A 35-year-old Caucasian female presents with anemia, malaise, bloating, and diarrhea. Past genetic testing revealed that this patient carries the HLA-DQ2 allele. The physician suspects that the patient's presentation is dietary in cause. Which of the following findings would definitively confirm this diagnosis?

Biopsy of the duodenum showing atrophy and blunting of villi

CT scan showing inflammation of the small bowel wall

Biopsy of the colon showing epithelial cell apoptosis

Esophageal endoscopy showing lower esophageal metaplasia

Liver biopsy showing apoptosis of hepatocytes

A 23-year-old man presents to the office complaining of weight loss and fatigue for the past 2 months. He states that he has been experiencing foul-smelling, light-colored stools but thinks it is because he hasn’t been eating well, recently. He has a past medical history significant for cystic fibrosis, which is well-controlled medically. He denies any shortness of breath, chest or abdominal pain, nausea, vomiting, or melena. On physical examination, his skin is pale and dry. Which of the following would be the most likely etiology of a malabsorption syndrome giving rise to this patient’s current condition?

Decreased recycling of bile acids

Autoimmune damage to parietal cells

Chronic damage to intestinal mucosa

Damage to intestinal brush border

A previously healthy 20-year-old woman comes to the physician because of recurrent abdominal cramps, bloating, and diarrhea for 4 months. She describes her stools as greasy, foul-smelling, and difficult to flush. During this time she has had a 6-kg (13.2-lb) weight loss. She has no personal or family history of serious illness. Physical examination shows pallor and cheilitis. Laboratory studies show a hemoglobin concentration of 11 g/dL. Serum concentrations of electrolytes, urea nitrogen, and creatinine are within the reference range. Test of the stool for occult blood is negative and stool microscopy reveals no pathogens and no leukocytes. Analysis of a 24-hour stool sample shows 12 g of fat. The patient is asked to consume 25 g of d-xylose. Five hours later, its concentration is measured in urine at 2 g (N = > 4 g/5 h). The test is repeated after a two-week course of rifaximin, but the urinary concentration of d-xylose remains the same. Which of the following is the most likely diagnosis?

Exocrine pancreatic insufficiency

Bacterial overgrowth in the small intestine

An 82-year-old woman presents with 2 months of foul-smelling, greasy diarrhea. She says that she also has felt very tired recently and has had some associated bloating and flatus. She denies any recent abdominal pain, nausea, melena, hematochezia, or vomiting. She also denies any history of recent travel and states that her home has city water. Which of the following tests would be most appropriate to initially work up the most likely diagnosis in this patient?

Tissue transglutaminase antibody test

CT of the abdomen with oral contrast

A 24-year-old man comes to the physician for the evaluation of a severely pruritic skin rash. Physical examination shows a symmetrical rash over the knees and elbows with tense, grouped vesicles, and several excoriation marks. Microabscesses in the papillary dermis are seen on light microscopy. Immunofluorescence shows deposits of immunoglobulin A at the tips of dermal papillae. This patient's skin findings are most likely associated with which of the following?

Gliadin-dependent hypersensitivity

A 24-year-old woman with 45,X syndrome comes to the physician because of diarrhea for 4 months. She also reports bloating, nausea, and abdominal discomfort that persists after defecation. For the past 6 months, she has felt tired and has been unable to do her normal chores. She went on a backpacking trip across Southeast Asia around 7 months ago. She is 144 cm (4 ft 9 in) tall and weighs 40 kg (88 lb); BMI is 19 kg/m2. Her blood pressure is 110/60 mm Hg in the upper extremities and 80/40 mm Hg in the lower extremities. Examination shows pale conjunctivae and angular stomatitis. Abdominal examination is normal. Laboratory studies show: Hemoglobin 9.1 mg/dL Leukocyte count 5100/mm3 Platelet count 200,000/mm3 Mean corpuscular volume 67 μmm3 Serum Na+ 136 mEq/L K+ 3.7 mEq/L Cl- 105 mEq/L Glucose 89 mg/dL Creatinine 1.4 mg/dL Ferritin 10 ng/mL IgA tissue transglutaminase antibody positive Based on the laboratory studies, a biopsy for confirmation of the diagnosis is suggested, but the patient is unwilling to undergo the procedure. Which of the following is the most appropriate next step in management of this patient's gastrointestinal symptoms?

Intravenous immunoglobulin therapy

Trimethoprim-sulfamethoxazole therapy

A 54-year-old man comes to the physician because of diarrhea that has become progressively worse over the past 4 months. He currently has 4–6 episodes of foul-smelling stools per day. Over the past 3 months, he has had fatigue and a 5-kg (11-lb) weight loss. He returned from Bangladesh 6 months ago after a year-long business assignment. He has osteoarthritis and hypertension. Current medications include amlodipine and naproxen. He appears pale and malnourished. His temperature is 37.3°C (99.1°F), pulse is 76/min, and blood pressure is 140/86 mm Hg. Examination shows pale conjunctivae and dry mucous membranes. Angular stomatitis and glossitis are present. The abdomen is distended but soft and nontender. Rectal examination shows no abnormalities. Laboratory studies show: Hemoglobin 8.9 g/dL Leukocyte count 4100/mm3 Platelet count 160,000/mm3 Mean corpuscular volume 110 μm3 Serum Na+ 133 mEq/L Cl- 98 mEq/l K+ 3.3 mEq/L Creatinine 1.1 mg/dL IgA 250 mg/dL Anti-tissue transglutaminase, IgA negative Stool culture and studies for ova and parasites are negative. Test of the stool for occult blood is negative. Fecal fat content is 22 g/day (N < 7). Fecal lactoferrin is negative and elastase is within normal limits. Which of the following is the most appropriate next step in diagnosis?

