NovelCTSCmutations in a patient with Papillon-Lefèvre syndrome with recurrent pyoderma and minimal oral and palmoplantar involvement

Abstract

Conflicts of interest: None declared. Sir, Papillon–Lefèvre syndrome (PLS) is an autosomal recessive genodermatosis mainly characterized by early‐onset periodontitis and palmoplantar keratoderma. Recurrent pyogenic skin infections, usually of mild degree and self‐healing, are relatively common additional features.1, 2 PLS is caused by loss‐of‐function mutations in the CTSC gene, which encodes for cathepsin C, a lysosomal cysteine protease required for the activation of granule‐associated serine proteases in immune/inflammatory cells.3 Cathepsin C consists of four identical subunits, each composed of three distinct polypeptide chains, the heavy chain, light chain and the N‐terminal fragment, held together by noncovalent interactions. The heavy and light chains form a two‐domain papain‐like structure, which contains the catalytic site, whereas the N‐terminal fragment shapes the ‘exclusion’ domain, which is crucial for substrate binding and selectivity.4 More than 60 distinct CTSC mutations have been identified, most of which are missense mutations that alter protein folding and function.5 We report a 24‐year‐old Italian woman, who underwent dermatological evaluation for recurrent pyoderma. She was the only affected child of healthy nonconsanguineous parents. Primary dentition was normal. In infancy, the gingiva surrounding the erupted teeth started to become inflamed with consequent premature tooth loosening. All remaining deciduous teeth were extracted before spontaneous exfoliation. The first permanent tooth erupted at 6 years of age. Progression of periodontal disease was slow, requiring extraction of only two permanent teeth. At the age of 4 years, multiple suppurative and inflamed skin lesions appeared on the cheeks and, subsequently, involved most of the body surface. These lesions had a protracted course and healed with scar formation. Since childhood the patient has complained of multiple and painful plantar callosities. Examination of the oral cavity revealed gingival inflammation and recession, and slight tooth mobility (Fig. 1a). A panoramic radiograph revealed bone resorption of mild to moderate degree around the teeth. In addition, the patient exhibited multiple callosities and minimal diffuse erythema of the soles (Fig. 1b,c). Palmar skin appeared slightly xerotic. Mild longitudinal ridging was also evident on the fingernails. Over the buttocks, thighs and calves, there were numerous polymorphic scarring lesions at sites of previous pyogenic infections. The most recent lesions appeared as violaceous nodules and plaques, while the oldest ones were hypopigmented and atrophic scars frequently showing subcutaneous fat herniation (Fig. 1d,e). A 10‐month course of isotretinoin (0·5 mg kg−1 daily) improved both the skin infections and the plantar keratoderma.