Pachyonychia congenita in a father and son

presented by

Omid Zargari, MD, FAAD

Farzam Gorouhi, M.D.

Rasht, Iran

December 3, 2008

 
Abstract A 9-month-old boy presented with early signs of pachyonychia congenita
Patient
9-month-old boy
Duration
6 months
Distribution
Toes
History

A 9-month-old boy presented with keratotic lesions on the plantar surfaces of his toes and nails since 3 months ago. His father is the only involved member of a family with 9 children. The father has similar but much more severe involvement of palmoplantar areas. The boy's grandparents were first cousin.

Physical Examination

Boy: A 9-month-old boy presented with keratotic lesions on the plantar surfaces of his first toes plus hyperkeratotic nails since 3 months ago.

Father: Severe palmoplantar keratodermy were obvious. In addition All of the nail plates were substantially thickened. Leukokeratosis were seen in the posterior surface of the tongue.

Images

Fig 1: toes of the boy

Fig 2: palms and soles of the father

Laboratory Data

Blood counts and biochemistry was normal.

Histopathology

nil

Diagnosis

Pachyonychia congenita

Reasons Presented

Pachyonychia congenita (PC) is a rare form of hereditary palmoplantar keratoderma (PPK). An autosomal dominant mode of inheritance is observed in most cases of PC, but sporadic cases do occur. There are two primary clinical types of PC (PC-1 and PC-2) which correlate with mutations in K6a/K16 and K6b/K17, respectively.(1)

Currently, no ideal treatment for this disease is available. The goals of treatment for patients with pachyonychia congenita (PC) are designed to address the four major manifestations of the disease: (1) excess keratin accumulation in the nail unit, the skin or the mucous membranes; (2) blisters; (3) the pain that is associated with blisters in some, but not in all, of the hyperkeratotic areas; (4) the keratin cysts in the dermis. In considering therapies, it is useful to remember that the keratins associated with PC are normally and constitutively expressed in hair follicles and nails and ridged skin of adults (Swensson et al, 1998; McGowan and Coulombe, 2000); those keratins are not thought to be normally expressed in interfollicular epidermis, but can be induced in those locations by friction, trauma, or other acquired insult.

It remains an open question as to whether expression of those keratins occurs in neonatal palm or sole or in palm or sole of adults at bed rest. This implies that identification and reduction or removal of the trauma or ''insult'' should be part of the therapeutic regimen for palmoplantar and interfollicular manifestations of the disease, but might be of less help for the hypertrophic nails and cysts. Systemic treatment with retinoids in a daily dose of 1 mg/kg is partially effective; However the patient (father) failed to respond to a one month trial therapy with Etretinate. Furthermore, due to economical issues, he cannot afford the medication for long-term usage.

Questions
  1. Frankly, the father is well aware of the progressive nature of his disease and brought his 9-month-old baby to me to do some preventive therapies. Is there any established or suggested preventive therapy for this disease?
  2. What is your impression about using retinoids for this disease?
References
  1. McGowan KM, Coulombe PA: Keratin 17 expression in the hard epithelial context of the hair and nail, and its relevance for the pachyonychia congenita phenotype. J Invest Dermatol 114:1101–1107, 2000
  2. Swensson O, Langbein L, McMillan JR, et al: Specialized keratin expression pattern in human ridged skin as an adaptation to high physical stress. Br J Dermatol 139:767–775, 1998
  3. Milstone LM, Fleckman P, Leachman SA, Leigh IM, Paller AS, van Steensel MA, Swartling C. Treatment of pachyonychia congenita. J Investig Dermatol Symp Proc. 2005 Oct;10(1):18-20.
  4. Leachman SA, Kaspar RL, Fleckman P, Florell SR, Smith FJ, McLean WH, Lunny DP, Milstone LM, van Steensel MA, Munro CS, O'Toole EA, Celebi JT, Kansky A, Lane EB. Clinical and pathological features of pachyonychia congenita. J Investig Dermatol Symp Proc. 2005 Oct;10(1):3-17.
Keywords Pachyonychia congenita, Leukokeratosis,
Comments from Faculty and Members

