Diagnosing A Rare Skin Disorder With A Common Chief Complaint

A 29-year-old male presented to our institution with the chief complaint of severe pain associated with callus formation on the plantar aspect of his feet bilaterally. He also had trouble with elongated, thickened nails that rub on his shoes and cause pain.

The patient stated that he has had calluses and blisters since he was a child, but has not received treatment in the past. He denied having any lesions on his hands or any other area of his body. The patient worked as a messenger and in a storage facility, requiring him to be on his feet for long periods of time. Due to the pain, he was unable to continue working and instead was receiving financial support from his sister.

The patient’s past medical history was remarkable for thrush. He denied any psychiatric disorders. The patient had a current history of illicit drug use and tobacco use. His family history was unremarkable. He was unaware if other family members had a history of excessive callus formation and thickened nails.

The patient’s physical exam revealed a healthy appearing man. Pedal pulses were palpable bilaterally with immediate capillary refill to the digits. Varicosities were present at the ankle region bilaterally. The neurologic exam with a 10-gram monofilament revealed an intact protective sensation. His deep tendon reflexes were 2+ bilaterally and symmetric.

The dermatologic exam revealed extensive hyperkeratotic tissue on all plantar weightbearing surfaces of the foot bilaterally. The plaques of hyperkeratosis were yellow with surrounding mild erythema. There was also hyperkeratotic tissue with maceration present at the right first interspace. No vesicle formation, pitting or weeping were evident. Toenails were elongated, thickened and dystrophic bilaterally. His fingernails were also thickened and dystrophic. There was pain with palpation of the hyperkeratotic lesions of the foot bilaterally.

Key Questions To Consider

1. What are the main characteristics of this condition?
2. What is the most likely diagnosis?
3. What is your differential diagnosis?
4. How can one make a definitive diagnosis?
5. What is the treatment?

Answering The Key Diagnostic Questions
1. Painful plantar hyperkeratosis, nail dystrophy (can affect toes and fingers), palmar keratoderma, blistering of the feet, oral leukokeratosis, follicular hyperkeratosis, hyperhidrosis, natal teeth at birth, cysts, hoarseness
2. Pachyonychia congenita
3. Plantar verrucae, palmoplantar keratoderma, psoriasis, tinea pedis and onychomycosis
4. Genetic testing
5. There is no specific treatment for pachyonychia congenita. Mechanical debridement on a regular basis is necessary to alleviate pain. Use of keratolytics, retinoids, mutation specific small interfering RNA (siRNA) injections and rapamycin may be beneficial. For pain associated with dystrophic toenails, treatments include debridement and thinning, or a total matrixectomy as a last resort.

Keys To The Differential Diagnosis
The differential diagnosis associated with painful hyperkeratotic appearing lesions on the plantar foot and associated nail pathology includes plantar verrucae (warts), palmoplantar keratoderma, psoriasis, tinea pedis and onychomycosis.

Plantar verrucae is a human papilloma virus (HPV) found on the plantar foot. It is most commonly the result of HPV serotypes 1, 2, 4 and 63. Immunocompromised individuals are particularly susceptible and traumatized skin creates portals of entry. The lesions are hyperkeratotic, skin-colored papulonodules or plaques with black dots that are thrombosed capillaries on the plantar surface of the foot. These lesions can range in size from a few millimeters to several centimeters in diameter. The lesions may be painful and bleed, or they can be asymptomatic. They tend to appear on areas of pressure but not in all cases. Many times, patients present with multiple lesions that may be mosaic in appearance. Unlike calluses, there are no skin lines extending through the lesions and there is more pain with medial and lateral squeezing versus direct palpation.  

Treatment options include topical salicylic acid, fluorouracil (Efudex), cryotherapy, bleomycin, cantharidin, laser therapy and excision. Unfortunately, plantar warts have a high recurrence rate, are difficult to eradicate quickly and no particular treatment technique seems to be superior.

Psoriasis is a chronic inflammatory disease that affects up to 5 percent of the population.¹ It is classified as an autoimmune disease with a genetic predisposition. There is no cure for the disease but it can be controlled. Psoriasis may present as red, brown or yellow slightly raised, well-defined patches with silvery scales on an erythematous base. Lesions may or may not itch. Psoriasis is more common in fair-skinned people and the disease can present at any age without gender preference. The majority of cases arise in patients younger than 30 years of age. The condition may wax and wane with remission and exacerbation.

There are many forms of psoriasis including psoriasis vulgaris (the more stable form), guttate psoriasis (usually follows a Strep infection), pustular psoriasis (mainly affects the palms and soles), general foot and nail psoriasis, and interdigital psoriasis. Treatment options include topical steroids, ultraviolet light therapy, methotrexate, cyclosporine, retinoids and biologics.

