Overview

Definition:
-Celiac disease is a chronic, autoimmune disorder triggered by the ingestion of gluten in genetically susceptible individuals
-It leads to inflammation and damage of the small intestinal mucosa, resulting in malabsorption and a wide spectrum of clinical manifestations.
Epidemiology:
-The prevalence of celiac disease in India is estimated to be between 0.5% and 1%
-It can affect individuals of any age, but diagnosis is most common in childhood and early adulthood
-Genetic predisposition (HLA-DQ2 and HLA-DQ8 genes) is a prerequisite.
Clinical Significance: Accurate and timely diagnosis of celiac disease is crucial in pediatrics to prevent long-term complications such as growth failure, nutritional deficiencies, osteoporosis, infertility, and increased risk of certain malignancies (e.g., enteropathy-associated T-cell lymphoma).

Clinical Presentation

Symptoms:
-Classic presentation includes diarrhea
-Steatorrhea
-Abdominal pain and bloating
-Weight loss or failure to thrive
-Irritability or behavioral changes
-Associated symptoms may include anemia (iron deficiency unresponsive to oral iron)
-Constipation can also occur, especially in younger children
-Dermatitis herpetiformis is rare in children.
Signs:
-Physical examination may reveal poor growth, abdominal distension, and signs of malabsorption such as pallor, muscle wasting, and edema
-In infants, delayed puberty and short stature are common
-Neurological symptoms like ataxia or peripheral neuropathy can be seen in some cases.
Diagnostic Criteria:
-Current guidelines recommend a stepwise diagnostic approach
-For individuals with symptoms and positive specific antibodies, a biopsy may be considered if gluten-free diet (GFD) has not been initiated
-If specific antibodies are highly positive, a biopsy might be omitted in certain high-prevalence populations according to some guidelines, but confirmation with biopsy is still preferred in many cases for definitive diagnosis and to assess severity.

Diagnostic Approach

History Taking:
-Detailed dietary history is essential, focusing on gluten intake
-Inquire about gastrointestinal symptoms, growth concerns, family history of celiac disease or autoimmune disorders, and presence of other autoimmune conditions
-Red flags include persistent diarrhea, failure to thrive, unexplained iron deficiency anemia, and recurrent abdominal pain.
Physical Examination:
-Assess growth parameters (height, weight, BMI) using age-appropriate growth charts
-Perform a thorough abdominal examination for distension, tenderness, or organomegaly
-Evaluate for signs of nutritional deficiencies (pallor, edema, skin changes).
Investigations:
-Initial screening involves serological tests: tissue transglutaminase IgA (TTG-IgA) is the primary test
-it has high sensitivity and specificity
-If IgA deficiency is suspected or confirmed, endomysial IgA (EMA-IgA) or deamidated gliadin peptide IgG (DGP-IgG) antibodies should be tested
-Positive serology in a patient consuming gluten strongly suggests celiac disease
-Further confirmation typically requires small intestinal biopsy (duodenal biopsy) showing villous atrophy, crypt hyperplasia, and increased intraepithelial lymphocytes (IELs)
-HLA-DQ2/DQ8 typing can be useful to exclude celiac disease if negative, but is not diagnostic if positive.
Differential Diagnosis: Other causes of diarrhea and malabsorption in children include: lactose intolerance, cow's milk protein allergy, food protein-induced enterocolitis syndrome (FPIES), giardiasis, inflammatory bowel disease, cystic fibrosis, and short bowel syndrome.

Serologies And Biopsy Indications

Serological Markers:
-Tissue Transglutaminase IgA (TTG-IgA) is the most sensitive and specific serological marker
-Endomysial IgA (EMA-IgA) is highly specific but less sensitive
-Deamidated Gliadin Peptide IgG (DGP-IgG) is useful in young children (<2 years) or in cases of IgA deficiency
-Total IgA levels should be measured concurrently to rule out IgA deficiency, which can lead to false-negative TTG-IgA and EMA-IgA results.
When To Perform Biopsy:
-Biopsy is indicated to confirm diagnosis in patients with positive celiac serology (TTG-IgA >10 times the upper limit of normal may allow diagnosis without biopsy in select cases, according to ESPGHAN guidelines, but this approach is not universally adopted and biopsy is still preferred for definitive diagnosis)
-Biopsy is also crucial to assess the degree of villous atrophy and monitor response to treatment
-It is not recommended for asymptomatic individuals with low-titer positive antibodies or those already on a strict gluten-free diet.
Biopsy Interpretation:
-Histopathological findings include: villous atrophy (partial, subtotal, or total), crypt hyperplasia, and increased number of intraepithelial lymphocytes (IELs) (>20 per 100 enterocytes)
-Marsh classification is commonly used to grade the severity of changes.
Gluten-free Diet Before Biopsy:
-Patients should be consuming gluten regularly for at least two weeks before serological testing and biopsy to ensure accurate results
-Starting a gluten-free diet before testing can lead to false-negative results.

Management

Initial Management:
-The cornerstone of management is a strict, lifelong gluten-free diet (GFD)
-This involves eliminating all sources of wheat, barley, and rye from the diet
-Careful reading of food labels is essential.
Nutritional Support:
-Nutritional assessment and supplementation may be required to address deficiencies (iron, calcium, vitamin D, folate, B12)
-Lactose intolerance may be present due to damaged mucosa and can improve with GFD
-Monitoring growth is critical in pediatric patients.
Long Term Monitoring:
-Regular follow-up with a pediatric gastroenterologist and a registered dietitian is essential
-This includes monitoring for symptoms, growth, nutritional status, and periodically repeating serological markers to assess adherence to the GFD
-Follow-up duodenal biopsies may be considered to confirm mucosal healing, though this is not always mandatory if serological markers normalize and clinical improvement occurs.

Complications

Late Complications: Long-term complications of untreated or poorly managed celiac disease include: osteoporosis, infertility, neurological disorders (ataxia, neuropathy), anemia, malnutrition, and an increased risk of certain cancers, particularly small intestinal lymphoma and esophageal cancer.
Refractory Celiac Disease:
-A rare complication where symptoms persist despite a strict GFD
-It requires specialist management and may involve further investigations to rule out other causes or complications.
Prevention Strategies: The primary prevention strategy is early diagnosis and strict adherence to a gluten-free diet, which reverses the intestinal damage and prevents the development of long-term complications.

Key Points

Exam Focus:
-High-yield for DNB/NEET SS: Recognize classic and atypical presentations
-Understand the stepwise diagnostic algorithm
-Know the primary serological tests (TTG-IgA) and indications for biopsy
-Be aware of potential complications.
Clinical Pearls:
-Always consider celiac disease in a child with unexplained iron deficiency anemia unresponsive to oral iron
-Remember that constipation can be a presenting symptom in pediatric celiac disease, not just diarrhea
-Educate parents thoroughly on the importance of a strict gluten-free diet and label reading.
Common Mistakes:
-Starting a gluten-free diet before diagnosis or serological testing
-Relying solely on serology without considering biopsy in equivocal cases
-Underestimating the prevalence of celiac disease or its varied presentations
-Inadequate patient and family education regarding dietary adherence.