To describe current trends in arthritis related joint surgery among a population based cohort of patients with rheumatoid arthritis (RA) and to examine the influence of joint surgery on mortality.
A retrospective medical record review was performed of all orthopedic surgeries following diagnosis in cases of adult onset RA in Olmsted County, Minnesota incident in 1980–2007. Surgeries included primary total joint arthroplasty, joint reconstructive procedures (JRP), soft tissue procedures (STP) and revision arthroplasty. Cumulative incidence (CI) of surgery was estimated using Kaplan-Meier methods. Time trends, sex differences and mortality were examined using Cox models with time-dependent covariates for surgery.
A total of 189 of 813 patients underwent ≥1 surgical procedures involving joints during follow-up. The cumulative incidence of any joint surgery at 10 years after RA incidence for the 1980–1994 cohort was 27.3% compared to 19.5% for the 1995–2007 cohort (p=0.08). The greatest reduction was in STP, which decreased from 12.1% in 1980–1994 to 6.0% in 1995–2007 at 10 years after RA incidence (p=0.012). Obese patients, and women (cumulative incidence 26.6% at 10 years for women; 20.4% for men; p=0.049) had more surgery. JRP was significantly associated with mortality (hazard ratio [HR]: 2.6; 95 % CI 1.8, 3.9; p <0.001) compared to patients not requiring JRP.
The rates of joint surgery continue to decrease for patients more recently diagnosed with RA. JRP, is associated with increased mortality. These findings may reflect both improved treatments for RA as well as continued higher disease burden among some patients.
Infection risk is increased in patients with rheumatoid arthritis (RA), and accurate assessment of infection risk could inform clinical decision-making. The purpose of this study was to develop and validate a score to predict the 1 year risk of serious infections.
We utilized a population based cohort of Olmsted County, Minnesota residents with incident RA ascertained in 1955–1994 that were followed longitudinally through their complete medical records until January 2000. The validation cohort included residents with incident RA ascertained in 1995–2007. The outcome measures included all serious infections (requiring hospitalization or intravenous antibiotics). Potential predictors were examined using multivariable Cox models. The risk score was estimated directly from the multivariable model and performance was assessed in the validation cohort using Harrell’s c-statistic.
Among the 584 patients with RA (mean age 58 years; 72% female; median follow-up 9.9 years), 252 had ≥ 1 serious infection (646 total infections). The risk score included age, previous serious infection, corticosteroid use, elevated erythrocyte sedimentation rate, extraarticular manifestations of RA and comorbidities (coronary heart disease, heart failure, peripheral vascular disease, chronic lung disease, diabetes mellitus, alcoholism). Validation revealed good discrimination (c-statistic =0.80).
RA disease characteristics and comorbidities can be used to accurately assess the risk of serious infection in patients with RA. Knowledge of risk of serious infections in patients with RA can influence clinical decision making and inform strategies to reduce and prevent the occurrence of these infections.
Patients with rheumatoid arthritis (RA) suffer from an excess burden of cardiovascular disease (CVD). CV risk scores for the general population may not accurately predict CV risk for patients with RA. A population-based inception cohort of patients who fulfilled 1987 American College of Rheumatology criteria for RA in 1988–2007 was followed until death, migration, or 12/31/2008. CV risk factors and CVD (myocardial infarction, CV death, angina, stroke, intermittent claudication and heart failure) were ascertained by medical record review. The 10 year predicted CVD risk was calculated using the general Framingham and the Reynolds risk scores. Standardized incidence ratios were calculated to compare observed and predicted CVD risks. The study included 525 patients with RA aged ≥30 years without prior CVD. The mean follow-up was 8.4 years, during which 84 patients developed CVD. The observed CVD risk was 2-fold higher than the Framingham risk score predicted in women and 65% higher in men, and the Reynolds risk score revealed similar deficits. Patients aged ≥75 years had observed CVD risk >3 times the Framingham predicted risk. Patients with positive rheumatoid factor or persistently elevated erythrocyte sedimentation rate also experienced more CVD events than predicted. In conclusion, the Framingham and Reynolds risk scores substantially underestimated CVD risk in patients with RA of both sexes, especially in older ages and in patients with positive rheumatoid factor. These data underscore the need for more accurate tools to predict CVD risk in patients with RA.
rheumatoid arthritis; cardiovascular disease; risk scores
To assess the incidence and mortality impact of upper and lower gastrointestinal (GI) events in rheumatoid arthritis (RA) compared to non-RA subjects.
