Abstract

The autoimmune-related basis in the pathogenesis of celiac disease is merely supported by the increased frequency of association with other autoimmune disorders. We present a peculiar case report associating three different autoimmune disorders in a teenage boy: Celiac Disease, Type1 Diabetes and Crohn Disease.

1. Introduction

Celiac Disease (CD) is an autoimmune disorder triggered by gluten consumption in genetically susceptible individuals and characterized by the presence of a specific enteropathy ¹.

It exhibits an indreasing worldwide prevalence, specially in North African Maghreb countries ^{2, 3}, and is frequently reported to be associated with other autoimmune conditions ⁴.

Here is summarized a rare association combining CD, Type1 Diabetes (T1D) and Crohn Disease (CrD).

2. Case Presentation

We report the case of a young male teenager aged thirteen and suffering from type 1 diabetes from several years and difficultly managed for his chronic, complicated dysglycemia..

He was diagnosed with T1D at age of 6, but could not achieve a balanced glycemia despite tight follow up and increasing insulin doses.

He suffers from refractory, watery, painful diarrhea since a couple of months is revealing a Celiac disease, confirmed by both serology and histology.

However, a gluten free diet could not reequilibrate his bowel and, specially, a capricious melena was noted; as well as persistant dyspepsia.

In fine, the boy was diagnosed (on endoscopy and histology) with a Crohn disease ... another autoimmune, chronic and hard-to-manage, condition.

Human leukocyte antigen (HLA) typing was ordered and confirmed the presence of both HLA DQ2 (leading to CD and T1D susceptibility) and HLA DR4 (well recognized as a severeity biomarker in CrD)

3. Discussion

Autoimmune diseases associated to CD are widely and increasingly reported ^{4, 5}.

However, the peculiar association of these three conditions (e.g CD, T1D and Crohn Disease) is very uncommon: we performed a Medline search through Pubmed® using the Medical Subheading (Mesh) terms: "Diabetes Mellitus, Type 1", "Celiac Disease" and "Crohn Disease" with a final search request:

"Diabetes Mellitus, Type 1"[Mesh]) AND "Celiac Disease"[Mesh]) AND "Crohn Disease"[Mesh] "

Surprisingly, we retrieved only thirteen articles, and no similar case report using the Pubmed® Search Filter: "Case Report". ⁶

Several pathophysiological similarities may explain this particular association:

-Immunity, at first: the autoimmune-related background of CD is confirmed by the frequent associations between different autoimmune disorders and CD. The association of CD and autoimmune disorders can be explained by the frequent finding of organ-specific autoantibodies, similar lymphocyte and mononuclear cell infiltrations at target organ level, and common HLA phenotypes ⁷.

- Genetics: mainly through the above mentioned HLA. Associations between HLA antigens and autoimmune diseases were reported since the 1970s. After the development of wide-screen genotyping and finemapping, HLA was increminated in major autoimmune diseases like CD, Rheumatoid Arthritis, psoriasis, ankylosing spondylitis, systemic lupus erythematosus, Type 1 Diabetes, multiple sclerosis, Graves disease, and dermatomyositis ^{1, 8}

CD is strongly associated with the HLA: more than 95% of patients with CD share the HLA-DQ2 heterodimer, and the remainder present the HLA-DQ8 heterodimer, both located on chromosome 6 ⁹.

In a modern context of increased prevalence of CD as well as other autoimmune diseases, HLA typing emerges as an important tool to discriminate individuals genetically susceptible to develop CD or T1D in at-risk groups such as those with autoimmune conditions ¹⁰.

- Finally, the involvment of intestinal hyperpermeability in the common genesis of these three conditions ^{11, 12, 13}, as well as the expending role of the gastrointestinal microbiota ^{14, 15, 16}, complete the puzzle of such an "autoimmune implosion".

4. Conclusion

Several autoimmune disorders may share, at least partially, the same immunogenetic core (i.e. HLA) that could be analysed in the early management of targetted autoimmune conditions in order to guide future treatment.

Keep in mind that an autoimmune dysregulation may predispose to other ones with a potential deep impact on clinical management.

Acknowledgements

The authors would thank the biochemistry laboratory at University Hospital of Setif for kind collaboration.

References