Congenital Variations Discovered in the Clinical Presentation of Hyperkeratosis of the Hand and Foot: A report of 2 cases

by Al Kline, DPM1

The Foot & Ankle Journal 2 (1): 3

Case presentations describing a congenital variation of palmoplantar keratosis are presented. The majority of these conditions are autosomal dominant with associated nail dystrophy. A variant condition is described with little palmar keratosis; however, finger nail and toe nail dystrophy is the most common identifying feature. Gene identification and treatment protocol are presented. Fortunately, these conditions are rare. A good knowledge of these conditions will help in proper diagnosis and treatment.

Key words: Palmoplantar keratosis (PPK), hand, foot, congenital, hyperkeratosis

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: December, 2008
Published: January, 2009

ISSN 1941-6806
doi: 10.3827/faoj.2009.0201.0003

Congenital hyperkeratosis is an uncommon condition of the foot. There are a number of congenital conditions that cause hyperkeratotic lesions of the foot. Fortunately, these conditions remain rare in the population. These lesions can be divided into diffuse and punctuate. There is also a subclass of hereditary diseases defined as either epidermolytic or nonepidermolytic. Conditions characterized by palmoplantar keratosis (PPK) are the most causes of congenital hyperkeratosis. These conditions include Unna-Thost disease, Vohwinkel’s syndrome, Papillon-Lefèvre syndrome and pachyonychia congenita. [1,2,3,4]

Unna-Thost disease was first described in 1880 by Herrmann Arthur Thost and again described in 1883 by Paul Gerson Unna. [5,6,7] Synonyms for the disease include Brünauer-Fuhs-Siemens syndrome, Brauer’s syndrome and Brünauer’s syndrome. [7] It is a disease of autosomal dominant origin characterized by severe palmoplantar keratosis. Deep fissures and hypohidrosis with thickened skin of the palms of the hands and soles of the feet usually occur within the first year after birth. [1] Vohwinkel’s syndrome or keratoderma hereditaria mutilans is a rare autosomal dominant condition first described in 1929. [2] Clinical manifestations first appear in infants and then proceed through childhood into adulthood. Keratosis described as honeycomb and starfish-like in appearance is common. In the later stages of the disease, pseudoainhum or auto amputation of the digits can occur due to constricting bands of keratosis around the digit.

In fact, pseudoainhum is characteristic in a number of hereditary hyperkeratosis. [1,2,3,4] Papillon-Lefèvre syndrome (PLS), also known as Mal de Meleda , was first described by two French physicians in 1924. [3,8,9] It is an extremely rare genodermatosis inherited as an autosomal recessive trait, affecting children between the ages of 1-4. [3] Psoriatic-like plaques involving the palms, soles and elbows are described that worsen in winter and are often hyperhidrotic resulting in a foul odor. [3] Pachyonychia congenita (PC) is a rare genodermatosis that affects the nails of all the toes and fingers. [4] Other names and synonyms of this condition are called congenital dyskeratosis and pachyonychia ichthyosiformis.

Most cases appear within the first or second years of life, although cases of late onset have been reported in the second and third decades. (which is termed PC tarda) [4] Diagnostic features include symmetrical thickening of skin, dysmorphic nails and hyperkeratotic skin lesions. The disease fits into two major types: Jadassohn-Lewandowsky syndrome (JLS-1) and Jackson-Lawler syndrome (JLS-2). It is an autosomal dominant trait. Some recessive forms have been described. JLS-1 is characterized by nail hypertrophy, nail dystrophy, PPK, follicular keratosis and oral leukokeratosis and is the most common form of PC (56.2%). [4] JLS-2 usually lacks oral leukokeratosis and is commonly associated with epidermolytic bullae of the palms and soles (24.9%). [4]

Secondary symptoms are commonly associated with hereditary hyperkeratosis. This is called complex keratodermas. Unna-Thost disease is commonly associated with secondary fungal and bacterial infections. [1] Corneal opacities, pilitorti, hearing loss, hypohidrosis and dental abnormalities have also been described. [7]

Vohwinkel’s syndrome can be associated with deafness, cancer, cardiomyopathy and adrenal insufficiency. [2] PLS is often associated with severe periodontitis which usually starts at the age of three or four. [3] This is seen with gingivitis and rapid destruction of the periodontium when deciduous teeth proceed normally. Other associated conditions of PLS include pyogenic liver abscesses with impaired immunodeficiency. [3] The most common secondary associated symptom with PC is oral leukokeratosis with associated periodontitis and loss of teeth. [4] The teeth develop normally and are lost within 1 year.

