Use of Hydroxychloroquine Is Associated With Improved Lipid Profile in Rheumatoid Arthritis Patients.

BACKGROUND/PURPOSE: We examined the association between hydroxychloroquine (HCQ) and plasma lipid and glucose levels in rheumatoid arthritis (RA) cohort. METHODS: This is a retrospective cohort analysis of 1261 RA patients comparing fasting lipid profiles and plasma glucose between patients who were and were not taking HCQ. We divided patients into 3 groups based on HCQ exposure during follow-up: those who had never taken HCQ, those who took it intermittently, and those who took it continuously. We used multivariable models and propensity scoring to compensate for the effect of nonrandom treatment assignment. RESULTS: We followed 1261 RA patients for a total of 4605 observations between 1996 and 2014. After adjusting for age, sex, ethnicity, other disease-modifying antirheumatic drugs (DMARDs), lipid-lowering medications, body mass index (BMI), and smoking, patients taking HCQ at baseline had significantly lower total cholesterol (TC) (P ≤ 0.001), low-density lipoprotein (LDL) (P ≤ 0.001), triglycerides (P = 0.013), and lipid profile ratios TC/high-density lipoprotein (HDL) (P ≤ 0.001) and LDL/HDL (P ≤ 0.001), as well as higher HDL (P ≤ 0.001).In longitudinal analyses, after adjusting for confounders, patients who continuously took HCQ showed significantly lower TC, LDL, TC/HDL, and LDL/HDL and higher HDL (P ≤ 0.01). Fasting plasma glucose levels were not significantly associated with HCQ exposure. CONCLUSIONS: Hydroxychloroquine use was associated with lower lipid levels but not with the plasma glucose in this RA cohort. These findings support the need for a randomized trial to establish the role of HCQ in cardiovascular disease prevention in RA patients.

Genetic Variants Influencing Joint Damage in Mexican Americans and European Americans With Rheumatoid Arthritis.

Joint destruction in rheumatoid arthritis (RA) is heritable, but knowledge on specific genetic determinants of joint damage in RA is limited. We have used the Immunochip array to examine whether genetic variants influence variation in joint damage in a cohort of Mexican Americans (MA) and European Americans (EA) with RA. We studied 720 MA and 424 EA patients with RA. Joint damage was quantified using a radiograph of both hands and wrists, scored using Sharp's technique. We conducted association analyses with the transformed Sharp score and the Immunochip single nucleotide polymorphism (SNP) data using PLINK. In MAs, 15 SNPs from chromosomes 1, 5, 9, 17 and 22 associated with joint damage yielded strong p-values (p < 1 × 10(-4) ). The strongest association with joint damage was observed with rs7216796, an intronic SNP located in the MAP3K14 gene, on chromosome 17 (ß ± SE = -0.25 ± 0.05, p = 6.23 × 10(-6) ). In EAs, 28 SNPs from chromosomes 1, 4, 6, 9, and 21 showed associations with joint damage (p-value < 1 × 10(-4) ). The best association was observed on chromosome 9 with rs59902911 (ß ± SE = 0.86 ± 0.17, p = 1.01 × 10(-6) ), a synonymous SNP within the CARD9 gene. We also observed suggestive evidence for some loci influencing joint damage in MAs and EAs. We identified two novel independent loci (MAP3K14 and CARD9) strongly associated with joint damage in MAs and EAs and a few shared loci showing suggestive evidence for association.

Systemic inflammation and cardiovascular risk factors predict rapid progression of atherosclerosis in rheumatoid arthritis.

