Overview
Definition:
Celiac disease (CD) is a chronic, immune-mediated enteropathy triggered by the ingestion of gluten-containing foods in genetically predisposed individuals
It is characterized by inflammation and damage to the small intestinal mucosa, leading to malabsorption.
Epidemiology:
The prevalence of celiac disease varies geographically, with estimates ranging from 1 in 100 to 1 in 400 in Western populations, and is thought to be similar or higher in India
It can occur at any age, but diagnosis in children often happens during periods of rapid growth or when symptoms become apparent
HLA-DQ2 and HLA-DQ8 genes are present in over 95% of affected individuals.
Clinical Significance:
Undiagnosed or untreated celiac disease can lead to severe nutritional deficiencies, growth retardation, osteoporosis, infertility, neurological issues, and an increased risk of certain cancers (like enteropathy-associated T-cell lymphoma)
Early and accurate diagnosis is crucial for preventing long-term complications and improving patient outcomes.
Clinical Presentation
Symptoms:
Classic symptoms include chronic diarrhea, abdominal pain, bloating, and failure to thrive
Atypical presentations are common in children and can include iron deficiency anemia, constipation, vomiting, irritability, short stature, delayed puberty, dermatitis herpetiformis, and neurological symptoms
Symptoms can be exacerbated by a gluten challenge.
Signs:
Physical examination may reveal abdominal distension, tenderness, and signs of malnutrition such as decreased muscle mass, pallor due to anemia, and delayed development
Dermatitis herpetiformis, a characteristic itchy rash, may be present on elbows, knees, buttocks, and scalp.
Diagnostic Criteria:
Current guidelines generally recommend a stepwise approach
Serological testing (anti-tissue transglutaminase IgA [anti-tTG IgA] and total IgA) is the initial step
In children with high antibody titers and symptoms, a small intestinal biopsy showing villous atrophy, crypt hyperplasia, and increased intraepithelial lymphocytes may be omitted if specific criteria are met
However, for ambiguous cases or after a gluten challenge, biopsy is essential
Genetic testing for HLA-DQ2/DQ8 can be helpful in excluding the disease, as its absence is highly predictive.
Diagnostic Approach
History Taking:
A detailed dietary history focusing on gluten-containing foods (wheat, barley, rye) is paramount
Inquire about the onset and duration of symptoms, associated symptoms (GI and extra-intestinal), family history of celiac disease or other autoimmune conditions, and previous investigations
A history of unexplained anemia or growth failure is a red flag.
Physical Examination:
A complete physical examination should assess for signs of malnutrition, abdominal distension, tenderness, and dermatological manifestations like dermatitis herpetiformis
Growth parameters (height, weight, BMI, head circumference) should be meticulously recorded.
Investigations:
Initial investigations include IgA anti-tTG and total IgA levels
If IgA deficient, IgG-based antibodies (e.g., IgA anti-tTG, anti-endomysial antibodies IgA/IgG, anti-deamidated gliadin peptide IgG) are used
Confirmation usually requires a small intestinal biopsy demonstrating characteristic histological changes
Monitoring of iron, vitamin D, B12, folate, and bone mineral density may be indicated based on clinical suspicion and severity.
Differential Diagnosis:
Other causes of malabsorption and chronic diarrhea in children include lactose intolerance, cow's milk protein allergy, inflammatory bowel disease, giardiasis, cystic fibrosis, autoimmune enteropathy, and food protein-induced enterocolitis syndrome
Conditions causing villous atrophy include other autoimmune enteropathies and infections like Giardia
Gluten challenge should only be performed after a proper diagnostic workup of other conditions.
Gluten Challenge And Re Testing
Gluten Challenge Protocol:
A gluten challenge is typically performed in children who have been on a strict gluten-free diet (GFD) and are suspected of having celiac disease, or to re-evaluate adherence to GFD
It involves reintroducing a standardized daily amount of gluten (e.g., 3-10 grams, equivalent to 2-3 slices of bread) for a period of 3-12 months, or until symptoms recur or serological markers change
The challenge must be supervised by a clinician.
