Surgery and risk for multiple sclerosis: a systematic review and meta-analysis of case–control studies

Abstract

BackgroundAlthough the precise etiology of multiple sclerosis is largely unknown, there is some speculation that a prior history of surgery may be associated with the subsequent risk for developing the disease. Therefore, we aimed to examine surgery as a risk factor for the diagnosis of multiple sclerosis.MethodsWe searched for observational studies that evaluated the risk for developing multiple sclerosis after surgery that occurred in childhood (≤ 20 years of age) or “premorbid” (> 20 years of age). We specifically included surgeries classified as: tonsillectomy, appendectomy, adenoidectomy, or “surgery”. We performed a systematic review and meta-analyses and calculated odds ratios (OR) and their 95% confidence intervals (CIs) using a random effects model.ResultsWe identified 33 case–control studies, involving 27,373 multiple sclerosis cases and 211,756 controls. There was a statistically significant association between tonsillectomy (OR = 1.32, 95% CI 1.08-1.61; 12 studies, I2 = 44%) and appendectomy (OR = 1.16, 95% CI 1.01-1.34; 7 studies, I2 = 0%) in individual’s ≤ 20 years of age and the subsequent risk for developing multiple sclerosis. There was no statistically significant association between risk for multiple sclerosis and tonsillectomy occurring after age 20 (OR = 1.20, 95% CI 0.94-1.53; 9 studies, I2 = 32%), in those with appendectomy at > 20 years (OR = 1.26, 95% CI 0.92-1.72; 5 studies, I2 = 46%), and in those with adenoidectomy at ≤ 20 years of age (OR = 1.06, 95% CI 0.68-1.68; 3 studies, I2 = 35%). The combined OR of 15 studies (N = 2,380) looking at “surgery” before multiple sclerosis diagnosis was not statistically significant (OR = 1.19, 95% CI 0.83-1.70; I2 = 71%).ConclusionsWe found a small but statistically significant and clinically important increased risk for developing multiple sclerosis, in those with tonsillectomy and appendectomy at ≤ 20 years of age. There was no convincing evidence to support the association of other surgeries and the risk for multiple sclerosis. Well-designed prospective etiological studies, pertaining to the risk for developing multiple sclerosis, ought to be conducted and should include the examination of various surgeries as risk factors.

Environmental exposures and the risk of multiple sclerosis investigated in a Norwegian case-control study

“…In contrast to others [ 41 , 42 ], we found no differences between the patients and controls in the frequency of tonsillectomy, appendectomy or other autoimmune diseases than MS.…”

Childhood infections, vaccinations, and tonsillectomy and risk of first clinical diagnosis of CNS demyelination in the Ausimmune Study

“…In a recent meta-analysis, a history of tonsillectomy prior to age 20 years was associated with an increased risk of MS (pooled OR = 1.32, 95%CI 1.08-1.61, p = 0.006; 12 studies, I 2 = 44%), consistent with our findings for a first clinical diagnosis of CNS demyelinatio (Lunny et al, 2013). This effect was not apparent for tonsillectomy after 20 years of age (pooled OR = 1.20, 95%CI 0.94-1.53, p = 0.15; 9 studies, I 2 = 32%).…”

“…previous 5 years, rather than age at vaccination (DeStefano et al, 2003, Hernan et al, 2006, Farez and Correale, 2011, Zilber and Kahana, 1996, Lucas et al, 2007, Lucas et al, 2011, Rothman, 1990, Greenland et al, 2016, Haile et al, 1982, Burgess, 2003, ABS. Children's Immunisation Australia 1996, Lunny et al, 2013, Dias et al, 2009, Sumaya et al, 1978, Hernan et al, 2004. In a recent large case-control study using administrative data, 'any vaccination' in the previous 5 years was associated with a reduced risk of developing MS, particularly vaccination for influenza or tickborne encephalitis (Hapfelmeier et al, 2019).…”

Multiple sclerosis and immunological-related risk factors: Results from a case-control study

“…It is likely that if more people were included in the study groups, the results might show significant differences. Since, it seems that appendectomy may have a role in increasing the risk of MS. As, numerous studies have been conducted by other researchers, Lunny et al [34] used a metaanalysis of case-control studies to investigate and examine surgery as a risk factor for MS. The scientists searched for observational studies that evaluated the risk for developing multiple sclerosis after surgery in childhood ( 20 years of age) or "premorbid" (> 20 years of age).…”