Advances in our understanding of the pathogenesis of Henoch-Schönlein purpura and the implications for improving its diagnosis

Abstract

Henoch-Schönlein purpura (HSP) is a leukocytoclastic vasculitis classically characterized by palpable purpura, arthritis, abdominal pain and renal disease. In this article, we summarize our current understanding of the pathogenesis of HSP and the implications for improving its diagnosis. Although the pathogenesis of HSP is not fully understood yet, exciting new information has emerged in recent years, leading to a better understanding of its pathogenesis. Here, we discuss genetic predisposition, immunoglobulins with a particular emphasis on IgA1, activated complements, cytokines and chemokines, abnormal coagulation and autoantibodies in the underlying pathogenic mechanisms. Finally, diagnostic criteria for HSP developed by institutions such as the American College of Rheumatology and the European League against Rheumatism/Paediatric Rheumatology European Society were proposed to improve early detection and diagnosis.

Keywords::

• cytokines
• diagnosis
• genetic susceptibility
• Henoch-Schönlein purpura
• immunoglobulins
• pathogenesis
• vasculitis

Financial & competing interests disclosure

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

No writing assistance was utilized in the production of this manuscript.

Key issues

• • To date, no confirmed genetic loci for Henoch-Schönlein purpura (HSP) were found. Genome-wide linkage study of familial cases should be performed to identify susceptibility genes.

• • Renal involvement is the critical factor determining the long-term outcome of children with HSP. The pathogenesis of Henoch-Schönlein purpura nephritis (HSPN) is related to the deposition of IgA and IgA-containing immune complexes in the glomerular mesangium.

• • Aberrant glycosylation of IgA1, IgA circulating immune complexes, stimulation of IgE-sensitized mast cells and eosinophils by specific antigens, activation of complement, release of vasoactive substances, increased permeability of capillary, elevated proinflammatory cytokines and chemokines and perivascular deposition of IgA circulating immune complexes are all associated with the pathogenesis of HSP.

• • Atypical presentations and severe, varied complications make it difficult to diagnose HSP.

• • HSP can overlap with other autoimmune diseases or systemic vasculitis such as microscopic polyangiitis.

• • International collaboration to study epidemiology is necessary to investigate the genetic polymorphism and variants for a better understanding of the predisposing and protective factors in relation to complications in HSP.