline (54 OR 55 OR 56 OR 57) 858
59 Medline (52 AND 58) 13
60 Medline (53 AND 58) 5
61 PubMed (osteoarthritis).ti,ab 80277
62 PubMed (hallux).ti,ab 6554
63 PubMed (metatarsophalangeal).ti,ab 4096
64 PubMed (injection).ti,ab 708493
65 PubMed (steroid).ti,ab 936715
66 PubMed (hallux limitus).ti,ab 167
67 PubMed (hallux rigidus).ti,ab 656
68 PubMed (61 AND 62) 251
69 PubMed (61 AND 63) 298
70 PubMed (66 OR 67 OR 68 OR 69) 1054
71 PubMed (64 AND 70) 26
72 PubMed (65 AND 70) 10

Table 1 Search terminology and results yielded by database.

Risk of bias

In order to assess their validity, RCTs were reviewed using the Critical Appraisal Skills Programme (CASP) checklist [20], which uses six quality assessments of studies and considers the risk of (selection, performance, detection, attrition and reporting) bias. Systematic reviews were appraised using a Centre for Evidence-Based Medicine (CEBM) appraisal tool for systematic reviews [21] which uses six quality assessments to determine validity of reviews based on methodological design. Each quality assessment for data was awarded a ‘low’, ‘high’ or ‘unclear’ risk of bias. Two reviewers independently (GB, GF) appraised the studies and results were collated. If there was disparity between results, a discussion was to be raised. If consensus could not be achieved the senior author (INR – a consultant podiatric surgeon with a special interest in injection therapy) was appointed to make the final decision. Evidence from the identified literature was considered and an appropriate weighting awarded based on the quality of evidence they provided.

Initial inter-rater results following an appraisal of studies was 84% consistent between two reviewers. Following a discussion regarding the variation in quality assessment, 100% consensus between reviewers was achieved. Evidence from the identified literature was considered and an appropriate weighting awarded based on the quality of evidence they provided. Themes regarding joint pain, function and the safety of CSIs are discussed. Due to only one RCT being identified for inclusion, no meta-analysis was possible.

Data extraction

Data was extracted from research that fulfilled the inclusion criteria by using a predetermined list of parameters to determine the efficacy of the intervention and validity of methods used for testing.

Figure 1 PRISMA flow chart for trials selected for review [17].

These parameters considered: the design of study, sample size, demographics, diagnostic criteria used, disease severity, intervention tested (type, dosage, method of administration), outcomes, follow up and results. Reported adverse effects (type, duration and severity) were recorded to determine the safety of the intervention. Data from these themes was entered into a spreadsheet to be used for discussion.

Results

A search of electronic databases identified 111 studies for possible inclusion. Sixty-four duplicates were excluded and 47 titles and abstracts were assessed. Titles and abstracts were assessed independently (GB and GF) and evaluated against the aims of this study and its predetermined selection criteria. Full-text articles believed to be appropriate were accessed and further assessed for relevance against the predetermined inclusion criteria. If there was a difference in opinion as to whether an article should be included for review, a discussion was raised between the two main authors and if it was not possible to reach a consensus then the senior author was given the final vote on selection. 36 articles were rejected and 11 full-text articles were retrieved for assessment against the selection criteria (Figure 1). One RCT and one systematic review were identified for inclusion in this review.

Randomized controlled trials

One single blinded randomized trial that compared the efficacy of a single dose of intra-articular triamcinolone acetonide (TA) with sodium hyaluronate (SH) delivered without image guidance for mild symptomatic hallux rigidus in thirty-seven adults was identified for inclusion [22] – see Table 2. The title of the paper was misleading (sodium hyaluronate in the treatment of hallux rigidus. A single blind randomized study) in that its use of CSI was not mentioned.

Pons et al. 2007 [22]
Quality Assessment: Result: Bias Risk: Quality score:
Did the trial ask a clearly focused question? Yes Screening question 2/2
Was the assignment of patients randomized? Unclear Selection bias 1/2
Were all the patients who entered the trial properly accounted for at its conclusion? Yes Attrition bias, reporting bias 2/2
Were patients, health care workers and study personnel ‘blind’ to treatment? No Performance bias, detection bias 0/2
Were the groups similar at the start of the trial? Unclear Selection bias 1/2
Aside from the experimental intervention, were the groups treated equally? Yes Performance bias 2/2

Table 2 Quality assessment of randomised controlled trials (CASP checklist).

Zammit et al. 2010 [16]
Quality Assessment: Result: Quality Score:
What question did the systematic review address? Which interventions are optimal for treating osteoarthritis of the big toe? 2/2
Is it unlikely that important, relevant studies were missed? Yes 2/2
Were the criteria used to select articles for inclusion appropriate? Yes 2/2
Were the included studies sufficiently valid for the type of question asked? No, identified a lack of available evidence and high risk of bias. 0/2
Were the results similar from study to study? One study identified for inclusion only. 0/2

Table 3 Quality assessment of systematic reviews (CEBM framework).

Changes in joint pain and function

A reduction in mean visual analogue scale (VAS) pain scores at rest or on palpation was observed in both treatment groups. Mean VAS scores (n/100 mm) reduced at baseline from 58.7 mm to 34.1 mm in the TA group. A significant decrease in dorsiflexion or plantarflexion VAS pain scores was also observed in both groups: mean VAS scores decreased from 64.2 mm to 41.6 mm in the TA group. TH demonstrated reduced improvement in VAS pain scores on walking 20 metres compared to SH. Recipients of TA were reported to have a mean improvement in hallux function of 4.1 on the American Orthopaedic Foot and Ankle Society Score (AOFAS) for hallux evaluation. Overall, TA was found to be inferior in terms of the number positive responders to treatment, pain reduction and improvement in hallux function when compared to those treated with SH. Benefits were reported as relatively short lasting in both arms of the trial: 52.9% in the TA group and 46.6 % in the SH group progressed to surgery within 12 months.

The mean quality score for the RCT reviewed was 66% demonstrating limited methodological quality and potential bias. In this trial there was no attempt to blind investigators involved in data collection and evaluation of outcome measures. The trial had a small sample size with a significant female gender bias and all participants had mild joint disease potentially limiting the application of conclusions drawn from this to other patient populations. However, the most significant limitation with this trial was that interventions were administered to participants with 1st MPJ OA and hallux valgus with no sub-group analysis provided according to condition. This caused the paper to be rejected from the 2015 Cochrane review [16]. Given that the underlying pathophysiology of these distinct conditions differs, it is reasonable to expect that treatment outcomes relating to joint pain and function following an IA SCI may vary between recipients with different conditions. Furthermore, the proportion of recipients reported to have progressed to surgery may have been skewed given that the usual treatment for hallux valgus is surgical correction of the deformity. From this trial it was not possible to determine the efficacy of corticosteroids as an intervention to treat osteoarthritis at the 1st MPJ.

Adverse effects

Similarly, the lack of blinding in data collection and evaluation of adverse effects associated with the interventions administered poses a significant bias risk. Due to the lack of sub group analysis it was not possible to determine whether the frequency or type of adverse effects differed by condition. Data relating to adverse effects was collected by non-blinded investigators post intervention, were mild and arose in just 5% of recipients; no serious adverse effects were reported.

Systematic reviews

A recent review [14] that set out to provide a comprehensive list of evidence-based recommendations regarding conservative treatment modalities for 1st MPJ OA included a review of injection therapy. Authors of the review found ‘fair evidence’ to support the use of IA CSIs to treat 1st MPJ OA. However, the methodology was neither systematic nor comprehensive: only a single database was searched for clinical trials and the risk of pertinent literature having been missed was high. The author’s recommendations were made based on an appraisal system [23] that allocates a level of evidence for an intervention based solely on the design of studies identified; it does not consider the methodological quality of trials or risk of bias. Rama [24] pointed out that this system is a derivative of the levels of evidence system [25] and cautioned regarding the limitations of this style of review. He highlighted the need to not generalise evidence in order to avoid misleading conclusions being drawn.

The injection therapy trials identified in this review lacked heterogeneity in terms of solutions tested and design of trials. In spite of this, the authors grouped six trials relating to injection therapy together for data analysis and a collective level of evidence was allocated to injection therapy as a whole. Since this review did not consider the risk of bias and validity or clinical significance of outcomes from trials it identified, and failed to use a systematic methodology the study was excluded from this review as it was deemed to provide a summary of interventions for healthcare professionals only [24].

This review identified one systematic review that considered the efficacy of any treatment modality, including but not limited to injection therapy, for 1st MPJ OA [16]. The 2010 systematic review (see table 3) was a comprehensive piece of research with high quality methodology and low risk of bias. It identified one low quality study with a high risk of bias to support the use of physical therapy to reduce the pain of osteoarthritis at the big toe joint. It found no evidence to support the efficacy of corticosteroid injections for hallux rigidus (see note above re Pons et al, 2007).

Discussion

Originally suggested by Cotterill in 1887 [26], hallux rigidus/limitus (1st MPJ OA) are terms used to describe arthritic changes at the 1st MPJ. Many theories regarding the etiology of 1st MPJ OA have been postulated. Traditionally, osteoarthritis was viewed simply as a degenerative condition characterized by the degeneration of joint cartilage over time that resulted in progressive pain, stiffness and loss of joint function. However, a greater understanding of the pathophysiology of osteoarthritis indicates that symptoms arising from the disease are caused by the body’s attempt to repair damaged cartilage and that it is this process of repair and remodelling that results in abnormal bone growth and inflammation that involves the entire joint [16].

In a review of 114 patients it was found that irrespective of age, females are twice as likely to develop 1st MPJ OA [27]. A positive family history is strongly associated with bilateral joint disease, whereas unilateral joint involvement is often precipitated by trauma and does not routinely progress to involve both feet. Little consensus exists between studies regarding other possible causes although Coughlin and Shurnas [27] discuss pes planus, Achilles tendon contracture, hallux valgus, hallux valgus interphalangeus, a flat metatarsal head, metatarsus adductus, a long first metatarsal, metatarsus primus elevatus, and first ray hypermobility in the development of this condition. Furthermore, a number of recent retrospective studies that have considered the natural course of 1st MPJ OA suggest that progression of the disease is far more variable than previously thought and that for many it may follow a more benign course with symptoms that can be adequately managed with conservative treatment methods such as physical, mechanical or pharmacological therapy [28]. It is therefore increasingly important for clinicians to understand when to administer IA CSIs and which patients would derive the greatest benefit from treatment.

Corticosteroid is a synthetic version of the endogenous hormone glucocorticoid found in vertebrates that is produced in the adrenal gland cortex. Amongst its other functions in the cardiovascular, metabolic and nervous systems; glucocorticoids provide a feedback mechanism within the immune system to reduce inflammation. Synthetic corticosteroids administered orally or via injection can be exploited to mimic this action and can be used to suppress unwanted, immune mediated inflammatory responses caused by many disease processes including osteoarthritis. Corticosteroids act to reduce inflammation and suppress the immune response at various levels:

  • Leukocytes and monocytes transform into macrophages, a larger and more bactericidal cell that releases lysosomal enzymes that ushers in further inflammatory processes. By suppressing the adhesion of leukocytes, the formation of macrophages is reduced which inhibits the release of lysosomal enzyme and leads to a reduction in further inflammation [29].
  • Lymphocytes aid in activation of T cells and macrophages that have been produced causing rapid division and cytokine secretion. Cytokines are associated with both the initial activation and ongoing sensitization of the nociceptive receptors on sensory neurons perceived as chronic pain mediators. By reducing the effect of lymphocytes by depleting the amount of T cells and secretion of cytokines pain is reduced [30].
  • Cytokines are also responsible for releasing eicosanoid, a signalling molecule that stimulates other inflammatory mediators including histamine and prostaglandins. Both histamine and prostaglandins cause vasodilation of the surrounding blood vessels. This vasodilation leads to increased swelling and also contributes to the sensitisation of nerves resulting in pain perception. By reducing vasodilation and stimulation of pain receptors swelling and pain are reduced [31].

