Tag Archives: Gout

Comparing the etiologies, signs and drug treatments of gout: Literature review

by Ebony Love DPM1, Lesly Robinson DPM1, Tracey Vlahovic DPM1*, Ziad Labbad DPM1, Gilbert K Huang BS2

The Foot and Ankle Online Journal 12 (3): 1

Gout affects millions of patients each year.  This inflammatory arthritis results from elevated body uric acid, which leads to deposition of monosodium urate crystals mainly in joints. Since this condition can be affected by different factors within our lifestyles, modern medications have not been made to specifically target the causative factor. This article reviews recent literature by presenting the common etiologies and discussing drug innovations.

Keywords: gout, hyperuricemia, colchicine

ISSN 1941-6806
doi: 10.3827/faoj.2018.1203.0001

1 – Faculty, Temple University School of Podiatric Medicine
2 – PGY-4 Temple University School of Podiatric Medicine
* – Corresponding author: traceyvlahovicdpm@yahoo.com

Affecting millions, gout has persisted throughout a long span of human civilization when first identified by the Egyptians and recognized by Hippocrates. It was thought to be a “disease of kings” due to its association with luxury foods and alcohol consumption, which were affordable to only the wealthy. Today, we know that gout is a form of inflammatory arthritis resulting from elevated body uric acid pool, which leads to deposition of monosodium urate (MSU) crystals mainly in joints [1]. Since this condition can be affected by different factors within our lifestyles, modern medications have not been made to specifically target the causative factor, which ultimately only suppress the symptoms. This article reviews recent literature by presenting the common etiologies and discussing drug innovations.


A thorough search of the published literature regarding (i) the epidemiology of gouty arthritis; (ii) signs and lab results presentation; (iii) drug management for gouty arthritis patients; and (iv) new drugs on the rise. The searches were then prioritized on usage based on the date of publication and degree of relevance to the four topics mentioned. 


The epidemiology of gout can be characterized by its prevalence and risk factors such as diet, comorbidities, and heredity. The prevalence of gout among US was 3.9% (8.3 million individuals); 6.1 million men and 2.2 million women [2-4]. In terms of diet for gouty patient, fructose, red meat, and alcohol intake increases serum uric acid levels drastically. Major comorbidities within the population include obesity, renal disease, hypertension, and metabolic syndrome [1]. ATP-binding gene (ABCG2) and sodium-dependent monocarboxylate transporter gene (SLC2A9) showed significant association with development of gout [3]. Although radiologic evidence assists in the diagnosis of gout, the presence of MSU crystals with needle aspiration remains the gold standard [5-6]. Standard drug management of choice remains an NSAID (indomethacin) and colchicine for acute gout; regimen for chronic patient varies [7-9]. Research continues for the latest FDA approved drug Lesinurad as well as producing IL-1 inhibiting biological therapies [10].


In terms of prevalence of gout among US, all relevant paper referenced the study data from NHANES 2007-2008 which estimated 6.1 million men and 2.2 million women have gout. Furthermore, the survey was compared to a previous data over the past two decades and presented an overall 1.2% increase prevalence of gout and 3.2% on hyperuricemia. Since the increase of hyperuricemia was greater, it is indicated that many people in the US are on the borderline of developing gouty arthritis. Possible overuse of diuretics and aspirin as well as comorbidities such as obesity and hypertension could attribute to that increase as well. 

In most studies, hyperuricemia is classified when serum urate level is greater than 7.0 mg/dL. When purine-rich diet foods were compared, red meat and seafood produced significantly more purine and led to increased risk of gout incident as opposed to purine-rich vegetables and low-fat dairy products. Fructose degrades purine nucleotides and acts as a substrate for uric acid production, which increases the risk of gouty attacks. Consumption of sugar-sweetened soft drinks of two or more servings per day increases the risk of gout incident by an average of 106%. Alcohol consumption, particularly beer, is predispose to gout due to production of purine metabolic substrate guanosine, which enhances nucleotide turnover and impair renal urate excretion via lactic acidosis. Although moderate consumption of alcohol (2-6 oz/wk) did not affect increase gouty incident, those who drink two or more drinks per day had 2.5 times the risk. 

Figure 1 Average percentage of comorbidities with gout.

On the other hand, coffee and vitamin C were examined and found to decrease gouty incidence due to their antioxidant properties that increase insulin sensitivity and enhance renal urate excretion. Additionally, caffeine is a methylxanthine that competitively inhibits xanthine oxidase, which is the major enzyme in purine metabolic pathway.