PAS-stained biopsy of small bowel

IgG against deamidated gliadin peptide

A 42-year-old woman presents with exertional dyspnea and fatigue for the past 3 months. Her past medical history is significant for multiple episodes of mild diarrhea for many years, which was earlier diagnosed as irritable bowel syndrome (IBS). She denies any current significant gastrointestinal symptoms. The patient is afebrile and vital signs are within normal limits. Physical examination reveals oral aphthous ulcers and mild conjunctival pallor. Abdominal examination is unremarkable. There is a rash present on the peripheral extremities bilaterally (see image). Laboratory findings are significant for evidence of microcytic hypochromic anemia. FOBT is negative. Which of the following is the most likely diagnosis in this patient?

Small intestinal bacterial overgrowth

Celiac disease for USMLE Step 1: High-Yield Internal Medicine Lessons

Pathophysiology & Genetics - Gluten's Gut Grudge

Genetic Predisposition: Over 95% of patients have HLA-DQ2 or HLA-DQ8 haplotypes. This is necessary but not sufficient for disease development.
Pathogenesis:
- Trigger: Gliadin, a component of gluten, is resistant to degradation.
- Key Enzyme: Tissue transglutaminase (tTG) deamidates gliadin, increasing its immunogenicity.
- Immune Cascade: Antigen-presenting cells (APCs) present deamidated gliadin on HLA-DQ2/8 molecules to CD4+ T-cells, initiating a Th1-mediated inflammatory response.
- Result: Leads to characteristic small bowel findings: villous atrophy, crypt hyperplasia, and ↑ intraepithelial lymphocytes.

Celiac Disease: Histopathology and Endoscopy

⭐ Dermatitis herpetiformis, an intensely pruritic papulovesicular rash on extensor surfaces, is a pathognomonic skin manifestation caused by IgA deposition in the dermal papillae.

Clinical Presentation - The Celiac Chameleon

Classic GI (Malabsorptive): Chronic diarrhea, steatorrhea, weight loss, bloating, abdominal distension.
Atypical (Extra-intestinal): More common in adults.
- Dermatologic: Dermatitis herpetiformis (pruritic papulovesicles on extensor surfaces).
- Hematologic: Refractory iron deficiency anemia, folate deficiency.
- Skeletal: ↓ bone mineral density, osteomalacia, osteoporosis.
- Neurologic: Peripheral neuropathy, cerebellar ataxia.
- Reproductive: Infertility, recurrent fetal loss.

Dermatitis herpetiformis rash and IgA deposits

⭐ Celiac disease is strongly associated with other autoimmune conditions, especially Type 1 Diabetes and autoimmune thyroiditis (Hashimoto's).

Diagnosis - Catching the Culprit

Initial Screening:
- IgA anti-tissue transglutaminase (tTG) antibody is the single best serologic test.
- If suspicion is high despite negative IgA tTG, check for selective IgA deficiency. If present, order IgG-based tests (e.g., IgG-DGP).
Gold Standard:
- Small bowel biopsy (duodenal) is required for confirmation.
- 📌 VACIng the gut: Villous Atrophy, Crypt hyperplasia, Intraepithelial lymphocytosis.
Genetic Testing:
- HLA-DQ2/DQ8 testing has a >99% negative predictive value. Useful to rule out the disease.

Celiac disease histopathology: normal vs. villous atrophy

⭐ Dermatitis herpetiformis (pruritic papules/vesicles on extensor surfaces) is pathognomonic. A skin biopsy showing granular IgA deposits at the dermal-epidermal junction can confirm the diagnosis without needing an intestinal biopsy.

Management & Complications - Dodging the Dough

Primary Treatment: Lifelong, strict gluten-free diet (GFD).
- Avoid wheat, barley, rye. 📌 Mnemonic: Barely Reaching Wheat.
- Permitted: Rice, corn, soy, potatoes.
Nutritional Support: Correct deficiencies at diagnosis.
- Commonly supplement iron, folate, vitamin B12, calcium, and vitamin D.
Monitoring: Follow-up with serology (tTG-IgA) to ensure dietary adherence and intestinal healing.
Complications of Untreated/Refractory Disease:
- Anemia (iron deficiency), osteoporosis.
- Dermatitis Herpetiformis: Pruritic papules/vesicles on extensor surfaces.
- Malignancy: Increased risk of small bowel adenocarcinoma & Enteropathy-Associated T-cell Lymphoma (EATL).

⭐ EATL is a rare but aggressive T-cell lymphoma of the small intestine; it is a feared complication almost exclusively seen in celiac disease.

High‑Yield Points - ⚡ Biggest Takeaways

Celiac disease is an autoimmune disorder triggered by gliadin in genetically susceptible individuals, primarily those with HLA-DQ2/DQ8.

The most specific and sensitive initial test is IgA anti-tissue transglutaminase (tTG) antibody.

The gold standard for diagnosis is a small bowel biopsy showing villous atrophy, most prominent in the duodenum.

Strongly associated with dermatitis herpetiformis, a pruritic papulovesicular rash.

Management is a strict, lifelong gluten-free diet.

Continue reading on Oncourse

CONTINUE READING — FREE

or get the app

App Store|Google Play

Celiac disease