This systematic review was conducted in order to assess the effectiveness and safety of intra-articular corticosteroid injection as a treatment modality for 1st MPJ OA. A thorough and systematic literature search was completed in order to identify pertinent literature on the subject area and forty-seven studies were identified for possible inclusion. After exclusions were applied from the selection criteria to ensure that the correct condition, joint and treatment were being considered 11 pieces of literature remained of which two have been considered in detail. The remaining literature was mainly comprised of studies that provide low level evidence such as narrative reviews, retrospective case studies or non-controlled clinical trials.

One single blind randomized trial that compared the efficacy of a single corticosteroid injection with hyaluronate was identified [22]. A critical appraisal of this trial found it to have a high risk of bias. Furthermore, the solutions administered to participants were for two distinct conditions, hallux valgus and hallux rigidus and no details for sub group analysis were provided. It was therefore not possible to determine what influence this may have had on the outcome measures relating to pain reduction and improved joint function for hallux rigidus. From this trial it was not possible to determine with any level of certainty or specificity the efficacy of corticosteroids as an intervention to treat osteoarthritis at the hallux.

CSIs are generally considered safe drugs with steroid flare being the most commonly reported adverse event, though rare complications that may arise following administration of intra-articular steroid including anaphylaxis, disturbance of menstrual pattern and avascular necrosis [32]. Data relating to adverse effects was collected by Pons, et al., post intervention were mild, and arose in just 5% of recipients. It was not possible to determine the quality of reporting of adverse effects in this trial or whether adverse effects arose in hallux valgus and/or hallux rigidus joints. However, the reported rate of adverse effects is homogenous with the 6% rate of mild adverse effects reported by following 1,708 steroid injections into both soft tissue and joints of the foot and ankle [33]. The most common side effect reported was a steroid ‘flare’, an acute inflammatory reaction to the steroid solution which made up 75% of the reported side effects. Vasovagal episodes, facial flushing, local skin reactions, short term paraesthesia and a temporary increase in blood glucose levels were also reported but were rare. No infections were reported by the study, a result consistent with the view that joint infection is a very rare complication resulting in septic arthritis. No adverse effects following the administration of 22 CSIs for hallux rigidus were noted by Grice, et al., [34] although they do report that the positive results (seen in 20 of the 22 patients) only lasted longer than three months in three of that cohort. At two years, two patients (9%) remained asymptomatic, but 12 patients (55%) had undergone surgery. Peterson and Hodler [35] and Kilmartin [36] also note that most adverse effects experienced following an intra-articular joint injection of steroid are mild and transient and can be managed by the patient with self-care advice. These papers support the anecdotal view that in general, CSIs are safe and that adverse effects tend to be moderate and time-limited.

Numerous narrative reviews exist regarding treatments for hallux rigidus and include CSIs but provide no evidence-based recommendations for treatment. An exception to this was a comprehensive review [14], the aim of which was to provide evidence-based recommendations regarding conservative treatment modalities for hallux rigidus and included a review of injection therapy. Authors of the review based their recommendations on an established appraisal system [23] that allocates a level of evidence for an intervention based on the design of studies identified. Rama [24] pointed out that this system is a derivative of the widely established levels of evidence system [25] and cautioned regarding the limitations of this style of review. He highlighted the need to not generalize evidence in order to avoid misleading conclusions being drawn. King, et al., grouped six trials relating to injection therapy together for data analysis regardless of the fact that interventions and trial designs differed. A ‘collective’ level of evidence was allocated to injection therapy in general rather than by individual solutions. This led to skewed results given that the quality of trial design that had tested hyaluronate was superior to other interventions such as corticosteroid. Given that this review did not use a methodology that considered the risk of bias, validity or clinical significance of results of trials this study was excluded from this review as it was deemed to provide a narrative review.

One systematic literature review that included an appraisal of the efficacy of corticosteroid injections for osteoarthritis at the big toe joint [16] was included in this review. The Cochrane review was well designed, well executed and found to have a low risk of bias. Zammit, et al., [16] did not identify any robust evidence to support the efficacy of corticosteroid injections for the treatment of hallux rigidus and made no recommendations regarding its safety due to the high risk of bias. This view is consistent with the findings of this review that found it was only possible to make generalizations relating to the safety of intra-articular corticosteroid injections.

This review did not find evidence of sufficient quality to confirm whether intra-articular corticosteroid injections are an effective intervention for the management of symptomatic osteoarthritis at the 1st MPJ. The current literature that exists was found to be of poor methodological design. In the only randomized controlled clinical trial that tested corticosteroid, it was found to be mildly inferior to hyaluronate in terms of pain reduction for patients with mild osteoarthritis [22]. However, in a robust randomized placebo controlled [38] trial of intra-articular injections for osteoarthritis no benefit was derived from sodium hyaluronate vs saline placebo.

Conclusion

There are a number of narrative reviews concerned with the conservative and surgical treatment modalities that can be used to inform the management of symptomatic hallux rigidus. A number of cases and retrospective [26,27] studies have evaluated the use of injectable corticosteroids in the foot or ankle but controlled clinical trials in this area are few.

Many interventions exist that are intended to reduce the symptoms associated with OA of the 1st MPJ. In spite of the lack of evidence to support their use, IA CSI remains popular amongst health care professionals and patients alike because they are quick and inexpensive to administer with the perception of rapid relief, minimal recovery time and few side effects [32]. In cases of mild osteoarthritis, some retrospective studies indicate that CSIs may provide months and occasionally, years of relief for hallux rigidus [28]; a retrospective study by Smith, et al., in 2000 [37] found 75% of patients that had previously declined surgical treatment for symptomatic hallux rigidus were happy with this decision, had not experienced an increase in pain undergone despite degeneration of the joint, and were able to manage symptoms with stiff soled shoes and accommodative footwear. It is unclear whether progression to surgery has any association with the administration of intra-articular corticosteroid but given the risk of chondrotoxicity [15] this warrants further investigation.

This review found no high quality evidence to support the use of IA CSI as an effective treatment modality for symptomatic 1st MPJ OA. Uncertainty regarding variables that may influence treatment outcomes such as concomitant footwear use [39] remains. Existing research that tested intra-articular corticosteroid was found to be of poor methodological design with a high risk of bias. High quality, randomized, controlled clinical trials that test the efficacy of IA CSI are required. The severity of 1st MPJ OA amongst recipients in trials should be classified prior to intervention by clinical and radiological examination [19] and a sub group analysis of outcome measures provided according to disease severity. Further research to determine whether treatment outcomes are improved by the use of image guidance, extrapolation of side effects [40] and whether the use of IA CSI in 1st MPJ reduces surgical burden would be beneficial.

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Expansive unicameral bone cyst occupying the distal tibia: A case report

by Andrew Robitaille, DPM1*; Lawrence M. Fallat, DPM, FACFAS 2

The Foot and Ankle Online Journal 13 (3): 11

Unicameral bone cysts (UBC) of the distal tibia are usually incidental findings. We present a case of a 50-year-old female who initially presented with chronic bilateral heel pain. Initial radiographs revealed plantar heel spurs, but also a large intraosseous cyst in the distal right tibia. Computed tomography was obtained which showed a large, multiseptated, lucent, expansile bone lesion in the central medullary canal the distal metaphyseal-diaphyseal junction of the distal tibia. To prevent fracture of the thin cortex and stop expansion of the cyst, surgical intervention was chosen. This case report serves to show how standard x-ray revealed a large UBC that could result in fracture of the distal tibia.

Keywords: bone tumor, cyst, unicameral, tibia, benign

ISSN 1941-6806
doi: 10.3827/faoj.2020.1303.0011

1 – Resident, Submitted during Postgraduate Year 1, Beaumont Hospital, Wayne, MI, Podiatric Foot and Ankle Surgical Residency
2 – Director, Beaumont Health Wayne Podiatric Foot and Ankle Surgical Residency, Beaumont Hospital, Wayne, MI
* – Corresponding author: andrew.robitaille@beaumont.org


Unicameral bone cysts (UBC) are relatively uncommon benign bone tumors found mostly in the metaphysis of long bones, such as the humerus or femur with a male to female ratio of 3:1 [1]. UBC represents about 3% of primary tumors seen within the first two decades of life. In a meta-analysis by Kadhim, et al., in 2014, the distal tibia was only affected by UBC in 0.07% of reported cases [1]. Most of these lesions go unnoticed as they are usually asymptomatic in the absence of pathologic fracture [2]. In 1876, Virchow first described these lesions as cystic structures caused by abnormalities in local circulation [3].

Treatment goals for UBC include reestablishing bone strength, cortical thickness and elimination of the cyst [1,2]. There are various treatment modalities for UBC, which include conservative and surgical treatment [4]. Before surgical intervention, a thorough examination and clinical history must be obtained. Plain film radiography is usually sufficient for visualization and diagnosis of bone tumor [1]. Computed tomography (CT) or magnetic resonance imaging (MRI) should be obtained to evaluate the extent, size, and character of the tumor for treatment planning [2].

In this report, we present an unusual case of an adult female patient who was diagnosed on standard radiographs with an incidental finding of a large cystic lesion occupying the metaphyseal-diaphyseal region of the distal tibia. With the aid of CT, the lesion was further evaluated and then surgically treated with curettage and filled with allogenic bone chips and demineralized bone matrix (DBM).

Case Report

A 50-year-old female presented to the clinic with the chief complaint of bilateral plantar heel pain. Plain films were obtained and a large cystic lesion was noted to the patient’s right distal tibia (Figure 1). The patient denied any inciting event. Upon physical exam, there was mild dull pain at the end range of dorsiflexion to the right ankle, but was otherwise unremarkable. Computed tomography (CT) of her right ankle was obtained to further evaluate the cystic lesion.

Figure 1 Lateral and anteroposterior radiographs showing initial clinical presentation of a large expansive cystic lesion of the distal tibia.

Figure 2 Computed tomography imaging revealing a large multiseptated cyst in the metaphyseal-diaphyseal junction of the tibia with noted thinning of the medial cortex.

CT results showed a large, multiseptated, lucent, expansile bone lesion with thin medial cortex in the central medullary canal in the metaphyseal-diaphyseal junction of the distal tibia. The lesion measured 3.9 x 4.1 x 6.8 cm (Figure 2). The patient was booked for surgical excision and curettage of the right distal tibia bone cyst with insertion of allogenic bone graft, DBM, and included a biopsy.

The patient was brought into the operating room and placed on the operating room table in the supine position. General anesthesia was administered. The right lower extremity was prepped, marked and draped in the usual aseptic manner and a pneumatic thigh tourniquet was then inflated to 325mmHg.

Figure 3 A) Cortical window on the anterior distal tibia B) Cystic contents which included fatty tissue with hard and soft bone.

Figure 4 Intraoperative anteroposterior and lateral views after filling of cyst cavity with allograft and demineralized bone matrix. Also shown is the fixation of the bone window with one third tubular plate with two 3.5mm nonlocking cortical screws placed proximally and one distally.

