Differentials
Peptic duodenitis
SIGNS / SYMPTOMS
Patients present with chronic or recurrent abdominal pain or discomfort centred in the upper abdomen that is commonly related to eating. There may be a history of non-steroidal anti-inflammatory drug use and use of antacid medications to relieve the discomfort.
INVESTIGATIONS
Peptic duodenitis is associated with acid injury and leads to a spectrum of histological mucosal changes that may be difficult to distinguish from that seen in coeliac disease.[115] For this reason, biopsies should be taken both in the duodenal bulb and in the second or third portion of the duodenum (relatively protected from peptic injury). Biopsies from the bulb and distal duodenum should be submitted to pathology in separate jars.
Crohn's disease
SIGNS / SYMPTOMS
Crohn's disease can affect any part of the gastrointestinal tract, and symptoms may be extremely variable.
INVESTIGATIONS
The classical findings on histological examination include granulomas, ulcerations, and acute and chronic inflammation often extending throughout all layers of the bowel wall.
Tissue transglutaminase serology is usually negative, and there should be no response to gluten withdrawal.
Giardiasis
SIGNS / SYMPTOMS
Giardiasis is a diarrhoeal illness caused by infection with a waterborne parasite, Giardia lamblia. A history of exposure to contaminated water may suggest the diagnosis.[116]
INVESTIGATIONS
Stool microscopy with direct fluorescence antibody testing is the most sensitive test.[116] Alternative methods for detection are antigen detection tests by enzyme immunoassays and detection of parasites by immunofluorescence, rapid immunochromatographic cartridge assays, microscopy with trichrome staining, and molecular assay.[116]
Small intestinal bacterial overgrowth
SIGNS / SYMPTOMS
History may show conditions that alter intestinal anatomy, motility, and gastric acid secretion (such as use of proton pump inhibitors or anatomical disturbances in the bowel, including fistulae, diverticula, and blind loops created after surgery).[117]
INVESTIGATIONS
The definitive investigation requires culture of jejunal fluid that grows in excess of 10⁵ bacteria/mL. Hydrogen breath testing is a non-invasive, clinically available test, but it is not very sensitive or specific for bacterial overgrowth.[118]
Post-gastroenteritis
SIGNS / SYMPTOMS
In some children a clinical episode indistinguishable from acute gastroenteritis is followed by protracted diarrhoea. This may be related to prolonged rotavirus infection[119] or transient lactose intolerance.
INVESTIGATIONS
Usually no investigations are required.
Eosinophilic enteritis
SIGNS / SYMPTOMS
Eosinophilic enteritis may affect any part of the gastrointestinal tract and can present with anaemia, diarrhoea, abdominal pain, and weight loss. Often no cause is identified, although nematode infections may be isolated.[120]
INVESTIGATIONS
Diagnosis follows endoscopic or laparoscopic biopsy of the affected bowel, with histology showing eosinophilic infiltrates.[120]
Tropical sprue
SIGNS / SYMPTOMS
Tropical sprue causes progressive villous atrophy in the small intestine that is similar to coeliac sprue.
There are no clinical, endoscopic, or histological features that can differentiate tropical sprue from coeliac disease.[121] Specific serological tests for coeliac disease are required.
Tropical sprue is believed to be initiated or sustained by a still-undefined infection. The relapse rate is substantial in treated patients who remain in, or return to, endemic areas in the tropics.[122]
INVESTIGATIONS
Negative for anti-tissue transglutaminase and anti-endomysial antibodies.[123]
Common variable immune deficiency (CVID) and other immunodeficiency states
SIGNS / SYMPTOMS
CVID and related disorders have a history of recurrent infections.
INVESTIGATIONS
Negative tissue transglutaminase serology and decreased immunoglobulin levels suggest immunodeficiency. Absence of plasmocytes in the lamina propria.
Graft-versus-host disease (GVHD)
SIGNS / SYMPTOMS
GVHD can occur with any organ transplantation but is most common after bone marrow transplantation. Patients have high-volume watery diarrhoea about 3 weeks after transplantation if GVHD is present.[124]
INVESTIGATIONS
Endoscopic biopsy showing the presence of increased numbers of apoptotic epithelial cells in the intestinal crypts is diagnostic.[124]
Autoimmune enteropathy
SIGNS / SYMPTOMS
This condition is characterised by villous atrophy that is unresponsive to any dietary restrictions.[125]
INVESTIGATIONS
Negative for immunoglobulin A tissue transglutaminase and anti-endomysial antibodies.
Immunofluorescence staining may show enterocyte antibodies.[125] Lymphocytic infiltration in the crypt epithelium, crypt abscesses, and apoptotic bodies; absent goblet cells.
Drug-induced enteropathy
SIGNS / SYMPTOMS
May be clinically and pathologically indistinguishable from coeliac disease.
Olmesartan, an angiotensin-II receptor antagonist, has been associated with enteropathy.[126]
There have also been case reports with other angiotensin-II receptor antagonists and mycophenolate.[127] Use of non-steroidal anti-inflammatory drugs is also associated with lymphoplasmacytic infiltrate and partial villous atrophy.
INVESTIGATIONS
Tissue transglutaminase serology is normal.
Symptoms remit once the causative drug is stopped.
Non-coeliac gluten sensitivity
SIGNS / SYMPTOMS
May share similar symptoms with coeliac disease, with improvement on a gluten-free diet. There should not be any villous atrophy.
INVESTIGATIONS
Tissue transglutaminase serology remains normal. FBC, iron, folate, vitamin B12, and vitamin D levels are typically within normal ranges, but may be deficient in a minority of patients.[128] Small intestinal histology is normal. There is improvement of symptoms after 6 weeks (or less) on the gluten-free diet and recurrence with reintroduction of gluten.
Diabetic hypoglycaemia
SIGNS / SYMPTOMS
Usually patient is known to have diabetes and is taking medication with potential to cause hypoglycaemia. In addition to nausea and lethargy, patients may report symptoms of irritability, feeling warm, palpitations, anxiety, sweating, and shakiness.
INVESTIGATIONS
Laboratory definitions vary according to specific patient/clinical situation. Random serum blood glucose level <70 mg/dL (level 1 hypoglycaemia) suggests a need for clinical management.
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