LETTERS TO EDITOR
Serum prevalence of celiac disease in children and adolescents with type 1 diabetes mellitus
Dear Editor,
We would like to make some comments about the article entitled "Serum prevalence of celiac disease in children and adolescents with type 1 diabetes mellitus."1
In most diabetic patients, celiac disease (CD) is insidious and asymptomatic; therefore, serological screening for CD is crucial for an early diagnosis and introduction of appropriate treatment.2 In a cross-sectional study, Araújo et al.1 found a prevalence of 10.5% for CD among children and adolescents with type 1 diabetes mellitus (DM-1) using the anti-tissue transglutaminase (anti-tTG) antibody assay, recommended as the test of choice for the initial screening of CD in diabetic patients.3
Serological tests for the detection of anti-tTG and anti-endomysial antibodies should be reserved for IgA isotypes; therefore, it is necessary to identify patients with IgA deficiency (IgAD) beforehand in order to rule out false-negative results.
Of 361 diabetic patients selected by Araújo et al.1, seven (1.9%) had IgAD.
In a previous study carried out at Hospital de Clínicas of Universidade Federal do Paraná Brazil, eight out of 149 diabetic children and adolescents screened for CD had IgAD (IgA < 5 mg/dL), which corresponds to a prevalence of 5.3%. Serum IgA levels were measured by the enzyme-linked immunosorbent assay (ELISA), standardized to determine serum IgA titers below the radial immunodiffusion sensitivity level in the low-concentration plate and turbidimetry. In this same group of diabetic patients, the diagnosis of CD was confirmed in 8.7% (13/149) by anti-endomysial antibody testing and intestinal biopsy.4
Liblau et al.5 reported that one out of 261 diabetic patients in France had IgAD, a higher prevalence rate than that for the normal French population, which corresponds to 1:1,400. In Italy, IgAD was detected in seven of 191 diabetic patients, i.e., a prevalence of 1:27, higher than that for the normal Italian pediatric population (1:500).6
The prevalence of CD in DM-1 patients, recently assessed by anti-endomysial antibody testing and intestinal biopsy in the state of São Paulo, Brazil, amounted to 4.8%, comparable to the prevalence rate described in U.S. and European studies.7
Tanure et al. found a prevalence of 2.6% for CD in diabetic patients from the Brazilian state of Minas Gerais.8 The patients were identified based on the positive results for antigliadin antibodies (AGA), anti-endomysial antibodies and intestinal biopsy.7 However, only diabetic patients with positive IgG-AGA and negative IgA-AGA results had their IgA level measured by nephelometry. The 12 patients who were positive only for IgG-AGA had normal serum IgA levels.
We agree that multicenter studies should be conducted in Brazil on the association of CD and DM-1 and that diabetics should be screened for CD on a routine basis. However, due to the higher prevalence of IgAD among diabetic patients, the serum IgA level should be determined before the serological tests for the detection of anti-tTG and anti-endomysial antibodies of the IgA isotype class for the screening of CD. This eliminates false-negative results, by the use of criteria established for IgAD, and by more sensitive methods for IgA measurement, such as ELISA (Table 1).
References
1. Araújo J, Silva GA, Melo FM. Serum prevalence of celiac disease in children and adolescents with type 1 diabetes mellitus. J Pediatr (Rio J). 2006;82:210-14.
2. Mahmud FH, Murray JA, Kudva YC, Zinsmeister AR, Dierkhising RA, Lahr BD, et al. Celiac disease in type 1 diabetes mellitus in a North American community: prevalence, serologic screening and clinical features. Mayo Clin Proc. 2005;80:1429-34.
3. Hill ID, Dirks MH, Liptak GS, Colleti RB, Fasano A, Guandalini S, et al. Guidelines 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;40:1-19.
4. Landgraf LF. Prevalência de deficiência de Imunoglobulina "A" em pacientes com diabetes mellitus tipo 1 e sorologia positiva para doença celíaca [dissertação]. Curitiba (PR): Universidade Federal do Paraná; 1999.
5. Liblau RS., Caillat-Zucman S, Fischer AM, Bach JF, Boitard C. The prevalence of selective IgA deficiency in type 1 diabetes mellitus. APMIS. 1992;100:9-12.
6. Cerutti F, Urbino A, Sacchetti C, Palomba E, Zoppo M, Tovo PA. Selective IgA deficiency in juvenile-onset insulin-dependent diabetes mellitus. Pediatr Med Chir. 1998;10:197-201.
7. Baptista ML, Koda YK, Mitsunori R, Nisihara N, Ioshi SO. Prevalence of celiac disease in Brazilian children and adolescents with type 1 diabetes mellitus. J Pediatr Gastroenterol Nutr. 2005;41:621-4.
8. Tanure MG, Silva IN, Bahia M, Penna FJ. Prevalence of celiac disease in Brazilian children with type 1 diabetes mellitus. J Pediatr Gastroenterol Nutr. 2006;42:155-9.
Nelson Rosário
Professor titular, Universidade Federal do Paraná (UFPR), Curitiba, PR
Loraine Farias Landgraf
Pediatra. Mestre em Pediatria, Universidade Federal do Paraná (UFPR), Curitiba, PR. Especialista em Alergia e Imunologia
Authors' reply
To the Editor,
It was with great interest that we read the letter to the editor of Jornal de Pediatria sent by Dr. Loraine Farias Landgraf and Dr. Nelson Rosário, from the Department of Pediatrics of Universidade Federal do Paraná Brazil, regarding the article "Serum prevalence of celiac disease in children and adolescents with type 1 diabetes mellitus."1
The comments made by our colleagues are extremely relevant and confirm the findings of our study by pointing out the necessity to measure serum IgA in type 1 diabetes mellitus (DM-1) patients under investigation for celiac disease (CD). This is due to the fact that serological screening using tissue anti-transglutaminase and anti-endomysial antibodies is not appropriate for patients with IgA deficiency.
This is an important concern in population-based studies (of seroprevalence) and in clinical trials, in order to guarantee that the prevalence of CD is not underestimated and that patients with false-negative serological results are further investigated.
In the table where the four Brazilian studies are cited, we observed that the results regarding the frequency of IgA deficiency and of CD among DM-1 patients are similar, since numerical differences are likely to result from methodological factors rather than from actual differences in frequency itself.
We reinforce the final recommendations made by our colleagues: multicenter studies should be conducted in Brazil on the association of CD and DM-1 and diabetics should be screened for CD on a routine basis.
Reference
1. Araújo J, Silva GA, Melo FM. Serum prevalence of celiac disease in children and adolescents with type 1 diabetes mellitus. J Pediatr (Rio J). 2006;82:210-14.
3. Hill ID, Dirks MH, Liptak GS, Colleti RB, Fasano A, Guandalini S, et al. Guidelines 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;40:1-19.
Publication Dates
-
Publication in this collection
23 Feb 2007 -
Date of issue
Oct 2006
