Gender differences in experience of rheumatism

Autism and gender


Rheumatoid arthritis is often a more painful experience for women than it is for men, even though the visible symptoms are the same. Scientists are now saying that doctors should take more account of these subjective differences when assessing the need for medication. This and other findings are being presented at a congress currently in progress on gender medicine arranged by Karolinska Institutet.

For reasons yet unknown, rheumatoid arthritis is roughly three times more common amongst women than men. Moreover, several studies also suggest that rheumatoid arthritis eventually impairs the life quality of female suffers more than it does that of male sufferers. Here, too, the underlying reasons are unclear, but scientists have speculated that the medicines used affect women and men differently.

Researchers at Karolinska Institutet are now to present a study that gives vital clues as to why the prognosis is gender-specific. They have shown that men who undergo standard therapy for rheumatism respond significantly better than women having the same treatment – both objectively, such as in the degree of swelling in the joints, and subjectively in terms of their own experience of the disease.

“Purely objectively, the drug had a somewhat better effect on the men than on the women,” says associate professor Ronald van Vollenhoven, who led the study. “But the greatest difference was of a subjective nature. The women in the study felt sicker even when their joints showed the same improvements.”

According to Dr van Vollenhoven, it is important to take into account subjective difference when judging the severity of the disease. If doctors only consider the physical symptoms, people with severe pain might be deprived of the most effective medicine, which, owing to high costs and the risk of side-effects, is only given to the worst sufferers.

In a follow-up analysis, scientists compared the degree of disease in men and women who had received ‘biological’ medicines, which are only given to people who are considered seriously ill. The results of their study showed that while women and men who had been put on a course of treatment were at the same level as regards the objective manifestations of the disease, women felt themselves to be sicker than the men.

“Women and men have been treated on equal terms from the perspective of the doctors, but it’s possible that no one has been aware of the fact that the pain can be worse for women than for men,” says Dr van Vollenhoven. “Since our objective is to reduce suffering, we should try to take more account of the subjective aspects of rheumatoid arthritis.”

Continuation versus discontinuation of anti-rheumatic biologics during the perioperative period: What does the evidence support?

For patients with rheumatic arthritis and other chronic inflammatory diseases, discontinuing biologic disease-modifying anti-rheumatic drugs (bDMARDs) prior to orthopaedic surgery does not appear to increase the risk of surgical site infections or delayed wound healing, concludes a review and meta-analysis in The Journal of Bone & Joint SurgeryThe journal is published in the Lippincott portfolio in partnership with Wolters Kluwer.

However, patients discontinuing bDMARDs may be more likely to experience a disease flare following orthopaedic surgery, according to the report by Bernard H. van Duren of University of Leeds, UK, and colleagues.

Decisions regarding bDMARD discontinuation must balance the risk of disease flares

bDMARDs have represented a major advancement in the treatment of rheumatic arthritis and other inflammatory diseases. Although effective in slowing disease progression, these biologic agents have traditionally been associated with an increased risk of infection.

In the case of total joint replacement, infections are a potentially devastating complication; thus, some surgeons and other specialists recommend discontinuing  bDMARD therapy during the perioperative period. “[H]owever,” the researchers write, “there has been no definitive evidence showing a clear benefit of discontinuing the use of bDMARDs, and in doing so, patients may be at an increased risk for higher disease activity.”

Toward clarifying the issue, Dr. van Duren and colleagues performed a systematic review of 11 studies that included 4,959 patients who discontinued their bDMARDs and 2,385 patients who continued their bDMARDs. The most common diagnosis among these patients was rheumatoid arthritis, and tumor necrosis factor inhibitors were the most common type of bDMARD. However, other diagnoses and bDMARDs were represented.

The meta-analysis found no significant difference in the rate of surgical site infections between patients who discontinued (3.06 percent) versus continued their bDMARDs (2.90 percent). The rates of delayed wound healing were also similar between those discontinuing (2.28 percent) and continuing their bDMARDs (0.99 percent). Subgroup analysis of patients undergoing total joint arthroplasty also showed no significant difference in the rate of surgical site infection.

However, patients who discontinued their bDMARDs were substantially more likely to experience a disease flare during the postoperative period: 25.71 percent compared with 7.32 percent among patients who continued their bDMARDs. The pooled analysis suggested a 78 percent reduction in the odds of having a flare for patients who continued bDMARD therapy.

Disease flares compromise patient rehabilitation following orthopaedic surgery. In addition, patients who experience a flare often require treatment with corticosteroids, introducing an additional risk of infection. “It is therefore important to balance the risk of flares against the risk of infection if bDMARDs are continued during the perioperative period,” Dr. van Duren and coauthors write.

The researchers note that their review is among the first “to comprehensively investigate the effect of continuing or discontinuing bDMARDs perioperatively across inflammatory diseases in patients undergoing orthopaedic surgery.” However, although the analysis included data on a large number of patients, the ability to draw conclusions is limited by the “generally low” quality of the available studies, as reflected by the inconsistency of current guidelines regarding perioperative bDMARD discontinuation. Dr. van Duren and colleagues emphasize the need for randomized controlled trials “to provide definitive answers in this important area.”

Large genetic study uncovers potential new treatments for inflammatory diseases

Tie One on for Multiple Sclerosis


Researchers from the Research Centre of Applied and Preventive Cardiovascular Medicine at the University of Turku, Finland, have studied over ten million DNA variations and found new links between the human genome and inflammation tracers. The study uncovered new possibilities for treatment of diseases such as multiple sclerosis, Crohn’s disease and coeliac disease.