An anterior incision 8 cm in length, just medial to the tibialis anterior tendon, was made overlying the anterior ankle which allowed direct visualization of the distal tibia. Four drill holes were made in the anterior tibia outlining the planned cortical window which measured 4 cm x 2cm. The window was cut and removed in one piece revealing the contents of the cyst which contained multiple osseous septa with both hard and soft bone (Figure 3). The entire area of the bone cyst was curetted and excised. Complete cyst excision was confirmed with fluoroscopy and direct visualization. It was noted that there was a large posterior portion of the cyst tunneling 2 cm proximally and inferiorly from the cortical window. Following intramedullary debridement, the cortex remained intact on all sides with no evidence of fracture.  All the material was removed from the cyst and was sent to pathology. The cavity of the cyst was irrigated and 89% phenol was applied to the entire bone cyst area.

Figure 5 Histological slides displaying fragments of sclerotic trabecular bone, consistent with unicameral bone cyst (original magnification 10x and 40x, hematoxylin and eosin).

Due to the large defect post-curettage, the cavity was filled with a combination of crushed allogenic bone chips and DBM. The cystic cavity was completely packed and the bone window was replaced and tamped into position. To prevent displacement of the cortical window, a 7-hole 1/3 tubular plate was placed anteriorly with a distal bend to fit the contour of the tibia. Alignment of the plate was confirmed both visually and with fluoroscopy. Following this, two 3.5 non-locking cortical screws were placed proximal, and one 3.5 non-locking cortical screw was placed distally (Figure 4). The surgical site was flushed with copious amounts of antibiotic solution and closure was completed. Following the procedure, the patient was placed in a well-padded, bivalved, below-the-knee cast and instructed to remain non-weightbearing with the use of crutches. She was prescribed hydrocodone for pain and aspirin 325 mg twice daily to be taken for deep vein thrombosis prophylaxis. The pathology specimen revealed fragments of sclerotic trabecular bone with spindle cells, most consistent with unicameral bone cyst (Figure 5).

Figure 6 Anteroposterior and lateral foot view of patient at twelve months postoperatively highlighting complete consolidation of cortical window.

The patient continued to present to the clinic on a regular basis for postoperative evaluation and serial radiographs. On the first two postoperative appointments (week 1 and 3), the patient’s visual analog pain score (VAS) was 2 out of 10. Radiographs showed incorporation of bone graft material and the patient was allowed to partial weight bear as tolerated. By the patient’s third postoperative appointment (8 weeks), the patient’s VAS score was 0 out of 10. Radiographs were taken, revealing consolidation of the cortical window in the right tibia with no recurrence of bone cyst. At this time, the patient was transitioned into normal shoe gear and sent to physical therapy with goals of decreasing edema, increasing range of motion, and increasing strength. At the patient’s one-year follow-up, radiographs were taken revealing no recurrence of bone cyst and the patient remained asymptomatic and had no limitations on full activity (Figure 6).

Discussion

Multiple theories have been postulated for the pathogenesis of unicameral bone cysts. Blockage in the venous drainage is the most favored mechanism which occurs in rapidly growing and remodeling cancellous bone [2, 3, 4]. This increased pressure may lead to the resorption of bone. Others have postulated that there could be a disturbance in bone growth, intramedullary hemorrhages secondary to trauma that do not completely resolve, degenerative phase of benign tumor, and osteomyelitis [2,10]. Cyst fluid analysis has shown increased levels of prostaglandin e2, IL1 beta, and proteolytic enzymes which could lead to bone resorption and cyst formation [5].

Treatment for UBCs is either observation or surgical intervention [2]. Reported surgical treatment includes medullary decompression with cannulated screws or intramedullary nails, steroid injections, or curettage with autograft or allograft [1, 2, 5-8]. Scaglietti, et al., were first to describe percutaneous injection of methylprednisolone acetate for UBC treatment in 1974 with only 24% healing rate after one injection [8]. Several authors have found satisfactory results with healing rates between 50-90% with steroid injections, but most reported that several procedures were necessary for cyst consolidation [1,6]. It has been reported that steroid injection may prevent the pro-inflammatory cytokine activity that leads to cyst formation as well as to relieve cyst pressure due to trepanation [1, 8].

Other injectable materials including bone graft and demineralized bone matrix (DBM) have been evaluated. Lokiec, et al., in 1996 was the first to report the use of autologous bone marrow injections for UBC treatment in children with 100% success rate [9]. Other studies have used bone marrow graft in combination with DBM [7, 11]. These studies attribute the high success rate due to bone marrow’s osteoprogenitor cells in combination with the osteoinduction and osteoconduction properties of DBM [7, 11]. Multiple authors have evaluated the effectiveness of DMB alone as an injection with high success rates [6,7]. Cho, et al., in 2012 evaluated twenty-five patients with a unicameral bone cyst who were treated with intramedullary decompression followed by grafting of demineralized bone matrix [2]. They used a small incision to create a cortical window to allow for curettage and decompression of the cyst and subsequently injection a mixture of allograft bone and DMB. Their success rate was 100% with a mean healing time of 6.6 months. Two patients required a second procedure, which they determined the initial amount of bone void filler was not enough to fill the entire space. The authors concluded that mixture of bone graft material, DBM, and completely filling the cyst was successful with satisfactory results [2].

Due to the size of our patient’s cyst, we used a longer incision and created a cortical window over the anterior distal tibia. This approach made it possible for visualization and use of curettes to completely remove all cyst material and to obtain a biopsy. This approach may appear more aggressive than other reported procedures, but because of the large size of the cyst and age of the patient, it was necessary for visualization and complete curettage, biopsy, and filling of the cyst with allograft and DBM. Similar techniques have been reported from multiple authors with healing rates greater than 90% [1, 6, 7]. The surgical curettage is necessary to resolve the cyst, but also allows for biopsy, which is necessary to rule out malignancy such as Ewing’s sarcoma and osteosarcoma because they also present as cystic lesions radiographically [5].

Unicameral bone cysts are usually incidental finding with many factors that could contribute to their formation. Although there is no standardized treatment for UBC, the goal of treatment is to prevent pathological fracture and, in children and adolescents, to prevent skeletal deformities during growth. Surgical procedures such as curettage with allogenic bone graft have been shown to be successful treatment with low rates of recurrence [1, 6, 7]. The surgical curettage is necessary to obtain tissue for biopsy to determine pathology including Ewing’s sarcoma and osteosarcoma [5]. In this report, we present a patient who was treated successfully with surgical curettage and allogenic bone graft for a distal tibia UBC with no cyst recurrence after one year. Long-term clinical follow-up is necessary for observation of potential cyst recurrence.

References

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  2. Cho, HS, Seo, SH, Park, SH, Park, JH, Shin, DS, & Park, IH. Minimal invasive surgery for unicameral bone cyst using demineralized bone matrix: a case series. BMC Musculoskelet Disord 2012;13:124.
  3. Virchow R. On the formation of bony cysts, in Uber die Bildung von Knochencysten. In SB Akad Wiss, 1876; pp 369–381, Berlin.
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  6. Kanellopoulos AD, Mavrogenis AF, Papagelopoulos PJ, Soucacos PN. Elastic intramedullary nailing and DBM-bone marrow injection for the treatment of simple bone cysts. World Journal of Surgical Oncology 2007;5, 1:111.
  7. Rougraff BT, Kling TJ. Treatment of active unicameral bone cysts with percutaneous injection of demineralized bone matrix and autogenous bone marrow. J Bone Jt Surg Am 2002;84-A 6:921–929.
  8. Scaglietti O, Marchetti PG, Bartolozzi P. Final results obtained in the treatment of bone cysts with methylprednisolone acetate (depo-medrol) and a discussion of results achieved in other bone lesions. Clin Orthop Relat 1982;165:33‐42.
  9. Lokiec F, Ezra E, Khermosh O, Wientroub S: Simple bone cysts treated by percutaneous autologous marrow grafting. A preliminary report. J Bone Joint Surg 1996;78: 934-937.
  10. Rosario, MS, Yamamoto, N, Hayashi, K, Takeuchi, A, Kimura, H, Miwa, S, Tsuchiya, H. An unusual case of proximal humeral simple bone cyst in an adult from secondary cystic change. World Journal of Surgical Oncology 2017;15:102.
  11. Di Bella C, Dozza B, Frisoni T, Cevolani L, Donati D. Injection of demineralized bone matrix with bone marrow concentrate improves healing in unicameral bone cyst. Clin Orthop Relat 2010;468: 3047-3055.

Treatment criteria for madura foot: Case report and literature review

by Wathmi Wijesinghe, MS21; Andrew Lee, MS21; Adrienne Estes, DPM2; David Shofler, DPM, MSHS2; Laura O’Connell, DPM3

The Foot and Ankle Online Journal 13 (3): 10

Mycetoma is a chronic granulomatous infection of the skin and underlying tissues, which affects remote populations in tropical and subtropical countries. We report the case of a 35-year-old male with an over 10 year history of left foot mycetoma, who initially presented with diffuse non-draining papules, edema, and dull chronic pain of the left foot. Radiographic imaging depicted erosive changes throughout the left midfoot and forefoot, while bone biopsy of the left navicular and first metatarsal confirmed actinomycetes. After being prescribed amoxicillin-clavulanate and trimethoprim-sulfamethoxazole and undergoing surgical debridement, the patient had marked improvements with less frequent pain and fewer blisters. One year later, the patient’s ankle joint remained untouched by mycetoma, yet his condition began to deteriorate with the reemergence of draining granules and chronic pain. As of now, the patient has been scheduled for below-the-knee limb amputation. The treatment of mycetoma aims to preserve limb function and prevent recurrences, but further research and investigations are necessary.

Keywords: Actinomycetoma, eumycetoma

ISSN 1941-6806
doi: 10.3827/faoj.2020.1303.0010

1- Podiatric Medical Student, Western University of Health Sciences
2- Assistant Professor of Podiatric Medicine, Surgery & Biomechanics, Western University of Health Sciences
3- Podiatric Medicine and Surgery Resident, Chino Valley Medical Center
* – Corresponding author: andrew.lee@westernu.edu


Mycetoma, also known as Madura foot, is a neglected tropical disease that induces a granulomatous inflammatory response in the subcutaneous tissue or deep dermis. The etiology of mycetoma can be fungal or bacterial, respectively termed as eumycetoma or actinomycetoma. Even though mycetoma is dispersed throughout the world, it was found to be indigenous to tropical and subtropical areas between latitudes 15° South and 30° North, an area commonly known as the “Mycetoma Belt”. Male populations living in these rural areas earn for their families by engaging in manual labor without proper footwear. Thus, transmission most commonly occurs through lacerations from cactus thorns, corn husks, or acacia trees. Manifestation includes foot pain with swelling and firm lesions to the site of laceration; raised ulceration sites; draining sinus tracts; and induration [1]. Diagnosis is best approached with biopsy, organism granule evaluation, serological and molecular methods, and imaging [1,2]. Magnetic resonance imaging (MRI) is generally more sensitive than radiographs, especially at earlier stages [1]. An antifungal or antibiotic regimen in conjunction with surgical debridement is considered to be the gold standard for treatment [1,2]. In its advanced stages, mycetoma may invade deeper structures including muscle, fascia, and bone and increase the risk of mortality or severe disability via amputations [1].

