Journal of Clinical and Diagnostic Research, ISSN - 0973 - 709X

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Dr Mohan Z Mani

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On Sep 2018




Prof. Somashekhar Nimbalkar

"Over the last few years, we have published our research regularly in Journal of Clinical and Diagnostic Research. Having published in more than 20 high impact journals over the last five years including several high impact ones and reviewing articles for even more journals across my fields of interest, we value our published work in JCDR for their high standards in publishing scientific articles. The ease of submission, the rapid reviews in under a month, the high quality of their reviewers and keen attention to the final process of proofs and publication, ensure that there are no mistakes in the final article. We have been asked clarifications on several occasions and have been happy to provide them and it exemplifies the commitment to quality of the team at JCDR."



Prof. Somashekhar Nimbalkar
Head, Department of Pediatrics, Pramukhswami Medical College, Karamsad
Chairman, Research Group, Charutar Arogya Mandal, Karamsad
National Joint Coordinator - Advanced IAP NNF NRP Program
Ex-Member, Governing Body, National Neonatology Forum, New Delhi
Ex-President - National Neonatology Forum Gujarat State Chapter
Department of Pediatrics, Pramukhswami Medical College, Karamsad, Anand, Gujarat.
On Sep 2018




Dr. Kalyani R

"Journal of Clinical and Diagnostic Research is at present a well-known Indian originated scientific journal which started with a humble beginning. I have been associated with this journal since many years. I appreciate the Editor, Dr. Hemant Jain, for his constant effort in bringing up this journal to the present status right from the scratch. The journal is multidisciplinary. It encourages in publishing the scientific articles from postgraduates and also the beginners who start their career. At the same time the journal also caters for the high quality articles from specialty and super-specialty researchers. Hence it provides a platform for the scientist and researchers to publish. The other aspect of it is, the readers get the information regarding the most recent developments in science which can be used for teaching, research, treating patients and to some extent take preventive measures against certain diseases. The journal is contributing immensely to the society at national and international level."



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Sri Devaraj Urs Medical College
Sri Devaraj Urs Academy of Higher Education and Research , Kolar, Karnataka
On Sep 2018




Dr. Saumya Navit

"As a peer-reviewed journal, the Journal of Clinical and Diagnostic Research provides an opportunity to researchers, scientists and budding professionals to explore the developments in the field of medicine and dentistry and their varied specialities, thus extending our view on biological diversities of living species in relation to medicine.
‘Knowledge is treasure of a wise man.’ The free access of this journal provides an immense scope of learning for the both the old and the young in field of medicine and dentistry as well. The multidisciplinary nature of the journal makes it a better platform to absorb all that is being researched and developed. The publication process is systematic and professional. Online submission, publication and peer reviewing makes it a user-friendly journal.
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Dr Saumya Navit
Professor and Head
Department of Pediatric Dentistry
Saraswati Dental College
Lucknow
On Sep 2018




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Their prompt and timely response to review's query and the manner in which they have set the reviewing process helps in extracting the best possible scientific writings for publication.
It's a honour and pride to be a part of the JCDR team. My very best wishes to JCDR and hope it will sparkle up above the sky as a high indexed journal in near future."



Dr. Arunava Biswas
MD, DM (Clinical Pharmacology)
Assistant Professor
Department of Pharmacology
Calcutta National Medical College & Hospital , Kolkata




Dr. C.S. Ramesh Babu
" Journal of Clinical and Diagnostic Research (JCDR) is a multi-specialty medical and dental journal publishing high quality research articles in almost all branches of medicine. The quality of printing of figures and tables is excellent and comparable to any International journal. An added advantage is nominal publication charges and monthly issue of the journal and more chances of an article being accepted for publication. Moreover being a multi-specialty journal an article concerning a particular specialty has a wider reach of readers of other related specialties also. As an author and reviewer for several years I find this Journal most suitable and highly recommend this Journal."
Best regards,
C.S. Ramesh Babu,
Associate Professor of Anatomy,
Muzaffarnagar Medical College,
Muzaffarnagar.
On Aug 2018




Dr. Arundhathi. S
"Journal of Clinical and Diagnostic Research (JCDR) is a reputed peer reviewed journal and is constantly involved in publishing high quality research articles related to medicine. Its been a great pleasure to be associated with this esteemed journal as a reviewer and as an author for a couple of years. The editorial board consists of many dedicated and reputed experts as its members and they are doing an appreciable work in guiding budding researchers. JCDR is doing a commendable job in scientific research by promoting excellent quality research & review articles and case reports & series. The reviewers provide appropriate suggestions that improve the quality of articles. I strongly recommend my fraternity to encourage JCDR by contributing their valuable research work in this widely accepted, user friendly journal. I hope my collaboration with JCDR will continue for a long time".



