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Coeliac disease and Crohn’s disease are among the most well known gastrointestinal disorders, with distinct pathogenic mechanisms. However, because of some overlapping features between these two conditions, there may be some inevitable misdiagnoses. In addition, diarrhoea and changes in bowel habit may lead the physician to misdiagnose more common disorders such as irritable bowel syndrome. There are a few cases reporting both coeliac and Crohn’s disease in the same patient. Here we report a case of a 32-year-old woman suffering from long term diarrhoea who was eventually discovered to have coeliac disease and Crohn’s disease simultaneously.
Chronic diarrhoea still ranks among the most common complaints for which patients seek medical care.1 The aetiology of the disorder varies according to the patient’s demographic features—for example, in Iran the most common cause of chronic non-inflammatory diarrhoea is coeliac disease.2 Coeliac disease is one of the well known malabsorption syndromes, with a large number of various presentations. It is defined by characteristic pathological findings along with certain serological markers; in disease development, hereditary and environmental factors are the main offenders, of which HLA class II and gliadin are the most important. In light of these facts, coeliac disease may develop in the context of some other disease states such as polyglandular autoimmune disorder type 2, collagenous colitis, and inflammatory bowel disorders.3,4 However, there are a few reports of simultaneous coeliac and Crohn’s disease developing in the same patient. Here we report a case of a 32-year-old woman from the southern part of Iran who presented with a 12 year history of diarrhoea, who eventually was found to have suffered from both coeliac disease and Crohn’s disease.
The 32-year-old woman was an inhabitant of Masjed Soleyman, one of the southern cities of Iran with the highest levels of crude oil production. Overall, she was healthy until 12 years ago when she developed chronic diarrhoea. The diarrhoea did not have any significant response to fasting. It was accompanied by significant weight loss of more than 40 pounds (18 kg) but without any noticeable abdominal pain over the ensuing years. There was no considerable amount of flatulence or mucus discharge. Intermittently she noticed fresh blood mixed with loose stool. The diarrhoea severity was irrelevant to the type of foods ingested. Her close relatives had no similar symptoms.
Shortly after the onset of diarrhoea, the patient developed a secondary form of amenorrhoea which had lasted to the present time. During this period she was treated with various antidiarrhoeal agents but with little effect, only causing her to become less compliant with her physician’s advice. A week before admission, she developed a few painful oral aphthous ulcers and also some painful skin lesions over her digits and dorsa of the hands. The lesions consisted of a central pustular formation with a surrounding erythematous patch. There was no pruritus. Grossly they were similar to the lesions of neutrophilic dermatosis. They soon became necrotic and eventually resolved with no remaining scars. A biopsy sample was consistent with eczematous dermatitis.
The patient looked ill with a “wasted” appearance. Her blood pressure recordings were all below 120 mm Hg and were accompanied with orthostatic change. Otherwise, the physical findings were normal.
The combination of diarrhoea, secondary amenorrhea, low blood pressure, wasted appearance, and oral and skin ulcers led us to consider that the patient was suffering from polyglandular autoimmune disorder type 2 accompanied by coeliac disease. We started a thorough workup. Surprisingly, the endocrinology workup revealed secondary amenorrhoea. According to adrenocorticotropic hormone (ACTH) stimulation test results, there was no sign of adrenal insufficiency. She underwent upper gastrointestinal endoscopy. Pathologic review of the samples taken from the second part of the duodenum was compatible with gluten sensitive enteropathy type IIIA. Detection of high titre antiendomysial antibody (IgA) in blood also verified the diagnosis. A gliadin and lactose free diet was commenced. Analysis of the stool samples repeatedly revealed the presence of inflammatory diarrhoea with a large number of red and white blood cells. This provided the stimulus for us to seek evidence of simultaneous inflammatory bowel disease. On colonoscopy, there were a very large number of haemorrhagic superficial ulcers extending from the rectum proximally; of course, due to the presence of severe inflammation, examination of the entire colon was not feasible. Our assumption was ulcerative colitis, but pathologic review of a large bowel specimen and a high level of anti-Saccharomyces cerevisiae (ASCA) in the blood confirmed the presence of Crohn’s disease. Figure 1 shows the histology of the biopsy of the colonic mucosa, and fig 2 the mucosal biopsy of the duodenum. The patient was diagnosed with simultaneous Crohn’s disease and coeliac disease.
