Overview

Immunoglobulin A vasculitis (IgAV), also known as Henoch–Schönlein purpura, is the most common primary vasculitis in children (peak incidence 4–7 years), with seasonal peaks after upper respiratory tract infections. It is defined as a small-vessel vasculitis with IgA1-dominant immune deposits affecting capillaries, venules, and arterioles, underscoring the central role of IgA in its pathogenesis. Clinically, IgAV can be divided into two forms: a skin-limited form, characterised by cutaneous IgA-dominant vasculitis without systemic organ involvement and manifesting solely as non-thrombocytopenic purpura, and a systemic form, where skin involvement is accompanied by at least one other organ, most commonly the joints, gastrointestinal tract, and kidneys, and rarely the lungs or central nervous system.

The disease is often self-limiting, but recurrence occurs in around one-third of paediatric cases. Renal involvement is the most important determinant of prognosis. Between 20% and 80% of children develop nephritis within four to six weeks of presentation, and 1–7% progress to renal failure or end-stage renal disease (ESRD). IgA vasculitis is milder in children younger than two years, but more severe in adults, with worse outcomes.

Aetiology & Risk Factors

Aetiology

• Post-infectious mucosal immune dysregulation (commonly URTI) → increased Gd-IgA1 ± anti-Gd-IgA1 autoantibodies → immune complex deposition
• Genetic predisposition

Risk Factors for Severe/Renal Disease

• Older age (especially adults)
• Male sex
• Persistent proteinuria
• Hypertension
• Reduced GFR at onset

Pathophysiology

IgA vasculitis (IgAV) is a leukocytoclastic vasculitis characterised by IgA-dominant immune complex deposition in small vessels. Two main pathogenic models explain its phenotypes.

Anti-Gd-IgA1 autoantibodies: IgA vasculitis nephritis (IgAVN) mechanism parallels the “four-hit” theory of IgA nephropathy: 

• Trigger (often mucosal infection) → overproduction of Gd-IgA1
• Formation of anti-Gd-IgA1 autoantibodies → circulating immune complexes
• Deposition in small vessels/mesangium → activation of alternative/lectin complement pathways
• FcαRI-mediated neutrophil recruitment → leukocytoclastic vasculitis in skin, bowel wall edema/bleeding, mesangial proliferation with proteinuria/hematuria [1,3,11]

Anti-endothelial cell antibodies (AECA) 

• Neutrophil-driven small-vessel injury initiated by IgA1-type anti-endothelial cell antibodies (AECA) binding to β2 glycoprotein I receptors on endothelial cells
• Induces interleukin-8 production, neutrophil recruitment, and endothelial damage via antibody-dependent cellular cytotoxicity, complement activation, and reactive oxygen species. 

Clinical Manifestations

Signs and symptoms may develop over days to weeks in any sequence. The onset of IgA vasculitis typically follows an upper respiratory infection. Joint involvement and abdominal pain are more common in children, whereas adults are more likely to have lower-extremity edema and hypertension

• Cutaneous: Palpable purpura (gravity-dependent; legs/buttocks ± arms/trunk), may form bullae or ulcerate in adults
• Musculoskeletal: Arthralgia/arthritis (knees/ankles common), transient, non-erosive
• GI: Colicky abdominal pain, GI bleeding, intussusception (children), bowel ischemia/edema
• Renal: Microscopic hematuria, proteinuria (range to nephrotic), hypertension, AKI
• Other: Scrotal edema, pulmonary hemorrhage

Diagnosis

EULAR/PRINTO/PRES classification criteria (2010)

• Mandatory: Purpura or petechiae
• Plus at least one of the following:
  
  • Abdominal pain
  • Arthritis or arthralgia
  • Renal involvement
  • Leukocytoclastic vasculitis with predominant IgA deposits or proliferative glomerulonephritis with predominant IgA deposits

Investigations

• Urinalysis (RBCs, protein), urine ACR/PCR
• Serum creatinine/eGFR
• Stool/occult blood if GI symptoms
• Abdominal US/CT for severe GI symptoms or suspected intussusception
• Renal biopsy if significant proteinuria, hematuria with casts, impaired GFR, or atypical course
• Skin biopsy for IgA-predominant leukocytoclastic vasculitis if uncertain
  