Treatment and management of mycetoma have been difficult in rural regions due to factors such as low health education, poor access to health care, social stigma, and socioeconomic burden; thus resulting in late presentation to clinical care and poor compliance to treatment [3]. It has been difficult to correct these factors as there is a limited bank of research and knowledge about mycetoma around the world. There is an increased need for more epidemiological studies to obtain a clear understanding and accurate data on transmission, prevalence, and incidence of this condition [4]. Though advanced diagnostic techniques are available in resourceful regions, health care professionals in endemic regions mostly rely on visual inspection for diagnosis thus increasing the need for more accessible diagnostic modalities [5]. Research on more aggressive treatments for mycetoma and the implementation of prevention methods may be required to improve the quality of life of the patient. However, when medication and surgical debridement are not the solution, health care professionals may resort to amputation to reduce the risk of mortality in these patients [6].

In the present report, we describe a 35-year-old male presenting with an advanced manifestation of this uncommon clinical condition. A review of the condition, including presentation, conservative treatment options, and surgical treatment options, is then discussed.

Case Report

A 35-year-old male construction worker with a history of a heart murmur and streptococcal pharyngitis presented for podiatry consultation for left foot pain and swelling in December, 2017. He was unclear on how the pain occurred. However, there was a high suspicion for Madura foot on this patient by his primary care physician (PCP). Further discussion in a follow-up visit revealed injuring himself from a corn husk while working on a corn field in Mexico. The symptoms had been slowly progressing over the preceding 10+ years before he presented to our care in 2017. The patient reported the pain to be chronic and dull. He had no known allergies, pertinent surgical history and pertinent family history. His medications included 875mg-125 mg per tablet of oral amoxicillin-clavulanate (Augmentin) which needs to be taken 2x day and 800mg-160mg per tablet of oral trimethoprim-sulfamethoxazole which needs to be taken 2x day. His physical exam of the extremities revealed hyperpigmentation and rigidity on the entire left foot with pain on the medial aspect (Figures 1 and 2). Papules were evident diffusely with no obvious purulence or drainage. This consultation ended with discussions and informed consent for his left foot bone biopsy as requested by his PCP.

Figure 1 Clinical image at presentation, Left dorsal foot. Hyperpigmentation noted diffusely from digits, extending proximally to the ankle with patches of fibrotic hypopigmentation.

Figure 2 Clinical image at presentation, Left plantar foot. Roughened, plantar bumps and papules of mycetoma with contour irregularity and hyperpigmentation.

A bone biopsy was performed on the left first metatarsal and the navicular. The first metatarsal biopsy was 0.5 cm in length and 2 mm in diameter for a dumbbell shaped portion of brown-colored osseous tissue. The pathology report of the first metatarsal identified benign-appearing fibro-osseous tissue however it was in part non-viable. The navicular bone biopsy was several fragments of light tan-colored osseous tissue measuring in aggregate of 0.5×0.2×0.2 cm. The report identified osseous tissue with numerous plasma cells, acute inflammation, periosteal fibrosis, and aggregates of filamentous microorganisms indicative of actinomycetes.  Wound cultures were positive for Staphylococcus aureus.

Radiographic images demonstrated destructive and erosive changes throughout the left midfoot and forefoot (Figure 3). An MRI revealed rounded lesions of intermediate signal with low signal central foci in the talar neck and body, calcaneus, cuboid, navicular, tarsal bones, cuneiforms, and metatarsals. Nodules were present in the dorsal soft tissue, medial soft tissue adjacent to the first metatarsal, and the plantar soft tissue adjacent to first and second metatarsals. Soft tissue edema was also noted extending to sinus tarsi. Bone marrow edema and intraosseous/extraosseous lesions surrounded by subcutaneous edema were identified with enhancement. Increased signal intensity on T2 views was evident of the intrinsic musculature and of the distal aspect of flexor hallucis longus muscle.

Three months later, he demonstrated marked improvements with only 1-2 blisters resurfacing with intermittent throbbing pain for 1-2 times per month. At this point, his surgical history included left foot biopsy, irrigation, and debridement of his left foot. He was still on the same medication plan however has not been consistent with his management of Madura foot. His physical exam revealed improved edema on his left foot but mild serous drainage from the dorsal aspect were present. And, indurated skin was present from digits to rear foot without any pain. Given the slow progression of the infection at that point, it was decided to continue his medications and closely monitor his conditions to see whether it reached the ankle joint.

After one year has passed, he presented with worsening pain over the past 4 months with granules which open and close. His current medications included a 500mg capsule of oral cephalexin (Keflex) which needed to be taken 1 capsule 2x daily. Next medication was 5-325mg per tablet of oral hydrocodone-acetaminophen (NORCO) which needed to be taken 1 tablet every 6 hours prn. Next medication included an 800 mg tablet of oral ibuprofen which needed to be taken 1 tablet every 8 hours prn. His physical exam of the lower extremity revealed improved edema on the left foot however with an appreciable amount of drainage. Indurated skin was present from digits to rear foot. Pain was noted on midtarsal joint range of motion.

Figure 3 Radiographic images taken in June, 2017. Left foot dorsoplantar view. Degeneration and erosions throughout the midfoot and forefoot with superimposed sclerosis and significantly narrowed joint spaces.

His recent x-ray images taken in December of 2019 have revealed the extent of erosions from phalanges to calcaneus however erosions still have not penetrated the ankle joint.

He continued to cycle between improvements and deterioration of symptoms. This may be attributable to his non-compliance to the given recommendations such as taking the appropriate medications in a timely manner and frequent visits to the health care providers. At this time, he has been experiencing deterioration of his symptoms with worsening pain and granule drainage. Therefore, he consented to a below the knee amputation (BKA) in hopes of obtaining permanent relief of his symptoms. As of now, the amputation was scheduled to take place sometime in 2020.

Figure 4 MRI image, sagittal view of the left foot. Rounded lesions of intermediate signal with low signal central foci were present in the talar neck and body, calcaneus, cuboid, navicular, tarsal bones, cuneiforms, and metatarsals. Soft tissue nodules were present in the dorsal soft tissue, medial soft tissue adjacent to the first metatarsal, and the plantar soft tissue adjacent to first and second metatarsals.

Figure 5 MRI axial view of the calcaneus, depicting rounded lesions of low to intermediate signal intensity with low signal central foci, characteristic of mycetoma.

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Figure 6 X ray images taken December, 2019. Degeneration and erosions have increased in number throughout midfoot and forefoot with superimposed sclerosis and significantly narrowed joint spaces. The erosions had extended to involve the rear foot with involvement of talus and calcaneus. However, his erosions still have not reached the ankle joint.

Discussion

Mycetoma is a chronic granulomatous infection of the subcutaneous tissue caused by true fungi (eumycetoma) or filamentous bacteria (actinomycetoma) residing in various habitats, including soil and residing organisms such as earthworms. Thus, mycetoma poses an occupational hazard to cultivators, farm laborers, shepherds, or agricultural workers. Offending bacterial or fungal pathogens penetrate via an abrasion site to permeate subcutaneous tissues. The infection remains dormant until spreading to deeper tissues and skeletal systems. Early diagnosis may be essential for better prognosis of these conditions however patients seeking medical treatment are usually at late stages making management extremely difficult [1]. Some of the contributing factors may include misdiagnoses and the lack of resources, trained health care professionals, and familiarity of the condition [4].

Clinical manifestations of mycetomas are similar despite the causative microorganism. Current research does not define a precise incubation period but suggests that it may range from three months to 50 years. During early stages, pain is not an essential component of the clinical picture. Overall the initial appearance of mycetoma can be characterized by papules, nodules, abscesses or indurated tissue without clear boundaries [3]. With time, draining nodules expel grains from interconnected sinuses tracking from the innermost abscesses [7]. Fungal organisms tend to generate different colors but mostly white or black granules, whereas bacterial granules generate a range of colors except black. Even though these granules help the offending organisms to evade immune detection, granule colorations are not pathognomonic for diagnostic purposes [8].

The advanced stage is characterized by a triad of symptoms including swollen, indurated, and deformed tissues; numerous communicating sinus tracts; and discharging aggregates of granules [9,10]. The affected skin retains the ability to heal draining sinus tracts, however, new tracts continuously form with discharge from various deep abscesses [1]. As the granuloma enlarges, the affected skin continuously deforms as a result of stretching of skin, pigmentation, and hyperhidrosis. Sweat gland hyperplasia and hypertrophy may be a consequence of overactivation of sympathetic nerves and/or rise in temperature due to extensive vascularization of the enlarging lesion [1,7]. During the period preceding highly advanced stages, this vascularization is apparent on angiography as dilated and convoluted arterial branches and veins proximal to the affected skin [1]. Blood supply is sufficient to preserve nerves and tendons until advanced stages of mycetoma [3,7]. During the advanced stages, pain may result from subsequent bacterial infections, metastasis to bone, and nerve damage. Despite the shared similarities in clinical presentation of mycetoma, it is notable that actinomycetoma is rapidly destructive and tends to extend to bone faster than eumycetoma [3]. Actinomycetoma was reported to invade the lymphatic system in rapid fashion leading to enlarged region lymph nodes [7]. Ultimately, delayed care can limit options and lead to poor outcomes, which may include severe disability, limb amputation or the need for multiple staged surgical excisions [4].

According to Hay et al., many health care professionals in endemic regions mostly rely on dermatological manifestations of the affected region for diagnosis due to lack of a required training and availability and economic burdens of other diagnostic tools [5]. This may contribute to numerous false positive outcomes and delays in accurate treatment for patients [11]. Since patients present in advanced stages of mycetoma, other diagnostic modalities are imperative to determine the extent of disease, staging of the disease, rule out differential diagnoses, such as Yaws and elephantitis, and confirm the exact causative treatment before starting treatment [12]. Cultures can be isolated via swab of sinus drainage or fine needle aspiration to distinguish the etiological agent, but cultures tend to be unreliable due to species variation, time needed for specimen growth, and high risk of contamination. Serological diagnosis via immunoelectrophoresis and enzyme-linked immunosorbent assay (ELISA) is another diagnostic option but is costly and unreliable with the need for purified antigens and the cross-reactivity between organisms. Yet, these disadvantages may be overcomed via histopathology [7].

Histopathology is a required diagnostic procedure with the potential to distinguish between eumycetoma and actinomycetoma before starting treatment [3,7]. Specimens need to be obtained from a deep surgical biopsy from a deep sinus tract or abscess to avoid contamination [7]. Grains can be visualized via Hematein-eosin-safran (HES), Periodic acid Schiff, and Gomori silver staining. More specifically, H&E staining illustrates eumycetoma as branched hyphae that arrange in groups and form vacuoles. Actinomycetoma with H&E staining demonstrates granules that are surrounded by eosinophilic fringe. Despite these benefits of histopathology, a major drawback includes the ability to only identify the mycetoma type not the causative agent [6].

In Western countries, molecular systematic protocols have been adapted to identify particular species and genera, allowing accurate selection of appropriate treatment options [11]. For actinomycetoma, 16S rRNA gene sequencing, PCR coupled with restriction endonuclease analyses, DNA fingerprinting with PCR amplification, or mass spectrometry can be employed to ascertain etiological species. For eumycetoma, fungal species can be recognized through PCR on an internal transcribed spacer sequence on fungal ribosomal DNA regions, PCR-restriction fragment length polymorphism analysis, and molecular typing via restriction endonuclease analyses and amplified fragment length polymorphism analyses [1,11] Despite these advantages, molecular diagnostics should not be a substitute for traditional methods, as molecular techniques are typically unavailable and costly in endemic regions [3]. Thus, traditional methods in conjunction with diagnostic imaging should be ordered initially if possible.

