Expanding the Clinical Features of Autoinflammation and PLCγ2-associated Antibody Deficiency and Immune Dysregulation by description of a Novel Patient.

Autoinflammation and phospholipase Cγ2-associated antibody deficiency and immune dysregulation (APLAID) is an exceedingly rare monogenic autoinflammatory disease. To date, only 5 cases have been reported with four distinct pathogenic mutations.We present a novel case of APLAID, corroborated by molecular analysis, with newly described clinical findings including central nervous system vasculitis (CNSV); and distinctive histopathological characteristics that may expand our knowledge of this rare disease's phenotype.This is a case report presentation of a 3 year-old boy, seen at a reference pediatric hospital in Mexico. His parents authorized the use of his clinical information and photographs.A 3-day-old boy presented to the emergency department with a vesiculopustular rash that resolved within one week. Two months later he developed widespread papules and pseudovesicles that evolved into infiltrated plaques. He also had periodical flares of conjunctivitis, diarrhea, and erythematous blistering acral plaques triggered by upper respiratory infections. By the age of 10 months, he experienced seizures and CNSV. Laboratory work-up showed mild neutropenia, decreased serum levels of immunoglobulins, and B cell lymphopenia. A skin biopsy revealed a dense, perivascular and interstitial histiocytic and granulomatous infiltrate, with palisading granulomas, and leukocytoclastic vasculitis with karyorrhexis. APLAID syndrome was confirmed by Sanger sequencing of PLCG2 gene [heterozygous genotype LRG_376t1:c.2543T>C or p.(Leu848Pro)].Presence of CNSV has not been previously described in APLAID, however as the number of reported patients with APLAID is very small, it is possible that the overall spectrum of clinical manifestations has not been completely elucidated. The herein identified p.(Leu848Pro) variant was also documented in a Portuguese patient; suggesting that it could be a PLCG2 gene "hot-spot". This article is protected by copyright. All rights reserved.