Etiology

IgAV is an autoimmune disease involving IgA immune complexes. Disease presentation is believed to derive from an abnormal glycosylation status of the IgA protein prompting an autoimmune response.[7]

A variety of infectious and chemical triggers have been proposed. IgA is released from the mucosa as the first line of defence when faced with immune challenges, therefore many cases of IgAV in children occur after a viral or bacterial upper respiratory tract infection, especially streptococcal infections.[15][17]

A complex interaction of several factors, including age, sex, ethnic background, and environmental influences, may contribute.[18] Geographical variation is seen, and IgAV is more common in Asian populations. Genetic factors also seem to be implicated, including genes associated with general autoimmunity (e.g., human leukocyte antigen [HLA] alleles) and genes that regulate vascular system response to an insult (e.g., endothelial nitric oxide synthase [eNOS], angiotensin-converting enzyme [ACE]). HLA-subtypes and genes encoding host defence mechanisms are associated with a predisposition to developing the condition.[7]

Drug-related cases of IgAV occur in adults and children. Causative drugs include penicillin, cefaclor, minocycline, hydralazine, or phenytoin.[19][20]​​

Pathophysiology

IgAV is a small-vessel leukocytoclastic vasculitis characterized by the tissue deposition of IgA, and IgA-containing immune complexes, within affected organs. Skin biopsies of lesions show neutrophils and monocytes as the predominant cell types. Fluorescence microscopy reveals IgA, C3, and fibrin deposition within the small vessels.[21] Deposition of these proteins, and occasionally that of IgG, is a prominent feature in the mesangial region of the kidney.[21][22]​ The renal pathogenesis of this disease is believed to be sufficiently similar to that of IgA nephropathy.[23]

Classification

International Study of Kidney Disease in Children classification[4][5]​​

Used to classify renal biopsies.

  • Grade I: Minimal changes

  • Grade II: Mesangial proliferation

  • Grade III: Crescents <50% of the glomeruli; (A) focal or (B) diffuse

  • Grade IV: Crescents 50% to 75% of the glomeruli; (A) focal or (B) diffuse

  • Grade V: Crescents >75% of the glomeruli

  • Grade VI: Membranoproliferative glomerulonephritis

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