Malabsorption Syndromes

Etiology

There are three stages of nutrient absorption: luminal, mucosal, postabsorptive. Malabsorption syndromes are categorized according to which of these three stages is or are affected.

• The luminal phase involves mechanical mixing and digestive enzymes.
• The mucosal phase requires a properly functioning mucosal membrane for absorption.
• The postabsorptive phase becomes facilitated by an intact blood supply and lymphatic system.

Because malabsorption syndromes arise from dysfunction at any level of digestion or absorption, this discussion briefly addresses general components of digestion and absorption and gives examples of malabsorption diagnoses according to which nutrients are affected.[3] 

Fat Malabsorption

Fat malabsorption is one of the most common malabsorption syndromes, and it arises from defects in fat digestion and absorption. Lipid processing is emulsification, which is the process of suspending fat molecules in aqueous humor to expose lipid molecule surface areas to hydrolytic enzymes. Emulsification starts in the mouth via mastication and lingual lipase and continues with gastric mixing. Although lipid digestion begins in the mouth, approximately only 15% of ingested fat gets digested before reaching the duodenum, with the rest of the fat arriving in the duodenum intact before moving to the jejunum. The stomach and pancreas release lipolytic enzymes, and the majority of lipid absorption occurs in the proximal two-thirds of the jejunum (i.e., proximal small intestine). Additional fat solubilization is achieved by increasing intraluminal pH to 6.5 and mixing with bile salts released by the gallbladder to form micelles. The overall mixture of lipolytic products and other products of fat digestion aggregate into micelles or liposomes (larger aggregates than micelles). These specialized fat aggregates are the form in which fats can be absorbed. Diffusion, temporary integration into the lipid bilayer, and a multitude of transporters and co-transporters contribute to micelle and liposome-assisted fat absorption. Bile salts remain in the intestinal lumen and are reabsorbed in the terminal ileum and recycled via the enterohepatic circulation.[4]

Causes

Significant disruption of fat breakdown typically results in steatorrhea.

