What is the most likely unifying diagnosis in a 24‑year‑old with peripheral eosinophils 4%, esophagitis, gastritis and duodenitis on endoscopy, positive IgA endomysial antibodies, IgA anti‑deamidated gliadin peptide >150 U, IgA tissue transglutaminase >100 U, total IgA 191 mg/dL, severe iron deficiency (low serum iron, ferritin 6 ng/mL), folate 2 ng/mL, vitamin D 24 ng/mL, HbA1c 8.8 %, normal vitamin B12 507 pg/mL, methylmalonic acid 167 nmol/L, and total serum IgE 5644 IU/mL?

Celiac Disease with Iron Deficiency Anemia and Possible Eosinophilic Gastrointestinal Disease

The most likely unifying diagnosis is celiac disease with secondary iron deficiency anemia, malabsorption of multiple nutrients, and poor glycemic control; the markedly elevated total IgE (5644 IU/mL) and peripheral eosinophilia (4%) raise concern for concurrent eosinophilic gastroenteritis or hypereosinophilic syndrome that requires further evaluation. 1, 2

Primary Diagnosis: Celiac Disease

The serologic profile is diagnostic for celiac disease:

• IgA anti-tissue transglutaminase >100 U (highly specific, sensitivity 85-92%, specificity 97-98%) 3, 4
• IgA anti-endomysial antibodies positive (sensitivity and specificity approaching 100%) 3, 4
• IgA anti-deamidated gliadin peptide >150 U (specificity 90-98%, sensitivity 92%) 5
• Total IgA 191 mg/dL is normal, excluding IgA deficiency that could cause false-negative serology 1

The endoscopic findings of esophagitis, gastritis, and duodenitis are consistent with celiac disease, which causes villous atrophy and inflammatory changes throughout the upper GI tract 6, 7. Duodenal biopsies showing villous atrophy with crypt hyperplasia and intraepithelial lymphocytosis would confirm the diagnosis 6, 7.

Secondary Complications from Celiac Disease

Severe Iron Deficiency Anemia

• Ferritin 6 ng/mL with serum iron 36 μg/dL indicates severe iron deficiency 1, 8
• Hemoglobin 14 g/dL is at the lower limit of normal for a 24-year-old male (WHO defines anemia as <13 g/dL in men) 1
• Celiac disease accounts for 2-6% of iron deficiency anemia cases and impairs iron absorption in the proximal small intestine 1, 8

Nutritional Deficiencies

• Folate 2 ng/mL is low (normal >3 ng/mL), consistent with proximal small bowel malabsorption 1
• Vitamin D 24 ng/mL is insufficient (<30 ng/mL), common in celiac disease due to fat-soluble vitamin malabsorption 1
• Vitamin B12 507 pg/mL and methylmalonic acid 167 nmol/L are normal, indicating intact terminal ileal absorption 1

Poor Glycemic Control

• HbA1c 8.8% indicates uncontrolled diabetes or prediabetes, which may be type 1 diabetes (strongly associated with celiac disease) or secondary to malabsorption affecting glucose homeostasis 7

Concurrent Eosinophilic Gastrointestinal Disease

The combination of peripheral eosinophils 4% (absolute count needed but likely elevated) and total IgE 5644 IU/mL (markedly elevated, normal <100 IU/mL) raises three critical differential diagnoses:

1. Eosinophilic Gastroenteritis (Most Likely)

• Esophagitis, gastritis, and duodenitis on endoscopy fit the distribution of eosinophilic gastrointestinal disease 1, 2
• 50-80% of patients with eosinophilic gastroenteritis have atopic comorbidities (asthma, allergic rhinitis, eczema, food allergy) 2, 9
• Diagnosis requires >20 eosinophils per high-power field in gastric biopsies 2
• Peripheral eosinophilia occurs in 10-50% of adults with eosinophilic esophagitis and even higher rates in eosinophilic gastroenteritis 2, 9

2. Hypereosinophilic Syndrome (Must Exclude)

• When peripheral eosinophil counts exceed 1,500 cells/µL, hypereosinophilic syndrome must be considered 2, 9
• Up to 38% of HES patients develop gastrointestinal symptoms including epigastric pain 1, 9
• Calculate absolute eosinophil count immediately: if >1,500 cells/µL with organ damage, urgent hematology referral is required due to risk of cardiac involvement 2, 9

