A. Epidemiology

1. Three main types
   1. Primary - most common form
   2. Secondary - acquired form, follows any intestinal illneess that damages brush border
   3. Congenital - rare form; dysfunctional mutations of lactase
2. Primary Adult Hypolactasia
   1. Most common form
   2. Humans have "normal" decline in lactase levels during lifetime
   3. Different ethnic groups have different rates of decline over lifetime
   4. Most Northern Europeans maintain sufficient levels of lactase throughout life
   5. Asians and American Indians: ~100% incidence of hypolactasia over lifetime
   6. Blacks and Ashkenazi Jews: ~70% lactose intolerance
   7. Latinos: ~65% lactose intolerance
3. Likely that primary adult hypolactasia is a "normal variant" in human populations
4. High incidence of incorrect self-reporting of "severe" lactose intolerance [2]
5. Therefore, patients with self-diagnosed severe lactose intolerance should be evaluated

B. Causes of Secondary Hypolactasia (Table 1, Ref [1])

1. Small Bowel
   1. HIV Enteropathy
   2. Severe gastroenteritis
   3. Other causes of malabsorption
2. Multisystem
   1. Caricnoid Syndrome
   2. Diabetic gastropathy
   3. Zollinger-Ellison Syndrome
   4. Cystic Fibrosis
   5. Kwashiorkor
3. Iatrogenic
   1. Chemotherapy
   2. Radiation enteritis
   3. Colchicine (in patients with familial Mediterranean fever)

C. Pathophysiology

1. Lactase is a normal untestinal brush border enzyme found in microvilli
2. Converts lactose into glucose and galactose
3. These are transported across cell membranes (lactose is not)
4. Impaired lactose breakdown leads to delivery of lactose into colon
   1. Lactose metabolism (fermentation) by bacteria in colon
   2. High concentration of lactose into colon
   3. Breakdown into monosaccharides by colonic mucosa with release of gas
   4. Monosaccharides are not absorbed by colon
   5. This leads to increased osmotic load in colon
   6. Overgrowth of colonic bacteria leading to small intestinal colonization
5. Gas overproduction and increased colonic fluid loads result

D. Signs and Symptoms

1. Abdominal Distension
2. Crampy abdominal pain
3. Increased flatulence
4. Watery diarrhea
5. Symptoms triggered by milk and other dairy products

E. Diagnosis

1. Usually made on history and response to dietary change
2. Watery, non-bloody diarrhea should be verified
3. Breath Hydrogen Test
   1. Preferred test with ~90% sensitivity
   2. Ingestion of 25-50gm of lactose
   3. Increase in breath hydrogen of >20 ppm over baseline after lactose is suggestive
   4. Use of 12gm lactose (amount in 8 ounces, 250mL, milk) has been advocated
4. Lactose Tolerance Test
   1. Sensitivity and specificity are ~80% (not as good as breath hydrogen test)
   2. Oral dose of 1-1.5gm/kg lactose is given
   3. Serial blood samples are drawn over next ~1 hour
   4. Intestinal symptoms along with rise in blood glucose level >20 mg/dL is suggestive
5. Acidic Stools - due to increased colonic bacterial metabolism

F. Differential Diagnosis

1. Irritable Bowel Syndrome (IBS; diarrhea or mixed variant)
2. Ulcerative Colitis
3. Crohn's Disease (including Crohn's Colitis)
4. Cystic Fibrosis
5. Bowel Polyp
6. Colonic or small intestinal neoplasm
7. Diverticular Disease
8. Infections
   1. Viral - echoviruses, enteroviruses
   2. Bacterial - Whipple's disease, others
   3. Parasitic - particularly giardiasis
9. Laxative abuse, bran overuse
10. Mechanical Compromise
    1. Endometriosis
    2. Adhesions
    3. Gynecologic mass
11. Celiac Disease
12. Tropical Sprue

G. Treatment

1. Reduced lactose diet
2. Lactose-free diet is usually not required
   1. May initiate with lactose free diet
   2. Then, gradual addition of low lactose containing foods, such as yogurts
   3. Maintain milk intake <250-300 mL per day unless special products used
   4. Some patients can improve lactose handling by gradually increasing lactose ingestion
3. Minimize dairy intake
   1. Special lactose-free products may be used
   2. Products containing "Lactaid" may also be used
4. Lactase Pills - "Lactaid®"
5. Critical to maintain adequate calcium and vitamin D intake

Resources

Coefficient of Fat Absorption

References

1. Swagerty DL Jr, Walling AD, Klein RM. 2002. Am Fam Phys. 65(9):1845
2. Suarez FL, Savaiano DA, Levitt MD. 1995. NEJM. 333(1):1