What is sprue?

Understanding Sprue: Types, Diagnosis, and Management

Sprue refers to a group of malabsorption disorders characterized by villous atrophy in the small intestine, with the two main types being celiac disease (gluten-sensitive enteropathy) and tropical sprue, each requiring distinct diagnostic approaches and treatments. 1

Types of Sprue

Celiac Disease (Celiac Sprue)

• A chronic autoimmune disorder triggered by gluten ingestion in genetically susceptible individuals
• Characterized by small intestinal villous atrophy and malabsorption
• Prevalence: 1:120 to 1:300 in Western populations 2
• Requires lifelong gluten-free diet for management

Tropical Sprue

• Occurs in residents of or travelers to tropical regions
• Characterized by folate and/or vitamin B12 deficiency
• Responds to treatment with antibiotics (tetracycline or doxycycline) and folic acid 1
• Biopsies typically show partial villous atrophy with less intraepithelial lymphocytosis than celiac disease

Refractory Sprue

• Defined as persistent or recurrent malabsorption and diarrhea with villous atrophy despite strict adherence to a gluten-free diet for at least 12 months 1
• Rare condition (approximately 1% of celiac disease patients)
• Divided into two types:
  • Type 1: Normal intraepithelial lymphocyte population
  • Type 2: Aberrant, clonal intraepithelial lymphocyte population (worse prognosis)

Unclassified Sprue (Idiopathic Villous Atrophy)

• Sprue-like histology without evidence of other etiologies 1
• May represent a heterogeneous group of conditions
• Some cases resolve spontaneously without intervention 1

Clinical Presentation

Common Symptoms

• Diarrhea (often pale, yellow, or light brown in small bowel disease) 3
• Weight loss
• Malabsorption with nutritional deficiencies
• Steatorrhea (bulky, malodorous, pale stools that may float) 3
• Abdominal pain or bloating

Associated Findings

• Anemia (often macrocytic due to folate/B12 deficiency in tropical sprue)
• Osteopenia/osteoporosis
• Neurological disorders
• Associated autoimmune conditions (thyroid disease, diabetes)

Diagnostic Approach

Initial Evaluation

• Serologic testing for celiac disease:
  • IgA tissue transglutaminase antibodies (IgA-TG2)
  • IgA endomysial antibodies (EMA)
  • Consider IgG-based tests if IgA deficiency is present 1

Endoscopic Evaluation

• Upper endoscopy with multiple duodenal biopsies is essential
• Histological findings to look for:
  • Villous atrophy
  • Crypt hyperplasia
  • Intraepithelial lymphocytosis

Additional Testing Based on Clinical Suspicion

• Travel history (for tropical sprue)
• Medication review (olmesartan, mycophenolate, methotrexate can cause enteropathy) 1
• Evaluation for other causes of villous atrophy:
  • Common variable immunodeficiency
  • Autoimmune enteropathy
  • Small intestinal bacterial overgrowth
  • Giardiasis
  • HIV enteropathy
  • Whipple's disease 1

Differential Diagnosis of Sprue-like Conditions

Immune-Related Disorders

• Common variable immunodeficiency
• IgA deficiency
• Autoimmune enteropathy

Infections

• Giardiasis
• Small intestinal bacterial overgrowth
• HIV enteropathy
• Tuberculosis
• Whipple's disease 1

Medication-Induced

• Olmesartan and other angiotensin receptor blockers
• Mycophenolate mofetil
• Methotrexate
• Azathioprine 1

Other Conditions

• Crohn's disease
• Microscopic colitis
• Radiation enteritis
• Eosinophilic gastroenteritis 1

Management Approach

Celiac Disease

• Strict lifelong gluten-free diet
• Nutritional supplementation as needed
• Regular follow-up to monitor adherence and response

Tropical Sprue

• Tetracycline or doxycycline for 6 months
• Folic acid supplementation
• Vitamin B12 if deficient 1, 4

Refractory Sprue

• Type 1:

  • Open-capsule budesonide (preferred) or prednisone
  • Consider azathioprine or 6-mercaptopurine if steroid-dependent 1, 5

• Type 2:

  • More aggressive treatment needed
  • Options include azathioprine, 6-mercaptopurine, infliximab, or cladribine 1
  • Higher risk of progression to enteropathy-associated T-cell lymphoma (EATL)

Supportive Care

• Nutritional assessment and supplementation
• Consider parenteral nutrition in severe malabsorption 1
• Regular monitoring for complications

Monitoring and Follow-up

Celiac Disease

• Regular follow-up with gastroenterologist and dietitian
• Serologic testing to monitor adherence to gluten-free diet
• Consider repeat biopsy if symptoms persist

Refractory Sprue

• Close monitoring for development of lymphoma
• Small bowel imaging if symptoms or signs concerning for EATL
• Consider referral to specialized center for management 1

Pitfalls to Avoid

1. Initiating gluten-free diet before serologic testing for celiac disease, which can lead to false-negative results 1

2. Failing to consider other causes of villous atrophy in patients not responding to gluten-free diet 1

3. Missing medication-induced enteropathy, particularly olmesartan which can cause severe illness but responds rapidly to drug cessation 1

4. Overlooking tropical sprue in patients with travel history to endemic regions 1

5. Failing to perform flow cytometry and T-cell receptor rearrangement studies in suspected refractory celiac disease, which are crucial for distinguishing between type 1 and type 2 1