Cytokines and growth factors, which circulate in the bloodstream, are important proteins for regulating inflammation reactions. Changes in their mode of operation have been linked with many inflammatory diseases, such as Crohn’s disease, multiple sclerosis, atherosclerosis, ulcerative colitis and many types of cancer.

In this latest study, based on population data and coordinated by the University of Turku’s Research Centre of Applied and Preventive Cardiovascular Medicine, an investigation was made of the links between 41 different cytokines and growth factors and 10.7 million DNA variations.

? We wanted to find out the molecular-level processes that lead to an increased risk of developing inflammatory diseases. Understanding these processes will enable more effective treatment of diseases, explains Professor Olli Raitakari, Director of the Research Centre.

Researchers noticed that the medicine daclizumab, previously used for treating organ rejection reactions, could possibly also be used in the treatment of multiple sclerosis and Crohn’s disease. In addition, an increase in the activity of MIP1b-cytokine could also serve as a method of treatment against coeliac disease and Behcet disease. Further clinical studies are required to confirm the observations.

Evidence from human genetics speeds up medical development

Technological development has enabled the practice of genome-wide association studies since the turn of the century.

? In these kinds of studies, millions of DNA variations are examined and their impact is assessed for each property being studied. The studies carried out so far have succeeded in uncovering, for example, over one hundred genomic loci which have an impact on the risk of developing Crohn’s disease or ulcerous colitis.

In studies of connections between genetic variations and disease risks, the precise molecular process causing the increased risk often remains unclear. In order to uncover this molecular process, genome-wide association studies use as response variables molecules that mediate disease-risk through the bloodstream, such as cytokines and growth factors, instead of using the diseases themselves.

Rheumatoid Arthritis – COVID-19 booster vaccination is safe and effective in immunosuppressed patients


Patients under immunosuppressive therapy, who do not respond to primary COVID-19 vaccination, have an increased risk for severe COVID-19 disease courses. Until now, it was not clear whether those patients at risk can benefit from an additional booster vaccination. Recent research findings from MedUni Vienna show that a third vaccination is safe and effective in those patients who were initially unable to produce antibodies after vaccination. The study was recently published in the acclaimed journal Annals of the Rheumatic Diseases.

Even after two vaccinations, patients receiving immunosuppressive treatment for autoimmune diseases often fail to develop an adequate immune response after vaccination to protect them against COVID-19. In particular patients treated with the B-cell depleting drug rituximab, e.g. for rheumatoid arthritis, are considered to be particularly at risk for severe disease courses. Up until now, it had not been established whether these patients can benefit from a third vaccination and whether they should be vaccinated with the same vaccine or a different vaccination strategy.

Booster vaccination essential
This question has now been answered by a recently published study conducted by an interdisciplinary research group from MedUni Vienna, coordinated by the Division of Rheumatology of the Department of Medicine III. First author Michael Bonelli and his study team were able to show that even patients under rituximab treatment who did not respond to primary vaccination are able to develop an immune response following a booster vaccination. “Since patients under certain immunosuppressive therapy are at high risk for an insufficient vaccination response and therefore a severe COVID-19 disease, an early booster vaccination should be considered” explains Michael Bonelli.

Included in vaccination recommendations
“Our study is the first randomised, blinded trial to show the efficacy and safety of a booster vaccination in patients without an immune response after two vaccinations because of an rituximab treatment. In addition, ongoing studies investigate the efficacy of a forth vaccination in our patients at risk.” points out Daniel Aletaha, Head of the Division of Rheumatology at MedUni Vienna. The results obtained with the chosen study design are considered particularly reliable within the scientific community. Daniel Aletaha says: “Accordingly, our study, which also compared the efficacy and safety of different vaccination strategies, has already been included in the World Health Organization (WHO) and Australian Technical Advisory Group on Immunization (ATAGI) Covid-19 vaccination recommendations for immunosuppressed patients.”

Disease-modifying antirheumatic drugs do not seem to protect people with rheumatoid arthritis against Parkinson’s disease


The autoimmune disorder rheumatoid arthritis has been associated with a lower risk of Parkinson’s disease (PD) in previous studies, with antirheumatic drugs as one possible explanation. However, most of the disease-modifying antirheumatic drugs (DMARDs) were not associated with the risk of PD in individuals with rheumatoid arthritis, a new register-based study from the University of Eastern Finland shows. An exception was the use of chloroquine or hydroxychloroquine which associated with a lower risk of PD. The findings were published online on January 21, 2022, in Neurology®, the medical journal of the American Academy of Neurology.

Risk factors for PD are still unclear. Rheumatoid arthritis has been linked to PD with conflicting findings, and both risk lowering and increasing findings have been reported. The medications used to treat rheumatoid arthritis could be one possible explanation for the potential lower risk of PD in individuals with rheumatoid arthritis but there are only few previous studies.

According to the newly published study, previous use of methotrexate, sulfasalazine, gold preparations or immunosuppressants at least three years before the PD diagnosis was not associated with the risk of PD in individuals with rheumatoid arthritis. However, users of chloroquine or hydroxychloroquine had a 26% lower relative risk of PD. Different comorbidities, such as cardiovascular diseases and diabetes, along with age, sex, and duration of rheumatoid arthritis, were controlled for in the study.

Chloroquine and the more commonly used hydroxychloroquine have various effects on the immune system. These medicines have been found to have antiparkinson potential in animal models of PD. According to researchers, the possible protective association of chloroquine and hydroxychloroquine should be further investigated.

This study was conducted as part of the FINPARK study, which covers 22,189 community-dwelling Finns with PD and a matched comparison cohort. The study was limited to persons who had been diagnosed with rheumatoid arthritis at least three years before PD.