We identified incident upper and lower GI events and estimated their incidence rates using person-year methods in a population-based incident RA cohort of residents of Olmsted County, Minnesota, USA (1987 American College of Rheumatology criteria first fulfilled between January 1, 1980, and January 1, 2008) and non-RA subjects from the same population.
The study included 813 patients with RA and 813 non-RA subjects (mean followup 10.3 and 10.8 yrs, respectively); 68% women; mean age 55.9 yrs in both cohorts. The rate of upper GI events/100 person-years was 2.9 in RA versus 1.7 in the non-RA cohort (rate ratio 1.7, 95% CI 1.4, 2.2); for lower GI events, the rates were 2.1 in RA versus 1.4 in the non-RA cohort (rate ratio 1.5, 95% CI 1.1, 1.9). The incidence of upper GI bleed, perforation, ulcer, obstruction, and any upper GI event in RA declined over calendar time; the incidence of lower GI events remained unchanged. Exposure to glucocorticoids, prior upper GI disease, abdominal surgery, and smoking were associated with lower GI events in RA. Both upper and lower GI events were associated with increased mortality risk in RA.
There is increased risk of serious upper and lower GI events in RA compared to non-RA subjects, and increased GI-related mortality in RA. Prominent declines in incidence of upper, but not lower GI events in RA highlight the need for studies investigating lower GI disease in patients with RA.
RHEUMATOID ARTHRITIS; GASTROINTESTINAL DISEASE; INCIDENCE
The Rochester Epidemiology Project (REP) is a patient record-based database based upon a medical records-linkage system for all residents of the Olmsted County, MN, USA. This comprehensive system includes all health-care providers of patients resident in this geographically defined region. It uniquely enables long-term population-based studies of all medical conditions occurring in this population; their incidence and prevalence; permits examination of disease risk and protective factors, health resource utilization and cost as well as translational studies in rheumatic diseases.
Rheumatic diseases; Epidemiology; Registry; Health sciences research; Outcomes; Cost
1) To evaluate the utility of erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) for the diagnosis of giant cell arteritis (GCA) 2) to determine the frequency of normal ESR and CRP at diagnosis of GCA.
All patients undergoing temporal artery biopsy (TAB) between 2000 and 2008 were identified. Only subjects with both ESR and CRP at the time of TAB were included. The medical records of all patients were reviewed.
We included 764 patients (65% women), mean age 72.7 (±9.27) years, who underwent TAB. Biopsy was consistent with GCA in 177 patients (23%). Elevated CRP and elevated ESR provided a sensitivity of 86.9% and 84.1% respectively, for a positive TAB. The odds ratio (OR) of a concordantly elevated ESR and CRP for positive TAB was 3.06 (95% CI 2.03, 4.62) while the OR for concordantly normal ESR and CRP was 0.49 (95% CI 0.29, 0.83).
Seven patients (4%) with a positive TAB for GCA had a normal ESR and CRP at diagnosis. Compared to GCA patients with elevated markers of inflammation, a greater proportion of these patients had polymyalgia rheumatica symptoms (p=0.008) while constitutional symptoms, anemia and thrombocytosis were observed less often (p<0.05).
CRP is a more sensitive marker than ESR for a positive TAB that is diagnostic of GCA. There may be clinical utility in obtaining both tests in the evaluation of patients with suspected GCA. A small proportion of patients with GCA may have normal inflammatory markers at diagnosis.
