A Tale of Two Flares: Case of Granulomatosis with Polyangiitis and Systemic Lupus Erythematosus in IgA Deficiency

Introduction: Primary or acquired immunoglobulin A (IgA) deficiency has been linked to an increased susceptibility to infections, allergies, and autoimmune conditions. We report a unique case of a 29-year-old male with a history of granulomatosis with polyangiitis who subsequently developed lupus nephritis in the context of IgA deficiency. Case Description: A 29 year-old male with past medical history of necrotizing glomerulonephritis secondary to Granulomatosis with Polyangiitis (GPA) diagnosed when he was 13 years old presented to the hospital with involuntary weight loss and fatigue for two weeks. Patient had been previously treated with Cyclophosphamide and Rituximab and Azathioprine for maintenance. He did not experience any relapses after achieving remission though he developed an acquired hypogammaglobinemia after rituximab for which he received IVIG until the age of 21. On presentation, serum creatinine was at baseline. Urine analysis showed microscopic hematuria. Urine random protein to creatinine ratio was 450 mg/g. C3 was 91mg/dl and C4 was 3mg/dl. Proteinase 3 antibody was 113IU/ml. ANA was positive (1:1280), and anti-ds DNA was more than 300. Anti-smith RNA Ab was positive. IgA level was <10, IgG 1725, and IgM 49. Patient underwent kidney biopsy which showed focal glomerulonephritis consistent with Class III lupus nephritis. The patient was started on hydroxychloroquine, steroids and mycophenolic acid, which were continued at discharge. Discussion: IgA deficiency whether primary or secondary can be associated with development of autoimmune conditions. Patients with IgA deficiency have an 8-fold higher prevalence of Systemic Lupus Erythematosus (SLE) compared to the general population. Although Rituximab and Cyclophosphamide have been linked to hypogammaglobulinemia that can persist even after discontinuation of treatment, IgA level is less affected. In our case, the early-onset diagnosis GPA, which has a rare incidence of 1 in 1,000,000 among pediatric patients, and the persistent lack of IgA reconstitution despite recovery of other immunoglobulins, suggest that this patient likely had a primary rather than acquired immunodeficiency, predisposing him to the development two distinct autoimmune diseases with different treatment approaches. This case underscores the importance of broadening differentials and repeating renal biopsy when clinical suspicion is high.