OBJECTIVE: To estimate atherosclerosis progression and identify influencing factors in rheumatoid arthritis (RA). METHODS: We used carotid ultrasound to measure intima-media thickness (IMT) in RA patients, and ascertained cardiovascular (CV) risk factors, inflammation markers and medications. A second ultrasound was performed approximately 3 years later. We calculated the progression rate by subtracting the baseline from the follow-up IMT, divided by the time between the two scans. We used logistic regression to identify baseline factors predictive of rapid progression. We tested for interactions of erythrocyte sedimentation rate (ESR) with CV risk factors and medication use. RESULTS: Results were available for 487 RA patients. The mean (SD) common carotid IMT at baseline was 0.571 mm (0.151). After a mean of 2.8 years, the IMT increased by 0.050 mm (0.055), p≤0.001, a progression rate of 0.018 mm/year (95% CI 0.016 to 0.020). Baseline factors associated with rapid progression included the number of CV risk factors (OR 1.27 per risk factor, 95% CI 1.01 to 1.61), and the ESR (OR 1.12 per 10 mm/h, 95% CI 1.02 to 1.23). The ESR×CV risk factor and ESR×medication product terms were significant, suggesting these variables modify the association between the ESR and IMT progression. CONCLUSIONS: Systemic inflammation and CV risk factors were associated with rapid IMT progression. CV risk factors may modify the role of systemic inflammation in determining IMT progression over time. Methotrexate and antitumour necrosis factor agents may influence IMT progression by reducing the effect of the systemic inflammation on the IMT.

Mortality in Rheumatoid Arthritis (RA): factors associated with recording RA on death certificates.

BACKGROUND: Death certificates can be used to assess disease prevalence and incidence; however, rheumatoid arthritis (RA) often remains unreported in death certificates. We sought to determine to what extent RA is underreported and what demographic and clinical characteristics could predict mention of RA in the death certificate. METHODS: We recruited 1328 patients with RA from private, public and military rheumatology practices and followed them prospectively for yearly evaluations. A rheumatologist assessed clinical characteristics of RA and comorbidities at each evaluation. Deaths were identified through family members, other physicians, obituaries and public death databases. All were confirmed with state-issued death certificates. Patients with and without RA in death certificate were compared using bivariate and multivariate analyses. RESULTS: By December 2013, 326 deaths had occurred. We received and reviewed death certificates for all confirmed deaths, of which 58 (17.7 %) mentioned RA on the death certificate. Bivariate analysis revealed that younger age, a greater number of deformities, higher Sharp score and lower socioeconomic status were each associated with recording RA. Multivariable analyses revealed that comorbidity [OR (95 % CI) = 0.84 (0.73, 0.97); P = 0.022] was inversely associated with listing RA on the death certificate, while the number of deformities [OR (95 % CI) = 1.04 (1.00, 1.07); P = 0.033] and a certified physician's signature on the death certificate [OR (95 % CI) = 4.79 (1.35, 16.9); P = 0.015] increased likelihood of reporting RA. CONCLUSION: In this cohort, RA was not listed in over 80 % of death certificates. Younger patients with fewer comorbidities and more joint deformities were more likely to have RA reported. DISCUSSION: RA is often not included in death certificates. The findings of this study suggest that older patients may have a greater number of comorbidities, thus decreasing the likelihood that RA be included when completing the death certificate.

Dual-Energy Computed Tomography Demonstrating Destructive Calcium Pyrophosphate Deposition Disease of the Distal Radioulnar Joint Mimicking Tophaceous Gout.

Calcium pyrophosphate dihydrate deposition (CPPD) disease is a common etiology of crystalline arthropathy; however, it can manifest in multiple patterns such as acute calcium pyrophosphate (CPP) crystal arthritis, osteoarthritis with CPPD, and chronic CPP crystal inflammatory arthritis. Tumoral or tophaceous-like CPPD is a rare manifestation that is occasionally mistaken for gouty tophus or a soft tissue malignancy. Dual-energy computed tomography (DECT) is a new imaging modality currently utilized in assessing monosodium urate crystal deposition; however, its value in CPPD is uncertain. We describe a case using DECT to diagnose tumoral CPPD mimicking tophaceous gout versus recurrence of a previous synovial sarcoma. The imaging findings on DECT prevented unnecessary surgery to assess for possible malignancy, allowing for the prompt diagnosis of tumoral CPPD. Further studies should be performed to determine the role of DECT in assessing for crystalline deposition disease other than gout.