Since gout is created through the body’s inability to decrease serum urate level, systemic comorbidities can potentially worsen and exacerbate the attack. Through 13 studies comparing comorbidities with gout, hypertension, dyslipidemia, cardiovascular disease, diabetes mellitus, and renal disease are all highly prevalent in individuals with gout. Hypertension was present in 40-74% of individuals with gout, dyslipidemia in 15-59%, cardiovascular disease in 13-41%, diabetes mellitus in 6-32%, and renal disease in 13-44% (Figure 1). 

ATP-binding cassette subfamily G member 2 (ABCG2) gene produces the transporter that causes the export of uric acid out of the proximal tubules which overall decreases the intracellular urate concentration. With mutation of this gene, serum uric acid levels remain high and contribute to roughly 10% of individuals with gout. The gene SLC2A9, encodes a glucose/fructose transporter in the kidneys, which when coupled with the principal renal urate reabsorption transporter, will cause the excretion of urate from the tubule cells. Once again, a mutation within this specific gene will cause a decrease count of transporter produced to reduce urate levels in the serum. 

Colchicine is a lipophilic alkaloid with short half-life but long actual half-life in plasma and metabolized by cytochrome P450. The anti-inflammatory effects can disrupt microtubule function in activated neutrophils and prevent crystal-induced inflammation, which is why it’s indicated as the initial drug of choice for gouty attacks. Colchicine can also be used as prophylaxis for gout patients (0.6 mg bid) for 90 days and indomethacin (50 mg tid) for 10 days. After administering colchicine to reduce acute inflammatory attacks, appropriate steps can be taken to determine if the patient is under-secreting or overproducing uric acid. Further medication can then be prescribed for each specific case:

  • Indomethacin (NSAID) –analgesic, antipyretic, and anti-inflammatory by decreasing prostaglandin synthesis (50mg PO q8)
  • Colchicine (Colcrys) – modulates anti-inflammatory pathways for gout, prevents microtubule assembly, and disrupts inflammasome activation (0.6-1.2mg PO initially, 0.6mg PO q1 until GI symptoms or pain relief; 0.6mg PO once daily or q12 as prophylaxis)
  • Allopurinol (Zyloprim) – blocks uric acid production by inhibiting xanthine oxidase (100-600mg PO daily)
  • Febuxostat (Uloric) – non-purine xanthine oxidase inhibitor (40-80mg PO daily)
  • Probenecid (Benemid) – decrease uric acid reabsorption (250mg PO bid for 1 week, then 500mg PO bid)

Lesinurad (Zurampic) is the most recent FDA approved medication. It is the first selective uric acid resorption inhibitor and inhibits urate transporter-1 (URAT1), which promotes uric acid excretion. Additionally, lesinurad is indicated for hyperuricemia with gout patients that have not achieved target serum urate levels. This requires the drug to be co-administered with a xanthine oxidase inhibitor. Interleukin-1 is a pro-inflammatory cytokine that can mediate and initiate inflammation within the body. By creating inhibitors that specifically target the cytokine and inflammasome, gouty inflammations can be reduced. 


Although the criteria for diagnosing and managing gout are beginning to solidify in modern standard of care settings, the results of this literature review demonstrate a need of long-term research with advancing technologies on new medications to understand their specific effects on the suppression of recurrent gouty episodes.


  1. Schlesinger N. Difficult-to-treat gouty arthritis: a disease warranting better management. Drugs. 2011;71(11):1413-39.
  2. Zhu Y, Pandya BJ, Choi HK. Prevalence of gout and hyperuricemia in the US general population: the National Health and Nutrition Examination Survey 2007-2008. Arthritis Rheum. 2011;63(10):3136-41.
  3. Newcombe D. S. (2013). Gout Basic Science and Clinical Practice. London: Springer International Publishing AG.
  4. Roddy E, Choi H. (2014). Epidemiology of Gout. Elsevier Inc. 
  5. Schlesinger N. Diagnosis of gout: clinical, laboratory, and radiologic findings. Am J Manag Care. 2005;11(15 Suppl):S443-50.
  6. Watt I, Middlemiss H. (1975). The radiology of gout. Elsevier Inc.
  7. Shekelle P. G, FitzGerald J, Motala A, et al. (2016). Management of Gout. Agency for Healthcare Research and Quality.
  8. Perez-Ruiz F., Herrero-Beites A. M. (2014). Managing Gout in Primary Care. Springer International Publishing AG.
  9. Burns CM, Wortmann RL. Latest evidence on gout management: what the clinician needs to know. Ther Adv Chronic Dis. 2012;3(6):271-86.
  10. Keenan RT, Schlesinger N. New and Pipeline Drugs for Gout. Curr Rheumatol Rep. 2016;18(6):32.
  11. Neogi T, Jansen TL, Dalbeth N, et al. 2015 Gout Classification Criteria: an American College of Rheumatology/European League Against Rheumatism collaborative initiative. Arthritis Rheumatol. 2015;67(10):2557-68.
  12. Newcombe D. S. (2013). Diagnostic Procedures in the Management of Gout. London: Springer.
  13. Burns CM, Wortmann RL. Gout therapeutics: new drugs for an old disease. Lancet. 2011;377(9760):165-77.