Gene Identification

Often, the clinical presentation is not as straight forward as the texts present. Clinical evaluation can present with diffuse as well as punctuate keratodermas and associated nail dystrophy. Clinical diagnosis is usually made by presentation and secondary associated conditions in complex keratodermas.

Recent molecular biological studies indicate the presence of two variants of Vohwinkel’s syndrome, an ichthyosis-associated variant, associated with an insertional mutation of the loricrin gene, and a deafness-associated variant, associated with a missense mutation of the connexin-26 gene. [2] In PLS, there is a reported loss-of-function mutation affecting both alleles of the cathepsin-C gene identified on chromosome 11q14.1-q14.3.3 In Pachyonychia congenita (PC) mutations in the KRT16 and KRT 17 gene encoding keratins K6a and K16 (KRT16) that can trigger JLS-1 and JLS-2 respectively have recently been identified. [4]

Case Studies

Case 1: A 9 year-old female presents to our office with diffuse and punctate hyperkeratosis of both feet. (Fig. 1) Clinically, the hyperkeratosis is located on the soles of both feet with associated severe nail dystrophy to all fingers and toes.

hkfig1ahkfig1b

Figure 1  A 9 year old-female with severe plantar regions of hyperkeratosis (A and B).  The toe nails are severely dystrophic (C).  This condition began in infancy and is congenital.

Interestingly, there is little palmar hyperkeratosis. (Fig. 2) The patient’s father, grandmother and aunt are affected with the same condition. All have PPK with associated fingernail and toenail dystrophy and discoloration. The patient presented with the condition at birth. The patient’s grandfather and uncle are asymptomatic. The condition is characterized by extreme pain.

hkfig2ahkfig2b

Figure 2  Although there is severe plantar congenital hyperkeratosis, the hands show very little palmar keratosis (A and B).

The patient’s father has been treated with narcotics for a number of years. Most of the adults in the family abuse tobacco. The father, grandmother and aunt have undergone multiple surgical debridements in attempts to reduce keratosis. This included surgical debridement of deep keratomas, removal of nail plates and beds and metatarsal head compression osteotomies and 5th metatarsal head resections. To date, surgery was only temporarily effective.

Retinoids were not used at the time. The family did not exhibit any complex symptoms and dentition was normal. No oral leukokeratosis was seen on examination. The entire family has diffuse hyperkeratosis and hyperkeratosis of all nails affecting both hands and feet symmetrically.

The daughter is now treated routinely treated with Retinoid creams, keratolytic agents, debridement and accommodative padding on a regular basis. It appears that most family members affected had the condition worse on the soles of the feet than the hands. Although there is very little palmar keratosis in the 9 year-old female, both the nails of the hands and feet are affected. The patient’s hands reveal discolored, dystrophic changes to the finger nails, but very little palmer keratosis.

Case 2: A 37 year-old female presents with severe plantar keratoderma and secondary inflammation and interdigital bacterial infection. She has allergies to iodine and seafood. The patient has diffuse plantar foot keratosis with nail involvement. (Fig. 3)

hkfig3ahkfig3b

Figure 3  A 39 year-old female with diffuse keratosis to both feet (A).  Secondary infectious tinea is also observed along the medial border of the foot (B).  In this variant form, the hyperkeratosis is more diffuse rather than punctate along the soles of the feet. 

However, her hands appeared to be almost spared of the condition. There is some distal darkening just under the distal region of the finger nail. (Fig. 4).

hkfig4ahkfig4b

Figure 4  As in case 1, this 39 year-old female has very little palmar keratosis.  Distal nail discoloration is observed (A and B).

Her family history shows that most family members were affected by the disease. Her grandmother had the condition, but not the grandfather. They had eight children, 4 boys and 4 girls.

All of the boys inherited the disease and only one girl. Three girls were unaffected. Her mother (who is unaffected) and father (who is one of the boys affected) had 2 boys and 4 girls. Of this group, her 2 oldest sisters have the condition and one brother is also affected.

Only one male was unaffected. Some of the siblings have the condition much worse than the others.