Association of statins and risk of fractures in a military health system: a propensity score-matched analysis.

BACKGROUND: Contradictory evidence exists regarding statin use and risk of osteoporotic fractures. OBJECTIVE: The study objective was to examine the effect of statins on fracture risk in a Military Healthcare System (MHS) with similar access and standard of health care for its beneficiaries. METHODS: This is a retrospective study of patients enrolled in an MHS encompassing the period from October 1, 2003, to March 1, 2010. Statin users were defined as those receiving a statin for ≥90 days in Fiscal Year 2005, whereas nonusers were defined as individuals not receiving a statin throughout the study period. A propensity score-matched cohort of statin users and nonusers was created using 42 variables. The outcomes were identified using ICD-9-CM codes in the follow-up period (October 1, 2006, to March 1, 2010). In all, 4 outcomes were examined: all fractures, femoral neck fractures, upper-extremity fractures, and lower-extremity fractures. RESULTS: Of 46 249 patients, 6967 pairs of statin users and nonusers were matched. Statin users had a lower risk of femoral neck fracture in comparison to nonusers (odds ratio=0.58, 95% CI=0.36-0.94) but similar risk of all fractures, lower-extremity fractures, and upper-extremity fractures. CONCLUSIONS: In this cohort of patients managed in an MHS, statin use was associated with a lower risk of femoral neck fractures, but not all fractures, upper-extremity fractures, or lower-extremity fractures.

Child Health Needs and the Pediatric Rheumatology Workforce: 2020-2040.

The Pediatric Rheumatology (PRH) workforce supply in the United States does not meet the needs of children. Lack of timely access to PRH care is associated with poor outcomes for children with rheumatic diseases. This article is part of a Pediatrics supplement focused on anticipating the future pediatric subspecialty workforce supply. It draws on information in the literature, American Board of Pediatrics data, and findings from a model that estimates the future supply of pediatric subspecialists developed by the Sheps Center for Health Services Research at the University of North Carolina at Chapel Hill, Strategic Modeling and Analysis Ltd., and the American Board of Pediatrics Foundation. PRH has a smaller workforce per capita of children than most other pediatric subspecialties. The model demonstrates that the clinical workforce equivalent of pediatric rheumatologists in 2020 was only 0.27 per 100 000 children, with a predicted increase to 0.47 by 2040. Although the model predicts a 72% increase in providers, this number remains inadequate to provide sufficient care given the number of children with rheumatic diseases, especially in the South and West regions. The likely reasons for the workforce shortage are multifactorial, including lack of awareness of the field, low salaries compared with most other medical specialties, concerns about working solo or in small group practices, and increasing provider retirement. Novel interventions are needed to increase the workforce size. The American College of Rheumatology has recognized the dire consequences of this shortage and has developed a workforce solutions initiative to tackle these problems.

Carotid atherosclerosis predicts incident acute coronary syndromes in rheumatoid arthritis.

OBJECTIVE: The role of atherosclerosis in the acute coronary syndromes (ACS) that occur in patients with rheumatoid arthritis (RA) has not been quantified in detail. We undertook this study to determine the extent to which ACS are associated with carotid atherosclerosis in RA. METHODS: We prospectively ascertained ACS, defined as myocardial infarction, unstable angina, cardiac arrest, or death due to ischemic heart disease, in an RA cohort. We measured carotid atherosclerosis using high-resolution ultrasound. We used Cox proportional hazards models to estimate the association between ACS and atherosclerosis, adjusting for demographic features, cardiovascular (CV) risk factors, and RA manifestations. RESULTS: We performed carotid ultrasound on 636 patients whom we followed up for 3,402 person-years. During this time, 84 patients experienced 121 new or recurrent ACS events, a rate of 3.5 ACS events per 100 patient-years (95% confidence interval [95% CI] 3.0-4.3). Among the 599 patients without a history of ACS, 66 incident ACS events occurred over 3,085 person-years, an incidence of 2.1 ACS events per 100 person-years (95% CI 1.7-2.7). The incidence of new ACS events per 100 patient-years was 1.1 (95% CI 0.6-1.7) among patients without plaque, 2.5 (95% CI 1.7-3.8) among patients with unilateral plaque, and 4.3 (95% CI 2.9-6.3) among patients with bilateral plaque. Covariates associated with incident ACS events independent of atherosclerosis included male sex, diabetes mellitus, and a cumulative glucocorticoid dose of ≥ 20 gm. CONCLUSION: Atherosclerosis is strongly associated with ACS in RA. RA patients with carotid plaque, multiple CV risk factors (particularly diabetes mellitus or hypertension), many swollen joints, and a high cumulative dose of glucocorticoids, as well as RA patients who are men, are at high risk of ACS.

