Approach

Diagnosis of lactase deficiency manifesting as lactose intolerance is based on a characteristic clinical history of precipitation of gastrointestinal and/or systemic symptoms within minutes to a few hours after consumption of products containing lactose (dairy and non-dairy).

[Figure caption and citation for the preceding image starts]: Lactose-containing productsCreated by BMJ using content from Dr Mohammad Azam [Citation ends].com.bmj.content.model.Caption@46cd407d

A 2-week trial of dietary lactose elimination, with resolution of symptoms, and subsequent challenge, with recurrence of symptoms, is generally diagnostic.[2] Biochemical diagnostic tests are rarely required in practice.

For more subtle cases, the lactose hydrogen breath test can be used to confirm the diagnosis.​​[2][25]​​ The milk-tolerance test, where blood glucose is measured after administration of 500 mL of milk, or a fixed mass of lactose (12.5 to 50.0 grams), has relatively low sensitivity and specificity and is no longer performed.[26]

Historical factors

Patients usually present with symptoms of abdominal pain (typically, cramping in periumbilical area), bloating, tummy rumbling, or loud tinkling sounds from abdomen (borborygmi), flatulence (which may help relieve symptoms in some patients), and diarrhoea (typically, explosive, bulky, frothy, and watery) after consuming dairy products.

[Figure caption and citation for the preceding image starts]: Symptoms in people with lactose intoleranceDr Mohammad Azam adapted from: Matthews SB, Waud JP, Roberts AG, et al. Systemic lactose intolerance: a new perspective on an old problem. Postgrad Med J. 2005;81:167-173 [Citation ends].com.bmj.content.model.Caption@60082430

Symptoms in people with lactose intolerance

Nausea and vomiting may also be present, especially in adolescents. Most patients are also aware of symptomatic improvement after avoiding products containing lactose (dietary lactose elimination). Other, less common, presentations include constipation, vomiting, faltering growth (especially with congenital lactase deficiency), and increased frequency of associated systemic symptoms.[1] Evidence, though relatively limited, suggests that systemic symptoms may include headache, poor short-term memory, poor concentration, light-headedness, severe tiredness, joint pain, muscle pain, eczema, mouth ulceration, arrhythmia, and asthma.[1] Systemic symptoms are more common in adults. Patients with systemic symptoms, and those in whom symptoms are due to lactose from non-dairy products (hidden lactose), are generally not aware of the relationship between their symptoms and lactose.

It is important to enquire about the timing of symptom onset. Symptoms typically develop between a few minutes and a couple of hours after ingestion of lactose from dairy and non-dairy products. However, it can take some patients up to 12 hours to develop symptoms.

Many patients say that they have previously been diagnosed with irritable bowel syndrome, which has very similar symptoms and may even coexist with lactase deficiency.[1][23][24]

Patients with secondary lactase deficiency may have additional symptoms; for example:

  • Skin rashes and Kaposi sarcoma with HIV enteropathy

  • Anaemia and weight loss with eosinophilic enteritis

  • Short stature, anaemia, and weight loss with coeliac disease

  • Steatorrhoea and history of residence in endemic areas with tropical sprue

  • Joint pain and arthritis with Whipple's disease

  • Fever with severe gastroenteritis

  • Flushing and palpitations with carcinoid syndrome

  • Progressive disability with cystic fibrosis

  • Sensory loss with diabetic gastropathy

  • Oedema and skin ulceration with kwashiorkor

  • Steatorrhoea, peptic ulcer disease, and gastro-oesophageal reflux disorder with Zollinger-Ellison syndrome

  • Hair loss and mouth ulceration with chemotherapy use

  • Hair loss and rash with colchicine use (for familial Mediterranean fever)

  • Hair loss and rash with radiation enteritis.

Physical examination

Abdominal examination may reveal abdominal tenderness and distension that is tympanic to percussion.

Trial of dietary lactose elimination

A trial of elimination of lactose-containing dairy and non-dairy products that results in resolution of symptoms, followed by resumption of symptoms with reintroduction of dietary lactose, is suggestive of lactase deficiency.[2] The threshold for lactose varies among people. Most patients can tolerate a glass of milk (240 mL = 11 g lactose) a day, whereas others develop symptoms with just 2-3 g lactose from a chocolate bar.[27] Patients should be encouraged to acquaint themselves with the lactose content of common foods. University of Virginia Digestive Health Center: lactose content of common dairy foods Opens in new window

Routine blood tests

Patients with abdominal pain and diarrhoea should have a full blood count. Normal results do not differentiate lactase deficiency; however, if anaemia is present, it may point toward the underlying cause of secondary lactase deficiency (e.g., coeliac disease).

