Malabsorption: Clinical practice
Medicine and surgery
AssessmentsMalabsorption: Clinical practice
USMLE® Step 2 style questions USMLE
A 47-year-old man comes to the physician for evaluation of abdominal cramps, bloating, and diarrhea. The symptoms began several weeks ago. He describes the diarrhea as “greasy and difficult to flush.” He has unintentionally lost 13-lb over this time period and has also felt significantly more fatigued. The patient has not had any recent rashes, joint pains, or blood in the diarrhea. He has been sexually active with 3 partners over the past year and uses condoms inconsistently. Past medical history is noncontributory. He lives in the Dominican Republic. Temperature is 37.0°C (98.6°F), pulse is 94/min, respirations are 14/min, and blood pressure is 122/84 mmHg. Physical examination reveals conjunctival pallor. Mild abdominal tenderness is elicited with palpation, and bowel sounds are hyperactive. Fecal occult blood test is negative, and stool microscopy shows no parasites or leukocytes. Laboratory testing reveals the following findings:
|Anti-tissue transglutaminase antibodies (IgA, IgG)||Negative|
|Anti-endomysial antibody (IgA)||Negative|
|Deamidated gliadin peptide (IgG)||Negative|
Upper endoscopy reveals flattening of the duodenal folds. Biopsy of the small intestine shows blunted villi and elongated crypts with increased inflammatory cells. A peripheral blood smear shows hypersegmented neutrophils. Which of the following is the most appropriate treatment for this patient?
Content Reviewers:Robyn Hughes, MScBMC, Rishi Desai, MD, MPH
Contributors:Elizabeth Nixon-Shapiro, MSMI, CMI, Alex Aranda, Anca-Elena Stefan, MD
With malabsorption, nutrients are no longer effectively absorbed in the small intestines. Nutrients can either be macronutrients, such as fats, proteins and carbs or micronutrients like vitamins and minerals. Malabsorption can either be global meaning that the absorption of all nutrients is affected or it can be partial meaning that only specific nutrients cannot be absorbed. Malabsorption presents differently based on which nutrients are being malabsorbed, the severity of the disease, and the underlying cause. Global malabsorption can present with chronic or recurrent diarrhea with pale, greasy, voluminous and terrible smelling stools and unintentional weight loss. In contrast, partial malabsorption causes symptoms specific to the nutrient involved.
With fat malabsorption, symptoms include steatorrhea - meaning fatty stools. To confirm that it’s really steatorrhea, a fecal fat test can be done to check for fat. If it’s negative and fat malabsorption is still suspected, then a 72 hours stool collection should be done because that’s the gold standard for diagnosing fat malabsorption. To do that, an individual has to have a diet that includes 70 to 120 grams of dietary fat per day, which is the equivalent of eating about 300 grams of cheese per day. Stool is collected for 72 hours, and if there’s more than 6 grams of fat per day, then it’s considered fat malabsorption. Typically if there’s steatorrhea, the stool fat exceeds 20 grams per day.
If fat malabsorption is present, then the fat soluble vitamins - A, D, E, and K, might also not be getting absorbed. Vitamin A deficiency causes symptoms like night blindness and thickened skin due to hyperkeratosis. Vitamin D deficiency causes symptoms like paresthesias, and fractures due to osteomalacia. Vitamin E deficiency can cause symptoms like muscle weakness. And finally, vitamin K deficiency causes symptoms like easy bruising, excessive bleeding from wounds, gastrointestinal bleeds, or hematuria.
With protein malabsorption, edema and muscle atrophy may be present and on the lab tests, there may be hypoalbuminemia and a low total protein level in the blood. With carbohydrate malabsorption, symptoms include watery diarrhea, flatulence, and bloating. To identify carbohydrate malabsorption, the D-xylose test can be done. That’s where an individual fasts overnight and then eats 25 grams of D-xylose, which is a monosaccharide that’s normally absorbed by the small intestine. The serum D-xylose is checked after an hour and if it’s below 20 milligrams per deciliter that suggests malabsorption. In addition, urine is collected over the next five hours as fasting continues, and if urine excretion of D-xylose is below 4.5 grams, that also suggests malabsorption. False-positive results can occur, especially in older individuals with a decreased glomerular filtration rate.
Now, malabsorption can also lead to anemia either because of reduced iron absorption in the small intestine leading to iron deficiency anemia or reduced vitamin B12 or folate absorption in the small intestine leading to megaloblastic anemia. Usually, if the mean corpuscular volume or MCV is less than 80 femtoliters, then it’s microcytic and this usually happens with iron deficiency anemia. With iron deficiency anemia, serum iron and ferritin are decreased and total iron binding capacity or TIBC is increased. If the MCV is above 100 femtoliters, then a blood smear is necessary to see if the macrocytic anemia is megaloblastic. If so, vitamin B12 or folate deficiency is the most likely cause, and can be confirmed by obtaining Vitamin B12 and folate levels.
