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Autoimmune Comorbid Conditions in Multiple Sclerosis


Table 2: Some of the Autoimmune Conditions More Frequently Associated with Disease-Modifying Agents used in MS Condition


Description Liver dysfunction Myasthenia gravis Panniculitis Psoriasis Thyroid dysfunction Ulcerative colitis Vasculitis In a study of 40 RRMS patients treated with IFNβ, transient liver function alteration was seen


but did not require treatment discontinuation, with the exception of one patient who was already suffering from a drug-induced hepatopathy at baseline


Cases of myasthenia gravis have been reported in MS patients following IFNβ therapy Several cases of panniculitus associated with IFNβ treatment and GA treatment in MS patients


Worsening of cutaneous psoriasis and activation of psoriasis in an MS patient during IFNβ therapy, which resolved after treatment discontinuation. Cases of activation of psoriasis reported during IFNβ treatment in MS patients


In a study of 40 RRMS patients treated with IFNβ, three cases of persistent autoimmune thyroid dysfunction were reported. Autoimmune thyroid disease has been reported in patients receiving IFNβ, but not in patients receiving GA


Several reported cases of ulcerative colitis in MS patients during IFNβ therapy Several reported cases of vasculitis in MS patients during IFNβ therapy GA = glatiramer acetate; IFNβ = interferon beta; MS = multiple sclerosis; RRMS = relapsing-remitting multiple sclerosis.


Studies of Autoimmune Comorbidities in Multiple Sclerosis


Until recently, clinical data relating to the co-occurrence of autoimmune diseases in MS have been predominantly based on uncontrolled case series or small case-control studies, with few studies accounting for confounding factors such as age and sex. There are many difficulties inherent to such studies, such as selection or ascertainment bias. Results may differ depending on which conditions are included and how the diagnosis is reached.18


In ethnically-mixed populations such as that


of North America, the use of spouses as controls allows ethnic matching19


(the use of such controls is fairly common in genetic studies but much less widespread in clinical trials20–22


). However, since MS is


significantly more prevalent in females, this approach can increase a potential gender imbalance between cases and controls.


In a study of families in which several members had been diagnosed with MS (176 families, 386 individuals with MS, and 1,107 first-degree relatives), participants were studied for a history of coexisting autoimmune disorders (see Figure 1).23


Of the 386 individuals with MS,


26 % had a coexisting autoimmune disorder. Of the 1,107 first-degree relatives, 64 % had a history of autoimmune conditions. The most commonly reported autoimmune conditions in MS patients and their relatives were Hashimoto’s thyroiditis, psoriasis, and inflammatory bowel disease (IBD).


A recent American population-based case-control study using a large database (5,296 MS cases and 26,478 matched controls) found that individuals with MS were more likely than controls to have uveitis, IBD, and Bell’s palsy prior to MS diagnosis.24


They were also more likely to


develop Guillain–Barré syndrome and bullous pemphigoid. However, the study found no increased likelihood of MS patients having or developing rheumatoid arthritis (RA), lupus, or thyroiditis. The study concluded that MS may share environmental triggers, genetic susceptibilities, and/or


US NEUROLOGY


alterations in immune homeostasis with IBD and uveitis, but not with other autoimmune disorders. The study had limitations relating to its methodology and reliance on electronic patient records. By grouping certain diseases together, opportunities to gain valuable information were lost; for example, IBD incorporates Crohn’s disease and ulcerative colitis (UC), which have immunopathological differences, and to differentiate between the two might have given clues to shared mechanisms with MS.


A Danish registry study showed that autoimmune disorders tended to co-occur with MS and to occur in MS patients’ families, but that this was not a uniform phenomenon across all diseases.25


Patients with type


1 diabetes were found to have more than a threefold increased risk of developing MS. Compared with the general Danish population, MS patients were found to have increased incidences of type 1 diabetes, UC, autoimmune thyroiditis, and pemphigoid, but a decreased incidence of RA. MS and RA appear to have a reduced likelihood of co-existence.26 This inverse association between MS and RA has also been found in a population-based cohort study using the UK General Practice Research Database.27


While the above studies show similarities, there are inconsistencies in the data regarding the association between thyroiditis and MS. Autoimmune thyroiditis was found to be significantly more prevalent in male MS patients than in male controls (9.4 versus 1.9 %; p=0.03). However, there was no significant difference in the prevalence of autoimmune thyroiditis in female MS patients and female controls (8.7 versus 9.2 %). Further studies are required to determine the cause of this increased prevalence of autoimmune thyroiditis in males with MS.28 This finding illustrates the importance of avoiding gender bias in studies of comorbidities in MS.


A large North American study found no association between MS and asthma,24


although asthma associated with chronic obstructive 135


Blake and Murphy, 1997;60 et al., 2004;78


Soós, et al., 2004;48 Poulin, et al., 2009;81 et al., 200682


Dionisiotis,


Gharagozli, et al., 201179 Ball, et al., 2009;80 Soares Almeida,


López-Lerma, et al., 2009;83 and Capsoni, 2010;84 200585


Durelli, et al., 1998;54 201161


Schott, et al., 2007;59 2010;86


La Mantia Navne, et al., Rotondi, et al., Rodrigues, et al., Tuna, et al., 2011;87


Palao-Duarte, et al., 200588 Daza-Barriga, 2008;89 et al., 2004;90


Débat Zoguéreh, Szilasiová, et al., 200991 Reference Durelli, et al., 199955


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