Sex-Specific Differences in Patients With Psoriatic Arthritis: A Systematic Review.

OBJECTIVE: A systematic review of published literature was conducted to collate evidence on sex-specific differences in clinical characteristics, disease activity, and patient-reported outcomes (PROs) in psoriatic arthritis (PsA), including response to treatment. METHODS: Searches of MEDLINE, Embase, and the Cochrane Database of Systematic Reviews were performed in November 2020 for observational studies of adults with PsA reporting outcomes by sex (published from January 1, 2015, to November 13, 2020). In addition, hand searches of systematic literature reviews and (network) metaanalysis bibliographies were performed. Searches of ClinicalTrials.gov and congress abstracts from the European Alliance of Associations for Rheumatology, the American College of Rheumatology (ACR), and the American Academy of Dermatology (2019-2020) were also carried out. Eligible studies with 100 or more patients prespecified a comparison by sex and reported clinical characteristics and/or disease activity. Data extracted included patient characteristics, study design, baseline clinical characteristics, and disease activity results, including PROs. RESULTS: Database searching yielded 3283 unique records; 31 publications of 27 unique studies were included. The review found generally higher rates of peripheral disease in women, including higher tender joint counts. There was some evidence of more axial disease in men, plus greater skin disease burden. There were consistently no differences in Dermatology Life Quality Index scores, though across other PROs, women had worse scores, including pain and fatigue. Women had poorer responses to treatment, indicated by outcome measures such as ACR responses and minimal disease activity. CONCLUSION: This review indicates that important differences exist between the sexes in PsA. However, the limited evidence for this conclusion underlines the need for additional research in this area.

Residual Disease Associated with Suboptimal Treatment Response in Patients with Psoriatic Arthritis: A Systematic Review of Real-World Evidence.

OBJECTIVE: This systematic literature review aimed to identify and summarise real-world observational studies reporting the type, prevalence and/or severity of residual symptoms and disease in adults with psoriatic arthritis (PsA) who have received treatment and been assessed against remission or low disease activity targets. METHODS: Patients had received treatment and been assessed with treat-to-target metrics, including minimal disease activity (MDA), Disease Activity Index in PsA (DAPSA) and others. MEDLINE, Embase® and the Cochrane Database of Systematic Reviews (CDSR) were searched using search terms for PsA, treatment targets and observational studies. Screening of search results was completed by two independent reviewers; studies were included if they reported relevant residual disease outcomes in adults with PsA who had received one or more pharmacological treatments for PsA in a real-world setting. Non-observational studies were excluded. Information from included studies was extracted into a prespecified grid by a single reviewer and checked by a second reviewer. RESULTS: Database searching yielded 2328 articles, of which 42 publications (27 unique studies) were included in this systematic literature review. Twenty-three studies reported outcomes for MDA-assessed patients, and 14 studies reported outcomes for DAPSA-assessed patients. Physician- and patient-reported residual disease was less frequent and/or severe in patients reaching targets, but often not absent, including when patients achieved very low disease activity (VLDA) or remission. For example, studies reported that 0-8% patients in remission according to DAPSA (or clinical DAPSA) had > 1 tender joint, 25-39% had Psoriasis Area and Severity Index (PASI) score > 1 and 0-10% had patient-reported pain > 15. Residual disease was usually less frequent and/or severe among patients achieving MDA-assessed targets versus DAPSA--assessed targets, especially for skin outcomes. CONCLUSION: The findings demonstrate a need for further optimisation of care for patients with PsA.

Analysis of Specialist and Patient Perspectives on Strategies to Improve Cardiovascular Disease Prevention Among Persons With Psoriatic Disease.

