Thomas Mason

Dual-energy CT for the diagnosis of gout: an accuracy and diagnostic yield study

Objectives To assess the accuracy of dual-energy CT (DECT) for diagnosing gout, and to explore whether it can have any impact on clinical decision making beyond the established diagnostic approach using polarising microscopy of synovial fluid (diagnostic yield). Methods Diagnostic single-centre study of 40 patients with active gout, and 41 individuals with other types of joint disease. Sensitivity and specificity of DECT for diagnosing gout was calculated against a combined reference standard (polarising and electron microscopy of synovial fluid). To explore the diagnostic yield of DECT scanning, a third cohort was assembled consisting of patients with inflammatory arthritis and risk factors for gout who had negative synovial fluid polarising microscopy results. Among these patients, the proportion of subjects with DECT findings indicating a diagnosis of gout was assessed. Results The sensitivity and specificity of DECT for diagnosing gout was 0.90 (95% CI 0.76 to 0.97) and 0.83 (95% CI 0.68 to 0.93), respectively. All false negative patients were observed among patients with acute, recent-onset gout. All false positive patients had advanced knee osteoarthritis. DECT in the diagnostic yield cohort revealed evidence of uric acid deposition in 14 out of 30 patients (46.7%). Conclusions DECT provides good diagnostic accuracy for detection of monosodium urate (MSU) deposits in patients with gout. However, sensitivity is lower in patients with recent-onset disease. DECT has a significant impact on clinical decision making when gout is suspected, but polarising microscopy of synovial fluid fails to demonstrate the presence of MSU crystals.

Increased mortality in adults with a history of juvenile rheumatoid arthritis: A population-based study

OBJECTIVE To assess mortality in a population-based cohort of adults with a history of juvenile rheumatoid arthritis (JRA). METHODS The Rochester Epidemiology Project database was used to identify all cases of JRA diagnosed among Rochester, Minnesota residents under the age of 16 between January 1, 1960 and December 31, 1993. Fifty-seven patients in this cohort are now adults (ages 18-53 years, mean age 34.3 years), and this subgroup was contacted for a long-term followup study. The average length of followup from the time of diagnosis was 25.6 years. RESULTS Four deaths occurred in this cohort of 57 adults with a history of JRA. All 4 deceased patients had other autoimmune illnesses and died of complications of these diseases. The observed frequency of 4 deaths was significantly greater (P < 0.0026 by one-sample log-rank test) than the 1 death that would be expected among Minnesota whites of similar age and sex, and corresponds to a mortality rate of 0.27 deaths per 100 years of patient followup compared with an expected mortality rate of 0.068 deaths per 100 years of followup in the general population. CONCLUSION The results indicate a significant, unexpected increase in mortality in this population-based cohort of adults with a history of JRA in comparison with the rate in the general population. The deaths in this group were all associated with other autoimmune disorders, suggesting that special emphasis should be given to the diagnosis and treatment of other autoimmune diseases, including immunodeficiencies, in JRA patients. The frequency of deaths in this cohort suggests that JRA patients are at substantial risk for mortality, and highlights the need for longitudinal followup and care into adulthood.

Health-related quality of life in children and adolescents with juvenile localized scleroderma

OBJECTIVES To examine the health-related quality of life (HRQOL) of children with juvenile localized scleroderma (JLS) and to compare them with patients with atopic dermatitis (AD) and healthy controls. METHODS The cohorts were identified through a diagnostic index and were seen between January 1996 and December 2006. We identified 81 JLS patients to whom we age- and sex-matched 75 AD patients and 75 healthy controls. All patients were mailed a survey containing the English-language version of the German Revised Childrens Quality of Life Questionnaire (KINDL) and the Childrens Dermatology Life Quality Index (CDLQI). Linear regression models, adjusted for age and sex, examined differences in the KINDL and CDLQI scores. RESULTS Survey completion rates in the JLS, AD and healthy control groups were 40, 28 and 44%, respectively. There was no difference in KINDL scores between JLS vs AD (73 vs 74, P = 0.3) and JLS vs healthy controls (73 vs 74, P = 0.8). However, CDLQI scores showed some impairment in HRQOL in JLS patients as compared with a healthy reference population, but not to the degree seen in AD (2 vs 4, P = 0.05). An exploratory analysis showed that HRQOL did not differ among the types of JLS with either measure. CONCLUSION JLS patients have some impairment in skin disease-specific HRQOL when compared with a healthy reference population, but not as severe as that seen in AD patients. Overall HRQOL in this JLS cohort was as good as healthy controls, a reassuring finding for patients, families and healthcare providers.

