Smoldering Inside: Clinical Presentation and Genetics of Autoinflammatory Disorders: Case Series of 15 Patients
Year: 2025
Type: article
Study design: Observational Study
Abstract: Introduction Autoinflammatory diseases are inborn errors of immunity caused by dysregulation of the innate immune system. Despite increasing recognition of genetically defined disorders, reports from Mexico remain limited. We describe fifteen Mexican patients with monogenic autoinflammatory diseases, summarizing their clinical, genetic, and therapeutic features to expand phenotypic understanding. Presentation Among the fifteen patients, 66% were female, with a median symptom onset age of 2.5 years (range 0.2–16 years). According to the inflammatory pathways, patients were categorized as: inflammosomopathies (20%; NLRP12, NLRC4, MVK), type I interferonopathy (26.7%; TREX1, TMEM173, PSMB8, POMP), cell death–driven mechanism (26.7%; TNFAIP3,RELA, RNF31, RIPK1), and uncategorized monogenic autoinflamatory disease (26.6%; NOD2 [two cases], IL1RN, PLCG2). Common clinical features included recurrent fever (20%), oral ulcers (20%), cutaneous involvement (60%), arthritis (26.7%), hemophagocytic lymphohistiocytosis (HLH) (20%), uveitis (20%), vasculitis (20%), hepatosplenomegaly (33%), lymphadenopathy (33%), central nervous system involvement (33%), and serositis (6.6%). Laboratory findings revealed anemia (66%), leukocytosis (60%), thrombocytosis (40%), autoantibody positivity (40%), dysgammaglobulinemia (46%), elevated erythrocyte sedimentation rate/PCR (73%), and hyperferritinemia (20%). Biologic or immunosuppressors included anti-CD20 (n = 3), anti-TNF (n = 5), IL-6 blockers (n = 4), JAK inhibitor (n = 1), colchicine (n = 5), conventional synthetic disease-modifying antirheumatic drugs (n = 14), and intravenous immunoglobulin (n = 10). At last follow-up, outcomes among living patients (n = 13) were remission in 30.8% (n = 4), minimal activity in 23% (n = 3), and moderate activity in 46% (n = 6). Two patients (13%) died. Conclusion This first large Mexican cohort from a single referral center highlights the clinical and genetic heterogeneity of monogenic autoinflammatory diseases. Cutaneous manifestations were the most frequent, followed by joint involvement and HLH. Universal genetic confirmation enabled targeted therapies; however, 69% of patients remain with minimal or moderate activity, reflecting challenges in early diagnosis and access to precision treatments, which are essential for optimal outcomes in these patients.
Source: Journal of Human Immunity
Authors: Hiromi Onuma-Zamayoa, Selma Cecilia Scheffler-Mendoza, María del Mar Saez De Ocariz-Gutiérrez, Juan Carlos Bustamante-Ogando, Melissa Ivonne Espinosa-Navarro, Francisco Eduardo Rivas-Larrauri, Marco Antonio Yamazaki-Nakashimada, Edgar Alejandro Medina-Torres, Sara Elva Espinosa-Padilla, Saúl O. Lugo-Reyes
Institution: Instituto Nacional de Pediatria
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: diamond
OpenAlex ID: W7116766601
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