Diagnostic imaging is essential for confirmation of appropriate pathology and disease severity. Radiographic evaluation of mycetoma can be characterized by soft tissue edema, periosteal reactions, thickened and eroded cortex, destroyed joints, moth eaten appearance, osteopenia, and osteolysis [13]. Radiographic details suggestive of eumycetoma include a small number of bone lesions which are typically ≥ 1 cm in diameter while actinomycetoma contains more numerous, but smaller bone cavities [8]. Radiographic stages are defined in order to determine the severity and direction of metastasis. Radiographic stages are defined in order to determine the severity and direction of metastasis. Stage 1 features an enlarging granuloma with external pressure on bone. Stage 2 demonstrates periosteal reaction or reactive sclerosis. Stage 3 depicts the first indication of osseous involvement with erosion or cavitation on a single bone. Stage 4 demonstrates vertical progression into a single bone. Stage 5 is characterized by metastasis in horizontal direction to affect neighboring structures. Stage 6 is the most advanced stage of progression with metastasis of multiple planes [13].

Ultrasound is preferred for an accurate diagnosis of mycetoma even though it might not be readily available in endemic regions [1]. Granuloma containing granules adapt unique appearances which may aid in ruling out differential diagnoses and distinguishing actinomycetoma from eumycetoma [12]. The most distinguishing feature to confirm mycetoma diagnosis from ultrasound images is the “dot in the circle sign”. This sign can be defined by multiple round hypoechoic lesions with a hyperechoic focus in the center [4]. Doppler ultrasound can demonstrate the effect on mycetoma on vasculature of the affected region. Also, bacterial and fungal grains with a capsule and the accompanying granuloma have distinguishing ultrasound features which may be helpful in ruling out differential diagnoses [12]. Ultrasound can be helpful to determine the severity of mycetoma which may be essential for surgical planning [3].

In addition to ultrasound, MRI images are accepted to be highly essential in examining the extent of lesions and metastasis to adjacent structures [1]. Dot in the circle sign is not solely seen on ultrasound as it may be seen on MRI as oval hyperechoic lesions with a hypoechoic center [14]. On MRI images, high signal regions represent inflammatory granuloma while low signal regions within represent the granules. This is highly pathognomonic of mycetoma. Despite these advantages, MRI is expensive in rural regions, requires a high level of expertise to interpret the results and cannot be used to discriminate between actinomycetoma and eumycetoma [3,12].

Medical Management

The treatment and outcome of mycetoma depend on the causative agent and stage of disease progression [7]. Generally, patients with actinomycetoma have more favorable prognoses to medical treatment than those with eumycetoma [13]. Greater drug penetrance, due to the smaller granules (~1µm diameter) in actinomycetoma, effectively supports a wider array of antibiotic regimen options [15,16]. Since the 1960s, trimethoprim-sulfamethoxazole (TMP-SMX) has been the gold standard for first-line treatment of actinomycetoma, either as monotherapy or in conjunction with dapsone, a penicillin, or an aminoglycoside for more resistant organisms [17]. Currently, combination drug therapy is recommended to avoid resistance and enhance efficacy [7,18]. Antibiotic sensitivity testing should be performed to select the most optimal combination, treatment duration, and number of cycles, all of which vary from case-to-case and depend on soft-tissue or osseous involvement [6,16].

The Welsh regimen is a well-acknowledged combination therapy that has achieved cure rates of more than 90% in previous studies [16,19]. Interestingly, most of the cases from Welsh’s studies were from Mexico, where 98% of mycetoma is due to actinomycetes (86% is further classified as Nocardia brasiliensis) [20]. During the intensive phase, intramuscular amikacin (15 mg/kg/day) is administered in two divided doses, combined with oral TMP-SMX (7+35 mg/kg/day) in three divided doses for 21 days. One to three cycles are performed at 15-day intervals. While in the maintenance phase, oral TMP-SMX (7+35 mg/kg/day) is administered at the same dose for 15 days after the last cycle [3,16,21]. Using the Welsh regimen as a template, other case studies have published modifications to optimize drug efficacy [16].

Damle et al. modified the Welsh regimen by incorporating rifampicin, which resulted in successful remission of all 16 patients included in the study who had all previously had unsatisfactory responses to therapy [16,22]. Rifampicin was specifically selected for its potency as a second-line drug and its medical familiarity within developing regions in the treatment of leprosy and tuberculosis. Agarwal et al. then modified the procedure presented by Damle et al. by increasing the number of cycles to three cycles in cases with soft-tissue involvement and up to five cycles in those with osseous involvement.

Another well-established treatment schedule is the modified two-step Ramam regimen, which consists of intravenous gentamicin (80 mg) twice daily and oral cotrimoxazole (320/1600 mg) twice daily for 4 weeks in the intensive phase. The successive step includes oral doxycycline (100 mg) twice daily and oral cotrimoxazole (320/1600 mg) twice daily in the maintenance phase until five-six months after the complete healing of all sinus tracts is noted [3,16,23]. Although amikacin is the preferred aminoglycoside due to less nephrotoxicity and its characteristic resistance to bacterial aminoglycoside-inactivating enzymes, the Ramam regimen instead utilizes gentamicin primarily due to cost [16,23].

In patients with allergy or noted drug resistance, TMP-SMX can be substituted with amoxicillin-clavulanate, and amikacin can be replaced by netilmicin [1,6]. Additionally, amoxicillin-clavulanate can be used as monotherapy during pregnancy. Amikacin can also be combined with a carbapenem in cases refractory to sulfonamides [1,24]. Importantly, patients must be routinely monitored during and in between treatment cycles for any adverse effects from antimicrobial usage [6]. Especially for amikacin or other aminoglycosides, testing for renal, liver, and auditory function should be performed every three to five weeks to detect potential toxicity [25]. Surgery is rarely indicated in actinomycetoma, but may be advantageous for reducing disease load in larger lesions to enhance drug response or to control secondary bacterial infections in unresponsive patients [19,26].

Eumycetoma is associated with larger granules and extensive fibrosis, thus requiring more prolonged treatment durations ranging from one-to-three years for eumycetoma, compared with three months to one year for actinomycetoma due to lower drug penetrance [8,15]. Itraconazole (200-400 mg daily) for 9 to 12 months followed by surgical intervention has demonstrated favorable clinical responses in many studies and is currently the gold standard for treating eumycetoma [8,27]. In prior decades, Ketoconazole (400-800 mg daily) was a popular antifungal regimen, but has more recently fallen out of favor due to the risk for liver and adrenal toxicity [1,6]. It should be noted that disappointing and inconsistent results are common in pharmacotherapy of eumycetoma with recurrence rates between 20% and 90% [11,13]. Itraconazole and ketoconazole may not necessarily be curative, but their extended usage has exhibited the formation of thick fibrous capsules around the lesions, thus promoting the localization of disease for an easier and more complete surgical excision [7,26]. In a 20-patient open-label study, high-dose terbinafine (1000 mg daily) was administered for 24-48 months and demonstrated moderate efficacy. Results stated that 25% of patients were cured, while 55% had notable clinical improvement by the completion of the study [27,28]. Newer antifungal drugs from the azole class are currently being investigated for their promising potential, featuring broad spectra, low toxicity and favorable bioavailability [6,11].

Treatment therapies for both actinomycetoma and eumycetoma must be continued until the conditions for complete cure are met. Those criteria include clinical healing of sinus tracts, complete resolution of soft tissue masses both clinically and radiologically, restoration of normal osseous appearance with radiological evidence of remodeling, cytological absence of granules, and ultrasonographic absence of cavities [7,26].

Surgical Intervention

Generally, mycetoma of fungal origin requires more extensive surgical management than that of bacterial etiology [19]. In cases with no osseous involvement, wide surgical excision is indicated for localized early lesions to reduce disease burden and to facilitate therapeutic response [7,19,29]. If osseous involvement is confirmed, surgical debridement can be carefully performed to remove granules and damaged tissue from the cavities [6].

Amputation may be considered in advanced stages of mycetoma, when massive osseous destruction, secondary bacterial infection, or sepsis occur [6]. Still, is it important to note that amputation will not necessarily result in a complete cure, as noted by high postoperative recurrence rates of 25% to 50% [2]. In a 1013 patient retrospective study by Wadal, et al., several indicators were correlated to predicting post-operative recurrences, including lesion size greater than 10 cm at initial presentation, positive family history of mycetoma, previous surgeries, and disease duration of more than five years [30]. In addition, surgeons must meticulously excise with wide margins to ensure adequate excision of infected tissues or there may be a risk of new satellite lesions forming from lymphatic spread [2,6,26].

Limb amputation is accompanied by significant socioeconomic, functional and psychological consequences. Mycetoma most commonly affects young men between 20 and 40 years of age, who are generally the highest producers and earners in endemic communities [1]. Disabilities and deformities resulting from mycetoma can compromise employment and relationship opportunities in adults, while children are susceptible to becoming socially rejected and discontinuing education [3]. In a 2015 case study of two drug-resistant patients, Maiti, et al., examined the outcomes between an actinomycetoma patient who had undergone amputation after 9 years of treatment and an eumycetoma patient who continued to manage the slow progression of disease for 16 years after refusing amputation. The actinomycetoma patient was diagnosed with moderate depression post-amputation and also developed disease recurrence on her amputated stump 3 years later. The eumycetoma patient, however, maintained sufficient functionality for daily activities and was spared from anxiety or depression associated with amputation [31]. Thus, Maiti, et al., proposed that symptomatic management of drug-resistant mycetoma may perhaps be more beneficial to a patient’s quality of life than amputation and the corresponding morbidities [31].

Conclusion

Mycetoma is an exceedingly rare condition that is most commonly encountered in underdeveloped regions. Experimental studies and randomized clinical trials may help determine the efficacy of various treatment regimens to prevent the progression of Mycetoma to more advanced stages [11]. Further, there exists a need for further research and development of a standardized treatment regimen available at low cost in endemic countries.

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Distraction osteogenesis for treatment of a shortened first metatarsal after failed first metatarsophalangeal joint arthroplasty

by Tyler Reber DPM1*; Lindsey Hjelm , DPM2; Mallory Schweitzer, DPM, AACFAS3; Craig E Clifford, DPM, MHA, FACFAS, FACPM4

The Foot and Ankle Online Journal 13 (3): 9

Distraction osteogenesis is well documented in the literature as a viable treatment option for large bony defects and brachymetatarsia. Few studies have examined the use of this technique after failed arthrodesis or arthroplasty of the 1st metatarsophalangeal joint (MPJ). Acute correction with autograft is typically the procedure of choice for treatment of defects of the 1st MPJ. However, the amount of length that can be achieved is limited in acute correction and distraction osteogenesis should be considered for larger defects. This case study presents our treatment of a failed first MPJ arthroplasty that resulted in a defect at the 1st MPJ of greater than 2 centimeters and our technique of using external fixation followed by internal fixation to regain desired length and minimize time in the external fixator.

