How to differentiate IgA (Immunoglobulin A) vasculitis from other conditions in a patient with palpable purpura, abdominal pain, and arthralgias?

Diagnosing IgA Vasculitis: Key Distinguishing Features

IgA vasculitis is diagnosed by the clinical tetrad of palpable purpura (predominantly on lower extremities), arthralgias/arthritis, abdominal pain, and glomerulonephritis, with skin biopsy showing leukocytoclastic vasculitis and IgA deposits being confirmatory when the diagnosis is uncertain. 1

Clinical Presentation: The Diagnostic Foundation

The diagnosis of IgA vasculitis relies primarily on recognizing the characteristic clinical pattern rather than a single diagnostic test:

Essential Clinical Features

• Palpable purpura is the hallmark manifestation, presenting as round or oval retiform lesions predominantly on the lower legs and buttocks 1
• Arthralgias or frank arthritis affecting large joints, particularly knees and ankles 1, 2
• Gastrointestinal involvement manifesting as colicky abdominal pain, gastrointestinal bleeding, hematemesis, or hematochezia 1, 3
• Renal involvement presenting as glomerulonephritis with mesangial IgA deposits (IgAVN) 1

Urinalysis Findings in Renal Involvement

When kidney involvement is present, specific urinary findings help distinguish IgA vasculitis from other conditions:

• Dysmorphic RBCs are the hallmark finding indicating glomerular bleeding, requiring inverted phase contrast microscopy for optimal visualization 4
• Red cell casts are virtually pathognomonic for glomerular bleeding, though relatively insensitive 4
• Moderate proteinuria (1-3 g/day) is typical 4, 5
• Microscopic hematuria with positive urine dipstick for blood 4

Key Differentiating Features from Other Vasculitides

Distinguishing from ANCA-Associated Vasculitis (AAV)

The most critical differential diagnosis is separating IgA vasculitis from ANCA-associated vasculitides (granulomatosis with polyangiitis, microscopic polyangiitis, EGPA):

ANCA Testing:

• IgA vasculitis is ANCA-negative 1
• In contrast, approximately 90% of patients with AAV have positive ANCA (PR3-ANCA or MPO-ANCA) using high-quality antigen-specific immunoassays 6, 7
• Test for both PR3-ANCA and MPO-ANCA using high-quality antigen-specific assays as the primary screening method 6

Clinical Distinctions:

• Upper respiratory tract involvement (sinusitis, nasal crusting, epistaxis, hearing loss) strongly suggests AAV rather than IgA vasculitis 5
• Pulmonary manifestations including hemoptysis and diffuse alveolar hemorrhage are characteristic of AAV, not typical IgA vasculitis 5
• Mononeuritis multiplex suggests AAV over IgA vasculitis 5
• IgA vasculitis shows dominant lower extremity purpura, while AAV can have more widespread cutaneous involvement 1

Distinguishing from Large Vessel Vasculitis

Large vessel vasculitides (Giant Cell Arteritis, Takayasu Arteritis) present distinctly different clinical pictures:

• Temporal headache, jaw claudication, and visual symptoms indicate Giant Cell Arteritis, not IgA vasculitis 5
• Limb claudication, pulse discrepancies, and blood pressure differences between limbs suggest Takayasu Arteritis 5
• These conditions require vascular imaging (ultrasound of temporal/axillary arteries for GCA) rather than skin biopsy 6

Diagnostic Algorithm

Step 1: Clinical Assessment

Evaluate for the tetrad of palpable purpura (lower extremities), arthralgias, abdominal pain, and hematuria 1, 2

Step 2: Laboratory Evaluation

• Urinalysis with microscopy looking specifically for dysmorphic RBCs and red cell casts using phase contrast microscopy 4
• 24-hour urine protein to quantify proteinuria (>1 g/day warrants nephrology referral) 4
• ANCA testing (PR3 and MPO) using high-quality immunoassays to exclude AAV 6
• Serum creatinine to assess renal function 7
• ESR and CRP (typically elevated but non-specific) 5

Step 3: Histopathological Confirmation (When Needed)

• Skin biopsy showing leukocytoclastic vasculitis with perivascular IgA deposits on immunofluorescence is confirmatory when clinical presentation is atypical 1
• Renal biopsy showing mesangial IgA deposits distinguishes IgA vasculitis nephritis from other glomerulonephritides and guides prognosis 1, 2

Critical Pitfalls to Avoid

Do not rely on ANCA testing alone: A negative ANCA does not exclude AAV in patients with limited respiratory tract disease or renal-limited vasculitis (small proportion are ANCA-negative) 6. However, in the context of palpable purpura, arthralgias, and abdominal pain, negative ANCA strongly supports IgA vasculitis over AAV.

Do not miss infectious triggers: Upper respiratory tract infections frequently trigger IgA vasculitis, and concurrent gastrointestinal infections (bacterial, viral, parasitic) can complicate the presentation 1, 3. Consider HIV testing as immune dysfunction can trigger IgA vasculitis 8.

Age matters for prognosis: While IgA vasculitis is more common in children (150-200:1 ratio), adults have more severe disease with higher risk of chronic renal disease and worse long-term outcomes 1, 2. Baseline proteinuria >1-1.5 g/day and renal function impairment predict progression to end-stage renal disease 2.

Distinguish skin-limited from systemic disease: Skin-limited IgA vasculitis exists as a variant restricted to cutaneous manifestations without systemic involvement, requiring less aggressive monitoring 1.