The prevalence of inflammatory bowel disease (IBD) in patients with multiple sclerosis (MS): A systematic review and meta-analysis

Amirreza Nasirzadeh; Reza Jahanshahi; Mahsa Ghajarzadeh; Aida Mohammadi; Abdorreza Naser Moghadasi

doi:10.4103/ijpvm.ijpvm_44_22

REVIEW ARTICLE

Year : 2023 | Volume : 14 | Issue : 1 | Page : 81

The prevalence of inflammatory bowel disease (IBD) in patients with multiple sclerosis (MS): A systematic review and meta-analysis

Amirreza Nasirzadeh¹, Reza Jahanshahi², Mahsa Ghajarzadeh³, Aida Mohammadi⁴, Abdorreza Naser Moghadasi³
¹ Student Research Committee, Mashhad University of Medical Sciences, Mashhad, Iran
² Department of Neurology, University of Medical Sciences, Gorgan, Iran
³ Multiple Sclerosis Research Center, Neuroscience Institute, Tehran University of Medical Sciences, Tehran, Iran
⁴ Universal Council of Epidemiology (UCE), Universal Scientific Education and Research Network (USERN), Tehran University of Medical Sciences, Tehran, Iran

Date of Submission	07-Feb-2022
Date of Acceptance	27-Oct-2022
Date of Web Publication	22-Jun-2023

Correspondence Address:
Abdorreza Naser Moghadasi
Sina Hospital, Tehran
Iran

Source of Support: None, Conflict of Interest: None

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DOI: 10.4103/ijpvm.ijpvm_44_22

Abstract

Background: This systematic review and meta-analysis aim to update the pooled prevalence of Inflammatory bowel disease (IBD) in patients with multiple sclerosis (MS). Methods: Two researchers independently and systematically searched PubMed, Scopus, EMBASE, Web of Science, and google scholar. They also searched for references of the included studies, and conference abstracts that were published up to September 2021. Results: The literature search revealed 5719 articles, after deleting duplicates 3616 remained. Finally, 17 studies were included. The pooled prevalence of IBD in MS was 1% (I² = 96.3%, P < 0.001). The pooled odds ratio of developing IBD in MS cases was 1.36 (95% CI: 1.1–1.6) (I² = 58.3, P = 0.01). Conclusions: The results of this systematic review and meta-analysis show that the pooled prevalence of IBD in MS patients was 1% and the pooled odds ratio of developing IBD in MS cases was 1.36.

Keywords: Inflammatory bowel disease, multiple sclerosis, prevalence

How to cite this article:
Nasirzadeh A, Jahanshahi R, Ghajarzadeh M, Mohammadi A, Moghadasi AN. The prevalence of inflammatory bowel disease (IBD) in patients with multiple sclerosis (MS): A systematic review and meta-analysis. Int J Prev Med 2023;14:81

How to cite this URL:
Nasirzadeh A, Jahanshahi R, Ghajarzadeh M, Mohammadi A, Moghadasi AN. The prevalence of inflammatory bowel disease (IBD) in patients with multiple sclerosis (MS): A systematic review and meta-analysis. Int J Prev Med [serial online] 2023 [cited 2023 Oct 1];14:81. Available from: https://www.ijpvmjournal.net/text.asp?2023/14/1/81/379416

Introduction

Multiple sclerosis (MS) is an inflammatory disease targeting the central nervous system (CNS) mostly affecting youth in productive age.^[1],[2] Patients with MS have a wide range of physical and psychological co-morbidities.^{[3],[4],[5],[6],[7]} These comorbidities are associated with a decreased quality of life, more hospitalization, imposing a cost to both the health system and the patients, and a higher rate of mortality.^[8]

Previous studies suggested that the presence of co-morbidities in MS is related to diagnostic delays, more MS-related disability, and a greater risk of disability progression during the disease.^[9]

Inflammatory bowel disease (IBD) including ulcerative colitis (UC) and Crohn's disease, is another autoimmune disorder.^[10] It is shown that the prevalence of IBD before and after diagnosis is higher in MS patients than in controls.^[11] In recent years, evidence for reciprocal comorbidity of MS and IBD has increased.^[12],[13] Literature suggests that MS share genetic risk with IBD but the magnitude of this overlap is not clear.^[14] TNF alpha play role in the pathogenesis of both diseases.^[15]

In a previous systematic review and meta-analysis, Kosmidou et al.^[16] reported that MS patients have an increased risk of having IBD of 50%. Their study was published in 2017 and in this systematic review, we want to update their results. So, the goal of this systematic review and meta-analysis is to update the pooled prevalence of IBD in MS patients.

Methods

Literature search

Two researchers independently and systematically searched PubMed, Scopus, EMBASE, Web of Science, and google scholar. They also searched for references of the included studies, and conference abstracts published up to September 2021.

Inclusion criteria were

We included cross-sectional studies which had reported the prevalence of IBD (UC/CD) in MS patients.

Exclusion criteria were

Letters to the editor, case-control, case reports, and cross-sectional studies which had no clear data.

