The term “associated conditions” refers to conditions that are found at an increased frequency in celiac disease but that are not thought to be due to gluten ingestion.
Dermatitis herpetiformis is a skin lesion associated with celiac disease characterized by the presence of symmetric papulovesicular lesions on the arms, legs, buttocks, truck, neck and scale. Histology reveals immunofluorescence with granular deposits of IgA. Dermatitis herpetiformis often responds to a gluten free diet.
One of the most intensely studied associations with celiac disease is the association with type 1 diabetes. Approximately 5–10% of patients with type 1 diabetes have positive TG antibodies, with up to 75% having abnormalities on small intestinal biopsy (26
). Celiac disease and type 1 diabetes share HLA risk genotypes. The highest risk HLA genotypes for type 1 diabetes DQ2 and DQ8 are found in 90% and 8–10% of people with celiac disease respectively. Therefore, the known association between the two disorders is likely largely related to shared genetic risk. Indeed, 33% of patients with type 1 diabetes homozygous for DQ2 are positive for TG autoantibodies (26
). In contrast, only 1% of subjects with type 1 diabetes with neither DQ2 nor DQ8 have celiac disease related antibodies (26
). Using a combination HLA genotyping and identification of a population (patients with type 1 diabetes), subgroups with very high and low risk for celiac disease can be identified.
Patients with type 1 diabetes and positive celiac disease related antibodies can be identified at onset of diabetes (54
). This implies that the two diseases may have developed concurrently or at least in a similar time frame. In some patients, the diagnosis of celiac disease may precede the diagnosis of type 1 diabetes. In a report analyzing the risk for type 1 diabetes in patients with celiac disease (n=9243) are at a 3.9 increased hazard for the development of diabetes by age 20 years (55
). Observations such as these have lead to hypotheses regarding a common environmental etiology for celiac disease and type 1 diabetes. Given that the environmental cause of celiac disease is known (gluten) it has been hypothesized that gluten may play an important role in the development of type 1 diabetes. Through prospective studies of high-risk infants for type 1 diabetes and celiac disease, it has been shown that early introduction (prior to 4 months of age) is associated with an increased risk for autoimmunity associated with both conditions (56
). In contrast, diabetes prevention trials using a gluten free diet have not shown any efficacy in delay of diabetes onset (59
). Therefore, the relationship between the two disorders is likely quite complex.
The clinical significance of celiac disease in the population with type 1 diabetes remains controversial (60
). Many of the patients are asymptomatic or mildly symptomatic when identified with celiac disease related autoantibodies and they represent the portion of the iceberg that is underneath the water (i.e. silent or latent celiac disease). However, abnormalities are found in a high proportion of small intestinal biopsies of patients with diabetes and positive celiac disease related antibodies indicating that a pathologic process is occurring which may present itself clinically during adulthood or carry with it risks for complications of celiac disease including gastrointestinal malignancy or osteoporosis. Often children do not realize they were symptomatic and report that they feel better upon institution of a gluten free diet. A comparison between children with type 1 diabetes and celiac disease and those with type 1 diabetes alone confirms a lower BMI in the group with celiac disease (61
) and increased proportion of symptoms (78% reporting at least one symptom compared with 13% of controls) (9
). Maintaining a gluten free diet is not a trivial matter, particularly in the setting of type 1 diabetes which has its own set of dietary restrictions, and patients who have not had an obvious symptomatic course for celiac disease may thus be less motiviated to adhere to this diet.
Therefore, significant debate in the literature exists regarding the significance of positive celiac disease-related antibodies in the population with type 1 diabetes and the importance of ongoing screening and treatment with a gluten free diet. Currently, the American Diabetes Association recommends screening for celiac disease related autoantibodies at diagnosis of diabetes and with signs or symptoms of celiac disease (62
). Our current practice is to screen at onset of diabetes and every 2 years thereafter.
Celiac disease also shares genetic risk factors with autoimmune thyroid disease. Patients with autoimmune thyroid disease are at an increased risk for celiac disease related antibodies. Patients with celiac disease are at an increased risk for autoimmune thyroid disease. In a series of 104 Dutch patients with Hashimoto’s thyroiditis, 8 (7.6%) were positive for TG autoantibodies and 5 (4.8%) had biopsies consistent with celiac disease. In this same report, researchers screened 184 patients with celiac disease and diagnosed hypothyroidism in 22 (12%) with 21% positive for antibodies associated with thyroid disease (28
). This some observations holds true for pediatrics, in a series of 90 children with autoimmune thyroid disease, 7 (7.8%) were diagnosed with celiac disease after identification of positive EMA and small intestinal biopsy (27
There are no current recommendations for screening for celiac disease in the setting of autoimmune thyroid disease, at the very least a complete review of systems should be elicited, growth and pubertal status should be monitored and any evidence for growth failure or symptoms of celiac disease should be addressed with screening for TG autoantibodies. In patients with celiac disease, it is relatively easy to screen for thyroid abnormalities and certainly should be done in the setting of poor growth, weight loss or other signs or symptoms of hypo- or hyperthyroidism.
Celiac disease has also been found at an increased rate in patients with both Turner syndrome and Down syndrome. Celiac disease related antibodies have been identified in between 4–6% of girls with Turner Syndrome, the diagnosis of celiac disease can be made as early as 4 years of age (30
). Recently published clinical practice guidelines for the care of girls with Turner syndrome recommend screening for celiac disease beginning at age 4 with measurement of TG autoantibodies. It is recommended to repeat this screening every 2–5 years indefinitely (64
). In Down Syndrome, celiac disease has been identified during childhood and at rates that are similar to those identified in Turner syndrome (7–16%) (31
). Many of these children are mildly or asymptomatic. Current practice guidelines recommend screening at 2–3 years of age with TG autoantibodies with repeat screening in adolescence (65