A 42-year-old Indian woman presents with a 2-month history of fever, malaise, and progressive dyspnea. She has palpable purpura on her lower extremities and abdomen. Urinalysis shows hematuria and proteinuria. Serum creatinine is 1.8 mg/dL. Complement levels (C3, C4) are normal. ANCA testing is negative. Skin biopsy shows IgA-dominant immune complex deposition on immunofluorescence. What is the most likely diagnosis?

## Diagnosis: IgA Vasculitis (Henoch–Schönlein Purpura) **Key Point:** IgA vasculitis is a small-vessel, IgA-immune-complex-mediated vasculitis characterized by the tetrad of palpable purpura, arthritis/arthralgia, abdominal pain, and glomerulonephritis. The **gold standard for diagnosis is skin or kidney biopsy showing IgA-dominant immune complex deposition** on immunofluorescence. **High-Yield:** IgA vasculitis is the most common systemic vasculitis worldwide and the most common primary glomerulonephritis in children and young adults. In adults, it often presents with renal involvement and systemic features. The normal complement levels and negative ANCA help exclude other small-vessel vasculitides. **Clinical Pearl:** Although classically taught as "Henoch–Schönlein purpura" in children, the modern nomenclature is **IgA vasculitis** (Chapel Hill Consensus Conference 2012). The disease can occur at any age; adult-onset IgA vasculitis often has more severe renal involvement. **Mnemonic: IgA Vasculitis Features** — **P**urpura, **A**rthritis, **A**bdominal pain, **R**enal disease = **PAAR** ## Diagnostic Criteria & Differentiation | Feature | IgA Vasculitis | Microscopic Polyangiitis | Anti-GBM Disease | Polyarteritis Nodosa | | --- | --- | --- | --- | --- | | **Vessel size** | Small | Small | Small (basement membrane) | Medium | | **Immune complex** | IgA-dominant | ANCA-associated (pauci-immune) | Linear anti-GBM | Immune complex | | **Purpura** | Palpable, lower extremities | Palpable, variable | Rare | Rare | | **Glomerulonephritis** | IgA-dominant IF | Pauci-immune ANCA | Linear IF (anti-GBM) | No | | **ANCA** | Negative | Positive (MPO or PR3) | Negative | Negative | | **Complement** | Normal | Normal | Normal | Normal | | **GI involvement** | Common (abdominal pain) | Rare | No | Common (mesenteric ischemia) | | **Arthritis** | Common | Rare | No | Rare | ## Pathophysiology ```mermaid flowchart TD A[Trigger: infection, drugs, IgA dysregulation]:::outcome A --> B[Increased IgA1 production]:::outcome B --> C[IgA1-dominant immune complex formation]:::outcome C --> D[Deposition in small vessels: skin, kidney, GI, joints]:::outcome D --> E[Complement activation via alternative pathway]:::action E --> F[Leukocyte infiltration & inflammation]:::action F --> G[Clinical manifestations]:::outcome G --> H[Purpura, GN, arthritis, abdominal pain]:::outcome ``` ## Clinical Presentation in Adults **Classic Tetrad (not all required for diagnosis):** 1. **Palpable purpura** — typically lower extremities and buttocks (100% of patients) 2. **Arthritis/arthralgia** — knees and ankles (75%) 3. **Abdominal pain** — colicky or diffuse (50–65%) 4. **Glomerulonephritis** — hematuria ± proteinuria (40–50%) **Renal Involvement (MEST-C Score):** - Mesangial proliferation (M) - Endocapillary proliferation (E) - Segmental sclerosis (S) - Tubular atrophy/interstitial fibrosis (T) - Crescent formation (C) **Why This Patient Has IgA Vasculitis:** - ✓ Palpable purpura on lower extremities and abdomen - ✓ Hematuria + proteinuria (glomerulonephritis) - ✓ **IgA-dominant immune complex deposition on skin biopsy** (diagnostic) - ✓ Normal complement levels (IgA vasculitis is complement-mediated but does not cause hypocomplementemia) - ✓ Negative ANCA (excludes ANCA-associated vasculitis) ## Management Approach ```mermaid flowchart TD A[Confirmed IgA vasculitis]:::outcome A --> B{Renal involvement?}:::decision B -->|Mild: hematuria only| C[Supportive care + NSAIDs]:::action B -->|Moderate: proteinuria <1g/day| D[ACE inhibitor/ARB]:::action B -->|Severe: proteinuria >1g/day or GFR decline| E[Corticosteroids + immunosuppression]:::action C --> F[Monitor renal function, proteinuria]:::action D --> F E --> G[Prednisolone 0.5-1 mg/kg/day + azathioprine or mycophenolate]:::action G --> F F --> H[Assess for remission/relapse]:::outcome ``` **Treatment Principles:** - **Mild disease:** Supportive care, NSAIDs for arthritis, ACE-I/ARB for proteinuria - **Moderate-to-severe renal disease:** Corticosteroids (0.5–1 mg/kg/day prednisolone) ± immunosuppression (azathioprine, mycophenolate mofetil) - **Rapidly progressive GN or crescentic disease:** Pulse methylprednisolone + cyclophosphamide or rituximab **Prognosis:** - ~10% progress to end-stage renal disease (ESRD) in adults - Proteinuria >1 g/day and elevated creatinine at presentation are poor prognostic markers - Remission rates: 50–60% with treatment [cite:Harrison 21e Ch 318; Robbins 10e Ch 11]