The patient was started on a gliadin and lactose free diet. She also received appropriate drug treatment for Crohn’s disease (steroid and 5-ASA based regimen).
The patient was recommended to return for follow-up in order to rule out the presence of colonic dysplasia or small bowel tumour, and to investigate whether the therapeutic regimen needed to be changed.
Coeliac disease may initially be confused with other diarrhoeal syndromes such as irritable bowel syndrome. According to Emami et al, the sensitivity of serologic marker tests for coeliac disease may not be equal to the reference figures, especially of those performed in commercial laboratories.4 However, Malekzade et al reported that coeliac disease is the most common cause of chronic non-bloody diarrhoea in patients from the country’s capital, Tehran.5 It has been reported that one out of 166 healthy Iranians have coeliac disease.6 Interestingly, because wheat is one of the major components of the regular diet in the Middle East, North Africa, India and Iran, causing some degree of immune tolerance, patients from these countries may therefore present with milder, longer and even more challenging clinical manifestations of the disease. It has been estimated that 3–20% of the population in these areas suffer from some variation of the disease.7 Both genetic and environmental factors are involved in the disease pathogenesis and it is associated with immunologic disorders such as autoimmune thyroiditis. So there is a question still remaining to be answered: is it just the effect of hereditary predisposition or coeliac disease which may trigger autoimmunity per se. It has been shown that autoimmune thyroiditis responds well to a gluten free diet, and transglutaminase 2 autoantibody may be involved in the development of thyroiditis.8 The association of Crohn’s disease and coeliac disease is of tremendous interest to physicians. More commonly Crohn’s disease is discovered after the pre-existing coeliac disease, yet the reverse has also been reported.9 Ig G anti-transglutaminase antibody may be found in patients with inflammatory bowel disease. Consequently, this type of antibody has been considered of low specificity in the diagnosis of coeliac disease.10 On the other hand, ASCA and antineutrophilic antibodies, that are well known markers for discriminating between ulcerative colitis and Crohn’s disease, may become detectable in patients with coeliac disease. Of interest, not only is the degree of seropositivity for ASCA related to the severity of mucosal injury, but also this autoantibody may disappear on a gluten free diet in coeliac disease. It is wondered if there is a surplus of immune response to microbial agents involved in the pathogenesis of such different gastrointestinal disorders as coeliac disease and Crohn’s disease.11–14
Altered permeability hypothesis may justify these observations; there are some gene products such as those produced by MAG12 maintaining intestinal integrity. Gene polymorphism results in disrupting epithelial integrity, unless the relevant protein is fully functional.15 Another explanation for the simultaneous presence of these two disorders may lie in the hypothesis of shared susceptibility loci such as IL23R.16–18 Similarly, reduced expression of paraoxonase in different parts of the intestine results in coeliac disease, Crohn’s disease or ulcerative colitis. Paraoxonase works not only as an antioxidant but also as a local defence system protecting the epithelium from oxidative stress injury. It has been shown that there are significantly reduced levels of mRNA expression of the enzyme in the duodenum and terminal ileum in coeliac or Crohn’s disease, respectively.19
As mentioned above, collagenous colitis is associated with coeliac disease from which inflammatory bowel disease may evolve.4
Whatever causes the development of these two related diseases in the same patient, it needs to be investigated further; however, the commitment of an astute physician is required to detect the second latent disease in advance, before any serious consequences—such as, for example, intestinal lymphoma—can occur.20,21
According to our knowledge, to date there have been very few cases of simultaneous coeliac disease and Crohn’s disease in the same patient. The underlying mechanism of this association is not yet precisely defined. However, it is important to consider the association, especially when the patient’s diarrhoea seem unusual from the point of its poor response to treatment or its odd characteristics,22–28 because establishing an appropriate therapeutic regimen focusing on both diseases may prevent the patient from developing such noticeable repercussions such as severe growth retardation, delayed puberty, social isolation, and so forth.
We would like to thank the patient for her consent and for supplying her medical history for publication.
Competing interests: None.
Patient consent: Patient/guardian consent was obtained for publication.