Definition/General
Introduction:
Tropical sprue is a malabsorption syndrome endemic to tropical regions
It shows villous atrophy and chronic inflammation
It affects both small and large intestines
It responds to antibiotics and folate therapy.
Origin:
Etiology remains unclear
Postulated causes: infectious agents (bacteria, viruses)
Nutritional deficiencies (folate, B12)
Environmental toxins
Autoimmune mechanisms
Likely multifactorial pathogenesis.
Classification:
Acute tropical sprue: recent onset (<6 months)
Chronic tropical sprue: prolonged disease (>6 months)
Based on severity: mild, moderate, severe
Geographic variants: Indian subcontinent, Caribbean, Southeast Asian forms.
Epidemiology:
Endemic to tropical regions: India, Southeast Asia, Caribbean
High prevalence in India (especially South India)
Adults primarily affected
No gender predilection
Seasonal variation observed.
Clinical Features
Presentation:
Chronic diarrhea and steatorrhea
Weight loss and malnutrition
Abdominal distension
Megaloblastic anemia (folate/B12 deficiency)
Glossitis and angular cheilitis
Peripheral neuropathy.
Symptoms:
Bulky, frothy stools (steatorrhea)
Significant weight loss
Abdominal cramping and bloating
Fatigue and weakness
Anorexia and nausea
Borborygmi and flatulence.
Risk Factors:
Residence in tropical areas
Poor sanitation and hygiene
Malnutrition
Recent travel to endemic areas
Bacterial overgrowth
Immunocompromised states.
Screening:
Stool examination (steatorrhea)
D-xylose absorption test
Small bowel biopsy
Serum folate and B12 levels
Complete blood count (megaloblastic anemia)
Barium follow-through.
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Gross Description
Appearance:
Villous atrophy and mucosal flattening
Edematous mucosa
Loss of normal fold pattern
Pale, thickened bowel wall
Dilated bowel loops
Normal serosal surface usually.
Characteristics:
Jejunum and ileum primarily affected
Mucosal pallor and edema
Flattened villi or complete villous atrophy
Thickened bowel wall
Dilated lacteals.
Size Location:
Jejunum most severely affected
Progressive involvement distally
Entire small bowel may be involved
Colonic involvement possible
Variable severity along bowel length.
Multifocality:
Diffuse small bowel involvement
Jejunum most severe
Patchy involvement initially
Progressive extension
Concurrent colonic changes possible.
Microscopic Description
Histological Features:
Villous atrophy (partial to complete)
Crypt hyperplasia
Chronic inflammation in lamina propria
Surface epithelial damage
Increased intraepithelial lymphocytes
Plasma cell infiltrate.
Cellular Characteristics:
Chronic inflammatory infiltrate: lymphocytes, plasma cells
Increased intraepithelial lymphocytes (>40/100 epithelial cells)
Surface epithelial flattening
Goblet cell reduction
Paneth cell hyperplasia.
Architectural Patterns:
Villous shortening to complete atrophy
Crypt elongation and hyperplasia
Increased crypt:villous ratio
Surface epithelial irregularity
Lamina propria expansion.
Grading Criteria:
Villous architecture: Grade I (partial atrophy), Grade II (subtotal atrophy), Grade III (total atrophy)
Inflammation: mild, moderate, severe
Intraepithelial lymphocyte count.
Immunohistochemistry
Positive Markers:
CD3 (T-lymphocytes increased)
CD8 (cytotoxic T-cells predominant)
Ki-67 (increased crypt proliferation)
CD68 (macrophages)
Chromogranin A (enteroendocrine cells).
Negative Markers:
CD20 (fewer B-cells typically)
Viral markers (CMV, EBV typically negative)
Parasitic antigens (excludes specific parasites).
Diagnostic Utility:
Demonstrates T-cell predominant inflammation
Assesses intraepithelial lymphocytes
Evaluates epithelial proliferation
Excludes specific infections
Confirms inflammatory nature.
Molecular Subtypes:
T-cell mediated inflammation
Th1-type response
Increased IFN-γ production
Altered cytokine profile.
Molecular/Genetic
Genetic Mutations:
HLA associations reported
Cytokine gene polymorphisms
TNF-α gene variants
IL-10 gene polymorphisms
Host genetic susceptibility factors.
Molecular Markers:
Elevated inflammatory cytokines
Increased TNF-α
IL-1β elevation
Interferon-γ upregulation
Altered tight junction proteins.
Prognostic Significance:
Early treatment: excellent response to antibiotics
Chronic untreated disease: malnutrition complications
Folate/B12 deficiency: neurological complications
Response to therapy: generally good prognosis.
Therapeutic Targets:
Antibiotics: tetracycline, doxycycline (first-line)
Folate supplementation (essential)
Vitamin B12 replacement
Nutritional support
Supportive care.
Differential Diagnosis
Similar Entities:
Celiac disease
Giardiasis
Whipple disease
Bacterial overgrowth
Crohn disease
Radiation enteritis.
Distinguishing Features:
Tropical sprue: tropical residence, responds to antibiotics/folate
Celiac: gluten sensitivity, anti-endomysial antibodies
Giardia: parasites identified
Whipple: PAS-positive macrophages
Crohn: granulomas, skip lesions.
Diagnostic Challenges:
Distinguishing from celiac disease
Excluding infectious causes
Identifying nutritional deficiencies
Correlation with geographic exposure
Response to specific therapy.
Rare Variants:
Collagenous sprue
Post-infectious tropical sprue
Pediatric forms
Refractory tropical sprue
Association with other tropical diseases.
Sample Pathology Report
Template Format
Sample Pathology Report
Complete Report: This is an example of how the final pathology report should be structured for this condition.
Specimen Information
Small bowel biopsy from [duodenum/jejunum], [number] fragments
Diagnosis
Small intestinal biopsy showing villous atrophy and chronic inflammation consistent with tropical sprue
Villous Architecture
Villous architecture: [partial/subtotal/total] villous atrophy
Crypt Changes
Crypt hyperplasia with increased crypt depth
Inflammation
Chronic inflammation in lamina propria with lymphocytes and plasma cells
Intraepithelial Lymphocytes
Intraepithelial lymphocytes: [number]/100 epithelial cells (normal <40/100)
Special Studies
CD3: [result], CD8: [result]
PAS stain: [negative for organisms]
[other study]: [result]
Recommendations
Clinical correlation with tropical exposure, consider antibiotic and folate therapy
Final Diagnosis
Small intestinal changes consistent with tropical sprue