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. [21]
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. [21]
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). [21]
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. [22, 23, 24]
Pharmaceutical treatment of pachyonychia congenita includes systemic retinoids, such as isotretinoin [25] and etretinate. [26] 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.
Evidence suggests that treatment with rapamycin (or rapamycin analogues) may also be a promising option for treatment. The proposed mechanism of action is selective inhibition of expression of an inducible keratin (K6a) in human keratinocytes. [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] A 2018 report of compounded topical 1% sirolimus ointment found it to be a safe and effective treatment for the plantar keratoderma in two patients. [29]
Based on in vitro evidence that simvastatin and a statin precursor, compactin, decrease KRT6A gene transcription, [30] statin therapy has been proposed as worthy of investigation; a 2018 case report of successful treatment with rosuvastatin in a pediatric patient with a KRT6A mutation suggests it may be a promising option. [31]
An innovative and new approach to treating pachyonychia congenita was 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. [32, 33]
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. [21]
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, evidence suggests that a significant portion of the pain experienced by patients with pachonychia congenita may be neuropathic in nature and thus warrants neuropathic pain medications, with which most pachyonychia congenita patients have traditionally been undertreated. [13, 14] Topical anesthetics for painful blisters and fissures have also been reported to be helpful for some patients. [12, 21]
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, 21, 34]
Excision and grafting of plantar skin has not shown promise in pachyonychia congenita, owing to the reappearance of the hyperkeratosis. [21, 35]
Consultations
A geneticist may be consulted for genetic counseling.
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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The most prominent feature is a substantially thickened, brownish gray nail plate with a rough surface.
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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.
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Hyperkeratotic lesions of the skin may involve acanthosis, hyperkeratosis, and parakeratosis.
