Sjögren's disease activity associates with cardiovascular disease and monoclonal gammopathy: a university cohort study of disease activity and comorbidities.

BACKGROUND: We used the University of Wisconsin cohort to determine the extent to which the EULAR Sjögren's syndrome disease activity index (ESSDAI) was associated with comorbidities that contribute to mortality. METHODS: Our University of Wisconsin, Madison cohort had 111 patients with Sjögren's Disease (SjD) by 2016 ACR/EULAR criteria and 194 control patients with sicca. Our study was performed from March 1st, 2020 through April 1st, 2023. We collected data using a standardized collection tool, including components of the Charlson Comorbidity Index (CCI). Stratifying our SjD patients by ESSDAI < 5 and ESSDAI ≥ 5, we assessed differences in comorbidities associated with mortality. RESULTS: At time of SjD diagnosis, the ESSDAI ≥ 5 group had increased odds of peripheral vascular disease compared to controls (OR 10.17; 95% CI 1.18-87.87). Patients with a current ESSDAI ≥ 5 were more likely to have a myocardial infarction compared to controls (OR 9.87; 95% CI 1.17-83.49). SjD patients had increased prevalence of monoclonal gammopathy compared to controls (9.3% vs 0.5%, p < 0.001). SjD patients with high ESSDAI at diagnosis had greater prevalence of monoclonal gammopathy compared to the SjD patients with a low ESSDAI (16% vs 5%, p = .04). As reported elsewhere, the ESSDAI ≥ 5 group had increased odds of chronic pulmonary disease (OR 4.37; 95% CI 1.59-11.97). CONCLUSION: We found high ESSDAI scores were associated with worse cardiovascular outcomes, specifically peripheral vascular disease and myocardial infarction. Furthermore, monoclonal gammopathy was more frequent in SjD patients compared to sicca controls, supporting screening for monoclonal gammopathy in the appropriate clinical scenario. Key Points • High ESSDAI scores are associated with worse cardiovascular outcomes, specifically peripheral vascular disease and myocardial infarction. • Monoclonal gammopathy is more frequent in SjD patients than sicca controls, supporting screening for monoclonal gammopathy in the appropriate clinical scenario.

What Bedside Skills Could the Modern Rheumatologist Possess? Part II. "Certain Technical Procedures".

ABSTRACT: Rheumatologists have never been reluctant to adopt procedures that might enhance their diagnostic or therapeutic powers. Their propensity to penetrate the joints of the patients they were treating set them apart from the general internist. Since the 1980s, when a chance to look inside the joints they were treating attracted a few rheumatologists, other things that could be done at the bedside emerged with now an array of bedside procedures that could be part of a rheumatologist's skill set. Besides gains in diagnosis and/or therapy, each constitutes a chance to restore the physical contact between physician and patient, riven by factors of the last decade, such as electronic medical records and COVID. With such contact so important to satisfaction of the patient and physician alike, acquisition of proficiency in certain technical procedures described herein offers one path to begin restoring rheumatology to the richly fulfilling practice it once was.

What Bedside Skills Could the Modern Rheumatologist Possess? Part I. The Basics.

ABSTRACT: The hands-on aspect of rheumatologic practice serves to balance its more cerebral features with the everyday necessity to touch patients to assess their condition, obtain samples for diagnosis, and deliver therapy, all cementing the important bond between patient and physician. Factors over recent years, ranging from the intercession of the electronic medical record to COVID, have weakened this bond, which we must restore if the practice of rheumatology is to return to previous levels of satisfaction. We review herein, in 2 parts, the many ways rheumatologists may interact physically with patients, with hope that pursuit of these measures can enhance satisfaction of physician and patient alike. This first installment reviews those simple skills in place before more involved technical bedside skill began to evolve over the last half century.

Bedside labial salivary gland biopsy (LSGBx: Lip biopsy): An update for rheumatologists.

Retrieval of minor salivary glands from a labial submucosal site through a minimally invasive bedside procedure was first described nearly 60 years ago and remains an attractive alternative to more invasive surgical procedures to obtain salivary gland tissue for pathologic examination. Examination of glands for features of Sjögren's has constituted the primary use of this procedure but other systemic disorders can affect minor salivary glands and their diagnoses can be supported by biopsy. Performance of the procedure does not require specialized training in head and neck surgery or dentistry, only simple wound closure skills. Skill in performing the procedure enables the clinician to acquire potentially diagnostic material without the need for referral while offering immediate expert feedback to the patient being biopsied. Material obtained at biopsy can also be the focus of research investigations.

