Intended for healthcare professionals

Endgames Case Review

A woman with a 10 year history of abdominal pain

BMJ 2018; 360 doi: (Published 29 March 2018) Cite this as: BMJ 2018;360:k603
  1. Jessica Richelieu, medical student1,
  2. John WI Morse, internist and gastroenterologist2,
  3. David C Pfeiffer, professor3
  1. 1University of Washington School of Medicine, Seattle, Washington, USA
  2. 2Kings Lane Medical Clinic, Salt Spring Island, British Columbia, Canada
  3. 3Department of Biological Sciences and WWAMI Medical Education Program, University of Idaho, Moscow, Idaho, USA
  1. Correspondence to D Pfeiffer dpfeiffer{at}

A 64 year old woman with a history of Still’s disease presented with more than 10 years of abdominal pain and bloating. Her symptoms were initially intermittent, but over the last six months they had worsened and she had experienced weight loss of 10 kg.

She recalled being told that she had a “leaky gut” by a health professional nine years ago, and that she was advised to follow a gluten-free diet. She believed her symptoms had improved after this, but over time she returned to her original diet and her symptoms eventually returned. Computed tomography scanning and abdominal ultrasound two years ago were normal. A hepatobiliary scan showed a borderline low gallbladder ejection fraction of 34%. She underwent an upper endoscopy to rule out the possibility of a peptic ulcer. No ulcer was found, but several small gastric fundal polyps were observed and biopsied. These were attributed to proton pump inhibitor (pantoprazole) use. Antral biopsies were normal but duodenal biopsies (figs 1 and 2) showed mild villus blunting and intraepithelial lymphocytosis. These were attributed to a disease of autoimmune origin; however, anti-transglutaminase (tTG) testing was negative. A colonoscopy revealed hyperplastic polyps, but was otherwise unremarkable.

Fig 1
Fig 1

Duodenal biopsy showing mild villus blunting (arrows) (haematoxylin and eosin stain, original magnification×200)

Fig 2
Fig 2

Duodenal biopsy showing intraepithelial lymphocytosis. Arrows indicate nuclei of representative lymphocytes (haematoxylin and eosin stain, original magnification×200)


  • 1. What is the most likely diagnosis?

  • 2. Is there a definitive diagnostic test for this condition?

  • 3. What is the treatment for this condition?


1. What is the most likely diagnosis?

Short answer

Coeliac disease.


Change in bowel habits, weight loss, and bloating in a 64 year old woman are red flags for colon cancer and warrant colonoscopy.

Other differential diagnoses for a patient with these symptoms include mild coeliac disease, the overuse of anti-inflammatory drugs, Crohn’s disease, and small bowel bacterial overgrowth (SBBO).

The patient was not using anti-inflammatory drugs and there was no evidence of Crohn’s disease or colon cancer from colonoscopy, imaging, or histopathology.

Duodenal biopsies revealed mild villus blunting and intraepithelial lymphocytosis consistent with mild coeliac disease. While it is difficult to exclude SBBO without a trial of antibiotics, the patient’s history of positively responding to a gluten-free diet supports coeliac disease as the diagnosis.

Coeliac disease is an autoimmune disorder that is triggered by consumption of gluten-containing products. It occurs in about 1% of the worldwide population.1 Factors that increase risk for the disease include genetics and the use of antibiotics. Preliminary studies also suggest a strong association between the use of drugs that suppress gastric acid secretion, such as proton pump inhibitors, with a subsequent diagnosis of coeliac disease.2

The pathogenesis differs from immediate IgE controlled hypersensitivity reactions. In coeliac disease, the gluten protein itself causes a release of cytokines and subsequent inflammation. The gluten protein is activated by tissue tTG, and gluten tTG complexes are presented to CD4 T cells found in the lamina propria of the small intestine, resulting in the generation of autoantibodies against tTG.3

Clinical features can present in childhood or adulthood. Common symptoms include chronic diarrhoea, bloating, constipation, and abdominal pain. Malabsorption is an important sequela of these, often leading to weight loss, iron deficiency, chronic fatigue, headache, and osteoporosis.2

2. Is there a definitive diagnostic test for this condition?

Short answer

No. Duodenal biopsy, anti-tTG testing, and human leucocyte antigen genetic analysis are supportive but not specific for coeliac disease.


Previously, the gold standard for the diagnosis of coeliac disease was histological examination of multiple biopsies from the patient’s duodenum. Multiple biopsies increased the chances of detecting the patchy distribution of coeliac disease and diagnosis was made upon finding intraepithelial lymphocytosis, villous atrophy, and crypt hyperplasia. Diseased areas were often classified using the Marsh system with Marsh II and IIIa-c lesions demonstrating increased damage of the villi and mucosa, indicating coeliac disease. However, it is now known that these changes can also be seen with drug overuse, other immunodeficiency, and infection with organisms such as Giardia lamblia or Helicobacter pylori. Therefore, biopsies often must be confirmed with serology, and follow-up biopsies should be taken after restriction of gluten to determine efficacy.4

Serology testing uses detection of IgA anti-tissue tTGA by enzyme linked immunosorbent assay. This test is 97% sensitive, 96% specific, and can be confirmed by IgA anti-endomysial (IGA EMA) analysis when positive, increasing the specificity to nearly 100%. However, false negatives can be observed in individuals who have concurrent IgA deficiency and tTG-IgG testing might also be recommended. Antigliadin (AGA) antibodies are no longer a standard of practice for diagnosis because of low sensitivity and specificity.1 Autoimmune disorders, cancer, liver disease, and infectious processes can also yield abnormal anti-tTG levels on analysis. However, EMA testing is often negative in cancer, liver disease, and infectious processes, making the EMA test more specific for coeliac disease.

More recently, genetic testing has been included to assess the risk of coeliac disease in symptomatic patients, and to identify individuals at high risk.3

3. What is the treatment for this condition?

Short answer

The only effective treatment is adherence to a strict gluten-free diet; however, rates of adherence are low and novel treatments are being researched. Some show potential for being effective, but none has made it past the trial phase.


Early detection and adequate disease education through healthcare providers and/or local coeliac disease support groups is important to increase the likelihood of patients choosing appropriate foods. Being aware of the adverse outcomes of untreated coeliac disease can also improve compliance.

The Coeliac Disease Foundation recommends that patients have repeat serology testing, starting at their 3-6 month follow-up visit and annually thereafter. Failure of autoantibodies to decrease or completely return to normal limits within 6-12 months on a strict, gluten-free diet could indicate the presence of non-responsive coeliac disease or other co-existing conditions. The foundation also recommends that patients be monitored by dietitians and primary care providers for compliance and effectiveness of treatment.

It is also important that patients are monitored to ensure anaemia, vitamin deficiencies, and mineral deficiencies do not occur through malabsorption by a damaged digestive tract.5

Adherence to a gluten-free diet involves major lifestyle changes and is particularly difficult in patients with lower socioeconomic status, less education, and inadequate knowledge of their disease.6 Gluten-free foods are also often more expensive and lacking in desirable flavours and textures. Patients can also accidentally ingest trace amounts of gluten in foods that were believed to be gluten free.

Patient outcome

After discussion with her doctor, the patient decided to restart a gluten-free diet with follow-up in one month. A repeat anti-tTG at this follow-up was negative.

One month after starting a gluten-free diet the patient’s symptoms had resolved and she had regained 1 kg in weight.


  • Patient consent obtained.

  • We have read and understood the BMJ policy on declaration of interests and declare that we have no competing interests.

  • Provenance and peer review: not commissioned; externally peer reviewed.


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