Henoch-Schoenlein purpura (HSP) like lesions in IL12RB1 and IL12B defects - A multi-centric experience from India

INTRODUCTION: Mendelian Susceptibility to Mycobacterial Disease (MSMD), caused by IL12RB1 or IL12B mutations, typically presents with intra-cellular infections such as BCG-adenitis or Salmonella. Rarely, patients with IL12RB1/IL12B defects can exhibit cutaneous manifestations like Henoch-Schonlein purpura (HSP). This study aimed to evaluate such vasculitic manifestations in genetically confirmed cases with MSMD in India and review the literature for similar associations. METHODS: We included nine patients with genetically proven MSMD presenting with features of HSP-like small vessel vasculitis from pediatric immunology clinics across three tertiary care centers in India. Clinical, laboratory, histopathological, and genetic data were recorded using a structured proforma. Skin biopsy findings, IgA levels, renal involvement, and infection history were analyzed. Additionally, a literature review was performed using PubMed, Scopus, and Google Scholar databases to identify similar reported cases. RESULTS: In our cohort, 8 patients had IL12RB1 defect, and one had IL12B defect. All had maculopapular purpuric rash in lower limbs, predominantly in the anterior aspect of legs and posterior thighs resembling the rash of HSP. Leukocytoclastic vasculitis (LCV) was observed in 77.7% patients (n=7), with 2 out of 5 had IgA deposits in dermo-epidermal junction. Concurrent infections due to Salmonella sp. and Pandorea apista were documented in 44.4% (n=4) and 22.2% (n=2), respectively. Treatment focused on antimicrobial therapy led to clinical improvement. CONCLUSION: The HSP-like vasculitic rash usually occurred in setting of underlying bacterial infections in patients with particularly IL12RB1/IL12B defects. These skin lesions can also be considered as one of the potential clinical clues for underlying IL12RB/IL12B defects.