Jaime de Inocencio

Clinical management algorithm of uveitis associated with juvenile idiopathic arthritis: interdisciplinary panel consensus

Uveitis associated with juvenile idiopathic arthritis (JIA) typically involves the anterior chamber segment, follows an indolent chronic course, and presents a high rate of uveitic complications and a worse outcome as compared to other aetiologies of uveitis. Disease assessment, treatment, and outcome measures have not been standardized. Collaboration between pediatric rheumatologists and ophthalmologists is critical for effective management and prevention of morbidity, impaired vision, and irreparable visual loss. Although the Standardization of Uveitis Nomenclature Working Group recommendations have been a great advance to help clinicians to improve consistency in grading and reporting data, difficulties arise at the time of deciding the best treatment approach in the individual patient in routine daily practice. For this reason, recommendations for a systematized control and treatment strategies according to clinical characteristics and disease severity in children with JIA-related uveitis were developed by a panel of experts with special interest in uveitis associated with JIA. A clinical management algorithm organized in a stepwise regimen is here presented.

Dissecting the heterogeneity of macrophage activation syndrome complicating systemic juvenile idiopathic arthritis.

Objective. To seek insights into the heterogeneity of macrophage activation syndrome (MAS) complicating systemic juvenile idiopathic arthritis (sJIA) through the analysis of a large patient sample collected in a multinational survey. Methods. International pediatric rheumatologists and hemato-oncologists entered their patient data, collected retrospectively, in a Web-based database. The demographic, clinical, laboratory, histopathologic, therapeutic, and outcome data were analyzed in relation to (1) geographic location of caring hospital, (2) subspecialty of attending physician, (3) demonstration of hemophagocytosis, and (4) severity of clinical course. Results. A total of 362 patients were included by 95 investigators from 33 countries. Demographic, clinical, laboratory, and histopathologic features were comparable among patients seen in diverse geographic areas or by different pediatric specialists. Patients seen in North America were given biologics more frequently. Patients entered by pediatric hemato-oncologists were treated more commonly with biologics and etoposide, whereas patients seen by pediatric rheumatologists more frequently received cyclosporine. Patients with demonstration of hemophagocytosis had shorter duration of sJIA at MAS onset, higher prevalence of hepatosplenomegaly, lower levels of platelets and fibrinogen, and were more frequently administered cyclosporine, intravenous immunoglobulin (IVIG), and etoposide. Patients with severe course were older, had longer duration of sJIA at MAS onset, had more full-blown clinical picture, and were more commonly given cyclosporine, IVIG, and etoposide. Conclusion. The clinical spectrum of MAS is comparable across patients seen in different geographic settings or by diverse pediatric subspecialists. There was a disparity in the therapeutic choices among physicians that underscores the need to establish uniform therapeutic protocols.

Discontinuation of Etanercept After Successful Treatment in Patients with Juvenile Idiopathic Arthritis

To the Editor: Etanercept (ETN) has been used to treat patients with juvenile idiopathic arthritis (JIA) with demonstrated efficacy and safety1,2. However, few studies have addressed the appropriate time and the way to discontinue the drug once the disease is inactive. We analyzed the progress of patients with JIA after discontinuation of ETN and the clinical response to reintroduction of the drug in those who relapsed. A retrospective chart review 2004 to 2009 revealed that therapy with ETN had been discontinued in 26 patients with JIA due to inactive disease (16 female, 10 male). The mean age at discontinuation of drug was 11 ± 2 (range 2.6–18.8) years. The clinical subtypes of JIA were 11 cases of enthesitis-related arthritis, 7 rheumatoid factor-negative polyarthritis, 2 systemic JIA with polyarticular involvement, 1 psoriatic arthritis, and 1 persistent oligoarticular arthritis. Inactive disease was defined according to the criteria of Wallace, et al 3, which required no joints with active arthritis, no … Address correspondence to Dr. Remesal; E-mail: agusremesal{at}hotmail.com

