Severe Extra-articular Manifestation Of Rheumatoid Arthritis Research Articles

Decline in Incidence of Extra-Articular Manifestations of Rheumatoid Arthritis: A Population-Based Cohort Study.

The focus of this study was to assess changes in the cumulative incidence of extra-articular manifestations of rheumatoid arthritis (ExRAs) and associated mortality risk. This study evaluated trends in occurrence of ExRAs using a population-based inception cohort that included all adult patients with incident rheumatoid arthritis (RA) from 1985 through 2014 meeting the 1987 American College of Rheumatology criteria. Patients were divided into two cohorts based on the incidence date of RA, 1985 to 1999 and 2000 to 2014. The occurrence of ExRAs was determined by manual chart review, and the 10-year cumulative incidence was estimated for each ExRA in both cohorts. Cox proportional hazard models were used to determine associations between specific demographic and RA disease characteristics and ExRAs and between ExRAs and mortality. There were 907 patients included, 296 in the 1985 to 1999 cohort and 611 in the 2000 to 2014 cohort. The 10-year cumulative incidence of any ExRA decreased significantly between the earlier and later cohorts (45.1% vs 31.6%, P < 0.001). This was largely driven by significant declines in subcutaneous rheumatoid nodules (30.9% vs 15.8%, P < 0.001) and nonsevere ExRAs (41.4% vs 28.8%, P = 0.001). Identified risk factors for the development of any ExRAs include rheumatoid factor positivity (hazard ratio [HR] 2.02, 95% confidence interval [CI] 1.43-2.86) and current smoking (HR 1.61, 95% CI 1.10-2.34). Mortality was increased in patients with either nonsevere (HR 1.83, 95% CI 1.18-2.85) or severe ExRAs (HR 3.05, 95% CI 1.44-6.49). The incidence of ExRAs has decreased over time. Mortality remains increased in patients with ExRAs.

Scleritis in rheumatoid arthritis: Before and during biologic era.

Scleritis represents a severe extra-articular manifestation of rheumatoid arthritis (RA). Recent clinical observations suggest a decreasing incidence of scleritis in RA, attributed to improved treatment options. Our study reports on the incidence and clinical characteristics of scleritis in RA observed in the biological era and reflects on our results in a historical perspective. We performed a retrospective evaluation of all 1623 consecutive patients with RA diagnosed at the department of rheumatology between 2011 and 2021 at the Erasmus Medical Center to investigate the incidence of scleritis. We also reviewed clinical and laboratory data of all patients with scleritis and RA from the department of ophthalmology at our center. In addition, we reviewed the literature on this topic and discuss our results in view of changes over time. The incidence of scleritis within recent series of patients with a diagnosis of RA in our tertiary center was 0,25% in 10 years (4 out of 1623; 2011-2021).The cumulative incidence of scleritis in RA based on literature review from the pre-biologic era varied from 0.7% per 8 years to 0,8% per 30 years. Manifestations and complications of scleritis remained unchanged over time, with scleral necrosis developing in more than 80% of cases and mortality of RA patients with scleritis remained similar to pre-biologic era (30% in 9 years after the onset of scleritis). The RA patients with scleritis often exhibited autoantibodies (rheumatoid factor and/or anti-citrullinated protein antibody) and erosive disease. Although our recent series is characterized by a slightly lower incidence of scleritis in RA compared to the pre-biologic era, clinical presentation remained severe and similar to the pre-biologic era. Ophthalmologists and rheumatologists should be aware of scleritis as a severe extra-articular manifestation of RA.

Clinical Correlates, Outcomes, and Predictors of Inflammatory Ocular Disease Associated with Rheumatoid Arthritis in the Biologic Era.

Inflammatory ocular disease (IOD) is a rare but severe extraarticular manifestation of rheumatoid arthritis (ExRA) with high mortality. The aim of our study was to examine clinical characteristics of IOD in rheumatoid arthritis (RA) and their effect on disease severity and outcomes in recent years. A retrospective cohort of RA patients with IOD evaluated between 1996 and 2013 was assembled and compared to RA comparators without IOD and matched for age, sex, and disease duration. We identified 92 patients (69% female; mean age 62 yrs) with IOD: 33 scleritis, 23 episcleritis, 21 peripheral ulcerative keratitis (PUK), 14 uveitis, and 1 with orbital inflammation. The majority of patients with scleritis, episcleritis, and PUK was seropositive versus uveitis (> 80% vs 62%, p = 0.048). PUK and scleritis were more symptomatic compared to episcleritis and uveitis, and often required systemic therapy. Time to resolution was longer in scleritis than episcleritis (p = 0.01). PUK, scleritis, and uveitis had severe ocular sequelae. Prevalence of severe ExRA (18% vs 4%, p = 0.004) and dry eye syndrome (42% vs 26%, p = 0.024) was higher among patients with IOD than comparators. The incidence of new ExRA over 5-year followup was also higher among cases (29% vs 11%, p = 0.022). Ten-year survival was similar among RA patients with and without IOD (66% vs 64%, p = 0.56), with no differences noted among IOD subtypes. This large single-center study highlights the variable presentation and outcomes of IOD in RA. Although ocular complications are associated with significant morbidity, it is reassuring that survival among those with IOD is now similar to those without ocular disease.

Extraarticular manifestations of rheumatoid arthritis develop in patients receiving anti-tumor necrosis factor-α treatment: a retrospective chart review from a UK center.

