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MKSAP: 32-year-old woman with loose stools, bloating, and weight loss

mksap
Conditions
February 8, 2020
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Test your medicine knowledge with the MKSAP challenge, in partnership with the American College of Physicians.

A 32-year-old woman is evaluated for a 6-month history of loose stools, bloating, and a 3.2-kg (7-lb) weight loss. Her medical history is otherwise unremarkable. Her brother has type 1 diabetes mellitus, and her mother has autoimmune thyroid disease. She reports no other symptoms and takes no medication.

On physical examination, vital signs and other findings are normal; BMI is 19.

Laboratory studies:

Hemoglobin 11.0 g/dL (110 g/L)
Alanine aminotransferase 60 U/L
Aspartate aminotransferase 42 U/L
Total bilirubin 0.9 mg/dL (15.4 µmol/L)
Ferritin 6 ng/mL (6 µg/L)

Which of the following is the most appropriate test to perform next?

A. Anti–gliadin IgA antibody
B. Anti–Saccharomyces cerevisiae IgA antibody
C. Anti–smooth muscle antibody
D. Anti–tissue transglutaminase IgA antibody

MKSAP Answer and Critique

The correct answer is D. Anti–tissue transglutaminase IgA antibody.

Testing for anti–tissue transglutaminase (tTG) IgA antibody is the most appropriate next test for this patient, who has symptoms of celiac disease, including diarrhea, bloating, and weight loss. She is underweight due to malabsorption related to immune destruction of small intestinal villi, and she has laboratory abnormalities associated with celiac disease, including iron deficiency anemia and elevated liver transaminases. Her family history of autoimmune diseases is also consistent with celiac disease due to common genetic predisposition (HLA-DQ2 and DQ8). The best initial screening test for celiac disease is anti–tTg IgA antibody testing. Given increased prevalence of IgA deficiency in celiac disease, total IgA levels should be measured in patients with high suspicion for celiac disease. If patients are IgA deficient, IgG-based antibody testing (such as deamidated gliadin peptide [DGP] IgG or transglutaminase IgG) should be performed. Positive antibody screening for celiac disease should prompt upper endoscopy and biopsies of the duodenum for definitive diagnosis. Treatment is a lifelong, strict gluten-free diet.

Gliadin antibodies are neither sensitive nor specific for the diagnosis of celiac disease and are no longer recommended for the evaluation of celiac disease. Newer gliadin-based serology tests, anti–DGP IgA and anti–DGP IgG, have greater sensitivity and specificity than older antigliadin antibodies. Anti–DGP IgG is particularly useful in cases of total IgA deficiency for diagnosing celiac disease.

Anti–Saccharomyces cerevisiae antibodies have been proposed as a serologic method for differentiating Crohn disease from ulcerative colitis, but they are neither adequately sensitive nor specific and can lead to false-positive results if used as a screening test for gastrointestinal symptoms. In addition, the absence of fever, bloody diarrhea, or abdominal pain makes the diagnosis of inflammatory bowel disease unlikely in this patient.

Anti–smooth muscle antibody testing can be helpful in the diagnosis of autoimmune hepatitis. Autoimmune hepatitis is a chronic inflammatory liver disease that is usually seen in women and can be associated with other autoimmune diseases (most commonly autoimmune thyroiditis, synovitis, or ulcerative colitis). The disease presentation ranges from asymptomatic to acute liver failure. Serum aminotransferase levels are elevated and range from mild elevations to greater than 1000 U/L. Serum IgG levels are also elevated. Patients with autoimmune hepatitis do not present with loose stools, bloating, and weight loss.

Key Point

  • Anti–tissue transglutaminase IgA antibody testing is the best screening test for celiac disease.

This content is excerpted from MKSAP 18 with permission from the American College of Physicians (ACP). Use is restricted in the same manner as that defined in the MKSAP 18 Digital license agreement. This material should never be used as a substitute for clinical judgment and does not represent an official position of ACP. All content is licensed to KevinMD.com on an “AS IS” basis without any warranty of any nature. The publisher, ACP, shall not be liable for any damage or loss of any kind arising out of or resulting from use of content, regardless of whether such liability is based in tort, contract or otherwise.

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