Microscopic Colitis in Patients with ‎Unexplained Chronic Watery non-‎Bloody Diarrhea: A Cross Sectional ‎Study‎ ‎

• Microscopic colitis is an important cause of chronic watery non bloody diarrhea and accounting for about 10 % of these patients and up to 15 - 20 % of elderly patients.
• MC is frequently missed in diagnosis as most of patients have apparently normal mucosa during colonoscopy examination and it diagnosed mainly by histopathological examination of colonic biopsy from patients with chronic watery non-bloody diarrhea.
• Chronic watery non-bloody diarrhea in developing countries require more studies to confirm prevalence of microscopic colitis accurately and to determine risk factor for its development.
•  Prevalence of microscopic colitis among studied patients is about 21.7% (15% lymphocytic colitis and 6.7% collagenous colitis). MC is more common among females.
• Patients with microscopic colitis suffered from diarrhea for longer durations. Prolonged use of non-steroidal anti-inflammatory drugs and proton pump inhibitors is an important risk factor for MC development. 

Epidemiological studies reported an increasing incidence of MC in western countries, and this ‎could be due to genetic, environmental factors or concomitant association with other ‎autoimmune diseases. Geographic variations in the incidence of MC have been recorded; ‎however, the low number of studies from developing countries, make it difficult to determine ‎actual incidence of MC in our region [5-8]. ‎

Table (1): Demographic data and history of all the studied patients.

Microscopic colitis is an important cause of chronic watery non bloody diarrhea and accounting for about 10 % of these patients and up to 15 - 20 % of elderly patients [16]. Previous studies showed high heterogeneity and are not directly comparable. This could be due to differences in geographical and genetic background, different definitions of chronic watery diarrhea, the lack of clearly defined diagnostic criteria for MC and diagnostic work‐up prior to colonoscopy. The aim of this study is to estimate frequency of MC among patients with CWND and to identify the role of some risk factors for its occurrence.

This study showed that more than half of included patients diagnosed with MC were females (69.2%) and mean age was about 45.7 years. These findings agreed with Stoicescu et al., 2012 who showed that the mean age of cases diagnosed with MC was about 45.9 years (range 22.5 - 76) and most of cases were females [17]. Similarly, Larsson et al., 2014 showed that most patients with MC were females (77%) [18]. However, Fumery et al., 2017 reported that the incidence of MC increased with age, reaching a peak of 28/105 in the eighth decade [19]. The present study revealed that there is no relationship between the family history or history of autoimmune diseases and MC. Also, all included patients were negative for celiac disease. However, Stoicescu et al., 2012 diagnosed 6 patients (40%) with MC and associated autoimmune diseases as celiac disease and diabetes mellitus type 1 [17]. Also, familial cases of MC have been described [20]. This difference could be due to geographical, genetic, or population variations, as most of these studies were conducted in western countries with a high prevalence of autoimmune diseases.   

We found that there was strong positive association between patients with MC and the history of use of PPIs and NSAIDs. All MC patients had a history of chronic PPI use, 92.3% of MC patients had a history of recurrent NSAID use, and 30.8 % of MC patients had a history of SSRIs use. In line with our results, many previous retrospective studies had been found a strong association between PPIs usage and MC, especially when used for 4 to 12 months regularly. Prolonged use of NSAIDs was also associated with increased incidence of MC [21-23]. The use of both NSAIDs and PPIs together may raise the risk of MC [24]. As regard SSRIs, there was no significant association between use of SRRIs and patients with MC in. In contrast, Yen et al., 2017, Guagnozzi et al., 2015 and masclee et al., 2015 reported strong association between SSRIs exposure and MC [25,21,22]. This difference could be due to low number of patients with history of SRRIs intake included in our study. It is important to clarify that our study and previous all studies lack information about appearance of clinical symptoms after drug exposure and if symptoms disappear after stopping of drugs in order to establish a causal relationship.

Diarrhea was the main symptom in all patients which was non bloody and watery with mean duration of 4 months in patients diagnosed with MC versus 1.64 months in patients without MC. This finding agreed with Stoicescu et al., 2012 who found that in patients with MC, stool frequency per day was 5/day (range 3 – 12/day) for about 4 months [17]. Similarly, Kane et al., 2017 showed 286 patients out of 540 (53.0%) presents with diarrhea more than 1 month duration [26]. All patients with MC in our study presented with nocturnal diarrhea, abdominal pain, and 23 % of them had weight loss. However, Stoicescu et al., 2012 reported that nocturnal diarrhea is present in (73.33%) of patients, abdominal pain in 53.33% of patients and slight loss of weight in 40 % of cases [17]. Similarly, in a study by Macaigne et al., 2014, abdominal pain had been observed in half of the patients and loss of weight observed in about 40% of patients [27].

