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Lactose Intolerance

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  • Primary lactose intolerance usually begins in late childhood.

  • No consensus exists on whether young children (<5 years of age) should avoid lactose following diarrheal illness.

  • Lactose-free formulas are available.

  • Exclude milk protein allergy.

‚  

EPIDEMIOLOGY


Incidence
  • ≥50% of infants with acute or chronic diarrheal disease have lactose intolerance. Particularly common with rotavirus infection.
  • Lactose intolerance is common with giardiasis, ascariasis, irritable bowel syndrome (IBS), tropical and nontropical sprue, and the AIDS malabsorptive syndrome.

Prevalence
  • In South America, Africa, and Asia, rates of lactose intolerance are >50%.
  • In the United States, the prevalence is 15% among whites, 53% among Hispanic Americans, and 80% among African Americans.
  • In Europe, lactose intolerance varies from 15% in Scandinavian countries to 70% in Italy.
  • Predominant age:
    • Primary: teenage and adult
    • Secondary: depends on underlying condition
  • Predominant sex: male = female

ETIOLOGY AND PATHOPHYSIOLOGY


  • Primary lactose intolerance: Normal decline in the lactase activity in the intestinal mucosa is genetically controlled and permanent after weaning from breastmilk.
  • Secondary lactose intolerance: associated with gastroenteritis in children and with nontropical and tropical sprue, regional enteritis, abetalipoproteinemia, cystic fibrosis, inflammatory bowel disease, celiac disease, and immunoglobulin deficiencies in both adults and children

Genetics
  • In Caucasians, lactase deficiency has been associated with a single nucleotide polymorphism (SNP) consisting of a nucleotide switch of T for C 13.910.bp on chromosome 2. This results in variants of CC-13910 (lactase nonpersistence) OR CT-13910/TT-13910 (lactase persistence) (1).
  • SNP (C/T-13910) is associated with lactase persistence in northern Europeans.
  • Other SNPs (G/C-14010, T/G-13915, and C/G-13907) have been linked to lactase persistence in Africans.

RISK FACTORS


  • Adult-onset lactase deficiency has wide geographic variation.
  • Age:
    • Signs and symptoms usually do not become apparent until after age 6 to 7 years.
    • Symptoms may not be apparent until adulthood, depending on dietary lactose intake and rate of decline of intestinal lactase activity.
    • Lactase activity correlates with age, regardless of symptoms.

GENERAL PREVENTION


Lactose avoidance relieves symptoms. Patients can learn what level of lactose is tolerable in their diet. ‚  

COMMONLY ASSOCIATED CONDITIONS


  • Tropical or nontropical sprue
  • Giardiasis
  • Inflammatory bowel disease
  • Immunoglobulin deficiencies
  • Celiac disease
  • Cystic fibrosis

DIAGNOSIS


  • Lactose intolerance is defined by a positive lactose hydrogen breath test result plus accompanying clinical symptoms.
  • Lactose intolerance can mimic symptoms of functional gastrointestinal disorders. Lactose intolerance can also be a coexisting condition.

HISTORY


  • Assess patient 's daily lactose consumption. A single dose of lactose (12 g, equivalent to 1 cup of milk) consumed alone produces no or minor symptoms in persons with lactose intolerance or maldigestion.
  • Lactose doses of 15 to 18 g are well tolerated with other nutrients. Doses >18 g cause progressively more symptoms, and quantities >50 g elicit symptoms in most individuals.
  • Symptoms may arise 30 minutes to 2 hours after consumption of lactose-containing products.
  • Symptoms include bloating, cramping, abdominal discomfort, vomiting diarrhea or loose stools, and flatulence.
  • Symptoms tend to appear 30 minutes to 2 hours after eating.
  • Abdominal pain may be crampy in nature and often is localized to the periumbilical area or lower quadrant.
  • Stools usually are bulky, frothy, and watery
  • Only ’ … “; to ’ … •; of individuals with lactose malabsorption develop symptoms.