Infected Gouty Tophous at the Posterior Ankle, Leg, and Achilles Tendon in a Diabetic Patient: A Case Report

by Sutpal Singh, DPM, FACFAS, FAPWCA1, Long K. Truong, DPM2, pdflrgMaria Mejia, DPM3, W. Scott Davis, DPM4, Jennifer Chen, DPM5, Kamran Chaudhary, MD6, Marie Cleto-Quiaoit, MD7

The Foot and Ankle Online Journal 6 (5): 1

The clinical presentation of a diabetic patient with an open infected lesion and concomitant chronic tophaceous gout of the Achilles tendon is evaluated and treatment is described. The 42-year-old man suffered from chronic tophaceous gout with multilobular, solid, tender, enlarged subcutaneous nodules affecting the right hand and both feet. The patient was neuropathic and wearing tight shoes which resulted in laceration of the posterior skin near the soft tissue mass. This resulted in an infected ulcer and cellulitis. He was treated by incision and drainage with removal of the tophaceous mass from the Achilles tendon, sural nerve decompression, as well as debridement of the Achilles tendon.

Keywords: Achilles tendon, Gout, Diabetic foot, surgical debridement

Accepted: April, 2013
Published: May, 2013

ISSN 1941-6806
doi: 10.3827/faoj.2013.0605.001

Address correspondence to: Sutpal Singh, DPM, FACFAS, FAPWCA,
Currently at St. Alexius Medical Center, Hoffman Estates, IL

1Chief Ilizarov Surgical Instructor at Doctors Hospital West Covina, California.
2,3,4,5Residency, Doctors Hospital of West Covina, California. (PM&S 36).
6Greater Chicago Rheumatology, Chicago, Illinois.
7Pathologist, St Alexius Medical Center, Hoffman Estates, Illinois.

Gout is a condition characterized by deposition of monosodium urate crystals in tissues. Acute gout is preceded by elevated serum uric acid levels, although hyperuricemia is often not present during a gouty attack.[4] It is also important to note that most patients with hyperuricemia never experience a gout flare.[1]

As crystal deposition favors areas of the body with lower temperatures, and therefore further from the heart, it has a high tendency to affect the foot, particularly the first metatarsal-phalangeal joint, in about 56-78% of patients.[10] This is known as podagra. An acute gout flare is often characterized by a red, hot, and swollen joint that is very painful to touch, representing a similar clinical presentation as cellulitis.[4]

InfGtFig1a InfGtFig1b

Figure 1 Infected right posterior ankle and lower leg area.

Definitive diagnosis of acute gout is made by observation of negatively birefringent crystals in fluid aspirated from the affected joint. Joint aspirate analysis has been shown to have sensitivity of 85 percent and specificity of 100 percent.[2,13] In the absence of joint aspirate analysis, clinical diagnosis may be made based on meeting certain criteria which include podagra, hyperuricemia, history of monoarticular arthritis followed by asymptomatic periods, palpable tophi and knowledge of certain known co-morbidities associated with gout.[15]

Gout is a multifactorial condition, and as such, must be treated in a multifactorial manner. Gout is caused by altered purine metabolism, but other factors, including high purine diet, alcohol intake, and reduced renal clearance may also contribute. Therefore, lifestyle modification must be a part of any treatment regimen.[4] Acute gout attacks usually resolve without treatment within days to weeks. However, treatment can decrease the duration of an attack and decrease frequency of future attacks. NSAIDs (i.e. indomethacin), corticosteroids (i.e. Prednisone) and colchicine are first-line therapies in cases of acute gout. Colchicine is less commonly used due to the potential side effects.[4] Uric acid lowering agents are often used to treat chronic hyperuricemia.