Dr. Arundhathi. S
MBBS, MD (Pathology),
Sanjay Gandhi institute of trauma and orthopedics,
Bengaluru.
On Aug 2018




Dr. Mamta Gupta,
"It gives me great pleasure to be associated with JCDR, since last 2-3 years. Since then I have authored, co-authored and reviewed about 25 articles in JCDR. I thank JCDR for giving me an opportunity to improve my own skills as an author and a reviewer.
It 's a multispecialty journal, publishing high quality articles. It gives a platform to the authors to publish their research work which can be available for everyone across the globe to read. The best thing about JCDR is that the full articles of all medical specialties are available as pdf/html for reading free of cost or without institutional subscription, which is not there for other journals. For those who have problem in writing manuscript or do statistical work, JCDR comes for their rescue.
The journal has a monthly publication and the articles are published quite fast. In time compared to other journals. The on-line first publication is also a great advantage and facility to review one's own articles before going to print. The response to any query and permission if required, is quite fast; this is quite commendable. I have a very good experience about seeking quick permission for quoting a photograph (Fig.) from a JCDR article for my chapter authored in an E book. I never thought it would be so easy. No hassles.
Reviewing articles is no less a pain staking process and requires in depth perception, knowledge about the topic for review. It requires time and concentration, yet I enjoy doing it. The JCDR website especially for the reviewers is quite user friendly. My suggestions for improving the journal is, more strict review process, so that only high quality articles are published. I find a a good number of articles in Obst. Gynae, hence, a new journal for this specialty titled JCDR-OG can be started. May be a bimonthly or quarterly publication to begin with. Only selected articles should find a place in it.
An yearly reward for the best article authored can also incentivize the authors. Though the process of finding the best article will be not be very easy. I do not know how reviewing process can be improved. If an article is being reviewed by two reviewers, then opinion of one can be communicated to the other or the final opinion of the editor can be communicated to the reviewer if requested for. This will help one’s reviewing skills.
My best wishes to Dr. Hemant Jain and all the editorial staff of JCDR for their untiring efforts to bring out this journal. I strongly recommend medical fraternity to publish their valuable research work in this esteemed journal, JCDR".



Dr. Mamta Gupta
Consultant
(Ex HOD Obs &Gynae, Hindu Rao Hospital and associated NDMC Medical College, Delhi)
Aug 2018




Dr. Rajendra Kumar Ghritlaharey

"I wish to thank Dr. Hemant Jain, Editor-in-Chief Journal of Clinical and Diagnostic Research (JCDR), for asking me to write up few words.
Writing is the representation of language in a textual medium i e; into the words and sentences on paper. Quality medical manuscript writing in particular, demands not only a high-quality research, but also requires accurate and concise communication of findings and conclusions, with adherence to particular journal guidelines. In medical field whether working in teaching, private, or in corporate institution, everyone wants to excel in his / her own field and get recognised by making manuscripts publication.


Authors are the souls of any journal, and deserve much respect. To publish a journal manuscripts are needed from authors. Authors have a great responsibility for producing facts of their work in terms of number and results truthfully and an individual honesty is expected from authors in this regards. Both ways its true "No authors-No manuscripts-No journals" and "No journals–No manuscripts–No authors". Reviewing a manuscript is also a very responsible and important task of any peer-reviewed journal and to be taken seriously. It needs knowledge on the subject, sincerity, honesty and determination. Although the process of reviewing a manuscript is a time consuming task butit is expected to give one's best remarks within the time frame of the journal.
Salient features of the JCDR: It is a biomedical, multidisciplinary (including all medical and dental specialities), e-journal, with wide scope and extensive author support. At the same time, a free text of manuscript is available in HTML and PDF format. There is fast growing authorship and readership with JCDR as this can be judged by the number of articles published in it i e; in Feb 2007 of its first issue, it contained 5 articles only, and now in its recent volume published in April 2011, it contained 67 manuscripts. This e-journal is fulfilling the commitments and objectives sincerely, (as stated by Editor-in-chief in his preface to first edition) i e; to encourage physicians through the internet, especially from the developing countries who witness a spectrum of disease and acquire a wealth of knowledge to publish their experiences to benefit the medical community in patients care. I also feel that many of us have work of substance, newer ideas, adequate clinical materials but poor in medical writing and hesitation to submit the work and need help. JCDR provides authors help in this regards.
Timely publication of journal: Publication of manuscripts and bringing out the issue in time is one of the positive aspects of JCDR and is possible with strong support team in terms of peer reviewers, proof reading, language check, computer operators, etc. This is one of the great reasons for authors to submit their work with JCDR. Another best part of JCDR is "Online first Publications" facilities available for the authors. This facility not only provides the prompt publications of the manuscripts but at the same time also early availability of the manuscripts for the readers.
Indexation and online availability: Indexation transforms the journal in some sense from its local ownership to the worldwide professional community and to the public.JCDR is indexed with Embase & EMbiology, Google Scholar, Index Copernicus, Chemical Abstracts Service, Journal seek Database, Indian Science Abstracts, to name few of them. Manuscriptspublished in JCDR are available on major search engines ie; google, yahoo, msn.
In the era of fast growing newer technologies, and in computer and internet friendly environment the manuscripts preparation, submission, review, revision, etc and all can be done and checked with a click from all corer of the world, at any time. Of course there is always a scope for improvement in every field and none is perfect. To progress, one needs to identify the areas of one's weakness and to strengthen them.
It is well said that "happy beginning is half done" and it fits perfectly with JCDR. It has grown considerably and I feel it has already grown up from its infancy to adolescence, achieving the status of standard online e-journal form Indian continent since its inception in Feb 2007. This had been made possible due to the efforts and the hard work put in it. The way the JCDR is improving with every new volume, with good quality original manuscripts, makes it a quality journal for readers. I must thank and congratulate Dr Hemant Jain, Editor-in-Chief JCDR and his team for their sincere efforts, dedication, and determination for making JCDR a fast growing journal.
Every one of us: authors, reviewers, editors, and publisher are responsible for enhancing the stature of the journal. I wish for a great success for JCDR."



Thanking you
With sincere regards
Dr. Rajendra Kumar Ghritlaharey, M.S., M. Ch., FAIS
Associate Professor,
Department of Paediatric Surgery, Gandhi Medical College & Associated
Kamla Nehru & Hamidia Hospitals Bhopal, Madhya Pradesh 462 001 (India)
E-mail: drrajendrak1@rediffmail.com
On May 11,2011




Dr. Shankar P.R.