Giant cell (GCA) and Takayasu’s arteritis (TAK) are 2 forms of large-vessel vasculitis (LVV) that involve the aorta and its major branches. GCA has a predilection for the cranial branches, while TAK tends to affect the extracranial branches. Both disorders may also cause nonspecific constitutional symptoms. Although some clinical features are more common in one or the other disorder and the ages of initial presentation differ substantially, there is enough clinical and histopathologic overlap between these disorders that some investigators suggest GCA and TAK may be 2 processes within the spectrum of a single disease. There have been few randomized therapeutic trials completed in GCA, and none in TAK. The lack of therapeutic trials in LVV is only partially explained by the rarity of these diseases. It is likely that the lack of well validated outcome measures for LVV and uncertainties regarding trial design contribute to the paucity of trials for these diseases. An initiative to develop a core set of outcome measures for use in clinical trials of LVV was launched by the international OMERACT Vasculitis Working Group in 2009 and subsequently endorsed by the OMERACT community at the OMERACT 10 meeting. Aims of this initiative include: (1) to review the literature and existing data related to outcome assessments in LVV; (2) to obtain the opinion of experts and patients on disease content; and (3) to formulate a research agenda to facilitate a more data-based approach to outcomes development.
VASCULITIS; OUTCOMES; TAKAYASU’S ARTERITIS; GIANT CELL ARTERITIS
To determine the frequency of hypothyroidism in patients with rheumatoid arthritis (RA), and to elucidate the association of hypothyroidism and development of cardiovascular disease in these patients.
A retrospective medical record review was performed using all incident cases of adult onset RA from a defined geographic population base that fulfilled criteria for RA in the years 1988–2007. Patients with and without thyroid disease were followed longitudinally for the development of cardiovascular disease (CVD).
A cohort of 650 patients with RA and an age and sex matched comparison cohort of 650 patients without RA was assembled (both cohorts mean age 55.8; 69% female). There was no significant difference between cohorts in the presence of hypothyroid disease or subclinical hypothyroidism at time of RA diagnosis. No significant difference was found in the cumulative incidence of hypothyroid disease between the two cohorts. Hypothyroid disease was found to be significantly associated with CVD in patients with RA (hazard ratio 2; 95% confidence interval 1.1,3.6). This difference remained significant and unchanged after adjustment for traditional cardiovascular risk factors (HR: 2.0; 95% CI: 1.1, 3.6).
No significant difference was found in either incidence or prevalence of hypothyroidism between patients with or without RA. Hypothyroid disease was significantly associated with CVD in patients with RA, even after adjustment for other traditional cardiovascular risk factors.
Rheumatoid arthritis; Hypothyroidism; Cardiovascular Disease
Tumor necrosis factor (TNF) inhibitors are useful in the treatment of numerous inflammatory and immunologic disorders. Since many of these conditions occur in women of childbearing age, safety during pregnancy and breastfeeding is of considerable importance.
This paper is a review of the literature on the safety of TNF inhibitors during pregnancy and breastfeeding published between 2001 and 2011.
TNF inhibitors do not appear to be associated with a high risk of teratogenicity or intrauterine death. However, a small magnitude increase in risk cannot be ruled out given the paucity of data on the subject. Although TNF inhibitor use may be associated with a higher rate of preterm delivery, this may in fact be due to an active, underlying disease. Therefore, the decision to use these medications should be made on a case-by-case basis. If the disease cannot be managed with first line agents, TNF inhibitors may be helpful in reducing the number of disease exacerbations. Nevertheless, when using TNF inhibitors, it is prudent to discontinue treatment around the third trimester when transfer across the placenta is greatest and to restart postpartum.
tumor necrosis factor (TNF) inhibitors; uveitis; pregnancy; breastfeeding
Background. The systemic vasculitides are syndromes characterized by inflammation and injury (necrosis or thrombosis) of blood vessels, resulting in clinical manifestations according to the affected vascular bed, but not classically in stocking-glove neuropathy. Objective. To describe a form of primary vasculitis affecting strictly peripheral nerves manifesting as stocking-glove neuropathy. Methods. Case series of 110 patients seen in three centers in Bogotá who presented with symptoms and signs of polyneuropathy and/or were identified with vasculitis affecting only the peripheral nerves, and who underwent sural nerve biopsy. Results. Six patients had a vasculitis affecting only the peripheral nerves diagnosed on sural nerve biopsy which demonstrated a mixed infiltrate of monocytes/macrophages and lymphocytes especially in the small epineurial blood vessels. Over time, all had worsening of symptoms, with grip weakness and motor deficits in the hand and feet. Serologies and acute phase reactants were normal in all patients. Treatment response to immunosuppression was satisfactory in 5 patients; 1 patient had progressive neurologic damage. Conclusions. There is a distinct form of primary vasculitis of the peripheral nervous system characterized by distal sensory polyneuropathy with stocking-glove distribution with good prognosis, few and minor relapses and good response to treatment even after delayed diagnosis.
