Characteristics of mpox positive, versus mpox negative, and mpox unsuspected clients from the Centre of Sexual Health, Public Health Service of Amsterdam, 20 May to 15 September 2022.

BACKGROUND: In May 2022, an outbreak of mpox (monkeypox) in men-who-have-sex-with-men (MSM) emerged and quickly affected over 100 countries. In the early stages of the outbreak, overlap in symptoms with sexually transmitted infections (STI) made triage for mpox testing challenging. More information was needed on whom to screen and the main route of transmission. OBJECTIVES: We aimed to identify characteristics of mpox cases to further strengthen case definitions. We also compared Cycle threshold (Ct) values of the DNA positive mpox samples as a proxy for viral load by body location. METHODS: From 20 May 2022 to 15 September 2022, we tested all MSM who presented with malaise, and/or ulcerative lesions, and/or proctitis and/or a papular-vesicular-pustular eruption attending the Centre of Sexual Health in Amsterdam, the Netherlands, for mpox, with a PCR test. In the same period, 6932 MSM mpox unsuspected clients were not tested. We compared those tested positive for mpox with those tested negative and those unsuspected for mpox. RESULTS: Of the 374 MSM tested, 135 (36%) were positive for mpox. The mpox-positive MSM were older (median age, respectively, 36, 34 and 34 years, p = 0.019) and more often lived with HIV (30% vs. 16% and 7%, p < 0.001). Furthermore, mpox-positive patients more often reported receptive anal sex without a condom, sexualized drug use, more sex partners, and were more often diagnosed with bacterial STI (p < 0.001). Systemic symptoms and anogenital lesions were associated with mpox infection. For mpox-positive patients, anal samples (p = 0.009) and lesional samples (p = 0.006) showed significantly lower median mpox Ct values compared to throat samples. CONCLUSIONS: Mpox-positive patients more often reported receptive anal sex without a condom, had more sex partners and more often lived with HIV. Our results suggest that in the current mpox outbreak among MSM, sexual transmission is the main route.

Blocking the receptor for C5a in patients with rheumatoid arthritis does not reduce synovial inflammation.

OBJECTIVES: All complement pathways lead to the formation of C5a, which is believed to contribute to the influx and activation of C5a-receptor (C5aR) bearing cells into the joints of patients with rheumatoid arthritis (RA). Studies in animal models of RA have suggested therapeutic potential of C5aR blockade. In this study, we examined the effects of the C5aR blockade on synovial inflammation in RA patients. METHODS: We performed a double-blind, placebo-controlled study using an orally administered C5aR-antagonist. Twenty-one patients with active RA were randomized 2:1 to treatment with a C5aR-antagonist AcF- (OpdChaWR) (PMX53) vs placebo for 28 days. Serum concentrations of PMX53 were determined. Synovial tissue was obtained at baseline and after 28 days of treatment for pharmacodynamic analysis using immunohistochemistry and digital image analysis. RESULTS: All patients completed the study. Areas under the curve (AUCs) of PMX53 in patients' blood samples showed a mean of 40.8 nmol h/l. There was neither decrease in cell infiltration, nor changes in key biomarkers associated with clinical efficacy after active treatment. In addition, there was no trend towards clinical improvement in the C5aR-antagonist-treated group compared with placebo nor was there a correlation between the AUC and clinical response. CONCLUSIONS: Treatment with PMX53 did not result in a reduction of synovial inflammation despite reaching serum levels of PMX53 that block C5aR-mediated cell activation in vitro. The data suggest that C5aR blockade does not result in reduced synovial inflammation in RA patients.

[Pseudogout in 3 patients with presumed therapy-resistant rheumatoid arthritis]. / Pseudo-jicht bij 3 patiënten met vermeende, therapieresistente reumatoïde artritis.

3 patients, 2 women aged 71 and 76 and a 55-year-old man, were originally diagnosed with rheumatoid arthritis (RA) and treated with disease-modifying antirheumatic drugs (DMARDs); two of these patients fulfilled the American College of Rheumatology criteria for RA. Because the symptoms persisted, the diagnosis was reconsidered. It turned out that they had pseudogout, which is an arthropathy caused by the deposition of calcium pyrophosphate crystals; the younger woman had no obvious metabolic disorder, the older woman had underlying hyperparathyroidism, and in the man the arthropathy was probably due to benign hypercalcaemia. DMARDs were replaced by NSAIDs. Varying degrees ofarthropathy persisted in the women, but in the man they were clearly decreased. In addition to resembling gout, the clinical manifestations of pseudogout can also mimic RA. It is important to distinguish pseudogout from RA because their treatment is completely different. Furthermore, pseudogout can be the first or sole symptom of a metabolic disorder.

The role of chemokines in rheumatoid arthritis and osteoarthritis.

The directed movement of immune cells is highly dependent on the chemokine network. Chemokines are key molecules early in the embryogenesis of lymph nodes and throughout adult life, where they regulate immune responses against pathogens. Although immune cells are best known for expressing chemokine receptors, through which they can respond to matching chemokines, endothelial cells also express chemokine receptors. The directed movement of endothelial cells facilitates angiogenesis. In chronic inflammatory conditions, such as rheumatoid arthritis (RA), chemokines are abundantly present at the site of inflammation and form a group of potential therapeutic targets. Some agents that block chemokine-chemokine receptor interaction are already under clinical investigation. The expression of chemokine receptors has also been found in cell types other than immune cells and endothelial cells. Chondrocytes, for instance, express several chemokine receptors. Elucidating their function may provide new insights into joint degradation in RA as well as in other conditions, including osteoarthritis (OA).