Differential Diagnosis

Onychomycosis. While the hyperkeratotic nail thickening seen in pachyonychia congenita (PC) may be mistaken for onychomycosis, dermatophytic infections do not affect all finger and toenails, particularly at an early age. In the rare conditions of autoimmune endocrinopathy-candidiasis-ectodermal dystrophy (APECED) and systemic mucocutaneous candidosis, all nails may be affected. Oral leukokeratosis together with nail dystrophy is often an indication of pachyonychia congenita and may be mistaken for Candida albicans (thrush), white sponge nevus, and/or leukoplakia. Epidermolysis bullosa simplex (EBS) or other palmoplantar keratodermas can result in a similar pattern of plantar blister formation or hyperkeratosis, respectively; however, they do not share the characteristic nail changes of PC.

Source: GeneReviews — "Pachyonychia Congenita"

Management Guidelines

Evaluations Following Initial Diagnosis

To establish the extent of disease and needs in an individual diagnosed with pachyonychia congenita, the following evaluations are recommended:

• Thorough clinical examination to assess each affected area. These will vary based on the specific gene involved and may need to be repeated once genetic testing is completed in order to fully understand the phenotype of the affected individual.

• Consultation with a clinical geneticist and/or genetic counselor

Treatment of Manifestations

Preliminary treatment guidelines have been published and continue to be refined. The current treatment modalities primarily center on symptomatic relief of pain, hygienic grooming practices including paring of hyperkeratotic areas, treatment of secondary infection when indicated, and use of various walking aids including wheelchairs, crutches, and canes. Palmoplantar keratoderma. Frequent grooming of the feet is essential and includes paring down the hyperkeratotic areas. However, trimming too aggressively can greatly increase pain. Some find it helpful to soak the feet prior to the paring. The surface of the skin and the instruments used should be clean to avoid infection. Blisters should be punctured with a sterile needle, the fluid drained, and the blister roof left in place until it dries and is shed away. Topical therapies to remove the hyperkeratosis:

Source: GeneReviews — "Pachyonychia Congenita"

Clinical Guidance

Some report that higher temperatures and higher humidity worsen the condition.

Source: GeneReviews — "Pachyonychia Congenita"

Therapies Under Investigation

In 2014, a Phase 1b clinical trial sponsored by PC Project and TransDerm was performed using topical sirolimus. This study included 15 affected individuals and was conducted by Dr Joyce Teng at Stanford University. Background research for this trial was previously published . Short interfering RNA (siRNA) can selectively block expression of a specific K6a-causing pathogenic variant . The siRNA trial included treatment of a single individual with a specific KRT6A pathogenic variant in a dose-escalation trial of an siRNA directed against the p.Asn171Lys mutated allele . The affected individual did not experience any adverse effects from the experimental treatment. The affected person also experienced callus regression on the foot treated with siRNA.

Source: GeneReviews — "Pachyonychia Congenita"