PHYSICAL EXAM


Borborygmi may be audible on physical examination and to the patient. The exam is otherwise typically nonspecific. ‚  

DIFFERENTIAL DIAGNOSIS


  • Sucrase deficiency
  • Cow 's milk protein allergy
  • IBS
  • Bacterial overgrowth
  • Celiac disease
  • Inflammatory bowel disease

DIAGNOSTIC TESTS & INTERPRETATION


Initial Tests (lab, imaging)
  • The lactose breath hydrogen test (LBT) is the best diagnostic test for lactose intolerance. It is noninvasive, easy to perform, and cost effective. It is limited by suboptimal sensitivity (2)[B]. Intestinal bacteria digest carbohydrates and produce hydrogen and methane that are measurable in expired air:
    • Oral lactose is administered in the fasting state, (2 g/kg; max dose 25 g). Breath hydrogen is sampled at baseline and at 30-minute intervals for 3 hours. The postlactose and baseline values are compared. A breath hydrogen value of 10 ppm is normal. Values between 10 and 20 ppm may be indeterminate unless accompanied by symptoms; values >20 ppm are considered diagnostic of lactose malabsorption.
  • The biochemical assay of lactase activity on duodenal sampling is as sensitive as LBT in detecting lactase deficiency. It is more accurate than LBT in predicting the clinical response to a lactose-free diet. Cost and invasiveness limit clinical utility
  • For patients with symptoms of lactose intolerance who are undergoing endoscopy for other reasons, a biochemical assay on duodenal biopsies can rule out lactose malabsorption.
  • A positive LBT confirms lactose malabsorption but does not define the etiology.

Diagnostic Procedures/Other
Lactose absorption test is an alternative to LBT in adults (more invasive and equivalent in sensitivity and specificity to breath test). Following oral administration of a 50-g test dose in adults (2 g/kg in children), blood glucose levels are monitored at 0, 60, and 120 minutes. An increase in blood glucose of <20 mg/dL (1.1 mmol/L) with the concurrent development of symptoms is diagnostic. False-negative results may occur in patients with diabetes or bacterial overgrowth. ‚  
Test Interpretation
Lactase deficiency in intestinal mucosa may be patchy or focal. ‚  

TREATMENT


There is insufficient evidence on treatments (including probiotics, colonic adaptation, and other supplements) to recommend any as definitive first-line. ‚  
  • Treatment of lactose malabsorption in the absence of a correctable underlying disease includes four general principles (3)[B].
    • Patients should avoid milk and dairy products in order to improve symptoms.
    • Up to 12 to 15 g of lactose can be tolerated in patients with lactose intolerance without significant symptoms (1 cup of milk).
    • Lactose should be gradually reintroduced along with other nutrients until the patient 's threshold for symptoms is reached. Spreading lactose servings throughout the day instead of a single dose has been shown to improve tolerance.
    • If symptoms persist, patients can substitute fermented and matured milk products for lactose.
  • Certain strains, concentrations, and preparations of probiotics may alleviate symptoms.
  • Incrementally increasing doses of lactose to induce colonic adaptation have met with limited success.
  • To date, insufficient scientific evidence exists to strongly recommend lactose-reduced or hydrolyzed milk, lactase supplements taken with milk, probiotics, or colonic adaptation to treat lactose intolerance. Use of these supplements should be considered on a case-by-case fashion.
  • Maintain calcium and vitamin D intake.

MEDICATION


First Line
Lactase (Lactaid, Lactrase): ‚  
  • Commercially available "lactase "  preparations are bacterial or yeast Ž ²-galactosidases.
  • Take 1 to 2 capsules or tablets prior to ingesting milk products.
  • Vary in effectiveness at preventing symptoms
  • Can add tablets or contents of capsules to milk (1 to 2 caps/tabs per quart of milk) before drinking; also available in milk in some areas
  • Not effective for all people with lactose intolerance
  • High-quality, large, randomized controlled trials showing efficacy and safety are lacking.

COMPLEMENTARY & ALTERNATIVE MEDICINE


Certain probiotic formulations taken with meals may alleviate some symptoms of lactose intolerance (4)[B]. ‚  

ONGOING CARE


DIET


  • Reduce or restrict dietary lactose to control symptoms. This is patient-specific and done as "trial-and-error. " 
  • Yogurt and fermented products such as hard cheese are often better tolerated than milk.
  • Supplement calcium (e.g., calcium carbonate)
  • Prehydrolyzed milk (Lactaid) is available.