Is It Time to Bring Back Knee Washout?

Washout of knee joint contents, whether by arthrotomy, arthroscopy, or percutaneous methods, can remove phlogistic material contributing to the problem at hand. Observations dating from the turn of the last century coupled with multiple trials suggest such that an intervention can be useful in the management of osteoarthritis, inflammatory arthropathies, crystal arthritis, and septic arthritis. We suggest that this intervention-applicable at the bedside with minimal cost, preparation, or expertise-be reconsidered as an adjunct in management of these disorders.

Regarding Arthroscopy: Can Orthopedists and Rheumatologists Be Friends?

BACKGROUND/OBJECTIVE: Rheumatologists' interest in arthroscopy began before the 1980s, when many era practitioners began to take up the procedure in earnest. Some of the important players in pre-World War II explorations of arthroscopy were rheumatologists, and the father of modern arthroscopy Makei Watanabe counted many rheumatologists among his postwar students, who were publishing about arthroscopic insights into rheumatic conditions in the 1960s and 1970s. We chose to review this evolution to demonstrate the diverging interests of rheumatologists and orthopedists in arthroscopy and emphasize the chances for reconciliation and cooperation. Methods involve our personal recollection and review of the literature. RESULTS: Guidelines for the practice of arthroscopy were published by the American Rheumatism Association (now the American College of Rheumatology) 7 years before similar guidelines appeared from the Arthroscopy Association of North America. American rheumatologists ceased arthroscopy when controlled trials showed no effect in osteoarthritis beyond placebo and biologics for synovitis virtually eliminated situations in which synovectomy might be considered. The research potential of arthroscopy has been realized mainly by European rheumatologists, although the ultrasound-guided biopsy is supplanting arthroscopy as means to secure synovium for investigation, despite the advantages of the latter, such as the ability to obtain larger amounts of tissue, select tissue based on macroscopic appearance, sample multiple area in the same joint, and deliver the potentially therapeutic effect of washout. New miniscopes suitable for office use could restore some of the lagging interest in arthroscopy for investigation. Orthopedists have generally been resistant to rheumatologists doing arthroscopy but would not be sharing any turf with rheumatologists using the miniscope. CONCLUSIONS: We hope that we orthopedists and rheumatologists could be friends as we enter this new phase of arthroscopy as we use the technique for different purposes.

Will rheumatologists ever pick up the arthroscope again?

Conditions prompting physicians and surgeons first adapting endoscopes to peer into joints were mainly the sort of synovial conditions that would concern today's rheumatologists. Rheumatologists were among the pre-World War II pioneers developing and documenting arthroscopy. The post-War father of modern arthroscopy, Watanabe, found rheumatologists among his early students, who took back the technique to their home countries, teaching orthopedists and rheumatologists alike. Rheumatologists described and analyzed the intra-articular features of their common diseases in the '60s and '70s. A groundswell of interest from academic rheumatologists in adapting arthroscopy grew considerably in the '90s with development of "needle scopes" that could be used in an office setting. Rheumatologists helped conduct the very trials the findings of which reduced demand for their arthroscopic services by questioning the efficacy of arthroscopic debridement in osteoarthritis (OA) and also developing biological compounds that greatly reduced the call for any resective intervention in inflammatory arthropathies. The arthroscope has proven an excellent tool for viewing and sampling synovium and continues to serve this purpose at several international research centers. While cartilage is now imaged mainly by magnetic resonance imaging, some OA features - such as a high prevalence of visible calcinosis - beg further arthroscopy-directed investigation. A new generation of "needle scopes" with far superior optics awaits future investigators, should they develop interest.

Arthroscopy in rheumatology: where have we been? Where might we go?

The aim of our manuscript is to illustrate the past, present and future role of rheumatologists performing arthroscopy. Doctors first began adapting endoscopes to inspect joints to assess synovial conditions that concern rheumatologists. Rheumatologists were among the pioneers developing arthroscopy. Students of the father of modern arthroscopy, Watanabe, included rheumatologists, who taught others once home. Rheumatologists assessed the intra-articular features of their common diseases in the 60s and 70s. Improvements in instrumentation and efforts by a few orthopaedists adapted a number of common joint surgical procedures for arthroscopy. Interest from rheumatologists in arthroscopy grew in the 90s with 'needle scopes' used in an office setting. Rheumatologists conducting the first prospective questioning arthroscopic debridement in OA and developing biological compounds reduced the call for arthroscopic interventions. The arthroscope has proven an excellent tool for viewing and sampling synovium, which continues to at several international centres. Some OA features-such as calcinosis-beg further arthroscopic investigation. A new generation of 'needle scopes' with far superior optics awaits future investigators.

