Overview
Definition:
Celiac disease (CD) is a chronic autoimmune disorder triggered by gluten ingestion in genetically susceptible individuals, leading to small intestinal villous atrophy and malabsorption
however, a subset of patients may present with negative celiac-specific serology despite clinical suspicion, necessitating further diagnostic considerations
Total IgA deficiency is the most common primary immunodeficiency and can lead to false-negative results for IgA-based celiac serological assays.
Epidemiology:
The prevalence of celiac disease is estimated to be around 1% worldwide, but it is significantly underdiagnosed
In individuals with IgA deficiency (estimated at 1 in 400 to 1 in 2000 in Western populations), the prevalence of celiac disease is higher than in the general population, estimated between 2-5% or even higher in some studies
This makes IgA deficiency a critical consideration in children with suspected celiac disease who have negative IgA-based serology.
Clinical Significance:
Accurate diagnosis of celiac disease is crucial for preventing long-term complications such as growth failure, nutrient deficiencies, osteoporosis, infertility, and increased risk of certain malignancies (e.g., enteropathy-associated T-cell lymphoma)
Failure to diagnose celiac disease, especially in the presence of IgA deficiency where standard serology can be misleading, leads to continued intestinal damage and associated morbidities
Understanding this diagnostic challenge is vital for pediatricians and residents preparing for DNB and NEET SS examinations.
Clinical Presentation
Symptoms:
Typical symptoms include chronic diarrhea
Abdominal pain and bloating
Failure to thrive or growth retardation
Anemia (iron deficiency)
Irritability or behavioral changes
Constipation (less common)
Vomiting
Weight loss
Dermatitis herpetiformis (rare in children).
Signs:
Abdominal distension
Decreased muscle tone
Pallor
Peripheral edema (due to hypoproteinemia)
Signs of micronutrient deficiencies (e.g., rickets, glossitis).
Diagnostic Criteria:
The ESPGHAN guidelines (2012 and updated 2020) recommend a stepwise approach
Initially, IgA anti-tissue transglutaminase (tTG) and IgA anti-endomysial antibodies (EMA) are tested
In suspected cases with negative IgA-based serology, particularly in those with suspected IgA deficiency, total serum IgA levels must be assessed
If total IgA is low or deficient, testing for IgG-based antibodies (e.g., IgG tTG, IgG EMA) is indicated
A positive result, coupled with a compatible clinical presentation and characteristic small intestinal biopsy showing villous atrophy, crypt hyperplasia, and increased intraepithelial lymphocytes, confirms the diagnosis, although biopsy may be omitted in specific high-serological-positivity scenarios (not applicable when serology is negative)
Genetic testing for HLA-DQ2/DQ8 is supportive but not diagnostic.
Diagnostic Approach
History Taking:
Detailed dietary history, focusing on gluten intake
Onset and duration of symptoms
Family history of celiac disease or autoimmune disorders
History of recurrent infections or allergies suggestive of immunodeficiency
Previous investigations and treatments
Symptoms of malabsorption and nutritional deficiencies.
Physical Examination:
Assess growth parameters (height, weight, BMI) using WHO growth charts
Evaluate for abdominal distension or tenderness
Examine skin for any rashes, especially dermatitis herpetiformis
Assess for signs of anemia, dehydration, and nutritional deficiencies
Palpate for hepatosplenomegaly.
Investigations:
1
**Serum IgA levels:** Essential to identify total IgA deficiency
2
**Celiac serology:** If total IgA is normal: IgA anti-tTG, IgA EMA
If total IgA is low/deficient: IgG anti-tTG, IgG EMA, potentially IgG DGP (deamidated gliadin peptides)
3
**Complete blood count (CBC):** To detect anemia (microcytic, normocytic)
4
**Iron studies:** Ferritin, serum iron, TIBC
5
**Vitamin and mineral levels:** Vitamin D, B12, folate, zinc, calcium
6
**Liver function tests (LFTs):** To assess for associated liver involvement
7
**Stool studies:** To rule out other causes of diarrhea (e.g., parasitic infections)
8
**Small intestinal biopsy:** Gold standard, obtained during upper endoscopy, showing villous atrophy, crypt hyperplasia, and increased intraepithelial lymphocytes
Biopsy is crucial when serology is negative or equivocal, especially in IgA-deficient individuals
9
**HLA-DQ2/DQ8 genotyping:** Can help rule out celiac disease if negative, but positive results are not diagnostic.
Differential Diagnosis:
Other causes of malabsorption: **Lactose intolerance:** Symptoms often acute after dairy intake
**Inflammatory bowel disease (IBD):** Crohn's disease or ulcerative colitis
typically involves terminal ileum/colon, may have blood in stool
**Infectious enteritis:** Acute diarrhea, often self-limiting
**Food protein-induced enteropathy:** Common in infancy, may involve other proteins
**Autoimmune enteropathy:** Rare, severe malabsorption without gluten trigger
**Lymphangiectasia:** Dilated lymphatic vessels in the mucosa
**Giardiasis:** Parasitic infection causing malabsorption
**Dumping syndrome:** Post-gastric surgery
**Short bowel syndrome:** Post-surgical resection.
Management
Initial Management:
Strict, lifelong gluten-free diet (GFD) is the cornerstone of management
Dietary counseling by a registered dietitian is essential
Supplementation of identified nutrient deficiencies (iron, vitamins, minerals)
Hydration and electrolyte balance if significant diarrhea or vomiting.