"On looking back through my Gmail archives after being requested by the journal to write a short editorial about my experiences of publishing with the Journal of Clinical and Diagnostic Research (JCDR), I came across an e-mail from Dr. Hemant Jain, Editor, in March 2007, which introduced the new electronic journal. The main features of the journal which were outlined in the e-mail were extensive author support, cash rewards, the peer review process, and other salient features of the journal.
Over a span of over four years, we (I and my colleagues) have published around 25 articles in the journal. In this editorial, I plan to briefly discuss my experiences of publishing with JCDR and the strengths of the journal and to finally address the areas for improvement.
My experiences of publishing with JCDR: Overall, my experiences of publishing withJCDR have been positive. The best point about the journal is that it responds to queries from the author. This may seem to be simple and not too much to ask for, but unfortunately, many journals in the subcontinent and from many developing countries do not respond or they respond with a long delay to the queries from the authors 1. The reasons could be many, including lack of optimal secretarial and other support. Another problem with many journals is the slowness of the review process. Editorial processing and peer review can take anywhere between a year to two years with some journals. Also, some journals do not keep the contributors informed about the progress of the review process. Due to the long review process, the articles can lose their relevance and topicality. A major benefit with JCDR is the timeliness and promptness of its response. In Dr Jain's e-mail which was sent to me in 2007, before the introduction of the Pre-publishing system, he had stated that he had received my submission and that he would get back to me within seven days and he did!
Most of the manuscripts are published within 3 to 4 months of their submission if they are found to be suitable after the review process. JCDR is published bimonthly and the accepted articles were usually published in the next issue. Recently, due to the increased volume of the submissions, the review process has become slower and it ?? Section can take from 4 to 6 months for the articles to be reviewed. The journal has an extensive author support system and it has recently introduced a paid expedited review process. The journal also mentions the average time for processing the manuscript under different submission systems - regular submission and expedited review.
Strengths of the journal: The journal has an online first facility in which the accepted manuscripts may be published on the website before being included in a regular issue of the journal. This cuts down the time between their acceptance and the publication. The journal is indexed in many databases, though not in PubMed. The editorial board should now take steps to index the journal in PubMed. The journal has a system of notifying readers through e-mail when a new issue is released. Also, the articles are available in both the HTML and the PDF formats. I especially like the new and colorful page format of the journal. Also, the access statistics of the articles are available. The prepublication and the manuscript tracking system are also helpful for the authors.
Areas for improvement: In certain cases, I felt that the peer review process of the manuscripts was not up to international standards and that it should be strengthened. Also, the number of manuscripts in an issue is high and it may be difficult for readers to go through all of them. The journal can consider tightening of the peer review process and increasing the quality standards for the acceptance of the manuscripts. I faced occasional problems with the online manuscript submission (Pre-publishing) system, which have to be addressed.
Overall, the publishing process with JCDR has been smooth, quick and relatively hassle free and I can recommend other authors to consider the journal as an outlet for their work."



Dr. P. Ravi Shankar
KIST Medical College, P.O. Box 14142, Kathmandu, Nepal.
E-mail: ravi.dr.shankar@gmail.com
On April 2011
Anuradha

Dear team JCDR, I would like to thank you for the very professional and polite service provided by everyone at JCDR. While i have been in the field of writing and editing for sometime, this has been my first attempt in publishing a scientific paper.Thank you for hand-holding me through the process.


Dr. Anuradha
E-mail: anuradha2nittur@gmail.com
On Jan 2020

Important Notice

Original article / research
Year : 2022 | Month : June | Volume : 16 | Issue : 6 | Page : EC01 - EC05 Full Version

Clinico-pathological Evaluation of Chronic Diarrhea with Microscopic Colitis: A Cross-sectional Study


Published: June 1, 2022 | DOI: https://doi.org/10.7860/JCDR/2022/52798.16445
Girija, CS Sheeladevi, HV Aradhya

1. Resident, Department of Pathology, Gadag Institute of Medical Sciences, Gadag, Karnataka, India. 2. Professor, Department of Pathology, JSS, Mysuru, Karnataka, India. 3. Associate professor, Department of Gastroenterology, JSS, Mysuru, Karnataka, India.

Correspondence Address :
Dr. CS Sheeladevi,
House No-367, Adarsha, 6th Cross, Kamakshi Hospital Road, Kuvempunagar, Mysuru, Karnataka, India.
E-mail : devi.sheela1@gmail.com

Abstract

Introduction: Chronic diarrhea is common in the older population accounting for 7-9 % which often markedly affects their quality of life. The causes are many and include infectious, endocrine, metabolic, neoplastic, functional, drugs. Microscopic Colitis (MC) has emerged as a distinct diagnostic entity, where the colon appears endoscopically normal, but the biopsy reveals characteristic features in the mucosa. It has two histological forms i.e, Collagenous Colitis (CC) and Lymphocytic Colitis (LC).

Aim: To study the clinico-pathological spectrum of lesions in random colonic biopsies of patients with chronic diarrhea having normal colonoscopy.

Materials and Methods: This cross-sectional study was conducted in Department of Pathology at JSS Hospital, Mysuru, Karnataka, India, from October 2017 to September 2019. Multiple random biopsies were taken from 80 patients with chronic diarrhea who had normal colonoscopy. The slides were stained with Hematoxylin and Eosin (H&E) and Masson’s Trichrome Stain (MTS). The histological features were studied under light microscopy and using computer-assisted image analysis. The Chi-square test was used to statistically analyse the data.