Now, global malabsorption is caused by diseases that cause damage to the small intestine mucosa, reducing the surface area available for absorption. A common cause of this is celiac disease -sometimes called celiac sprue- which is an autoimmune condition triggered by the gluten found in foods like wheat bread. Individuals can develop symptoms of global malabsorption, like chronic or recurrent diarrhea - with steatorrhea, unintentional weight loss, abdominal distention, and bloating. In addition celiac disease can cause iron deficiency anemia; and vitamin B12 and folate deficiency. Celiac disease is also associated with dermatitis herpetiformis -which is a chronic skin condition, along with short stature, delayed puberty, and reduced fertility.
The diagnosis of celiac disease starts with checking for Immunoglobulin A anti-tissue transglutaminase antibody or TTGA IgA. If TTGA IgA is positive, then an upper endoscopy with biopsy is done to look for evidence of damage, villous atrophy, and crypt hyperplasia in the duodenal mucosa. If the TTGA IgA is negative, then total serum IgA levels are obtained. If they’re low, then TTGA IgG and deamidated gliadin peptide or DGP are checked. If either one of those is positive, then an upper endoscopy with biopsy is done. Finally, many individuals who suspect having celiac disease can keep a food journal and can try to eliminate gluten from their diet to see if that improves symptoms.
Okay, so some individuals and groups are managed slightly differently. For example, those with a first degree relative with celiac disease, get an upper endoscopy with biopsy and have TTGA IgA levels checked. If both are normal, then celiac disease is unlikely. If either are positive, then total serum IgA levels, TTGA IgG, and DGP are obtained. In addition, Human leukocyte antigen testing or HLA testing is often performed when there seems to be a genetic predisposition, because HLA DQ2 and HLA DQ8 are both known to be linked with celiac disease.
Another group that gets managed slightly differently are children suspected of having celiac disease. Typically these children have classic symptoms of celiac disease, but may also have a failure to thrive or pubertal delay. In symptomatic children, a TTGA IgA is checked and if it’s positive, then an upper endoscopy with biopsy is performed to see if histology is consistent with celiac disease. If there are signs of celiac disease, then the individual is placed on a gluten-free diet to see if symptoms improve. If histology is not consistent with celiac disease or if symptoms don’t improve after a gluten-free diet, then HLA testing is done. However, if the TTGA IgA is negative but symptoms suggest celiac disease, then additional tests like total serum IgA levels, anti-endomisium antibody or EMA, and DGP can be done, and if any of these suggest celiac disease, then an upper endoscopy with biopsy is performed.
In addition children with other conditions like autoimmune thyroiditis, type 1 diabetes mellitus, and Down syndrome are at high-risk for developing celiac disease. In these children, a TTGA IgA level is checked. If it’s normal, then the workup only continues if symptoms begin. If the TTGA IgA is slightly elevated but less than 3 times the upper limit of normal, then the EMA is tested for. If the EMA is negative, then the workup only continues if symptoms begin. Now if the TTGA IgA level is above 3 times the upper limit of normal or if the EMA is positive, then an upper endoscopy with biopsy is performed. If histology suggests celiac disease, then the individual is placed on a gluten-free diet and if there is no clinical improvement, then HLA testing should be done to see if HLA DQ2 or DQ8 are present. However, if there is clinical improvement, then celiac disease is confirmed.
The main treatment of celiac disease is eliminating the trigger - gluten - from the diet. Because gluten is included in a variety of foods, it requires careful attention to ingredients when buying processed foods. Typically, a gluten free diet improves symptoms within 2 weeks and after 6 weeks, the individual should have repeat lab testing including a complete blood count, folate, vitamin B12 and iron studies, and TTGA IgA. There should also be a repeat upper endoscopy with biopsy, 6 months after being on a gluten free diet to make sure that there are signs of healing.
Another cause of global malabsorption is tropical sprue- and it occurs mostly in a tropical region that includes Haiti, the Dominican Republic, Puerto Rico, and Cuba. The disease may be caused by a pathogen that hasn’t yet been identified. The individual typically has global malabsorption symptoms, like chronic or recurrent diarrhea - with steatorrhea, unintentional weight loss, abdominal distention, and bloating, as well as vitamin B12 and folate deficiency. It’s a diagnosis of exclusion, that requires ruling out infectious and inflammatory causes of diarrhea. That includes doing stool testing for ova and parasites to look for Entamoeba histolytica or Giardia lamblia.
Serologic testing starts with TTGA IgA to identify celiac disease. If the workup is negative for other causes, then an upper endoscopy with biopsy is done to look for evidence of damage, villous atrophy, and crypt hyperplasia in the duodenal mucosa - the same sort of findings as in celiac disease. A key difference is that in tropical sprue the damage is typically less severe. Tropical sprue is treated with 250 milligrams of tetracycline taken four times a day, along with 5 milligrams of folate taken daily for three to six months. Unfortunately, even with this treatment, relapses sometimes occur.