Synovial Biopsy in the Diagnosis of Crystal-Associated Arthropathies.

BACKGROUND/ OBJECTIVE: This study seeks to assess the utility of synovial biopsy in the diagnosis of crystal-associated arthropathies (CAAs) in a clinical setting. METHODS: In this retrospective study, we reviewed biopsy reports involving synovial tissue between 1988 and 2015. We then reviewed the records of patients where the biopsy was performed for a clinical suspicion of CAA-the clinical group-and calculated the frequency of a positive diagnosis. The t test, Mann-Whitney-Wilcoxon test, and Fisher test were used to compare clinical characteristics of patients with and without a tissue diagnosis of CAA. We also reviewed cases of unexpected detection of crystalline disease involving synovial tissue-the incidental group. RESULTS: Among 2786 biopsies involving the synovium, we identified 65 cases in the clinical group and 33 cases in the incidental group. In the clinical group, a relevant diagnosis was obtained from synovial tissue in 36.9%, and a CAA was diagnosed in 20%. Restricting analysis to clinical biopsies performed for a primary suspicion of CAA, a relevant diagnosis was obtained in 61.3%, and a CAA was diagnosed in 38.7%. The incidental group comprised 1.2% of all synovial biopsies and included 7 mass lesions. Basic calcium phosphate was not reported on any biopsy in the study period. CONCLUSIONS: Synovial biopsy is a diagnostic option when suspected CAA is resistant to conventional modes of diagnosis. Crystalline diseases should be considered in the differential diagnosis of musculoskeletal mass lesions mimicking neoplasms.

Transcriptional Profiling of Synovial Macrophages Using Minimally Invasive Ultrasound-Guided Synovial Biopsies in Rheumatoid Arthritis.

OBJECTIVE: Currently, there are no reliable biomarkers for predicting therapeutic response in patients with rheumatoid arthritis (RA). The synovium may unlock critical information for determining efficacy, since a reduction in the numbers of sublining synovial macrophages remains the most reproducible biomarker. Thus, a clinically actionable method for the collection of synovial tissue, which can be analyzed using high-throughput strategies, must become a reality. This study was undertaken to assess the feasibility of utilizing synovial biopsies as a precision medicine-based approach for patients with RA. METHODS: Rheumatologists at 6 US academic sites were trained in minimally invasive ultrasound-guided synovial tissue biopsy. Biopsy specimens obtained from patients with RA and synovial tissue from patients with osteoarthritis (OA) were subjected to histologic analysis, fluorescence-activated cell sorting, and RNA sequencing (RNA-seq). An optimized protocol for digesting synovial tissue was developed to generate high-quality RNA-seq libraries from isolated macrophage populations. Associations were determined between macrophage transcriptional profiles and clinical parameters in RA patients. RESULTS: Patients with RA reported minimal adverse effects in response to synovial biopsy. Comparable RNA quality was observed from synovial tissue and isolated macrophages between patients with RA and patients with OA. Whole tissue samples from patients with RA demonstrated a high degree of transcriptional heterogeneity. In contrast, the transcriptional profile of isolated RA synovial macrophages highlighted different subpopulations of patients and identified 6 novel transcriptional modules that were associated with disease activity and therapy. CONCLUSION: Performance of synovial tissue biopsies by rheumatologists in the US is feasible and generates high-quality samples for research. Through the use of cutting-edge technologies to analyze synovial biopsy specimens in conjunction with corresponding clinical information, a precision medicine-based approach for patients with RA is attainable.

Genome-wide Association Analysis of Psoriatic Arthritis and Cutaneous Psoriasis Reveals Differences in Their Genetic Architecture.

