N-terminal pro-B-type natriuretic peptide diagnostic algorithm versus American Heart Association algorithm for Kawasaki disease.

BACKGROUND: Diagnosis of Kawasaki disease (KD) can be challenging in the absence of a confirmatory test or pathognomonic finding, especially when clinical criteria are incomplete. We recently proposed serum N-terminal pro-B-type natriuretic peptide (NT-proBNP) as an adjunctive diagnostic test. METHODS: We retrospectively tested a new algorithm to help KD diagnosis based on NT-proBNP, coronary artery dilation (CAD) at onset, and abnormal serum albumin or C-reactive protein (CRP). The goal was to assess the performance of the algorithm and compare its performance with that of the 2004 American Heart Association (AHA)/American Academy of Pediatrics (AAP) algorithm. RESULTS: The algorithm was tested on 124 KD patients with NT-proBNP measured on admission at the present institutions between 2007 and 2013. Age at diagnosis was 3.4 ± 3.0 years, with a median of five diagnostic criteria; and 55 of the 124 patients (44%) had incomplete KD. CA complications occurred in 64 (52%), with aneurysm in 14 (11%). Using this algorithm, 120/124 (97%) were to be treated, based on high NT-proBNP alone for 79 (64%); on onset CAD for 14 (11%); and on high CRP or low albumin for 27 (22%). Using the AHA/AAP algorithm, 22/47 (47%) of the eligible patients with incomplete KD would not have been referred for treatment, compared with 3/55 (5%) with the NT-proBNP algorithm (P < 0.001). CONCLUSION: This NT-proBNP-based algorithm is efficient to identify and treat patients with KD, including those with incomplete KD. This study paves the way for a prospective validation trial of the algorithm.

Hereditary Heterozygous C2 Deficiency: Variable Clinical and Serological Manifestations Among Three Sisters.

The causal link between inherited complement deficiencies and systemic lupus erythematosus (SLE) has been well established, although it remains a rare cause of the disease. We present the case of three biological sisters with hereditary heterozygous C2 deficiency, but who differ widely in their clinical and serological manifestations. Patient 1 is 25 years old and was diagnosed with SLE at the age of 12. Further testing revealed positive ANA and anti-dsDNA, antiphospholipid syndrome (APS) and decreased C2, C3 and C4 levels. Patients 2 and 3 are 21-year-old dizygotic twins. Both have positive ANA and antiphospholipid (APL) antibodies, and decreased C2 and C4 levels. We present a case of familial heterozygous C2 deficiency with different disease phenotypes. The presence of positive APL antibodies in all 3 patients is significant, as this association has been rarely described. The variable clinical and serological manifestations among our patients further reflect the complex and multifactorial nature of SLE.

Rapidly progressive aortic aneurysmal dilation in a child with systemic lupus erythematosus: too early too severe.

About 10-20% of systemic lupus erythematosus cases occur in children, often with more severe features at onset and more active disease over time compared with adults. Cardiovascular complications are common in this population but thoracic aortic aneurysms rarely occur. Although the pathophysiology of this complication remains unclear, vasculitis seems to play an important role, leading to degeneration and fibrosis of the media and formation of the aneurysm. We report the case of a 9-year-old systemic lupus erythematosus patient with important renal involvement, who underwent aortic replacement surgery for the treatment of an aortic aneurysm. This case highlights the importance of monitoring the thoracic aorta in children with systemic lupus erythematosus and the need for the development of appropriate early management strategies for this serious complication.

Glucocorticoid-related changes in body mass index among children and adolescents with rheumatic diseases.

