Diagnóstico clínico e laboratorial da intolerância a lactose

CLINICAL MANIFESTATIONS — The term lactose intolerance is applied to the development of characteristic symptoms after the ingestion of lactose: abdominal pain, bloating, flatulence, diarrhea, and, particularly in adolescents, vomiting. The abdominal pain may be crampy in nature and is often localized to the periumbilical area or lower quadrant. Borborygmi may be audible on physical examination and to the patient. The stools are usually bulky, frothy, and watery.
There is a variability of symptoms among patients with lactose intolerance. Important factors include the osmolality and fat content of the food in which the sugar is ingested, the rate of gastric emptying, the sensitivity to intestinal distension produced by the osmotic load of unhydrolyzed lactose in the upper small bowel, the rate of intestinal transit, and the response of the colon to the carbohydrate load. The following general principles apply to the patient with lactose intolerance:
• Meals with higher osmolality and fat content slow gastric emptying and reduce the severity of lactose-induced symptoms.
• The rate of intestinal transit is also influenced by individual motility patterns. People with more rapid movement of lactose to the cecum will generally be more symptomatic.
• Individuals have variable sensitivity to the abdominal distension produced when undigested lactose stimulates an influx of water into the lumen of the small intestine or gas production leads to distension of the colon.
These subjective responses are difficult to quantify. As an example, patients with lactose intolerance who also have irritable bowel syndrome (IBS) may have increased pain after lactose ingestion. In one report of 427 healthy subjects, 15 percent of both lactose digesters and maldigesters met the symptom criteria for IBS. Although the prevalence of lactase deficiency was not higher in patients with IBS, patients who reported an intolerance of milk products had a higher likelihood of meeting the symptom criteria for IBS compared with patients who were tolerant to milk products (OR 4.6; 95% CI 2.1 to 10.1). A five-year prospective study evaluated a lactose restricted diet in patients with lactose malabsorption and irritable bowel syndrome. The study demonstrated improvement in both short- and long-term symptoms as well as a reduction in outpatient visits by 75 percent. Other studies have confirmed the importance of subjective and perhaps psychological factors in the development of lactose-induced symptoms. Given the similarity that may occur with regard to symptoms, a lactose breath hydrogen test or an empiric trial of a lactose free diet should be part of the evaluation of patients suspected of having irritable bowel syndrome.
Fecal flora can adapt to a chronic increase in dietary lactose, reducing the incidence and severity of symptoms following a lactose load. In a crossover study of this phenomenon, 20 patients with confirmed lactose maldigestion were randomized to lactose or dextrose supplementation for 10 days; the dose was gradually increased to 0.6 to 1.0 g/kg per day in three equal doses. There was no significant difference in symptoms during these periods. Lactose challenge was performed after an overnight fast at the end of these periods. Lactose supplementation was associated with a 50 percent reduction in flatus passage and severity and a marked reduction in the hourly breath hydrogen concentration compared with dextrose supplementation.
However, somewhat different results were noted in another crossover trial with a similar design. Two weeks of lactose supplementation led to bacterial adaptation as evidenced by increased fecal beta-galactosidase activity and reduced breath hydrogen excretion after a lactose load. All symptoms except diarrhea regressed but equivalent clinical improvement occurred in the placebo group in which bacterial adaptation did not occur.
Relation of symptoms of lactose intolerance to lactose — The symptoms associated with lactose ingestion may not necessarily be related to lactose malabsorption. One study evaluated 30 subjects who complained of severe lactose intolerance who said they consistently developed symptoms after ingestion of less than 240 mL (8 oz) of milk. The ability to digest lactose was assessed by a breath hydrogen test after a lactose load, which was abnormal in 21 subjects. Daily during breakfast, the subjects were then given 240 mL of lactose-hydrolyzed milk containing 2 percent fat or 240 mL of 2 percent fat milk that was sweetened with aspartame to simulate the taste of lactose-hydrolyzed milk. There was no difference in symptoms during the two study periods.
The authors drew two conclusions: symptoms in lactose maldigesting subjects with severe intolerance may mistakenly be attributed to lactose; and symptoms are likely to be negligible if lactose intake is limited to the equivalent of 240 mL of milk per day. A subsequent report from the same group found that 240 mL of milk could be tolerated twice daily if given in widely divided doses with food. However, one quart (946 mL) of milk (equivalent to 50 grams of lactose) usually induced symptoms in adults with malabsorption when administered as a single dose without meals.
Similar observations were made in a study of 45 African-Americans with documented lactose maldigestion and intolerance to less than 240 mL of milk. Two-thirds reacted appropriately to the presence or absence of lactose in ingested milk, but one-third had equivalent symptoms with lactose-containing and low-lactose milk.
Individuals with lactose malabsorption may still be able to tolerate a diet of calcium rich dairy products. A study involving women with lactose maldigestion demonstrated tolerance to a diet that provided 1500 mg of Ca/day by a variety of dairy products (hard cheese, yogurt, and milk) that were spread throughout the day. Another study involving adolescent girls with lactose maldigestion demonstrated that a dairy based diet providing 1200 mg of calcium per day was also well tolerated with negligible gastrointestinal symptoms.
