Polymyalgia rheumatica (PMR) is an inflammatory disorder of unknown etiology, sharing symptoms with giant cell arthritis (GCA) and rheumatoid arthritis (RA). The pathogenic inflammatory roots are still not well understood, and there is a lack of extensive biomarker studies to explain the disease debut and post-acute phase. This study aimed to deeply analyze the serum proteome and inflammatory response of PMR patients before and after glucocorticoid treatment. We included treatment-naïve PMR patients, collecting samples before and after 3 months of treatment. For comparison, disease-modifying antirheumatic drug (DMARD)-naïve RA patients were included and matched to healthy controls (CTL). The serum proteome was examined using label-free quantitative mass spectrometry, while inflammation levels were assessed using multiplex inflammatory cytokine and cell-free DNA assays. The serum proteomes of the four groups comprised acute phase reactants, coagulation factors, complement proteins, immunoglobulins, and apolipoproteins. Serum amyloid A (SAA1) was significantly reduced by active PMR treatment. Cell-free DNA levels in PMR and RA groups were significantly higher than in healthy controls due to acute inflammation. Complement factors had minimal changes post-treatment. The individual serum proteome in PMR patients showed over 100 abundantly variable proteins, emphasizing the systemic impact of PMR disease debut and the effect of treatment. Interleukin (IL)-6 and interferon-gamma (IFN-γ) were significantly impacted by glucocorticoid treatment. Our study defines the PMR serum proteome during glucocorticoid treatment and highlights the role of SAA1, IL-6, and IFN-γ in treatment responses. An involvement of PGLYRP2 in acute PMR could indicate a response to bacterial infection, highlighting its role in the acute phase of the immune response. The results suggest that PMR may be an aberrant response to a bacterial infection with an exacerbated IL-6 and acute phase inflammatory response and molecular attempts to limit the inflammation.

OBJECTIVE: Multicause-of-death methods were used to analyze mortality and leading causes of death associated with polymyalgia rheumatica (PMR) in the United States from 1999 to 2020.
METHODS: We analyzed mortality data from the Centers for Disease Control and Prevention (CDC) Data analysis system and selected death certificates that listed PMR as the cause of death based on the International Statistical Classification of Diseases and Related Health Problems (ICD-10) category code. Relevant mortality rates, number of deaths and historical trends were analyzed. The number of PMR-related deaths and age-standardized mortality rate (ASMR) trend charts were made using Excel 2010 version and trend lines were added.
RESULTS: Over the last 22 years, the total number of PMR-related deaths in the United States was 15,421 women (89.8%), a ratio of about 1:9 men to women. When PMR is listed as the underlying cause of death, the ASMR for women and men (per 100,000 people) is approximately 1.8-5.1:1, and when it is listed as the non-underlying cause of death, it is 1.8-3.3:1. PMR deaths are more frequent in individuals aged 70 years and above, with patients aged 80 years and above being most affected. Among different ethnicities, the highest number of deaths was found in Caucasians, followed by Black or African American. When it comes to causes of death, heart disease still ranks first, followed by cancer. In addition, we also found that when PMR combined with malignant tumors as a multiple cause of death, the number of female deaths was higher than that of male deaths, the overall number of deaths of both showed an upward trend, and the overall ASMR of both showed a downward trend.
CONCLUSIONS: In the past 22 years, we have observed a low mortality rate of PMR in the United States. However, for patients with PMR, especially elderly women, medical workers should be vigilant and pay attention to whether they are combined with other complications, such as malignant neoplasms, and make timely diagnosis and treatment to further reduce the mortality rate of patients with PMR.

Immune-checkpoint inhibitors (ICIs) have changed the management of advanced cancers. However, patients with pre-existing autoimmune diseases (ADs) have usually been excluded from clinical trials of ICIs due to concerns about exacerbation of AD. Here, we combined ICIs with selective immunosuppressant treatment in a metastatic lung adenocarcinoma patient with active pre-existing polymyalgia rheumatica (PMR). Remarkably, the strategy led to durable response and no exacerbation of PMR. Thus, we provide the first clinical evidence of treating metastatic cancer with ICIs and concomitant use of tocilizumab and hydroxychloroquine for active pre-existing PMR.

