DISCUSSION 

Type 1 diabetes mellitus (T1DM) and celiac disease (CD) are autoimmune disorders that frequently coexist because of their shared genetic susceptibility, particularly HLA class II haplotypes such as DR3-DQ2 and DR4-DQ8. More than 90% of patients with CD carry the HLA-DQ2 haplotype, supporting the rationale for routine CD screening in children with T1DM. REF 6 In our patient, CD was detected through routine screening, consistent with current recommendations.

​

To evaluate the novelty of this case, we conducted a structured literature search using PubMed/MEDLINE with combinations of the terms "cystic fibrosis," "celiac disease," "coeliac disease," "type 1 diabetes," "type 1 diabetes mellitus," "insulin-dependent

diabetes," and "autoimmune diabetes." The search identified reports describing the coexistence of cystic fibrosis and celiac disease, including a Scandinavian cohort study in which one patient also had type 1 diabetes mellitus. 7 However, detailed pediatric case reports focusing on the diagnostic process and the impact of overlapping gastrointestinal manifestations remain exceptionally uncommon. Therefore, rather than representing the first documented coexistence of these three disorders, our case contributes additional educational value by illustrating how diagnostic anchoring may delay recognition of genetically confirmed cystic fibrosis in a child with established autoimmune disease.

​

The diagnosis of type 1 diabetes mellitus was established based on the patient's characteristic clinical presentation together with hyperglycemia, ketonuria, metabolic acidosis, and elevated HbA1c. Because this report is retrospective, complete historical documentation regarding diabetes-associated autoantibodies, C-peptide concentration, and additional biochemical parameters was unavailable. We acknowledge that inclusion of these data would have provided more comprehensive documentation of autoimmune diabetes and recognize this as a limitation of the present report.

​

The diagnosis of celiac disease was based on markedly elevated tTG-IgA levels in an IgA-sufficient child together with HLA susceptibility and evaluation by a pediatric gastroenterologist. Because this case was diagnosed before the current ESPGHAN recommendations were widely implemented in routine clinical practice at our institution, neither endomysial antibody (EMA-IgA) testing nor duodenal biopsy was performed. 8 We acknowledge that, according to current pediatric diagnostic guidelines, these data would further strengthen the diagnostic documentation and recognize their absence as a limitation of this retrospective case report.

​

Both diseases are characterized by dysregulated CD4⁺ T-cell–mediated immune responses directed against distinct target antigens. In genetically predisposed individuals, this immune dysregulation contributes to the development of multiple autoimmune disorders. The institution of a gluten-free diet is generally associated with improvements in intestinal inflammation and nutrient absorption. However, mucosal recovery and normalization of celiac serology vary considerably among individuals, and the effect on glycemic control in children with concomitant T1DM and CD is not uniform. Persistent elevation of tTG-IgA in patients receiving a gluten-free diet requires careful clinical reassessment. Potential explanations include ongoing gluten exposure, persistent active celiac disease, pancreatic exocrine insufficiency, gastrointestinal manifestations of cystic fibrosis, and other gastrointestinal disorders. In the present case, the coexistence of severe pancreatic exocrine insufficiency and subsequently confirmed cystic fibrosis likely contributed to the persistence of gastrointestinal symptoms. Because this is a retrospective case report, complete historical documentation regarding serial celiac serology, dietary reassessment, and evaluation of competing gastrointestinal diagnoses was unavailable. Consequently, the relative contribution of each potential mechanism cannot be determined with certainty.

​

Despite adherence to a gluten-free diet, our patient continued to experience persistent gastrointestinal symptoms, which were initially attributed to celiac disease. In retrospect, persistent gastrointestinal symptoms together with severe pancreatic exocrine insufficiency raised the possibility that cystic fibrosis had been present for several years before the diagnosis was established. Although the interval between the diagnoses of celiac disease and cystic fibrosis was approximately seven years, the retrospective nature of this report does not allow for a precise determination of when cystic fibrosis first became clinically recognizable. Nevertheless, overlapping gastrointestinal manifestations may have contributed to the delayed consideration of cystic fibrosis in the differential diagnosis. Several clinical factors may have contributed to the delayed recognition of cystic fibrosis. The patient did not experience recurrent severe respiratory infections during early childhood, and the sweat chloride concentration was within the intermediate range (42 mmol/L), necessitating CFTR genetic analysis to establish the diagnosis.

​

The overlap between CD and CF further complicated the diagnostic process in this patient. Both disorders may present with malabsorption, abdominal pain, bloating, nutritional deficiencies, and impaired growth. Consequently, persistent gastrointestinal complaints were initially attributed to CD rather than prompting evaluation for an additional disorder. Furthermore, pancreatic exocrine insufficiency secondary to CF likely aggravated intestinal malabsorption despite appropriate dietary treatment, thereby contributing to persistent gastrointestinal symptoms.

​

The coexistence of CD and CF has been recognized since the first published report in 1969. 9 Although the exact pathogenic relationship remains uncertain, several mechanisms have been proposed. Pancreatic enzyme deficiency may increase exposure of the intestinal mucosa to incompletely digested gluten peptides. In contrast, chronic intestinal inflammation in CF may increase intestinal permeability and facilitate autoimmune responses. 10 The patient demonstrated severe pancreatic exocrine insufficiency, reflected by a fecal elastase concentration of 3 μg/g, and experienced partial clinical improvement after initiation of pancreatic enzyme replacement therapy (Creon®). At the most recent follow-up, she remained clinically stable with ongoing multidisciplinary management. Because this is a retrospective case report, detailed longitudinal nutritional assessments, pulmonary function testing, chest computed tomography, and respiratory microbiological surveillance were not available. We acknowledge that these investigations would have provided a more comprehensive characterization of the patient's cystic fibrosis phenotype and recognize their absence as a limitation of the present report.

​

The patient's first episode of pneumonia occurred two years after the diagnosis of cystic fibrosis. Although this respiratory event is compatible with pulmonary involvement in cystic fibrosis, no pulmonary function testing, chest computed tomography, or microbiological evaluation was available to further characterize the respiratory disease. Therefore, the extent of pulmonary involvement cannot be determined from this retrospective report.

​

This case also emphasizes the importance of genetic counseling for families of patients with cystic fibrosis. Family counseling should include discussion of the hereditary nature of the disease, recurrence risk, and the potential role of genetic evaluation for biological relatives, where clinically appropriate. Early recognition of affected family members may facilitate timely diagnosis, multidisciplinary follow-up, and initiation of appropriate disease-specific management.

​

This report has several limitations inherent to its retrospective design. Complete historical documentation of the original diagnostic work-up for type 1 diabetes mellitus, celiac disease, and cystic fibrosis was unavailable, and several investigations requested by current diagnostic guidelines—including diabetes-associated autoantibodies, endomysial antibodies, pulmonary function testing, chest computed tomography, and comprehensive nutritional assessments—were not available for review. The principal diagnostic challenge in this case was the overlap of gastrointestinal manifestations between celiac disease and cystic fibrosis, which complicated clinical interpretation and delayed consideration of an additional underlying disorder. Despite these limitations, the present case provides educational value by illustrating the diagnostic complexity associated with overlapping gastrointestinal manifestations in children with multiple chronic disorders.