A 42-year-old Indian woman with a 6-week history of fever, arthralgia, and palpable purpura on the lower extremities and buttocks presents to the emergency department. She also reports abdominal pain and hematuria. Urinalysis shows 3+ proteinuria and RBC casts. Serum creatinine is 1.8 mg/dL. Complement levels (C3, C4) are normal. What is the most likely diagnosis?

## Diagnosis: IgA Vasculitis (IgA-V) **Key Point:** This patient presents with the classic tetrad of IgA vasculitis: palpable purpura (typically lower extremities and buttocks), arthralgia, abdominal pain, and glomerulonephritis with hematuria and proteinuria. The **normal complement levels** are a crucial diagnostic clue that excludes other vasculitides. ### Clinical Features of IgA Vasculitis | Feature | Frequency | Clinical Significance | |---------|-----------|----------------------| | **Palpable purpura** | 100% | Typically lower extremities, buttocks; IgA-dominant immune deposits on skin biopsy | | **Arthralgia/arthritis** | 75% | Knees and ankles; non-erosive | | **Abdominal pain** | 65% | May include GI bleeding, intussusception | | **Glomerulonephritis** | 40–50% | Hematuria, proteinuria, RBC casts; IgA-dominant on kidney biopsy | | **Complement levels** | Normal | Distinguishes from post-infectious GN and other immune complex vasculitides | **High-Yield:** IgA vasculitis is the **most common systemic vasculitis worldwide** and the most common primary glomerulonephritis in developed countries. It is a **small-vessel vasculitis** mediated by IgA1-dominant immune complexes. ### Pathophysiology ```mermaid flowchart TD A[IgA1 overproduction]:::outcome --> B[Immune complex deposition<br/>in small vessels]:::outcome B --> C[Skin, joints, GI, kidneys]:::outcome C --> D{Organ involvement}:::decision D -->|Skin| E[Palpable purpura]:::action D -->|Joints| F[Arthralgia]:::action D -->|GI| G[Abdominal pain]:::action D -->|Kidneys| H[IgA nephropathy<br/>RBC casts, proteinuria]:::action H --> I[Assess renal prognosis<br/>by MEST-C score]:::decision ``` ### Why Normal Complement Levels? IgA vasculitis is an **IgA-mediated** (not classical complement-activating) immune complex disease. Complement consumption does not occur, so C3 and C4 remain normal. This distinguishes it from: - **Post-infectious GN** (low C3) - **Lupus nephritis** (low C3, C4) - **Cryoglobulinemia** (low C4, often low C3) **Clinical Pearl:** The diagnosis is confirmed by **skin or kidney biopsy showing IgA-dominant deposits on immunofluorescence microscopy**. This is the gold standard. ### Management 1. **Supportive care:** ACE inhibitors/ARBs for proteinuria reduction 2. **Corticosteroids:** Prednisolone 0.5–1 mg/kg/day for active glomerulonephritis (especially if crescentic) 3. **Immunosuppression:** Azathioprine or mycophenolate mofetil for severe/progressive renal disease 4. **Monitoring:** Serial creatinine, urinalysis; renal biopsy if deteriorating function **Mnemonic — IgA Vasculitis Tetrad:** **PAGA** — Purpura (palpable), Arthralgia, GI symptoms, Glomerulonephritis (hematuria/RBC casts). ## Differential Diagnosis | Vasculitis | Purpura | Arthralgia | Abdominal Pain | GN | Complement | Key Distinguisher | |-----------|---------|-----------|-----------------|----|-----------|-----------| | **IgA vasculitis** | ✓ (lower/buttocks) | ✓ | ✓ | ✓ (IgA-dominant) | Normal | **IgA deposits on IF** | | **MPA** | ✓ (variable) | ✗ | ✗ | ✓ (pauci-immune) | Normal | **ANCA+ (MPO); no IgA** | | **Goodpasture** | ✗ | ✗ | ✗ | ✓ (crescentic) | Normal | **Anti-GBM antibodies; pulmonary hemorrhage** | | **Cryoglobulinemia** | ✓ | ✓ | ✗ | ✓ | **Low C4** | **Cryoglobulins; HCV serology** | **Warning:** Do NOT confuse IgA vasculitis with IgA nephropathy (isolated renal involvement without systemic features). IgA vasculitis is systemic; IgA nephropathy is renal-limited.