Figure 2 Magnetic resonance image (MRI) of the right lower extremity shows a large mass engulfing the Achilles Tendon.

These agents are not started during an acute gouty attack, as they can exacerbate the symptoms. These include allopurinol, which is the most commonly prescribed, as well as probenecid and febuxistat (Uloric®, Takeda Pharmaceuticals U.S.A., Inc).[4] The primary treatment for tophaceous gout is to lower the uric acid level with dietary and medical therapy but this may not be easy to achieve therefore, surgical treatment maybe indicated. Surgical intervention has been shown to have a high incidence of complications6, therefore it is mainly recommended when tophi cause pain, skin necrosis, ulcerations, sinuses, nerve compression, interference with tendon function, or when joints are being destroyed and painful.[12]


Figure 3 Right hand.

It is important to distinguish gout from other conditions, as symptoms of acute gout may mimic those of other conditions, and vice versa. Septic arthritis may display the involvement of a single joint, with leukocytosis and elevated erythrocyte sedimentation rate (ESR). Septic arthritis and acute gout may even occur simultaneously.[1] This report describes a case of lower extremity infection in the presence of gouty tophi in a diabetic neuropathic patient with infiltration into the sural nerve.

Case Report

A 42-year-old diabetic patient was seen in the hospital for pus draining from the ankle and back of the leg. He said that he was wearing boots and that it may have cut the back of the leg several weeks ago. He noticed large amounts of pus draining from the posterior ankle and lower leg. He was subsequently admitted. His past medical history was significant for gout and insulin diabetes mellitus. Physical examination showed an infected abscess at the posterior ankle and leg on the right, with pus draining from the ulcerated area. (Fig 1) magnetic resonance imaging (MRI) shows the extent of infiltration of the tophus on the right lower extremity. (Fig 2)


Figure 4 Left posterior ankle without any infection.

On the right hand (Fig 3) as well as the left posterior ankle (Fig 4), there were indurated soft tissue masses for which the patient denied any pain. He had a large non-infected tophi on the left lower extremity.

Surgical Technique

The patient was placed in a prone position under general anesthesia with a thigh tourniquet. A curvilinear incision was made from the middle of the leg on the medial side, going inferiorly across the open wound and ulcer and then crossing over onto the inferior lateral heel area. The incision was deepened down to the subcutaneous tissue and then down to the deep tissue. There was a tremendous amount of brown pus draining from the wound area. Culture and sensitivity for gram positive, gram negative, anaerobic and aerobic organisms were performed. There was a large amount of adhesions noted at the subcutaneous and deep tissue. There was also a large soft tissue mass engulfing the Achilles tendon and sural nerve (Fig. 5 and Fig. 6). Neuroplasty of the sural nerve with surgical loupes was performed.

InfGtFig5 InfGtFig5b

Figure 5 Infiltration of the soft tissue mass engulfing the Achilles tendon.

The entire mass from the posterior, medial, lateral and anterior aspect of the Achilles tendon was removed. The Achilles tendon was also debrided of any degenerative tissue (Fig. 7 and Fig. 8). The necrotic skin was debrided and the skin edges were approximated using 3-0 ProleneTM, Ethicon Inc in simple as well as horizontal mattresses. The open wound area was loosely approximated and packed with Iodoform gauze. The surgical site was dressed with XeroformTM, Covidien, gauze, and KerlixTM, Covidien.


Gout, a common metabolic disorder has increased in prevalence worldwide and is estimated to have doubled in the US alone within the last three decades.[9] Though gouty tophi are typically found in joints, it may also be present in tendons and soft tissue such as Achilles tendon, ear helices, sclera, and sub conjunctivae.[2] Despite many studies which report that gout may be found in these places, there are currently little to no studies reporting the epidemiology of gout present in places like the soft tissue or rearfoot.


Figure 6 Sural nerve entrapment (forceps) with the soft tissue mass.

In this case study, we reported on an infected tophaceous wound. (Fig 7) Histology of the mass is shown in Fig 9-12. Culture and sensitivity revealed infiltration by Streptococcus agalactiae, also known as Group B streptococcus or GBS, which is a beta-hemolytic Gram-positive streptococcus. Though rare, it is important to note that tophi, when left untreated for a long duration, may accumulate and can lead to ulceration which can become infected. A 2011 case study reported a patient who was noncompliant with his allopurinol regimen, and resulted in a tophaceous ulcerated nodule overlying the dorsal first and second metatarsophalangeal joint of the left foot.[5]


Figure 7 Removal of the soft tissue mass. Gross description: 17.2 gm of dark brown to pale yellow soft tissue mass. Sectioning reveals cystic mass with chalky white substance.