The present study revealed that level of hemoglobin, total leucocytic count, and platelets count was within normal values in patients with MC. Also, there was no statistically significant difference between patients with MC and patients without MC as regard liver function tests, kidney function tests and glycosylated hemoglobin. This agreed with Gustafsson et al.,2013 and Larsson et al.,2014 who showed the same findings in patients with MC [28,18]. Regarding thyroid functions, this study showed no abnormalities in thyroid functions in patients with microscopic colitis except for elevated total T3 level which was clinically not significant with normal TSH level in these patients. In contrast, a study by Williams et al., 2008 included 164 patients with MC showed that 18 cases (11%) had previously been diagnosed with hypothyroidism [20]. In addition, Gustafsson et al., 2013 found that the total prevalence of thyroid abnormalities was greater in patients with MC than in the control sample [28].

Colonoscopy examination of all 60 patients in our study was normal with no obvious pathological mucosal findings and multiple biopsies are taken for histopathology. In consistent with our results, a study by Stoicescu et al. ,2012 which was conducted on 247 patients with no detected any mucosal pathological lesions during colonoscopy examination and had been previously diagnosed IBS with diarrhea [17]. In contrast, Mellander et al., 2015 reported endoscopic mucosal abnormalities as oedema, erythema, or abnormal vessel pattern in 37% of collagenous colitis patients and 25% of lymphocytic colitis patients [29]. Similarly, Nguyen et al., 2014 showed there are macroscopic endoscopic abnormalities in 20 - 30% of patients with MC [30]. This difference between studies could be due to endoscopist-related factors including experience and degree of training, which can influence the detection of subtle endoscopic pathological mucosal abnormalities [31].

In the present study according to histopathological assessment of colonic biopsies, MC was diagnosed in 13 patients (21.7%) with 9 patients’ lymphocytic colitis (15%) and 4 patients’ collagenous colitis (6.7%). This high prevalence more than western countries could be explained by recurrent infectious gastroenteritis which may disturb gut immune system, growing increases incidence of autoimmune diseases, and prolonged unnecessary drug exposure especially PPIs and NSAIDs. Fernandez et al., 1999 found 23 patients (6%) with collagenous colitis and 37 patients (10%) with lymphocytic colitis among 375 patients evaluated for chronic diarrhea, which is nearly similar to our findings [32]. Also, Olesen et al., 2004 studied 1018 patients presented with CWND and coloscopy examination was done, the prevalence of MC was about 20% if only cases more than 70 years old are considered [33].

In Egypt, there was large difference between results of study regarding prevalence of MC. Gado et al., 2011 and Saleh et al., 2016 reported prevalence of MC among patients with chronic watery diarrhea about 50 % and 29.5 %, respectively [9,10], while Gomaa et al., 2017 and Abdelmageed et al., 2020 reported prevalence of MC about 10 % and 14 %, respectively [11,12]. This difference may be due to small sample size and population characteristics of included patients. So, large multicenter studies with wide scale are needed to determine the actual prevalence and possible risk factors of MC in Egypt.

This study has some limitations; this study was conducted with a small sample size of patients, which not unable us to find possible associations and differences between subtypes of MC. Patients with lymphocytic colitis and collagenous colitis were considered as a one group in our study as the number of both were small to be compared.

CONCLUSION

Prevalence of microscopic colitis among studied patients was about 21.7% (15% lymphocytic ‎colitis and 6.7% collagenous colitis). MC was more common among females. Patients with ‎microscopic colitis suffered from diarrhea for longer durations. The use of proton pump ‎inhibitors and non-steroidal anti-inflammatory drugs is an important risk factor for MC ‎development.‎

Acknowledgment:

The authors would thank all colleagues who helped to conduct this study.

Funding: None

Conflicts of interest: None.

Ethical consideration:

Permission and official approval to carry out the study was obtained. All patients signed a written informed consent before inclusion into this study and the institutional ethical committee at Zagazig University, Faculty of Medicine approved the study. The study protocol conforms with the ethical guidelines of the 1975 Declaration of Helsinki.

Abbreviations:

MC: Microscopic colitis.

CWND: Chronic watery non-bloody diarrhea.

LC: Lymphocytic colitis.

CC: Collagenous colitis.

NSAIDs: Non-steroidal anti-inflammatory drugs.

PPIs: Proton pump inhibitors.

SSRIs: Selective serotonin reuptake inhibitors.

IBS: Irritable bowel syndrome.