To investigate the incidence of noncardiac vascular disease in a community-based incidence cohort of patients with rheumatoid arthritis (RA) and compare to that in the general population. To investigate trends in incidence of noncardiac vascular disease in patients with RA.
A population-based inception cohort of patients with RA in Olmsted County, Minnesota with incident RA between 1/1/1980 and 12/31/2007 and a cohort of non-RA subjects from the same population base was assembled and followed until 12/31/2008. Venous thromboembolic events (VTE), cerebrovascular events, and peripheral arterial events were ascertained by medical record review.
The study population included 813 patients with RA (mean age [SD] 55.9 [15.7] years, 68% women), with average length of follow-up of 9.6 years [SD 6.9]. Compared to non-RA subjects of similar age and sex, patients diagnosed with RA between 1995 and 2007 had a higher incidence (%) of VTE compared to non-RA subjects (cumulative incidence [±SE] 6.7 ± 1.7 vs 2.8 ± 1.1, respectively; p=0.005), but similar rates of cerebrovascular and peripheral arterial events. Among patients with RA, the incidence of VTE, cerebrovascular events, and peripheral arterial events was similar in the 1995–2007 time period compared to the 1980–1994 time period.
The incidence of VTE appears to be increased in patients with RA compared to non-RA subjects. The incidence of cerebrovascular events and peripheral vascular disease events was similar in patients with RA compared to non-RA subjects. Among patients with RA, the incidence of noncardiac vascular disease has remained stable in recent decades.
The past decade has brought important advances in the understanding of rheumatoid arthritis and its management and treatment. New classification criteria for rheumatoid arthritis, better definitions of treatment outcome and remission, and the introduction of biologic response-modifying drugs designed to inhibit the inflammatory process have greatly altered the approach to managing this disease. More aggressive management of rheumatoid arthritis early after diagnosis and throughout the course of the disease has resulted in improvement in patient functioning and quality of life, reduction in comorbid conditions, and enhanced survival.
ACPA, anti–citrullinated protein antibody; ACR, American College of Rheumatology; BeSt, Behandel-Strategieën [trial]; CDAI, Clinical Disease Activity Index; CRP, C-reactive protein; CTLA-4:Ig, cytotoxic T lymphocyte–associated antigen 4:immunoglobulin fusion protein; DAS28, Disease Activity Score in 28 joints; DMARD, disease-modifying antirheumatic drug; EULAR, European League Against Rheumatism; HCQ, hydroxychloroquine; MTX, methotrexate; SDAI, Simplified Disease Activity Index; SSZ, sulfasalazine; TEAR, Treatment of Early Aggressive Rheumatoid Arthritis [study]; TNF, tumor necrosis factor
Psoriasis is associated with an atherogenic lipid profile but longitudinal changes in lipids around disease onset are unknown. The purpose of our study is to examine the effect of psoriasis onset on serum lipid profiles.
We compared changes in lipid profiles in a population based incident cohort of 689 patients with psoriasis and 717 non-psoriasis subjects. All lipid measures performed 5 years before and after psoriasis incidence/index date were abstracted. Random-effects models adjusting for age, sex and calendar year were used to examine trends in lipid profiles.
There were significant declines in total cholesterol (TC) and low-density lipoprotein (LDL) levels during the 5 years before and after psoriasis incidence/index date in both the psoriasis and the non-psoriasis cohorts, with a greater decrease noted in the TC levels (p=0.022) and LDL (p=0.054) in the non-psoriasis cohort. High-density lipoprotein (HDL) levels increased significantly both before and after psoriasis incidence date in the psoriasis cohort. Triglyceride (TG) levels were significantly higher (p<0.001), and HDL levels significantly lower (p=0.013) in patients with psoriasis compared to non-psoriasis subjects. There were no differences in prescriptions for lipid lowering drugs between the two cohorts.