David Elpern MD, Dermatologist, The Skin Clinic, Williamstown, MA, USA on December 3, 2008

This is a fascinating problem. It illustrates well the Shelley's concept of "the orphan patient." There must be an "expert" out there who has adopted this group of patients. How to find her or him? If not, Drs. Zargari and Garouhi will need to become the experts. Howard Baden used to have an interest in keratinizing disorders -- He might comment. I will think about this before I shoot from the hip. The child's father is right -- now is the time to start prevention -- possibly protective footwear from the earliest age may help to some degree.

Richard K. Scher, MD, FACP. Professor of Dermatology, Head, Section for Diagnosis and Treatment of Nail Diseases, University of North Carolina, Chapel Hill, NC. on December 3, 2008

Thank you very much for your inquiry regarding the difficult condition of pachyonychia congenita. As you have already stated, the available therapies are very limited in both numbers and efficacy. My experience has been predominantly in regard to the nails. I know of no treatment that is preventative or that retards progression with age. Retinoids have been used or suggested, as you point out, but I believe the results are inconsistent and probably not indicated in children because of bone complications. However, I do not have any personal experience with them.

For the nails, management is essentially palliative, that is, keeping them short, burring down the plates to thin them out, and topical urea to soften. Under more severe circumstances, avulsion and debridement have been employed. Two people who have a significant experience with the cutaneous and non-nail manifestations are Paller and Leachman, both of whom are noted in your references. They may have a few therapeutic suggestions regarding the skin and/or progression. I hope my comments are of some help to you. All the best of good wishes.

Khalid Al Hawsawi M.D., Consultant Dermatologist, King Abdul Aziz Hospital, Makkah, Saudi Arabia on December 4, 2008

Excellent case. I recommend chemical avulsion of the nails and potent keratolytics for the palmoplanter keratoderma.

Greg Sakamoto MD, Resident, Harvard Dermatology, Boston, MA, USA on December 8, 2008

Fascinating case. As already iterated, there are no specific treatments available for the genetic disorders. Milstone et. al put together a compilation of anecdotes based on surverys that were sent to families affected by pachyonychia congenita. Here is a summary of the salient points:

1. Application of various chemicals to hyperkeratotic areas has been used as monotherapy or as a preliminary step to facilitate mechanical removal. Empirical observations have shown that water, humectants such as urea or propylene glycol, and weak organic acids such as salicylic and a-hydroxy acids all serve to facilitate removal of the outer keratin layers.

2. Periodic soaks in dilute bleach to reduce microbial colonization

3. Patients found that systemic retinoids were effective in reducing hyperkeratosis, but it also increases tenderness and blistering.

4. Secondary infections of bullae, hyperkeratotic plaques with fissures, and the nail apparatus is a concern, so appropriate antibiotic/antifungal treatments should be instituted.

5. For thickened, hyperkeratotic nails, pastes of 20%40% urea or 15%20% salicylic acid, often applied overnight under occlusion, seem to be favorite methods to soften the nails.

6. Many report hyperhidrosis as a bothersome manifestation of their disease. There is a suggestion of hyperhidrosis leading to increased blister formation. Aluminum chloride or botox has been used to decrease the palmoplantar hyperhidrosis.

7. Itching is a common complaint. It is unknown whether topical corticosteroids or oral antihistamines alleviate itch, but may be worth a try.

8. Patients often complaint of angular cheilitis or fissures, which can be combatted with heavy emollients.

9. For cysts/steatocytomas associated with the disease, excision, incision, hyfrecation or diathermy are all tx options.

Secondary infection of blister fluid, hyperkeratotic masses, or the nail unit is an ever present danger. Culture and treatment with appropriate anti-mycotic or anti-bacterial agents is a periodic feature of the treatment regimen for many patients.

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