Arthritis in children with LRBA deficiency – case report and literature review

Abstract

BackgroundLipopolysaccharide (LPS)-responsive and beige like anchor (LRBA) deficiency is categorized as a subtype of common variable immune deficiency (CVID). A growing number of case reports and cohorts reveal a broad spectrum of clinical manifestations and variable phenotype expression, including immune dysregulation, enteropathy and recurrent infections. The association between rheumatic disease and CVID generally has been well established, arthritis has been less frequently reported and minimal data regarding its clinical features and characteristic in LRBA deficiency has been published. This case report and literature review evaluates the characteristics and features of arthritis in LRBA deficiency patients.Case presentation and review resultsHerein, we describe a unique case of LRBA deficiency first presented with poly articular arthritis. Alongside the report, a literature review focusing on LRBA deficiency, rheumatic disease and arthritis has been conducted. We reviewed 43 publications. Among these, 7 patients were identified with arthritis. Age of first presentation was six weeks to 3 years. Male to female ratio was 4/3. Two patients were diagnosed with polyarticular Juvenile idiopathic arthritis (JIA) and three with oligoarticular JIA. Each patient was found to have different genomic mutation. The treatment was diverse and included corticosteroids, cyclosporine, methotrexate, adalidumab and abatacept.ConclusionJoint involvement is variable in LRBA deficiency, hence it should always be kept in mind as a differential diagnosis for a patient with combination of juvenile arthritis and clinically atypical immune dysregulation and / or immunodeficiency.

Comprehensive comparison between 222 CTLA-4 haploinsufficiency and 212 LRBA deficiency patients: a systematic review

“…It contains one non‐coding and 57 coding exons that encode a large 2863‐amino acid protein, LRBA. Among the 212 LATAIE patients (166 families) identified in our study, 183 (86·3%) patients (in 33 families) had homozygous mutations, 27 (12·7%) patients (in eight families) had compound heterozygous LRBA mutations, and for four patients the mutations were not reported [24–27]. Monoallelic (heterozygous) mutations were reported in two patients [28].…”

Case Report: Refractory Autoimmune Gastritis Responsive to Abatacept in LRBA Deficiency

“…LRBA deficiency is a protean disorder that can often present early in life with gastrointestinal complaints, in addition to infections, lymphoproliferation and organ or hematological autoimmunity (1,(10)(11)(12)(13)(14)(15)(16). It can represent the underpinning immune defect in cases of inflammatory bowel disease or autoimmune enteropathy with very-early onset (11,17,18).…”

Beyond the guidelines management of juvenile idiopathic arthritis: a case report of a girl with polyarticular disease refractory to multiple treatment options and Leri Weill syndrome

“…In our patient, a variety of steroid-sparing agents with different mechanisms of action have been employed with limited or no clinical success. Some of these agents were used in line with current treatment recommendations, but many were used based on anecdotal reports [24][25][26][27][28]. Finally, due to signs of systemic inflammation characterized by increased inflammatory markers (CRP and ESR) and cytokines (IL-6 and TNF-alfa), which is indicative for the activation of JAK/STAT pathway, treatment with tofacitinib, a first generation JAK inhibitor, was initiated with a good clinical response.…”