2026-06-15 | Secukinumab for lamellar ichthyosis in an adolescent: a case report.

Lamellar ichthyosis (LI) is a rare hereditary disorder of keratinization, most commonly inherited in an autosomal recessive manner and frequently associated with pathogenic variants in the TGM1 gene. Patients usually present with generalized scaling, xerosis, and pruritus from birth. Current therapeutic options remain limited, and systemic retinoids are often associated with considerable adverse effects. A 14-year-old female individual presented with generalized pruritic, lamellar scale-like skin changes present since birth. The diagnosis of LI was established based on clinical findings, histopathological evaluation, and genetic testing [two pathogenic variants in the TGM1 gene, consistent with autosomal recessive congenital ichthyosis type 1, Online Mendelian Inheritance in Man (OMIM): 242300]. Oral administration of acitretin (10 mg twice daily) was initiated; however, treatment was discontinued due to elevated hepatic transaminase levels and severe xerosis with pruritus. Subcutaneous administration of secukinumab (150 mg weekly) was subsequently initiated. After five weekly doses, the dosing frequency was reduced to once monthly. Over 8 weeks, substantial clinical improvement was observed, with a satisfactory therapeutic response. The patient remained on active treatment at the time of reporting. Secukinumab appeared to be effective in this patient with LI and may warrant further investigation as a potential therapeutic option for inherited ichthyosis.

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2026-04-11 | Mutation Analysis in Ten Cases With PNPLA1-Nonsyndromic Epidermal Differentiation Disorder: Evidence of a Founder Effect.

Autosomal recessive congenital ichthyosis (ARCI) belongs to a heterogeneous group of nonsyndromic epidermal differentiation disorders (nEDD). Variants in PNPLA1, which encodes a transacylase essential for the formation of epidermal lipid barrier, underlie ARCI10. This study aims to unveil the underlying genetic basis in ten Chinese cases diagnosed with ARCI, and to determine the origin of a prevalent variant. Ten cases, encompassing twelve patients with ARCI, were recruited for this study. Whole-exome sequencing combined with Sanger sequencing was used to detect the underlying variants. Haplotype analysis using flanking highly polymorphic SNPs was used to trace the origin of the c.1300delG variant in the PNPLA1 gene. All patients developed generalized fine scales and erythema shortly after birth. Marked phenotypic heterogeneity was observed among the affected individuals, leading to diagnosis of either generalized or localized nEDD. In total, we detected three recurrent variants (c.1300delG, p.A434Hfs*22; c.434 T > C, p.Ile145Thr; c.488C > T, p.Pro163Leu) and five novel variants (c.205 + 1G > A, splicing; c.74C > T, p.Ser25Phe; c.473G > A, p.Cys158Tyr; c.731A > G, p.Tyr244Cys; c.1318C > T, p.Arg440*) in PNPLA1. The c.1300delG variant, prevalent in 7 unrelated ARCI cases, was associated with a common haplotype. Furthermore, we presented the beneficial effect of secukinumab treatment in one of our patients. Our findings suggest that the c.1300delG variant is a highly prevalent variant in Chinese PNPLA1-associated nEDD patients, and indicate that the recurrent variant may originate from a common ancestor in southern China, suggesting a regional founder effect. The observed response with secukinumab in one patient suggests that it might represent a potential therapeutic option for PNPLA1-nEDD patients.

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2026-01-20 | Harlequin ichthyosis: diagnosis, standards of care, and treatment — a systematic review

Background. Harlequin ichthyosis (HI) is the most severe form of autosomal recessive congenital ichthyosis (ARCI), caused by mutations in the ABCA12 gene. Impaired lipid transport in keratinocytes leads to profound dysfunction of the epidermal barrier and, consequently, to the severe clinical phenotype already evident at birth. Despite the rarity of this condition, HI remains one of the most dramatic dermatological disorders of the neonatal period. The aim of this study is to present the current state of knowledge on the etiology, clinical presentation, diagnosis and treatment methods of HI. This paper seeks to compile the available data in one place and to discuss the diagnostic and therapeutic challenges. Methods. A systematic analysis of the available scientific literature was carried out, including clinical studies, case reports, review articles, and reports on modern diagnostic and therapeutic techniques. Results. The development of methods enabling genetic diagnosis has allowed for early and precise detection of ABCA12 gene mutations, which has improved the possibilities for prenatal diagnosis and perinatal care planning. Multidisciplinary care and early use of retinoids have reduced mortality in newborns with HI. Nevertheless, the disease remains associated with a high risk of systemic complications and long-term sequelae. Conclusions. Harlequin ichthyosis remains a severe disease that requires rapid diagnosis, interdisciplinary management and continuous monitoring. Technological and therapeutic advances have improved the prognosis; however, further studies are needed to optimize retinoid therapy, management protocols and strategies supporting skin barrier regeneration in patients affected by HI.

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