Kevin W. Baszis

Development of consensus treatment plans for juvenile localized scleroderma: A roadmap toward comparative effectiveness studies in juvenile localized scleroderma

Juvenile localized scleroderma (LS) is a chronic inflammatory skin disorder associated with substantial morbidity and disability. Although a wide range of therapeutic strategies has been reported in the literature, a lack of agreement on treatment specifics and accepted methods for clinical assessment has made it difficult to compare approaches and identify optimal therapy. Our objective was to develop standardized treatment plans, clinical assessments, and response criteria for active, moderate to high severity juvenile LS.

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.

Clinical outcomes after withdrawal of anti–tumor necrosis factor α therapy in patients with juvenile idiopathic arthritis: A twelve-year experience

OBJECTIVE To estimate the length of time to disease flare and the likelihood of achieving clinical remission after discontinuation of treatment with tumor necrosis factor α (TNFα) blockers in patients with juvenile idiopathic arthritis (JIA). METHODS We conducted a retrospective chart review in a cohort of patients with JIA treated with TNFα inhibitors between January 1, 1998 and November 1, 2009. Demographic information, laboratory data, and medication exposure were extracted using a standardized tool. Outcomes of interest were based on preliminary criteria for remission in JIA. RESULTS One hundred seventy-one patients with 255 discrete episodes of anti-TNFα treatment were reviewed. The median duration of patient observation was 59.7 months (range 5.8-211.2 months). Among patients in whom disease was inactive after discontinuation of anti-TNFα therapy, 50% had persistently inactive disease at 6 months, and 33% had clinical remission at 12 months. The median duration of anti-TNFα therapy after inactive disease was obtained was 6.1 months (range 0-67.9 months). No significant association was observed between the time to disease flare after cessation of treatment with TNFα antagonists and the length of time from the diagnosis of JIA to the initiation of anti-TNFα therapy, the duration of therapy following the onset of inactive disease, or the total duration of treatment with TNFα antagonists prior to discontinuation. The category of JIA, sex, and age at diagnosis were not associated with the risk of relapse. CONCLUSION One-third of patients with JIA can successfully undergo withdrawal of treatment with TNFα antagonists and be spared the cost and potential morbidity of treatment for at least 12 months. Further studies are needed to identify factors to accurately identify these patients.

Recurrent Parotitis as a Presentation of Primary Pediatric Sjögren Syndrome

Parotitis is a common condition seen in the pediatric population, usually as an isolated occurrence associated with viral or bacterial infection. The differential diagnosis expands when recurrent parotitis is encountered. One etiology is primary pediatric Sjögren syndrome (SS), an autoimmune condition typically associated with dryness of the eyes and mouth in adults. Pediatric patients often present with isolated recurrent bilateral parotitis, however, and we describe 4 such cases in children aged 9 to 17 years at presentation. Despite lack of ocular complaints, 3 of these patients had ocular findings on ophthalmologic exam. Our patients also exhibited classic laboratory abnormalities, including positive antinuclear antibody, SS A, and SS B antibodies; presence of rheumatoid factor; and hypergammaglobulinemia. Consideration of SS in the child with recurrent parotitis is important for timely and appropriate referral and treatment. We review the differential diagnosis of parotitis in children as well as the salient features of pediatric SS.

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.

The use of electroconvulsive therapy in a patient with juvenile systemic lupus erythematosus and catatonia

Catatonia is a rare manifestation in patients with systemic lupus erythematosus (SLE). As catatonia can be associated with both psychiatric and organic conditions, this could create a diagnostic dilemma once this occurs in SLE patients. The report describes a 15-year-old female with SLE who developed catatonia three days after the diagnosis of SLE was made. Her catatonia was refractory to the treatment with immunosuppressive therapy, which included pulse methylprednisolone, intravenous cyclophosphamide, rituximab, intravenous immunoglobulin (IVIG) and plasmapheresis. Given her persistent catatonia, electroconvulsive therapy (ECT) was initiated three months after the onset of her symptoms. After the third ECT treatment, her mental status dramatically improved and returned nearly to baseline while she was continued on the immunosuppression. This is the first report of a successful ECT therapy in catatonic lupus in children.