• Decreased duodenal pH: optimal duodenal pH 6.5.
  • Zollinger-Ellison syndrome - Lowers pH through the destruction of pancreatic enzymes by secreting gastric stomach acids.
• Lost absorptive intestinal surface area: lost functional small intestine mucosa results in decreased transit time and reduced exposure to digestive enzymatic activity. The loss occurs through diffuse mucosal injury, enterocyte disease, functional loss, or complete loss of small intestinal mucosa (surgical resection).
  • Diffuse mucosal or enterocyte disease
    • Crohn disease (an inflammatory bowel disease)
    • Ulcerative colitis (an inflammatory bowel disease)
    • Celiac disease
  • Small bowel resection - most often the result of elective bariatric surgery.
• Impaired lipid processing by bile acids: This occurs when bile acid synthesis fails to reach levels sufficient for adequate fat absorption, bile acid secretion is impaired, or bile acids remain in the intestinal lumen instead of being absorbed. Unabsorbed bile acids are unavailable for reuse for fat digestion and stimulate colonic water and electrolyte secretion. Insufficient bile acid synthesis can be due to inborn errors and often present as cholestasis but can present atypically as fat malabsorption. Impaired bile acid synthesis affects both fat and fat-soluble absorption.[5]
  • Liver disease - liver disease such as hepatic cirrhosis impair bile acid synthesis. In gastrointestinal amyloidosis, the amyloid deposition in liver stellate cells can cause similar pathologies to fibrotic liver disease.[6]
  • Cholestasis - decreased or obstructed bile secretion and flow due to intrahepatic and/or extrahepatic pathology.[7]
• Small intestinal bacterial overgrowth (SIBO): results from disruption of the normal, established ecology of the small bowel. Overgrowth of certain bacteria deconjugate bile acids rendering bile acids ineffective for fat absorption. Bacterial overgrowth could be concurrent with atrophic gastritis or proton pump inhibitors (PPIs). PPIs could interfere with vitamin B12 absorption (rarely to a clinically significant degree). SIBO can also result from prolonged lactose deficiency, blind loops formed by inflammatory processes such as IBD, any cause of GI stasis, or medical conditions that can lead to gastric dumping of food whose pH is still too basic. SIBO bacterial overgrowth is patchy, which is different from the diffuse distribution seen in celiac disease. Prolonged SIBO can eventually progress to brush border damage and increased antigliadin antibodies, and symptoms can be confused with celiac disease. Malabsorption of various nutrients can ensue.[8]
• Pancreatic exocrine insufficiency: defective production of pancreatic lipase, colipase, and bicarbonate.[9]
  • Chronic pancreatitis - often from alcohol use disorder or chronic biliary obstruction
  • Pancreatic resection - loss of pancreatic tissue reduces the amount of tissue available to produce pancreatic enzymes.
  • Cystic fibrosis - obstructs pancreatic outflow by mucous plugging and is commonly accompanied by a history of recurrent respiratory tract infections.
  • Pancreatic cancer - obstruction and loss of functional pancreatic tissue
  • Schwachman syndrome
  • Zollinger-Ellison syndrome
  • Celiac disease
  • Gastric surgery
• Defective chylomicron/lipoprotein secretion:
  • Abetalipoproteinemia - defective apoproteins impair chylomicron packaging and secretion into the lymphatics. Mutations in the MTP gene cause it.[4]
• Lymphatic system disorders:
  • Intestinal lymphangiectasia - impaired lymphatic flow impacting fat processing; this is one of the most common but often overlooked etiologies of chronic, non-infectious infantile diarrhea. More common reasons for infantile diarrhea include cow’s milk protein allergy and cystic fibrosis.[10]
  • Whipple disease - a systemic disease caused by Tropheryma whipplei that typically presents with diarrhea and weight loss, which may suggest malabsorption. Accompanying symptoms are fever, arthralgias, and abdominal pain. Additional symptoms can be lymphadenopathy, endocarditis, pulmonary disease, and CNS infection. On biopsy, Whipple disease, in some cases, might be indistinguishable from the effects of Mycobacterium avium. Acid-fast stains can differentiate between the two.[2]

Carbohydrate Malabsorption

Carbohydrate digestion and absorption often refer to the starch, lactose, and sucrose of the human diet. Cellulose is not digestible in the human small intestine. Appropriate digestion into monosaccharides is necessary for adequate absorption. Carbohydrate digestion begins with salivary and pancreatic amylase. The resulting products get further processed at the microvillus membrane. Brush border enzymes, then hydrolyze that carbohydrate mixture into monosaccharides. Monosaccharides can be absorbed passively or actively. Any remaining carbohydrates that are not absorbed (including the non-absorbable cellulose) get fermented in the colon (i.e., degraded by bacteria). When fatty acids get released due to bacterial fermentation, colonic epithelial cells can absorb them for energy. Symptoms of excessive bacterial fermentation in carbohydrate malabsorption include acidic stool, flatulence, and bloating.[4]