Results: The age of patients ranged from 11-82 years with a mean age of 43 years. Out of total 80 patients, 65 (81.25%) of the cases had non specific inflammation, 14 (17.4%) had microscopic colitis and one patient (1.25%) had probable eosinophilic colitis. The histological features were observed in computer-assisted image analysis using morphometry and interpreted by two pathologists with agreement.

Conclusion: Random biopsies are required for the diagnosis of microscopic colitis in the absence of macroscopic abnormalities on colonoscopy, which may affect the treatment strategy. A histologic examination combined with histochemical stain MTS and interpretation utilising computerized image analysis program with morphometry is more effective in cases with diagnostic uncertainty.

Keywords

Biopsy, Colonoscopy, Image analysis, Intestinal mucosa

Chronic diarrhoea is the persistent alteration from the norm of stool consistency and increased frequency with ≥3 loose stools per day for greater than 4 week’s duration (1). Microscopic Colitis (MC) is one of the common causes of persistent diarrhoea and is divided into two subtypes i.e, Collagenous Colitis (CC) and Lymphocytic Colitis (LC). It is a triad of persistent watery non bloody diarrhoea, a normal/near normal endoscopy and distinctive tissue morphology (2),(3),(4).

When it was first described in 1980, it was thought to be a rare condition. Over the last two decades, the number of patients diagnosed with MC has shown an increasing trend (5).

The incidence and prevalence of MC in developed countries accounts for 4-13% of cases of chronic diarrhea. In developing countries prevalence ranges from 15 to 50% (6). However, physicians, especially those in primary care, are not as much aware of MC as a cause of chronic diarrhea. It is important to create awareness among general practitioners, surgeons, and pathologists, as MC is a frequent disease and should always be considered in patients with chronic diarrhoea (7).

Though several biomarkers exist for the diagnosis of MC, there is currently no reliable marker, and Histopathological Examination (HPE) of multiple biopsies remains the cornerstone in the diagnosis of MC (5),(6). The histological identification of each lesion will help in appropriate specific treatment (6). The histological features can be subjective. Besides the histochemical stains, the use of image analysis and morphometry may be more objective in the assessment of histological features.

Hence, objective of this study was to use a computer-assisted image analysis tool to describe the histological features in random colonic biopsies of individuals with persistent diarrhea who had a normal colonoscopy.

Material and Methods

This was a hospital-based cross-sectional study conducted in Department of Pathology at JSS, Mysuru, Karnataka, India, from October 2017 to September 2019. Institutional Ethical Committee clearance was obtained before the commencement of the study (Ethical clearance no.-JSSMC/PG/4700/2017-18).

Inclusion criteria: Biopsies of the patients who came with the history of chronic watery diarrhea of minimum three times a day lasting for more than 4 weeks but having normal colonoscopy were included in the study.

Exclusion criteria: The patients who were passing blood and mucus in stools, known case of inflammatory bowel disease, intestinal tuberculosis, bacterial overgrowth, and visible lesions on endoscopy including ulcers, growths, and inadequate biopsy were excluded from the study. The biopsies were considered inadequate when the entire thickness of mucosa was not represented in the biopsy.

Sample size calculation: Based on the number of patients who presented with chronic diarrhea to the gastroenterology clinic, the sample size of 73 was calculated using the following formula (8):

N= Z2pq/d2
Where,
Z= 1.96 (constant);
q=1-p;
d=margin of error;
p=proportion of prevalence
N=1.96x1.96x0.05x0.95/ 0.05x0.05.

Procedure

Patients who came to Gastroenterology Department with history of chronic diarrhea were evaluated clinically. The clinical details such as duration of diarrhea, other gastrointestinal symptoms such as abdominal pain, weight loss and nausea were noted. History of smoking and alcohol intake, presence of co-morbidities like hypertension, diabetes, hypothyroidism, hyperthyroidism and autoimmune diseases were documented. The laboratory data including complete blood counts, stool microscopy, thyroid, liver and renal function tests were documented if available.

Stool Microscopy: The numbers of leucocytes present were counted and expressed as the average numbers under the following categories: 0, 1-10, 11-20, 21-50 and >50 per High Power Field (HPF). The inflammation was graded arbitrarily based on the number of inflammatory cells (9) as:

• Occasional (1-4/hpf)
• Mild (5-20/hpf)
• Moderate (>20-50/hpf)
• Severe (>50/hpf)

The biopsy slides were observed for the presence of intraepithelial lymphocytes, type of inflammatory cells in lamina propria, presence of lymphoid follicles, number of eosinophils, severity of inflammation and thickness of subepithelial collagen. The severity of inflammation was categorised arbitrarily as mild when there was unequivocal increase, and severe when there was marked increase in chronic inflammatory cells (10).

Total 41 out of 80 patients underwent stool examination. Some of the patients denied, while others wanted to get it done during follow-up. Among them, some were lost for follow-up while others were free of symptoms.

All the patients were subjected to colonoscopy as a part of evaluation for chronic diarrhea after ruling out other common causes enumerated above. Random biopsies were taken from ascending colon, descending colon, sigmoid colon, rectum and ileum from those patients who had normal colonoscopic findings. The biopsy tissue was immediately placed in separate vials with 10% formalin, processed conventionally in paraffin blocks and cut into 5 micron thick sections. The slides were stained with Hematoxylin and Eosin (H&E) and Masson’s Trichrome stain (MTS).