Patients with psoriasis had a significant decrease in TC and LDL levels during the 5 years before psoriasis incidence. Higher mean TG and lower mean HDL levels were noted in the 5 years before psoriasis incidence. These changes are unlikely to be caused by lipid lowering treatment alone and require further exploration.
Psoriasis; Lipids; Epidemiology
Prior studies have suggested an association of human retrovirus 5 with rheumatoid arthritis. The purpose of this study was to determine if human retrovirus-5 proviral DNA is present in synovial tissue and blood specimens from patients with rheumatoid arthritis or osteoarthritis, or those without joint disease.
Synovial tissue and whole blood from 75 patients with rheumatoid arthritis, 75 patients with osteoarthritis, and 50 patients without a primary arthritis diagnosis were assayed by real-time quantitative polymerase chain reaction (PCR) using primers that amplify a 186-bp fragment of human retrovirus-5 proviral DNA.
A total of 200 tissue specimens, 200 mononuclear cells, and 196 of 200 granulocyte specimens tested negative for human retrovirus-5 proviral DNA. No association between human retrovirus 5 and rheumatoid arthritis or osteoarthritis (P = 0.516) was identified. Granulocyte specimens from 4 patients, 2 with rheumatoid arthritis and 2 with osteoarthritis, yielded a low positive human retrovirus-5 proviral DNA signal (83–1,365 copies of human retrovirus-5 proviral DNA/ml blood).
Contrary to prior reports, we did not find an association between human retrovirus 5 and rheumatoid arthritis or osteoarthritis using a real-time PCR assay. Our findings are consistent with the recent finding that human retrovirus 5 is actually rabbit endogenous retrovirus H.
Human retrovirus-5; Rheumatoid arthritis; Osteoarthritis
Persons with rheumatoid arthritis (RA) suffer a high burden of infections, but currently no biomarkers are available to identify individuals at greatest risk. A prospective longitudinal study was therefore conducted to determine the association between the responsiveness of ex vivo cytokine production and 6-month risk of infections. Infections were identified by billing codes and validated by medical record review. At baseline, the release of 17 cytokines by peripheral blood mononuclear cells in response to stimulation, or media alone, was measured using multiplexed cytokine analysis. Production of IL-2, IL-8, IL-10, IL-17, TNF-α, IFN-γ, and GM-CSF, induced by various conditions, was significantly associated with the occurrence of infections. A multivariable prediction model based on these data provided new information on the risk of infection beyond standard assessments of disease activity, severity, and treatment. Future studies could utilize this information to devise new biomarkers for the prediction of infection in patients with RA.
Immune signature; immune response; peripheral blood mononuclear cells
The aim of this study was to assess long-term golimumab therapy in patients with rheumatoid arthritis (RA) who discontinued previous tumour necrosis factor alpha (TNFα) inhibitor(s) for any reason.
Results through week 24 of this multicentre, randomised, double-blind, placebo-controlled study of active RA (≥4 tender, ≥4 swollen joints) were previously reported. Patients received placebo (Group 1), 50 mg golimumab (Group 2) or 100 mg golimumab (Group 3) subcutaneous injections every 4 weeks. Patients from Groups 1 and 2 with <20% improvement in tender/swollen joints at week 16 early escaped to golimumab 50 mg and 100 mg, respectively. At week 24, Group 1 patients crossed over to golimumab 50 mg, Group 2 continued golimumab 50/100 mg per escape status and Group 3 maintained dosing. Data through week 160 are reported.