Causes

• Pancreatic amylase deficiency
• Inadequate disaccharidase activity:
  • Lactase deficiency (also known as hypolactasia) - the most common disaccharidase deficiency. Adult-onset lactase deficiency is present in the majority of the world’s population. Lactase is located on the surface of small intestinal microvilli and serves to cleave lactose into glucose and galactose. During early childhood, lactase activity is down-regulated, leaving some individuals completely devoid of lactase enzymes. In this way, lactase deficiency is actually the result of decreased enzyme synthesis rather than a lactase defect. Lactase deficiency can also be congenital, like other disaccharidase deficiencies.[11]
  • Sucrase deficiency
  • Trehalase deficiency
• Lost absorptive intestinal surface area:
  • Diffuse mucosal injury:
    • Celiac disease (gluten-sensitive enteropathy, gluten-induced enteropathy, celiac sprue, non-tropical sprue) - An inappropriate response to ingested gluten in the proximal duodenum and jejunum. Anemia is a common finding, even in the absence of GI symptoms.[12]
    • Tropical sprue (post-infective tropical malabsorption) - an inappropriate response to ingested gluten through all three small intestine segments.  Tropical sprue has a higher association with megaloblastic anemia through folate and vitamin B12 deficiency than celiac sprue. It is notable for affecting residents of or visitors to Puerto Rico, the Caribbean, northern South America, West Africa, south-east Asia, and India. Overgrowth of aerobic bacteria is a common finding.
    • Autoimmune enteropathy - a likely family of diseases that occurs primarily in children and has histological findings of villous blunting and crypt hyperplasia like celiac disease
    • Intestinal lymphangiectasia - abnormal intestinal lymphatics/lacteals lead to protein loss, fat malabsorption, peripheral edema, and lymphocytopenia. Often occurs secondary to other conditions.
    • Inflammatory bowel disease (IBD) - can create blind loops or cause lymphatic outflow obstruction.
      • Crohn disease - a systemic disease that can affect any part of the GI tract and significantly impact the small intestine
      • Ulcerative colitis - a condition that typically affects the colon and atypically can also include the terminal ileum.
    • Functional loss of small intestine mucosa:
      • Blind loops - can be caused by IBD and can cause bacterial overgrowth.
        • Entero-enteric fistula
        • Entero-colic fistula
      • Mural disease - impedes peristalsis and ultimately intestinal stasis.
        • Systemic sclerosis - smooth muscle cells of the muscularis propria become replaced by collagen (fibrosis). The fibrosed tissue causes upstream dilation and the formation of diverticula.
      • Absolute loss of small intestinal mucosa:
        • Small bowel resection
      • Ingestion of unabsorbable carbohydrates:
        • Sorbitol, cellulose

Protein Malabsorption

Protein digestion and absorption begin as proteolysis in the stomach with proenzymes that become automatically activated at low pH levels (i.e., an acidic environment). The extent of proteolysis depends on pH levels, gastric motility for mixing, and other dietary constituents present during the process. For example, the duodenal and jejunal release of cholecystokinin (CCK) depends on the release of amino acids in the stomach. Amino acids stimulate the release of CCK, and CCK stimulates the release of pancreatic enzymes. Additional release of amino acids occurs in the duodenum through the action of other proteases. After various levels of protein digestion by pancreatic enzymes, amino acids, dipeptides, and tripeptides are ready for absorption via brush border sodium-dependent amino acid co-transporters. These sodium-dependent amino acid co-transporters transport the products of proteolysis both passively and secondarily through their indirect use of energy from a sodium-potassium ATPase pump. Different classes of amino acid transporters exist and select out amino acids based on being neutral, basic, or acidic. Further selectivity exists for the specific transport of dipeptides and tripeptides.[4]

Causes

• Impaired pancreatic bicarbonate and protease secretion and/or activity:
  • Chronic pancreatitis
  • Cystic fibrosis
• Lost absorptive intestinal surface area:
  • Diffuse mucosal injury:
    • Inflammatory bowel disease (IBS)
    • Intestinal lymphangiectasia
  • Bowel resection

Vitamin, Mineral, and Trace Element Malabsorption

Various intestinal transport mechanisms accomplish the absorption of vitamins, minerals, and trace elements. Dysfunction at any one of these levels results in malabsorption of that specific vitamin, mineral, trace element, or any nutrient dependant on them to be successfully absorbed. Deficiencies include but are not limited to deficiencies in vitamin B12, calcium iron, folate, vitamin D, magnesium, carotenoids, thiamin, copper, selenium, and more. The effects of malabsorption of these vitamins, minerals, or trace elements depend on which is deficient and the degree to which they are deficient. Exploring the various mechanisms and covering the numerous etiologies are beyond the scope of this discussion.