IMPORTANCE: Patients with psoriatic disease are at increased risk of cardiovascular disease (CVD), which is a leading cause of mortality in this population. However, many of these patients do not have an active relationship with a primary care physician, and there may be a role for specialist-led care in prevention of CVD. OBJECTIVE: To explore clinician and patient perspectives regarding strategies to improve CVD prevention via specialist-led care. DESIGN, SETTING, AND PARTICIPANTS: Using electronically collected surveys, a best-worst scaling experimental survey study was conducted among dermatologists through the National Psoriasis Foundation as well as the American Academy of Dermatology from October 27, 2020, to April 1, 2021, to rank the strategies according to their potential to improve CVD prevention among patients with psoriatic disease. Participants were asked about the feasibility of specialist-led screening through an electronically delivered survey from the National Psoriasis Foundation conducted between February 1 and April 21, 2021. Patients with psoriatic disease were asked about whether they would like the specialist to screen for CVD risk factors. In addition, patients reported their likelihood to engage in CVD risk screening and management behaviors in scenarios in which either the primary care physician or specialist was making the recommendations. MAIN OUTCOMES AND MEASURES: For the clinician surveys, the primary outcome was the ratio scaled preference score (range, 0-100; higher is more preferred), as well as whether they think calculating a 10-year CVD risk score and prescribing statins seems feasible. For the patient surveys, the primary outcome was the likelihood to check cholesterol level, incorporate diet and exercise, or use statin therapy depending on whether recommended by the specialist or primary care physician, whether they would like their specialist to educate them about CVD risk, and whether they would find it convenient to have their cholesterol level checked by their specialist. RESULTS: Among 183 dermatologists (102 [55.7%] women; mean [SD] age not collected), clinical decision support (preference score, 22.3; 95% CI, 20.7-24.0), patient education (preference score, 14.1; 95% CI, 12.5-15.7), and clinician education (preference score, 15.8; 95% CI, 14.3-17.3) were ranked as strategies likely to improve CVD prevention in patients with psoriatic disease. In addition, 69.3% (95% CI, 62.2%-76.0%) of dermatologists agreed or strongly agreed that checking lipid levels was feasible. Among 160 patients with psoriasis and 162 patients with psoriatic arthritis (226 [70.2%] women; mean [SD] age, 54 [13.3] years), patients reported they were as likely to engage in cardiovascular risk screening and management behaviors whether recommended by their primary care physician or their specialist. In addition, 60.0% (95% CI, 52.0%-67.7%) of patients with psoriasis and 75.3% (95% CI, 67.9%-81.7%) of those with psoriatic arthritis agreed that it would be convenient for them to have their cholesterol checked by their dermatologist/rheumatologist. CONCLUSIONS AND RELEVANCE: In this survey study, dermatologists and patients with psoriatic disease expressed positive perspectives about engaging in a specialist-led model of care to improve CVD prevention. Dermatologists appear to view several strategies as having potential to improve cardiovascular risk prevention.

Multisystem Inflammation and Organ Dysfunction After BNT162b2 Messenger RNA Coronavirus Disease 2019 Vaccination.

The U.S. Food and Drug Administration has to date granted approval or emergency use authorization to three vaccines against severe acute respiratory syndrome coronavirus 2 and coronavirus disease 2019. In clinical trials and real-use observational studies, the Pfizer-BioNTech BNT162b2 messenger RNA coronavirus disease 2019 vaccine, as well as the Moderna mRNA-1273 messenger RNA coronavirus disease 2019 vaccine, have demonstrated high efficacy and few adverse events. CASE SUMMARY: A 20-year-old male college student in good health developed tinnitus and hematuria shortly after vaccination and progressed swiftly to a syndrome of: systemic inflammation; acute kidney injury requiring hemodialysis; acute, bilateral, complete sensorineural hearing loss; radiographic evidence of acute multifocal ischemic strokes; pericardial effusion complicated by tamponade physiology requiring pericardial evacuation; pleural effusions requiring evacuation; and systemic capillary leak. An extensive clinical and research investigation, including cytokine analysis, whole blood cytometry by time of flight, and whole exome sequencing, did not reveal a definitive explanatory mechanism. CONCLUSION: While the overall safety profile of the BNT162b2 coronavirus disease 2019 vaccine remains excellent for the general population, rare serious events have been reported. In this report, we describe a case of multisystem inflammation and organ dysfunction of unknown mechanism beginning shortly after administration of the first dose of BNT162b2 coronavirus disease 2019 vaccine in a previously healthy recipient.