The nodule and resulting ulceration were so large that amputation of the left foot was strongly considered.[5] Though bacterial cultures were negative for septic arthritis in this case, ciprofloxacin was given as prophylaxis and the patient healed well with adequate surgical debridement. [5]

It is important to monitor gout, especially in manifestations at the Achilles tendon because if left untreated it may exhibit traumatic effects. Though not as common as in the joints, tophi have been known to be found in the Achilles tendon. A 1981 case study of an acute Achilles rupture alluded to the rupture possibly being caused by gout with deposits consistent with tophi found throughout the tendon, especially at the rupture site.[14]

Often times when assessing the aspirate of a red, hot, swollen joint, if synovial crystals are found a diagnosis of a crystal arthritis such as gout or CPPD is automatically assumed. However, a retrospective study based at a US urban medical center looked at records of all the joint synovial crystal aspirates from a seven year span, containing a total of 265 synovial crystal joint aspirates.[11]


Figure 8 Surgical appearance after removal of the mass from the Achilles tendon as well as debridement of the Achilles tendon.

Of those 265 aspirates, 4, or 1.5%, came back positive for bacterial cultures confirming concomitant septic arthritis with crystal arthritis.[11] While this may seem a small amount, if left untreated may have deleterious effects on the patient.

Another study of 30 cases of concomitant septic and gouty arthritis in 2003 from Taiwan stated that wounds as the result of subcutaneous tophi rupture were the most common source of concomitant septic and gouty arthritis, with the most common infectious organism being Staphylococcus aureus.[14] Fourteen went on to receive surgical debridement with 9 having no reported complications.[14]


Figure 9 Low power of chronic gouty inflammatory reaction with foreign body giant cell proliferation.


Figure 10 Formalin Fixation has destroyed the uric acid crystals to leave amorphous eosinophilic material. Note the multinucleated giant cells indicating chronic inflammatory process (upper right).

With the degeneration in Western diet consisting of increased intake of fast food, soft drinks, and meat it is no surprise that gout and diabetes are common co morbidities. A 2008 study based at the University of Pennsylvania Medical Centre expanded on the notion that hyperuricemia, gout, and metabolic syndrome are associated with each other. This suggests that gout in men with a high cardiovascular risk profile is at a higher risk of developing type 2 diabetes.[3]


Figure 11 Low power of acute gouty inflammation showing gouty casts.


Figure 12 Note the inflammatory neutrophils.

When dealing with diabetic patients, wounds and resulting infection can lead to limb loss or even death.[9] Therefore it is pertinent to monitor both gout and diabetes, because gout left untreated could be a means for ulceration.


Figure 13 Several months after surgery shows complete healing with good Achilles tendon strength.

The case study presented in this article highlighted the significance of the necessity of a thorough examination for patients with numerous risk factors. While our outcome was positive (Fig 13), without a thorough debridement and attentive follow up, this case had the potential to result in a below the knee amputation. This is especially true with the known potentially poor healing capacity of diabetics. Moreover, it vital that in order to prevent recurrence patients with gout must be tightly controlled.


As discussed before, infected gouty tophus of the Achilles tendon is a rare finding even though gout commonly affects the foot and ankle. A thorough history and physical examination with assistance of advanced diagnostic tools and laboratory studies is essential to properly diagnose this condition. Differential diagnosis of gout should always be considered in patients with a history of hyperuricemia even if symptoms are masked by cardinal signs of infection. Medical and surgical therapy has been reported to successfully treat this condition. Our case report demonstrates good prognosis with early recognition and successful surgical debridement.