Criteria for the Diagnosis of Microscopic Colitis are (4),(8)

Lymphocytic colitis: Mild to moderate increase in mononuclear inflammation in lamina propria, >20 Intraepithelial Lymphocytes (IEL)/100 epithelial cells, normal/slightly increased subepithelial collagen, damage to surface epithelium.

Collagenous colitis: Mild to moderate increase in mononuclear inflammation in lamina propria, subepithelial collagen >10 μ, normal/slightly increased intraepithelial lymphocytes but < than 20 IEL/100 epithelial cells, flattening and detachment of epithelial layer (4),(8).

Nonspecific inflammation: This is characterised by an increase in inflammatory cells beyond what would be expected physiologically in the corresponding anatomical sites. Predominantly chronic cellular infiltrate is seen, without architectural distortion and multiple basal lymphoid aggregates or plasma cells are present immediately above the muscularis mucosae. Lack of pathological feature of other types of inflammation of colon precludes nonspecific type of colitis (11).

Eosinophilic colitis: This is characterised by >30 eosinophils/hpf in the lamina propria. Other histological findings are eosinophil microabscesses, eosinophilic cryptitis, and eosinophils within the surface epithelial compartment (12).

Evaluation of subepithelial collagen by morphometry on both H&E and MT stains was done in all the cases. The Olympus BX41 research microscope with Jenoptix (Germany) progress Charged-Coupled Device (CCD) camera and progress capture proimaging software was used for morphometric analysis. The digital images were captured with 1X C mount CCD adapter. After transferring the microscopic images to the computer, thickness of collagen was measured by image analysis program using free style line. Histological features were analysed in light microscopy as well as in computer assisted image analysis program by two pathologists with agreement and the findings were documented. The thickness of collagen >10 μ was considered as collagenous colitis. The Subepithelial Collagen (SEC) was measured on H&E and MTS by morphometry.

Statistical Analysis

It is a descriptive study and the following descriptive statistics were employed including, mean, standard deviation, frequency and percent. Chi-square test was used to tabulate variables into categories. The statistical software namely Statistical Package for Social Sciences (SPSS) version 16.0 and Minitab (11.0) was used for the analysis of the data.

Results

The age of patients ranged from 11 to 82 years, with a mean of 43±19.23 years There was a slight male preponderance with male:female ratio of 3:2. Along with chronic diarrhea, 45 patients presented with other symptoms like pain abdomen, loss of weight and nausea which were present either alone or in combination. Total 46 patients had co-morbidities including hypertension, type 2 diabetes mellitus, hypothyroidism and ischaemic heart disease. One patient each had chronic kidney disease, schizophrenia, bronchial asthma and post renal transplant. History of smoking and alcohol consumption was present in one case of lymphocytic colitis.

Total 65 cases revealed nonspecific inflammation of varying severity. Ileal biopsies were done in 45 cases, and majority showed mild to moderate inflammation. Out of 80, 41 patients underwent stool examination. It was mild in 14 patients (34.2%), moderate in 6 (14.6%), severe in 3 (7.3%) patients and occasional inflammatory cells in one patient.

One case of collagenous colitis showed a moderate increase in inflammatory cells. Five cases of CC showed mild increase in inflammatory cells. None of the samples revealed micro-organisms. Liver Function Tests (LFT) and Renal Function Tests (RFT) were done in 46 patients as a part of evaluation since they had co-morbidities. They were within normal limits in 43 (93%) patients. Two patients showed deranged RFT, while one patient showed deranged LFT (Table/Fig 1).

Histological features were observed and analysed in light microscopy. The mucosal lining epithelium was normal in 76 cases (93.8%). There was an increase in inflammatory cell infiltrate in the lamina propria in all the cases and was comprised of lymphocytes, eosinophils, plasma cells, and neutrophils in varying proportions. The other features observed were congestion and edema, which was seen in 5 (6.25%) cases. The crypt architecture was normal in majority (n=67) of the patients. Cryptitis/crypt abscess were observed in 13 cases. Majority of the cases (47) had mild inflammation in the lamina propria, which included seven cases of collagenous colitis, two cases of lymphocytic colitis and 38 cases of non-specific inflammation (Table/Fig 2). The average normal subepithelial collagen thickness was 5.4 μ (Table/Fig 3).

Active inflammation was noted in 13 (16.5%) cases. The number of eosinophils was counted per high power field in lamina propria. Scattered eosinophils were present in all the cases with 15 to 25 per hpf in 8 cases. An increase in intraepithelial lymphocytes was seen in four cases and was diagnosed as lymphocytic colitis (Table/Fig 4). The subepithelial collagen thickness was patchy to diffuse and was measured by morphometry on both H&E and MT stained slides. An increase in subepithelial collagen of more than 10 μ was seen in 16 cases on H&E stain. It was confirmed by MT stain in 10 cases. The SEC thickness was in the range of 10-15μ and more than 15μ in five cases each which led to a diagnosis of collagenous colitis in 10 patients (Table/Fig 5), (Table/Fig 6), (Table/Fig 7). The extravasated plasma and edema in the lamina propria were falsely interpreted on H&E stain, and MT stain was used for confirmation.

A single case showed more than 30 eosinophils per hpf and was diagnosed as probable eosinophilic colitis (Table/Fig 8). The patient was on thyroxine for hypothyroidism and had presented with skin rashes and chronic watery diarrhea. She also took Non Steroidal Anti-inflammatory Drugs (NSAID’s). Her peripheral blood and bone marrow showed eosinophilia. The antinuclear antibodies, including perinuclear- antineutrophilic cytoplasmic antibodies (pANCA) and c- ANCA (cytoplasmic) were not detected. The stool microscopy did not reveal any parasites. The other laboratory parameters including LFT and RFT were within normal limits. She was treated with steroids and her symptoms subsided. She was on follow-up since 1 year with minimal dose steroids and she was asymptomatic with normal blood counts. However, revised colonoscopy was not done.

