Introduction
Crohn disease (CD) is a form of inflammatory bowel disease (IBD) that is characterized by intestinal inflammation that may result from a combination of multiple factors such as environmental or immunological factors [1]. In Saudi Arabia, the incidence of CD has been intensely Increasing reaching 6.72/100,000 population [2]. Extraintestinal manifestations include rheumatic, metabolic, dermatologic, ophthalmologic, hepatobiliary, pancreatic, urologic, pulmonary, neurological, hematological and thromboembolic during the CD course is well known, however the coexistence of CD and Grave’s disease (GD) has not been well documented [1-3], as to date, only few literature reviews of cases of GD coexisting with CD have been reported, and still uncertain whether such association is due to a specific reason or a coincidence [4-7]. Some immunological processes are suggested to be implicated in the pathogenesis of this association; however, the exact mechanism remains unclear [3-7]. Herein, we report the case of a young Saudi lady developing Grave’s disease three years after being diagnosed with CD disease, and we conducted a literature search and review to evaluate such cases of concomitant GD and CD, from 1999 to 2020.

Discussion
We performed a review of the English and French literature regarding the coexistence of GD and CD, from 1999 to 2020. We used PubMed and science direct for the English and French literature, respectively. The characteristics of the six known reported cases of concomitant CD and GD are summarized in the (table 1) [4-7]. Of the six cases of concomitant CD and GD that were identified in this review (including our case), Four cases were male and two were female. The diagnosis of the concomitant diseases was made between the ages of 14 and 53 years. In three cases (including our case), CD was diagnosed before the development of GD and the interval between the diagnoses of the primary and concomitant diseases was 2–16 years [6,7]. In two cases, each disease was diagnosed simultaneously [4,5]. However, in one case, the GD is preceding the development of CD, which was very rare. As the best of our knowledge this was the only case of GD preceding CD reported in the literature [7].

Although some cases of GD coexisting with CD have been reported since 1999 [4-7], it is still unclear whether such association is due to a specific reason or a simple coincidence [6]. The authors suggested some immunological processes to be contributed to the mechanisms of this association, however, the exact pathogenesis remains unclear [4-7]. We postulated also a genetic or environmental pathogenesis may have implicated to the coexistence of these diseases [6].

In some papers, genetic factors were suggested, because the familial occurrence of both diseases is well known [6]. However, is some other publications the family history was negative for Crohn’s disease or thyroid disease in reviewed cases [7]. As for environmental factors, it is well known that smoking is a serious risk factor for Crohn’s disease [1-6]. At the same time, the effect of smoking on thyroid disorders is still controversial, since various environmental and genetic factors are incriminated in the development of thyroid dysfunctions [6]. Brix TH et al revealed that there is association between cigarette smoking and autoimmune thyroid disease even when the effect of genetic factors is eliminated, using twin pairs discordant for thyroid disease [8]. Thus, smoking appears to be a double risk factor for GD and Crohn’s disease [6]. However, taking into consideration that all the patient collected in the table 1, were non-smokers, smoking seems not considered to be a contributory factor in our study. The same findings were confirmed by T. Inokuchi et al [6]. As for immune factors, it has become recognized that Th1/Th2 balance controls the immune system. The autoimmune thyroiditis and Graves’ disease are considered to be a Th2-type cytokine profile [7,9] similarly, to ulcerative colitis, which is also a Th2-cytokine illness [10], while CD is considered Th1- type cytokine disease [11-14]. Therefore, regarding Th1/Th2 imbalance it is expected that the prevalence of Graves’ disease might be higher in ulcerative colitis as compared with CD [15].

Conclusion
At present, there is no clear explanation for the coexistence of GD and CD, therefore, accumulation and analysis of such cases is necessary to clarify the underlying etiology of those associations. Physicians should take into consideration that thyroid disorders, particularly GD, could be an associated condition in patient with GD especially in cases refractory to treatment.