Endgames Case Review

A premenopausal woman with abdominal discomfort and iron deficiency anaemia

BMJ 2015; 351 doi: https://doi.org/10.1136/bmj.h4664 (Published 03 September 2015) Cite this as: BMJ 2015;351:h4664
  1. Abdulkani Yusuf, gastroenterology specialist registrar1,
  2. Bhamini Vadhwana2,
  3. core surgical trainee,
  4. Ujjwala Mohite, associate specialist in histopathology3,
  5. Carole Collins, consultant gastroenterologist4
  1. 1Department of Gastroenterology, Chelsea and Westminster Hospital, London, UK
  2. 2Department of Surgery, North Middlesex University Hospital, London
  3. 3Department of Pathology, West Middlesex University Hospital, London
  4. 4Department of Gastroenterology, West Middlesex University Hospital
  1. Correspondence to: A Yusuf abdyus12{at}gmail.com

A 48 year old premenopausal woman presented to our clinic with a 12 month history of intermittent abdominal discomfort associated with bloating, constipation, and weight loss of 6.3 kg. Her medical history included chronic iron deficiency anaemia, vitamin D deficiency, and episodes of fresh rectal bleeding caused by haemorrhoids, which required sclerotherapy. She had undergone a diagnostic laparoscopy for abdominal pains, which did not detect any abnormalities. There was no family history of colorectal cancer. On examination she looked well, weighed 50 kg, with a body mass index of 20. Her abdomen was soft, non-tender, and without palpable masses. The results of a digital rectal examination were normal. Routine blood tests showed iron deficiency anaemia, with haemoglobin 109 g/L (reference range 117-155), mean corpuscular volume 80.6 fL (80-100), mean corpuscular haemoglobin 27.3 pg/cell (27-33), and ferritin 4 ng/mL (10-232)


1. What are the most important common causes of iron deficiency anaemia in Western countries?

  • 2. What is the most likely diagnosis in this patient and how would you confirm it?

  • 3. What are the complications of this condition?

  • 4. How would you follow up the patient long term?


1. What are the most important common causes of iron deficiency anaemia in Western countries?

Short answer

The most important common causes of iron deficiency anaemia in men and postmenopausal women in Western countries are colorectal cancer and malabsorptive disorders. In premenopausal women menstrual blood loss is the primary cause.1 2


Iron deficiency anaemia is the most common form of anaemia worldwide,3 4 and it occurs in 2-5% of the Western adult population.1 A cause can be identified in most cases. In men and postmenopausal women, occult gastrointestinal blood loss from aspirin or non-steroidal anti-inflammatory drug use, colorectal cancer, benign gastric ulceration, and angiodysplasia are the most common causes. Malabsorptive disorders, such as coeliac disease, are also important causes and can manifest with no overt bleeding or gastrointestinal symptoms. Menstrual blood loss is the primary cause of iron deficiency anaemia in premenopausal women.1 2 Worldwide the most common causes are dietary deficiency and parasitic infestations.1 5

2. What is the most likely diagnosis in this patient and how would you confirm it?

Short answer

The combination of abdominal symptoms, such as bloating and weight loss, iron deficiency anaemia, and vitamin D deficiency suggests an underlying malabsorptive state. The most likely diagnosis is coeliac disease. The diagnosis is suggested by raised tissue transglutaminase antibody (tTGA) and is confirmed by the presence of villous atrophy on duodenal biopsy.


The combination of bloating and weight loss associated with iron deficiency anaemia and vitamin D deficiency suggests an underlying malabsorptive state. The most likely diagnosis is coeliac disease. Once the diagnosis is suspected an initial screening blood test for IgA tTGA should be carried out. This test, which has practically replaced the labour intensive endomysial antibody (EMA) test, has a sensitivity and specificity of more than 95% for coeliac disease, although its accuracy varies between manufacturers. The best assays have a higher sensitivity than EMA testing and comparable specificity, both around 98%. In addition, both of these serological tests are falsely negative in the 2% of patients with coeliac disease who have selective IgA deficiency. For this reason, immunoglobulin levels should be checked together with standard serological testing, and if IgA deficiency is present, duodenal biopsies should be obtained.6 More recently the deaminated gliadin peptide antibody test has become available, but a recent meta-analysis has shown that it is inferior to tTGA testing.6

If initial tTGA levels are raised, an oesophagogastroduodenoscopy is usually performed to obtain duodenal biopsies for confirmation of the diagnosis. If coeliac disease is suspected, four duodenal biopsies should be obtained from different sites, including the duodenal bulb. Histological features of coeliac disease include partial or total villous atrophy, increased numbers of intraepithelial lymphocytes, increased numbers of plasma cells in the lamina propria, and crypt hyperplasia (figs 1-3 ).