To assess the evolution of preexisting extraarticular manifestations of rheumatoid arthritis (EA-RA) in patients treated with anti-tumor necrosis factor-α (TNF-α), as well as the development of new EA-RA. We assessed EA-RA in 152 patients receiving anti-TNF-α treatment. In 22 cases, a new EA-RA developed. In 5 cases, there was evidence of progression of preexisting EA-RA. Regression was found in 4 cases. Some patients were in disease remission when they developed EA-RA, whereas some patients had moderate/high disease activity. EA-RA are still present in patients treated with anti-TNF-α. Development of new severe EA-RA is rare in patients receiving anti-TNF therapy.

Extra-articular manifestations in a community-based sample of patients with rheumatoid arthritis: incidence and relationship to treatment with TNF inhibitors

Objectives: To determine the incidence of severe extra-articular rheumatoid arthritis (ExRA) in a community-based cohort of RA patients, and to evaluate whether treatment with tumour necrosis factor (TNF) inhibitors has any effect on the risk of ExRA.Methods: In a review of clinical records from 1 July 1997 to 31 December 2004, severe ExRA manifestations were classified according to predefined criteria. Patients were censored at the development of ExRA, death, emigration, or 31 December 2004. Exposure to anti-TNF treatment has continuously and independently been recorded as part of a regional follow-up system.Results: During treatment with TNF inhibitors, there were two patients with new onset of ExRA in 408 person-years at risk (pyr) [0.49/100 pyr, 95% confidence interval (CI) 0.06–1.77]. Among those without anti-TNF treatment there were 63 patients with ExRA in 5425 pyr (1.16/100 pyr, 95% CI 0.89–1.49). The relative risk comparing those treated to those not treated with TNF inhibitors was 0.42 (95% CI 0.10–1.73).Conclusion: Our data show a lower incidence of ExRA in patients treated with TNF inhibitors but further studies with a larger sample size are needed for a more accurate estimate of the size of the effect.

Pragmatic prognostic approach of rheumatoid arthritis-associated interstitial lung disease

Rheumatoid arthritis (RA) affects approximately 1% of the adult population, with female predominance. Pulmonary involvement is common, and may include a variety of manifestations namely RA-associated interstitial lung disease (ILD) 1, 2, pleural disease 3, rheumatoid nodules and airway complications (crico-arytenoid arthritis, bronchiectasis, bronchiolitis 4). ILD is usually detected in patients already diagnosed with RA (mostly between the ages of 50 and 60 yrs and more commonly in males), but isolated pulmonary disease may precede the onset of articular disease. Clinically significant RA-ILD affects approximately 7% of patients with RA 5, whereas a higher prevalence was found by autopsy studies or prospective screening studies using high-resolution chest tomography (HRCT) 1. Thus, RA-ILD may affect up to one out of 1,000 adult persons in the general population. When present, it may decrease the survival of patients by 3.5 to 4.9 yrs 6, although the outcome is highly variable, with indolent course and conversely rapid deterioration being reported. Tobacco smoking, a potentially reversible risk factor, increases the incidence and severity of RA 7 through a proposed mechanism of epitope citrullination in a predisposing genetic background 8, increases the risk of severe extra-articular manifestations of RA 5 and might increase the risk of having ILD in patients with RA although conflicting results have been reported 1, 9. Much of the complexity of interstitial pneumonia arises from the lack of a definite relationship between histopathological and imaging phenotypes. The currently available data indicate that the histopathological pattern of usual interstitial pneumonia (UIP) may be equally as frequent as non-specific interstitial pneumonia (NSIP) in patients with RA-ILD 10, contrasting with the predominance of NSIP in the other connective tissue diseases. Patterns of organising pneumonia, lymphocytic interstitial pneumonia, diffuse alveolar damage, and even desquamative …

Association of HLA–C3 and smoking with vasculitis in patients with rheumatoid arthritis

To compare HLA-C genotypes and smoking habits in patients with vasculitis or other severe extraarticular manifestations of rheumatoid arthritis (ExRA) with those in RA patients without extraarticular disease. Patients were recruited from a large research database of patients with RA at the Mayo Clinic, from 2 Swedish cohorts of prevalent RA cases, and from a regional Swedish early RA cohort. Patients with severe ExRA (n = 159) and control patients with RA but no history of ExRA (non-ExRA controls) (n = 178) were matched for duration of RA and for clinical center. Data on smoking at RA onset, rheumatoid factor (RF) status, and antinuclear antibodies (ANAs) were extracted from the medical records. Polymerase chain reaction-based HLA-C genotyping was performed using a sequence-specific primer kit. The distribution of HLA-C alleles was significantly different between patients with RA-associated vasculitis and non-ExRA controls (P = 0.014). This was mainly due to a positive association of the HLA-C3 allele with vasculitis (allele frequency 0.411 in vasculitis patients versus 0.199 in non-ExRA controls; P < 0.001) and a decreased frequency of HLA-C7 (0.122 and 0.243, respectively; P = 0.018). The association between HLA-C3 and vasculitis was not due to linkage disequilibrium with HLA-DRB1. Smoking (P = 0.001), RF positivity (P < 0.0001), and presence of ANAs (P < 0.0001) were all associated with ExRA. HLA-C3 and smoking were both significant predictors of vasculitis in a multivariate model. Vasculitis in RA is associated with HLA-C3. Smoking is an independent predictor of vasculitis and other types of severe ExRA. Our results suggest that these variables are among the genetic and environmental factors that contribute significantly to the pathomechanisms of systemic RA.