Psoriasis vulgaris (PsV) is a common inflammatory and hyperproliferative skin disease. Up to 30% of people with PsV eventually develop psoriatic arthritis (PsA), an inflammatory musculoskeletal condition. To discern differences in genetic risk factors for PsA and cutaneous-only psoriasis (PsC), we carried out a genome-wide association study (GWAS) of 1,430 PsA case subjects and 1,417 unaffected control subjects. Meta-analysis of this study with three other GWASs and two targeted genotyping studies, encompassing a total of 9,293 PsV case subjects, 3,061 PsA case subjects, 3,110 PsC case subjects, and 13,670 unaffected control subjects of European descent, detected 10 regions associated with PsA and 11 with PsC at genome-wide (GW) significance. Several of these association signals (IFNLR1, IFIH1, NFKBIA for PsA; TNFRSF9, LCE3C/B, TRAF3IP2, IL23A, NFKBIA for PsC) have not previously achieved GW significance. After replication, we also identified a PsV-associated SNP near CDKAL1 (rs4712528, odds ratio [OR] = 1.16, p = 8.4 × 10(-11)). Among identified psoriasis risk variants, three were more strongly associated with PsC than PsA (rs12189871 near HLA-C, p = 5.0 × 10(-19); rs4908742 near TNFRSF9, p = 0.00020; rs10888503 near LCE3A, p = 0.0014), and two were more strongly associated with PsA than PsC (rs12044149 near IL23R, p = 0.00018; rs9321623 near TNFAIP3, p = 0.00022). The PsA-specific variants were independent of previously identified psoriasis variants near IL23R and TNFAIP3. We also found multiple independent susceptibility variants in the IL12B, NOS2, and IFIH1 regions. These results provide insights into the pathogenetic similarities and differences between PsC and PsA.

Genome-wide association analysis identifies three psoriasis susceptibility loci.

We carried out a meta-analysis of two recent psoriasis genome-wide association studies with a combined discovery sample of 1,831 affected individuals (cases) and 2,546 controls. One hundred and two loci selected based on P value rankings were followed up in a three-stage replication study including 4,064 cases and 4,685 controls from Michigan, Toronto, Newfoundland and Germany. In the combined meta-analysis, we identified three new susceptibility loci, including one at NOS2 (rs4795067, combined P = 4 × 10⁻¹¹), one at FBXL19 (rs10782001, combined P = 9 × 10⁻¹°) and one near PSMA6-NFKBIA (rs12586317, combined P = 2 × 10⁻8). All three loci were also associated with psoriatic arthritis (rs4795067, combined P = 1 × 10⁻5; rs10782001, combined P = 4 × 10⁻8; and rs12586317, combined P = 6 × 1⁻5) and purely cutaneous psoriasis (rs4795067, combined P = 1 × 10⁻8; rs10782001, combined P = 2 × 10⁻6; and rs12586317, combined P = 1 × 10⁻6). We also replicated a recently identified association signal near RNF114 (rs495337, combined P = 2 × 10⁻7).

Ultrasound of the knee during voluntary quadriceps contraction: a technique for detecting otherwise occult effusions.

OBJECTIVE: To describe 1) a technique that can detect synovial effusions not seen on static ultrasound (US) examination and 2) the characteristics of patients with knee osteoarthritis (OA) for whom this technique proved useful. METHODS: From reviewed records of 76 patients with knee OA (112 knees) that we had seen for US-guided injections over a defined period, we found 45 knees with no detectable effusion on static US, of which 18 (14 patients) showed fluid when scanned during voluntary quadriceps contraction. For all patients, we had recorded effusion features (physical examination, presence and size on US), and success of joint entry was determined by getting synovial fluid and/or seeing an air echo or inflow of injected material. RESULTS: The 14 patients we studied were obese (mean +/- SEM body mass index 32.7 +/- 2.3 kg/m(2); 3 morbidly obese), with moderate to severe OA by radiography in most (Kellgren/Lawrence class 3 or 4 in 10 of 14 knees for which radiographs were available). The suprapatellar synovial space seen by US was small (mean +/- SEM depth 0.38 +/- 0.04 cm). Arthrocentesis obtained 0.5-16 ml of synovial fluid (mean +/- SEM 2.9 +/- 0.6 ml), which correlated with the depth of effusion as seen on US with the quadriceps in maximum contraction (Spearman's rho = 0.5597, P = 0.0157). In 4 knees where arthrocentesis failed to retrieve fluid, we observed at injection the inflow of material and a linear air echo. CONCLUSION: US of the knee during voluntary quadriceps contraction can find effusions not detectable on static US. Such effusions provide targets for accurate aspiration and injection that would not be appreciated with static US.