Age-appropriate cancer screening: A cohort study of adults with psoriasis prescribed biologics, adults in the general population, and adults with hypertension.

BACKGROUND: Psoriasis is associated with increased risk of developing and dying from cancer. OBJECTIVE: To evaluate whether psoriasis patients who are prescribed biologics receive the recommended screening for cervical, breast, and colon cancer. METHODS: We conducted a retrospective cohort study using the Optum deidentified Electronic Health Record data set. Incidence rates for cervical, breast, and colon cancer screening were compared between psoriasis patients who were prescribed biologics and 2 matched comparator cohorts: general patient population and patients being managed for hypertension. Multivariable Cox proportional hazards regression was performed to assess for differences in the rates of cancer screening. RESULTS: Compared with those in the general population without psoriasis, psoriasis patients who were prescribed biologics had higher screening rates for cervical cancer (adjusted hazard ratio [aHR] 1.09; 95% confidence interval [CI] 1.02-1.16) and colon cancer (aHR 1.10; 95% CI 1.02-1.18). Compared with those with hypertension, patients with psoriasis who were prescribed biologics had lower screening rates for breast cancer (aHR 0.88; 95% CI 0.83-0.94) and colon cancer (aHR 0.89; 95% CI 0.83-0.95). CONCLUSIONS AND RELEVANCE: Patients with psoriasis who are prescribed biologic therapies may not be receiving adequate age-appropriate cancer screening, especially for breast and colon cancer.

Amyloid arthropathy associated with multiple myeloma: polyarthritis without synovial infiltration of CD20+ or CD38+ cells.

OBJECTIVES: To describe histological, immunohistochemical and ultrastructural features of synovial biopsies of amyloid arthropathy associated with multiple myeloma (MM). METHODS: Synovial biopsies from affected joints of two patients with MM and amyloid arthropathy were examined with light and electron microscopy, and immunohistochemically for expression of CD3, CD8, CD20, CD38, CD68, Ki-67 and vWF. Results were compared to values from osteoarthritis (OA, n = 26), rheumatoid arthritis (RA, n = 24) and normal (n = 15) synovial membranes. RESULTS: There was no or only mild lining hyperplasia. Vascular density was not elevated, and there were few Ki-67+ proliferating cells in the stroma. The Krenn synovitis score classified one specimen as "low-grade" and one as "high-grade" synovitis. CD68+ and CD3+ cells were the predominant mononuclear inflammatory cells, whereas CD20+ and CD38+ cells were absent from both synovial membrane and synovial fluid sediment. Electron microscopy demonstrated amyloid phagocytosis by synovial macrophages. In hierarchical clustering the two amyloid arthropathy specimens were more closely related to OA than to RA or normal synovium. CONCLUSIONS: This first detailed immunohistological analysis of MM-associated amyloid arthropathy suggests that it is a chronic synovitis that evolves despite the loss of humoral immunity seen in advanced MM. Instead, amyloid phagocytosis by synovial macrophages likely triggers and perpetuates local disease.

Amyloid arthropathy associated with multiple myeloma: a systematic analysis of 101 reported cases.

