Mortality outcomes in pediatric rheumatology in the US

Abstract

Objective. To describe mortality rates, causes of death, and potential mortality risk factors in pediatric rheumatic diseases in the US.Methods. We used the Indianapolis Pediatric Rheumatology Disease Registry, which includes 49,023 patients from 62 centers who were newly diagnosed between 1992 and 2001. Identifiers were matched with the Social Security Death Index censored for March 2005. Deaths were confirmed by death certificates, referring physicians, and medical records. Causes of death were derived by chart review or from the death certificate. Standardized mortality ratios (SMRs) and 95% confidence intervals (95% CIs) were determined.Results. After excluding patients with malignancy, 110 deaths among 48,885 patients (0.23%) were confirmed. Patients had been followed up for a mean ؎ SD of 7.9 ؎ 2.7 years. The SMR of the entire cohort was significantly decreased (0.65 [95% CI 0.53-0.78]), with differences in patients followed up for >9 years. The SMR was significantly greater for systemic lupus erythematosus (3.06 [95% CI 1.78-4.90]) and dermatomyositis (2.64 [95% CI 0.86-6.17]) but not for systemic juvenile rheumatoid arthritis (1.8 [95% CI 0.66-3.92]). The SMR was significantly decreased in pain syndromes (0.41 [95% CI 0.21-0.72]). Causes of death were related to the rheumatic diagnosis (including complications) in 39 patients (35%), treatment complications in 11 (10%), non-natural causes in 25 (23%), background disease in 23 (21%), and were unknown in 12 patients (11%). Rheumatic diagnoses, age at diagnosis, sex, and early use of systemic steroids and methotrexate were significantly associated with the risk of death.Conclusion. Our findings indicate that the overall mortality rate for pediatric rheumatic diseases was not increased. Even for the diseases and conditions associated with increased mortality, mortality rates were significantly lower than those reported in previous studies.The practice of pediatric rheumatology includes more than 170 conditions, both inflammatory and noninflammatory (1). Approximately 3 in 1,000 children have a rheumatic condition (1). While we tend to study pediatric rheumatology outcomes in terms of remission versus active disease, organ and radiologic damage, function, and quality of life, there is a small but significant increase in mortality rates among these patients. An increased rate of mortality has been found in juvenile rheumatoid arthritis (JRA) (2-12), childhood systemic lupus erythematosus (SLE) (13-21), dermatomyositis (DM) (22-25), various vasculitides (26-30), and systemic sclerosis (SSc) (31-33).However, most of those studies were of relatively small cohorts, reported mortality outcomes only on specific diseases, had a followup time of Ͻ10 years, and were conducted prior to the 1990s, when new therapies were developed. Even larger studies were flawed; most were based on physician surveys and questionnaires with no strategies to verify response accuracy (4,8). The diagnoses in studies of national cohorts were usually not assigned by pediatric rheumatologists (...

Two Randomized Trials of Canakinumab in Systemic Juvenile Idiopathic Arthritis

“…Seven cases of the macrophage activation syndrome were reported in these trials, with two associated deaths. 38,39 The mortality rate in phase 2 18 and phase 3 trials of canakinumab (2% over an average of 547 days) is in line with the mortality rate associated with systemic JIA, as reported by Hashkes et al 40 A limitation of the two studies is that patients without fever were excluded from participation. Indeed, in a subset of patients with systemic JIA, systemic symptoms eventually resolve while chronic arthritis continues.…”

Late sequelae of systemic lupus erythematosus in children

“…Studies conducted in Cleveland also revealed a persistent significant mortality among jSLE patients in comparison to that observed over the previous years [14]. In this study, the analysis also demonstrated a changed incidence of various clinical and immunological manifestations.…”

Elevated circulating levels of interferon-γ and interferon-γ-induced chemokines characterise patients with macrophage activation syndrome complicating systemic juvenile idiopathic arthritis

“…Laboratory abnormalities include decrease in white blood cells, platelet and haemoglobin, hypertransaminasemia, hyperferritinemia and evidence of intravascular coagulation 1. MAS causes significant morbidity and mortality accounting for a significant portion of the deaths due to sJIA 2 3…”