Rationale For Challenge:
The gluten challenge is crucial when the initial diagnosis was made on a GFD, or to assess if disease remission has occurred
It helps confirm the diagnosis by observing the re-emergence of symptoms or serological markers upon gluten reintroduction
It also helps differentiate between true celiac disease and potential non-celiac gluten sensitivity (NCGS).
Re Testing Strategy:
During a gluten challenge, serological markers (anti-tTG IgA) should be re-checked every 3-6 months
Histological assessment via repeat biopsy may be performed if serological markers do not change or if symptoms are ambiguous, especially if the initial diagnosis was made without biopsy
Endoscopic procedures should be performed cautiously in symptomatic children during the challenge phase.
Interpretation Of Results:
A positive gluten challenge is indicated by the reappearance of symptoms, a significant rise in anti-tTG IgA levels, or the development of histological changes (villous atrophy) in the small intestine after gluten reintroduction
Negative results do not definitively rule out CD if the challenge was insufficient in duration or gluten load.
Management
Initial Management:
The cornerstone of management for diagnosed celiac disease is a lifelong, strict gluten-free diet
Nutritional support is essential, addressing any deficiencies identified during the diagnostic workup
Patients should receive comprehensive education on GFD from a dietitian.
Medical Management:
A strictly GFD is the primary medical management
Regular follow-up with a dietitian and gastroenterologist is necessary
Monitoring of nutritional status, antibody levels, and bone health is vital
Pharmacological interventions are not a substitute for GFD and are reserved for complications.
Supportive Care:
Psychosocial support is important for children and families adapting to a GFD
Nutritional counseling should focus on ensuring adequate intake of micronutrients and fiber while avoiding gluten
Education on reading food labels and identifying hidden gluten is crucial
Support groups can provide valuable resources.
Complications
Early Complications:
Refractory celiac disease (unresponsive to GFD), rapid onset malabsorption, dehydration, and electrolyte imbalances can occur shortly after diagnosis or dietary indiscretion
Increased risk of infections is also a concern due to compromised immune function.
Late Complications:
Long-term complications include osteoporosis/osteopenia, infertility, increased risk of lymphomas (especially enteropathy-associated T-cell lymphoma), other autoimmune diseases (Type 1 diabetes, autoimmune thyroiditis), neurological complications (ataxia, neuropathy), and severe malnutrition.
Prevention Strategies:
Strict adherence to a GFD is the most effective prevention strategy
Regular clinical and serological monitoring, nutritional assessment, and bone health evaluation help detect and manage potential complications early
Prompt diagnosis and treatment are key to preventing long-term sequelae.
Prognosis
Factors Affecting Prognosis:
Prognosis is generally excellent with strict adherence to a GFD
Factors negatively impacting prognosis include delayed diagnosis, non-adherence to GFD, development of complications (especially refractory celiac disease or malignancy), and co-existing autoimmune conditions.
Outcomes:
With proper management, children with celiac disease can achieve normal growth and development, resolve symptoms, and have a normal life expectancy
Serological markers typically normalize within 6-12 months of initiating a GFD
Histological recovery may take longer.
Follow Up:
Lifelong follow-up is recommended
This includes regular clinical assessments, serological testing (anti-tTG IgA) to monitor GFD adherence and disease activity, nutritional status evaluation, and assessment for bone mineral density, especially in adolescents and adults
Repeat biopsy may be considered if serological markers remain elevated or symptoms persist.
Key Points
Exam Focus:
Understand the diagnostic pathway for celiac disease, including the role of serology and biopsy
Recognize the indications and protocol for a gluten challenge, and the interpretation of results
DNB/NEET SS often tests management of refractory CD and long-term complications.
Clinical Pearls:
Always check total IgA levels when ordering IgA antibodies to rule out IgA deficiency
A gluten-free diet should NOT be initiated before appropriate diagnostic testing (serology and/or biopsy) is completed, unless there are contraindications to biopsy
The gluten challenge requires careful monitoring and patient/family adherence.
Common Mistakes:
Diagnosing celiac disease solely on symptoms without serological or histological confirmation
Starting a GFD before diagnosis, thereby rendering serological and biopsy results unreliable
Underestimating the importance of strict lifelong GFD adherence and regular follow-up
Failing to consider extra-intestinal manifestations.