2015 American College of Rheumatology Workforce Study and Demand Projections of Pediatric Rheumatology Workforce, 2015-2030.

OBJECTIVE: To describe the character and composition of the 2015 pediatric rheumatology workforce in the US, evaluate current workforce trends, and project future supply and demand of the pediatric rheumatology workforce through 2030. METHODS: The American College of Rheumatology created the workforce study group to study the rheumatology workforce. The workforce study group used primary and secondary data to create a representative workforce model. Pediatric rheumatology supply and demand was projected through 2030 using an integrated data-driven framework to capture a more realistic clinical full-time equivalent (FTE) and produce a better picture of access to care issues in pediatric rheumatology. RESULTS: The 2015 pediatric rheumatology workforce was estimated at 287 FTEs (300 providers), while the estimated excess demand was 95 (33%). The projected demand will continue to increase to almost 100% (n = 230) by 2030 if no changes occur in succession planning, new graduate entrants into the profession, and other factors associated with the workforce. CONCLUSION: This study projects that the pediatric rheumatology workforce gap will continue to worsen significantly from the 2015 baseline, and by 2030 the demand for pediatric rheumatologists will be twice the supply. Innovative strategies are needed to increase the workforce supply and to improve access to care.

The cutaneous and systemic manifestations of azathioprine hypersensitivity syndrome.

BACKGROUND: Azathioprine (AZA) hypersensitivity syndrome is a rare side effect that typically occurs early in the initiation of therapy and may include a cutaneous eruption. It is often under-recognized because it mimics infection or disease exacerbation. Until recently, the cutaneous findings associated with AZA hypersensitivity have been reported using nonspecific, descriptive terms without a supportive diagnostic biopsy. OBJECTIVE: To characterize the cutaneous and histologic findings associated with AZA hypersensitivity syndrome. METHODS: We conducted a retrospective analysis of two cases of AZA hypersensitivity syndrome and describe the cutaneous manifestations and histological findings of each case. A review of the English literature for cases of AZA hypersensitivity or allergic or adverse reactions associated with AZA was performed. RESULTS: Sixty-seven cases of AZA hypersensitivity were reviewed; 49% (33/67) had cutaneous manifestations. Of those cases presenting with cutaneous findings, 76% (25/33) had biopsy results or clinical features consistent with a neutrophilic dermatosis, whereas the other 24% (8/33) were reported as a nonspecific cutaneous eruption. LIMITATIONS: Only case reports in which the skin findings could be classified were reviewed. CONCLUSIONS: The predominant cutaneous reaction reported in the literature and observed in the present case series is a neutrophilic dermatosis. Hypersensitivity to AZA can manifest along a wide clinical spectrum from local neutrophilic disease to a systemic syndrome. Skin findings may be an important early clue to the diagnosis of AZA hypersensitivity and aid in prompt recognition and treatment of this potentially life-threatening adverse drug effect.

A returning traveler with fever.

Active duty military personnel and civilian government employees are at risk for exposure to a variety of pathogens as they meet their mission requirements throughout the world. When they present with a systemic disease, the clinician must entertain a broad differential diagnosis due to the multitude of infectious, neoplastic, and noninfectious inflammatory disorders that can have similar clinical presentations. Since treatment varies significantly, and lack of appropriate therapy may be deadly, the search for the definitive diagnosis should be aggressive and thorough. We present a case of adult-onset Still's disease (AOSD) masquerading as an infectious disease process in a man with recent travel to Sudan. A discussion of the differential diagnosis is included along with a review of the diagnostic criteria, prognosis, and current therapeutic options for AOSD.

