IgA Vasculitis (Henoch-Schönlein Purpura)

Risk factors

• Preceding upper respiratory infection (group A Streptococcus most common)
• Other infections: parvovirus B19, varicella, hepatitis B/C, mycoplasma, COVID-19
• Vaccinations (rare temporal association)
• Drugs: ACE inhibitors, NSAIDs, antibiotics (case reports)
• Insect bites, food allergens (anecdotal)
• Underlying malignancy in adults (especially lung cancer; consider workup)

Pathophysiology

Aberrantly galactosylated IgA1 (Gd-IgA1) is produced — typically following mucosal infection — and recognized as a neoantigen by IgG and IgA autoantibodies. The resulting circulating immune complexes deposit in the skin, joints, gut, and renal mesangium, activating complement (primarily alternative pathway) and producing leukocytoclastic small-vessel vasculitis and mesangial proliferative glomerulonephritis indistinguishable on biopsy from primary IgA nephropathy.

Clinical presentation

Differential diagnosis

• IgA nephropathy — Same renal lesion but without systemic vasculitis features; relapsing macroscopic hematuria after URI
• ANCA-associated vasculitis — Pauci-immune on IF, ANCA positive, often older patients with pulmonary disease
• Cryoglobulinemic vasculitis — HCV common, low C4, positive cryoglobulins, neuropathy
• Acute hemorrhagic edema of infancy — Children <2 years, large purpuric medallions, no renal or GI involvement, self-limited
• Meningococcemia / DIC — Septic, hemodynamically unstable, rapidly evolving purpura — emergency
• Drug-induced cutaneous vasculitis — Recent new medication, lesions confined to skin, resolves with withdrawal
• Thrombocytopenic purpura (ITP, TTP) — Low platelets in ITP; schistocytes and thrombocytopenia in TTP

Diagnostic workup

Diagnostic algorithm

Treatment

Complications

• Intussusception (most common abdominal complication in children) — typically ileoileal rather than ileocolic
• GI bleeding, bowel perforation, bowel ischemia
• Chronic kidney disease (5-15% of nephritis cases progress); higher in adults than children
• Rare: pulmonary hemorrhage, intracerebral hemorrhage, orchitis, ureteritis
• Relapse within first 6 months in ~30% of patients

PANCE pearls

• IgA vasculitis is now the preferred term; Henoch-Schönlein purpura remains widely used clinically.
• Steroids relieve abdominal and joint symptoms but do NOT prevent the development of nephritis — counsel families accordingly.
• Intussusception in IgA vasculitis is typically ileoileal (small-bowel to small-bowel), so it may be missed by air-contrast enema (which mainly reduces ileocolic intussusception).
• Adults with IgA vasculitis have higher rates of severe renal disease — always biopsy if significant proteinuria or rising creatinine.
• Search for an underlying malignancy in adults presenting with IgA vasculitis, particularly age >50.

References

• Chapel Hill 2012 — Jennette JC et al. 2012 Revised International Chapel Hill Consensus Conference Nomenclature of Vasculitides (Arthritis Rheum 2013;65:1-11)
• EULAR/PRINTO/PReS — Ozen S et al. EULAR/PRINTO/PReS criteria for Henoch-Schönlein purpura, childhood polyarteritis nodosa, childhood Wegener granulomatosis and childhood Takayasu arteritis (Ann Rheum Dis 2010;69:798-806)
• SHARE — Ozen S et al. European consensus-based recommendations for diagnosis and treatment of immunoglobulin A vasculitis (Rheumatology 2019;58:1607-1616)
• KDIGO 2021 — KDIGO 2021 Clinical Practice Guideline for the Management of Glomerular Diseases (Kidney Int 2021;100:S1-S276)