Introduction
Celiac disease (CD) is often diagnosed in childhood and the treatment is a lifelong gluten-free diet (GFD)1,2. It may take several years to gain competence in the skills required to follow a GFD successfully. Inadequately treated CD is associated with bone fractures, nutritional deficiencies and lymphoma3,4. Healthcare providers are key resources for patients with CD. Consultation with a dietitian with GFD expertise at diagnosis and annual disease-specific follow-up care is recommended2,5. The primary objective of this study was to evaluate adherence to guidelines for dietitian consultation and follow-up for children with CD. A secondary objective was to identify factors associated with loss to follow-up.
Methods
A retrospective cohort of 250 subjects (50/year) were randomly selected from an existing database of children (<18 years) diagnosed with biopsy-confirmed CD at Boston Children’s Hospital (BCH) between January 1st, 2010 and December 31st, 2014. Medical records were reviewed from diagnosis through December 31st, 2017 to allow a minimum three year observation period. Children who did not have a GI visit for >18 months were considered lost to follow-up. Cox Proportional-Hazards modelling was used for multivariate analysis. The BCH Institutional Review Board approved the study.
Results
Of 250 patients selected, 9 were excluded because they were seen for a second opinion, yielding 241 eligible subjects (63% female). Median age at diagnosis was 9.7 years (IQR 6.2– 13.3). Abdominal pain (24%) and constipation (14%) were common at diagnosis; only 2% were asymptomatic. Of 237 subjects with primary insurance information, 20 (8%) had Medicaid.
Most subjects (83%) consulted a dietitian with 31% attending both a dietitian-led class and an individual visit. One-quarter of children were lost to follow-up within a year of diagnosis and twenty-two (9%) had no GI visits after their diagnostic biopsy (Table 1). Having a sibling with CD (HR 1.90), using Medicaid (HR 2.19), and rescheduling or not attending >50% of appointments (HR 2.43) were associated with loss to follow-up. Children lost to follow-up within the first year were older at diagnosis than those who adhered to follow-up for longer (median 11.4 vs 8.7 years; P=0.01). Similarly, subjects who reached age 18 who continued to follow-up were diagnosed at a younger age than those who did not (median 14.4 vs. 16.2 years, P<0.01).
Table 1:
Adherence to gastroenterology follow-up visits and serum TTG IgA levels
| Category | At Last Gastroenterology Follow-up Visit |
|||
|---|---|---|---|---|
| N (%) | Median time since diagnosis Months [IQR] | TTG IgA N (%) | TTG elevated N (%) | |
| Entire Cohort | 241 (100%) | 141 (59%) | (25%) | |
| 1) Lost to gastroenterology follow-up after diagnosis | 22 (9%) | N/A | N/A | N/A |
| a) Did not attend GFD education visit with a dietitian | 8 (3%) | -- | -- | -- |
| b) Attended GFD education visit with a dietitian | 14 (6%) | -- | -- | -- |
| 2) Lost within the first year, attended at least one follow-up gastroenterology visit | 37 (16%) | 5.7 [3.2 – 7.6] | 23 (62%) | 9 (40%) |
| 3) Lost after one year, attended ≥ 1 follow-up gastroenterology visit > 12 months after diagnosis | 61 (25%) | 26.3 [19.6 – 42.4] | 44(72%) | 16 (36%) |
| 4) Still attending follow-up gastroenterology visits | 104 (43%) | |||
| a) Non-adherent to recommended schedule | 55 (23%) | 57.6 [46.3 – 70.0] | 35 (64%) | 4 (7%) |
| b) Adherent to recommended schedule | 49 (20%) | 45.3 [36.4 – 58.7] | 32 (65%) | 3(6%) |
| 5) Attended gastroenterology visit after age 18, then lost | 17 (7%) | 27.8 [19.8 – 45.3] | 12 (71%) | 3 (25%) |
GFD – gluten-free diet; IQR – interquartile range; TTG IgA – serum tissue transglutaminase IgA
Overall, 73% visited another department at BCH during the observation period with 47% of those who were lost to GI follow-up maintaining a care relationship at BCH >12 months after their last GI visit.