Treatment

Treatment regimes are based on surgical techniques, medications and ancillary treatments designed to decrease painful keratosis. Surgical debridement or paring of keratosis is effective, but only temporary. Surgical bone debridement under regions of intense hyperkeratosis rarely works in our experience. There is very little information in the literature concerning full thickness surgical removal of tissue and skin grafting. Unfortunately, hyperkeratotic areas may return as soon as 1-2 weeks following simple debridement. Medications designed to improve PPK include keratolytic agents and oral or topical retinoids. The most common keratolytic agent used today is Vanamide®. Vanamide is a keratolytic, emollient cream designed to soften the skin. This can be used topically under occlusion for the best results. We have used Vanamide under occlusion for 3 or 4 days before the office visit. It helps most in the debridement of keratosis by softening or hydrating the region of hard keratosis. Vanamide’s main ingredient is 40% urea, so it is especially useful in nail as well as skin debridement. [10] Probably, the most widely used oral retinoid is Accutane or Isotretinoin. Retinoids are a class of medications derived from vitamin A and used to treat various skin conditions from psoriasis to warts to skin cancers. Oral retinoids were first released for use in the United States and Europe in 1982. [11] Oral accutane is most commonly used for cystic acne. Etretinate and Acitretin are more commonly used in the treatment of hyperkeratosis. [11] Oral retinoids should be carefully used in females. The drugs are teratogenic causing serious birth defects.[11] However, when carefully used, they have been found to be very effective in the treatment of various PPK disorders. [2] There have also been reports of elevated liver enzymes while taking oral retinoids, so careful monitoring of the liver enzyme panel is recommended. [11]

Topical and ancillary treatments can include saline soaks, topical Vaseline under occlusion, adding bleach to bath water, antibacterial soaps and a host of others too numerous to mention.

Discussion

Hereditary hyperkeratotic disorders appear to be heterogenous in nature. In the case studies presented, the autosomal dominant gene has no predilection for males or females and is randomized, passing the trait to some siblings while sparing others. Autosomal dominant carriers have a 50:50 chance of passing this gene on to their siblings and the individuals spared will not have the ability to pass on this disease and will not be carriers. [12] It also appears that genetic polymorphisms and mutations continue to occur in varied cases. This would explain why some individuals have the condition worse and some have milder forms of the disease. It can be safe to say that the majority of PPK disorders can have variant forms and severity. As varied as this disease can present, treatment results can also vary. We have found that aggressive debridement with use of topical keratolytics with oral retinoids provide some of the best results. Surgical procedures should only address regions that are most problematic and don’t respond readily to conservative treatment regimes. Educational instruction and understanding should include a thorough discussion with your patients that results can vary and may be unsuccessful or only temporary. Discussing the disease and treatment options will enable better care of the patient with this frustrating condition.

References

1. Kline A. Keratotic lesions of the footH. Podiatry Internet Journal 1 (1): 8, 2006.
2. Bari AU. Keratoderma hereditarium mutilans (Vohwinkel syndrome) in three siblings. Dermatology Online Journal. 12 (7): 10, 2006.
3. Janjua SA, Khachemoune A. Papillon-Lefèvre syndreom: Case report and review of the literature. Dermatology Online Journal. 10 (1): 13, 2004.
4. Caproni M, Fabbri P. Pachyonychia congenita Orphanet Encylopedia., (online PDF) accessed 21/12/2008.
5. Thost A. Über erbliche Ichtyosis palmaris et plantaris cornea. Dissertation. Heidelberg, 1880.
6. Unna PG. Über das Keratoma palmare et plantare hereditarium. Vierteljahrsschrift für Dermatologie und Syphilis. Wien. 15: 231, 1883.
7. Unna Thost Syndrome. Who named it? (online), accessed 21/12/2008.
8. Papillon MM, Lefèvre P. Deux cas de kératodermie palmaire et plantaire symétrique familiale (maladie de Meleda) chez le frère et la soeur. Coexistence dans les deux cas d’altérations dentaires graves.
Bulletin de la Société française de dermatologie et de vénéorologie. 4 (31): 82-87, 1924.
9. Papillon MM. Lefèvre syndrome. Who named it? (online), accessd 22/12/2008.
10. Vanamide Cream (online PDF) , accessed 21st December 2008.
11. Chan A, Hanna M, Abbott M, Keane R. Oral retinoids and pregnancy. The Medical Journal of Australia. 165: 164-167, 1996.
12. The Universe of Genetic Testing, online resource. [online] , accessed date 21/12/2008.


Address correspondence to: Al Kline, DPM
3130 South Alameda, Corpus Christi, Texas 78404.