Keywords: Distraction osteogenesis, external fixation, monolateral rail, mini rail, failed 1st metatarsal arthroplasty, infected implant

ISSN 1941-6806
doi: 10.3827/faoj.2020.1303.0009

1 – Resident Physician, PGY-2, Franciscan Foot & Ankle Institute, Federal Way, WA
2 – Resident Physician, PGY-2, Franciscan Foot & Ankle Institute, Federal Way, WA
3 – Fellow Physician, CHI Franciscan Health Advanced Foot & Ankle Reconstructive Surgery Fellowship, Burien, WA,
4 – Residency Director, Franciscan Foot & Ankle Institute, Federal Way, WA
* – Corresponding author: rebertyler@gmail.com


Failed arthrodesis or arthroplasty of the first MPJ can often leave the revision surgeon with limited surgical options. The literature recommends, when possible, acute correction of bony defect over distraction osteogenesis due to decreased complication rates, faster time to healing, and reduced psychological strain that an external fixator can potentially cause a patient [1-3]. However, acute correction is limited by the soft tissues with potential neurovascular compromise. In these instances, distraction osteogenesis should be considered as it allows for the soft tissues to adapt as the bone lengthens [4].

Distraction osteogenesis by external fixation has been widely used and studied since Dr. Ilizarov first described his technique in the 1950’s. Dr. Illizarov described two main phases: the first being distraction where he determined the ideal rate was 1 mm per day and the second being consolidation wherein the newly formed regenerate gains strength [5-7]. In the standard technique, the patient spends the entire consolidation period in the external fixator and this can more than double the amount of time the patient spends in the fixator. A new technique that is gaining popularity is the conversion of the external fixation to internal fixation to limit the duration the patient spends in the fixator, and this technique was used in this case [8-9].

This case study presents our treatment of a failed first MPJ arthroplasty from deep infection after a failed first MPJ arthrodesis due to a non-union that left a defect at the 1st MPJ of 22 millimeters.

https://lh4.googleusercontent.com/5bnygpI1Ghf8MjT7-gUvUB51hSJklyjVtp3kD_klZeNma3XlUigLNCJSNpkFjTZQe75PeiawZxcX-1lbeD2IO3t3DYMM5GhWMe5dVKm0c5637bkcXZFhcohASHvyglR8BTx2A4pei_E https://lh4.googleusercontent.com/D8lVo-bSk6WO4ECc1wxueQVKAzC-KW2LfQlwVtjNdT7PWy-0fDxWppfX9tU4rKRiKnViAZ13HLkZVkqDwo-47JbUojLFpHSUXAO6Sn7zt0ceOi9CimViepjrNS9GjUOcGZF0337XQYI

Figure 1 (A) Preoperative clinical photo (B) Preoperative X-ray with antibiotic spacer.

The objective of this case study is to present our surgical technique for lengthening of the first metatarsal by distraction osteogenesis with external fixation to show its use as a viable treatment option for a shortened first metatarsal.

Case Study

A case is presented of a 52-year-old female who failed all conservative care for 1st MPJ arthritis of the left foot and underwent a 1st MPJ fusion. The 1st MPJ fusion failed due to a non-union and the decision was made to convert to a first MPJ arthroplasty. Infection of the implant with osteomyelitis was subsequently diagnosed with MRI at 3 months post-arthroplasty. The implant was removed at 3 months postoperative and was replaced by an antibiotic spacer and the patient was able to tolerate the spacer for two years (Figure 1). The area eventually became painful and removal of the antibiotic spacer was deemed necessary. Labs were obtained for vitamin D, prealbumin, comprehensive metabolic panel, parathyroid, and thyroid panel which were all within normal range. The length able to be achieved with acute correction was not felt to be adequate to restore proper function of the first ray, so distraction osteogenesis was selected as the treatment option. After removal of the antibiotic spacer, a mono-lateral external fixator was applied and used to lengthen the first metatarsal 22 millimeters of length, which was achieved after 26 days of distraction.

https://lh3.googleusercontent.com/zMuv_t3pOvBlUJL3IzVE1cTiKX4sePxiRFFbC4lJ4jUdvvrclQDKMQjcV18zBzxs9jjXfnZXipfmV389-yr9fJYbEBsvDSAZa2bKOKSdzgpAYImtQryXOKFz3b9X5IUO6yBCIZldEyc https://lh6.googleusercontent.com/lk9Ksc7-dsMJSDjdU1oCNCL3HRCyfqNGFpeP8fZHQ1rtWPGdxEV9x691XdWQu3gaGMpDHy7YcQ9_eSDu_5tQd_FnFhJCHQHNycR-Hn50qKXdyib66RxZI4gpR-t3_vQTYhkDtedF3tQ https://lh4.googleusercontent.com/dM9ngSpoCOSE6huTfVoEMMl4w0PvbLGxThXoInM52wJhFToe-pJ2oImKEhPj8Bu1u1_e3VupJxCt939m6plP4IOhVQfeNVW9hTT5qJKLEUDw48DM6TcX-_CmVrKnZdqTuQOJ4UH4JP4 https://lh6.googleusercontent.com/wOqg2On9WrwutLiv8LtYiX8hWOblFdNMAddGvkfMBndOPusZaLqOxMWs_stK6ISV11bsmTNJIov49hpOD6ZxDp-48h8TgBRN99PVaEBzZVxNzN8-FdZQgWAzr1okq3fhkhv0RLg_Z9A

Figure 2 (A)Intraoperative, Closure with External fixator application (B) Immediate postoperative with compression at corticotomy site (C) X-ray after 26 days distraction, 22mm of lengthening (D) Consolidation period post external fixator removal and internal fixation.

The external fixator remained on for an additional month to allow consolidation of the regenerate, but was removed at the patients request and was replaced with a locking plate. After five months, the locking plate was removed due to hardware irritation. A CT confirmed partial union of the first MPJ prior to hardware removal and the fusion site was stressed intraoperatively and found to be stable. The locking plate and screws were then removed. The patient was able to ambulate in tennis shoes without pain and was able to perform activities of daily living 1 year postoperatively.

Surgical Technique

A longitudinal incision was made medially over the 1st metatarsocuneiform joint extending distally to the medial hallux interphalangeal joint. Layered dissection was carried along the length of the incision down to the level of the antibiotic spacer within the 1st metatarsophalangeal joint site.

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Figure 3 (A) CT scan 14 weeks status post 1st MTPJ fusion showing osseous consolidation at the first MPJ (B) Immediate post-op hardware removal.

The spacer was removed and the nonunion margins were curetted and fenestrated down to healthy bleeding bone. Orthobiologics were used to augment the fusion site. A 0.062” K-wire was inserted through the tip of the distal hallux, crossing the hallux interphalangeal joint, and into the 1st metatarsophalangeal nonunion site. Correct placement of this K-wire is key to help guide the axis of regenerate formation as the bone is lengthened.

An osteotomy was made 1 centimeter distal to the base of the first metatarsal by perforating the bone with a k-wire and then completing the osteotomy with an osteotome. Intraoperative fluoroscopy was used to confirm the completion of the osteotomy.

Thereafter, a monolateral external fixator was applied to the dorsal aspect of the foot with 3 proximal pins within the medial cuneiform, 1 pin in the base of the first metatarsal, and 2 distal pins in the midshaft of the metatarsal. The osteotomy site was then compressed utilizing the external fixator and the 0.062” K-wire was driven across the osteotomy and into the base of the first metatarsal.

The patient began lengthening at POD #12 at a distraction rate of 0.25 millimeters four times per day. After 26 days of distraction, there was 22 millimeters of length achieved and distraction was discontinued. One month into the consolidation phase the external fixator and K-wire were removed at the patients request. The metatarsal was docked to the proximal phalanx at this time after fenestrating the opposing bony surfaces and a locking plate was used to span the regenerate and provide stability (Figure 3).

Discussion

This case study supports the current literature that distraction osteogenesis is a viable option for treatment of a large bony defect at the 1st MPJ. The patient was able to gain 22 millimeters of length through distraction osteogenesis and was able to undergo a successful fusion at the 1st MPJ with a stable fusion site and regenerate bone at the time of hardware removal. Placement of the K-wire so that it parallels the first metatarsal in both the sagittal and transverse planes is key in order to avoid malalignment of the newly formed regenerate. Although the patient did require removal of her hardware, she was able to return to normal shoe gear without pain and was able to perform her activities of daily living that had previously been limited at her one-year follow-up.

The literature currently supports single-stage procedures over distraction osteogenesis when possible. Jones, et al., in 2015 performed a systematic review of the literature comparing single stage vs distraction osteogenesis in the treatment of brachymetatarsia. They found that the overall major complication rate of distraction osteogenesis was 12.62% compared to 3.72% with single stage procedures and the minor complications rate was 39.18% for distraction osteogenesis compared to 15.76% for single stage. They also found that distraction osteogenesis is associated with a greater time to heal with an average of 2.31 months for every centimeter gained compared to 1.9 month per centimeter with a single stage procedure [1].

Even with these disadvantages, distraction osteogenesis does have a major advantage over single stage bone grafting in that much greater length can be achieved and donor site complications can be avoided. Recommendations have been made that no more than 15 millimeters or 25% of the original length of the bone be attempted with a bone graft. With callus distraction, the recommendation has been that the metatarsal can be increased in length up to 40% of its original length [11-12].

This case study also supports the conversion to internal fixation at the time of external fixation removal during the consolidation period. This allows for the benefits of external fixation in being able to gain greater lengths of correction while also limiting the time the patient spends in the external fixator. This technique is well supported in the literature and can help make external fixation more tolerable for the patient [8-9].

In any patient with a history of a non-union it is important to rule out any underlying conditions that may have caused the non-union. There are a variety of different causes for a non-union from improper joint preparation, improper/loss of fixation, smoking, low vitamin D levels, underlying metabolic disorders, among others [14-15]. It is important to order the appropriate labs pre-operatively and medically optimize the patient before considering return to the OR for surgical intervention. The protocol for ruling out underlying metabolic bone conditions for the senior author in our study (C.C.) is to order labs for vitamin D, prealbumin, a comprehensive metabolic panel, parathyroid, and a thyroid panel. In our patient these labs all came back normal indicating they most likely did not contribute to the patient’s original non-union.

In conclusion, bony defects too large for acute correction in the 1st MPJ provide difficult challenges to the surgeon but distraction osteogenesis is a viable option. Converting the external fixation to internal fixation can also help make distraction osteogenesis more tolerable to patients that are hesitant to spend extended periods of time in an external fixator.