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.

Contralateral cutaneous and MRI findings in a patient with Parry–Romberg syndrome

A 23-year-old man was admitted for management of simple partial status epilepticus. He was diagnosed with Parry–Romberg syndrome at the age of 5 years after developing left hemifacial atrophy (figure 1A). Biopsy of a focally hyperpigmented depressed plaque of his left ear showed changes consistent with morphea. He subsequently developed simple partial seizures involving left arm/leg shaking. Serial MRIs revealed progressive right cerebral/cerebellar and left occipital atrophy, all without contrast enhancement (figure 1B). T2 hyperintensities within the right cerebral white matter were noted (figure 1C). Biopsy of an area of such hyperintensity revealed perivascular lymphocytic T cell infiltrates with marked rarefaction and gliosis (figure 1D). There were increased CD3 and CD45 cells, further indicating T cell …

Assessing the performance of the Birmingham vasculitis activity score at diagnosis for Children with antineutrophil cytoplasmic antibody-associated vasculitis in a registry for childhood vasculitis (ARChiVe)

Objective. There are no validated tools for measuring disease activity in pediatric vasculitis. The Birmingham Vasculitis Activity Score (BVAS) is a valid disease activity tool in adult vasculitis. Version 3 (BVAS v.3) correlates well with physician’s global assessment (PGA), treatment decision, and C-reactive protein in adults. The utility of BVAS v.3 in pediatric vasculitis is not known. We assessed the association of BVAS v.3 scores with PGA, treatment decision, and erythrocyte sedimentation rate (ESR) at diagnosis in pediatric antineutrophil cytoplasmic antibody-associated vasculitis (AAV). Methods. Children with AAV diagnosed between 2004 and 2010 at all ARChiVe centers were eligible. BVAS v.3 scores were calculated with a standardized online tool (www.vasculitis.org). Spearman’s rank correlation coefficient (rs) was used to test the strength of association between BVAS v.3 and PGA, treatment decision, and ESR. Results. A total of 152 patients were included. The physician diagnosis of these patients was predominantly granulomatosis with polyangiitis (n = 99). The median BVAS v.3 score was 18.0 (range 0–40). The BVAS v.3 correlations were rs = 0.379 (95% CI 0.233 to 0.509) with PGA, rs = 0.521 (95% CI 0.393 to 0.629) with treatment decision, and rs = 0.403 (95% CI 0.253 to 0.533) with ESR. Conclusion. Applied to children with AAV, BVAS v.3 had a weak correlation with PGA and moderate correlation with both ESR and treatment decision. Prospective evaluation of BVAS v.3 and/or pediatric-specific modifications to BVAS v.3 may be required before it can be formalized as a disease activity assessment tool in pediatric AAV.

Aseptic meningitis in adult onset Still’s disease

Adult onset Still’s disease (AOSD) is a systemic inflammatory disease characterized by high-fevers, articular involvement, maculopapular rash, hepatosplenomegaly, lymphadenopathy, and a neutrophilic leukocytosis. Though systemic complications of AOSD or its treatment are well described in the literature, CNS involvement in AOSD is exceedingly rare and can have protean manifestations. We present a patient with AOSD who developed chronic meningitis and sensorineural hearing loss on treatment, with a review of prior reported cases of aseptic meningitis, to highlight this rare complication of this uncommon illness.

