Nutritional & Malabsorptive Syndromes

Nutritional & Malabsorptive Syndromes: Identification, Workup, and Support

Celiac Disease

Celiac disease is an autoimmune-mediated enteropathy triggered by the ingestion of gluten (a protein found in wheat, rye, and barley) in genetically susceptible individuals expressing HLA-DQ2 or HLA-DQ8.

• Clinical Presentation: Classical symptoms include chronic diarrhea, steatorrhea, abdominal pain, bloating, weight loss, and nutritional deficiencies (particularly iron deficiency anemia and vitamin D deficiency). A pathognomonic extraintestinal manifestation is dermatitis herpetiformis, characterized by intensely pruritic, grouped vesicles on extensor surfaces (knees, elbows, buttocks); skin biopsy shows IgA deposition in the dermal papillae.
• Diagnosis: The initial screening test of choice is the serum tissue transglutaminase (tTG) IgA antibody, which has high sensitivity and specificity. However, because selective IgA deficiency is significantly more common in patients with celiac disease than in the general population, clinicians must simultaneously measure total serum IgA levels. If a patient is IgA deficient, deamidated gliadin peptide (DGP) IgG or tTG IgG antibodies must be checked instead. The gold standard for confirmation is a duodenal biopsy showing intraepithelial lymphocytosis, crypt hyperplasia, and villous atrophy. Importantly, serologic and histologic testing must be performed while the patient is maintaining a gluten-containing diet to avoid false-negative results.
• Management: Treatment is lifelong adherence to a strict gluten-free diet. Follow-up includes monitoring for resolution of symptoms, normalisation of serology, and screening for bone loss with a dual-energy X-ray absorptiometry (DEXA) scan. Refractory celiac disease raises concern for enteropathy-associated T-cell lymphoma (EATL).

Lactose Intolerance and Small Intestinal Bacterial Overgrowth (SIBO)

• Lactose Intolerance: Caused by a deficiency of lactase, the brush-border enzyme that hydrolyzes lactose into glucose and galactose. Primary lactase deficiency is a genetically programmed decline in enzyme activity, common in Asian, African, and Native American populations. Secondary lactase deficiency occurs due to mucosal injury (e.g., from viral gastroenteritis, celiac disease, or Crohn's). Unabsorbed lactose acts as an osmotic agent, drawing water into the lumen, and is fermented by colonic bacteria to produce hydrogen gas, carbon dioxide, and short-chain fatty acids. This results in bloating, flatulence, abdominal cramps, and watery, acidic diarrhea. Diagnosis is typically clinical, but can be confirmed with a hydrogen breath test (showing an increase in breath hydrogen concentration >20 ppm after lactose ingestion). Management involves dietary restriction of lactose, lactase enzyme supplementation, and ensuring adequate calcium and vitamin D intake.
• Small Intestinal Bacterial Overgrowth (SIBO): SIBO is characterized by excessive bacterial proliferation in the small intestine, often due to altered motility (such as diabetic gastroparesis or scleroderma), anatomical alterations (such as blind loops, strictures, or a history of Roux-en-Y gastric bypass), or chronic acid suppression (long-term PPI therapy). The bacteria ferment carbohydrates, producing gas and causing bloating, diarrhea, flatulence, and malabsorption. SIBO characteristically causes vitamin B12 deficiency (as bacteria consume cobalamin) alongside elevated folate levels (as bacteria synthesize folate). The gold standard for diagnosis is a jejunal aspirate culture showing >=10^3 CFU/mL, but the non-invasive lactulose or glucose hydrogen breath test is more commonly used. Treatment involves addressing the underlying cause and prescribing a course of oral rifaximin.

Vitamin Deficiencies in Malabsorption

Malabsorptive states (including celiac disease, chronic pancreatitis, and Crohn disease) impair the absorption of fat-soluble and water-soluble vitamins:

• Fat-Soluble Vitamins (A, D, E, K):
  • Vitamin A: Deficiency leads to night blindness (nyctalopia), xerophthalmia (dry eyes), Bitot spots, and follicular hyperkeratosis.
  • Vitamin D: Presents with rickets in children and osteomalacia in adults, characterized by bone pain, muscle weakness, and hypocalcemia.
  • Vitamin E: Deficiency causes hemolytic anemia and a progressive neuromuscular disorder characterized by ataxia, loss of proprioception, and loss of vibratory sensation. This presentation mimics vitamin B12 deficiency, but can be distinguished by the absence of megaloblastic anemia, hypersegmented neutrophils, and elevated methylmalonic acid.
  • Vitamin K: Necessary for the gamma-carboxylation of clotting factors II, VII, IX, and X. Deficiency leads to easy bruising, mucosal bleeding, and an elevated prothrombin time (PT) and international normalized ratio (INR).
• Water-Soluble Vitamins:
  • Vitamin B12 (Cobalamin): Absorbed in the terminal ileum after binding to intrinsic factor. Deficiency leads to megaloblastic anemia and subacute combined degeneration of the spinal cord (due to demyelination of the dorsal columns and lateral corticospinal tracts), presenting with paresthesias, loss of vibration and proprioception, and spastic paresis. Labs show elevated methylmalonic acid (MMA) and homocysteine.
  • Folate (Vitamin B9): Deficiency causes megaloblastic anemia similar to B12 deficiency but without neurological symptoms. Labs show elevated homocysteine but normal MMA.

Enteral vs. Parenteral Nutrition

Step 3 examinations enforce the clinical maxim: "If the gut works, use it."

• Enteral Nutrition (EN): Provided via nasogastric, nasojejunal, percutaneous endoscopic gastrostomy (PEG), or jejunostomy tubes. EN is preferred over parenteral nutrition because it maintains the integrity of the gut mucosal barrier, prevents mucosal atrophy, decreases bacterial translocation, and is associated with significantly fewer infectious complications and lower costs.
• Parenteral Nutrition (PN): Indicated only when the gastrointestinal tract is non-functional or inaccessible (e.g., severe prolonged ileus, high-output enterocutaneous fistulas, short bowel syndrome, mechanical bowel obstruction, or severe hemodynamic instability).
• Complications of PN: Central venous catheter-associated bloodstream infections are the most common complication. Long-term PN can cause biliary sludge and cholelithiasis (due to lack of CCK stimulation from gut feeding) and metabolic bone disease.
• Refeeding Syndrome: A life-threatening complication of nutritional rehabilitation (both EN and PN) in severely malnourished patients. The introduction of carbohydrates causes an insulin surge, driving phosphorus, potassium, and magnesium intracellularly. This leads to profound hypophosphatemia, hypokalemia, and hypomagnesemia, resulting in cardiac arrhythmias, respiratory failure, seizures, and rhabdomyolysis. It is prevented by starting nutrition slowly ("feed low and slow") and aggressively checking and replacing electrolytes.