459 of the 461 randomised patients were treated; 236/459 (51%) continued treatment through week 160. From week 24 to week 100, ACR20 (≥20% improvement in American College of Rheumatology criteria) response and ≥0.25 unit HAQ (Health Assessment Questionnaire) improvement were sustained in 70–73% and 75–81% of responding patients, respectively. Overall at week 160, 63%, 67% and 57% of patients achieved ACR20 response and 59%, 65% and 64% had HAQ improvement ≥0.25 unit in Groups 1, 2 and 3, respectively. Adjusted for follow-up duration, adverse event incidences (95% CI) per 100 patient-years among patients treated with golimumab 50 mg and 100 mg were 4.70 (2.63 to 7.75) and 8.07 (6.02 to 10.58) for serious infection, 0.95 (0.20 to 2.77) and 2.04 (1.09 to 3.49) for malignancy and 0.00 (0.00 to 0.94) and 0.62 (0.17 to 1.59) for death, respectively.
In patients with active RA who discontinued previous TNF-antagonist treatment, golimumab 50 and 100 mg injections every 4 weeks yielded sustained improvements in signs/symptoms and physical function in ∼57–67% of patients who continued treatment. Golimumab safety was consistent with other anti-TNF agents, although definitive conclusions regarding long-term safety require further monitoring.
Heart failure is an important cause of mortality in patients with rheumatoid arthritis (RA). Evidence suggests that immune mechanisms contribute to myocardial injury and fibrosis, leading to left ventricular diastolic dysfunction (LVDD). In this study, we sought to identify a signature of LVDD in patients with RA by analyzing the responsiveness of the innate and adaptive immune systems to stimulation ex vivo.
Subjects (n=212) enrolled prospectively from a population-based cohort underwent echocardiography, and left ventricular function was classified as normal, mild LVDD, or moderate-to-severe LVDD. The release of 17 cytokines by blood mononuclear cells in response to stimulation with a panel of 7 stimuli or in media alone was analyzed using multiplexed immunoassays. Logistic regression models were used to test for associations between a multi-cytokine immune response score and LVDD after adjusting for clinical covariates.
An 11-cytokine profile effectively differentiated subjects with moderate-to-severe LVDD from those with normal LV function. An immune response score (range 0 – 100) was strongly associated with moderate-to-severe LVDD (odds ratio per 10 units: 1.5; 95% confidence interval: 1.2, 2.1) after adjusting for serum IL-6, brain natriuretic peptide, and glucocorticoid use, as well as other RA characteristics and LVDD risk factors.
The major finding of this study is that aberrant systemic immune responsiveness is associated with advanced myocardial dysfunction in patients with RA. The unique information added by the immune response score on the likelihood of LVDD warrants future longitudinal studies of its value in predicting future deterioration in myocardial function.
To assess incidence and mortality impact of extra-articular rheumatoid arthritis (ExRA) in patients with incident rheumatoid arthritis (RA) in 1995–2007 vs 1985–1994.
Data on incident ExRA were abstracted from medical records of RA patients, Olmsted County, Minnesota residents who first met the 1987 ACR criteria for RA between 1/1/1995 and 12/31/2007. Patients were followed until death, migration from Olmsted County, or 12/31/2008. ExRA were classified using the predefined criteria and compared to the corresponding 1985–1994 inception RA cohort (n=147).
The 1995–2007 cohort included 463 RA patients followed for a mean of 6.3 years. Mean age was 55.6 years (69% female; 67% rheumatoid factor [RF] positive). The 10-year cumulative incidence of any ExRA (50.1%) and severe ExRA (6.7%) in 1995–2007 cohort was similar to the 1985–1994 cohort (46.2% and 9.7%, respectively). The 10-year cumulative incidence of vasculitis, but not other ExRA, was significantly lower in 1995–2007 cohort (0.6%) compared to the 1985–1994 cohort (3.6%). RF positivity, erosions/destructive changes, use of methotrexate, other disease-modifying antirheumatic drugs and systemic corticosteroids were significantly associated with ExRA in the 1995–2007 cohort. ExRA were associated with mortality risk (HR 2.1, 95%CI 1.2, 3.7) in the 1995–2007 cohort. The decrease in mortality following ExRA in the 1995–2007 cohort vs 1985–1994 cohort did not reach statistical significance (HR 0.6, 95%CI 0.3, 1.2, p=0.16).
