Diagnostic Delay of Celiac Disease in Childhood: A Comprehensive Study

Celiac.com 06/26/2024 - Celiac disease is an immune-mediated, gluten-sensitive enteropathy that can have severe health implications if left undiagnosed. Despite its prevalence, especially among White populations where it affects close to 1% of people, many patients remain undiagnosed. Diagnosis in childhood can be particularly challenging due to the wide range of clinical presentations, from asymptomatic cases to severe gastrointestinal and systemic symptoms. This study aims to investigate the diagnostic delay of celiac disease in children, identify factors associated with these delays, and understand the implications for clinical practice.

Study Design and Methods

This was a multicenter, retrospective, cross-sectional study conducted across 13 pediatric tertiary referral centers in Italy. The study period spanned from 2010 to 2019, and data analysis was conducted from January to June 2023. The study was designed to include children aged 0 to 18 years who had a confirmed diagnosis of celiac disease based on the 2012 European Society for Paediatric Gastroenterology Hepatology and Nutrition (ESPGHAN) guidelines.

Participants and Data Collection

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A total of 3,171 pediatric patients with celiac disease were included in the study. The mean age of the patients was 6.2 years, with a higher prevalence of females (63.4%). The inclusion criteria required a confirmed diagnosis of celiac disease and the availability of relevant clinical data, including diagnostic delays. Exclusion criteria included uncertain histological findings, non-compatible HLA typing, incomplete data, and diagnoses made during the COVID-19 pandemic due to its impact on healthcare access.

Measures and Analysis

The primary measure was the overall diagnostic delay, defined as the time from the first indicative symptoms to the definitive diagnosis. This delay was further divided into pre-consultation delay (time from symptom onset to first medical consultation) and post-consultation delay (time from first consultation to diagnosis). Extreme diagnostic delay was defined as a delay 1.5 times the 75th percentile. Univariable and multivariable regression analyses were conducted to identify factors associated with diagnostic delays and misdiagnosis.

Results - Diagnostic Delays

The median overall diagnostic delay was 5 months, with a median pre-consultation delay of 2 months and a post-consultation delay of 1 month. Extreme diagnostic delays were observed in 18.5% of cases, with median delays of 11 months overall, 6 months pre-consultation, and 3 months post-consultation. Children diagnosed before the age of 3 years had shorter diagnostic delays compared to older children, with median delays of 4 months overall and 1 month post-consultation. Males also experienced shorter diagnostic delays than females.

Factors Associated with Delays

Several factors were identified as being associated with longer diagnostic delays. These included the presence of neurological symptoms, gastroesophageal reflux, and failure to thrive. Conversely, a family history of celiac disease and younger age at diagnosis were associated with shorter delays. The study also found that misdiagnoses, such as constipation, iron deficiency anemia, and gastroesophageal reflux disease, were common before the definitive diagnosis of celiac disease.

Clinical Implications

The findings suggest that while the overall diagnostic delay for pediatric celiac disease is relatively short, certain clinical features can contribute to prolonged delays. Younger children and those with a family history of the disease are more likely to be diagnosed promptly. However, nonspecific symptoms and initial misdiagnoses can significantly extend the time to diagnosis, potentially leading to more severe disease progression and complications.

Comparison with Previous Studies

This study provides a comprehensive overview of diagnostic delays in pediatric celiac disease within a large, well-characterized cohort. Compared to previous studies, the diagnostic delay in this cohort was shorter, likely due to the implementation of the biopsy-sparing ESPGHAN guidelines and increased awareness of the disease. The distinction between pre-consultation and post-consultation delays offers valuable insights into the different stages of the diagnostic process.

Clinical Significance

The study highlights the importance of timely diagnosis in improving patient outcomes. The findings underscore the need for heightened awareness and consideration of celiac disease in children presenting with a wide range of symptoms, particularly those with neurological issues, gastroesophageal reflux, or failure to thrive. The lower diagnostic delay in children with a family history of the disease emphasizes the benefits of targeted screening in high-risk populations.

Limitations and Future Research

The study's retrospective design and reliance on clinical records may introduce biases, and the exclusion of data from the COVID-19 period might limit the generalizability of the findings. Additionally, the study was conducted in Italy, where healthcare access is universally provided, which may not be applicable to other settings with different healthcare systems.

Future research should focus on identifying strategies to reduce diagnostic delays further and investigating the impact of different healthcare models on the timeliness of diagnosis. Exploring the role of emerging diagnostic tools and guidelines in various populations could also provide valuable insights into improving the early detection and management of celiac disease in children.

Conclusion

This study offers a detailed analysis of diagnostic delays in pediatric celiac disease, highlighting the relatively short delays overall but also identifying specific factors that contribute to longer delays. The findings emphasize the need for increased vigilance and targeted screening to ensure timely diagnosis and treatment, ultimately improving outcomes for children with celiac disease.

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