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Difficulty: HardMedical History Evaluation

A 65-year-old man is evaluated in the clinic for a 5-month history of progressive, voluminous watery diarrhea, abdominal bloating, and a 9-kg (19.8-lb) weight loss. He reports having 5 to 7 loose bowel movements daily that occasionally awaken him from sleep. His past medical history includes essential hypertension, type 2 diabetes mellitus, and hyperlipidemia. His past surgical history is unremarkable. He is a retired accountant who lives with his wife, drinks 1 to 2 glasses of wine on weekends, and has not traveled outside of his home state in the past decade. His medications include metformin, atorvastatin, and olmesartan. The olmesartan was initiated 8 months ago to replace lisinopril, which was discontinued due to a persistent dry cough.

Physical examination reveals a temperature of 37.0°C (98.6°F), blood pressure of 118/74 mmHg, and a heart rate of 88/min. The abdomen is soft and non-tender with hyperactive bowel sounds. Skin turgor is slightly decreased.

Laboratory evaluation shows:
- Hemoglobin: 11.2 g/dL
- Leukocyte count: 6,500/mm³
- Potassium: 3.2 mEq/L
- Bicarbonate: 18 mEq/L
- Tissue transglutaminase (tTG) IgA antibody: Negative
- Total serum IgA: 180 mg/dL (Normal: 70-400 mg/dL)

Stool studies are negative for enteric pathogens, ova, and parasites. The fecal osmotic gap is low, consistent with secretory diarrhea.

Due to the persistent symptoms and weight loss, an upper endoscopy with duodenal biopsy is performed. The histopathology report reveals severe villous blunting and atrophy with a marked increase in intraepithelial lymphocytes.

Based on the clinicopathologic findings, a thorough review of which of the following elements of the patient's medical history is MOST critical for establishing the definitive etiology of his condition?

  1. The precise timeline of initiation of his angiotensin II receptor blocker therapyAnswer
  2. B
    A detailed log of daily dietary gluten intake and potential cross-contamination sources
  3. C
    Recent consumption of grapefruit juice or macrolide antibiotics
  4. D
    A history of recurrent childhood and young adult sinopulmonary infections
  5. E
    The date and histopathologic findings of his most recent screening colonoscopy

Answer

The precise timeline of initiation of his angiotensin II receptor blocker therapy
The correct answer identifies the timeline of olmesartan (an ARB) initiation as the critical historical element. Olmesartan is a known cause of drug-induced sprue-like enteropathy. It presents with severe, chronic diarrhea and weight loss, and small bowel biopsy reveals villous atrophy and increased intraepithelial lymphocytes. Crucially, celiac serologies (like tTG IgA) are negative. The onset of symptoms can be months to years after starting the medication. Confirming the temporal relationship between starting olmesartan and symptom onset establishes the diagnosis, and the treatment is immediate discontinuation of the offending drug.

Step-by-Step Solution

1
Analyze the patient's primary symptoms and demographic.
A 65-year-old man presents with chronic, severe watery diarrhea and significant weight loss over 5 months.
Establishing the chief complaint helps narrow the broad differential diagnosis of chronic diarrhea.
2
Evaluate the endoscopic and histologic findings.
Duodenal biopsy demonstrates severe villous blunting and an increase in intraepithelial lymphocytes.
These findings are characteristic of a sprue-like enteropathy, classic for celiac disease but also seen in other conditions.
3
Correlate histologic findings with serologic data.
The patient has negative tTG IgA antibodies and a normal total IgA level.
Normal total IgA validates the negative tTG IgA test, making celiac disease highly unlikely and prompting a search for alternative causes of villous atrophy.
4
Review the patient's medical history for alternative etiologies.
The patient began taking olmesartan 8 months ago, which was 3 months prior to the onset of his symptoms.
Olmesartan is strongly associated with drug-induced sprue-like enteropathy, establishing the correct diagnosis.

Key Concept

Olmesartan-induced sprue-like enteropathy presents with severe diarrhea, weight loss, and duodenal villous atrophy, clinically and histologically mimicking celiac disease but featuring negative celiac serologies.
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Topics

Medical History Evaluation

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