Increased sensitivity of the European medicines agency algorithm for classification of childhood granulomatosis with polyangiitis.

OBJECTIVE: Granulomatosis with polyangiitis (Wegener's; GPA) and other antineutrophil cytoplasmic antibody (ANCA)-associated vasculitides (AAV) are rare in childhood and are sometimes difficult to discriminate. We compared use of adult-derived classification schemes for GPA against validated pediatric criteria in the ARChiVe (A Registry for Childhood Vasculitis e-entry) cohort, a Childhood Arthritis and Rheumatology Research Alliance initiative. METHODS: Time-of-diagnosis data for children with physician (MD) diagnosis of AAV and unclassified vasculitis (UCV) from 33 US/Canadian centers were analyzed. The European Medicines Agency (EMA) classification algorithm and European League Against Rheumatism/Paediatric Rheumatology International Trials Organisation/Paediatric Rheumatology European Society (EULAR/PRINTO/PRES) and American College of Rheumatology (ACR) criteria for GPA were applied to all patients. Sensitivity and specificity were calculated (MD-diagnosis as reference). RESULTS: MD-diagnoses for 155 children were 100 GPA, 25 microscopic polyangiitis (MPA), 6 ANCA-positive pauciimmune glomerulonephritis, 3 Churg-Strauss syndrome, and 21 UCV. Of these, 114 had GPA as defined by EMA, 98 by EULAR/PRINTO/PRES, and 87 by ACR. Fourteen patients were identified as GPA by EULAR/PRINTO/PRES but not by ACR; 3 were identified as GPA by ACR but not EULAR/PRINTO/PRES. Using the EMA algorithm, 135 (87%) children were classifiable. The sensitivity of the EMA algorithm, the EULAR/PRINTO/PRES, and ACR criteria for classifying GPA was 90%, 77%, and 69%, respectively, with specificities of 56%, 62%, and 67%. The relatively poor sensitivity of the 2 criteria related to their inability to discriminate patients with MPA. CONCLUSION: EULAR/PRINTO/PRES was more sensitive than ACR criteria in classifying pediatric GPA. Neither classification system has criteria for MPA; therefore usefulness in discriminating patients in ARChiVe was limited. Even when using the most sensitive EMA algorithm, many children remained unclassified.

Survival rates of children with acute lymphoblastic leukemia presenting to a pediatric rheumatologist in the United States.

BACKGROUND: Approximately 30% of pediatric acute lymphoblastic leukemia patients present with musculoskeletal symptoms and are often referred first to a pediatric rheumatologist. We examined the survival and causes of death of these patients presenting to a pediatric rheumatologist and compared the rates with that reported in the hematology-oncology literature. PROCEDURE: We used the Pediatric Rheumatology Disease Registry, including 49,023 patients from 62 centers, 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. RESULTS: There were 7 deaths of 89 patients (7.9%, 95% confidence interval: 3.9%-15.4%) with acute lymphoblastic leukemia with a 5-year survival rate of 95.5% (88.3 to 98.3) and 10-year survival rate of 89.8% (79.0% to 95.2%). The causes of death were sepsis (bacterial and/or fungal) in 4 (57%) patients, the disease in 2 (29%) and post bone-marrow transplantation in 1 (14%). CONCLUSION: The overall survival of patients with acute lymphoblastic leukemia seen first by pediatric rheumatologists is higher than the range reported in the pediatric oncology literature for the same period of diagnosis.

Mortality outcomes in pediatric rheumatology in the US.

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 > or =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.

A multicenter case-control study on predictive factors distinguishing childhood leukemia from juvenile rheumatoid arthritis.

OBJECTIVE: Acute lymphocytic leukemia (ALL) often presents with musculoskeletal concerns such as pain or swelling, even before appearance of blasts in the peripheral blood. Such presentation may lead to misdiagnosis of a child with juvenile rheumatoid arthritis (JRA). This study was designed to identify the predictive factors for leukemia using basic clinical and laboratory information. METHODS: A retrospective chart review was performed using a simple questionnaire to compare the clinical and laboratory findings present during the initial visit to a pediatric rheumatology clinic for 277 children who were ultimately diagnosed with either JRA (n = 206) or ALL (n = 71). Sensitivity and specificity analysis of a variety of parameters, both singly and in combination, was performed to identify predictive value for ALL. RESULTS: The majority (75%) of children with ALL did not have blasts in the peripheral blood at the time of evaluation by pediatric rheumatologists. In children presenting with unexplained musculoskeletal complaints, the 3 most important factors that predicted a diagnosis of ALL were low white blood cell count (< 4 x 10(9)/L), low-normal platelet count (150-250 x 10(9)/L), and history of nighttime pain. In the presence of all 3, the sensitivity and specificity for a diagnosis of ALL were 100% and 85%, respectively. Other findings, including antinuclear antibody, rash, and objective signs of arthritis, were not helpful in differentiating between these diagnoses because they occurred at similar rates in both groups. CONCLUSIONS: When a child develops new-onset bone-joint complaints, the presence of subtle complete blood count changes combined with nighttime pain should lead to consideration of leukemia as the underlying cause.