Henoch-Schönlein purpura (HSP)

Definition and Overview

IgA vasculitis, formerly known as Henoch-Schönlein purpura (HSP), is the most common childhood vasculitis.
It is a clinical, multisystem disorder defined by the presence of palpable purpura accompanied by one or more of the following features: arthritis or arthralgia, abdominal pain, renal involvement, or predominant IgA deposition.
While the disease largely affects the pediatric population and generally carries a favorable prognosis, the development of IgA vasculitis with nephritis is a feared complication that contributes to a poor long-term prognosis.

The pathogenesis of IgA vasculitis with nephritis is similar to that of IgA nephropathy.
The primary mechanism involves the mucosal production of galactose-deficient IgA1 (GdIgA1), which acts as an autoantigen.
This triggers an IgG autoimmune response, leading to the circulation and subsequent deposition of macromolecular IgA1 immune complexes within the kidneys.
The deposition of these complexes leads to complement activation, resulting in glomerular inflammation and subsequent renal damage.

Cutaneous Features: The hallmark skin lesions typically begin as symmetrical erythematous macules that evolve into slightly raised, palpable, urticarial papules and purpura. These eruptions predominantly affect the buttocks and the extensor surfaces of the lower legs and forearms, while characteristically sparing the trunk.
Gastrointestinal Features: Patients frequently present with gastrointestinal symptoms, including abdominal pain, vomiting, and melena.
Musculoskeletal Features: Joint involvement typically manifests as arthritis or arthralgia.
Renal Features (HSP Nephropathy): Renal involvement has a highly variable presentation, ranging from asymptomatic microscopic hematuria to a mixed nephritic-nephrotic syndrome with significantly diminished renal function.

The histological appearance of IgA vasculitis with nephritis is indistinguishable from IgA nephropathy.
Hallmark histological features include mesangial hypercellularity and the formation of glomerular crescents.
To prognosticate and standardize biopsy findings, two major histological classifications are utilized in clinical practice.

Classification System	Key Pathological Criteria	Clinical Utility
ISKDC Classification	Based on the degree of mesangial hypercellularity and the proportion of glomerular crescents (Classes I–VI). Class I indicates minimal abnormalities, while Classes III-V quantify crescents (<50%, 50-75%, and >75%).	Historically used by the International Study of Kidney Disease in Children; however, classifications based exclusively on acute lesions have shown a low predictive value for long-term outcomes.
MEST-C (Oxford) Classification	Evaluates Mesangial hypercellularity, Endocapillary hypercellularity, Segmental glomerulosclerosis, Tubular atrophy/interstitial fibrosis, and Crescents.	Incorporates chronicity indices (like S and T lesions) which provide a higher predictive value for long-term renal outcomes.

The overall prognosis of IgA vasculitis is generally favorable, but patients with significant nephritis require careful management.
The degree of proteinuria at presentation is a highly important clinical marker for predicting long-term renal outcomes.
Histologically, the presence of chronicity lesions—specifically segmental glomerulosclerosis (S1) and significant tubulointerstitial fibrosis (T1/2)—are strong negative predictors associated with a poor renal outcome (such as doubling of serum creatinine or progression to end-stage kidney disease).
Treatment recommendations are primarily aimed at controlling proteinuria and reducing active nephritis to prevent long-term, irreversible kidney damage.
Medical management strategies typically involve the use of corticosteroids and other targeted immunosuppressive medications.
All children with a history of IgA vasculitis with nephritis necessitate long-term monitoring for the development of adverse outcomes, including secondary hypertension, chronic kidney disease (CKD), and end-stage kidney disease (ESKD).