1 Adjunct Clinical Faculty, Barry University School of Podiatric Medicine. Private practice, Chief of Podiatry, Doctors Regional Medical Center. Corpus Christi, Texas, 78411.

© The Foot & Ankle Journal, 2009

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14 responses to “Congenital Variations Discovered in the Clinical Presentation of Hyperkeratosis of the Hand and Foot: A report of 2 cases

  1. Linda Ann White

    For 10 years I have battled this condition (mine is most similar to the second case depicted). My sister also has the condition but not as severe. The condition presented after a trip to Jamaica. I always thought that I picked something up while walking barefoot in the grass over there.

    Doctors have misdiagnosed me over the years. The only thing I have been able to do on my own (prior to finding the right treatment) was keep the condition from becoming so thick by continuously switching topicals in addition to the use of tea tree oil.

    I finally decided that once and for all, I wanted to know what was wrong and to “get rid of” the condition. My doctor referred me to a dermatologist who has done an awesome job of 1) properly diagnosing me; 2) providing me with steroid and topical treatment; and 3) close supervision. He advises that while I will live with the condition for the rest of my life, we will be able to manage and keep it under control. My feet haven’t looked as good as they do now in years.

    While my sister’s doctor has her on a different regimen, her feet are not doing as well as my own. She is continuing to be treated as if she has a fungal infection.

    Last, the information provided here has educated me in that I believe my grandmother suffered from this condition!!

    Thank you for providing information in terms that a laymen can understand.

  2. I am not very sure whether I should sharing my problem with you.

    I am from Chennai, India and my family has been suffering from a condition, which, as a layman, I think is PPK. My father, who was a twin got this when he was a child of around two years. I am his eldest son (around 50 years of age) and I also am a victim of this ever since childhood (around two years old). I have two sisters and a brother. While one my sister has been spared of this, my other sister and brother are suffering from this condition since childhood.

    I am married and have a son and a daughter. My son is affected with this condition, while my daughter is not affected.

    One uniform commonality about all of us is that the abnormality has manifested the moment we started taking our first baby steps.

    My father is no more, but my other siblings and my son continue to suffer from this. All of us have an yellowish, thickening of the skin in the balls of our feet, the heels, the fingers of our foot. We also get this problem in our hands, but it disappears when activity in our hands are limited. It is very painful and we cannot walk long distances or stand for long periods of time. The pain is very severe during winters.

    It would not be out of place to mention here that my sister suffered a major accident long time ago for which she had to be bed ridden for more than 9 months. During this period, her calluses amazingly disappeared from both her feet, but has regrown once she started normal movements.

    Our movements have been severely restricted and our gait has also changed drastically. The toes of our legs and foot nails are very unsightly and ugly and our social life has been severely affected.

    Is there any one in India, who can at least confirm us that we are indeed suffering from PPK? We have tried many doctors but nothing seems to be working.

    Sorry if I have written something which I shouldn’t have.

    I look forward to your reply

    Thanks & Regards
    Srinivasan

  3. Your best bet is to see a dermatologist and get a correct diagnosis of your condition, then begin seeking treatment. These congenital skin condition can be a challenge to diagnose and treat.

  4. 26yr with hardening of the palms and soles of the feet from birth. She does not know anything about her condition at birth.
    What could be the possible cause, diagnosis, prognosis and associations.
    Thanks
    Ngozi

  5. My family starting with my grandmother, including my aunt and my mother and 6 out of 12 of my siblings have palmoplantar keratosis. None of these conditions really describe our condition. We have the thick dry skin on the palms of our hands and the soles of our feet. we do not have any fungal problems associated with our callouses. The males tend to have a thicker coating and have a greater tendency to pass it on to their offspring. There is no loss of feeling or loss of dexterity as we get older. It seems to thin our as we age.

  6. Linda Ann White

    FOLLOW-UP:

    I have been in treatment with a dermatologist for nearly a year – as is my sister. The condition for both is improving. The treatment, per my dermatologist is going to be (pretty much) a life long fight. Both of our conditions manifest like case #2. I learned that I also have it on the palms of my hands although it is nothing like my feet. There is no fungus involved with the condition as I was told.

    Anyway, steroid shots every 2 or 3 months to calm my immune system and retard the growth, moisterizing cleanser, and two different ointments (one a steroid, the other 6% saliyic acid). While the appearance of my feet is still bad, it is nothing like they were a year ago. I am very thankful.