Differential Diagnosis

• ANCA-associated vasculitis (MPO/PR3+, pauci-immune GN)
• Cryoglobulinemic vasculitis (low C4, HCV+)
• SLE vasculitis (biopsy:  “full house” IF, ANA+)
• Infection-related GN (low complement, subepithelial humps)
• Drug-induced leukocytoclastic vasculitis (no IgA dominance)
• IgA Nephropathy (IgAN)
  

Classification

• Skin-limited IgAV
• Systemic IgAV without nephritis
• IgAV with nephritis (IgAVN) — most common in adults
  

Treatment

Supportive (all patients)

• Education, rest, analgesia, skin care
• Strict BP control
• RAAS blockade for proteinuria ≥0.5–1 g/day
• Avoid nephrotoxins

Glucocorticoids

• Not for prophylaxis of renal disease
• Indicated for severe GI involvement, scrotal edema, or established IgAVN [4,5]

IgAV Nephritis

• RAAS blockade ± glucocorticoids for moderate–severe proteinuria
• Cyclophosphamide for severe crescentic GN
• MMF, calcineurin inhibitors, rituximab in selected/refractory cases

Refractory Cutaneous Disease

• Dapsone as steroid-sparing; monitor Hb and methemoglobin
  

Complications & Prognosis

• Persistent proteinuria
• Hypertension
• CKD/ESKD (adults at higher risk) 
• Gastrointestinal Haemorrhage, ischemia/perforation
• Intussusception (children),
• Relapses: Usually cutaneous-predominant

Prognosis

• IgAV spontaneously resolves in >90% of children and 90% of adults, making supportive treatment the primary intervention
• IgAV without nephritis is usually self-limiting, especially in children
  • Higher IgM deposition in skin may indicate potential renal involvement
• IgAV with nephritis is associated with worse long-term prognosis. Not self-limiting — chronic inflammation can lead to permanent kidney damage
• Prognosis in children generally better than in adults. Adults have more severe and lasting kidney injury.

References

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2. Heineke MH, Ballering AV, Jamin A, Ben Mkaddem S, Monteiro RC, Van Egmond M. New insights in the pathogenesis of immunoglobulin A vasculitis (Henoch–Schönlein purpura). Semin Immunopathol. 2017;39(5):593-607.
   
3. Liu LJ, Chen HP, Yu F, Zhao MH. Pathogenesis of IgA Vasculitis: An up-to-date review. Front Immunol. 2021;12:771619.
   
4. The Royal Children’s Hospital Melbourne. Clinical Practice Guidelines: Henoch–Schönlein Purpura. 2021 (updated).
   
5. KDIGO Glomerular Diseases Work Group. KDIGO 2021 Clinical Practice Guideline for the Management of Glomerular Diseases. Kidney Int. 2021;100(4S):S1-S276.
   
6. Hočevar A, Rotar Ž, Jurčić V, et al. IgA vasculitis in adults: performance of the EULAR/PRINTO/PRES classification criteria. Arthritis Res Ther. 2016;18:58.
   
7. Bayindir Y, et al. Performance in adults of the EULAR/PReS/Ankara 2008 classification criteria for IgA vasculitis. RMD Open. 2025;11(3):e005728.
   
8. Davin JC, Ten Berge IJ, Weening JJ. IgA nephropathy and IgA vasculitis with nephritis share Gd-IgA1-oriented pathogenesis. Kidney Int. 2017;91(3):534-536.
   
9. Davin JC, Coppo R. The cause and pathogenesis of IgA nephropathy. Nat Rev Nephrol. 2014;10(6):339-352.
   
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11. Liu X, et al. Autoantibodies specific for Gd-IgA1 in IgA vasculitis nephritis. Kidney Int Rep. 2019;4(10):1553-1561.
    
12. Song Y, et al. Dapsone in refractory IgA vasculitis: systematic review. BMC Nephrol. 2020;21:241.
    
13. Kraitsidou E, et al. Adult-onset IgA vasculitis: update on therapy. Rev Med Interne. 2020;41(9):623-630.
    
14. Thiel J. What’s new in treatment: IgA vasculitis & IgA nephropathy. The Rheumatologist. 2024.
    
15. Glucocorticoids in IgA vasculitis. Acta Medica. 2024;65(4):e1100.