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 nondairy).
[Figure caption and citation for the preceding image starts]: Lactose-containing productsCreated by BMJ using content from Dr Mohammad Azam [Citation ends].
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] 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.[25]
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 diarrhea (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].
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 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 nondairy products (hidden lactose), are generally not aware of the relationship between their symptoms and lactose.
It is important to inquire 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 nondairy products. However, it can take some patients up to 12 hours to develop symptoms.
Many patients say 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
Anemia and weight loss with eosinophilic enteritis
Short stature, anemia, and weight loss with celiac disease
Steatorrhea and history of residence in endemic areas with tropical sprue
Joint pain and arthritis with Whipple disease
Fever with severe gastroenteritis
Flushing and palpitations with carcinoid syndrome
Progressive disability with cystic fibrosis
Sensory loss with diabetic gastropathy
Edema and skin ulceration with kwashiorkor
Steatorrhea, peptic ulcer disease, and gastroesophageal 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 exam
Abdominal exam 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 nondairy 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 between 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.[26] 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 diarrhea should have a complete blood count. Normal results do not differentiate lactase deficiency; however, if anemia is present, it may point toward the underlying cause of secondary lactase deficiency (e.g., celiac 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 noninvasive, easy-to-perform test (with high sensitivity and specificity).[2][27]
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.[27][28]
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.[27][28] 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 practiced in the US and Europe.[2][29][30]
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][30]
Sensitivity may be further increased if expired methane gas (especially in hydrogen nonproducers) is also measured and symptoms are recorded for 48 hours.[1][31] However, no positivity criteria have been internationally accepted.
Stool studies
Rarely, stool cultures are performed; used primarily in patients with short histories of diarrheal illness to help distinguish between infection and lactose intolerance. The stools of patients with diarrhea 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 fecal pH.[2]
Fecal reducing substances
Reducing substances are monosaccharide byproducts of carbohydrate metabolism.
Fresh stool samples are required and assays should be performed immediately.
In infants, measurable fecal reducing substances are due to carbohydrate metabolism, but the test cannot differentiate lactose from fructose, glucose, and galactose malabsorption, meaning specificity is quite low.
This is relatively less sensitive than the measurement of fecal pH.
Fecal pH
Measurement of fecal pH is an especially useful test in infants.
Fecal pH is reduced in hypolactasia, due 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.
Fecal 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). Due to the large number of false-positive and false-negative results, and 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 celiac serology, patients with convincing histories of exposure to giardiasis (e.g., well-water, 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., celiac 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.[32]
This invasive test is less sensitive than the noninvasive lactose hydrogen breath test.
Emerging tests
The 13C-labeled lactose breath test (currently primarily an investigational tool) may be used in the future to augment the accuracy of the lactose hydrogen breath test.[33][34]
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][31][35] 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.[36] However, lactase nonpersistent genotype is not necessarily accompanied by a malabsorption phenotype.
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