    I hope everyone else finds some relief.

  7. I had a mild case of this illness and my doctor prescribed me several shots of Interferon, I don’t remember which type.

    The reactions were strong (high fever, hair loss, weight loss) but after that no more stuff growing in my body. I had it in feet, shoulder, nose and back.

    A plastic surgeon removed all of them and I’m ok now.

    Please talk to your doctor, keep trying till you get answers.

  8. This pose is old, but I thought I’d throw in what I’ve experienced. I’ve had calluses cover the bottoms of my feet since as long as I can remember. My hands are pretty bad as well. Working is difficult, currently I have 7! cuts on my fingers and it hurts just to type. Nothing I do helps. I’ve been using a steroid ointment for about a week with little improvement. Anyway…. My sister has this condition also. Apparently our father had it and he has another daughter who found us and told us she has this same condition as well. We share two brothers one I’ve never met, one I grew up with. The one I grew up with has the same condition although it’s not as severe and my sisters and I. If I remember correctly my sister’s son has it but her daughter does not. My daughter does not have it either. She’s 8 now. I figured if she was going to show signs she’d have done it by now. Just thought I’d share some insight to the genetics of it. I’ll be calling your office one of these days. I’m so tired of living in pain all the time. This is the first time I’ve seen or heard about anyone else having anything like what we have. I’m almost excited.

  9. Hi, I am Srinivasan from Chennai. Please see article #2 above. Just a small question. How old are you and how long have you been having this problem. If it is an old case, you cannot expect improvements within one week of using steroid ointments. Have you tried any other medication apart from the steroid ointment application as mentioned in your article? As far as I am concerned, I have found some relief using salicylic acid along with steroid ointments. But I have resigned myself to the fact that I have to live with it for the rest of my life. Am a bit concerned about son and am trying to find out some ways and means by which he can be spared of the agony and pain. Anyway your post really gives some important insights into the genetics of this disorder.

    • No nothing else just the ointment. I only use it on my hands. I don’t really bother with my feet because I’m used to the constant uncomfortableness, but my hands get cuts so bad I find it hard to do anything so I’m trying to at least make my hands better. I’ve had this since I was about 2 or 3… so for as long as I can remember :) It’s part of life and I’ve accepted there is no cure. But hoping for something better is never a bad thing!

  10. Michele, I agree with Srinivasan. It took 6 months or more for me to begin to see any significant results. The steroid ointment and salicylic acid helped/helps soften the skin so that it does not crack so easily.

    As you can see from my 2009 post, it was years before I was properly diagnosed and began treatment. A year in, my dermatologist added the shots to the treatment plan. While I still have the condition and some of my skin looks “burned”, my skin is SO much better. Additionally, there are areas where my skin is actually regenerating to it’s “normal” condition.

    Again, you will have to stick with the treatment. Be consistent with your morning and evening applications. My sister’s treatment does not include the shots, and her skin is worsening and much more discolored than it was in 2009.

    Remember, it took a long time to find someone who understood your condition. It will take a long time before you will begin to see results.

    Be encouraged……

  11. Well as it turns out I can not use the steroid treatment. Just after writing my last post my hands turned red all in between my fingers. They hurt like they were burned and looked burned too. I called my Aunt who is a nurse and she said not to use it anymore and to use corn huskers? I think is what it’s called. I ended up using petrolium jelly with vitamine e my hands healed over a few days and peeled really bad. It was pretty awful. I’m still not even sure if this is what I have… it’s just the best info I’ve found. OH well I guess I’ll wait for the next treatment. BTW I used that heel on or whatever that stick is for cracked feet. One of those “As seen on TV” items when my hands get real bad or elbows or wherever and it works pretty good! Incase anyone wanted to try that! Not a cure all, but certainly helped.

  12. I’m married with three kids.I was diagnosed to have PKK.My dermatologist prescribed me a keratolytic lotion just to soften my callus in my hand and feet. Unfortunately my two kids inherited this kind of disease, Guys! what have you done to give remedy for this kind of inherited disease?What are the initial manifestations have you observed with PKK. Thank you so much!

  13. i have ppk and it did not show up on me until i was in my 30’s, i have 6 brothers and 3 sisters not sure why but only the brunetts have this, four out of nine all the blonde siblings do not have it not sure if there is a connection there, i use a dremel to sand mine down and then use the ointment can see much diff, i found useing duct tape on my feet works best even if it is crazy sounding

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