Early-onset recurrent panniculitis as a phenotype of NLRC4-associated autoinflammatory syndrome: Characterization of pathogenicity of the p.Ser445Pro NLRC4 variant.

Monoallelic NLRC4 gain-of-function variants cause an inflammasomopathy with diverse clinical forms including infantile enterocolitis, recurrent macrophage activation syndrome, cold-induced urticaria-like lesions (or familial-cold autoinflammatory syndrome, FCAS4), and painful subcutaneous nodules. Here, we identified a large family with six consecutive generations affected. Genetic analyses detected the heterozygous p.Ser445Pro NLRC4 variant in three patients, which has been previously reported in a Dutch family with FCAS4. We aimed to describe the clinicopathological features and the functional consequences of the detected NLRC4 variant. Patients presented an early-onset (3 months-6 years) inflammatory disease characterized by recurrent panniculitis, fever and arthralgia. Histopathological examination showed perivascular and interstitial lymphohistiocytic infiltrates in the dermis and mixed panniculitis. Functional analysis supported the conclusion that the p.Ser445Pro NLRC4 variant leads to a constitutive activation of NLRC4-inflammasome and increased plasma levels of IL-18. Prompt recognition of early-onset panniculitis through clinicopathological examination and laboratory biomarkers may allow targeted therapies.

Eritema necrolítico migratorio asociado a glucagonoma / Glucagonoma-related necrolytic migratory erythema

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Dermatitis herpetiforme. Patogenia, diagnóstico y tratamiento / Dermatitis herpetiformis. Pathogenesis, diagnosis and treatment

La dermatitis herpetiforme es una enfermedad ampollosa autoinmune poco frecuente. Las lesiones clínicas son polimorfos y el estudio de anatomíapatológica es inespecífico en un porcentaje elevado de casos, por ello su diagnóstico puede pasar desapercibido si no se realiza estudio de inmunofluorescenciadirecta y las pruebas complementarias pertinentes. Se considera la manifestación cutánea de una enteropatía por sensibilidad al gluten,asintomática en un elevado numero de casos. Frecuentemente se asocia a otras enfermedades autoinmunes y existe un riesgo de desarrollo de linfomano Hodgkin de células T. Su diagnóstico se basa en la clínica, pruebas tisulares ( histopatología e inmunofluorescencia directa) y serológicas ( anticuerposanti-endomisio, anti-transglutaminasa tisular y anti-transglutaminasa epidérmica). La base del tratamiento es la dieta sin gluten estricta quedebe instaurarse precozmente con la finalidad de evitar complicaciones posteriores y mantenerse de por vida. La sulfona y otros fármacos son útilespara inducir la remisión de los síntomas cutáneos hasta el inicio del efecto de la dieta (AU)

Dermatitis herpetiformis is a rare autoimmune bullous disease. Because the clinical lesions could be polimorphous, and the pathological changes areno specific in a high percentage of cases, it is often misdiagnosed if direct immunofluorescence study and other complementary tests are not performed.It is considered as a cutaneous manifestation of a gluten-sensitive enteropathy, asymptomatic in most of the patients. It is often associatedwith other autoimmune diseases and there is also an increased risk of non Hodgkin T cell lymphoma. Its accurate diagnosis is established clinically, andwith tisular ( cutaneous biopsy, direct immunofluporescence) and serological test( antibodies against endomisio, tisular transglutaminase and epidermaltransglutaminase). The mainstay of treatment is a strict gluten free diet, that must be instaured as early as possible with the aim of to avoid furthercomplications and must be lifelong continued. Dapsone and other drugs may be used until the gluten free diet is effective (AU)