What labs should be drawn for a patient with chronic pain syndrome, GI symptoms, and a suspected skin condition?

Laboratory Evaluation for Chronic Pain Syndrome with GI Symptoms and Suspected Skin Condition

For a patient presenting with chronic pain syndrome, GI symptoms, and a suspected skin condition, you should screen for hypermobile Ehlers-Danlos syndrome (hEDS) and its common comorbidities—particularly celiac disease, inflammatory bowel disease, and postural orthostatic tachycardia syndrome (POTS)—as these conditions frequently overlap and require specific diagnostic testing. 1, 2

Initial Blood Work

Complete Blood Count and Inflammatory Markers

• CBC with differential to evaluate for cytopenias, eosinophilia, or anemia that may suggest systemic involvement or nutritional deficiencies 2, 3
• C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR) for inflammatory assessment, though these have lower sensitivity for IBD compared to fecal markers 1, 3
• Comprehensive metabolic panel including liver and renal function 2, 3

Nutritional and Metabolic Assessment

• Vitamin B12, folate, and iron studies to identify nutritional deficiencies common in chronic GI conditions 3
• Calcium level 3
• Thyroid function tests (TSH, free T4) to exclude thyroid dysfunction as a cause of GI symptoms 3

Celiac Disease Screening (Priority Test)

• IgA tissue transglutaminase (tTG) antibody with total IgA level to identify IgA deficiency that could cause false-negative results 1, 3
• Testing for celiac disease should be performed earlier in patients with suspected hEDS who report any variety of GI symptoms, not just diarrhea, as the risk is elevated in this population 1
• If IgA-deficient, use IgG-tTG or IgG deaminated gliadin peptides 3

Stool Studies

Inflammatory Bowel Disease Screening

• Fecal calprotectin with threshold of 50 mg/g (or fecal lactoferrin 4.0-7.25 mg/g) to screen for IBD with optimized sensitivity 1, 3
• This is more sensitive than CRP/ESR for detecting IBD 1, 3

Infectious Evaluation

• Giardia antigen detection or PCR due to high prevalence and excellent test performance in chronic diarrhea 3

Screening for hEDS-Associated Comorbidities

POTS Evaluation

• Postural vital signs measuring heart rate increase ≥30 beats/min within 10 minutes of standing during active stand test 1, 2
• If POTS is confirmed, consider referral for tilt table testing and expanded autoantibody testing 1

Mast Cell Activation Syndrome (MCAS) Testing

• Baseline serum tryptase level if the patient has episodic symptoms suggesting generalized mast cell disorder (flushing, urticaria, wheezing, multisystem symptoms beyond isolated GI complaints) 1, 2
• Do NOT perform MCAS testing routinely in all patients with isolated GI symptoms, as validated clinical tests for mast cell-mediated mechanisms of abdominal pain are lacking 1, 2
• If MCAS is suspected, collect tryptase levels at baseline and 1-4 hours following symptom flares; increases of 20% above baseline plus 2 ng/mL are necessary for diagnosis 1

Genetic Testing Considerations

When Skin Findings Suggest Vascular EDS (Critical)

• COL3A1 gene mutation testing urgently if vascular EDS is suspected based on skin fragility, easy bruising, or family history of arterial rupture 2
• This is a life-threatening subtype requiring immediate identification 2

For Suspected hEDS

• Avoid routine genetic testing for hEDS, as no causative genes have been identified 1, 2
• Diagnosis is clinical using the Beighton score (≥5 required) and 2017 diagnostic criteria 2

Additional Testing Based on Specific GI Symptoms

Upper GI Symptoms with Suspected Gastroparesis

• Consider gastric emptying study earlier in patients with coexisting POTS, as underlying autonomic dysfunction may predispose to gastroparesis 1

Lower GI Symptoms with Incomplete Evacuation

• Anorectal manometry, balloon expulsion test, or defecography should be considered given the high prevalence of pelvic floor dysfunction (especially rectal hyposensitivity) in hEDS patients 1

Critical Pitfalls to Avoid

• Do not rely solely on CRP/ESR to screen for IBD when fecal calprotectin is more sensitive 1, 3
• Do not fail to check total IgA levels when testing for celiac disease, which could lead to false-negative results in IgA-deficient patients 3
• Do not perform routine MCAS testing in patients with isolated GI symptoms without evidence of generalized mast cell disorder 1, 2
• Do not order carbohydrate maldigestion/malabsorption testing routinely, as there is insufficient evidence for specific food-mediated mechanisms in hEDS 1
• Avoid invasive procedures if vascular EDS is suspected until genetic testing confirms or excludes this diagnosis, as procedures can lead to fatal complications 2