What initial tests should be ordered for a 32-year-old female (F) with complaints of fatigue, dry skin, and nail issues, who attributes her symptoms to gluten insensitivity, and should rheumatology tests be included?

Initial Testing for Suspected Gluten-Related Symptoms

Before attributing symptoms to gluten sensitivity, you must first rule out celiac disease with proper serologic testing while the patient is consuming gluten—this is non-negotiable because celiac disease carries significant risks for morbidity including nutritional deficiencies, osteoporosis, and lymphoma that require lifelong monitoring. 1, 2

First-Line Testing: Celiac Disease Serology

Start with these specific tests while the patient is eating gluten:

• IgA tissue transglutaminase (tTG-IgA) - this is your primary screening test with 93% sensitivity and 98% specificity 3, 1
• Total serum IgA level - must be measured simultaneously because IgA deficiency occurs 10-15 times more frequently in celiac patients and causes false-negative IgA-based testing 1, 2, 4
• If IgA deficient: order IgG tTG and deamidated gliadin peptide antibodies instead 3, 1

Critical pitfall to avoid: Never start a gluten-free diet before completing testing—serologic and histologic features normalize after diet initiation, making diagnosis impossible 1, 2. The patient must consume at least 10g of gluten daily (equivalent to 3-4 slices of bread) for 6-8 weeks before testing 2, 4.

When to Add Endoscopy

If serology is positive, upper endoscopy with duodenal biopsies is mandatory to confirm celiac disease before implementing significant dietary changes 1, 2. Obtain 6 total biopsies: 1-2 from the duodenal bulb and at least 4 from the second part of duodenum 2, 4.

Even with negative serology, if clinical suspicion remains high (family history, autoimmune thyroid disease like Hashimoto's, type 1 diabetes), proceed to endoscopy because seronegative celiac disease exists 3, 2, 4.

Rheumatology Testing: Not Indicated Initially

Rheumatology-specific testing is not warranted at this stage based on the presenting symptoms of fatigue, dry skin, and nail changes. However, recognize that:

• Celiac disease is strongly associated with autoimmune thyroid disease (particularly Hashimoto's thyroiditis), type 1 diabetes, and autoimmune liver disease 3, 1
• If celiac serology is positive, consider screening for these associated conditions 3
• Non-celiac gluten sensitivity has been linked to Hashimoto's thyroiditis, psoriasis, and rheumatologic diseases, but this association is less well-established 5

Additional Baseline Testing

Once celiac disease testing is underway, check for common nutritional deficiencies that occur with malabsorption:

• Iron studies (ferritin, iron, TIBC)
• Vitamin D level
• Vitamin B12
• Folate
• Complete blood count (to assess for anemia) 1

These deficiencies are common in celiac disease and can explain fatigue, dry skin, and nail changes 1.

If Celiac Disease is Ruled Out

Only after properly excluding celiac disease with both negative serology (while consuming gluten) and negative duodenal biopsies can you consider non-celiac gluten sensitivity 2, 4. The diagnostic approach then involves:

• Document symptom improvement on a strict gluten-free diet for 6-8 weeks
• Perform a gluten rechallenge to confirm symptom recurrence 2
• Consider HLA-DQ2/DQ8 genetic testing if diagnosis remains uncertain—absence of both alleles has >99% negative predictive value for celiac disease 2, 4

Thyroid Function Testing

Given the strong association between gluten-related disorders and autoimmune thyroid disease, and that her symptoms (fatigue, dry skin, nail changes) overlap significantly with hypothyroidism, check:

• TSH and free T4
• If abnormal, add thyroid peroxidase antibodies (TPO) and thyroglobulin antibodies 1, 5

This is particularly important because Hashimoto's thyroiditis is the most commonly associated autoimmune disorder with both celiac disease and non-celiac gluten sensitivity 5.

Summary Algorithm

1. While patient eats gluten: Order tTG-IgA + total IgA, TSH, CBC, iron studies, vitamin D, B12, folate
2. If tTG-IgA positive: Refer for upper endoscopy with duodenal biopsies
3. If tTG-IgA negative but high suspicion: Consider HLA-DQ2/DQ8 testing and/or proceed to endoscopy
4. Only after celiac disease excluded: Consider trial of gluten-free diet for non-celiac gluten sensitivity
5. Rheumatology testing: Not indicated unless celiac disease confirmed or other specific rheumatologic symptoms develop