Causes

• Pathology of the stomach or proximal small intestine (e.g., vitamin B12 deficiency)
• Fat malabsorption: caused when fatty acids bind calcium, magnesium, and other divalent cations.[5]
• Lost absorptive intestinal surface area:
  • Bariatric surgery
  • Intestinal resections
  • Intestinal diseases - such as those mentioned above and the following
    • Acrodermatitis enteropathica - autosomal recessive zinc malabsorption. Associated abnormalities are of the skin and mucosa, villous blunting and crypt hyperplasia, increased lamina propria inflammatory cells, and loss of brush border enzymes. Progression of the disease leads to impairment of other components of malabsorption.

Immunodeficiency and HIV/AIDS-Related Enteropathy

In some cases, malabsorption cannot readily be categorized into fat, carbohydrate, or micronutrient malabsorption when malabsorption is more global. The presentation may be diarrhea, weight loss, and generalized malnutrition. This situation can present in immunodeficiency. Immunocompromised states accompanied by diarrhea often are due to secondary or opportunistic infections. These infections interfere with proper digestion and absorption processes. Infectious organisms include Giardia and Cryptosporidium. A more extensive discussion of the relationships between HIV/AIDS and other immunodeficient states is beyond the scope of this article but is mentioned for completeness.[2]

Congenital Causes of Chronic Diarrhea (not previously discussed)[10]

• Congenital glucose-galactose malabsorption (GGM) - a rare autosomal recessive disease that typically presents prior to 6-months of age and is caused by defective brush border glucose and galactose transport. Improved with fructose-based formulas and avoidance of glucose and galactose.
• Congenital chloride diarrhea (CCD) - this condition is a rare autosomal recessive trait that typically presents before 6-months of age with remarkable watery diarrhea and is accompanied by hypokalemic, hypochloremic metabolic alkalosis. It responds well to electrolyte replacement, and high fecal chloride is an anticipated finding.
• Cow’s milk protein allergy (CMPA) - an immunologic response to at least one of the thirty types of proteins found in cow’s milk. Symptoms are non-specific and can range from mild to life-threatening. Diagnosis depends on the history and trial of cow’s milk protein elimination.[13]

Bacterial Malabsorption

Whether transient, curable, or permanent sequelae transpire, bacterial malabsorption is most often due to Giardia lamblia (giardiasis), Tropheryma whipplei, Cryptosporidium parvum (cryptosporidiosis), and the Phylum Microspora (microsporidiosis).[2]

Epidemiology

Malabsorption affects millions of people worldwide. The fact that malabsorption syndromes have multiple etiologies obscures the prevalence and incidence. However, some malabsorption syndromes can be estimated by discussing the epidemiology of subgroups.

Gluten-sensitive enteropathy (GSE) is present at its highest rates in Europeans and North Americans. GSE can be found in parts of India and is rarest in those of Asian, Caribbean, and African descent. Tropical sprue is known for affecting residents and visitors to Puerto Rico, the Caribbean, West Africa, northern South America, south-east Asia, and India.[2]

The exact prevalence of pancreatic exocrine insufficiency is unknown in the general population but can be appreciated through its prevalence in specific subgroups with predisposing conditions. In those with chronic pancreatitis, the incidence is 85% in those with severe disease and 30% in those with mild disease, and, again, 85% in newborns with cystic fibrosis. The prevalence ranges in diabetes with higher prevalence in diabetes type 1 (26% to 44%), in HIV/AIDS at 26% to 45%, in inoperable pancreatic cancer 50% to 100%, and with varying high incidence (19% to 98%) for surgeries (distal pancreatectomy, Whipple). Meanwhile, other populations show a lower prevalence (IBS, diabetes type 2).[9]

History and Physical

The history and physical are invaluable when initiating the evaluation of malabsorption syndromes. A malabsorption syndrome should be suspected when a patient’s history includes but is not limited to ongoing or chronic diarrhea, unintentional weight loss despite normal nutrient intake, greasy, voluminous, foul-smelling stools that reportedly float. Additional components of the history may include flatulence, bloating, borborygmi. Abdominal pain might be reported but is less common in most malabsorption syndromes. 