Medical Management:
The primary "medical" management is the gluten-free diet
No pharmacological therapy has been proven effective for reversing intestinal damage caused by gluten in diagnosed celiac disease
However, managing associated conditions like anemia or osteoporosis with appropriate supplements is critical
Monitoring for adherence to the GFD and symptom resolution is ongoing.
Surgical Management:
Surgical intervention is rarely indicated for celiac disease itself
It may be considered for complications such as small bowel obstruction due to adhesions (rare) or rarely for refractory celiac disease with complications like malignancy (enteropathy-associated T-cell lymphoma, EATL) where tumor resection might be necessary
The primary focus remains non-surgical management.
Supportive Care:
Nutritional support: Ensuring adequate caloric intake and micronutrient replacement is paramount
Regular monitoring of growth and development in children
Psychosocial support for the child and family to manage the challenges of a lifelong dietary restriction
Education on safe food preparation and cross-contamination prevention.
Complications
Early Complications:
Severe malabsorption with dehydration and electrolyte imbalances
Refractory celiac disease (rare, defined as persistent symptoms and villous atrophy despite strict GFD, often due to incorrect diagnosis or adherence issues).
Late Complications:
Nutritional deficiencies: Iron deficiency anemia, vitamin deficiencies (D, B12, folate), mineral deficiencies (calcium, magnesium, zinc)
Osteopenia/osteoporosis
Infertility and recurrent miscarriages
Increased risk of other autoimmune diseases (e.g., Type 1 diabetes, autoimmune thyroiditis)
Neurological manifestations (ataxia, neuropathy)
Dermatitis herpetiformis
Increased risk of certain malignancies: Enteropathy-associated T-cell lymphoma (EATL), non-Hodgkin lymphoma, esophageal cancer, small bowel adenocarcinoma.
Prevention Strategies:
Early diagnosis and strict adherence to a lifelong gluten-free diet are the most effective strategies for preventing complications
Regular follow-up appointments with a gastroenterologist and dietitian
Monitoring for nutritional deficiencies and bone health
Screening for associated autoimmune conditions.
Prognosis
Factors Affecting Prognosis:
Timeliness of diagnosis
Strict adherence to the gluten-free diet
Presence and severity of complications at diagnosis
Age at diagnosis (earlier diagnosis generally leads to better outcomes)
Presence of other autoimmune diseases or immunodeficiencies.
Outcomes:
With strict adherence to a gluten-free diet, most children with celiac disease experience significant symptom improvement, catch-up growth, and resolution of intestinal inflammation
Long-term prognosis is generally good, with a reduced risk of complications compared to untreated disease
However, the lifelong need for dietary vigilance remains.
Follow Up:
Regular follow-up every 6-12 months with a pediatrician and/or gastroenterologist and a dietitian is recommended
This includes monitoring for symptoms, growth, adherence to the GFD, and nutritional status
Periodic serological testing may be done to monitor GFD adherence (though less reliable in IgA deficient individuals)
Bone density scans may be indicated in older children or those with prolonged malabsorption
Screening for associated autoimmune conditions should be considered.
Key Points
Exam Focus:
The key focus for DNB/NEET SS is recognizing celiac disease presentation in children, understanding the diagnostic pathway, and critically, the implication of IgA deficiency leading to false-negative serology
Remember to check total IgA if initial serology is negative and clinical suspicion is high
Biopsy remains the gold standard in this scenario
The management is strictly a gluten-free diet.
Clinical Pearls:
Always consider IgA deficiency in a child with features of celiac disease but negative IgA tTG/EMA
Measuring total IgA is a simple, crucial step
Even if serology is negative, a biopsy is essential for confirmation in cases of suspected IgA deficiency
Educate families thoroughly on gluten-free living
it is a lifelong commitment.
Common Mistakes:
Attributing all gastrointestinal symptoms in a child with low IgA to the IgA deficiency itself without ruling out celiac disease
Relying solely on serology without considering total IgA levels or biopsy when indicated
Inadequate dietary counseling or follow-up, leading to poor adherence and persistent symptoms or complications.