3. Parasitic Infection (Must Exclude First)

• Helminth infections are a leading cause of eosinophilia after allergic disorders 2, 9
• Obtain stool ova-and-parasite examinations on three separate samples 2, 9
• Order Strongyloides serology as part of the helminth work-up 2, 9

Diagnostic Algorithm

Immediate Steps

1. Calculate absolute eosinophil count from the 4% peripheral eosinophils 2, 9

   • If >1,500 cells/µL: urgent hematology referral for hypereosinophilic syndrome work-up (serum tryptase, vitamin B12, bone marrow biopsy, flow cytometry) 2, 9

2. Exclude parasitic infection before any treatment 2, 9

   • Three stool ova-and-parasite examinations 2, 9
   • Strongyloides serology 2, 9

3. Review all medications for drug-induced eosinophilia (NSAIDs, bisphosphonates, tetracyclines) 2, 9

4. Obtain CT or MRI abdomen to assess for gastric/duodenal wall thickening (eosinophilic gastroenteritis), hepatic lesions (parasitic infection), or lymphadenopathy (hypereosinophilic syndrome) 2, 9

Histologic Confirmation

1. Review duodenal biopsies from the initial endoscopy for:

   • Villous atrophy, crypt hyperplasia, and intraepithelial lymphocytosis (celiac disease) 6, 7
   • Eosinophil counts in esophagus (≥15 eos/hpf for eosinophilic esophagitis), stomach (>20 eos/hpf for eosinophilic gastritis), and duodenum 1, 2

2. If biopsies were not adequate, repeat endoscopy with:

   • Multiple biopsies from at least two levels of esophagus (proximal and distal) 1
   • Multiple gastric biopsies from both inflamed and normal-appearing mucosa 2
   • Multiple duodenal biopsies for celiac disease confirmation 1

Management Priorities

Celiac Disease Treatment

• Initiate strict gluten-free diet immediately to reverse villous atrophy, resolve malabsorption, and prevent complications including osteoporosis and intestinal lymphoma 6, 7
• Referral to dietitian experienced in celiac disease is essential 1

Iron Deficiency Anemia Treatment

• Start oral ferrous sulfate 200 mg twice daily immediately 8
• Do not delay iron replacement while awaiting further investigations 8

Eosinophilic Gastrointestinal Disease Treatment (if confirmed)

• 8-week proton pump inhibitor trial (standard or double dose) can be considered, as PPI-responsive esophageal eosinophilia is increasingly recognized 1, 9
• Repeat endoscopy with biopsies after 8 weeks to assess histologic response 1, 9
• Swallowed topical corticosteroids (budesonide oral suspension) if PPI trial fails 1
• Elimination diet under dietitian guidance for eosinophilic esophagitis 1

Diabetes Management

• Evaluate for type 1 diabetes (anti-GAD, anti-islet cell antibodies) given strong association with celiac disease 7
• Optimize glycemic control with endocrinology referral 7

Nutritional Repletion

• Oral iron supplementation as above 8
• Vitamin D supplementation (typically 2,000-4,000 IU daily) 1
• Folic acid supplementation (1 mg daily) 1

Common Pitfalls to Avoid

• Do not attribute the gastrointestinal inflammation solely to celiac disease without quantifying eosinophils on biopsy, as dual pathology (celiac disease plus eosinophilic gastroenteritis) can coexist 2, 9

• Do not overlook hypereosinophilic syndrome when eosinophil counts are markedly elevated, as cardiac involvement can be life-threatening 2, 9

• Do not start a PPI trial before excluding parasitic infection if the patient has relevant exposure history 9

• Do not rely solely on symptoms and peripheral eosinophilia for diagnosing eosinophilic gastrointestinal disease; endoscopic biopsies are mandatory 2, 9

• Do not accept the diagnosis of celiac disease without histologic confirmation of villous atrophy, even with highly positive serology 1, 6

• Do not assume iron deficiency is solely due to celiac disease without excluding other causes, as dual pathology occurs in 10-15% of iron deficiency anemia cases 1, 8