What is the best course of action for an overweight patient with rosacea, facial flushing, gastrointestinal cramps, pain, low Immunoglobulin A (IgA) level, and elevated Neutrophil Cytosolic Protein (NCRP), despite negative celiac testing?

Evaluation and Management of Low IgA with Elevated Celiac Markers

Immediate Diagnostic Interpretation

Your patient has selective IgA deficiency (IgA 82 mg/dL is below normal range of ~90-450 mg/dL) which invalidates the standard IgA-based celiac testing, and you must proceed directly to upper endoscopy with duodenal biopsies while the patient continues consuming gluten. 1

The low IgA level means that IgA-based celiac antibody tests (tissue transglutaminase IgA, endomysial antibody IgA) are unreliable and will produce false-negative results even in the presence of active celiac disease. 1, 2

Critical Next Steps

Confirm IgA Deficiency and Order Appropriate Testing

• Repeat total IgA measurement to confirm selective IgA deficiency (defined as IgA <7 mg/dL in most definitions, though your patient's level of 82 mg/dL is borderline low). 1

• Order IgG-based celiac testing immediately: IgG tissue transglutaminase (tTG-IgG) AND IgG deamidated gliadin peptide (DGP-IgG), as these are the appropriate tests for IgA-deficient patients. 1, 3

• IgG DGP has superior diagnostic accuracy (93.6% sensitivity, 99.4% specificity) compared to IgG tTG in IgA-deficient patients. 3

Proceed to Endoscopic Evaluation

Schedule upper endoscopy with duodenal biopsies regardless of IgG antibody results, given the high clinical suspicion based on gastrointestinal symptoms (cramps, pain) and the inability to rely on standard serologic testing. 1

• Obtain at least 6 biopsy specimens: 1-2 from the duodenal bulb and at least 4 from the second part of the duodenum or beyond, as celiac disease changes can be patchy. 1, 3, 4

• Ensure the patient continues consuming adequate gluten (at least 10g daily) until after the biopsy is completed to avoid false-negative histology. 1, 5, 4

• Request evaluation by a pathologist with gastroenterology expertise, as poorly oriented mucosa can lead to misinterpretation. 1

Understanding the NCRP Result

The elevated NCRP (neutrophil cytosolic protein) at 15 is not a standard celiac disease marker and appears to be unrelated to celiac diagnosis. This may represent a separate inflammatory process or laboratory finding that requires independent evaluation based on clinical context.

Addressing the Rosacea and Facial Flushing

• Rosacea has documented associations with gastrointestinal disorders including celiac disease, irritable bowel syndrome, and small intestinal bacterial overgrowth (SIBO), potentially through shared immunological and microbiota factors comprising the "gut-skin axis." 6

• The combination of rosacea, facial flushing, and gastrointestinal symptoms strengthens the clinical suspicion for an underlying gastrointestinal disorder that warrants thorough investigation. 6, 7

• Consider evaluation for SIBO if celiac disease is excluded, as treatment for SIBO has shown effective and prolonged therapeutic response in rosacea patients. 6

Diagnostic Algorithm for This Patient

1. Confirm IgA deficiency status with repeat total IgA measurement
2. Order IgG-based celiac serology (IgG tTG and IgG DGP)
3. Schedule upper endoscopy with duodenal biopsies (minimum 6 specimens) while patient continues gluten consumption
4. Consider HLA-DQ2/DQ8 testing if histology is equivocal, as negative results (absence of both alleles) have >99% negative predictive value and essentially rule out celiac disease 1, 5, 4

Interpretation of Biopsy Results in IgA-Deficient Patients

• If biopsies show villous atrophy with positive IgG-based antibodies, diagnose as celiac disease with selective IgA deficiency (not seronegative celiac disease). 1

• If biopsies show villous atrophy but IgG antibodies are negative, consider the differential diagnosis of seronegative enteropathy including autoimmune enteropathy, common variable immunodeficiency, medication effects (especially olmesartan), infections, or other immune disorders. 1

• IgA deficiency itself is associated with increased risk of celiac disease (10-15 times more frequent than general population) and other autoimmune conditions. 5, 2

Common Pitfalls to Avoid

• Never rely on IgA-based celiac antibody tests in patients with low or deficient IgA levels, as this leads to missed diagnoses of celiac disease. 1, 3

• Never start a gluten-free diet before completing the diagnostic workup, as this causes false-negative serology and inconclusive biopsies, making definitive diagnosis impossible. 1, 5, 4

• Do not assume negative "celiac testing" excludes celiac disease when the testing performed was IgA-based in a patient with IgA deficiency. 1

Management After Diagnosis Confirmation

If celiac disease is confirmed:

• Initiate strict lifelong gluten-free diet immediately after biopsy confirmation (less than 10 mg gluten per day). 4, 8

• Refer to a registered dietitian experienced in celiac disease management for comprehensive dietary education. 3, 4

• Screen for nutritional deficiencies common at diagnosis: iron deficiency anemia, vitamin D, calcium, vitamin B12, folate, and fat-soluble vitamins. 4

• Monitor with IgG-based antibody testing (not IgA-based) at 6 months, 12 months, and annually thereafter. 4

• Address the rosacea with appropriate dermatologic management, which may improve with treatment of the underlying celiac disease. 6, 7