Olga Vougiouka

Benign hypermobility syndrome in Greek schoolchildren.

Since the incidence of benign hypermobility syndrome is significantly high in otherwise healthy children, paediatricians should consider this benign entity when they evaluate musculoskeletal complaints in childhood.

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.

The puzzling clinical spectrum and course of juvenile sarcoidosis

BackgroundJuvenile sarcoidosis is a rare, chronic, multisystem, granulomatous disease of obscure etiology which is seen in childhood and adulthood. The disease in childhood has a course different from that in adulthood.Data sourcesPubMed database was searched using terms sarcoidosis, children or childhood sarcoidosis or juvenile sarcoidosis in combination with one of the following terms: epidemiology, clinical manifestations, genetics, diagnosis, treatment, and prognosis. We also retrieved the terms such as early onset sarcoidosis and Blau syndrome. Furthermore, e-medicine and European Respiratory Society monographs for sarcoidosis were reviewed.ResultsSarcoidosis in childhood presents with two age dependent, distinct forms. In younger children it is clinically evident before the age of four years and characterized by the triad of rash, arthritis and uveitis. In their older counterparts, the juvenile late onset sarcoidosis involves several organs and its clinical appearance resembles the adult type of the disease, with the respiratory system being most frequently affected (hilar lymphadenopathy, pulmonary infiltrations). Steroid is the main agent of treatment whereas methotrexate is also used for beneficial steroid sparing effects. New, novel therapies may change the outcome of the disease especially in difficult morbid cases.ConclusionsSarcoidosis in childhood is recognized as a systemic disease affecting various organs and having diverse clinical course depending on the age of onset.

A54: Insulin Sensitivity Is Improved in sJIA Children With Insulin Resistance After Tocilizumab Treatment: Results From the TENDER Study

In adults with inflammatory arthritis, insulin resistance (IR) is associated with diabetes and cardiovascular disease. Interleukin‐6 (IL‐6) is postulated to play a mechanistic role in IR. The aim of this study was to evaluate the degree of IR among children with systemic juvenile idiopathic arthritis (sJIA) and to determine whether treatment with tocilizumab (TCZ) results in attenuation of IR in sJIA.

PReS-FINAL-2188: Insulin sensitivity is improved in sjia children with insulin resistance after tocilizumab treatment: results from the tender study.

In adults with inflammatory arthritis, insulin resistance (IR) is associated with diabetes and cardiovascular disease. Interleukin-6 (IL-6) is postulated to play a mechanistic role in IR.

Transient Effect of Anti-cd20 Therapy in a Child With 22q11.2 Deletion Syndrome and Severe Steroid Refractory Cytopenias: A Case Report

We report on the development of steroid-refractory recurrent cytopenias in a child with 22q11.2 deletion syndrome. His first hematological complication was autoimmune hemolytic anemia at 3 months of age. Thereafter, he developed severe autoimmune cytopenias of all 3 hematological lineages with poor response to steroids and intravenous immunoglobulin. At the age of 2½ years, a course of anti-CD20 therapy (Rituximab) was given with transient hematological recovery. Because of persistent symptoms, bone marrow transplantation from a matched unrelated donor was performed. Although the data in the use of anti-CD20 therapy in children with 22q11.2 deletion syndrome and autoimmune cytopenias are limited, our experience suggests its potential benefit.

The Greek 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 Greek language. The reading comprehension of the questionnaire was tested in 10 JIA parents and patients. Each participating centre was asked to collect demographics, clinical data, and the JAMAR from 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, test–retest reliability, and construct validity (convergent and discriminant validity). The Greek JAMAR was fully cross-culturally adapted with two forward and three backward translations. A total of 272 JIA patients (5.9% systemic, 57.7% oligoarticular, 21.3% RF negative poly-arthritis, 15.1% other categories), and 100 healthy children were enrolled in all centres. The JAMAR components discriminated well-healthy subjects from JIA patients; notably, there was no significant difference between healthy subjects and their affected peers in psychosocial quality of life and school-related items. All JAMAR components revealed good psychometric performances. In conclusion, the Greek 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 in clinical research.

