Pachyonychia congenita (PC) is a rare autosomal dominant genodermatosis caused by mutations in the keratin genes (KRT) 6A, 6B, 6C, 16, and 17.1 The primary clinical features include hypertrophic nail dystrophy, areas of focal palmoplantar keratoderma, follicular keratoses, mucosal leukokeratosis, cutaneous cysts, hoarseness, and, infrequently, natal teeth.1 Plantar keratoderma occurs in up to 95% of patients.1 It can manifest as callosities, blistering, fissures, thickened skin, and erosions, typically in pressure areas.1 Associated plantar pain, probably arising from blister formation between the hyperkeratotic epidermis and the dermis and exacerbated by sweating,2 has also been shown to have a neuropathic origin.3 It is present in almost all patients and has been shown to be the most relevant symptom affecting health-related quality of life in these patients.1

Multiple therapeutic modalities have been evaluated to treat the manifestations of PC, including mechanical debridement of calluses, emollients, topical keratolytics, retinoids, steroids,4 simvastatin, and sirolimus.4,5 However, all these treatments have shown limited efficacy.2,4 Several case reports have described the effectiveness of botulinum toxin (BT) injection in reducing plantar pain in these patients.2,6–8

We report the case of a 24-year-old patient with PC and a KRT6A mutation who presented with nail dystrophy, follicular keratoses, and plantar keratoderma causing incapacitating pain (Fig. 1).

Fig. 1.

Clinical image of the soles of the patient.

Previous treatment with simvastatin or sirolimus, both oral and topical, was associated with an incomplete response. The use of analgesics such as pregabalin and amitriptyline did not result in sufficient pain improvement. Pain during walking significantly restricted his daily activities, preventing school attendance and resulting in social isolation. At the age of 18 years, treatment with injection of 100U of onabotulinumtoxinA was initiated. Because of a positive response, treatment was repeated every 4–6 months. After 3 years of treatment, a progressive decrease in treatment efficacy was observed, requiring dose escalation to 300U and eventually leading to lack of response at the age of 23 years. At that time, the impact of PC on our patient's health-related quality of life was rated with a score of 20 on the Pachyonychia Congenita Quality of Life (PCQoL) questionnaire, a 0- to 36-point scale on which higher scores correspond to diminished quality of life.9

IncobotulinumtoxinA, 100U diluted in 1mL of normal saline, was injected subcutaneously under sedation and distributed across 10 points, 0.1mL/injection and 10U/injection, in the callused areas of each sole.

Although the extent of hyperkeratosis showed only marginal reduction, 2 weeks after this procedure, the patient experienced pain improvement, allowing him to resume walking and even engage in physical exercise. The PCQoL questionnaire score at that time was 0.

Treatment response lasted for 14 weeks, after which a new injection was administered, maintaining the positive results. The patient provided written informed consent for publication of the clinical case and figures.

This case contributes to the existing evidence regarding the effectiveness of BT injection in the management of PC.

BT inhibits sweat secretion by blocking the acetylcholine pathway and has proven effective in the treatment of PC signs exacerbated by sweating, reducing hyperhidrosis, maceration, and blistering.6 However, our patient did not present with plantar blistering or excessive sweating. The effect of BT on nociception in our case may be explained by a direct effect of BT on C-fiber sensory nerve axons, where it blocks the release of pain mediators such as substance P, calcitonin gene-related peptide, or glutamate.6

Koren et al.2 recently described significant improvement in quality of life in 5 patients with PC after onabotulinumtoxinA or abobotulinumtoxinA injection. Their treatment protocol consisted of injections of 20–40U of BT distributed in the central part of the callosity and injections of 8U along the border between healthy skin and calluses.2 Swartling et al.7 also reported significant improvement after curettage and abobotulinumtoxinA treatment of plantar pain in 8 patients with PC and painful plantar hyperkeratosis or blisters.

Loss of therapeutic response after repeated injections of BT has been described in other fields of medicine.10 This effect has been attributed mainly to the development of neutralizing antibodies.10 Swartling et al.7 described 3 cases of loss of response to onabotulinumtoxinA and reported good responses to injection of type B BT, which inhibits acetylcholine release by targeting a different intracellular protein than type A BT.

Unlike other type A BT formulations, incobotulinumtoxinA is purified, eliminating traces of inactive neurotoxin and other nonfunctional proteins that could stimulate the production of these antibodies.10 In our patient, switching to this formulation may have led to recovery of the therapeutic effect, likely due to evasion of the immune response. In conclusion, BT injection therapy is effective in reducing plantar pain in patients with PC. In the event of reduced or lost response to onabotulinumtoxinA, switching to incobotulinumtoxinA may allow regain of therapeutic control.