From the Guidelines
Patients with IgA deficiency experiencing gastrointestinal symptoms should be evaluated for seronegative celiac disease, as it is a common etiology of seronegative enteropathy, and managed with a gluten-free diet if diagnosed, as recommended by the 2021 clinical practice update on the evaluation and management of seronegative enteropathies 1.
Key Considerations
- IgA deficiency can lead to compromised mucosal immunity, resulting in recurrent diarrhea, malabsorption, and increased susceptibility to intestinal infections.
- Management involves treating specific symptoms, such as diarrhea with loperamide 2mg after each loose stool (maximum 8mg daily), and bacterial overgrowth with rotating antibiotics like rifaximin 550mg three times daily for 7-14 days.
- Probiotics containing Lactobacillus and Bifidobacterium strains can support gut flora balance, and patients should maintain good hand hygiene to prevent infections.
- Regular monitoring by a gastroenterologist and immunologist is crucial, as these patients have higher rates of autoimmune disorders like inflammatory bowel disease.
Diagnostic Approach
- The definition of seronegative celiac disease is inconsistent, but it is characterized by the presence of villous atrophy and compatible HLA genetics, without IgA/IgG tTG and IgA/IgG DGP and IgA/IgG EMA antibodies, and a clinical and histologic response to the gluten-free diet 1.
- Duodenal biopsies should be performed in individuals of white European, Middle Eastern, North African, or North Indian origin who undergo upper endoscopy for anemia, weight loss, or diarrhea, irrespective of serology results for celiac disease 1.
- A combination of immunoassays, including IgG-DGP and IgA-TG2, offers the best sensitivity for detecting celiac disease in patients with IgA deficiency 1.
From the Research
IGA Deficiency and G.I. Symptoms
- IGA deficiency can cause false-negative results in serological tests for celiac disease, leading to underdiagnosis 2
- Studies have shown that patients with celiac disease and IGA deficiency often exhibit gastrointestinal symptoms, but the prevalence of these symptoms can vary 3
- In some cases, IGA deficiency can lead to decreased sensitivity of IgA-tissue-transglutaminase antibody (IgA-tTG) tests, making diagnosis more challenging 3
- Research has also shown that IGA deficiency can increase the risk of immune dysregulation and symptomatic disease, particularly in patients with fecal IGA deficiency 4
Association with Celiac Disease
- The association between IGA deficiency and celiac disease has been known for over 50 years, but diagnostic procedures for patients with both conditions are still not definitive 5
- HLA haplotypes, particularly those including HLA-DQB1∗02 allelic variants, have been linked to an increased risk of celiac disease and may play a role in the association between IGA deficiency and celiac disease 6
- Studies have reported varying prevalence rates of IGA deficiency in patients with celiac disease, highlighting the need for further research to understand the relationship between these two conditions 2, 3
Diagnostic Challenges
- The diagnosis of celiac disease in patients with IGA deficiency can be complicated by the lack of reliable serological tests and the need for intestinal biopsy or other diagnostic methods 2, 5
- The European Society for Pediatric Gastroenterology, Hepatology and Nutrition (ESPGHAN) guidelines provide criteria for diagnosing celiac disease in IGA-deficient patients, but some issues remain unresolved 5
- Further studies are needed to develop more effective diagnostic protocols and to improve our understanding of the relationship between IGA deficiency and celiac disease 5, 6