1. Becker M. Clinical manifestations and diagnosis of gout. In: UpToDate. Basow DS (Ed), Waltham, MA, 2012.
2. Chen LX, Schumacher HR. Current trends in crystal identification. Current Opinion  Rheum 2006 18: 171-73. [PubMed]
3. Choi HK, De Vera MA, Kishnan E. (2008). Gout and risk of type 2 diabetes among men with a high cardiovascular risk profile. Rheumatology 2008  47: 1567-1570. [PubMed]
4. Eggebeen AT. Gout: an update. American family Physician 2007 76: 801-808. [PubMed]
5. Falidas E, Rallis E, Bournia V, Mathioulakis S, Pavlakis E, Villas C. Multiarticular chronic tophaceous gout with severe and multiple ulcerations: a case report. J Medical Case Reports 2011 5: 1-4. [PubMed]
6. Kumar S, Gow P. A Survey of indications, results, and complications of surgery for tophaceous gout. J New Zealand MedAssoc 2002 23: 115(1160). [PubMed]
7. Larmon WA,  Kurtz JF. The surgical management of chronic tophaceous gout. JBJS 195840 :743-772. [PubMed]
8. Mahoney PG, James PD, Howell CJ, Swannell AJ.  Spontaneous rupture of the Achilles tendon in a patient with gout. Annals Rheumatic Dis 1981 40: 416-418. [PubMed]
9. Ramsey SD, Newton K, Blough D, McCullouch DK, Sandhu NS, Reiber GE, Wagner EH. Incidence, outcomes, and cost of foot ulcers in patients with diabetes. Diabetes Care 1999 22: 382-387. [PubMed]
10. Roddy E. Revisiting the pathogenesis of podagra: why does gout target the foot? JFAR 2011 4:13. [PubMed]
11. Shah K, SpearJ, Nathanson LA, McCauley J, Edlow JA.  Does the presence of crystal arthritis rule out septic arthritis? J Emergency Med 2007 32: 23-26. [PubMed]
12. Terkeltaub R. (2010). Update on gout: New therapeutic strategies. Nature Reviews: Rheumatology 2010 6: 30-38.[PubMed]
13. Wallace SL, Robinson H, Masi AT,  Decker JL, McCarty DJ, Yü T. Preliminary criteria for the classification of the acute arthritis of primary gout. Arthritis Rheumatism 1977 20:  895-900. [PubMed]
14. Yu KH, Luo SF, Liou LB, Wu YJJ, Tsai WP, Chen JY, Ho HH. Concomitant septic and gouty arthritis—an analysis of 30 cases. Rheumatology 2003 42: 1062-1066. [PubMed]
15. Zhang W. EULAR evidence based recommendations for gout. Part I: Diagnosis. Report of a task force of the standing committee for international clinical ctudies including Therapeutics (ESCISIT). Annals Rheumatic Dis (2006) 65: 1301-311.  

Bony Ankylosis of the Subtalar Joint in Gout: A case report

by S.M. Shareef1, S. Sinha2 , A.C. Campbell3

The Foot & Ankle Journal 1 (11): 2

Bony ankylosis is a rare consequence of gouty arthritis. Ankylosis is typically a complication of long standing arthritis. Literature reports have shown that anti-hyperuricemic agents can reverse the urate deposition in a joint, but has no effect on the progression of eventual anklyosis of a joint. In this case, gouty ankylosis of the subtalar joint is reported after a relatively short episode of gout despite the use of anti-hyperuricemic agents and NSAID therapy.

Key words: Gout, anti-hyperuricemic agents, ankylosis, subtalar joint

This is an Open Access article distributed under the terms of the Creative Commons Attribution License.  It permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. ©The Foot & Ankle Journal (www.faoj.org)

Accepted: October, 2008
Published: November, 2008

ISSN 1941-6806
doi: 10.3827/faoj.2008.0111.0002

Bony ankylosis in gout is extremely rare. The few cases that have been reported in literature typically occur in patients with chronic, sub-optimally treated or severe gout. We report a case of bony ankylosis in a patient with gouty arthritis of short duration.

Case Report

A 43-year-old female presented with pain and swelling of the left ankle of four-month duration. There was no previous history of trauma, infection, or any other joint problem. Physical examination revealed fullness over the medial aspect of the ankle with mild tenderness. There was some restriction of movements of the ankle and subtalar joints. Laboratory tests revealed a normal ESR and CRP with Rheumatoid factor, Anti-nuclear antibody and HLA B27 antigen being negative. Serum uric acid was elevated.

Skin and nails did not show any psoriatic features. Radiographs of the ankle showed minor degenerative changes with slight narrowing of the subtalar joint space.

Patient was started on colchicine as an initial management, and subsequently commenced on allopurinol and NSAID’s. In spite of these measures pain and swelling of the ankle worsened. A bone scan showed increased activity within the subtalar joint. Debilitating nature of symptoms, even with optimal medical treatment, warranted fusion of the subtalar joint. Synovial biopsy revealed a patchy chronic inflammatory cell infiltrate, but monosodium urate crystals were not detected.

At one-year follow up, the joint remained solidly fused both clinically and radiologically, and the symptoms had resolved completely. However, the patient complained of pain in the opposite ankle. Examination revealed pain with restriction of movement of the right subtalar joint. Patient was advised to continue with allopurinol and NSAID.