References

  1. Jones MD, Pinegar DM, Rincker SA. Callus Distraction Versus Single-Stage Lengthening With Bone Graft for Treatment of Brachymetatarsia: A Systematic Review. J Foot Ankle Surg. 2015 Sep-Oct;54(5):927-31. doi:10.1053/j.jfas.2015.02.013. Epub 2015 May 19. Review. PubMed PMID: 25998479.
  2. Oh CW, Satish BR, Lee ST, Song HR. Complications of distraction osteogenesis in short first metatarsals. J Pediatr Orthop. 2004 Nov-Dec;24(6):711-5. PubMed PMID: 15502575.
  3. Mather R, Hurst J, Easley M, Nunley J. (2008). First Metatarsal Lengthening. Techniques in Foot & Ankle Surgery. 7. 25-30. 10.1097/BTF.0b013e318165c21c.
  4. Choi IH, Chung MS, Baek GH, Cho TJ, Chung CY. Metatarsal lengthening in congenital brachymetatarsia: one-stage lengthening versus lengthening by callotasis. J Pediatr Orthop. 1999 Sep-Oct;19(5):660-4. PubMed PMID: 10488871.
  5. Ilizarov GA. The tension-stress effect on the genesis and growth of tissues. Part I. The influence of stability of fixation and soft-tissue preservation. Clin Orthop Relat Res. 1989 Jan;(238):249-81. PubMed PMID: 2910611.
  6. Ilizarov GA. The tension-stress effect on the genesis and growth of tissues:Part II. The influence of the rate and frequency of distraction. Clin OrthopRelat Res. 1989 Feb;(239):263-85. PubMed PMID: 2912628.3. Skirving AP, Newman JH. Elongation of the first metatarsal. J Pediatr Orthop.3:508-510. 1983.
  7. Skirving AP, Newman JH. Elongation of the first metatarsal. J Pediatr Orthop. 1983 Sep;3(4):508-10. PubMed PMID: 6630498.
  8. Oh CW, et al. Submuscular plating after distraction osteogenesis in children. J Pediatr Orthop B. 2008;17(5):265–269. doi:10.1097/BPB.0b013e32830688d8
  9. Harbacheuski R, Fragomen AT, Rozbruch SR. Does lengthening and then plating (LAP) shorten duration of external fixation?. Clin Orthop Relat Res. 2012;470(6):1771–1781. doi:10.1007/s11999-011-2178-2
  10. Bartolomei FJ. Surgical correction of brachymetatarsia. J Am Podiatr Med Assoc. 1990;80(2):76–82. doi:10.7547/87507315-80-2-76
  11. Kim HT, Lee SH, Yoo CI, Kang JH, Suh JT. The management of brachymetatarsia. J Bone Joint Surg Br. 2003;85(5):683–690.
  12. Lee WC, Suh JS, Moon JS, Kim JY. Treatment of brachymetatarsia of the first and fourth ray in adults. Foot Ankle Int. 2009;30(10):981–985. doi:10.3113/FAI.2009.0981
  13. Harbacheuski R, Fragomen AT, Rozbruch SR. Does lengthening and then plating (LAP) shorten duration of external fixation?. Clin Orthop Relat Res. 2012;470(6):1771–1781. doi:10.1007/s11999-011-2178-2
  14. Moore KR, Howell MA, Saltrick KR, Catanzariti AR. Risk Factors Associated With Nonunion After Elective Foot and Ankle Reconstruction: A Case-Control Study. J Foot Ankle Surg. 2017;56(3):457–462. doi:10.1053/j.jfas.2017.01.011
  15. DeFontes K, Smith JT. Surgical Considerations for Vitamin D Deficiency in Foot and Ankle Surgery. Orthop Clin North Am. 2019;50(2):259–267. doi:10.1016/j.ocl.2018.10.008

 

Subchondroplasty in the lower extremity: A literature review

by Steven Cooperman, DPM1*; Thomas Yates, DPM1; David Shofler, DPM, MSHS1

The Foot and Ankle Online Journal 13 (3): 8

Osteoarthritis is one of the most common and debilitating conditions encountered by foot and ankle surgeons. This osteoarthritis is often accompanied by a coinciding bone marrow lesion (BML) which has been shown to result in poorer patient outcomes. The subchondroplasty procedure was developed with the aim of targeting these painful BMLs in order to slow the progression of osteoarthritic changes. There has been a trend in both orthopedic and podiatric literature towards the use of this procedure in the lower extremity. This review is meant to bring forward the information most pertinent to the procedure to help inform the foot and ankle surgeon of its uses and potential, as well as to encourage future research into the procedure.

Keywords: subchondroplasty, bone marrow lesion, osteoarthritis, calcium phosphate, bone substitute material

ISSN 1941-6806
doi: 10.3827/faoj.2020.1303.0008

1 – Department of Podiatric Medicine, Surgery, and Biomechanics, Western University College of Podiatric Medicine, 309 E 2nd Street, Pomona, CA 91766
* – Corresponding author: Scooperman@westernU.edu


Osteoarthritis (OA) remains one of most common and debilitating conditions encountered by foot and ankle surgeons. Whether the result of trauma or degenerative overuse, orthopedic and podiatric surgeons alike can agree that the sequelae of OA can be challenging to manage. The natural history of OA involves persistent joint pain, lack of normal function, and can include a vicious cycle which may progress to osteonecrosis of the affected bones. While the current body of evidence of in vitro cartilage repair and regenerative medicine is rapidly growing, there are perhaps other more readily available methods of treating OA which may ultimately demonstrate equal benefit to patients. Subchondroplasty® (SCP) (Zimmer Knee Creations, West Chester, PA) is a surgical system, developed in 2007, in which flowable bone substitute material (BSM) is injected into subchondral bone in order to fill a defect. The procedure acts to support the subchondral bone layer by providing a scaffold over which new, healthier osteochondral elements may be produced [1]. Although this technique has primarily been described in literature to treat bone marrow lesions (BMLs) in the knee joint, this technique has recently been applied to the foot and ankle with comparably successful outcomes.

This paper is not meant to serve as a technique guide, but a review of available relevant literature. As such, the use of the term subchondroplasty throughout the paper will be in reference to the procedure itself, not the proprietary system. The goal of this review is to benefit the foot and ankle surgeon by: first, providing a general understanding of the procedure and its expanding applications; second, by presenting the largely positive patient outcomes in both the orthopedic and podiatric literature in an attempt to encourage further study into a relatively new – yet promising – tool in the foot and ankle surgeon’s array of treatments.

Methods

An extensive search of available literature related to: 1) subchondral bone and the osteochondral unit; 2) lower extremity osteoarthritis; 3) bone substitute materials; 4) the subchondroplasty procedure, including its related radiographic findings and clinical outcomes in the lower extremity.

Background

Within joints, the subchondral bone layer is a supporting structure for the overlying articular cartilage. Subchondral bone is an underappreciated, yet vital component to the function of each osteochondral unit and overall joint health [2]. Bone metabolism is dynamic, in concert with Wolff’s law, and a normal subchondral bone plate displays the same capacity to increase in thickness according to physiologic loading [3].

In osteoarthritis, this typically dynamic nature of the subchondral bone plate is disrupted. Increased and imbalanced dispersion of joint forces, combined with a concentration of stresses and synovial fluid infiltration into the subchondral bone, can lead to reduced healing capacity and abnormalities within the underlying cancellous bone. These abnormalities can be identified both histologically and on magnetic resonance imaging (MRI) as bone marrow lesions (BMLs) [4-7].

The mechanism of coinciding pain associated with these BMLs is currently under debate, but has been attributed to the healing response secondary to trauma and trabecular injury and/or impaired venous drainage [8-10]. Histologically, BMLs have been shown to be focal areas of demineralization, increased fibrosis, and vascular abnormalities. These abnormalities can mimic chronic stress fractures, which may then progress to areas of focal necrosis [6,11-15]. Clinically, it is of great importance that BMLs be identified and treated, as they have been linked to increased arthritic pain and may hasten the progression of joint deterioration [5,16-18].

These potential consequences have been attributed to both improper load transmission across the affected joints and an underlying imbalance in bone metabolism––favoring bone resorption when a BML is present [19]. A direct correlation between increasing size of BMLs and increased pain in the knee was identified in a study by Felson, et al., in 2007. Patients experiencing pain were found to have a 3.31-fold greater likelihood of significant findings on MRI compared to non-painful patients with the same radiologic degree of arthrosis [20]. Additionally, Saltzman and Kijowski found that BML prevalence, depth, and cross-sectional area under arthroscopy were each directly correlated with worsening grades of corresponding articular cartilage defects [2,21].

Osteoarthritis occurring in the hip and knee joints primarily occurs as a degenerative process. However, due to histological, anatomic, and biomechanical differences in the cartilage of the ankle joint, arthritis in the ankle most commonly occurs after significant trauma [22-24]. Due to the post-traumatic presentation of ankle joint arthritis, there exists a propensity for a wider range of ages at which osteoarthritis may present in the affected ankle, which has important implications with how these patients are definitively treated. Younger and more active patients with ankle joint arthritis are less tolerant of arthrodesis or arthroplasty procedures than are their elderly and less active counterparts. As such, it stands to reason that there should be a great deal of interest in the potential for joint sparing procedures in these patients.

The Procedure

In this procedure, BMLs are triangulated using fluoroscopy, and subsequently injected and filled with flowable, biologically-compatible ceramic materials. The injected bone substitute material (BSM) then undergoes an endothermic reaction, resulting in crystallization of the BSM which affords properties similar to that of cancellous bone. This is believed to assist in supporting the trabecular structure of the bone, and to slow or even halt the pathologic processes at work. Typically, this procedure has been performed with calcium phosphate (CaP), calcium sulfate (CaS) or hydroxyapatite (HA), with CaP being the more commonly used of the three [25]. However, in terms of osteobiology, these products only offer one component of the osteobiology triad: osteoconduction. As such, these products only function as a scaffolding upon which healing may take place.

In 2016, Hood et al proposed that the two remaining osteobiologic properties, osteogenesis and osteoinduction, could be imparted via the addition of bone marrow aspirate concentrate (BMAC) to the osteoconductive materials used during the procedure [25]. It had previously been shown that osseous regeneration occurs at a faster rate with the use of a combination of BMA and osteoconductive ceramic materials, as opposed to either alone [26]. The premise behind this is that replacing the 0.9% normal saline solution (NSS)––which is typically used for rehydration of the bone substitute material––with autogenous BMAC, bone healing potential can be improved.

The addition of BMACs, the osteoconductive CaP would have the theoretical benefit of mesenchymal stem cells (MSCs), osteoprogenitor cells (OPCs), hematopoietic stem cells (HSCs), platelets, vascular endothelial growth factor (VEGF) and transforming growth factor beta (TGF-β) to assist in the reparative process [26-29]. In patients with concomitant cartilaginous defects, particulated juvenile allograft cartilage (PJAC) can be used to address the overlying cartilaginous defect after hardening of the CaP scaffold [8].

Hood et al. presented a case report for a 26 year old female with two years of recalcitrant left ankle pain after a motor vehicle accident. This patient eventually underwent the modified SCP® technique with rehydration using BMAC for a talar dome BML [25]. It was reported that the patient’s pain decreased from a preoperative VAS score of 9 to occasional 1-2/10 discomfort at 6 weeks postoperatively.

CaP with BMAC has since become a popular choice among bone and joint surgeons, though other orthobiologic combinations have also been reported with promising results: CaS with platelet-rich plasma (PRP), HA with BMAC, and HA-tri-CaP with MSC [30-32]. Subsequent studies have aimed to clarify the following: the ideal osteoinductive/osteogenic adjunct, the proper amount and consistency of adjunct, the effect on curing time and handling, and the adjunct’s effect on the scaffolding material.

In 2015, Colon et al. evaluated in vitro injectability of common commercially available bone substitute materials (BSMs). Histologically, bone marrow lesions (BMLs) demonstrate micro-trabecular damage characteristic of stress fractures [15]. For injection of materials into these microtrabeculae to be considered possible, the materials must have the ability to be injected into a highly pressurized space. Eight of the most common commercially available BSMs were tested (AccuFill® (Zimmer, Inc.), Beta-BSM™ (Zimmer, Inc.), Cerament™ (Biomet, Inc.), HydroSet™ (Styker®), Norian™ SRS (DePuy Synthes®), Pro-Dense® (Wright Medical Inc.), StrucSure™ CP (Smith & Nephew plc), Simplex™ (Stryker®)) using the polyurethane block material, while three were additionally tested in femoral condyle cadaveric bone blocks from healthy donors (AccuFill®, Beta-BSM™ and StrucSure™). The results found that although these materials are all considered injectable BSMs, only three were able to flow into the closed structure of the polyurethane block (AccuFill®, Simplex™ and StrucSure™). Additionally, AccuFill® was shown to outperform the other BSMs in several areas: the ability to flow within micro-architecture without damage from the applied force, the lowest injection force, the highest volume injected, the greatest area covered by material injected, and the ability to set without an exothermic reaction. The knowledge that these commercial calcium phosphate (CaP) products have differing properties, and understanding how this may affect different aspects of the procedure, can help inform the decision making of the surgeon.

