Johannes J. Rasker

In this study, methotrexate (MTX) was compared with placebo in the treatment of systemic sclerosis (scleroderma, SSc) in a 24 week randomized double-blind trial, followed by an observational trial of 24 weeks duration. Twenty-nine scleroderma patients were allocated to receive weekly injections of either 15 mg MTX or placebo. Patients who responded favourably after 24 weeks continued with the same regimen for a further 24 weeks; those who showed a poor response on placebo were allocated to further treatment with 15 mg MTX weekly, and those who responded poorly to treatment with 15 mg MTX weekly had their doses increased to 25 mg. A favourable response was defined as an improvement of total skin score (TSS) by ≧ 30%, of single breath diffusion capacity (DLco) by ≧ 15%, or of the score on a visual analogue scale of general well-being (VAS) by ≧ 30%, provided that such improvements were not accompanied by persistent digital ulcerations or worsening of DLco ≧15%. Seventeen patients were allocated to MTX treatment and 12 to treatment with placebo. After 24 weeks, a significantly larger number of patients receiving MTX (n = 8, 53%) who completed the first 24 weeks of the study had responded favourably compared to patients receiving placebo (n = 1, 10%, P = 0.03). Comparison of separate variables between the two treatment groups by intention-to-treat analysis at week 24 showed improvement in the MTX group of TSS (P = 0.06) and creatinine clearance (P = 0.07). At week 48, 13 patients received MTX from the start of the study and nine during 24 weeks. From these 22 patients, 15 (68%) responded favourably and compared with the start of the study they showed significant improvement of TSS (P = 0.04), VAS (P = 0.02), grip strength of the right hand (P = 0.02) and ESR (P = 0.01). Although the number of patients enrolled in this study is small, these results suggest that in a group of patients with active systemic sclerosis, low-dose MTX seems to be more effective than placebo according to pre-defined response criteria.

PURPOSE: Multiple clinical and epidemiological studies have provided estimates of fibromyalgia prevalence and sex ratio, but different criteria sets and methodology, as well as bias, have led to widely varying (0.4%->11%) estimates of prevalence and female predominance (>90% to <61%). In general, studies have failed to distinguish Criteria based fibromyalgia (CritFM) from Clinical fibromyalgia (ClinFM). In the current study we compare CritFM with ClinFM to investigate gender and other biases in the diagnosis of fibromyalgia. METHODS: We used a rheumatic disease databank and 2016 fibromyalgia criteria to study prevalence and sex ratios in a selection biased sample of 1761 referred and diagnosed fibromyalgia patients and in an unbiased sample of 4342 patients with no diagnosis with respect to fibromyalgia. We compared diagnostic and clinical variables according to gender, and we reanalyzed a German population study (GPS) (n = 2435) using revised 2016 criteria for fibromyalgia. RESULTS: In the selection-biased sample of referred patients with fibromyalgia, more than 90% were women. However, when an unselected sample of rheumatoid arthritis (RA) patients was studied for the presence of fibromyalgia, women represented 58.7% of fibromyalgia cases. Women had slightly more symptoms than men, including generalized pain (36.8% vs. 32.4%), count of 37 symptoms (4.7 vs. 3.7) and mean polysymptomatic distress scores (10.2 vs. 8.2). We also found a linear relation between the probability of being females and fibromyalgia and fibromyalgia severity. Women in the GPS represented 59.2% of cases. DISCUSSION: The perception of fibromyalgia as almost exclusively (≥90%) a women's disorder is not supported by data in unbiased studies. Using validated self-report criteria and unbiased selection, the female proportion of fibromyalgia cases was ≤60% in the unbiased studies, and the observed CritFM prevalence of fibromyalgia in the GPS was ~2%. ClinFM is the public face of fibromyalgia, but is severely affected by selection and confirmation bias in the clinic and publications, underestimating men with fibromyalgia and overestimating women. We recommend the use of 2016 fibromyalgia criteria for clinical diagnosis and epidemiology because of its updated scoring and generalized pain requirement. Fibromyalgia and generalized pain positivity, widespread pain (WPI), symptom severity scale (SSS) and polysymptomatic distress (PSD) scale should always be reported.