1. Celiac Disease

 

 

1. Celiac Disease Overview

  • Definition: Autoimmune disorder triggered by gluten ingestion (wheat, barley, rye) in genetically predisposed individuals (HLA-DQ2/DQ8 positive).
  • Pathophysiology:
    • Gluten-derived peptides are deamidated by tissue transglutaminase (tTG), enhancing their binding to HLA-DQ2/DQ8 on antigen-presenting cells.
    • This leads to CD4+ T-cell activation, cytokine release, and damage to intestinal villi.

2. Clinical Features

  • Gastrointestinal Symptoms: Diarrhea, weight loss, abdominal bloating, steatorrhea.
  • Extraintestinal Manifestations:
    • Iron deficiency anemia, fatigue, osteopenia/osteoporosis.
    • Dermatitis herpetiformis (pruritic vesicular rash, see images below).
    • Neurological symptoms: Ataxia, peripheral neuropathy.
  • Associated Conditions: Type 1 diabetes, autoimmune thyroid disease, selective IgA deficiency.

3. Diagnosis of Celiac Disease

  • Serological Tests:
    • Anti-tTG IgA (high sensitivity and specificity).
    • Anti-endomysial antibodies (EMA-IgA).
    • Total IgA levels to exclude IgA deficiency (as this can cause false-negative results).
  • Duodenal Biopsy:
    • Gold standard for diagnosis in adults.
    • Requires ≥4 biopsy samples from the duodenal bulb and distal duodenum.

4. Histological Staging (Marsh-Oberhuber Classification)

Stage

Histological Findings

Clinical Notes

0

Normal mucosa

Seen in potential CD (positive serology, normal histology).

1

Increased intraepithelial lymphocytes (IELs) >30/100 enterocytes

Earliest sign of mucosal immune activation.

2

Crypt hyperplasia without villous atrophy

Indicates active inflammation.

3a

Partial villous atrophy

Blunting of villi with retained architecture.

3b

Subtotal villous atrophy

Flattened mucosa with crypt elongation.

3c

Total villous atrophy

Complete loss of villous structure.

4 (Optional)

Total villous atrophy with complete architectural destruction

Advanced form found in some classifications.

Source: Villanacci et al., 2020

5. Refractory Celiac Disease (RCD)

  • Definition: Persistent or recurrent symptoms and villous atrophy despite strict adherence to a gluten-free diet (GFD) for at least 12 months.
  • Types of RCD:
    • Type I RCD: Normal intraepithelial lymphocytes (IELs) phenotype; responds to immunosuppressants (e.g., steroids, budesonide).
    • Type II RCD: Abnormal clonal expansion of IELs (CD3+, CD8-negative); carries a poor prognosis and is associated with high risk of progression to enteropathy-associated T-cell lymphoma (EATL).
  • Clinical Features: Severe malabsorption, weight loss, and risk of ulcerative jejunoileitis.
  • Management:
    • Type I RCD: Prednisolone or budesonide.
    • Type II RCD: Immunosuppressive agents (e.g., cladribine) and close monitoring for lymphoma.
    • Consider referral for hematology review in suspected malignant transformation.

6. Lymphoma Risk in Untreated Celiac Disease

  • Enteropathy-Associated T-cell Lymphoma (EATL):
    • Rare but aggressive lymphoma associated with longstanding or untreated celiac disease.
    • Location: Small intestine, especially the jejunum.
    • Presentation: Abdominal pain, weight loss, fever, and intestinal perforation.
  • Other Malignancies: Increased risk of small bowel adenocarcinoma.
  • Prevention: Early diagnosis and strict adherence to a GFD significantly reduce the risk of malignancy.

7. Management of Celiac Disease

  • Gluten-Free Diet (GFD): Lifelong strict avoidance of gluten-containing foods.
    • Engage a dietitian for patient education.
    • Regular follow-up with symptom review and serological testing.
  • Nutritional Support: Supplementation of calcium, vitamin D, folate, and iron as needed.
  • Screening for Complications: Bone mineral density (BMD) scans to assess for osteoporosis, and periodic review for symptoms of malabsorption or malignancy.

8. Differential Diagnosis of Villous Atrophy

  • Celiac Disease: Positive serology and histology.
  • Infectious Enteropathies: Whipple’s disease, giardiasis, tropical sprue.
  • Drug-Induced Enteropathy: NSAIDs, neomycin.
  • Autoimmune Enteropathy: Consider in cases unresponsive to a GFD.
 

References

  1. BMJ Open Gastroenterology
  2. Celiac Disease Guidelines
  3. Histologic Evaluation in CD
  4. Marsh Classification Resource

Images

  1. Histological Stages of Celiac Disease: Marsh Classification Examples.
  2. Dermatitis Herpetiformis Lesions (Pruritic Rash): DermNet Resource.
  3. Refractory Celiac Disease Biopsy (Type II RCD): Histology Resource.
  4. Enteropathy-Associated T-Cell Lymphoma (EATL): T-Cell Lymphoma Overview.