Discussion

The diseases associated with diarrhea are more common in elderly population and the causes are many including infectious, endocrine, metabolic, neoplastic, functional, drugs etc (2),(3). Read and colleagues coined the term “microscopic colitis” in 1980, for patients who had chronic watery diarrhea, with normal sigmoidoscopy and barium enema findings but with mucosal inflammation in their colonic biopsy specimens. Currently, “microscopic colitis” is a clinical term that refers to either collagenous or lymphocytic colitis (13).

In patients with normal colonoscopy, obtaining random colonic biopsies routinely to exclude microscopic colitis, is open to debate (14). The prevalence of MC is 4-13% in developed countries, while it is high in developing countries varying from 25-50%. The high prevalence of infectious gastroenteritis in the developing countries suggests an infectious etiology by isolation of organisms such as Clostridium jejuni, Y. enterocolitica, and Clostridium difficile in some patients and has been hypothesized that it precipitates MC by an autoimmune reaction (13). However, no organisms were isolated in the present study.

The mean age of patients with chronic diarrhea was 43 years, which is in concordance with various studies (6),(15). The age ranges from 19 to 98 years and even children may be affected rarely (16). Women are more commonly affected with Female-to-Male (F:M) ratio ranging from 3:1 to 9:1 in CC and 2.4:1 to 2.7:1 in LC (8),(17). The significance of association with gender may be undermined by the small sample size.

The patients with MC had symptoms of pain abdomen, weight loss and nausea, besides chronic watery, non bloody diarrhea. Temmerman F and Baert F, documented pain abdomen and weight loss in many of their patients accounting to 41% and 42% respectively (18). The seasonal variation in symptoms is also reported (19).

The association of smoking with collagenous colitis has been reported with and without statistical significance in many studies (8),(20). Vigren L et al., in their study of 116 CC patients found 37% to be smokers. It has become apparent that smoking has a negative impact in CC and it is hypothesized that smoking alters epigenetic events like methylation and histone modification of the genome (21). Only one case of LC had history of smoking which was statistically not significant.

Microscopic colitis is reported to be associated with various autoimmune diseases like rheumatoid arthritis, diabetes mellitus, psoriasis, celiac disease, autoimmune thyroiditis, antiphospholipid syndrome, with presence of antinuclear antibodies (13),(18),(21). Macaigne G et al., found autoimmune disease, particularly dysthyroidia to be a strong predictive factor for MC (22). Various studies have reported thyroid disease in 8.6 to 21% MC (22),(23). In the present study, MC was associated with co-morbidities with no statistical significance.

Because of their association with a variety of autoimmune conditions, researchers have focused their attention towards investigating HLA haplotypes and serum markers in MC (13).

Autoimmune markers may be positive, including antinuclear antibodies, pANCA (antineutrophilic cytoplasmic antibodies), rheumatoid factor, and complement C3 and C4 (17). These tests were not performed in our patients, which is a limitation. Authors found MT stain with morphometry to be very useful and objective in the interpretation of SEC thickness. The other features were moderate mononuclear inflammation in the lamina propria, flattening and detachment of epithelium. Though some authors describe the presence of IEL, others are of the opinion that it is not required for the diagnosis of CC (3),(4),(8).

The consistent expression of tenascin (an extracellular matrix protein) by IHC is an excellent aid in the diagnosis of CC (18). However, it was not done in the present study. The increased collagen is attributed to disturbances in the function of subepithelial myofibroblasts which synthesize tenascin (13). The automated image analysis of tissue sections minimizes the pathologists’ interobserver variation, as emphasized by Engel PJ et al., (4).

The biopsies are recommended from cecum and transverse colon as the thickest collagen layer is observed in these anatomical regions. There was no considerable difference in the SEC thickness at different sites of colon and rectum in the present study. The computer assisted images were analysed for IEL’s in LC and there was an agreement among two pathologists. The IHC for the identification of T-lymphocytes with CD3 may be done in cases of diagnostic uncertainty. Sonnenberg A et al observed 14% of their patients with MC to have a second lymphocytic disorder of the gastrointestinal tract, and therefore any lymphocytic disorder in the lower gastrointestinal tract should raise the suspicion for a upper gastrointestinal tract related disorder and vice-versa. In the present study, the patients were anti-Tissue Transglutaminase (TTG) negative with no gluten sensitivity and hence were not subjected for upper gastrointestinal biopsy (24). The study of rectum and sigmoid colon would provide a diagnosis in 99.5% of the patients (25).

The other histological features described in literature include, cryptitis, crypt abscesses, paneth cell metaplasia, crypt architectural distortion, surface ulceration and pseudomembranes (13). Some of the commonly used drugs like aspirin, NSAIDS, antibiotics, ranitidine, proton pump inhibitors, β-adrenergic receptor blockers and statins are known to cause MC. There was no such association in the present study (6),(13),(26).

Studies from Peru and Tunis, with high prevalence of infectious gastroenteritis, revealed MC in 40% and 29.3% of cases respectively (6). The prevalence of LC was more frequent than CC in some studies (27),(28).

The patients in the present study were treated with loperamide as a first-line therapy and with budesonide for non responders. Most of the patients responded to medications. But they were lost for follow-up and hence the data regarding management is limited. Williams JJ et al., have reported remission in 85% of LC and 91% of CC patients, when treatment is continued over 6 months (3).