ExRA remain a common complication associated with increased mortality in RA. The occurrence of vasculitis appears to be decreasing in the recent years.
rheumatoid arthritis; extra-articular manifestations; incidence; mortality; risk factors
Understanding of the personal risks for rheumatoid arthritis (RA) and other rheumatic diseases remains poor, despite advances in knowledge of their pathogenesis, therapeutics, and clinical impact, in part because the personal lifetime risk of developing these diseases is unknown.
To estimate the lifetime risk of RA, as well as other inflammatory autoimmune rheumatic diseases, including systemic lupus erythematosus, psoriatic arthritis, polymyalgia rheumatica (PMR), giant cell arteritis, ankylosing spondylitis, and Sjögren’s syndrome, and to provide an overall estimate of the risk for developing inflammatory autoimmune rheumatic disease over a lifetime.
Using the incidence rates obtained from our population-based studies of rheumatic diseases among residents of Olmsted County, Minnesota, and mortality rates from life tables for the general population, we estimated sex-specific lifetime risk of rheumatic disease.
The lifetime risk of RA developing in US adults is 3.6% for women and 1.7% for men, and the lifetime risk of rheumatoid factor positive RA is 2.4% for women and 1.1% for men. The second most common inflammatory autoimmune rheumatic disease is PMR with a lifetime risk of 2.4% for women and 1.7% among men. The overall lifetime risk of inflammatory autoimmune rheumatic disease was 8.4% for women and 5.1% for men.
One in 12 women and 1 in 20 men will develop inflammatory autoimmune rheumatic disease during their lifetime. These results can serve as useful guides in counseling patients regarding their lifetime risk of these conditions and have important implications for disease awareness campaigns.
The purpose of our study was to examine whether rheumatoid arthritis (RA) patients with no overt cardiovascular disease (CVD) have a higher prevalence of metabolic syndrome (MetS) than subjects without RA or CVD. We also examined whether RA disease characteristics are associated with the presence of MetS in RA patients without CVD.
Subjects from a population-based cohort of patients who fulfilled 1987 ACR criteria for RA between 1/1/1980 and 12/31/2007 were compared to non-RA subjects from the same population. All subjects with any history of CVD were excluded. Waist circumference, body mass index (BMI), and blood pressure were measured during the study visit. Data on CVD, lipids and glucose measures were ascertained from medical records. MetS was defined using NCEP/ATP III criteria. Differences between the 2 cohorts were examined using logistic regression models adjusted for age and sex.
The study included 232 RA subjects without CVD and 1241 non-RA subjects without CVD. RA patients were significantly more likely to have an elevated waist circumference and elevated blood pressure than non-RA subjects, even though BMI was similar in both groups. Significantly more RA patients were classified as having MetS. In RA patients, MetS was associated with Health Assessment Questionnaire disability index, large joint swelling and uric acid levels, but not with C-reactive protein or RA therapies.
Among subjects without a history of CVD, RA patients are more likely to have MetS than non-RA subjects. MetS in RA patients was associated some measures of disease activity.
Objectives. To determine the incidence of herpes zoster (HZ) in GCA.
Methods. Utilizing the resources of the Rochester Epidemiology Project, all incident cases of GCA diagnosed between 1 January 1950 and 31 December 2004 were identified. For each GCA patient, two subjects without GCA of the same gender and similar age and length of medical history were randomly selected from the population. Patients were followed until death, last contact or 31 December 2006.
Results. The study population included 204 GCA patients and 407 non-GCA subjects. The GCA cohort had 163 (79%) women and 41 (21%) men, with a mean age of 76.0 (8.2) years. The non-GCA cohort had 325 (80%) women and 82 (20%) men, with a mean age of 75.6 (8.4) years. During follow-up, 21 GCA patients and 38 non-GCA subjects developed HZ. There was no difference in the development of HZ in GCA patients compared with non-GCA patients [hazard ratio (HR): 1.22; 95% CI 0.71, 2.08; adjusted for age, sex and calendar year]. No GCA patient and one non-GCA subject developed HZ within 6 months of index date. The frequency of post-herpetic neuralgia was similar between both groups (P = 0.64).