Do adult disease severity subclassifications predict use of cyclophosphamide in children with ANCA-associated vasculitis? An analysis of ARChiVe study treatment decisions.

Objective. To determine whether adult disease severity subclassification systems for antineutrophil cytoplasmic antibody-associated vasculitis (AAV) are concordant with the decision to treat pediatric patients with cyclophosphamide (CYC). Methods. We applied the European Vasculitis Study (EUVAS) and Wegener’s Granulomatosis Etanercept Trial (WGET) disease severity subclassification systems to pediatric patients with AAV in A Registry for Childhood Vasculitis (ARChiVe). Modifications were made to the EUVAS and WGET systems to enable their application to this cohort of children. Treatment was categorized into 2 groups, “cyclophosphamide” and “no cyclophosphamide.” Pearson’s chi-square and Kendall’s rank correlation coefficient statistical analyses were used to determine the relationship between disease severity subgroup and treatment at the time of diagnosis. Results. In total, 125 children with AAV were studied. Severity subgroup was associated with treatment group in both the EUVAS (chi-square 45.14, p < 0.001, Kendall’s tau-b 0.601, p < 0.001) and WGET (chi-square 59.33, p < 0.001, Kendall’s tau-b 0.689, p < 0.001) systems; however, 7 children classified by both systems as having less severe disease received CYC, and 6 children classified as having severe disease by both systems did not receive CYC. Conclusion. In this pediatric AAV cohort, the EUVAS and WGET adult severity subclassification systems had strong correlation with physician choice of treatment. However, a proportion of patients received treatment that was not concordant with their assigned severity subclass.

Population-based study of outcomes of patients with juvenile idiopathic arthritis (JIA) compared to non-JIA subjects

OBJECTIVE Evaluate healthcare utilization and occurrence of comorbidities in a population-based cohort of patients of juvenile idiopathic arthritis (JIA) with an age- and sex-matched comparator group. METHODS Prevalent cases of JIA in 1994-2013 were identified in Olmsted County, Minnesota, along with age- and sex-matched non-JIA comparators. Surgeries, hospitalizations, pregnancies, and comorbidities were identified by medical record review. Poisson methods were used to generate rate ratios (RR) with 95% confidence intervals (CI) to compare outcomes between JIA and non-JIA cohorts separately during childhood (age < 18 years) and adulthood (age ≥ 18 years). RESULTS A total of 89 JIA and 89 non-JIA comparators were identified [64% female; mean (SD) age 8.6 (5.1) years at JIA incidence/index date and mean follow-up in childhood 6.3 (4.4) years for JIA; similar for comparators]. Among them, 38 pairs had follow-up into adulthood with mean follow-up of 8.0 (5.5) years for JIA. Children with JIA were more likely to have joint surgery (RR = 3.93, 95% CI: 1.18-24.94), non-joint surgery (RR = 1.90, 95% CI: 1.05-3.67), and hospitalizations (RR = 2.25, 95% CI: 1.04-5.53) than non-JIA comparators. As adults only joint surgeries remained significantly different (RR = 8.5, 95% CI: 2.27-120.1). Depression during childhood was more common in JIA (RR = 2.49, 95% CI: 1.01-6.13). There were no differences in educational achievement, employment status, or pregnancy outcomes between the 2 groups. CONCLUSIONS In a population-based cohort, inpatient healthcare utilization is higher for patients with JIA including surgery and hospitalization during childhood but not extending into adulthood. Understanding long-term comorbidities and healthcare needs for patients with JIA is necessary to provide comprehensive care.

Juvenile Idiopathic Arthritis in Olmsted County, Minnesota, 1960–2013

To evaluate the incidence and prevalence of juvenile idiopathic arthritis (JIA) in Olmsted County, Minnesota in 1994–2013 and trends in juvenile rheumatoid arthritis (JRA) in 1960–2013.