Tuesday, 5 July 2016

The autoimmune predilection: rheumatoid arthritis in MS

Medicine (Baltimore). 2016 Jun;95(26):e3999.

Increased incidence of rheumatoid arthritis in multiple sclerosis: A nationwide cohort study.

Tseng CC, Chang SJ, Tsai WC, Ou TT, Wu CC, Sung WY, Hsieh MC, Yen JH.

Abstract

Past studies have shown inconsistent results on whether there is an association between multiple sclerosis (MS) and rheumatoid arthritis. To investigate the possible relationship between the 2 autoimmune diseases, we performed a nationwide cohort study utilizing the National Health Insurance Research Database and the Registry of Catastrophic Illness.A total of 1456 newly diagnosed patients with MS and 10,362 control patients were matched for age, sex, and initial diagnosis date. Patients with MS had a higher incidence of rheumatoid arthritis (age-adjusted standardized incidence ratio: 1.72; 95% confidence interval = 1.01-2.91). There was a positive correlation in being diagnosed with rheumatoid arthritis in patients previously diagnosed with MS when stratified by sex and age. The strength of this association remained statistically significant after adjusting for sex, age, and smoking history (hazard ratio: 1.78, 95% confidence interval = 1.24-2.56, P = 0.002).In conclusion, this study demonstrates that a diagnosis of MS increased the likelihood of a subsequent diagnosis of rheumatoid arthritis in patients, independent of sex, age, and smoking history.

Figure: The cumulative incidence of rheumatoid were higher in MS than in controls (p=0.002)

Sometimes trouble comes in twos! Here, the authors report the occurrence of rheumatoid arthritis (RA) in MS. And like in MS, the occurrence of RA was higher in females. A study of this scale or larger is required to make this type of study work. Which may explain why there is conflicting data out there, as previous work have been in smaller samples of people.

If we look at autoimmune disorders as a whole, their link with MS is more than simply coincidence. The associations are attributable partly to genetics (HLA genotype association), immune system dysfunction (e.g. antibodies targeting self antigens in the body) and environmental factors (e.g. smoking). The list of well described associated autoimmune disorders include Type I diabetes, Grave's disease, Hashimoto's disease, rheumatoid arthritis, alopecia, psoriasis/scleroderma, vitiligo, uveitis and autoimmune glomerulonephritis.

The link between RA and MS may be the underlying autoimmunity; there's a role for T-helper type 17 (Th17) immune cell activation in both conditions, resulting in  increased disease activity and reduced response to treatment. Thus common immunological pathways may be the key to increased susceptibility to both RA and MS in a single individual.

The authors also allude to more aggressive treatment may be needed when they co-occur. They point out that depression observed in both disorders leads to higher mortality in RA (Ang, DC Comorbid depression is an independent risk factor for mortality in patients with rheumatoid arthritis. J Rheumatol 2005; 32: 1013-9). The major problem with this is that we know that anti-TNF treatment used in aggressive RA also leads to the onset of demyelinating disease, i.e. MS (Mohan N Demyelination occurring during anti-tumour necrosis factor alpha therapy for inflammatory arthritides. Arthritis Rheum 2001;44:2862-2869) and probable worsening of the MS (Van Oosten BW, Increased MRI activity and immune activation in two multiple sclerosis patients treated with the monoclonal anti-tumour necrosis factor antibody cA2. Neurology 1996; 47: 1531-1534). So treatment options need to be considered carefully.

9 comments:

  1. How interesting! I had a juvenile form of rheumatoid arthritis and my doctor then told me it was treatable but that, age 45, inflammation would come back. No idea why he thought so - but what came at age 45 was an ms diagnosis. Funnily the remainder of inflammation and pain I had in my feet from the arthritis vanished once I was on Fingolimod/Gilenya. Ha!

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    1. You may be even happier to know that fingolimod helped the rheumatoid mouse!

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  2. I thought that the association between MS and other autoimmune diseases was relativity weak (and limited to RA and ? something else) unlike the majority of other autoimmune diseases which commonly co-exist?

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    1. Thyroid autoimmune disease is the commonest, around 20% of MS subjects had thyroid antibodies in a Swedish study - this is not to say that everyone of the 20% will develop the clinical disease.

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    2. Grave's, although this could be bias as Hashimoto's is difficult to diagnose.

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  3. I am always intrigued because just the inhibition of TNF-alpha is MS gets worse or does arise disease, and in turn makes the RA improve...
    The root of 02 diseases can be there ...

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    1. Agree, it's probably in the balance of the cellular composition based around how skewed it becomes.

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