An Infant With Purpuric Rash and Edema

Diagnosis: Acute hemorrhagic edema of infancy. Biopsy of purpuric lesions showed leukocytoclastic vasculitis, and direct immunofluorescence studies showed vascular wall fibrinogen deposition without immunoglobulin A (IgA) deposition, findings consistent with acute hemorrhagic edema of infancy (AHEI) (Figure 1). The first case of AHEI was reported in 1913, and later Seidlmayer and Finkelstein characterized the disease [1]. The precise incidence of AHEI remains unknown because of its rarity and confusion with other diseases. Based on a recent review, the typical patient is a boy (67%), 6–24 months of age, without racial predominance [2]. However, 1 case has been reported at birth [3]. There seems to be a seasonal variation as most cases of AHEI tend to present during winter [4]. The usual clinical appearance of a patient with AHEI includes nontoxic presentation, low-grade fever, abrupt onset of large purpuric skin lesions, and edema in face and extremities [4]. The rapid appearance of the hemorrhagic rash, together with the excellent general condition of the patient, makes it necessary to recognize this disease and differentiate it from other severe diseases such as meningococcal septicemia. Although it is a self-limited disease and the prognosis is excellent, there are reports of relapses [5, 6]. Complete recovery usually occurs within 1–3 weeks [1]. However, some rare complications have been described such as renal and intestinal involvement, epididymo-orchitis, and necrotic ulcers of the purpuric lesions [7]. According to existing literature, AHEI is associated with some viruses and bacteria (adenovirus, cytomegalovirus, herpes simplex virus, varicella zoster virus, tuberculosis, streptococci, staphylococci, pneumococcus), but the etiology of this disease remains unknown [1, 8]. Many cases of AHEI are triggered by infection (respiratory infection, urinary tract infection, bacteremia), vaccination (H1N1, measlesmumps-rubella, BCG, diphtheria-tetanus-pertussis, polio, Haemophilus influenzae), or drug intake (penicillin, cephalosporin, trimethoprim-sulfamethoxazole, acetaminophen), which reveal a possible immune-mediated pathophysiology of AHEI [4, 9]. Our patient had enterovirus isolated from the throat, and hepatitis B vaccine was given 2 weeks before admission, signifying a possible association with AHEI. AHEI has nonspecific blood laboratory results. There might be thrombocytosis, leukocytosis, eosinophilia or lymphocytosis, and increased erythrocyte sedimentation rate or C-reactive protein. Proteinuria and microscopic hematuria have been reported, but urinalysis is usually normal [10]. Serum complement and immunoglobulin levels are frequently normal. Diagnosis is based on clinical features but if diagnosis is unclear, a skin biopsy of the rash will be helpful. The most common histopathological description is perivascular neutrophilic infiltration with nuclear fragments in the vascular wall and fibrinoid necrosis [4]. IgA deposition may be detected in up to one-third of cases, but the absence of IgA deposition with c1q deposition may be pertinent to distinguish AHEI from other leukocytoclastic vasculitis such as Henoch–Schönlein purpura (HSP) [1]. Figure 1. Acute hemorrhagic edema of infancy. Further spreading of purpuric rash with edema over limbs.

The response to hepatitis a vaccine in children with JIA on immunosuppresive treatment

methotrexate and 27 received both. The control group consisted of 76 healthy individuals (mean age 5.2 years). At four weeks after primary vaccination 48% of patients and 65% (P<0.01) of the controls attained seroprotection. Ninety-four percent of the patients and 99% (P=0.07) of the controls seroconverted four weeks after the second dose. Seroconversion rate was 91.5% for the patient group and 97% for the controls at 52 weeks post the second dose. Mean IgG concentration at 4 weeks was 45mIU/ml in the patient an d8 9mIU/ml in the control group (P=0.04) while it reached 118mIU/ml and 213 mIU/ml after the second dose respectively (P=0.03). Subgroup analysis showed patients on biologics had better seroconversion rates compared to children on MTX or children on biologics+MTX. Vaccines were well tolerated. Mild adverse events were noticed in 7 patients and 8 controls. None of the patients developed a flare. Conclusion Two doses of HAV vaccine are safe and effective in the majority of children with JIA, whereas a single dose seems inefficient. Systemic illness should not preclude from completion of the vaccination schedule. Seroconversion rates are lower in children whose treatment regime includes MTX. Disclosure of interest None declared.

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