What is the differential diagnosis for chronic small intestine pathology with fever?

Differential Diagnosis for Chronic Small Intestine Pathology with Fever

When evaluating chronic small intestinal pathology presenting with fever, prioritize excluding inflammatory bowel disease (particularly Crohn's disease), chronic infections (tuberculosis, Whipple's disease), and small intestinal bacterial overgrowth (SIBO) as these directly impact morbidity and mortality and require specific treatment.

Primary Diagnostic Categories

Inflammatory Bowel Disease

• Crohn's disease can present with fever and small bowel involvement without typical gastrointestinal symptoms, manifesting instead with extraintestinal complications including abscesses and fistulas 1
• Check inflammatory markers (CRP, albumin, platelets, and fecal calprotectin) as initial screening; normal values make active inflammatory bowel disease unlikely 2
• Small bowel imaging with CT or MR enterography is essential to identify strictures, fistulas, or inflammatory changes 1

Chronic Infections

• Intestinal tuberculosis remains a major diagnostic consideration globally and can mimic Crohn's disease; PCR-based diagnostic tests and imaging modalities can help differentiate these conditions 3
• Whipple's disease (caused by Tropheryma whipplei) presents with chronic small bowel inflammation and systemic symptoms; diagnosis requires intestinal biopsy 3
• Parasitic infections should be investigated, particularly with travel history; look for eosinophilic infiltrates on histology 2
• Chronic fungal infections carry high mortality and require rapid diagnosis, though they typically occur in immunocompromised patients 3

Dysmotility-Related Conditions

Visceral Neuropathy

• Autoimmune neuropathy can present with paraneoplastic or non-paraneoplastic antibodies (anti-Hu, ganglionic AChR, VGKC-complex antibodies) causing chronic intestinal pseudo-obstruction 2
• Mitochondrial disorders (particularly MNGIE) present between first and third decades with severe gastrointestinal dysmotility, cachexia, and neurological problems; test plasma/urine thymidine and deoxyuridine 2
• Inflammatory neuropathies show lymphocytic or eosinophilic plexitis/neuritis on histology 2

Visceral Myopathy

• Presents with chronic abdominal pain, distension, vomiting (often faeculent), and alternating diarrhea/constipation leading to malnutrition 2
• Can be associated with congenital muscular disorders, metabolic storage diseases, or systemic sclerosis 2

Radiation Enteropathy

• Occurs months to years after >45 Gy irradiation, causing diarrhea, perforation, fistulas, bleeding, and obstruction 2
• Risk increased with pre-existing malnutrition, diabetes mellitus, hypertension, or vasculitis 2

Small Intestinal Bacterial Overgrowth (SIBO)

• Results from impaired motility, leading to bacterial proliferation with bile salt deconjugation, steatorrhea, and malabsorption 2
• Can cause D-lactic acidosis (high anion gap) and elevated ammonia levels 2
• May present with subtotal villous atrophy on histology mimicking celiac disease 2

Critical Diagnostic Pitfalls to Avoid

Mechanical Obstruction Masquerading as Dysmotility

• Adhesive obstruction is frequently undiagnosed; suspect when there is history of multiple abdominal operations with intermittent colicky pain, distension, and vomiting 2
• Look for distinct transition point on CT imaging between dilated and normal bowel, though this may not be apparent if obstruction has resolved 2
• Obtain CT scan during acute pain episodes for better diagnostic yield 2

Drug-Induced Dysmotility

• Opioid-induced bowel dysfunction can mimic primary intestinal pathology; carefully review medication history including anticholinergic agents 2
• These medications must be discontinued or reduced before attributing symptoms to primary bowel disease 2

Premature Diagnostic Labeling

• Avoid giving definitive organic diagnosis without clear histological or imaging confirmation, as this complicates management if psychosocial factors are contributing 2
• Document diagnosis as "working" or "probable" when uncertainty exists 2

Essential Diagnostic Workup

Laboratory Testing

• Complete blood count, comprehensive metabolic panel (including potassium, magnesium), thyroid function, glucose 2
• Tissue transglutaminase IgA with total IgA level to exclude celiac disease 4
• Inflammatory markers: CRP, albumin, platelets, fecal calprotectin 2
• Antineuronal antibodies (anti-Hu, ganglionic AChR, VGKC-complex) if autoimmune neuropathy suspected 2
• Mitochondrial testing: plasma/urine thymidine and deoxyuridine, white blood cell thymine phosphorylase if MNGIE suspected 2

Imaging Studies

• CT or MR enterography with intravenous contrast to identify structural lesions, strictures, fistulas, or inflammatory changes 2
• Plain abdominal radiographs may show dilated small and large bowel in dysmotility 2
• MRI brain if mitochondrial disorder (MNGIE) suspected 2

Endoscopic Evaluation

• Upper endoscopy with small bowel biopsies if celiac serology positive or upper GI symptoms present 4
• Colonoscopy with biopsies to exclude inflammatory bowel disease and microscopic colitis 4
• Full-thickness small bowel biopsy may be needed for definitive diagnosis of myopathy or neuropathy, though interpretation remains challenging 2

Specialized Testing

• Small bowel manometry to detect abnormal motility patterns and absent migrating motor complexes 2
• Breath testing or jejunal aspirate culture for SIBO diagnosis 2

Multidisciplinary Team Approach Required

Management requires coordination between gastroenterology, gastrointestinal surgery, pain management, psychiatry/psychology, rheumatology, neurology, pathology, radiology, and nutrition support 2