Key questions in the history and a focused physical exam help create a more targeted approach to diagnosing the patient’s condition. A thorough history boosts cost-effectiveness and saves time. For those patients whose malabsorption syndrome is affected by emotions, early treatment can start through interviews alone. The therapeutic benefit comes from the nurturing of the patient-doctor relationship by empowering the patient and positively impacting the patient’s self-esteem in the face of their malabsorption syndrome.[14]

Questioning should include a review of systems, symptom duration, symptom timing, presence or absence of pain/pain radiation, location/location changes, intensity/intensity changes, known precipitating factors, associated symptoms (e.g., change in bowel habits/frequency), the appearance of the stool, whether or not the presenting symptoms have happened previously. Stool description could be of floating, pale, greasy stools, and a patient may report seeing oil droplets in the toilet, stool color, stool bulk, stool consistency, stool smell. Important additional questions include past medical history (e.g., peptic ulcer disease), family history (especially for systemic and gastrointestinal conditions), medications, surgeries, radiation exposure/treatments, caustic substance ingestion, allergies, and social history (e.g., smoking, drinking, recreational drug use past or present).[15]

Physical exam should include a full abdominal examination and inspection of neighboring systems to consider differential diagnoses that could also account for the patient’s clinical presentation. The physical exam may yield findings of hyper/hypoactive bowel sounds, abdominal distention, abdominal tenderness (less common), pallor (suggests anemia), muscle wasting, abnormal deep tendon reflexes, skeletal deformities, rashes, cardiac arrhythmia, delayed growth (in infants and children), poor wound healing, ecchymosis, decreased visual acuity, peripheral neuropathy, auditory disturbances, or cognitive impairment.

Findings through the history and physical exam guide the next steps for evaluation.

Evaluation

Evaluation begins with a thorough history and physical, as discussed previously. Those findings will guide the next steps of assessment that consider options utilizing laboratory testing, imaging, visualization, and biopsies. Sometimes the cause of malabsorption is clear, and additional workup may be unnecessary or tailored more quickly to the specific diagnosis highest on the differential.

General Evaluation for Malabsorption Syndromes

When the history and physical raise suspicion for malabsorption syndromes without strongly supporting a diagnosis requiring more specific testing, general testing may begin. An example is the non-specific symptoms of unintentional weight loss, ongoing diarrhea, or poor wound healing.

Laboratory testing is used to support the diagnosis but is not diagnostic.

Blood tests

• Comprehensive metabolic panel - electrolyte disturbances, hepatic function, renal function
• Complete blood cell count - contributes to evaluating anemia.
• Albumin
• Magnesium
• Zinc
• Phosphorous
• Vitamins (e.g., vitamin B12, folate, vitamin D)
• Iron panel (includes serum iron, total iron-binding capacity, ferritin)

Fecal tests: most sensitive for fat malabsorption syndromes

• Fecal fat - fecal fat is measured from a single specimen; if the test is positive or there remains high clinical suspicion of fat malabsorption syndrome, then testing proceeds to a 72-hour fecal fat excretion evaluation
• 72-hour fecal fat excretion - the gold standard for steatorrhea diagnosis; performed on a 72-hour stool collection, accurate interpretation of fecal fat depends on patient’s successful adherence to testing instructions
• Sudan III stain - performed on a spot stool sample, sensitive
• Acid steatocrit
• Near-infrared reflectance analysis (NIRA) - comparable accuracy to a 72-hour fecal fat excretion analysis but faster; it also measures nitrogen and carbohydrates while measuring fecal fat.

More Specific Evaluation of Malabsorption Syndromes

When the history and physical make the diagnosis fairly clear, general evaluation is not necessary. Clinicians can select other modalities for assessment based on the suspected/most likely malabsorption diagnosis. Such examples include a patient’s history of recurrent pancreatitis and alcohol use or abdominal discomfort resolved with gluten avoidance.