Fig 1 Duodenal biopsy (from our patient) showing intraepithelial lymphocytes (arrows). Haematoxylin and eosin stain; original magnification ×10


Fig 2 Duodenal biopsy (from our patient) showing crypt hyperplasia (boxed areas). Haematoxylin and eosin stain; original magnification ×4


Fig 3 Duodenal biopsy (from our patient) showing villous atrophy (arrows). Haematoxylin and eosin stain; original magnification ×4

Coeliac disease is an autoimmune small bowel enteropathy precipitated by dietary gluten, which is found in foods containing wheat, rye, and barley. Its prevalence is about one in 100 in the United Kingdom and the incidence is increasing.7 Coeliac disease is known to be underdiagnosed in both primary and secondary care,8 9 possibly because gastrointestinal symptoms are often subtle or even absent. British Society Of Gastroenterology guidelines on iron deficiency anaemia recommend screening all affected patients for coeliac disease.1

The pathophysiology of coeliac disease involves two factors: genetic predisposition and consumption of dietary gluten. Almost all patients express human leucocyte antigen HLA-DQ2 or HLA-DQ8, although 25% of the general population in the UK are positive for these subtypes.7 These two antigens facilitate the immune response against gluten proteins.10 The absence of HLA-DQ2 and HLA-DQ8 makes a diagnosis of coeliac disease highly unlikely and this can be of value when other diagnostic tests are inconclusive.11 Concordance rates among monozygotic twins and first degree relatives have been reported as 70% and 10%, respectively.12 13

Nutritional problems caused by coeliac disease include malabsorption of iron, folate, calcium, and fat soluble vitamins such as vitamin D.13 14 Patients are therefore at risk of iron and folate deficiencies as well as osteopenia. Mucosal damage is greatest in the duodenum, where most iron is absorbed, which is why iron deficiency anaemia is so common in this disease.15

Extra-intestinal symptoms include dermatitis herpetiformis and neurological symptoms, such as ataxia and peripheral neuropathy.16 Coeliac disease has also been associated with subfertility, abnormal liver biochemistry and function of unknown cause, Down’s syndrome, Turner’s syndrome, Sjögren’s syndrome and other autoimmune conditions including type 1 diabetes, autoimmune hypothyroidism, and autoimmune hepatitis.6 8 17 About 30% of patients have functional hyposplenism, which can be diagnosed on a blood film, and if this is present patients should be offered Haemophilus influenzae, pneumococcal, and annual influenza vaccinations.18

3. What are the complications of this condition?

Short answer

Non-compliance with a gluten-free diet is the most important factor predisposing patients to osteoporosis and splenic atrophy. Rare complications include small bowel T cell lymphoma and other gastrointestinal cancers.


The most common cause of an inadequate response is non-adherence to a strict gluten-free diet, which inevitably increases the risk of complications. Patients with coeliac disease are predisposed to osteoporosis, which can lead to osteoporotic fractures. A dual energy x ray absorptiometry (DEXA) scan is recommended at diagnosis, and evidence shows that bone density scores improve on a gluten-free diet.8 Patients can develop splenic atrophy, and some evidence suggests that they are at increased risk of overwhelming pneumococcal sepsis. Vaccination against pneumococcus is therefore recommended at diagnosis.8 18

Untreated coeliac disease has also been associated with a slightly increased risk of mortality and cancer compared with the standardised population rate. Associated cancers include non-Hodgkin’s lymphoma and oesophageal and small bowel adenocarcinomas; however a gluten-free diet reduces the risk of cancers in these patients.7 8 10 19

4. How would you follow up the patient long term?

Short answer

Patients with coeliac disease require regular follow-up to ensure and encourage compliance with a gluten-free diet and to monitor them for complications and associated autoimmune diseases.


Patients with coeliac disease are at risk of developing complications and therefore require regular follow-up. For asymptomatic patients, the British Society of Gastroenterology recommends a yearly check of full blood count, ferritin, folate, vitamin B12, calcium, and alkaline phosphatase. Associated autoimmune conditions (thyroid function tests and serum glucose) and liver disease should also be monitored. Serum tTGA might be used to confirm adherence to gluten-free diet. All patients should have a DEXA scan at presentation and be re-assessed every three years if the initial scan is abnormal. Men and women with a normal initial scan should have repeat scan at 55 years of age and menopause, respectively.8 If the patient’s symptoms return, dietary adherence should be checked and repeat duodenal biopsies perhaps performed. Clinicians should also be aware of the possibility of developing associated autoimmune diseases and cancer.

Patient outcome

Our patient had raised serum tTGA and duodenal biopsy confirmed that she had coeliac disease (figs 1-3). In accordance with British Society of Gastroenterology guidelines, colonoscopy was not indicated because she was under 50 years, she had a confirmed diagnosis of coeliac disease, and there was no family history of colorectal carcinoma. She had a DEXA scan at diagnosis, the results of which were normal. She was informed about a gluten-free diet and referred to a dietitian for further education. Regular follow-up is planned.


Cite this as: BMJ 2015;351:h4664


  • Competing interests: We have read and understood BMJ policy on declaration of interests and declare the following interests: none.

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

  • Patient consent obtained.


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