OBJECTIVE: To examine the temporal and dose-related effects of glucocorticoids (GCs) on body mass index (BMI) in children with rheumatic diseases. METHODS: Children initiating GCs for a rheumatic disease (n = 130) were assessed every 3 months for 18 months. BMI, weight, and height Z score trajectories were described according to GC starting dosage in prednisone equivalents: high (≥1.0 mg/kg/day), low (<0.2 mg/kg/day to a maximum of 7.5 mg/day), and moderate (between high and low) dosage. The impact of GC dosing, underlying diagnosis, pubertal status, physical activity, and disease activity on BMI Z scores and on percent body fat was assessed with longitudinal mixed-effects growth curve models. RESULTS: The GC starting dose was high in 59% and moderate in 39% of patients. The peak BMI Z score was +1.29 at 4 months with high-dose GCs and +0.69 at 4.2 months with moderate-dose GCs (P < 0.001). Overall, 50% (95% confidence interval 41-59%) of the children returned to within +0.25 SD of their baseline BMI Z score. Oral GC dose over the preceding 3 months was the most significant determinant of BMI Z score and percent body fat. The proportion of days in receipt of GCs, disease activity, and a diagnosis of systemic-onset juvenile idiopathic arthritis were also associated with BMI Z scores. The correlation between changes in BMI and changes in percent body fat was 0.09. CONCLUSION: In children with rheumatic diseases starting moderate and high doses of GCs, BMI Z scores peaked at 4 months, and only half returned to within +0.25 SD of their baseline BMI Z score after 18 months.

Value of amino-terminal pro B-natriuretic peptide in diagnosing Kawasaki disease.

BACKGROUND: The aim of the present study was to investigate the diagnostic value of the N-terminal B-type natriuretic peptide (NT-proBNP) in acute Kawasaki disease (KD) given that the clinical criteria and the current basic laboratory tests lack the necessary specificity for accurate diagnosis. METHODS: Basic biological tests and serum NT-proBNP levels obtained from acute KD patients were compared to that of febrile controls. NT-proBNP was considered abnormal based on the following definitions: above a cut-off determined on receiver operator characteristic (ROC) analysis, above the upper limit for age, or above 2 SD calculated from healthy children. Analyses were also performed for KD cases with complete or incomplete criteria combined and separately. RESULTS: There were 81 patients and 49 controls aged 3.60 ± 2.77 versus 4.25 ± 3.88 years (P= 0.69). ROC analysis yielded significant area under the curve for NT-proBNP. The sensitivity, specificity, positive and negative predictive values were 70.4-88.9%, 69.4-91.8%, 82.8-93.4%, and 65.2-79.1%. The odds ratios based on NT-proBNP definitions varied between 18.13 (95% confidence interval [CI]: 7.21-45.57), 20.82 (95%CI: 8.18-53.0), and 26.71 (95%CI: 8.64-82.57; P < 0.001). Results were reproducible for cases with complete or incomplete criteria separately. CONCLUSION: NT-proBNP is a reliable marker for the diagnosis of KD. Prospective clinical studies with emphasis on NT-proBNP in a diagnostic algorithm are needed.

Incident vertebral fractures among children with rheumatic disorders 12 months after glucocorticoid initiation: a national observational study.

OBJECTIVE: To determine the frequency of incident vertebral fractures (IVF) 12 months after glucocorticoid (GC) initiation in children with rheumatic diseases and to identify children at higher risk. METHODS: Children with rheumatic diseases initiating GC were enrolled in a prospective observational study. Annual spine radiographs were evaluated using the Genant semiquantitative method. Spine areal bone mineral density (aBMD) was measured every 6 months. Clinical features, including cumulative GC dose, back pain, disease and physical activity, calcium and vitamin D intake, and spine aBMD Z scores, were analyzed for association with IVF. RESULTS: Seven (6%) of 118 children (95% confidence interval 2.9-11.7%) had IVF. Their diagnoses were: juvenile dermatomyositis (n = 2), systemic lupus erythematosus (n = 3), systemic vasculitis (n = 1), and mixed connective tissue disease (n = 1). One child was omitted from the analyses after 4 months because of osteoporosis treatment for symptomatic IVF. Children with IVF received on average 50% more GC than those without (P = 0.030), had a greater increase in body mass index (BMI) at 6 months (P = 0.010), and had greater decrements in spine aBMD Z scores in the first 6 months (P = 0.048). Four (67%) of 6 children with IVF and data to 12 months had spine aBMD Z scores less than -2.0 at 12 months compared to 16% of children without IVF (P = 0.011). CONCLUSION: The incidence of VF 12 months following GC initiation was 6%; most children were asymptomatic. Children with IVF received more GC, had greater increases in BMI, and had greater declines in spine aBMD Z scores in the first 6 months.