The study aimed to analyze the mortality and leading causes of death associated with Sjögren\'s syndrome (SS) in the United States (US) between 1999 and 2020 using a multicause approach. We analyzed mortality based on SS as the cause-of-death. Using mortality rates, number of deaths, and historical trends, we examined sex, age of death, comparisons of SS- and polymyalgia rheumatica-related deaths (multiple cause-of-death) in the last 20 years, changes in the ranking of causes of death when SS was the underlying cause-of-death (UCD) in the first and last 5 years of the last 20 years, and the number of deaths and standardized mortality (per 100,000 people) when SS combined with interstitial lung disease (ILD) or tumor was the multiple cause-of-death. An SS-standardized mortality trend chart and a trend line were created. In 22 years, the total number of SS-related deaths in the US was 7,817, including 7,016 women. When SS was the UCD and non-UCD, the standardized ratios of female-to-male deaths (per 100,000 people) were approximately 4.6-13:1 and 6.8-19.6:1, respectively. SS-related deaths were more common in people aged >60 years and concentrated in patients aged 60-79. In cases where SS and polymyalgia rheumatica were the multiple cause-of-death, the number of deaths and age-standardized mortality of SS and polymyalgia rheumatica increased, although lower in SS than in polymyalgia rheumatica. Regarding SS as the UCD, heart disease ranks first. Concerning the number of deaths and standardized mortality in the first (1999-2003) and second (2016-2020) 5 years, when SS-ILD and SS combined with tumors were the multiple causes of death, the number increased in the second 5 years compared to that in the first 5 years. When SS combined with COVID-19 was the multiple cause-of-death, 73 deaths occurred, comprising 64 females and 9 males. Death predominance was observed among women and patients aged 60-79 years with SS. Although the SS-standardized mortality rate was low, an increasing trend was observed. When SS was the primary cause-of-death, heart disease remained primarily involved, followed by malignant neoplasms. The number of patients with SS-ILD and SS combined with tumors in the past 22 years and the standardized mortality rate after 5 years increased compared with those of the previous 5 years. Concurrent SS and COVID-19 may be related to the increased SS deaths.

BACKGROUND: The clinical manifestations of Fabry disease affect the nerves, kidneys, heart, skin, gastrointestinal tract and eyes. Our aim is to familiarize people with the FD diagnostic process by reporting this case.
METHODS: A 79-year-old-male patient presented with muscle pain and weakness in the extremities, also with an increasing erythrocyte sedimentation rate and C-reactive protein. Further examinations revealed that multiple organ involvement, such as rash, myocardial hypertrophy, peripheral neuropathy.
METHODS: Cardiac MR demonstrated hypertrophic cardiomyopathy, myocardial fibrosis and low myocardial T1 value. The patient was eventually diagnosed with Fabry disease through proteomics and genetic testing.
METHODS: The treatment is enzyme replacement therapy (ERT). But this patient could not afford ERT and was given only general symptomatic treatment, pregabalin, and a gradual reduction in glucocorticoid.
RESULTS: The patient\'s symptoms of joint pain and muscle weakness reduced significantly, and ESR and CRP had decreased to normal.
CONCLUSIONS: FD is a rare disease and difficult to diagnose, but rare does not mean invisible. FD may present with signs and symptoms of rheumatic diseases. Rheumatologists should be aware and concerned about this disease.

暂无摘要。

UNASSIGNED: This retrospective analysis was to assess the role of Janus kinases (JAK) inhibitors compared with conventional disease modifying anti-rheumatic drugs (DMRADs) in the treatment of polymyalgia rheumatica (PMR) with glucocorticoids (GCs) reduction.
UNASSIGNED: Clinical information was collected from PMR patients in the JAK inhibitor group and the DMARDs group from January 2020 to August 2021 at Jiaxing first Hospital. Serum C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), hemoglobin (Hb), albumin and dose of GCs before and after treatment were compared between two groups.
UNASSIGNED: Thirty female patients with PMR were included into this study. The dose of GCs in the JAK inhibitor group was significantly lower than in the DMARDs group at baseline and at 3 and 6 months after treatment. There were no significant differences in various laboratory parameters (including CRP, ESR, Hb and albumin) between two groups (P > 0.05) except that Hb in the DMARDs group was significantly higher than in the JAK inhibitor group at 3 and 6 months after treatment (P<0.05). One patient in the JAK inhibitor group developed herpes zoster, and received tofacitinib treatment after herpes zoster was relieved.
UNASSIGNED: Our study indicates that JAK inhibitors in the treatment of PMR are as effective as DMRADs and are also helpful for the reduction of GCs dose.