OBJECTIVE: Amyloid deposition in multiple myeloma (MM) may lead to an arthropathy resembling rheumatoid arthritis (RA). Since a systematic description of its natural history is lacking, we have performed a systematic analysis of all published cases. METHODS: Literature review featuring backward and forward database searches and direct inspection of reference lists. Inclusion criteria were as follows: publication between 1931 and 2012, diagnosis of multiple myeloma, and demonstration of light chain amyloid (AL) in any organ or in synovial fluid, arthritis, or synovitis. RESULTS: Overall, 101 cases were identified. Median age was 59 years and the male-to-female ratio was 1:1. A systemic manifestation of MM was reported in 88 cases. In 53 of these, characteristic physical findings (carpal tunnel syndrome, macroglossia, shoulder pad, and soft tissue swelling/masses) were present. Arthritis manifested before the diagnosis of MM in 63 cases, with 33 cases initially misdiagnosed as RA. There were 72 cases of poly-, 17 of oligo-, and three of monoarthritis. The shoulder joint was most commonly affected, followed by knees and small hand joints. Median synovial fluid leukocyte count was 2460 cells/mm(3), and was normal in seven cases. Synovial histopathology often featured mild synovitis without plasma cell infiltration. Imaging revealed articular or periarticular inflammation in many cases and bone lesions near 22% of affected joints. Treatments varied but led to some improvement in the majority of cases. CONCLUSIONS: These results solidify previous experience that MM arthropathy tends to feature a symmetric RF-negative nonerosive polyarthritis. However, the results also highlight the diversity of its presentations and stress the importance of arthropathy as a potentially under-recognized presenting manifestation of MM.

Teaching about how doctors think: a longitudinal curriculum in cognitive bias and diagnostic error for residents.

BACKGROUND: Trends in medical education have reflected the patient safety movement's initial focus on systems. While the role of cognitive-based diagnostic errors has been increasingly recognised among safety experts, literature describing strategies to teach about this important problem is scarce. METHODS: 48 PGY-2 internal medicine residents participated in a three-part, 1-year curriculum in cognitive bias and diagnostic error. Residents completed a multiple-choice test designed to assess the recognition and knowledge of common heuristics and biases both before and after the curriculum. Results were compared with PGY-3 residents who did not receive the curriculum. An additional assessment in which residents reviewed video vignettes of clinical scenarios with cognitive bias and debiasing techniques was embedded into the curriculum. RESULTS: 38 residents completed all three parts of the curriculum and completed all assessments. Performance on the 13-item multiple-choice knowledge test improved post-curriculum when compared to both pre-curriculum performance (9.26 vs 8.26, p=0.002) and the PGY-3 comparator group (9.26 vs 7.69, p<0.001). All residents correctly identified at least one cognitive bias and proposed at least one debiasing strategy in response to the videos. CONCLUSIONS: A longitudinal curriculum in diagnostic error and cognitive bias improved internal medicine residents' knowledge and recognition of cognitive biases as measured by a novel assessment tool. Further study is needed to refine learner assessment tools and examine optimal strategies to teach clinical reasoning and cognitive bias avoidance strategies.

Infectious, oncologic, and autoimmune comorbidities of psoriasis and psoriatic arthritis: a report from the GRAPPA 2012 annual meeting.

At the 2012 annual meeting of the Group for Research and Assessment of Psoriasis and PsA (GRAPPA) in Stockholm, Sweden, members addressed the infectious, oncologic, and autoimmune comorbidities of psoriasis and psoriatic arthritis (PsA). Members discussing infectious comorbidities asked whether patients with psoriasis or PsA are predisposed to particular types of infections, and whether the use of biologic agents is advisable in patients with certain preexisting infections. Regarding the oncologic comorbidities of psoriasis and PsA, members addressed cutaneous malignancy screening, lymphoproliferative malignancy risk and the need for screening, and treatment of patients with preexisting oncologic history requiring systemic therapy. Finally, GRAPPA members discussed autoimmune comorbidities associated with psoriasis and PsA; they agreed that research is nascent in this field and larger studies are necessary to determine the precise magnitude of these associations.

Light and electron microscopic features of synovium in patients with psoriatic arthritis.