A single case with marked mucosal eosinophilia was diagnosed as probable eosiniophilic colitis, which was attributed to NSAIDs. Eosinophilic Colitis (EC) is a rare entity and there is no consensus over its diagnosis and management. Bates A suggests to report the mean eosinophil counts per high-power field, if it is conspicuous, and not to use the term “eosinophilic colitis” (29). The comparison of present study with similar studies is given in (Table/Fig 9) (8),(25),(30),(31).

Limitation(s)

The CD3 T-cells, tenascin and other biomarkers were not evaluated and also the study was limited by small sample size and the lack of follow-up data in some patients.

Conclusion

Chronic diarrhea is one of the common symptoms for consulting a Gastroenterologist. In the context of wide range of conditions that can result in chronic diarrhoea, a pragmatic approach is necessary in the evaluation of these patients and should include colonoscopy. In the absence of macroscopic findings on colonoscopy, random biopsies from normal appearing colon is essential for the diagnosis of microscopic colitis, which may have an impact on the treatment strategy. Histologic examination still remains a valuable tool in diagnosis of patients with suspected MC. Additional histochemical stains and interpretation using computerized image analysis program with morphometry are more objective and effective in cases with diagnostic uncertainty.

References

1.
Arasaradnam RP, S, Forbes A, Fox MR, Hungin P, Kelman L, Major G, et al. Guidelines for the investigation of chronic diarrhoea in adults: British Society of Gastroenterology, 3rd edition. Gut. 2018;67:1380-99. Doi: 10.1136/gutjnl-2017-315909. [crossref] [PubMed]
2.
Pilotto A, Franceschi M, Vitale D, Zaninelli A, Di Mario F, Seripa D, et al. The prevalence of diarrhea and its association with drug use in elderly outpatients: a multicenter study. Am J Gastroenterol. 2008;103(11):2816. Doi: 10.1111/j.1572-0241.2008.02107.x. [crossref] [PubMed]
3.
Williams JJ, Beck PL, Andrews CN, Hogan DB, Storr MA. Microscopic colitis-a common cause of diarrhoea in older adults. Age Ageing. 2010;39(2):162-68. Doi: 10.1155/2013/352718. [crossref] [PubMed]
4.
Engel PJ, Fiehn AM, Munck LK, Kristensson M. The subtypes of microscopic colitis from a pathologist's perspective: past, present and future. Ann Transl Med. 2018;6(3). Doi: 10.21037/atm.2017.03.16. [crossref] [PubMed]
5.
Pisani LF, Tontini GE, Marinoni B, Villanacci V, Bruni B, Vecchi M, et al. Biomarkers and microscopic colitis: an unmet need in clinical practice. Front Med. 2017;4:54. Doi: 10.3389/fmed.2017.00054. [crossref] [PubMed]
6.
Gado AS, Ebeid BA, El Hindawi AA, Akl MM, Axon AT. Prevalence of microscopic colitis in patients with chronic diarrhea in Egypt: a single-center study. Saudi J G astroenterol. 2011;17(6):383-86. [crossref] [PubMed]
7.
Münch A, Sanders DS, Molloy-Bland M, et al. Undiagnosed microscopic colitis: a hidden cause of chronic diarrhoea and a frequently missed treatment opportunity. Frontline Gastroenterology. 2020;11:228-34. [crossref] [PubMed]
8.
Misra V, Misra SP, Dwivedi M, Singh PA, Agarwal V. Microscopic colitis in patients presenting with chronic diarrhea. Indian J Pathol Microbiol. 2010;53:15-19. http://www.ijpmonline.org/text.asp?2010/53/1/15/59176. [crossref] [PubMed]
9.
Khan A, Huq S, Malek MA, Hossain MI, Talukder KA, Faruque ASG, et al. Analysis of fecal leukocytes and erythrocytes in shigella infections in urban bangladesh. Southeast Asian J Trop Med Public Health. 2006;37(4):747-54.
10.
Amezaga AJ, Geerits A, Das Y, Lemmens B, Sagaert X, Bessissow T, et al. A Simplified Geboes Score for Ulcerative colitis. J Crohns Colitis. 2017;11(3):305-13.
11.
Geboes K, Villanacci V. Terminology for the diagnosis of colitis. J Clin Pathol. 2005;58(11):1133-34. Doi: 10.1136/jcp.2005.028175. [crossref] [PubMed]
12.
Lee CK, Kim HJ, Primary eosinophilic colitis as an unusual cause of chronic diarrhea. Endoscopy 2010; 42: E279-E280. Doi: 10.1055/s-0029-1244167. [crossref] [PubMed]
13.
Odze RD, Goldblum JR. Inflammatory disorders of large intestine. In Surgical pathology of the GI tract, liver, biliary tract, and pancreas. Philadelphia, Elsevier Health Sciences. 2009; 3rd Edition:436-511. [crossref]
14.
Hotouras A, Collins P, Speake W, Tierney G, Lund JN, Thaha MA. Diagnostic yield and economic implications of endoscopic colonic biopsies in patients with chronic diarrhoea. Colorectal Dis. 2012;14(8):985-88. Doi: 10.1111/j.1463-1318.2011.02847. Available from: http://www.saudigastro.com/text. asp?2011/17/6/383/871786. [crossref] [PubMed]
