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Pachyonychia Congenita Treatment & Management

  • Author: Saira J George, MD; Chief Editor: William D James, MD  more...
 
Updated: Mar 30, 2016
 

Medical Care

Like most genodermatoses, no specific treatment or cure is known for pachyonychia congenita. Therapy is generally directed towards symptomatically improving the most bothersome manifestations of the disease and, because of the rarity of pachyonychia congenita, is based largely on anecdotal findings.

The palmoplantar keratoderma and its associated pain are thought to be one of the most debilitating aspects of the disease. Pressure, weight, and trauma are significant cofactors in the development of the keratoderma, and efforts to redistribute and minimize them are important. This can be achieved with specially constructed shoes, orthotic inserts, insoles, and protective socks and gloves. For patients with severe pain and fissuring, the use of an ambulatory aid such as crutches or a wheelchair may be helpful or even necessary for pain management and healing.[19]

Mechanical thinning of keratotic nails and calluses with a variety of tools such as pumice stones, emery boards, rasps, and files may be helpful. Some patients have reported the successful use of electrical tools, such as grinders, polishers, and sanders, to reduce thickened nails.[19]

Softening of the nails and calluses can also be achieved with water, humectants (eg, urea, propylene glycol), and weak organic acids (eg, salicylic acid, alpha-hydroxy acid).[19]

Treatment of hyperhidrosis, which is a bothersome and common feature of pachyonychia congenita, appears to be helpful in decreasing blistering and pain and has been achieved with agents such as aluminum chloride or plantar injections of botulinum toxin.[20, 21, 22]

Pharmaceutical treatment of pachyonychia congenita includes systemic retinoids, such as isotretinoin[23] and etretinate.[24] The retinoids may be successful in reducing the follicular keratoses and the palmoplantar keratoderma but often cause an increase in tenderness and blistering. Their use as long-term therapy is also limited by their adverse effects, such as teratogenicity, mucocutaneous adverse effects, liver toxicity, hyperlipidemia, and skeletal abnormalities.

One report describes beneficial treatment with rapamycin and suggests that it (or rapamycin analogues) may be a good future treatment option. The proposed mechanism of action was selective inhibition of expression of an inducible keratin (K6a) in human keratinocytes.[25]

An innovative and new approach to treating pachyonychia congenita was recently investigated in a phase 1B trial involving a short-interfering RNA (siRNA) that specifically targets the N171k mutant keratin 6a (K6a) mRNA. The study was a single-patient prospective, vehicle-controlled trial in which the hyperkeratotic plantar plaques of a patient with the N171k mutation were injected with solution containing the siRNA and demonstrated callus regression in comparison to plaques injected with the vehicle control.[26, 27]

The US Food and Drug Administration (FDA) has designated sirolimus as an orphan drug for the treatment of pachyonychia congenita. The orphan sponsor is TransDerm, Inc (Santa Cruz, Calif).[28]

No effective methods are available for treatment of the oral leukokeratosis. Good dental hygiene is encouraged. Some patients report that brushing their tongue has beneficial effects on reducing the leukoplakia.[19]

Because of the discomfort associated with the keratoderma, pain management becomes an important intervention. In addition to measures such as reduction of weight bearing and treatment of hyperhidrosis, pain medications may be required.  Nonnarcotic analgesics (especially nonsteroidal anti-inflammatory drugs) are often tried initially and may be sufficient, but occasionally narcotic analgesics are also required for pain control. Interestingly, a 2016 study found that a significant portion of the pain experienced by patients with pachonychia congenita appears to be neuropathic in nature and thus warrants neuropathic pain medications, with which most pachyonychia congenita patients have traditionally been undertreated.[29] Topical anesthetics for painful blisters and fissures have also been reported to be helpful for some patients.[12, 19]

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Surgical Care

Surgical treatment of pachyonychia congenita is usually most helpful for the treatment of cysts, which are treated no differently than cysts occurring outside of pachyonychia congenita, with standard measures such as incision and drainage or excision.

Treatment of the pachyonychia with avulsion of the affected nails has not been shown to be effective because regrowth of the nails occurs, sometimes with worse dystrophy and distortion. Ablation of the nail matrix has been inconsistently effective. Improved function and appearance of the nails following matrix ablation has been reported in some patients but not in others.[12, 19, 30]

Excision and grafting of plantar skin has not shown promise in pachyonychia congenita, owing to the reappearance of the hyperkeratosis.[19, 31]

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Consultations

A geneticist may be consulted for genetic counseling.

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Activity

Activities that require the use of fine movements with hands or fingers may be difficult for pachyonychia congenita patients. Activities that result in excessive friction, prolonged weight bearing, or repetitive trauma should be avoided or limited.

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Contributor Information and Disclosures
Author

Saira J George, MD Assistant Professor of Dermatology, The University of Texas MD Anderson Cancer Center

Saira J George, MD is a member of the following medical societies: Alpha Omega Alpha, American Academy of Dermatology

Disclosure: Nothing to disclose.

Specialty Editor Board

David F Butler, MD Section Chief of Dermatology, Central Texas Veterans Healthcare System; Professor of Dermatology, Texas A&M University College of Medicine; Founding Chair, Department of Dermatology, Scott and White Clinic

David F Butler, MD is a member of the following medical societies: American Medical Association, Alpha Omega Alpha, Association of Military Dermatologists, American Academy of Dermatology, American Society for Dermatologic Surgery, American Society for MOHS Surgery, Phi Beta Kappa

Disclosure: Nothing to disclose.

Lester F Libow, MD Dermatopathologist, South Texas Dermatopathology Laboratory

Lester F Libow, MD is a member of the following medical societies: American Academy of Dermatology, American Society of Dermatopathology, Texas Medical Association

Disclosure: Nothing to disclose.

Chief Editor

William D James, MD Paul R Gross Professor of Dermatology, Vice-Chairman, Residency Program Director, Department of Dermatology, University of Pennsylvania School of Medicine

William D James, MD is a member of the following medical societies: American Academy of Dermatology, Society for Investigative Dermatology

Disclosure: Nothing to disclose.

Additional Contributors

Gregory J Raugi, MD, PhD Professor, Department of Internal Medicine, Division of Dermatology, University of Washington at Seattle School of Medicine; Chief, Dermatology Section, Primary and Specialty Care Service, Veterans Administration Medical Center of Seattle

Gregory J Raugi, MD, PhD is a member of the following medical societies: American Academy of Dermatology

Disclosure: Nothing to disclose.

Acknowledgements

The authors and editors of Medscape Reference gratefully acknowledge the contributions of previous author, Aleksej Kansky, MD, PhD, to the development and writing of this article.

References
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The most prominent feature is a substantially thickened, brownish gray nail plate with a rough surface.
Leukokeratosis of the oral mucosa is a prominent sign. Patchy whitish areas may be seen on the back of the tongue; the buccal mucosa; and sometimes, the gingiva.
Hyperkeratotic lesions of the skin may involve acanthosis, hyperkeratosis, and parakeratosis.
 
 
 
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