At review three months later, the right ankle pain had ceased. Radiographs revealed spontaneous ankylosis of the right subtalar joint without any intervention. (Figs. 1 A and B)


Figures 1 A and B  AP and lateral radiograph of the right ankle showing ankylosis of the subtalar joint. (A) Lateral radiograph clearly showing the ankylosed subtalar joint. (B)


Bony ankylosis is exceptional in gout patients. The first case was reported by Virchow in 1868. Most reported gout patients with ankylosis had severe disease with onset during adolescence or early adulthood. [1,2] Another common feature was suboptimal medical treatment. The most common sites of ankylosis were the carpus, tarsus and ankles. [3]

A highly unusual feature in our case was the fact that the patient developed ankylosis within a short duration of the first acute attack on that side. The patient had no evidence of rheumatic disease known to cause ankylosis, such as ankylosing spondylitis, psoriatic arthritis, or diffuse idiopathic skeletal hyperostosis.

Although biopsy did not reveal gouty crystals, Pascual, et al., [4] have shown total disappearance of crystals from joints in patients who were treated with urate lowering drugs, and have also determined the time needed for this to happen.

The pathophysiology of bony ankylosis in gout is not known. Anti-hyperuricemic agents can reverse urate deposition but may have no effect on the progression of ankylosis. [5,6]


1. Hughes GR, Barnes CG, Mason RM. Bony ankylosis in gout. Ann Rheum Dis. 27 (1): 67-70, 1968.
2. Ludwig AO, Bennet GA, Bauer W. A rare manifestation of gout: widespread ankylosis stimulating rheumatoid arthritis. Ann Intern Med. 11: 1248-1276, 1938.
3. Good AE, Rapp R. Bony ankylosis. A rare manifestation of gout. J Rheumatol. 5(3): 335- 337, 1978.
4. Pascual E, Sivera E. Time required for disappearance of urate crystals from synovial fluid after successful hypouricaemic treatment relates to the duration of gout. Ann Rheum Dis. 66: 1056-1058, 2007.
5. Cortet B, Duqesnoy B, Amoura I, Bourgeois P, Delcambre B. Gout with ankylosis. Rev Rheum [Engl. Ed.]. 61(1): 44-47, 1994.
6. Shoji A, Yamanaka H, Kamatani N. A retrospective study of the relationship between serum urate level and recurrent attacks of gouty arthritis: evidence for reduction of recurrent gouty arthritis with antihyperuricemic therapy. Arthritis Rheum. 51 (3): 321-325, 2004.

Address correspondence to: S. Sinha. Department of Orthopaedics
Monklands, Hospital. Monkscourt Avenue. Airdrie ML6-OJS
United Kingdom

1,2,3 Department of Orthopaedic Surgery, Monklands Hospital, Airdrie, UK.

© The Foot & Ankle Journal, 2008


The University of Texas Southwestern Medical School, Department of Family Medicine

by Atif Mahmood Qureshi, MD, Shobha Rao, MD2 , Dwight Bates, DPM3

Published online: February 1, 2008

Case History

A 62 year old black woman presented with a chief complaint of very painful right big toe of one day’s duration. She denied trauma, fever or prior history of a similar event. Her past medical history includes hepatitis C, and depression. Social history revealed that she does not smoke or drink alcohol and she is a widow. Her current medications include Zoloft and Tylenol for occasional pain.

On physical exam she appeared to be in pain while walking. There was an effusion in the right first MTP joint. Skin was warm and exquisitely tender to touch and movement.

On lab evaluation, white blood cell count was 6.5 mg per dl with normal differential. The uric acid level was 8.1 mg per dl (reference 2.0 to 7.0 mg per dl). The ESR was 30 mm per hour. Other blood tests including electrolytes, BUN, Creatinine and liver function tests was all normal. Results of foot radiography are shown in the accompanying figures.


Question: Based on the patient’s history, physical exam and radiographic findings, which one of the following is the correct diagnosis?
A. Osteosarcoma
B. Pigment Villonodular synovitis
C. Pathologic fracture secondary to gout
D. Calcific tendinopathy
E. Septic Joint
F. Metastasizing hepatoma

Answer: Pathologic fracture secondary to gout


The radiographic image shows right first distal metatarsal fracture (curved arrow) and a lytic lesion. It is important to observe the “Martel’s sign”, which is a radiological sign (straight arrow) to describe the overhanging margin of the new bone along the edge of erosion, named after W. Martel who first described this sign in 1968. Martel’s sign is not present in all cases of gouty arthritis.

