Initial Immunological Laboratory Tests for Recurring Fever and Abdominal Pain
For patients presenting with recurring fever and abdominal pain, initial immunological laboratory testing should include complete blood count with differential, C-reactive protein, erythrocyte sedimentation rate, comprehensive metabolic panel, liver function tests, serum albumin, and fecal calprotectin when possible. 1
Core Laboratory Testing Algorithm
First-line Testing
- Complete blood count with differential - Evaluate for anemia, leukocytosis/leukopenia, thrombocytosis/thrombocytopenia
- C-reactive protein (CRP) - More sensitive than ESR for acute inflammation 1
- Erythrocyte sedimentation rate (ESR) - Assess overall inflammatory status
- Comprehensive metabolic panel - Assess electrolyte balance and organ function
- Liver function tests - Evaluate for hepatic involvement
- Serum albumin - Important marker of inflammation and nutritional status 1
- Fecal calprotectin - Sensitive marker for intestinal inflammation 1
Infectious Disease Workup
- Blood cultures - Minimum of two sets (60 mL total) from different anatomical sites 1
- Stool cultures - For bacterial pathogens including Salmonella, Shigella, Campylobacter, and Yersinia 1
- Clostridium difficile toxin testing - Especially if recent antibiotic use 1
- Stool testing for parasites - Particularly when symptoms persist >14 days 1
Specific Clinical Scenarios
When Inflammatory Bowel Disease (IBD) is Suspected
- All first-line tests above with emphasis on fecal calprotectin
- Additional testing for infectious causes to rule out IBD mimics 1
- Consider abdominal imaging if symptoms persist despite negative infectious workup
When Autoinflammatory Syndrome is Suspected
- Genetic testing for familial Mediterranean fever (FMF) - Particularly in patients of Mediterranean descent with recurrent fever and abdominal pain 2
- Serum amyloid A - If available, to assess risk of amyloidosis
- Genetic testing for other periodic fever syndromes - Based on clinical presentation 1
When Immunodeficiency is Suspected
- Immunoglobulin levels (IgG, IgA, IgM, IgE)
- Lymphocyte subset analysis - To evaluate T-cell, B-cell, and NK-cell populations
- Complement levels (C3, C4, CH50)
- Specific antibody responses to vaccines 1
When Hemophagocytic Lymphohistiocytosis (HLH) is Suspected
- Ferritin - Markedly elevated in HLH 3
- Triglycerides and fibrinogen
- Soluble IL-2 receptor (if available)
- EBV PCR - Common trigger for HLH 3
Important Considerations
Timing of symptoms affects test selection and interpretation:
Avoid common pitfalls:
- Relying solely on CRP and WBC for triage decisions - these markers alone have insufficient diagnostic accuracy 4
- Failing to rule out infectious causes before diagnosing functional or inflammatory disorders
- Not considering ethnic background when evaluating recurrent fever with abdominal pain (e.g., FMF in Mediterranean populations) 2
Follow-up testing should be guided by initial results:
- Persistent abnormalities despite treatment warrant further investigation
- Normal initial tests with ongoing symptoms may require specialized testing
Remember that recurring fever with abdominal pain represents a broad differential diagnosis spanning infectious, inflammatory, autoimmune, and neoplastic etiologies. The laboratory evaluation should be comprehensive but targeted based on clinical presentation, patient demographics, and risk factors.