29 April 2022 at 2:49 am #887MParticipant
Hi Dr. Usher,
I hope this message reaches you but I would understand if you don’t find the time to answer.
I was prescribed Sulfasalazine by a reumatologist at an academic hospital in Germany to treat my AF. I will get my 2nd arthrolysis in 9 weeks. The idea is to already start now with the Sulfasalazine and continue as well after the surgery. Do you have thoughts on this medication? If so, I would be happy to hear your opinion!
Thank you for your research.29 April 2022 at 8:00 pm #888Kayley UsherKeymaster
Thanks for your question, it has lead me to some informative reading that’s helpful. I don’t know much about sulphasalazine, so I’ve been doing a little reading of the scientific literature. As you may know, this is an old drug that has been used to treat a range of inflammatory conditions, sometimes together with hydroxychloroquine. Sulphasalazine can, however, have some serious side effects including organ damage and loss of male fertility (the latter is usually reversible as I understand it).
The reason may be this. Sulphasalazine is broken down into two molecules by gut microbes, these molecules are called sulphapyridine (SP) and 5-aminosalicylic acid (5-ASA). The SP creates oxidative damage and sometimes allergic effects, and it’s thought that it’s this part of sulphasalazine that creates the majority of the serious side effects.
However, you may recognise the chemical composition of the second molecule, 5-ASA, since it’s structurally very similar to the acetylsalicylic acid found in aspirin. Aspirin is well known and widely prescribed for treating heart fibrosis (heart disease), and I have advocated for its use in treating arthrofibrosis, together with omega 3 fatty acid supplements, for some time. Unfortunately, aspirin can cause bleeding and stomach ulcers in the longer term, especially at the higher doses.
The good news is that there is a medication called mesalazine that only contains the 5-ASA, and the side effects are reportedly fewer than for Sulphasalazine – you can check with your rheumatologist about this. Mesalazine is widely available and used for treating inflammatory conditions, and is beginning to be investigated for treating fibrotic conditions.
A 2021 paper by Hoffman et al. (see below)1 studied the anti-fibrotic effects of mesalazine in heart cell culture. I’ll quote their findings “We found that mesalazine reduces fibroblast proliferation, myofibroblast differentiation, and collagen deposition after TGFβ induction. Furthermore, mesalazine ameliorated TGFβ-induced changes in fibroblast mechanical properties, such as cell stiffness, stress relaxation, and cell adhesion. Finally, we shed new light on the molecular mechanisms of mesalazine: we propose dual inhibition of SMAD2/3 and ERK1/2 phosphorylation as a novel concept by which mesalazine may prevent cardiac fibrosis.” This is very interesting because they found that mesalazine downregulated all the major pathway involved in fibrosis.
But we shouldn’t get too excited because this is only one study and it was only done in cell culture. However, this is an old and widely used medication that has been shown to be useful. Also, I’ve only just begun to read about this, and more reading is needed. Nonetheless, it seems that mesalazine may be a better medication to try than sulphasalazine, and it would be worth discussing this with your rheumatologist. I’m happy to communicate with him/her if they would like more information about the arthrofibrosis side of things.
I hope this helps.
1 Hoffmann, M. et al. Repurposing mesalazine against cardiac fibrosis in vitro. Naunyn Schmiedebergs Arch Pharmacol 394, 533-543, doi:10.1007/s00210-020-01998-9 (2021).1 May 2022 at 7:33 pm #889MParticipant
Thank you for your thorough reply Dr. Usher. That is very helpful. I will propose mesalazine as alternative to my rheumatologist. Given your clear reasoning I think he will be open to give it a try. I know it is just a start and there are no guarantees, but it at least seem to make sense in theory.2 May 2022 at 5:04 pm #890Kayley UsherKeymaster
Thanks, and all the best for your surgery! Feel free to ask more questions – as you probably know going easy on the leg exercises is very important.
I would appreciate it if you let me know how you go. You can use the “contact us” email if you like to keep it private.
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