Palmoplantar keratoderma is a group of disorders characterized by thickening of the skin on the palms of the hands and soles of the feet. This is one feature of pachyonychia congenita. There are hereditary forms with only skin problems, hereditary syndromes with palmoplantar keratoderma as an associated feature, and acquired forms of palmoplantar keratoderma. The diffuse hereditary form presents with widespread thickened skin over the palms and soles with an associated red band at the edge of the keratosis. The patient may also have lesions on the dorsal aspect of the feet and hands. Excessive perspiration and thickened nails are also characteristics of the disease. Treatment options include keratolytics, benzoic acid compounds and oral retinoids.

Tinea pedis is a dermatophyte infection of the soles and interdigital area of the feet. Dermatophytes use keratinases to invade the superficial keratin of the skin and the infection remains at this layer. The fungi infect the epidermis and in response, the basal layer expresses keratin and the skin becomes thick and scaly. The moccasin type presents as chronic plantar erythema with scaling and diffuse hyperkeratosis that can be asymptomatic or pruritic. Both feet are usually affected and may have coexisting onychomycosis. Performing a skin scraping and analyzing the specimen under the microscope can help one make the definitive diagnosis of tinea pedis. This will help differentiate the three most common scaling conditions of the feet: eczema, xerosis and tinea pedis.

Pertinent Insights On Pachyonychia Congenita
Pachyonychia congenita is a rare skin disorder caused by mutations in genes expressed only in palmoplantar skin, the nail bed, pilosebaceous unit and oral mucosa. Mutations in several genes, including KRT6A, KRT6B, KRT6C, KRT16 and KRT17, can cause pachyonychia congenita. All of these genes provide instructions for making keratins, which are tough, fibrous proteins. These proteins form networks that provide strength and resilience to the tissues that make up the skin, hair and nails. Mutations in keratin genes alter the structure of keratin proteins and strong, stable networks within cells do not develop.

The skin cells become fragile and are easily damaged, making the skin less resistant to friction and trauma. Even normal activities such as walking can cause skin cells to break down, resulting in the formation of severe, painful blisters and calluses. The defective keratins not only affect the skin, they also disrupt the growth and function of cells in the hair follicles and nails. Originally classified as a nail dystrophy, the most debilitating condition is exquisitely painful plantar keratoderma. In some cases, there is no associated nail dystrophy. More than 45 percent of cases appear with no family history of pachyonychia congenita.²

Based on the patient’s presenting symptoms, the initial diagnosis was pachyonychia congenita but we have not yet confirmed this through genetic testing. The patient returns to the clinic on a regular basis for debridement of the extensive callus at the plantar aspect of his feet along with nail care. At times, the patient must space out his visits due to financial constraints. We have also advised the patient to wear supportive shoe gear at all times, wear socks that wick moisture and maintain an ideal body weight.

Secondary fungal and bacterial infections are common with pachyonychia congenita. The patient has a history of tinea pedis, which he has treated in the past with antifungal creams and solution. Keratolytics have not been beneficial for the patient. He has also used topical Diprolene and betamethasone in the past, and the patient states that he has had some relief with their application. Overall, the best method to help control symptoms in this patient is regular debridement.

In Conclusion
Given the overlapping clinical presentation with other genetic disorders, only genetic testing can confirm the diagnosis. The International Pachyonychia Congenita Research Registry (IPCRR) and the Pachyonychia Congenita Project (PCC) are programs that connect patients, researchers and physicians in an effort to help those with pachyonychia congenita. Free genetic testing is available through the Pachyonychia Congenita Project along with genetic counseling and we will provide these resources for our patient.

Dr. Lacy is a third-year resident at Maricopa Medical Center in Phoenix.

Dr. Fishco is board-certified in foot surgery and reconstructive rear foot and ankle surgery by the American Board of Podiatric Surgery. He is a Fellow of the American College of Foot and Ankle Surgeons, and is a faculty member of the Podiatry Institute. Dr. Fishco is in private practice in Anthem, AZ.

References
1. Parisi R, Symmons DP, Griffiths CE, Ashcroft DM. Global epidemiology of psoriasis: a systematic review of incidence and prevalence. J Invest Dermatol. 2013; 133(2):377–85.
2. Eliason MJ, Leachman SA, Feng BJ, Schwartz ME, Hansen CD. A review of the clinical phenotype of 254 patients with genetically confirmed pachyonychia congenita. J Am Acad Dermatol. 2012;67(4):680-686.