High prevalence of primary immune deficiencies in children with autoimmune disorders.

OBJECTIVES: Autoimmunity is a well-recognised manifestation of primary immunodeficiency disorders. However, the prevalence of primary immunodeficiency among children with autoimmune diseases is not well characterised. The objective of this retrospective study was to describe the prevalence of primary immunodeficiency disorders in a paediatric population with autoimmune diseases. METHODS: We retrospectively analysed a cohort of patients investigated for diverse autoimmune conditions from June 1st 2005 to December 31st 2006 in the Rheumatology and Immunology service of a tertiary care paediatric hospital in Canada. The clinical data of patients were reported. Independently of their baseline characteristics, patients underwent a systematic immunologic workup, which was performed before treatment initiation. RESULTS: Thirty-three patients were included in this study. We identified 5 patients (15%) with a primary immunodeficiency disorder: common variable immunodeficiency (n=2), combined immunodeficiency (n=1) and complement component deficiency (n=2). Four other patients (12%) displayed decreased levels of immunoglobulins, B-cell lymphopenia and/or abnormal vaccinal response but did not fulfil the criteria of a defined primary immunodeficiency disorder at the time of the study. Importantly, none of these 9 patients had a particular familial history and none had a history of recurrent infections. CONCLUSIONS: A significant proportion of patients presenting with an autoimmune condition have an underlying primary immunodeficiency disorder that may not be clinically obvious. Additional prospective investigations are needed to further define the role for routine immunologic testing in daily clinical rheumatologic practice.

Fatal group A Streptococcus purpura fulminans in a child receiving TNF-α blocker.

Inhibition of tumor necrosis factor alpha (TNF-α) is effective in the treatment of many pediatric autoimmune diseases and inflammatory conditions. Commonly available biologic agents blocking TNF-α are infliximab, etanercept, and adalimumab. These agents have changed the management of rheumatic diseases in the adult population and are being used more and more in pediatric patients as safety and efficacy have been demonstrated. Infections have been the most commonly reported adverse effects of TNF-α inhibition. Granulomatous infections such as tuberculosis are well-known complications, but serious bacterial infections are also reported. We describe a fatal case of purpura fulminans caused by group A Streptococcus in an 8-year-old child with systemic juvenile idiopathic arthritis treated with etanercept. This case highlights the clinical association of severe bacterial infection and TNF-α inhibition in children. Pediatricians should educate their patients who are treated with TNF-α blockers regarding early warning symptoms and should also have a lower threshold for initiating antibiotic therapy in case of fever.

Early outcomes and improvement of patients with juvenile idiopathic arthritis enrolled in a Canadian multicenter inception cohort.

OBJECTIVE: To determine early outcomes and early improvements in a prospective inception cohort of children with juvenile idiopathic arthritis (JIA) treated with current standard therapies. METHODS: Patients selected were enrolled in an inception cohort of JIA, the Research in Arthritis in Canadian Children Emphasizing Outcomes Study. The juvenile rheumatoid arthritis core criteria set measures were completed at enrollment and 6 months later. Frequencies of normal values for each of the core set measures and the American College of Rheumatology (ACR) Pediatric 30, 50, and 70 (Pedi 70) criteria response rates achieved at 6 months after enrollment were calculated for each JIA-onset subtype group. RESULTS: Among 354 patients in the study, the median interval between diagnosis and enrollment was 0.7 months. At 6 months after enrollment, median values of active joint counts were highest in patients with rheumatoid factor (RF)-positive polyarthritis (4) and RF-negative polyarthritis (2), but were 0 or 1 for other subtypes. Fifty percent or more of patients with oligoarthritis, systemic arthritis, enthesitis-related arthritis, and undifferentiated arthritis had no active joints, and the ACR Pedi 70 criteria response rate was 48% or more in those with oligoarthritis, RF-negative polyarthritis, and systemic arthritis. CONCLUSION: With current management strategies in clinical practice, improvement in disease activity was noted in considerable proportions of patients in all of the JIA subtype groups, but low levels of disease activity persisted in many. We expect that these early outcomes will prove to be significant predictors of long-term outcomes.