Lactose hydrogen breath test with simultaneous recording of symptoms

If dietary elimination and subsequent challenge are inconclusive, further investigation may be undertaken with this non-invasive, easy-to-perform test (with high sensitivity and specificity).[2]​​[25][28]

Accurate results require proper equipment and preparation. Certified medical products for collection should be used. Ideally the patient should be fasting for at least 8 hours. Smoking and exercise may induce hyperventilation, and should be avoided. Guidelines recommend delaying breath testing until 4 weeks after completion of antibiotic therapy and 2 weeks after colonic cleansing.[28][29]​​

Patients are given lactose at a dose of 2 g/kg (up to a maximum of 25 g) after overnight fasting. Breath hydrogen is sampled at baseline and at 30-minute intervals for 3 hours, and symptoms of intolerance are recorded. Values between 10 and 19 parts per million (ppm) may be indeterminate unless accompanied by symptoms, while values ≥20 ppm are considered diagnostic.[28][29]​ Revised criteria (breath hydrogen at the sixth hour >6 ppm, or the sum of breath hydrogen at the fifth, sixth, and seventh hours >15 ppm) have been suggested but are not widely practised in the US and Europe.[2][30][31]

Sensitivity is increased if the test is continued for 6 hours, and hourly breath hydrogen samples are collected from 3-6 hours. However, this is not yet widely accepted as standard clinical practice.[1][2][31]

Sensitivity may be further increased if expired methane gas (especially in hydrogen non-producers) is also measured and symptoms recorded for 48 hours.[1][32]​ However, no positivity criteria have been internationally accepted.

Stool studies

Rarely, stool cultures are performed; used primarily in patients with short histories of diarrhoeal illness to help distinguish between infection and lactose intolerance. The stools of patients with diarrhoea and suspicion of lactose (or other carbohydrates) intolerance (e.g., negative stool culture) may also be screened for the presence of reducing substances and low faecal pH.[2]

Faecal reducing substances

  • Reducing substances are monosaccharide by-products of carbohydrate metabolism.

  • Fresh stool samples are required and assays should be performed immediately.

  • In infants, measurable faecal reducing substances are due to carbohydrate metabolism; but the test cannot differentiate lactose from fructose, glucose, and galactose malabsorption, so specificity is quite low.

  • This is relatively less sensitive than the measurement of faecal pH.

Faecal pH

  • Measurement of faecal pH is an especially useful test in infants.

  • Faecal pH is reduced in hypolactasia, owing to the formation of volatile fatty acids as a result of carbohydrate malabsorption.

  • It has lower sensitivity and specificity than the lactose hydrogen breath test, and it does not differentiate lactose from other carbohydrate malabsorption.

  • Faecal pH is lower in infants than in older children.

Lactose tolerance test

If stool studies are inconclusive, this test, which shows lactose malabsorption due to lactase deficiency, may be performed. It involves fasting serum glucose measurement, administration of lactose, and subsequent serial serum glucose measurements. False-negative results may occur in patients with diabetes mellitus or bacterial overgrowth. Abnormal gastric emptying can also affect the results (blood glucose may be relatively higher with rapid emptying or lower with delayed gastric emptying). Owing to the large number of false-positive and false-negative results, and to the cumbersome and time-consuming nature of the test, it has largely been replaced by the lactose hydrogen breath test.[2]

Small bowel biopsy

This may be performed in patients with persistent symptoms and positive coeliac serology, patients with convincing histories of exposure to giardiasis (e.g., water from wells, camping) or bacterial overgrowth (e.g., prior surgery), or if lactose hydrogen breath test is not available. It involves upper gastrointestinal endoscopy to take small bowel samples for direct measurement of lactase (and other disaccharides), and to investigate for some secondary causes of lactase deficiency (e.g., coeliac disease, giardiasis, small bowel bacterial overgrowth).[2] However, intestinal lactase concentrations do not seem to correlate well with the symptoms of lactose intolerance, and the biopsy results may be normal if mucosal abnormality is focal or patchy.[33]

This invasive test is less sensitive than the non-invasive lactose hydrogen breath test.

Emerging tests

The 13C-labelled lactose breath test (currently primarily an investigational tool) may be used in the future to augment the accuracy of the lactose hydrogen breath test.[34][35]

Emerging evidence regarding the role of genotyping suggests it might be a useful diagnostic test. It has high sensitivity and specificity, and is used in Germany and the Nordic countries.[1][32][36] It is not yet widely available in clinical practice elsewhere, but continues to be under further evaluation worldwide. Genotyping provides a definitive result of a hypolactasia genotype, without the need to consider cut-off levels, lactose dosing, patient age, or test duration.[37] However, lactase non-persistent genotype is not necessarily accompanied by a malabsorption phenotype.

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