Intravenous Immunoglobulin Therapy for Refractory Recurrent Pericarditis

Recurrent pericarditis is a troublesome complication of idiopathic acute pericarditis and occurs more frequently in pediatric patients after cardiac surgery (postpericardiotomy syndrome). Conventional treatment with nonsteroidal antiinflammatory drugs, corticosteroids, and colchicine is not always effective or may cause serious adverse effects. There is no consensus, however, on how to proceed in those patients whose disease is refractory to conventional therapy. In such cases, human intravenous immunoglobulin, immunosuppressive drugs, and biological agents have been used. In this report we describe 2 patients with refractory recurrent pericarditis after cardiac surgery who were successfully treated with 3 and 5 monthly high-dose (2 g/kg) intravenous immunoglobulin until resolution of the effusion. Our experience supports the effectiveness and safety of this therapy.

Subcutaneous Immunoglobulin in Refractory Juvenile Dermatomyositis

Juvenile dermatomyositis (JDM) is the most common form of juvenile idiopathic inflammatory myopathy. We report a child with steroid-dependent JDM refractory to hydroxychloroquine and subcutaneous methotrexate who experienced systemic reactions to intravenous immunoglobulin and was successfully treated with subcutaneous immunoglobulin. This form of therapy has been shown to be safe, has a very low rate of adverse effects, does not require hospital admission, reduces the number of missed school days, and decreases the costs associated with treatment.

Development and testing of a hybrid measure of muscle strength in juvenile dermatomyositis for use in routine care

To develop and test a hybrid measure of muscle strength for juvenile dermatomyositis (JDM), which is based on the combination of the Manual Muscle Testing in 8 muscles (MMT‐8) and the Childhood Myositis Assessment Scale (CMAS) but is more comprehensive than the former and more feasible than the latter.

Tocilizumab is a promising treatment option for therapy resistant juvenile localized scleroderma patients

Introduction Juvenile localized scleroderma (jlSc) usually responds well to treatment with methotrexate or mycophenolate. In case of nonresponse or partial response, tocilizumab (TOC) appears to be a promising option. Methods Participants of the Pediatric Rheumatology Email Board were asked to report patients with jlSc treated with TOC. Results Six centers responded and reported 11 patients. The mean age at disease onset was 5.5 years. Disease duration at time of the initiation of TOC was 4.5 years. A total of 5 patients had linear subtype, 2 Parry Romberg syndrome, and 1 morphea en coup de sabre. Three had a generalized subtype, 2 a mixed subtype, and 1 a limited subtype/morphea. Before starting TOC, 10 of 11 patients received methotrexate, 7/11 combination methotrexate and mycophenolate, 1 abatacept, and 1 antitumor necrosis factor therapy. The indications for starting TOC were: (i) an increase in the score of the Localized Scleroderma Activity Index (mLoSSI) in 9 patients; and (ii) evidence of increased extra-cutaneous activity in 2 patients. The mean duration of TOC therapy was 14.75 months. Three of 11 patients received TOC as monotherapy, and 8/11 as combination therapy. Therapy success was reflected by a decreased mLoSSI in 9/11 patients, no new lesion occurrence, and – with Parry Romberg syndrome subtype – no increase in facial atrophy. In 8/8 patients, both the physicians’ and patients’ global assessment of disease activity decreased. In 3/3 patients, the number of active joints decreased. The mean modified Rodnan skin score decreased from 8.7 to 5.6. Conclusions In this small cohort of patients, TOC seems to be a promising rescue medication.