Breath tests:

• Carbohydrate malabsorption syndromes
• Small intestinal bacterial overgrowth (SIBO) - positive glucose or lactulose breath test, but breath tests are not considered reliable for diagnosis.

Jejunal aspirate culture:

• The gold standard for small intestinal bacterial overgrowth

Computed tomography (CT):

• Pancreatitis

Magnetic resonance cholangiopancreatography (MRCP):

• Exocrine pancreatic insufficiency

Magnetic resonance (MR) elastography[16]:

• A non-invasive method to ascertain the stiffness of an object. In the case of liver stiffness, MR elastography is useful to diagnose liver fibrosis, hepatic amyloidosis, and other conditions that increase liver stiffness.

Endoscopic retrograde cholangiopancreatography (ERCP):

• Pancreatic insufficiency (i.e., history was positive for pancreatitis and alcohol use, or high fecal elastase) - magnetic resonance cholangiopancreatography (MRCP), followed by endoscopy if MRCP is negative

Endoscopy with biopsy (indicated for diagnoses that require both visualization and biopsy):

• Crohn disease - visualized duodenal mucosa cobblestoning.
• Celiac disease - visualized reduced duodenal folds or mucosal scalloping.
• Jejunoileitis

Colonoscopies and biopsies:

• Ulcerative colitis

Acid-fast stains:

• Acid-fast stains serve to differentiate Tropheryma whipplei vs. Mycobacterium avium because they appear virtually indistinguishable on biopsy.

Example of an evaluation for specific conditions:

• Celiac disease: A child presents with diarrhea, delayed growth, and abdominal discomfort within the first 24 hours of life. Symptoms worsen when cereals get introduced to the diet. Additional symptoms may include pallor. Untreated symptoms evolve into short stature, delayed puberty, and nutrient deficiencies (e.g., iron, vitamin D). Iron deficiency anemia and rickets are present in those patients. Some patients develop symptoms in adulthood, but symptoms could be mild. Celiac disease must be a consideration if history includes unexplained iron-deficiency anemia (the most common symptom). Folate deficiency may also yield megaloblastic anemia, vitamin D deficiency may yield hypocalcemia, and vitamin K deficiency may yield coagulopathy. Diagnosis depends on a combination of tests. Duodenal or jejunal mucosal biopsy (best diagnostic test), serologic studies, and a gluten-free diet are subsequent steps. Histology will show blunted villi or increased intraepithelial lymphocytes (IELs). Villous blunting so severe as to result in totally flattened mucosa. IELs can extend beyond the intestine and affect the stomach causing lymphocytic gastritis. The presence of IELs is not specific to celiac disease. Serological studies often include gliadin antibodies and tissue transglutaminase (TTG) antibodies. Anti-TTG historically had been seen as the most sensitive test for celiac disease. Symptom improvement with dietary removal of gluten (contains gliadin) also supports the diagnosis of celiac disease. In some cases, gluten removal can resolve the histological abnormalities of celiac disease.[2]

Trials of eliminating certain types of foods or ingredients can be both diagnostic and therapeutic. This elimination testing is often useful in carbohydrate malabsorption syndromes such as lactose intolerance or fructose intolerance.

Treatment / Management

Treatment in the setting of malabsorption syndromes targets correcting deficiencies, treating the underlying cause, avoiding triggers (typically dietary), and treating symptoms (e,g often diarrhea).

Misdiagnosis or missed diagnosis of a malabsorption syndrome could cause harm or have no effect. Therefore, treatment should focus on treating the underlying cause, which depends on the diagnosis since malabsorption syndromes stem from their defects.

Treatment could be as conservative as dietary changes such as food avoidance or supplementation but could be as invasive as surgery (e.g., transplants, resections).