Predictors of early inactive disease in a juvenile idiopathic arthritis cohort: results of a Canadian multicenter, prospective inception cohort study.

OBJECTIVE: To determine early predictors of 6-month outcomes in a prospective cohort of patients with juvenile idiopathic arthritis (JIA). METHODS: Patients selected were those enrolled in an inception cohort study of JIA, the Research in Arthritis in Canadian Children Emphasizing Outcomes Study, within 6 months after diagnosis. The juvenile rheumatoid arthritis core criteria set and quality of life measures were collected at enrollment and 6 months later. Outcomes evaluated included inactive disease, Juvenile Arthritis Quality of Life Questionnaire (JAQQ) scores, and Childhood Health Assessment Questionnaire (C-HAQ) scores at 6 months. RESULTS: Thirty-three percent of patients had inactive disease at 6 months. Onset subtype and most baseline core criteria set measures correlated with all 3 outcomes. Relative to oligoarticular JIA, the risks of inactive disease were lower for enthesitis-related arthritis, polyarthritis rheumatoid factor (RF)-negative JIA, and polyarthritis RF-positive JIA, and were similar for psoriatic arthritis. In multiple regression analyses, the baseline JAQQ score was an independent predictor of all 3 outcomes. Other independent baseline predictors included polyarthritis RF-negative and systemic JIA for inactive disease; C-HAQ score and polyarthritis RF-positive JIA for the 6-month C-HAQ score; and active joint count, pain, and time to diagnosis for the 6-month JAQQ score. CONCLUSION: Clinical measures soon after diagnosis predict short-term outcomes for patients with JIA. The JAQQ is a predictor of multiple outcomes. Time to diagnosis affects quality of life in the short term.

Natriuretic peptide as an adjunctive diagnostic test in the acute phase of Kawasaki disease.

Coronary arteritis rather than myocardial involvement is typically emphasized in Kawasaki disease (KD). Moreover, the criteria and the usual biological markers oversee the importance of cardiac-specific markers in diagnosing this disease. We sought to study the clinical usefulness of measuring B-type natriuretic peptide (BNP) and its N-terminal moiety (NT-proBNP) at the onset of KD. Our objective was to evaluate blood concentrations of BNP and NT-proBNP during the acute and subacute phases of KD. We conducted a prospective study comparing newly diagnosed KD patients to non-KD febrile controls. Blood specimens were collected at presentation, 6-12 h after intravenous immunoglobulin (IVIG) therapy, 1-2 weeks later, and 2-3 months later, or only upon reenrollment for controls. Forty-there KD and 19 control patients were enrolled consecutively. The mean age was 47.1 +/- 34.3 and 62.2 +/- 44.9 months, respectively (p = NS). Pre-IVIG NT-proBNP levels were significantly higher in KD patients than in controls (923.6 +/- 1361.7 vs. 186.2 +/- 198.0 ng/L; p < 0.001), with no statistical difference for BNP (141.9 +/- 227.5 vs. 59.9 +/- 72.4 ng/L; p = 0.112). In conclusion, our data indicate that NT-proBNP is a better marker of myocardial involvement in acute KD than BNP, particularly in cases with incomplete diagnostic criteria, and suggest that it may be a valid adjunctive diagnostic method to support the diagnosis of KD.

Renal granuloma and immunoglobulin M-complex glomerulonephritis: a case of common variable immunodeficiency?

Common variable immunodeficiency (CVID) is characterized by reduced serum immunoglobulin levels and recurrent bacterial infections. Granulomatous infiltrations are occasionally found in the lymphoid or solid organs of affected patients, but renal involvement is rare. We present a case of possible CVID with interstitial noncaseating granuloma and immunoglobulin (IgM)-complex glomerulonephritis with a membranoproliferative pattern and with a favorable response to corticosteroids, intravenously administered immunoglobulins (IVIGs) and rituximab. CVID must be included in the differential diagnosis of renal granuloma and should be differentiated from sarcoidosis to ensure appropriate therapy.