Scurvy revealed by difficulty walking: three cases in young children.

Scurvy is rare in developed countries but is known to cause lower-extremity pain and refusal to ambulate in children. Since the discovery of the link between scurvy and dietary deficiency of ascorbic acid, there has been a substantial decrease in its prevalence and recognition. Here we describe 3 cases of scurvy in young children presenting with difficulty walking. Only 1 of 3 patients had gingival lesions at the initial presentation. Two cases underwent an extensive evaluation for hematologic and rheumatologic diseases before the diagnosis of scurvy was made. Dietary histories eventually revealed that all 3 patients had sharply limited intake of fruits and vegetables secondary to oral aversion, and 1 patient had autism. Radiographic changes of long bones were observed in all patients. Interestingly, all patients had concomitant vitamin D deficiency. After replacement with vitamin C, all patients recovered and started to walk again with improved leg pain. These clinical manifestations and radiologic findings highlight the importance for rheumatologists to have a higher index of suspicion for scurvy in nonambulatory children.

Pediatric Vasculitis: Recognizing Multisystemic Manifestations at Body Imaging

Pediatric vasculitides are multisystem diseases that can be diagnostic challenges because of variable clinical manifestations. The clinical manifestation is determined by the size of the affected vessels, organs involved, extent of vascular injury, and underlying pathologic characteristics. Henoch-Schönlein purpura and Kawasaki disease are the two most common subtypes of pediatric vasculitis. Diagnosis of pediatric vasculitis can be difficult, and the outcome can be serious or fatal in the absence of timely intervention. Imaging plays a central role in establishing the diagnosis of vasculitis involving large- and medium-sized vessels, visualizing its vascular and extravascular manifestations, and monitoring the disease course and response to treatment. Although imaging cannot depict the vessel changes of small-vessel vasculitis directly, it can be used to detect tissue damage resulting from vessel inflammation. This article discusses the classification and clinical features of the major pediatric vasculitides. The imaging approach to and nonneurologic findings of major pediatric vasculitis subtypes are reviewed for the pediatric body imager.

Recurrent cardiac tamponade in a child with newly diagnosed systemic-onset juvenile idiopathic arthritis.

Abstract A previously healthy 5-year-old boy presented with prolonged fever, evanescent rash, and arthralgias. Diagnostic tests were significant for marked systemic inflammation. He rapidly developed pleural and pericardial effusions with cardiac tamponade, requiring placement of a pericardial drain. He briefly responded to nonsteroidal anti-inflammatory drugs and pulse methylprednisolone, but tamponade recurred shortly thereafter. Subsequently, he required high-dose intravenous immunoglobulin, infliximab, and anakinra. Thus, we report a patient with severe serositis and recurrent cardiac tamponade as the initial presentation of systemic juvenile idiopathic arthritis (sJIA) and review the literature regarding pericarditis and tamponade in sJIA. This potentially fatal complication of sJIA requires timely recognition and therapy to avoid significant morbidity and mortality.

Azathioprine therapy for steroid-resistant Henoch-Schönlein purpura: a report of 6 cases.

BackgroundA small percentage of children with Henoch-Schönlein purpura (HSP) develop a chronic form of the disease that often requires prolonged corticosteroid therapy. Disease modifying anti-rheumatic agents (DMARDs) or biologics have been successfully used to treat those refractory cases. Azathioprine is a DMARD that has been reported to be effective in HSP nephritis and in adult cutaneous leukocytoclastic vasculitis, a condition with cutaneous histology similar to HSP.Case presentationA description of 6 cases with relapsing HSP without significant renal involvement, treated with azathioprine are reported. All 6 cases met the classification criteria for the diagnosis of HSP, had relapsing symptoms despite corticosteroid use, were successfully treated with azathioprine and were tapered off of corticosteroids. The duration of azathioprine therapy ranged from 7–21 months and no adverse events were reported.ConclusionsAzathioprine is effective in controlling prolonged relapsing symptoms of HSP, allowing earlier discontinuation of corticosteroids. This report shows that azathioprine can be included in the therapeutic options for relapsing HSP and is the first case series in the literature of azathioprine use in HSP without significant renal involvement.