• Treatment for lactose intolerance, regardless of cause, includes avoidance of limiting dairy, lactase supplements, a plan to supplement calcium should calcium deficiency develop.
• Treating rheumatism with disease-modifying antirheumatic drugs (DMARDs), anti-necrosis factor-alpha, or glucocorticoids would spread Tropheryma Whipple infection in Whipple disease, which could prove fatal.[17]
• Endoscopic retrograde cholangiopancreatography (ERCP) could be curative when removing an obstructing stone in pancreatitis, and pancreatic enzyme replacement would be indicated for exocrine pancreatic insufficiency.
• Assessing and improving nutrition status should be included in any treatment plan regardless of diagnosis.[9][17]

Diagnosis-driven management is also necessary for the relief of patient symptoms. For example, it is important to determine the cause of a patient’s diarrhea because incorrect treatment could exacerbate symptoms.

As can be seen following resection and results from excess bile acids in the colon, secretory diarrhea is treated differently from malabsorption diarrhea. Bile salt binders are indicated in secretory diarrhea to reduce osmotic load but would exacerbate diarrhea if malabsorption due to insufficient bile salts or bile salt dysfunction is the cause. In more transient malabsorption syndromes, antibiotics could cause a patient’s diarrhea or the cure if due to a bacterial infectious process.

Therefore, malabsorption syndromes must be evaluated and diagnosed for successfully managing the patient’s condition and symptoms indicated for the etiology.

Differential Diagnosis

Due to the overlapping symptoms between other malabsorption syndromes, they are differential diagnoses for one another. Differential diagnoses also include conditions that masquerade as abdominal pain, such as pericarditis, myocardial infarction pulmonary infarction. These thoracic inflammatory events refer pain to the abdomen via the parietal diaphragmatic pleura or thoracic pleural.[9][14][18]

Some differentials are specific to a malabsorption syndrome or presenting symptom[18]:

• Primary intestinal lymphangiectasia (Waldmann disease) differential diagnoses constrictive pericarditis, Crohn disease. Whipple disease, systemic sclerosis, intestinal tuberculosis, sarcoidosis
• Ongoing diarrhea early in life: cystic fibrosis, congenital chloride malabsorption, congenital glucose-galactose malabsorption, pancreatic insufficiency, cow’s milk protein allergy

Prognosis

Malabsorption syndromes typically are not life-threatening. However, the severity and duration of some malabsorption syndromes can be life-threatening or even fatal. Examples include severe malnutrition from prolonged pancreatic exocrine insufficiency, life-threatening electrolyte disturbances from prolonged, intractable diarrhea, and bowel perforation.[9]

Meanwhile, other malabsorption syndromes such as lactose intolerance are unlikely to deteriorate a patient’s health significantly. That is partly due to disease progression and partly due to the efficacy of disease management (e.g., avoidance, supplementation, supportive care).

Complications

The complications that can arise from malabsorption and maldigestion are as numerous as the points at which these processes can be interrupted, delayed, or absent. When a malabsorption syndrome is severe enough, poorly controlled, or of long enough duration, complications can include (not a comprehensive list):

• Gastrointestinal symptoms (e.g., chronic diarrhea, bloating, flatulence)
• Malnutrition
• Weight loss/poor weight gain
• Vitamin, mineral, trace element deficiencies (e.g., vitamin D, B12, iron, folate)
  • Osteomalacia/rickets disease, coagulopathy, visual impairment, skin changes
• Hematologic disorders
  • Anemia
  • Coagulopathy
• Visual impairment
• Dermatologic manifestations
• Musculoskeletal dysfunction:
  • Growth delay (in children)
  • Skeletal deformities (e.g., rickets)
  • Bone mineral density abnormalities (e.g., osteoporosis)
  • Cachexia
• Electrolyte disturbances
• Cardiovascular disease:
  • Cardiac arrhythmias
• Neurologic dysfunction:
  • Peripheral neuropathy
  • Ataxia [9]
• Endocrine dysfunction:
  • Parathyroid dysfunction
  • Chronic fatigue