INTRODUCTION: Few ultrastructural studies have been reported in psoriatic arthritis (PsA). The authors report a series of synovial biopsies with emphasis on patients with early disease to look for distinctive light (LM) and electron microscopic (EM) features of possible importance. METHODS: The authors examined synovial biopsies obtained primarily by needle biopsy from 13 PsA patients using LM and/or EM. Sections from 12 patients were evaluated by LM for vascularity, synovial lining thickness, fibrin deposition, and inflammation via a semi-quantitative scale. Nine EM specimens were descriptively analyzed. Clinical, synovial fluid (SF), and radiographic characteristics were recorded. RESULTS: Patients were mostly male, with mean disease duration before biopsy of 2.19 ± 2.60 years; 7 patients had arthritis for less than 1 year. All patients had peripheral arthritis, 2 had axial involvement. SFs disclosed predominance of polymorphonuclear leukocytes. LM demonstrated proliferation of synovial lining cells, lymphocyte and plasma cell infiltration, as well as dramatic clusters of small vessels in the superficial synovium. EMs showed more detailed vascular changes, including small, subendothelial, electron-dense deposits and scattered microparticles in vessel lumens and walls. CONCLUSIONS: Prominent vascularity is confirmed as an important feature of some PsA. Vascular changes and other features, including the first EM demonstration of microparticles in PsA (identified as potent factors in other inflammatory joint diseases), are potential targets for therapy.

Seen through their eyes: residents' reflections on the cognitive and contextual components of diagnostic errors in medicine.

PURPOSE: Diagnostic errors in medicine are common and costly. Cognitive bias causes are increasingly recognized contributors to diagnostic error but remain difficult targets for medical educators and patient safety experts. The authors explored the cognitive and contextual components of diagnostic errors described by internal medicine resident physicians through the use of an educational intervention. METHOD: Forty-one internal medicine residents at University of Pennsylvania participated in an educational intervention in 2010 that comprised reflective writing and facilitated small-group discussion about experiences with diagnostic error from cognitive bias. Narratives and discussion were transcribed and analyzed iteratively to identify types of cognitive bias and contextual factors present. RESULTS: All residents described a personal experience with a case of diagnostic error that contained at least one cognitive bias and one contextual factor that may have influenced the outcome. The most common cognitive biases identified by the residents were anchoring bias (36; 88%), availability bias (31; 76%), and framing effect (23; 56%). Prominent contextual factors included caring for patients on a subspecialty service (31; 76%), complex illness (26; 63%), and time pressures (22; 54%). Eighty-five percent of residents described at least one strategy to avoid a similar error in the future. CONCLUSIONS: Residents can easily recall diagnostic errors, analyze the errors for cognitive bias, and richly describe their context. The use of reflective writing and narrative discussion is an educational strategy to teach recognition, analysis, and cognitive-bias-avoidance strategies for diagnostic error in residency education.

A roadmap for education to improve the quality of care in gout.

PURPOSE OF REVIEW: To describe obstacles to optimum management of gout by primary care physicians and to propose educational interventions to improve care. RECENT FINDINGS: In the past, gout education has been hampered by infrequency of continuing medical education courses, loss of excitement for a disease in which therapies have not changed (until recently), insufficient evidence-based medicine, and the lack of motivation by physicians to re-learn this disease once in active practice. We identify 10 common myths that impede appropriate treatment of gout, identify gaps in evidence-based medicine that perpetuate those myths, and propose opportunities to improve education on these myths. It is through better gout-centered education that quality of care in gout can be enhanced. Residency may be one of the key points of intervention. As more evidence-based medicine publications address the optimum management of gout, national re-education can occur. More outreach by community rheumatologists to primary care physicians through educational programs and improved referral letters can help re-educate practitioners. Lastly, an often overlooked engine to change physician practices is consumer education, but current patient education programs are lacking. SUMMARY: Novel education interventions for physician trainees, primary care physicians, and patients are proposed to improve the care of patients with gout.