Imaging

In 2016, Agten, et al., and Nevalainen, et al., both published papers describing diagnostic imaging related to the subchondroplasty procedure in the knee. The goal was to educate radiologists and familiarize them with expected post-procedure findings. Agten, et al., reviewed the pre- and postoperative imaging for nine patients, with the first postoperative imaging at three months post-operatively. Nevalainen, et al., discussed two knee subchondroplasty case studies. Preoperative imaging revealed that insufficiency fracture was associated with a greater amount of bone marrow edema than osteoarthritis [33].

Following the procedure, postoperative radiographs should display an increased radiodensity at the site of calcium phosphate injection, which should correlate with the locations of bone marrow edema (BME) on preoperative imaging [33,34]. CaP extravasation into soft tissues may occur along the track of the injection, which predictably mimics the appearance of heterotopic ossification. Extra-articular extravasation of calcium phosphate may resolve over time, while intra-articular leakage is a complication that should be addressed intraoperatively.

When evaluating patients, it is important to identify the cause of bone marrow edema, as this is a relatively non-specific finding, particularly on MRI. Trauma, including bone contusions, is the most common cause of positive BME findings on MRI [35]. The remaining causes of BME on MRI are transient BME syndromes (including transient osteoporosis, regional migratory osteoporosis, and complex regional pain syndrome), repetitive microtrauma and stress fractures, and non-traumatic causes such as avascular necrosis, spontaneous osteonecrosis, reactive polyarthritis, and neoplasms [2].

Classic findings of BMLs include a focal area of BME appearing as high signal intensity on T2-weighted, fat-saturated images and low signal intensity on T1-weighted, fat sensitive images. The increased signal intensity of BMLs on T2-weighted, fat-saturated MRI sequences has been suggested to be a result of increased subchondral vascularity [1]. Additionally, a low-signal-intensity line in the subchondral region of T2-weighted, fat-saturated images may be present, corresponding to impaction of the trabecular bone [35]. If present, it has been shown that a length and thickness of this line greater than 14mm and 4mm, respectively, are risk factors for lesion progression and subchondral collapse [36]. This signal should change to a decreased signal intensity on both T1-weighted fat-sensitive and T2-weighted fat-saturated images following injection of the CaP [33,34]. On fat-saturated, fluid-sensitive images there may also be a fine rim of increased signal intensity surrounding the CaP, representing surrounding edema [33,34]. It should be noted that a direct correlation between increasing BME signal intensity and more advanced cartilage degradation on MRI has also been identified [37].

Preoperative CT scan may be useful in conjunction with MRI, especially in the case of concurrent cartilage injury, as this can be difficult to assess on MRI [38,39]. Concurrent evaluation of the cartilage portion of the osteochondral unit should be considered of utmost importance, as 60% of patients with surgically confirmed chondral degeneration in the knee have been shown to have associated BMLs [21]. Additionally, both cartilage thinning and bony edema can lead to over- or underestimation of cartilage and bone damage on MRI [40]. Postoperatively on CT scan, any drill holes will be seen as a hypodense track with the surrounding hyperdense CaP [33].

Notably, the changes described correlating to post-procedure imaging have been shown to regress over time. Still, the specific time-frame is currently unclear and likely variable. In canine models, the majority of BSM has been found to be absorbed by two years postoperatively [41].

Use for OA/BML in the knee

Subchondroplasty was originally described for use in the treatment of moderate to severe osteoarthritic knee pain present for more than 2-6 months, with concomitant presence of a BML localized to the area of pain [42]. The presence of a BML in these patients is particularly concerning, as patients with knee OA compounded with a BML have a highly predictable progression to total knee arthroplasty (TKA). In fact, this occurs approximately nine times more frequently over a three year period when compared to OA in patients without a coinciding BML [4,43-45]. Previous treatment of cartilaginous defects in the knee by arthroscopic debridement alone has not been shown to yield success for patients suffering from moderate to end stage osteoarthritis, with several studies showing either no improvement or minor improvement at six months, and no improvement at two years. [4,45-48].

In 2016, a study by Cohen, et al., evaluated the combined treatment of subchondroplasty and arthroscopy in the knee in 66 patients who initially presented for TKA consultation [4]. Pain was significantly decreased and function significantly improved in all groups, including at both 6 and 24 months post-op. Notably, there was a 70% 2-year joint preservation survivorship. Patients who ultimately received TKA were significantly older and were more likely to have had a history of prior meniscectomy. A follow-up study from Brazil also noted positive results, with improvement on both VAS and knee injury and osteoarthritis outcome scores (KOOS) at 24 weeks postoperatively [14]. Longer-term outcomes of treatment with CaP in post-traumatic, impact-induced BMLs in a medial femoral condyle canine model have also shown symptomatic and functional benefits for up to two years [41].

The effect on TKA

Logically, the next question to address is whether the technique of treating BML using CaP bone substitutes affects outcomes in patients who fail this joint preserving technique and require knee replacement. It has previously been reported that the complexity of knee arthroplasty increases in patients who have had previous knee surgery, resulting in the potential for more complications and poorer outcomes [49-52]. In 2016, Yoo, et al., evaluated the effect of prior BML treatment on the complexity and outcomes of future knee arthroplasty procedures [53]. A total of 22 patients who had undergone prior arthroscopic repair of BMLs were demographically matched in a 1:2 ratio to a group of controls undergoing knee arthroplasty, either unicompartmental knee arthroplasty (UKA) or total knee arthroplasty (TKA). Patients were followed up for an average of 23.5 months (ranging from 12-52 months), with no significant differences identified between the groups. There were no cases of intra-operative UKA conversion to TKA, no differences in surgical complications or technical challenges between groups, and no cases of non-standard primary components required. Additionally, on intraoperative inspection of the CaP bone substitute, it was reported to be consistently well incorporated without signs of compromise or inconsistencies from the subchondral bone. Based on their findings, Yoo, et al., concluded that previous treatment of BMLs using CaP bone substitute did not compromise knee arthroplasty outcomes or surgical performance.

Functional/Subjective outcomes in the knee

Functional and subjective outcomes have been generally favorable following subchondroplasty. In 2018, a literature review of 8 articles and 164 total patients treated with CaP injection for BMLs in the femoral condyles or tibial plateau noted significant improvement in symptoms, few complications, and return to activity at an average of three months [42]. Of the articles reviewed, only a single paper reported a subgroup of patients who experienced poor outcomes from the procedure. Chatterjee, et al., identified an inverse relationship between the subjective postoperative Tegner-Lysholm knee scoring scale and preoperative Kellgren-Lawrence osteoarthritis grade [54]. In other words, a correlation was identified between poorer subjective outcomes and more severe preoperative osteoarthritis. Despite this, other studies have failed to report similar correlation between OA grade and outcomes. As such, future prospective studies would be valuable in confirming this finding.

Described use in the Foot and Ankle

At this time, the literature regarding treatment of BMLs using flowable calcium phosphate (CaP) has been primarily directed to cases in the knee. However, due to the need for joint-sparing procedures for ankle osteoarthritis and for the treatment of symptomatic BMLs, there has been growing interest in its application in the foot and ankle. Since subchondroplasty was first introduced into the field of foot and ankle surgery in 2015, more than six thousand foot and ankle subchondroplasty procedures have been performed [55]. The first reported subchondroplasty procedures performed in the foot and ankle were from Miller, et al., [56]. Two cases were reported, the first in a 48 year old male with complaints of chronic left ankle pain and instability, and the second in a 28 year old male with chronic ankle pain following a fibular non-union. In both cases, the patients exhibited talar BMLs on MRI that were recalcitrant to conservative treatments. Each patient underwent a subchondroplasty procedure, combined with other indicated procedures. The first patient was able to return to full activity at 12 weeks post-operatively, while the second sustained a tibial fracture due to a syncopal event at 13 weeks post-op. Miller, et al., reported minimal subjective pain in both cases at 10-month follow-up with no activity restrictions.

Shortly thereafter in 2018, Chan, et al., reported an 11-patient retrospective cohort study of symptomatic talar osteochondral defects (OCDs) treated with subchondroplasty with bone marrow aspirate concentrate (BMAC) injection [57]. In this cohort, the mean talar OCD size was 1.3 cm x 1.4 cm. All subjective outcomes improved from preoperative baseline to final one year follow-up, including visual analog pain scale and Foot and Ankle Outcome Score, with 10 out of the 11 patients reporting they would undergo the procedure again. There was a single reported complication in the cohort, with a talar neck stress fracture at bone-BSM interface after the patient had previously experienced full resolution of symptoms. All patients, except for the aforementioned complication, returned to full activity between three and nine weeks postoperatively.

Barp, et al., published two case reports, including a 25 year-old male tennis player and a 53 year-old female, treated with percutaneous injection of CaP into the 2nd metatarsal head (Frieberg’s infraction) and cuboid (stress fracture), respectively. Both patients were allowed protected weightbearing as tolerated at one week postoperatively, returned to full activity without pain at four weeks, and remained free of related complaints at final follow-up at one and three years, respectively [58].

BMLs in the foot have also been found to be associated with plantar fasciitis, specifically patients requiring surgical intervention [59]. This may have significant clinical implications. In a report by Bernhard, et al., a single case of recalcitrant plantar fasciitis was shown to have a concomitant calcaneal BML on MRI [60]. This patient was treated with repeat plantar fasciotomy and CaP injection of the BML, successfully resulting in full return to activity and pain-free follow-up at 3 and 10 months.

Complications

Perhaps due to the minimally invasive nature of the procedure, few complications of subchondroplasty have been reported in the literature. While rare, the surgeon should be aware of the following potential complications: pain secondary to overfilling with CaP, intra- or extra-articular extravasation of CaP, deep vein thrombosis of the operative limb, subsequent soft tissue or bone infection, stress fracture at the bone-BSM interface, and avascular necrosis [8,57,61].

Pain secondary to overfilling with CaP has been identified as the most common complication of the subchondroplasty procedure, and has been described clinically as a disproportionate pain which often resolves completely within 72 hours postoperatively [42]. Over-pressurization and failure to completely fill a BML have both been associated with poorer outcomes in the orthopedic knee literature and are highly preventable with increased surgeon experience [62]. A single case of osteomyelitis secondary to subchondroplasty in the medial femoral condyle was reported by Dold, et al. In their report, the authors considered that this procedure may have a predisposition for infectious complications due to direct seeding and the hydrophilic nature of CaP, which can result in prolonged wound drainage, poor healing, and eventual sinus tract formation [61]. In a series of 11 patients receiving CaP injection in the talus for painful osteochondral defects, Chan, et al., reported a single complication in a patient with a BMI of 34 kg/m² who experienced a talar neck stress fracture at the bone-BSM interface [57].

Conclusion

Overall, subchondroplasty for the treatment of BMLs has led to promising outcomes and infrequent complications. The range of potential applications of the technique is constantly expanding, with increasing use in the treatment of foot and ankle pathology. Additional studies may help clarify the potential benefits in the setting of osteoarthritis of the foot and ankle, including the procedures potential in delaying and/or preventing total ankle arthroplasty.

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