Data search and extraction

The search strategy included the MeSH and text words such as (“Disseminated Sclerosis” OR “multiple sclerosis” OR “MS” OR “Acute Fulminating”) AND (“IBD” OR “Inflammatory Bowel Disease” OR “Crohn's Enteritis” OR “Regional Enteritis” OR “Crohn's Disease” OR “Granulomatous Enteritis” OR “Ileocolitis” OR “Granulomatous Colitis” OR “Terminal Ileitis” OR “Regional Ileitis” OR “Regional Ileitides” OR “Idiopathic Proctocolitis” OR “Ulcerative Colitis” OR “Colitis Gravis”).

Two independent researchers independently evaluated the articles.

Data regarding the total number of participants, first author, publication year, country of origin, mean age, and the number of patients with IBD (UC/CD) was recorded.

Risk of bias assessment

We evaluated the risk of potential bias with the Hoy quality assessment scale (adapted for cross-sectional studies).^[17]

Statistical analysis

All statistical analyses were performed using STATA (Version 14.0; Stata Corp LP, College Station, TX, USA). We used random effects model. The pooled ODDs ratio (OR) was calculated.

To determine heterogeneity, Inconsistency (I²) was calculated.

Results

The literature search revealed 5719 articles, after deleting duplicates 3616 remained. Finally, 17 studies were included [Figure 1].

Figure 1: Flow diagram presenting the selection of eligible studies according to PRISMA 2020 flow diagram

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Finally, 17 articles were included. Totally105155 MS patients and 506423 controls were evaluated.

Basic characteristics of included studies are summarized in [Table 1].

Table 1: Basic characteristics of the included studies

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The pooled prevalence of IBD in MS was 1% (I² = 96.3%, P < 0.001) [Figure 2].

Figure 2: The pooled prevalence of IBD in MS

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The pooled odds ratio of developing IBD in MS cases was 1.36 (95%CI: 1.1-1.6) (I² = 58.3, P = 0.01) [Figure 3].

Figure 3: The pooled odds ratio of developing IBD in MS cases

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The results of Hoy quality assessment in seen in [Table 2].

Table 2: Quality assessment checklist for included studies

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Discussion

The results of this study show that the pooled prevalence of IBD in MS is 1% and the odds of developing IBD in MS cases was 1.36 which shows that MS patients 36% have significantly higher odds of developing IBD.

Kosmidou et al.^[16] evaluated both the risk of developing MS in IBD and IBD in MS and found that both IBD and MS patients have a fifty percent increased risk of developing MS or IBD. They estimated the pooled RR of IBD comorbidity in MS cases as 1.55 (95% CI: 1.32–1.88). The difference between the result of our systematic review and the previous one could be due to the higher number of included studies in our survey. A recent systematic review and meta-analysis showed the risk of developing IBD in MS as 1.53, P < 0.001.^[18]

MS patients suffer from a wide range of comorbidities (both physical and psychological) which are associated with many adverse outcomes such as utilizing health care and imposing costs.

Kirby et al.^[19] found that comorbid autoimmune disease is not associated with MS progression except asthma which was related to higher disability status.

Nielsen et al.^[20] enrolled 12403 MS and 20 798 controls and found that MS patients were at higher risk of developing ulcerative colitis (RR = 2). They also found that the first degree of MS patients is at higher risk of developing Crohn's disease and ulcerative colitis.

Castelo-Branco et al.^[21] enrolled 6602 MS patients and 61,828 healthy subjects and reported no significant difference in the frequency of UC and CD between the two groups.

The co-occurrence of IBD and MS could be explained by both genetic (single-nucleotide polymorphisms such as (rs13428812), UC (rs116555563) and CD (rs13428812, rs9977672)) and environmental risk factors (smoking, cold climate, socioeconomic status).^{[14],[22],[23],[24]} Yang et al.,^[14] using Mendelian randomization found evidence for the causal effect of MS on UC and IBD.

In a review which was conducted by Katsanos et al.,^[25] it was suggested that IBD cases have demyelinating events in both peripheral and central nervous systems and there is no exact evidence to decide if anti-TNF-α therapies result in developing demyelination or not.

As both MS and IBD are chronic inflammatory diseases there is no exact evidence that which of them preceded the other. The role of brain-gut interaction should not be ignored.

In a study by Lange and Shiner, jejunal biopsies of MS patients demonstrated intestinal inflammatory cell infiltration and villous atrophy.^[26]

Kosmidou et al.^[16] in their systematic review and meta-analysis found that the risk of developing IBD in MS cases and vice versa is similar in included studies.

The only point is that clinicians should consider gastrointestinal manifestations in MS cases.

IBD is a group of inflammatory relapsing autoimmune diseases that is the result of dysregulation of the adaptive and innate immune systems. In both MS and IBD, IL-17 level is high which prominent the role of T helper 17 in the pathogenesis of both diseases.^[27] MS and IBD have relapsing and remitting nature and evidence shows that MS medications such as interferons or rituximab could start or exacerbate the IBD in MS patients.^[27],[28]

Both neurologists and gastroenterologists should be aware of MS or IBD comorbidity to consider better therapy and follow-up.

This systematic review and meta-analysis have some strengths. First, it is the first study. Second, the number of included studies is high. But, prospective cohort studies should be done to assess the incidence of IBD in MS.

Conclusion

The result of this systematic review and meta-analysis shows that the pooled prevalence of IBD in MS patients was 1% The pooled odds ratio of developing IBD in MS cases was 1.36.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

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