Conclusions. Patients with GCA do not appear to be at increased risk of HZ compared with the general population, even during the first 6 months of therapy when glucocorticoid doses are usually highest.
Giant cell arteritis; Herpes zoster; Glucocorticoids
The advent of improved biomarkers promises to enhance the clinical care for patients with rheumatoid arthritis (RA) and other immune-mediated disorders. We have developed an innovative approach to broadly assess the cytokine responsiveness of human PBMC using a multi-stimulant panel and multiplexed immunoassays. The objective of this study was to demonstrate this concept by determining whether cytokine profiles could discriminate RA patients according to disease stage (early vs. late) or severity. A 10-cytokine profile, consisting of IL-12, CCL4, TNFα, IL-4, and IL-10 release in response to stimulation with anti-CD3/anti-CD28, CXCL8 and IL-6 in response to CMV/EBV lysate, and IL-17A, GM-CSF, and CCL2 in response to HSP60, easily discriminated the early RA group from controls. These data were used to create an immune response score, which performed well in distinguishing the early RA patients from controls and also correlated with several markers of disease severity among the patients with late RA. In contrast, the same 10-cytokine profile assessed in serum was far less effective in discriminating the groups. Thus, our approach lays the foundation for the development of immunologic ‘signatures’ that could be useful in predicting disease course and monitoring the outcomes of therapy among patients with immune-mediated diseases.
To study the association between previous cancer and giant cell arteritis (GCA).
Using the resources of the Rochester Epidemiology Project (REP), we identified incident cases of GCA diagnosed between January 1, 1950 and December 31, 2004. Each GCA patient was matched on age, gender and length of medical history to 2 subjects without GCA from the same population. Medical records were reviewed. Diagnosis of cancer was confirmed by histopathology.
We identified 204 GCA cases and 407 controls. The GCA group had 163 (79%) women and 41 (21%) men, mean age 76.0 years (± 8.2 years). The non-GCA group had 325 (80%) women and 82 (20%) men, mean age 75.6 years (± 8.4 years). At index date, 45 (22%) GCA patients and 125 (31%) non-GCA patients had a previous cancer (age, sex and calendar year adjusted OR: 0.63; 95% CI: 0.42, 0.94; p=0.022). Mean age at diagnosis of first cancer before index date was similar in cases (67.5 ±11.9 years) and controls (64.9 ±13.2 years), p =0.32. Mean duration from first cancer to index date was 9.8 years (±9.9) in cases and 11.7 years (±10.8) for controls (p=0.31). Cancer types were similar in both groups but fewer gynecological malignancies were noted in GCA patients (OR: 0.39; 95% CI 0.13, 1.15; p=0.09). Colon cancer also appeared less commonly in cases compared to controls (OR: 0.22; 95% CI 0.03, 1.74; p=0.15).
In this population-based case-control study, GCA patients had significantly fewer malignancies prior to index date compared to controls.
Giant Cell Arteritis; malignancy; case-control study
Patients with rheumatic diseases including rheumatoid arthritis (RA) are at increased risk for infections related to both the disease and its treatments. These include uncommonly reported infections due to histoplasmosis.
Medical record review of all patients with a diagnosis of RA who developed new histoplasmosis infection in an endemic region between Jan 1, 1998 and Jan 30, 2009 and who were seen at Mayo Clinic in Rochester, Minnesota was performed.
Histoplasmosis was diagnosed in 26 patients. Most patients were on combination therapies; 15 were on anti-tumor necrosis factor (anti-TNF) agents, 15 on corticosteroids and 16 on methotrexate. Most received more than 6 months of itraconazole and/or amphotericin treatment. Two patients died of causes unrelated to histoplasmosis. Anti-TNF treatment was restarted in 4/15 patients, with recurrence of histoplasmosis in one.
In this largest single center series of patients with RA and histoplasmosis in the era of immunomodulatory therapy, we found that most patients had longstanding disease and were on multiple immunomodulatory agents. Most cases were pulmonary; typical signs and symptoms of disease were frequently lacking.
Histoplasmosis; rheumatoid arthritis