Workforce Trends in Rheumatology.

The United States is facing a rheumatology provider shortage over the next decade, which will negatively affect care for patients with rheumatic disease across the nation if this deficit is not thoughtfully addressed. The increasing numbers of retiring rheumatology specialists, women entering the workforce, and rheumatology graduates seeking part-time employment were identified as the most significant factors driving the projected decline in supply of providers. The major factors driving the projected increase in demand include an aging and growing population and improved treatment options, both of which increase disease prevalence and the challenge of managing chronic rheumatologic diseases.

Common Soft Tissue Musculoskeletal Pain Disorders.

Soft tissue musculoskeletal pain disorders are common in the primary care setting. Early recognition and diagnosis of these syndromes minimizes patient pain and disability. This article gives a brief overview of the most common soft tissue musculoskeletal pain syndromes. The authors used a regional approach to organize the material, as providers will encounter these syndromes with complaints of pain referring to an anatomic location. The covered disorders include myofascial pain syndrome, rotator cuff tendinopathy, bicipital tendinopathy, subacromial bursitis, olecranon bursitis, epicondylitis, De Quervain disease, trigger finger, trochanteric bursitis, knee bursitis, pes anserine bursitis, Baker cyst, plantar fasciitis, and Achilles tendinopathy.

2015 American College of Rheumatology Workforce Study: The Role of Graduate Medical Education in Adult Rheumatology.

OBJECTIVE: Graduate medical education (GME), through fellowship training, plays a critical role in preparing new rheumatologists for our workforce and is an essential component when addressing the gap of excess demand for adult rheumatology care. This study was undertaken to assess the demographic characteristics and employment trends of new entrants entering the rheumatology workforce and the impact this will have on the supply of rheumatologits over the next 15 years. METHODS: Primary and secondary data sources were used to develop an integrated workforce model. Factors specific to new graduates entering the workforce included available and filled fellowship positions, gender shifts, planned work schedules (part-time or full-time), practice settings (academic or non-academic, private practice), and number of international medical graduates (IMGs) anticipating US practice. RESULTS: In 2015, there were 113 adult rheumatology programs, with 431 of 468 available positions filled. Using the 215 actual positions available annually in fellowship programs as a starting point, after all factors were applied, the projected clinical full-time equivalent number entering the workforce each year was 107; this number was affected significantly by gender and generational trends. In addition, 17% of IMGs self-identified their plan to practice outside the US. Confounding predictions included a large proportion of current rheumatologists planning retirement with substantially reduced patient loads by 2030. CONCLUSION: The current US adult rheumatology workforce is in jeopardy of accelerated decline at a time when demands on the workforce face tremendous growth. The current GME training structure cannot support the increased demand. Potential strategies to address this gap include innovative mechanisms for GME funding to increase fellowship training positions, incentives for pursuing rheumatology training (e.g., loan repayment programs), and novel means for recruitment of care to underserved areas of the US.

A genetic association study of carotid intima-media thickness (CIMT) and plaque in Mexican Americans and European Americans with rheumatoid arthritis.

