What are the clinical presentations and management of celiac disease?

Celiac Disease: Clinical Presentations and Management

Celiac disease (CD) is an immune-mediated small intestinal enteropathy triggered by gluten exposure in genetically predisposed individuals, presenting with diverse clinical manifestations ranging from classical gastrointestinal symptoms to extraintestinal manifestations, with strict lifelong adherence to a gluten-free diet being the only effective treatment. 1, 2

Clinical Presentations

Classical Gastrointestinal Manifestations

• Diarrhea, steatorrhea, and weight loss (traditional "classical CD" presentation) 1, 2
• Abdominal pain and bloating (often similar to irritable bowel syndrome) 1, 2
• Constipation (less common but still recognized presentation) 2
• Malabsorption symptoms (particularly in children presenting with failure to thrive) 1

Extraintestinal Manifestations

• Iron deficiency anemia (one of the most common extraintestinal manifestations) 1, 2
• Fatigue and general malaise 2
• Decreased bone mineral density, osteoporosis, and osteomalacia 1, 2
• Abnormal liver function tests (elevated transaminases) 1, 2
• Short stature and growth failure (particularly in children) 2
• Neurological manifestations (neuropathy, ataxia, headaches) 1, 3
• Dermatitis herpetiformis (skin manifestation of CD) 1
• Reproductive issues (infertility, miscarriages) 1, 4

Atypical and Silent Presentations

• Many patients present with non-classical or atypical symptoms with minimal or no gastrointestinal features 1, 5
• Asymptomatic CD is increasingly diagnosed through screening of high-risk populations 1, 4
• The prevalence of non-classical presentations has increased over time, making diagnosis challenging 4, 6

High-Risk Groups for Screening

• First-degree relatives of patients with CD (prevalence ~10%) 1, 2
• Type 1 diabetes mellitus (prevalence 2-5% in adults, 3-8% in children) 1, 2
• Autoimmune thyroid disease 2
• Down syndrome (prevalence 3-12%) and Turner syndrome (prevalence 2-10%) 1
• Unexplained iron deficiency anemia (prevalence 2-5% in asymptomatic, 10-15% in symptomatic) 1, 2
• Unexplained elevated liver transaminases 1, 2
• Premature osteoporosis 1, 2

Diagnostic Approach

Serological Testing

• IgA tissue transglutaminase antibody (tTG-IgA) is the preferred initial screening test 1, 2
• Total IgA level should be measured to rule out IgA deficiency 1, 2
• All serologic testing must be performed while the patient is on a gluten-containing diet 1, 2
• If the patient has already started a gluten-free diet, recommend consuming three slices of wheat bread daily for 1-3 months before testing 1

Histological Confirmation

• Small intestinal biopsy remains the gold standard for diagnosis in adults 1, 2
• Multiple biopsies should be taken from different parts of the duodenum, including the bulb 1
• Characteristic findings include villous atrophy, crypt hyperplasia, and increased intraepithelial lymphocytes 1, 2
• In patients with positive serology but negative biopsies, repeat biopsies should be considered if clinical suspicion remains high 1

Genetic Testing

• HLA-DQ2/DQ8 testing has limited diagnostic role but high negative predictive value 1, 2
• Useful to rule out CD in patients with seronegative histologic changes or with historic diagnosis without serologic confirmation 1

Management

Dietary Treatment

• Strict, lifelong adherence to a gluten-free diet (GFD) is the only effective treatment for CD 1, 2, 7
• Complete elimination of wheat, barley, and rye from the diet is essential 2
• Referral to a dietitian experienced in CD is crucial for nutritional assessment and counseling 2

Monitoring Response

• Follow-up serology should be performed at 6 and 12 months after diagnosis, and yearly thereafter 1, 2
• Negative serology does not guarantee intestinal mucosal healing; persistently positive serology usually indicates ongoing gluten exposure 1
• Patients with persistent or relapsing symptoms should undergo repeat endoscopic biopsies even if serology is negative 1

Management of Non-responsive CD

• Confirm the accuracy of the original diagnosis and thoroughly review the diet for hidden sources of gluten 2
• Consider associated conditions that may cause persistent symptoms, such as:
  • Microscopic colitis 2
  • Pancreatic exocrine dysfunction 2
  • Small intestinal bacterial overgrowth 2
  • Irritable bowel syndrome overlap (common in patients with persistent symptoms despite strict GFD adherence) 4
  • Lactose or fructose intolerance 2, 4

Nutritional Assessment and Management

• Test for common deficiencies at diagnosis: iron, folate, vitamin B12, vitamin D, and albumin 2
• Correction of deficiencies should begin with oral supplements and dietary counseling 2
• Regular follow-up (approximately every 12 months) is recommended to ensure nutritional adequacy 1, 2

Common Pitfalls to Avoid

• Initiating a gluten-free diet before diagnostic testing (reduces sensitivity of both serology and biopsy) 1, 2
• Failing to test for IgA deficiency when performing celiac serology 2
• Inadequate number of biopsy specimens (can miss patchy mucosal lesions) 1, 2
• Overlooking extraintestinal manifestations, leading to delayed diagnosis 2, 5
• Assuming all symptoms will resolve immediately after starting a GFD 2
• Incomplete elimination of gluten from diet leading to persistent symptoms 2

Long-term Follow-up

• Annual follow-up is recommended, though adherence to follow-up visits tends to decrease over time 1
• Approximately 20% of adult patients may develop therapy-resistant CD 1
• Teenagers are less adherent to GFD and less satisfied with the impact of CD on their lives 1
• Follow-up biopsies may be considered to identify patients at increased risk of lymphoma 1
• Follow-up biopsies are not mandatory if the patient is asymptomatic on a GFD 1