PATIENT EDUCATION


  • Patients must learn to read labels on commercial products because milk sugar is used in many products and may cause symptoms.
  • Lactose-intolerant patients may tolerate whole milk or chocolate milk better than skim milk due to slower rate of gastric emptying.
  • Lactose consumed with other food products is better tolerated than when consumed with milk alone.
  • Primary lactase deficiency is permanent; secondary lactose intolerance usually is temporary, although it may persist for months after the inciting event.
  • 20% of prescription drugs and 6% of over-the-counter (OTC) medicines use lactose as a base.
  • Most patients can tolerate 12 to 15 g of lactose, despite lactose intolerance or malabsorption.

PROGNOSIS


  • Normal life expectancy
  • Symptoms can be controlled through diet alone if lactase tablets are ineffective.

COMPLICATIONS


Calcium deficiency: Avoidance of milk and other dairy products can lead to reduced calcium intake, which may increase the risk for osteoporosis and fracture. ‚  

REFERENCES


11 Mattar ‚  R, de Campos Mazo ‚  DF, Carrilho ‚  FJ. Lactose intolerance: diagnosis, genetic, and clinical factors. Clin Exp Gastroenterol.  2012;5:113 " “121.22 Law ‚  D, Conklin ‚  J, Pimentel ‚  M. Lactose intolerance and the role of the lactose breath test. Am J Gastroenterol.  2010;105(8):1726 " “1728.33 Shaukat ‚  A, Levitt ‚  MD, Taylor ‚  BC, et al. Systematic review: effective management strategies for lactose intolerance. Ann Intern Med.  2010;152(12):797 " “803.44 Levri ‚  KM, Ketvertis ‚  K, Deramo ‚  M, et al. Do probiotics reduce adult lactose intolerance? A systematic review. J Fam Pract.  2005;54(7):613 " “620.

ADDITIONAL READING


  • Almeida ‚  CC, Lorena ‚  SL, Pavan ‚  CR, et al. Beneficial effects of long-term consumption of a probiotic combination of Lactobacillus casei Shirota and Bifidobacterium breve Yakult may persist after suspension of therapy in lactose-intolerant patients. Nutr Clin Pract.  2012;27(2):247 " “251.
  • Boettcher ‚  E, Crowe ‚  SE. Dietary proteins and functional gastrointestinal disorders. Am J Gastroenterol.  2013;108(5):728 " “736.
  • Fern ƒ ‘ndez-Ba ƒ ±ares ‚  F. Reliability of symptom analysis during carbohydrate hydrogen-breath tests. Curr Opin Clin Nutr Metab Care.  2012;15(5):494 " “498.
  • Furnari ‚  M, Bonfanti ‚  D, Parodi ‚  A, et al. A comparison between lactose breath test and quick test on duodenal biopsies for diagnosing lactase deficiency in patients with self-reported lactose intolerance. J Clin Gastroenterol.  2013;47(2):148 " “152.
  • Tan-Dy ‚  CR, Ohlsson ‚  A. Lactase treated feeds to promote growth and feeding tolerance in preterm infants. Cochrane Database Syst Rev.  2013;(3):CD004591.

CODES


ICD10


  • E73.9 Lactose intolerance, unspecified
  • E73.8 Other lactose intolerance
  • E73.1 Secondary lactase deficiency
  • E73.0 Congenital lactase deficiency

ICD9


271.3 Intestinal disaccharidase deficiencies and disaccharide malabsorption ‚  

SNOMED


  • 267425008 lactose intolerance (disorder)
  • 190751001 Primary lactose intolerance
  • 60414003 Acquired lactase deficiency
  • 5388008 Congenital lactase deficiency
  • 54250004 Lactose intolerance in children without lactase deficiency

CLINICAL PEARLS


  • The diagnosis of lactose intolerance is based on clinical history and typically confirmed by hydrogen breath testing.
  • Most lactose intolerant patients can tolerate 12 to 15 g of lactose per day.
  • Lactose-intolerant patients may tolerate yogurt and fermented products better than milk and cheese.
  • A food diary helps identify problematic foods.
  • Patients should read ingredient labels to look for milk, lactose, whey, and curd.
  • Lactose-intolerant patients may tolerate whole milk or chocolate milk better than skim milk due to a slower rate of gastric emptying.
  • Many patients with lactose intolerance unnecessarily avoid all dairy products, causing inadequate intake of calcium and vitamin D, which may predispose them to osteoporosis.
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