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

OBJECTIVE: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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.

Rheumatoid arthritis-associated corneal ulceration: mortality and graft survival.

PURPOSE: To investigate mortality and graft survival in patients undergoing penetrating keratoplasty (PKP) for rheumatoid arthritis-associated corneal ulceration (RACU), Fuchs' endothelial dystrophy (FED), and pseudophakic bullous keratopathy (PBK). DESIGN: Case-control study. PARTICIPANTS AND CONTROLS: Patients listed on the UK Transplant Registry who had undergone a PKP for RACU, FED, or PBK between January 4, 1999, and January 4, 2006. Comparative standardized mortality ratios (SMRs) and causes of death were obtained from the Office for National Statistics. METHODS: Outcome data were collected from the UK Ocular Tissue National Transplant database and supplementary questionnaires at transplantation and at 1, 2, and 5 years. Institutional review board approval for the National Health Service Blood and Transplant to undertake the study was obtained. MAIN OUTCOME MEASURES: Mortality and graft survival. RESULTS: A total of 3665 patients were included: RACU (117), PBK (1701), and FED (1847). Five-year survival of patients with RACU was 42% (95% confidence interval [CI], 26-56) compared with 76% (95% CI, 72-78) for FED and 55% for PBK (95% CI, 50-60; P < 0.01). The SMRs for female and male patients with RACU were 43.5 (95% CI, 19.5-63.3) and 12.2 (95% CI, 7.1-19.5), respectively, in comparison with 1.84 and 1.45 for patients with RA, respectively (P < 0.01). There were no significant differences in the causes of death among patients with RACU, FED, or PBK (P > 0.9), with infection the most common cause. The 5-year graft survival rate was 48% (95% CI, 32-62) for RACU, 59% (95% CI, 56-62) for PBK, and 84% (95% CI, 82-86) for FED (P < 0.01). CONCLUSIONS: Mortality and ocular morbidity were significantly increased in patients with RACU. Accelerated immunosenescence should be considered in the differential diagnosis of patients presenting with RACU, and a multidisciplinary approach to management is required.

Serious Pseudomonas aeruginosa infection in AIDS.

During a 7-year period, 32 patients with Pseudomonas aeruginosa infection were identified on an HIV treatment service at a university-affiliated teaching hospital. The number of cases increased from 2 in 1986 to 13 in 1992. Affected patients had evidence of advanced HIV infection. In those treated with antiretroviral therapy, 96% of infections occurred > 1 year after initial presentation with HIV disease. Eighteen cases of pneumonia and 14 nonpulmonary (central venous access device, soft tissue, middle ear-mastoid, corneal, and peritoneal) infections were seen. Comparison with matched controls identified use of a central venous access device and administration of aerosolized pentamidine, corticosteroids, or ganciclovir as risk factors for infection (odds ratios, 5.3, 6.5, 15.0, and 9.0, respectively; p = 0.004, 0.007, 0.02, and 0.02, respectively). Seventy-five percent of cases had community onset, but time since last hospital discharge was significantly shorter in study patients than in controls (mean difference, -85 days; 95% confidence interval, -24 to -146; p = 0.01). Among evaluable cases, outcome was fatal (survival < or = 30 days) in 2 of 16 (13%) patients in whom initial antibiotic therapy was appropriate and 8 of 14 (57%) patients in whom initial therapy was not appropriate (p = 0.016). Ten recurrent infections were seen in 8 of 21 patients who survived the initial infection. Median survival after onset of infection was only 80 days. Pseudomonas aeruginosa infection is an increasingly frequent, severe complication of advanced HIV disease. Several treatment and prevention strategies used in the management of advanced HIV disease are associated with an increased risk of infection.

Mortality rate in rheumatoid arthritis patients developing necrotizing scleritis or peripheral ulcerative keratitis. Effects of systemic immunosuppression.

We performed a nonrandomized clinical trial comparing the ocular and systemic efficacy of cytotoxic immunosuppression with steroidal and nonsteroidal anti-inflammatory therapy in the care of 34 patients with rheumatoid arthritis who developed peripheral ulcerative keratitis and/or necrotizing scleritis. Nine of the 17 patients managed with conventional therapy died of a vascular-related event during the ten-year period of the study. In 13 of the 17 patients, the ocular inflammatory process progressed, and in 5 patients extraocular, although nonlethal, vasculitic lesions developed. One of 17 patients treated with long-term immunosuppressive therapy died during the ten-year follow-up period, and this death occurred after cytotoxic therapy was withdrawn. None of the patients on immunosuppressive regimens developed extraocular vasculitis while taking the drug, and none had progression of the ocular destructive lesion. The results of this study emphasize that the eye is a sensitive indicator for potentially lethal occult systemic vasculitis in patients with rheumatoid arthritis who develop peripheral ulcerative keratitis or necrotizing scleritis. Our mortality data strongly suggest that the use of cytotoxic drugs may alter favorably the general as well as the ocular prognosis in these patients.