Chronic Diarrhea: Diagnosis and Causes

Approach to Chronic Diarrhea

• Chronic diarrhea is defined as having ≥3 loose stools per day for ≥6 weeks
• It impacts 3-5% of the general population, significantly affecting their quality of life.
• Diarrhea can originate from the small bowel (large volume, watery, non-bloody) or large bowel (smaller volume, bloody, tenesmus).

Small Bowel Diarrhea Causes

• Malabsorption is a key cause
• Fat malabsorption can occur due to pancreatic insufficiency, liver disease, or small intestinal bacterial overgrowth (SIBO)
• Carbohydrate malabsorption can result from lactose intolerance or post-infectious lactase deficiency.
• Reduced absorptive surface can be caused by celiac disease or short bowel syndrome
• Disordered motility, such as in irritable bowel syndrome (IBS-D) or hyperthyroidism, can be a cause.
• Other causes include neuroendocrine tumors (carcinoid syndrome), drug-induced diarrhea (antibiotics, SSRIs), and chronic infections (Giardia, Cryptosporidium).

Large Bowel Diarrhea Causes

• Inflammatory conditions like inflammatory bowel disease (Crohn’s, ulcerative colitis), microscopic colitis, radiation colitis, ischemic colitis, and chronic infections (C. difficile) contribute
• Disordered motility can cause IBS-D or overflow diarrhea from constipation.
• Colorectal cancer, though rare as a diarrhea presentation, is another consideration (more often presents as iron deficiency anemia).

Red Flags

• Watch out for unintentional weight loss (>5% in 6-12 months).
• Other red flags include nocturnal diarrhea, GI bleeding (melena, hematochezia), iron deficiency anemia, onset >50 years old, and a family history of IBD or colorectal cancer.

Diagnostic Workup

• Begin with a thorough history and physical exam
• Conduct blood tests including CBC, electrolytes, ferritin, TSH, and celiac serology
• Perform stool tests like fecal calprotectin tests (IBD marker), and check for ova & parasites, and C. difficile
• Endoscopy is recommended if there are any alarm features or persistent symptoms.

Management Overview

• Implement dietary modifications (gluten-free for celiac, lactose restriction if intolerance is suspected).
• Medication options include anti-diarrheals, antibiotics for infections, and immunosuppressants for IBD
• Treat the underlying cause of the diarrhea.

Malnutrition and Growth in Pediatrics Key Concepts

• Malnutrition is a nutrient imbalance that affects growth & development
• Failure to thrive (FTT) = inadequate weight gain
• Growth patterns are key indicators.
• Weight loss first indicates acute malnutrition.
• Weight and height loss indicate chronic malnutrition
• Weight, height, and head circumference loss indicates congenital/genetic disorders

Causes of Malnutrition

• Decreased intake can result from food insecurity or feeding difficulties (anatomical, neurological).
• Increased losses can be due to malabsorption (Celiac, cystic fibrosis, IBD) or chronic diarrhea/vomiting.
• Increased metabolic demands are seen in congenital heart disease, chronic lung disease, and malignancy.
• Genetic conditions like chromosomal abnormalities (Turner, Down syndrome)

Key Clinical Findings

• Muscle wasting can be observed in the temples, shoulders, and thighs
• Fat loss can be seen in the buttocks and cheeks.
• Vitamin deficiencies manifest as pallor, brittle hair, bruising, and nail ridges.

Management

• Provide nutritional support through caloric supplementation or enteral feeding if severe.
• Identify and treat the underlying cause
• Monitor growth trends

Colorectal Cancer & Polyps Key Concepts

• Colorectal cancer is common, but largely preventable with screening.
• Progression occurs from normal mucosa to adenoma (polyp) and then to carcinoma.
• It generally takes 8-10 years for a polyp to become cancerous.

Risk Factors

• Risk increases with age >50
• A family history of Lynch syndrome or familial adenomatous polyposis (FAP) is a risk factor
• Having inflammatory bowel disease, obesity, smoking, and alcohol use increase risk

Screening Recommendations

• For average risk individuals, FIT test every 2 years starting at age 50 is advised.
• Those with a family history should have a colonoscopy at 40 or 10 years before the affected relative’s diagnosis
• Individuals with Lynch syndrome or FAP need earlier & more frequent screening

Symptoms

• Iron deficiency anemia can occur with right-sided tumors
• Rectal bleeding and changes in bowel habits often occur with left-sided tumors
• Abdominal pain and weight loss suggest advanced disease

Diagnosis

• Colonoscopy is the gold standard
• CT colonography can be an alternative for those avoiding colonoscopy.

Single-Gene Disorders Key Concepts

• Single-gene disorders follow Mendelian inheritance patterns (autosomal dominant, autosomal recessive, X-linked).
• Dominant conditions require one pathogenic allele, while recessive conditions require two
• Pedigree analysis tracks inheritance in families.

