What is the best course of action for a 30-year-old female patient with 7 months of headaches, fatigue, 4 months of joint pain, and recent onset of diarrhea, who has iron deficiency anemia, negative autoimmune and tick panel results, and normal brain imaging?

Gastrointestinal Evaluation with Bidirectional Endoscopy

This 30-year-old woman with iron deficiency anemia requires bidirectional endoscopy (upper endoscopy and colonoscopy) to evaluate for gastrointestinal pathology, despite her premenopausal status and negative initial workup. 1

Rationale for Endoscopic Investigation

The combination of prolonged constitutional symptoms (7 months of headaches and fatigue), joint pain (4 months), and new-onset diarrhea alongside iron deficiency anemia raises concern for underlying gastrointestinal pathology that warrants direct visualization. 1

Key Clinical Features Supporting Investigation

• Gastrointestinal symptoms present: The recent onset of diarrhea is a red flag symptom that strengthens the indication for bidirectional endoscopy in this premenopausal woman. 1

• Prolonged systemic symptoms: Seven months of headaches and fatigue, combined with four months of joint pain, suggest a chronic inflammatory or malabsorptive process beyond simple menstrual blood loss. 2

• Celiac disease screening essential: The combination of iron deficiency anemia, diarrhea, joint pain, and fatigue is highly suggestive of celiac disease, which requires upper endoscopy with duodenal biopsies for definitive diagnosis. 1

Specific Investigations Required

Bidirectional Endoscopy Protocol

• Upper endoscopy with duodenal biopsies: Mandatory to evaluate for celiac disease, which can present with this exact symptom constellation and is a common cause of iron deficiency anemia in young women. 1, 3

• Colonoscopy with terminal ileum intubation: Necessary to evaluate for inflammatory bowel disease (particularly Crohn's disease), which commonly presents with iron deficiency anemia, diarrhea, joint pain, and fatigue. 4

• Detection of other pathology: Bidirectional endoscopy can identify erosive esophagitis, peptic ulcer disease, gastric antral vascular ectasia, and angioectasias. 1

Malignancy Risk Considerations

While the risk of gastrointestinal malignancy in premenopausal women with iron deficiency anemia is low (0.9% for lower GI malignancy and 0.2% for upper GI malignancy), the presence of diarrhea and prolonged constitutional symptoms justifies investigation. 1

Additional Diagnostic Workup

Celiac Serology

• Tissue transglutaminase IgA with total IgA: Should be obtained before endoscopy, though negative serology does not exclude celiac disease and duodenal biopsies remain necessary. 1

Inflammatory Markers

• C-reactive protein and erythrocyte sedimentation rate: Elevated inflammatory markers would support inflammatory bowel disease or other chronic inflammatory conditions. 1

Stool Studies

• Fecal calprotectin: Useful screening test for inflammatory bowel disease given the diarrhea. 4

• Comprehensive stool studies: Including culture, ova and parasites, and Giardia antigen to exclude infectious causes of chronic diarrhea. 4

Urinalysis

• Urine microscopy: To evaluate for microscopic hematuria as a potential source of iron loss, though less likely given the gastrointestinal symptoms. 1

Iron Replacement Therapy

Initiate Oral Iron Supplementation

• Ferrous sulfate 325 mg daily or on alternate days: Begin iron replacement while awaiting endoscopic evaluation, as treatment should not be delayed. 2

• Take on empty stomach or with vitamin C: Improves absorption, though may be taken with food if gastrointestinal side effects occur. 5, 6

• Avoid within 2 hours of tetracycline antibiotics: If prescribed for any reason. 6

Monitor Response

• Repeat hemoglobin after 4 weeks: To confirm diagnosis and assess response to therapy. 5

• Continue for 2-3 months after anemia correction: To replenish iron stores. 5

Common Pitfalls to Avoid

• Do not assume menstrual blood loss is the sole cause: Even in premenopausal women with heavy menses, the presence of gastrointestinal symptoms mandates investigation. 1

• Do not delay endoscopy for trial of iron therapy: The diarrhea and prolonged constitutional symptoms require prompt evaluation. 1

• Do not miss celiac disease: This is a highly treatable cause that requires duodenal biopsies for diagnosis and can explain the entire clinical picture. 1, 3

• Do not overlook inflammatory bowel disease: The combination of iron deficiency anemia, diarrhea, and joint pain is classic for IBD, which affects 13-90% of patients with iron deficiency. 2, 4

Alternative Consideration if Endoscopy Negative

If bidirectional endoscopy with appropriate biopsies is unrevealing:

• Small bowel imaging: Consider capsule endoscopy or MR enterography to evaluate for small bowel Crohn's disease, angioectasias, or other small bowel pathology. 1

• Repeat inflammatory markers and celiac serology: If not initially obtained. 1