Biologic therapy targeting IL‐17 ameliorates a case of congenital ichthyosiform cornification disorder

Abstract

We report the case of a 20-year-old male with severe congenital ichthyosiform erythroderma, arthritis and chronic liver disease who was successfully treated with secukinumab, a human monoclonal IgG1 antibody that binds to interleukin (IL)-17A. The patient was born to non-consanguineous parents. At birth, he presented as a collodion baby and subsequently developed severe erythroderma and large lamellar scales (Figure 1 a), palmoplantar keratoderma and nail dystrophy. Acute hepatitis of unknown origin and hepatosplenomegaly were diagnosed at the age of two years. Virus serology was negative and immune parameters including blood count, antinuclear antibodies and immunoglobulins were normal. In early childhood the patient was treated with topical and systemic corticosteroids with limited success. Retinoids were administered but were discontinued because of the hepatitis. At the age of nine, combination therapy with oral corticosteroids (0.5 mg/kg body weight) and mycophenolate mofetil (2 g per day) was initiated but had to be discontinued due to abnormal liver values. The patient then developed seronegative polyarthritis at the age of 18 years and azathioprine 2 × 50 mg per day was started. This improved the arthritis but had no effect on the skin. Careful consideration of a recently proposed multistep approach to the diagnosis of rare genodermatoses [ 1 ] did not result in identifi cation of a specifi c genetic cornifi cation disorder or syndrome. Whole-exome sequencing did not disclose any mutations in genes known to be associated with congenital ichthyoses ( TGM1 , ABCA12 , NIPAL4 , ALOX12B , CYP4F22 , ALOXE3 , PNPLA1 , CERS3 , SDR9C7 ) or psoriasis ( IL36RN , CARD14 , NOD2 ). A lipid storage disease such as the Chanarin-Dorfman syndrome was excluded since no mutation of the ABHD5 gene was detected. Mutations of the 3-keto-dihydrosphingosine reductase (KDSR) gene, which cause progressive symmetric erythrokeratoderma or connexin-related disorders, were also excluded. A skin biopsy taken before treatment (Figure 2 a) showed a psoriasis-like dermatitis with hyperparakeratosis, acanthosis and papillomatosis. The infl ammatory infi ltrate consisted of focal intraepidermal neutrophils and aggregation of lymphocyte-rich infl ammatory cells in the papillary plates, which were immunopositive for IL-17A (BIN677933, Bioss Antibodies (Massachusetts, USA). Although we have not yet detected a specifi c mutation in our patient, the clinical picture resembles a cornifi cation disorder such as congenital ichthyosiform erythroderma (CIE), which is one of the autosomal recessive congenital ichthyoses (ARCIs), rare genetic cornifi cation disorders associated with