Henoch-Schönlein purpura pathophysiology

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]

Henoch-Schönlein purpura (HSP) is an immune complex-mediated disease with circulating immune complexes and IgA rheumatoid factors usually follows upper respiratory tract infections, various viruses, and the bacteria have been implicated as triggers of the disease.

The pathophysiology of HSP:^[1][2][3]

• HSP is a small vessel leukocytoclastic vasculitis, but its pathophysiology is not completely understood.
• In patients with HSP the serum IgA levels are elevated, HSP is an immune complex-mediated disease with circulating immune complexes and IgA rheumatoid factors usually follows upper respiratory tract infections, various viruses, and the bacteria have been implicated as triggers of the disease.
• Patients with HSP have circulating IgA immune-complexes, patients with HSPN have an additional large molecular mass IgA1–IgG-containing circulating immune complexes.
• The IgA1 molecule has a hinge region containing up to six O-linked glycan chains consisting of N-acetylgalactosamine, usually with an attached β1,3-linked galactose.
• It has been reported that in patients with HSP, the activity of β1,3-galactosyltransferase in peripheral B cells is reduced, leading to a lack of terminal β1,3-galactosyl residues in the hinge region of IgA1.
• The primary defect leading to the production of such abnormally glycosylated IgA1 is probably heritable.
• These aberrantly glycosylated IgA1 molecules have been shown to form immune complexes with IgG antibodies specific for galactose-deficient IgA1, thereby inhibiting the binding of the IgA molecules to hepatic receptors and avoiding their internalization and degradation by hepatic cells.
• This formation results in an increased amount of IgA immune complexes in circulation.
• The complexes may then deposit in renal mesangial areas and activate the complement system by the alternative or lectin pathways, which play a major role in the pathophysiology of this disease.
• Further, after depositing in the mesangium, the galactose-deficient IgA1 immune complexes activate mesangial cells.
• This results in the proliferation of cells such as macrophages and lymphocytes and the production of inflammatory and profibrogenic cytokines and chemokines, which play a pivotal role in mesangial cell proliferation, matrix expansion, and inflammatory cell recruitment.
• Other mechanisms for developing HSP
  • Nephritis-associated plasmin receptor, a group A streptococcal antigen, has been reported in some cases of HSP.
  • Activation of the eosinophils and expression of the alpha-smooth muscle actin in the kidney also play a vital role in the pathogenesis of Henoch-Schönlein purpura.

Biopsy: ^[4][5][6]

• Indications
  • No rash
  • Abnormal renal function tests

Skin biopsy

• Light Microscopy
  • IgA deposition in postcapillary venules with IgA deposition and leukocytoclastic vasculitis in is a pathognomonic microscopic feature of Henoch-Schönlein Purpura.
  • Skin lesions less than 24 hrs are preferred as the chronic lesion lack the immunoglobulin isotypes essential for the diagnosis of HSP.
  • A biopsy from a different skin site is taken for the immunofluorescent studies to confirm the diagnosis.

Renal biopsy

• IgA deposition in the mesangium on immunofluorescence microscopy should be differentiated from the IgA nephropathy.
• Light microscopic features range from isolated mesangial proliferation to severe crescentic glomerulonephritis.

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