Autosomal Dominant Inheritance

• Affected individuals have one pathogenic allele
• Seen in every generation (vertical transmission)
• Examples include Huntington’s disease, Marfan syndrome, and Polycystic kidney disease

Autosomal Recessive Inheritance

• Both parents are usually carriers (one pathogenic allele each).
• It is seen in siblings but skips generations
• Examples include Cystic fibrosis, sickle cell anemia, and Tay-Sachs disease.

X-Linked Recessive Inheritance

• Males are more often affected (only one X chromosome).
• There is no male-to-male transmission
• Examples include Duchenne muscular dystrophy, Hemophilia A, and G6PD deficiency

X-Linked Dominant Inheritance

• Both males and females can be affected, but males often experience more severe symptoms
• Rett syndrome is an example

Key Terms

• Homozygous: Two identical alleles.
• Heterozygous: Two different alleles.
• Carrier: Has one pathogenic allele (recessive conditions).
• Penetrance: Likelihood of expressing the disease if you have the mutation.

Celiac Disease Key Concepts

• Celiac disease is gluten-sensitive enteropathy, an autoimmune destruction of small intestinal villi
• Triggered by gluten (wheat, rye, barley) in genetically susceptible individuals
• HLA-DQ2/DQ8 positive in >90% of cases

Symptoms

• GI symptoms include chronic diarrhea, bloating, weight loss, and steatorrhea.
• Extraintestinal symptoms: Anemia (iron deficiency), osteoporosis, and dermatitis herpetiformis

Diagnosis

• First-line test: IgA tissue transglutaminase (TTG-IgA) + total IgA.
• Confirmatory test: Small bowel biopsy showing villous atrophy and crypt hyperplasia
• Genetic testing (HLA-DQ2/DQ8) is useful if the biopsy is inconclusive

Management

• Strict lifelong gluten-free diet is essential
• Use nutritional supplementation: Iron, calcium, vitamin D, folate
• Monitor TTG-IgA levels to assess adherence.

Cystic Fibrosis (CF) Key Concepts

• Cystic Fibrosis is an autosomal recessive disorder caused by a mutation in CFTR gene
• Results in defective chloride transport, leading to thick mucus in lungs, pancreas, and intestines
• It is the most common fatal genetic disease in Caucasian children.

Clinical Presentation

• Respiratory issues include recurrent lung infections, bronchiectasis, and chronic cough
• GI issues include pancreatic insufficiency (fat malabsorption, steatorrhea, vitamin ADEK deficiency), and meconium ileus
• Endocrine symptoms include CF-related diabetes (CFRD).
• Reproductive issues include male infertility (absence of vas deferens).

Diagnosis

• Newborn screening involves immunoreactive trypsinogen (IRT) tests
• Confirmatory test: Sweat chloride test (>60 mmol/L)
• Genetic testing: CFTR mutation analysis

Management

• Pulmonary treatments include airway clearance (chest physiotherapy), inhaled mucolytics, and antibiotics
• Address Pancreatic insufficiency with pancreatic enzyme replacement (lipase, protease, amylase).
• Provide Nutritional support via a high-calorie, high-fat diet, vitamin ADEK supplementation.
• CFTR modulators like ivacaftor and lumacaftor target mutation-specific issues.

Inflammatory Bowel Disease (IBD) - Crohn’s vs. Ulcerative Colitis Key Differences

• Location: Crohn’s can be from mouth to anus with skip lesions. Ulcerative Colitis (UC) is in the colon only, continuous
• Layer Involvement: Crohn’s is transmural. UC affects the mucosal and submucosal layers only
• Symptoms: Crohn’s presents RLQ pain, non-bloody diarrhea. UC presents LLQ pain, bloody diarrhea
• Complications: Crohn’s leads to strictures, fistulas, abscesses. UC can cause toxic megacolon, PSC
• Smoking: Worsens Crohn’s but is protective for UC.

Extraintestinal Manifestations

• Eyes: Uveitis, episcleritis.
• Joints: Arthritis (large joints).
• Skin: Erythema nodosum, pyoderma gangrenosum.
• Hepatic: Primary sclerosing cholangitis (PSC, more common in UC).

Diagnosis

• Colonoscopy + biopsy is the gold standard
• Fecal calprotectin differentiates IBD from IBS
• Crohn’s shows cobblestone mucosa, skip lesions, and non-caseating granulomas
• UC shows continuous inflammation and crypt abscesses

Management

• Induction therapy (flare-ups): Steroids like prednisone or budesonide or 5-ASA (mesalamine) for UC
• Maintenance therapy: Immunomodulators (azathioprine, methotrexate) or Biologics (TNF inhibitors: infliximab, adalimumab)
• Surgery: UC is Curative with colectomy. Crohn’s: Non-curative; resection only for complications.

Overview of chronic diarrhea, defined as frequent loose stools lasting over 6 weeks. Explores causes related to small and large bowel issues. Discusses malabsorption, motility disorders, and infections that lead to chronic diarrhea.