Median time to TTG IgA normalization was 17.0 months (IQR 7.0–32.0; N = 155). Of 141 subjects who had recommended serology at last GI follow-up, 25% had an elevated TTG IgA. Eighteen subjects had celiac serology ordered by non-GI providers after loss to GI follow-up. Seven (39%) had abnormal serology a median of 43.6 months (IQR 38.6–72.3) after diagnosis and 13.9 months (IQR 12.5–21.5) after last GI visit.
Discussion
High rates of loss to specialist follow-up indicate significant shortcomings in the management of children with CD. Although guidelines recommended dietitian education regarding a GFD and annual GI follow-up visits2,5, many may not be receiving appropriate treatment as 1 in 6 patients did not receive GFD education and 9% had no GI follow-up after diagnosis. It cannot be assumed that patients lost to GI follow-up are doing well nor that they receive disease specific follow-up in primary care.
Follow-up throughout childhood and adolescence is important both to monitor for complications of CD and a GFD, and to provide developmentally appropriate guidance and education6. The association of reliance on Medicaid with loss to follow-up suggests that socioeconomic disparities may further compromise the health outcomes of children with CD beyond decreased resources to obtain gluten-free foods. Children with CD in low income families constitute a high-risk group, and further attention is needed to determine how to best support these particularly vulnerable children.
Rapid loss to follow-up, often before patients may be considered to have mastered the skills necessary to follow a GFD, is concerning. Children who are inadequately adherent to a GFD are subject to gluten exposure and persistent mucosal damage, which is associated with complications of CD. Establishing a pattern of regular GI follow-up for CD during childhood may establish the habit of continuous, lifelong follow-up and improve long-term outcomes7. Further studies are needed to understand why having a sibling with CD is a risk for loss to follow-up and to determine the extent to which loss to follow-up occurs across the lifespan. Educational interventions directed to patients, families and providers regarding the importance of continuity of follow-up care for patients with CD are needed to ensure the best long-term outcome for those with CD.
Acknowledgments
Grant support: JAS is supported by NIH T32 DK 07760.
Abbreviations
- BCH
Boston Children’s Hospital
- CD
Celiac disease
- GFD
Gluten-free diet
Footnotes
Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
Potential competing interests:
JAS has received consulting fees from Takeda Pharmaceuticals Inc, and research support from Biomedal SL and Glutenostics LLC.
References
- 1.Singh P, Arora A, Strand TA, et al. Global Prevalence of Celiac Disease: Systematic Review and Meta-analysis. Clin Gastroenterol Hepatol 2018;16(6):823–836.e2. doi: 10.1016/j.cgh.2017.06.037. [DOI] [PubMed] [Google Scholar]
- 2.Hill ID, Dirks MH, Liptak GS, et al. Guideline for the diagnosis and treatment of celiac disease in children: recommendations of the North American Society for Pediatric Gastroenterology, Hepatology and Nutrition. J Pediatr Gastroenterol Nutr 2005;40(1):1–19. http://www.ncbi.nlm.nih.gov/pubmed/15625418. [DOI] [PubMed] [Google Scholar]
- 3.Lebwohl B, Granath F, Ekbom A, et al. Mucosal healing and risk for lymphoproliferative malignancy in celiac disease: a population-based cohort study. Ann Intern Med 2013;159(3):169–175. doi: 10.7326/0003-4819-159-3-201308060-00006. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 4.Lebwohl B, Michaëlsson K, Green PHR, et al. Persistent mucosal damage and risk of fracture in celiac disease. J Clin Endocrinol Metab 2014;99(2):609–616. doi: 10.1210/jc.2013-3164. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 5.Rubio-Tapia A, Hill ID, Kelly CP, et al. ACG clinical guidelines: diagnosis and management of celiac disease. Am J Gastroenterol 2013;108(5):656–76; quiz 677. doi: 10.1038/ajg.2013.79. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 6.Fishman LN, Kearney J, DeGroote M, et al. Creation of Experience-based Celiac Benchmarks: The First Step in Pretransition Self-management Assessment. J Pediatr Gastroenterol Nutr 2018;67(1):e6–e10. doi: 10.1097/MPG.0000000000001908. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 7.Barnea L, Mozer-Glassberg Y, Hojsak I, et al. Pediatric celiac disease patients who are lost to follow-up have a poorly controlled disease. Digestion 2014;90(4):248–253. doi: 10.1159/000368395. [DOI] [PubMed] [Google Scholar]