15.
Gu HX, Zhi FC, Huang Y, Li AM, Bai Y, Jiang B, et al. Microscopic colitis in patients with chronic diarrhea and normal colonoscopic findings in Southern China. Int J Colorectal Dis. 2012;27:1167-73. Doi: 10.1007/s00384-012-1449-z. [crossref] [PubMed]
16.
Gremse DA, Boudreaux CW, Manci EA. Collagenous colitis in children. Gastroenterology. 1993;104:906-09. Doi: 10.1016/0016-5085(93)91030-l. [crossref]
17.
Kao KT, Pedraza BA, McClune AC, Rios DA, Mao YQ, Zuch RH, et al. Microscopic colitis: a large retrospective analysis from a health maintenance organization experience. World J Gastroenterol. 2009;15(25):3122-27. Doi: 10.3748/wjg.15.3122. [crossref] [PubMed]
18.
Temmerman F, Baert F. Collagenous and lymphocytic colitis: systematic review and update of the literature. Dig Dis. 2009;27(Suppl. 1):137-45. Doi: 10.1159/000268134. [crossref] [PubMed]
19.
LaSala PR, Chodosh AB, Vecchio JA, Schned LM, Blaszyk H. Seasonal pattern of onset in lymphocytic colitis. J Clin Gastroenterol. 2005;39(10):891-3. Doi: 10.1097/01.mcg.0000180634.84689.c2. [crossref] [PubMed]
20.
Saleem A, Brahmbhatt PA, Khan S, Young M, LeSage GD. Microscopic colitis with macroscopic endoscopic findings. Case reports in medicine.2013;Article ID 461485. Available from: https://doi.org/10.1155/2013/461485. [crossref] [PubMed]
21.
Vigren L, Sjöberg K, Benoni C, Tysk C, Bohr J, Kilander A, et al. Is smoking a risk factor for collagenous colitis?.Scand J Gastroenterol.2011;46(11):1334-9. doi:10.3109/00365521.2011.610005. [crossref] [PubMed]
22.
Macaigne G, Lahmek P, Locher C, Lesgourgues B, Costes L, Nicolas MP, et al. Microscopic colitis or functional bowel disease with diarrhea: a French prospective multicenter study. Am J Gastroenterol. 2014;109(9):1461-70. Doi: 10.1038/ajg.2014.182. Epub 2014 Jul 8. [crossref] [PubMed]
23.
Williams JJ, Kaplan GG, Makhija S, Urbanski SJ, Dupre M, Panaccione R, et al. Microscopic colitis-defining incidence rates and risk factors: a population-based study. Clin Gastroenterol Hepatol. 2008;6(1):35-40. Doi: 10.1016/j.cgh.2007.10.031. [crossref] [PubMed]
24.
Sonnenberg A, Turner KO, Genta RM. Associations of microscopic colitis with other lymphocytic disorders of the gastrointestinal tract. Clin Gastroenterol Hepatol. 2018;16(11):1762-7. Doi: 10.1016/j.cgh.2018.03.002. [crossref] [PubMed]
25.
da Silva JGN, De Brito T, Damiao AO, Laudanna AA, Sipahi AM. Histologic study of colonic mucosa in patients with chronic diarrhea and normal colonoscopic findings. J Clin Gastroenterol. 2006;40(1):44-48. Doi:10.1097/01.mcg.0000190760.72992.ed. [crossref] [PubMed]
26.
Beaugerie L, Luboinski J, Brousse N, Cosnes J, Chatelet FP, Gendre JP, et al. Drug induced lymphocytic colitis.Gut.1994;35:426-28. Doi: 10.1136/gut.35.3.426. [crossref] [PubMed]
27.
Valle Mansilla JL, León Barúa R, Recavarren Arce S, Berendson Seminario R, Biber Poillevard M. Microscopic colitis in patients with chronic diarrhea. Rev Gastroenterol Peru. 2002;22(4):275-78. PMID: 12525842.
28.
Essid M, Kallel S, Ben Brahim E, Chatti S, Azzouz MM. Prevalence of the microscopic colitis to the course of the chronic diarrhea: about 150 cases. Tunis Med. 2005 ;83(5):284-87. PMID: 16044902.
29.
Bates AW. Diagnosing eosinophilic colitis: histopathological pattern or nosological entity? Scientifica (Cairo). 2012;2012:682576. Doi: 10.6064/2012/682576. Epub 2013. PMID: 24278727; PMCID: PMC3820477. [crossref] [PubMed]
30.
Yusoff IF, Ormonde DG, Hoffman NE. Routine colonic mucosal biopsy and ileoscopy increases diagnostic yield in patients undergoing colonoscopy for diarrhea. J Gastroenterol Hepatol. 2002 Mar;17(3):276-80. Doi: 10.1046/j.1440-1746.2002.02686.x. [crossref] [PubMed]
31.
Shah RJ, Preiser CF, Bleau BL, Gianella RA. Usefulness of colonoscopy with biopsy in the evaluation of patients with chronic diarrhea. Am J Gastroenterol. 2001;96(4):1091-95. Doi: 10.1111/j.1572-0241.2001.03745.x. [crossref] [PubMed]

DOI and Others

DOI: 10.7860/JCDR/2022/52798.16445

Date of Submission: Oct 13, 2021
Date of Peer Review: Dec 14, 2021
Date of Acceptance: Mar 31, 2022
Date of Publishing: Jun 01, 2022

AUTHOR DECLARATION:
• Financial or Other Competing Interests: None
• Was Ethics Committee Approval obtained for this study? Yes
• Was informed consent obtained from the subjects involved in the study? Yes
• For any images presented appropriate consent has been obtained from the subjects. No

PLAGIARISM CHECKING METHODS:
• Plagiarism X-checker: Oct 14, 2021
• Manual Googling: Mar 16, 2022
• iThenticate Software: May 19, 2022 (16%)

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