BACKGROUND AND AIMS: Little is known about specific genetic determinants of carotid-intima-media thickness (CIMT) and carotid plaque in subjects with rheumatoid arthritis (RA). We have used the Metabochip array to fine map and replicate loci that influence variation in these phenotypes in Mexican Americans (MAs) and European Americans (EAs). METHODS: CIMT and plaque were measured using ultrasound from 700 MA and 415 EA patients with RA and we conducted association analyses with the Metabochip single nucleotide polymorphism (SNP) data using PLINK. RESULTS: In MAs, 12 SNPs from 11 chromosomes and 6 SNPs from 6 chromosomes showed suggestive associations (p < 1 × 10-4) with CIMT and plaque, respectively. The strongest association was observed between CIMT and rs17526722 (SLC17A2 gene) (ß ± SE = -0.84 ± 0.18, p = 3.80 × 10-6). In EAs, 9 SNPs from 7 chromosomes and 7 SNPs from 7 chromosomes showed suggestive associations with CIMT and plaque, respectively. The top association for CIMT was observed with rs1867148 (PPCDC gene, ß ± SE = -0.28 ± 0.06, p = 5.11 × 10-6). We also observed strong association between plaque and two novel loci: rs496916 from COL4A1 gene (OR = 0.51, p = 3.15 × 10-6) in MAs and rs515291 from SLCA13 gene (OR = 0.50, p = 3.09 × 10-5) in EAs. CONCLUSIONS: We identified novel associations between CIMT and variants in SLC17A2 and PPCDC genes, and between plaque and variants from COL4A1 and SLCA13 that may pinpoint new candidate risk loci for subclinical atherosclerosis associated with RA.

Data on genetic associations of carotid atherosclerosis markers in Mexican American and European American rheumatoid arthritis subjects.

Carotid Intima-media thickness (CIMT) and plaque are well established markers of subclinical atherosclerosis and are widely used for identifying subclinical atherosclerotic disease. We performed association analyses using Metabochip array to identify genetic variants that influence variation in CIMT and plaque, measured using B-mode ultrasonography, in rheumatoid arthritis (RA) patients. Data on genetic associations of common variants associated with both CIMT and plaque in RA subjects involving Mexican Americans (MA) and European Americans (EA) populations are presented in this article. Strong associations were observed after adjusting for covariate effects including baseline clinical characteristics and statin use. Susceptibility loci and genes and/or nearest genes associated with CIMT in MAs and EAs with RA are presented. In addition, common susceptibility loci influencing CIMT and plaque in both MAs and EAs have been presented. Polygenic Risk Score (PRS) plots showing complementary evidence for the observed CIMT and plaque association signals are also shown in this article. For further interpretation and details, please see the research article titled "A Genetic Association Study of Carotid Intima-Media Thickness (CIMT) and Plaque in Mexican Americans and European Americans with Rheumatoid Arthritis" which is being published in Atherosclerosis (Arya et al., 2018) [1].(Arya et al., in press) Thus, common variants in several genes exhibited significant associations with CIMT and plaque in both MAs and EAs as presented in this article. These findings may help understand the genetic architecture of subclinical atherosclerosis in RA populations.

2015 American College of Rheumatology Workforce Study: Supply and Demand Projections of Adult Rheumatology Workforce, 2015-2030.

OBJECTIVE: To describe the character and composition of the 2015 US adult rheumatology workforce, evaluate workforce trends, and project supply and demand for clinical rheumatology care for 2015-2030. METHODS: The 2015 Workforce Study of Rheumatology Specialists in the US used primary and secondary data sources to estimate the baseline adult rheumatology workforce and determine demographic and geographic factors relevant to workforce modeling. Supply and demand was projected through 2030, utilizing data-driven estimations regarding the proportion and clinical full-time equivalent (FTE) of academic versus nonacademic practitioners. RESULTS: The 2015 adult workforce (physicians, nurse practitioners, and physician assistants) was estimated to be 6,013 providers (5,415 clinical FTE). At baseline, the estimated demand exceeded the supply of clinical FTE by 700 (12.9%). By 2030, the supply of rheumatology clinical providers is projected to fall to 4,882 providers, or 4,051 clinical FTE (a 25.2% decrease in supply from 2015 baseline levels). Demand in 2030 is projected to exceed supply by 4,133 clinical FTE (102%). CONCLUSION: The adult rheumatology workforce projections reflect a major demographic and geographic shift that will significantly impact the supply of the future workforce by 2030. These shifts include baby-boomer retirements, a millennial predominance, and an increase of female and part-time providers, in parallel with an increased demand for adult rheumatology care due to the growing and aging US population. Regional and innovative strategies will be necessary to manage access to care and reduce barriers to care for rheumatology patients.