Gouty tophi are masses resulting from soft tissue deposition of urate crystals. The erosions of gouty arthritis are outlined with sclerotic margins. As the tophus erodes the bone, it produces an overhanging C-shaped edge of bone characteristic of gouty arthritis [7]. This gives the characteristic “Martel sign”. Intraosseus crystal deposition occurs in rare cases. Fracture secondary to gout is rare. The mainstay of treatment for tophaceous gout is pharmacologic control of hyperuricemia. Treatment can lead to shrinkage or resolution of tophi.

Differential Diagnosis of Radiograph

Most skeletal lesions affecting the metatarsal bones are non-malignant and are associated with conditions such as chondroblastoma, giant cell tumor, osteomyelitis, and gout. Malignant processes involving the metatarsals are unusual. The selected differential diagnosis for osteolysis on radiograph include calcific tendonopathy, osteosarcoma, pathologic fracture secondary to gout, pigmented villonodular synovitis, septic arthritis, hematoma with metastasis and rheumatoid arthritis. The following table describes each radiographic characteristic:

Table:  Differential diagnosis for osteolysis on radiograph.


The diagnosis of gout is confirmed by demonstrating negatively birefringent needle shaped monosodium urate crystals in synovial fluid. But in everyday clinical practice, providers often make a diagnosis of gout based on clinical presentation and radiographic findings.

It is important to perform an aspiration on an undiagnosed patient suspected of having acute gout unless the patient has an acute attack of podagra that responds promptly to an NSAID or Colchicine. [6] In the appropriate clinical scenario, a patient with hyperuricemia and classic podagra can be diagnosed and treated empirically.


The patient was initially treated with Indomethacin 50 mg three times daily by mouth and Colchicine 0.6 mg three times daily by mouth along with conservative measures including rest, icepacks and elevation of the affected joint. She initially responded well to this treatment but returned to clinic within a few days with worsening pain. X-rays showed a secondary pathological fracture with Martel’s sign as discussed above. She was given a cast walking boot for stabilization and was continued with the medicine treatment. Follow up uric acid levels after 2 weeks were found to be 7.0 mg/dl.

Our patient did respond to the NSAIDS and Colchicine. For that reason, a diagnostic tap was not necessary.

Colchicine should be reserved for cases in which the diagnosis of gout is not confirmed and a response may have diagnostic value. 5 Other options to treat acute gouty attacks include intra-articular steroid injection, steroids by mouth. IV colchicine is usually not recommended due to severe side effects such as bone marrow suppression.


Long term management, as described above relies on controlling hyperurecemia. Diet control involves avoiding foods rich in uric acid. Allopurinol , a Xanthine oxidase inhibitor, inhibits the breakdown of purines to uric acid and is mostly effective in overproducers of uric acid.. Probenecid is a uricosuric agent and is mostly used for under secretors Twenty four hour urine uric acid levels shall isolate overproducers from under secretors.. Weight loss with moderate exercise is also a very important lifestyle modification necessary to effectively control and prevent future gouty attacks.


1. Arash Nasim, M.D. Bilateral knee pain. American Family Physician; 74-78, 2006.
2. Bridge JA, Schwartz HS, Neff JR. Sarcomas of bone: Abeloff MD, ed. Clinical Oncology. 3rd ed. New York , N.Y. : Churchill Livingstone, 2477, 2004
3. Rosemberg AE. Tumors and tumor like lesions of the joints and related structures. In: Ruddy S, Harris ED Jr, Sledge CB, eds. Kelley’s Textbook of Rheumatology. 7th ed. Philadelphia , Pa. : Saunders, 1799, 2005
4. Squire’s Fundamentals of Radiology, Robert Novelline, MD 6th edition, Harvard University Press, 2004.
5. University of Iowa, The Family Practice handbook 4th edition 1997 Mark Graber MD, Matthew Lanternier, MD Mosby
6. Bennett G. Zier .MD Essentials of Internal Medicine In Clinical Podiatry ,WB Saunders, 1990
7. Stephen D. Weissman, DPM Radiology of the Foot, Williams and Williams, 1983.

1Third year Family Medicine Resident, University of Texas Medical School, Department of Family Medicine, Dallas , Texas
2Associate Professor, University of Texas Medical School, Department of Family Medicine, Dallas , Texas
3Faculty Associate Professor, University of Texas Medical School, Department of Family Medicine, Dallas , Texas

© The Foot & Ankle Journal, 2008

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