People with lactose intolerance often avoid taking medications in pill form because of the potential for lactose in the preparations to cause symptoms. In a study that addressed this issue, the investigators hypothesized that pills or tablets would be unlikely to contain more than 400 mg of lactose. They performed a randomized, cross-over, double-blind study that evaluated breath hydrogen production and symptoms in 77 lactose intolerant subjects after the ingestion of 400 mg of lactose or placebo. Neither breath hydrogen levels nor symptoms were different when subjects ingested low-dose lactose than when they ingested placebo.
DIAGNOSIS — The term lactose malabsorption is generally reserved for those patients with typical symptoms in whom the intestinal malabsorption of lactose has been confirmed by a test of absorption (eg, lactose absorption test) or malabsorption (lactose breath hydrogen test). Less direct tests, such as low fecal pH or reducing substances in the stool, are only valid when lactose has been ingested, intestinal transit time is rapid, stools are collected fresh, assays are performed immediately, and bacterial metabolism of colonic carbohydrate is incomplete. The importance of confirming the diagnosis was illustrated in the preceding study of African Americans.
Lactose tolerance test — The capacity for lactose absorption can be measured using a lactose absorption test. Following oral administration of a 50 g test dose in adults (or 2 g/kg in children), blood glucose levels are monitored at 0, 60, and 120 minutes. An increase in blood glucose by less than 20 mg/dL (1.1 mmol/L) plus the development of symptoms is diagnostic. False negative results may occur in patients with diabetes or bacterial overgrowth. Abnormal gastric emptying also can lead to spurious results; the blood glucose may be relatively higher with rapid emptying and depressed with delayed gastric emptying.
In adults, the lactose tolerance test has a sensitivity of 75 percent and a specificity of 96 percent. However, it is cumbersome (particularly in children) and time consuming, and has largely been replaced by the lactose breath hydrogen test.
Lactose breath hydrogen test — The breath hydrogen test measures lactose nonabsorption. It is simple to perform, noninvasive, and has a sensitivity and specificity that are superior to the absorption test.
The test is begun by giving oral lactose in the fasting state, at a usual dose of 2 g/kg (maximum dose, 25 g). Breath hydrogen is sampled at baseline and at 30-minute intervals after the ingestion of lactose for three hours. The post-lactose and baseline values are compared. We generally consider a breath hydrogen value of 10 ppm (parts per million) as normal. Values between 10 and 20 ppm may be indeterminate unless accompanied by symptoms, while values over 20 ppm are considered diagnostic of lactose malabsorption.
Both false-positive and false-negative results can occur. False-positive results are seen with inadequate pretest fasting or recent smoking; false-negative results can be seen after the recent use of antibiotics, in patients with lung disorders, or in the approximately 1 percent of subjects who are nonhydrogen producers. As noted above, intestinal lactase levels do not begin to fall until after age five. Thus, an abnormal lactose breath hydrogen test in children less than five years reflects either abnormal intestinal mucosa or bacterial overgrowth, both of which require further evaluation by appropriate diagnostic tests. A normal breath hydrogen test does not rule out an intestinal mucosal lesion and should not be used to avoid an intestinal biopsy.
On the other hand, small bowel biopsy cannot necessarily establish the diagnosis of disaccharidase deficiency. Although low values can identify subjects at risk for symptomatic lactose intolerance, low lactase activity induced by intestinal injury may be missed if the lesion is focal or patchy. Thus, clinical and biochemical data must always be compared to establish the diagnosis.
Once the diagnosis of lactose maldigestion is confirmed, the patient should be evaluated for one of the secondary causes described above. Patients with a treatable underlying disorder may recover lactase activity and not require enzyme replacement. In infants and young children, the possibility of cow's milk protein intolerance should be excluded.
Normal breath hydrogen tests — A significant proportion of patients with symptoms suggestive of lactose intolerance have normal breath hydrogen tests. In two series described above, for example, 30 and 42 percent of subjects with severe symptoms of milk intolerance had normal tests. Other possibilities that must be considered include psychologic factors and intolerance to other components in milk.
Some patients have symptoms similar to those of lactose intolerance that are related to the maldigestion of other simple carbohydrates (eg, fructose, sorbitol) or of complex carbohydrates (eg, high-fiber foods). Thus, a careful dietary history should be obtained and appropriate breath hydrogen testing or dietary modification performed.
Genetic test for primary lactose malabsorption — A test for the genetic polymorphism associated with the previously mentioned polymorphism that is 13.9 kb upstream from the 5' end of the lactase transcriptional start site has been developed. In one study, lactase enzyme levels obtained during duodenal biopsies as the "gold standard" for lactase status were compared to the genetic variant with C/C-13910. The majority of 8 year-olds and all children over 12 years of age had a tight correlation between the C/C variant and low lactase activity. Sensitivity and specificity were 93 and 100 percent, respectively, which is comparable to the accuracy of the lactose tolerance test and breath hydrogen tests. However, the test is expensive and may not be covered by the patient's insurance. Furthermore, the test may not be useful for patients of African origin. We generally prefer the lactose breath hydrogen test.

REFERÊNCIA
• http://www.uptodate.com/contents/lactose-intolerance?detectedLanguage=it&source=search_result&translation=diagnosing+lactose+intolerance&search=diagn%C3%B3stico+lactose+intolerance&selectedTitle=1~105&provider=google: