A case of intractable, familial nail and skin thickening
A 36-year-old Hispanic woman with recalcitrant onychomycosis had been treated with multiple courses of oral terbinafine by her primary-care clinician over several years. However, she felt that the antifungals had no effect on her nail condition. We met when she requested alternative therapy and was referred to the county dermatology clinic for further assessment and treatment.
The patient reported that her nails had been thick and discolored since she was a child. She denied any repeated trauma to the affected nails. In addition to the nail deformities, she reported the development of thick and scaly skin on her palms and soles during childhood. These areas had persisted and were also unaffected by the terbinafine. In answer to further questioning, she disclosed that multiple family members, including her father and two of her children, had similar nail and skin changes. They also had been prescribed antifungal agents, without improvement.
The woman was otherwise healthy and had no significant medical problems. She reported no known abnormalities at birth. There was no known family history of genetic disorders or psoriasis.
On examination, the patient was noted to have thickened fingernails with an omega shape (Figure 1). Most nails had a yellow hue, particularly at the distal nail plate. Her toenails were not as severely affected as her fingernails. No scaling of the periungual area or digital web spaces was observed. Thick scaly plaques covered the weight-bearing areas of the soles and a few focal areas on the palms. There were no similar plaques on other parts of her body, and her scalp was free of scale. Her oral mucosa was unremarkable. A physical examination was otherwise within normal limits.
A number of skin conditions can present with dystrophic nails, including onychomycosis, psoriasis, and trauma. Onychomycosis often produces nail thickening and discoloration. Moreover, associated scaly plaques of the skin might represent tinea corporis, which could be easily transferred among family members. However, tinea pedis often affects the web spaces and is usually not limited to the weight-bearing areas. To further investigate the possibility of a fungal etiology, a KOH preparation of skin and nail scrapings was performed, but it revealed no fungal elements.
Alternatively, fungal culture of the skin or nail would aid diagnosis.
Psoriasis often produces skin and nail changes and is occasionally familial. However, characteristic psoriatic nail changes, including brownish focal areas of discoloration (oil spots), pitting of the nail plate, and distal lifting of the nail plate (onycholysis), were not present in this case. While psoriasis can affect the palms and soles, it typically occurs on the elbows, knees, and scalp. A skin biopsy of the affected area can confirm the diagnosis of psoriasis. However, given the clinical setting, such investigation was not necessary in this case.
Nail trauma can result in nail dystrophy, though there would be irregular changes in the nail thickness rather than uniform hypertrophy. It also would not account for the skin findings or affected family members in this case. Several genetic conditions can produce nail changes, though they are much rarer than onychomycosis or psoriasis. In this patient, the clinical presentation of the characteristic pincer-shaped nails, palmoplantar keratoderma, similar symptoms in family members consistent with an autosomal dominant inheritance, and failure of oral antifungal agents suggest a diagnosis of pachyonychia congenita (PC). While molecular DNA analysis would confirm the diagnosis, the patient declined to undergo any genetic testing.
PC is an autosomal dominant disorder that results from keratin gene defects. These mutations disrupt the normal intermediate filament assembly and may play a role when frictional stressors are applied to epithelial cells. DNA molecular analysis can be used to confirm the diagnosis. Keratin 6a and 16 mutations cause type 1 (Jadassohn-Lewandowsky) PC, while keratin 6b and 17 mutations cause type 2 (Jackson-Lawler) PC.
Perhaps the most notable and constant feature of PC is nail dystrophy. Wedge-shaped thickening of the nail bed leads to nail-plate elevation and increased transverse curvature of the nail plate. The nails may assume an omega or pincer shape. Fingernails are affected more than toenails, and nail-plate shedding may occur. Nails often have a yellowish-brown color.
Palmoplantar keratoderma occurs in both types of PC, although it may be more severe in type 1 disease. Thickened plaques with dense scale develop over areas of friction, weight bearing, or pressure. There may be associated hyperhidrosis. The elbows and knees may exhibit follicular hyperkeratosis.
Type 2 PC is associated with natal teeth, while type 1 PC adults may exhibit oral leukokeratosis. The leukokeratosis is not premalignant and most commonly affects the tongue and buccal mucosa.
Treatment of PC includes topical agents, such as emollients and keratolytics. Affected nails can be pared. Systemic retinoids may improve both the nail and skin changes. Oral antifungals are not effective against the nail dystrophy.
Acitretin was initiated in this case, but the patient was unable to tolerate the drying side effects. She was given 40% salicylic acid in white petrolatum for both the nails and keratoderma, with some improvement.
This case illustrates the importance of accurate diagnosis and the need to re-evaluate the clinical findings as a whole when seemingly appropriate treatment fails. Additionally, enlisting the assistance of consultants is often a worthwhile request that can help redirect the clinician's analysis of a difficult case.