What are the possible causes of elevated Immunoglobulin A (IgA) levels in a person with abdominal pain?

Elevated IgA Levels in Abdominal Pain: Diagnostic Considerations

The most important reason to measure IgA in a person with abdominal pain is to evaluate for IgA vasculitis (Henoch-Schönlein purpura), which commonly presents with abdominal pain and can cause serious gastrointestinal complications including hemorrhage, perforation, and intussusception. 1, 2, 3

Primary Diagnostic Consideration: IgA Vasculitis

Clinical Presentation

• Abdominal pain occurs in 71% of confirmed IgA vasculitis patients, making it the most common gastrointestinal manifestation 1
• Approximately 40.7% of patients develop GI symptoms alone without any skin manifestations at initial presentation, which frequently leads to misdiagnosis 1
• The classic purpuric rash may appear after the onset of abdominal symptoms—13 of 16 patients in one series developed rash, with one patient developing it only after the initial biopsy 1
• Additional symptoms include bloody diarrhea/hematochezia (50% of cases), nausea/vomiting (31% of cases), and rarely intussusception 1, 2

Key Distinguishing Features

• Multi-regional purpura (affecting two or more body areas) significantly increases the likelihood of GI involvement and should raise immediate suspicion 4
• Adult-onset IgA vasculitis predominantly affects younger males (median age 37 years) when presenting with abdominal symptoms 4
• The duodenum is the most commonly affected GI site, followed by ileum and jejunum 4

Laboratory Risk Factors

• Elevated white blood cell count >10.34 × 10⁹/L is an independent risk factor for GI complications 4
• Elevated C-reactive protein/albumin ratio (CAR) >0.355 strongly predicts GI involvement 4
• Reduced IgM levels serve as a protective factor, meaning normal or elevated IgM makes GI complications less likely 4

Histologic Findings on Biopsy

Common Patterns (Not Classic Vasculitis)

• Lamina propria hemorrhage is present in 100% of GI biopsies from IgA vasculitis patients, making it the most consistent finding 1
• Lamina propria fibrin deposition with red cell sludging and nuclear debris occurs in 44% of cases 1
• Acute duodenitis is present in 75% of duodenal biopsies, with 25% showing severe erosive changes 1
• Acute jejunitis/ileitis occurs in 78% of small bowel biopsies 1
• Acute colitis/proctitis is seen in 75% of colorectal biopsies 1

Classic Leukocytoclastic Vasculitis (Uncommon)

• Leukocytoclastic vasculitis is found in only 25% of GI biopsies, despite being considered the "classic" finding 1
• When present, LCV affects small capillaries within the lamina propria, not deeper submucosal vessels 1
• IgA, C3, and fibrin deposits in submucosal arteries with fibrinoid necrosis confirm the diagnosis when present 5

Critical Diagnostic Pitfall

The most common error is misdiagnosing IgA vasculitis as inflammatory bowel disease or infectious gastroenteritis, particularly when the characteristic rash is absent at presentation 1, 2. The presence of erosive duodenitis with predominant small bowel involvement should immediately raise suspicion for IgA vasculitis rather than Crohn's disease 1.

Evaluation for Celiac Disease

When to Test IgA-tTG

• IgA tissue transglutaminase (IgA-tTG) testing is indicated for chronic diarrhea with or without abdominal pain lasting ≥4 weeks 6
• Testing is appropriate when evaluating functional diarrhea or IBS-like symptoms 6
• Total IgA levels must be checked simultaneously, as IgA deficiency occurs in approximately 2-3% of celiac disease patients and will cause false-negative IgA-tTG results 6

Seronegative Enteropathy Considerations

• When villous atrophy is present but celiac serology is negative, consider medication-induced enteropathy (olmesartan, mycophenolate, azathioprine), common variable immunodeficiency (IgG <5 g/L plus low IgA or IgM), tropical sprue, or autoimmune enteropathy 6
• Absence of plasma cells on biopsy with low total IgG, IgA, and IgM suggests common variable immunodeficiency 6

Other Conditions Associated with Elevated IgA

Alpha-Gal Syndrome

• Abdominal pain occurs in 71% of confirmed alpha-gal allergic patients 7
• The hallmark delayed onset (2-6 hours after mammalian meat consumption) distinguishes this from typical food allergies 7
• Many patients are misdiagnosed with IBS because clinicians fail to recognize the delayed meat-reaction pattern and don't order alpha-gal IgE testing 7

Inflammatory Bowel Disease

• Abdominal pain in IBD may be inflammatory (active disease, strictures, fistulae) or non-inflammatory (adhesions, fibrotic strictures, functional overlay) 6
• Pain persisting 3-6 months beyond resolution of inflammation indicates chronic pain with central sensitization mechanisms 6
• Elevated inflammatory markers (ESR, CRP) help distinguish active IBD from functional symptoms 6

Recommended Diagnostic Approach

1. Obtain complete IgA panel: Total IgA, IgA-tTG (if chronic symptoms), and consider alpha-gal IgE if delayed post-meat symptoms 6, 7
2. Check inflammatory markers: WBC, CRP, CAR ratio—elevations suggest IgA vasculitis risk 4
3. Examine skin carefully: Look for purpura in multiple body regions, which may appear after GI symptoms 1, 4
4. Perform urinalysis: Hematuria and proteinuria indicate renal involvement in IgA vasculitis 2, 3
5. Consider endoscopy with biopsy before initiating steroids: Look for erosive duodenitis, lamina propria hemorrhage, and fibrin deposition 1
6. If neutropenic with abdominal pain: CT abdomen/pelvis with IV contrast is the preferred initial imaging to detect neutropenic enterocolitis, abscesses, or perforation 6, 8