暂无摘要。

To evaluate the feasibility of standard uptake value (SUV) index (ratio lesional maximum SUV [SUVmax] to liver mean SUV [SUVmean]) as a metabolic parameter for diagnosing polymyalgia rheumatica (PMR).
A retrospective group of patients with PMR and controls with symptoms similar to PMR but diagnosed with other diseases. Semiquantitative and qualitative analysis of 2-[18F]-fluoro-2-deoxy-d-glucose (18F-FDG) uptake at 18 sites was undertaken for all patients. The diagnostic value of positron-emission tomography/computed tomography (PET/CT) for PMR was assessed by R software using logistic regression and a generalised additive model (GAM). All images were examined independently by two nuclear medicine physicians with extensive work experience.
The characteristic sites of PMR were the ischial tuberosity, interspinous bursa, periarticular hip, and symphysis pubis enthesis. The area under the curve (AUC) of the characteristic site SUV index was 0.930, and the best cut-off value was 1.685 with a sensitivity of 84.6% and a specificity of 92.6%. After adjusting for potential confounders, the probability of PMR diagnosis increased as the characteristic site SUV index increased and there was a nonlinear correlation between the two. When the characteristic site SUV index was ≥2.56, the probability of PMR gradually reached the threshold effect, which was as high as 90% or more.
The characteristic site SUV index is an independent factor for diagnosing PMR, and PMR should be highly suspected when it is ≥ 1.685. Nonetheless, it is important to note that these findings are based on an initial retrospective single-centre study and require external validation and further prospective evaluation before being translated into clinical practice.

BACKGROUND: Polymyalgia rheumatica (PMR) is a common inflammatory disease in elderly persons whose mechanism of pathogenesis has not been elucidated. Glucocorticoids are the main first-line treatments but result in numerous side effects. Therefore, there is a need to explore pathogenetic factors and identify possible glucocorticoid-sparing agents. We aimed to study the pathogenetic features of the disease and assess the efficacy and safety of Janus tyrosine kinase (JAK)-inhibitor tofacitinib in patients with PMR.
RESULTS: We recruited treatment-naïve PMR patients from the First Affiliated Hospital, Zhejiang University School of Medicine, between September 2020 and September 2022. In the first cohort, we found that the gene expression patterns of peripheral blood mononuclear cells (PBMCs) in 11 patients (10 female, 1 male, age 68.0 ± 8.3) with newly diagnosed PMR were significantly different from 20 healthy controls (17 female, 3 male, age 63.7 ± 9.8) by RNA sequencing. Inflammatory response and cytokine-cytokine receptor interaction were the most notable pathways affected. We observed marked increases in expression of IL6R, IL1B, IL1R1, JAK2, TLR2, TLR4, TLR8, CCR1, CR1, S100A8, S100A12, and IL17RA, which could trigger JAK signaling. Furthermore, tofacitinib suppressed the IL-6R and JAK2 expression of CD4+T cells from patients with PMR in vitro. In the second cohort, patients with PMR were randomized and treated with tofacitinib or glucocorticoids (1/1) for 24 weeks. All PMR patients underwent clinical and laboratory examinations at 0, 4, 8, 12, 16, 20, and 24 weeks, and PMR activity disease scores (PMR-AS) were calculated. The primary endpoint was the proportion of patients with PMR-AS ≤10 at weeks 12 and 24. Secondary endpoints: PMR-AS score, c-reactive protein (CRP), and erythrocyte sedimentation rate (ESR) at weeks 12 and 24. Thirty-nine patients with newly diagnosed PMR received tofacitinib, and 37 patients received glucocorticoid. Thirty-five patients (29 female, 6 male, age 64.4 ± 8.4) and 32 patients (23 female, 9 male, age 65.3 ± 8.7) patients completed the 24-week intervention, respectively. There were no statistically significant differences in primary or secondary outcomes. At weeks 12 and 24, all patients in both groups had PMR-AS <10. PMR-AS, CRP, and ESR were all significantly decreased in both groups. No severe adverse events were observed in either group. Study limitations included the single-center study design with a short observation period.
CONCLUSIONS: We found that JAK signaling was involved in the pathogenesis of PMR. Tofacitinib effectively treated patients with PMR as glucocorticoid does in this randomized, monocenter, open-label, controlled trial (ChiCTR2000038253).
BACKGROUND: This investigator-initiated clinical trial (IIT) had been registered on the website (http://www.chictr.org.cn/, ChiCTR2000038253).