Unexpected Relevant Role of Gene Mosaicism in Primary Immunodeficiency Diseases

Background: Postzygotic de novo mutations lead to the phenomenon of gene mosaicism. The 3 main types are called somatic, gonadal, and gonosomal mosaicism, which differ in terms of the body distribution of postzygotic mutations. Mosaicism has been reported occasionally in patients with primary immunodeficiency diseases (PIDs) since the early 1990s, but its real involvement has not been systematically addressed. Objective: We sought to investigate the incidence of gene mosaicism in patients with PIDs. Methods: The amplicon‐based deep sequencing method was used in the 3 parts of the study that establish (1) the allele frequency of germline variants (n = 100), (2) the incidence of parental gonosomal mosaicism in families with PIDs with de novo mutations (n = 92), and (3) the incidence of mosaicism in families with PIDs with moderate‐to‐high suspicion of gene mosaicism (n = 36). Additional investigations evaluated body distribution of postzygotic mutations, their stability over time, and their characteristics. Results: The range of allele frequency (44.1% to 55.6%) was established for germline variants. Those with minor allele frequencies of less than 44.1% were assumed to be postzygotic. Mosaicism was detected in 30 (23.4%) of 128 families with PIDs, with a variable minor allele frequency (0.8% to 40.5%). Parental gonosomal mosaicism was detected in 6 (6.5%) of 92 families with de novo mutations, and a high incidence of mosaicism (63.9%) was detected among families with moderate‐to‐high suspicion of gene mosaicism. In most analyzed cases mosaicism was found to be both uniformly distributed and stable over time. Conclusion: This study represents the largest performed to date to investigate mosaicism in patients with PIDs, revealing that it affects approximately 25% of enrolled families. Our results might have serious consequences regarding treatment and genetic counseling and reinforce the use of next‐generation sequencing–based methods in the routine analyses of PIDs. GRAPHICAL ABSTRACT Figure. No caption available.

The Ecuadorian Spanish version of the Juvenile Arthritis Multidimensional Assessment Report (JAMAR)

The Juvenile Arthritis Multidimensional Assessment Report (JAMAR) is a new parent/patient-reported outcome measure that enables a thorough assessment of the disease status in children with juvenile idiopathic arthritis (JIA). We report the results of the cross-cultural adaptation and validation of the parent and patient versions of the JAMAR in the Colombian Spanish language. The reading comprehension of the questionnaire was tested in ten JIA parents and patients. Each participating centre was asked to collect demographic, clinical data and the JAMAR in 100 consecutive JIA patients or all consecutive patients seen in a 6-month period and to administer the JAMAR to 100 healthy children and their parents. The statistical validation phase explored descriptive statistics and the psychometric issues of the JAMAR: the three Likert assumptions, floor/ceiling effects, internal consistency, Cronbach’s alpha, interscale correlations, and construct validity (convergent and discriminant validity). A total of 22 JIA patients (9.1% systemic, 27.3% RF-negative polyarthritis, 36.4% enthesitis-related arthritis, 27.2% other categories) were enrolled in the paediatric centre of Bogota. All JAMAR components revealed good psychometric performances. In conclusion, the Colombian Spanish version of the JAMAR is a valid tool for the assessment of children with JIA and is suitable for use both in routine clinical practice and clinical research.

Dissecting the heterogeneity of macrophage activation syndrome

Methods Patient data were collected retrospectively by pediatric rheumatologists (PR) or pediatric hemato-oncologists (PHO). Clinical features, treatments and outcome were compared between groups by Mann-Whitney or chisquare tests. “Severe course” was defined as ICU admission or death. Results 362 patients with MAS in sJIA were collected by 95 investigators from 33 countries. 179 patients (49.4%) were enrolled in Europe (EU), 72 (19.9%) in North America (NA) and 111 (30.7%) in other continents (OC). 79 (21.8%) patients were included by PHO. HP was detected in 44% of patients and was not detected or looked for in 56%. Severe course was reported in 92 (25%) patients. Comparison by geographic origin showed a lower frequency of CNS disease in EU patients. NA physicians used more frequently ivIg and biologics. Patients entered by PHO had greater frequency of multiorgan failure and were given more commonly biologics and etoposide, whereas PR used more frequently cyclosporine (CsA). Patients with HP had shorter duration of sJIA at MAS onset, higher prevalence of hepatosplenomegaly, lower levels of platelets and fibrinogen and received more frequently CsA, ivIg and etoposide. Patients with severe course were older, had longer duration of sJIA at MAS onset, greater frequency of haemorrhages and CNS dysfunction, lower levels of ESR, albumin and fibrinogen, higher levels of LDH and D-dimer and were treated more commonly with CsA, ivIg and etoposide. Conclusion