S100A12 and S100A8/9 proteins are biomarkers of articular disease activity in Blau syndrome.

OBJECTIVE: To identify biomarkers of articular and ocular disease activity in patients with Blau syndrome (BS). METHODS: Multiplex plasma protein arrays were performed in five BS patients and eight normal healthy volunteers (NHVs). Plasma S100A12 and S100A8/9 were subsequently measured by ELISA at baseline and 1-year follow-up in all patients from a prospective multicentre cohort study. CRP was measured using Meso Scale Discovery immunoassay. Active joint counts, standardization uveitis nomenclature for anterior uveitis cells and vitreous haze by Nussenblatt scale were the clinical parameters. RESULTS: Multiplex Luminex arrays identified S100A12 as the most significantly elevated protein in five selected BS vs eight NHVs and this was confirmed by ELISA on additional samples from the same five BS patients. In the patient cohort, S100A12 (n = 39) and S100A8/9 (n = 33) were significantly higher compared with NHVs (n = 44 for S100A12, n = 40 for S100A8/9) (P = 0.0000004 and P = 0.0003, respectively). Positive correlations between active joint counts and S100 levels were significant for S100A12 (P = 0.0008) and S100A8/9 (P = 0.015). CRP levels did not correlate with active joint count. Subgroup analysis showed significant association of S100 proteins with active arthritis (S100A12 P = 0.01, S100A8/9 P = 0.008). Active uveitis was not associated with increased S100 levels. CONCLUSION: S100 proteins are biomarkers of articular disease activity in BS and potential outcome measures in future clinical trials. As secreted neutrophil and macrophage products, S100 proteins may reflect the burden of granulomatous tissue in BS.

Blau syndrome: cross-sectional data from a multicentre study of clinical, radiological and functional outcomes.

OBJECTIVE: To report baseline articular, functional and ocular findings of the first international prospective cohort study of Blau syndrome (BS). METHODS: Three-year, multicentre, observational study on articular, functional (HAQ, Childhood HAQ and VAS global and pain), ophthalmological, therapeutic and radiological data in BS patients. RESULTS: Baseline data on the first 31 recruited patients (12 females and 19 males) from 18 centres in 11 countries are presented. Of the 31 patients, 11 carried the p.R334W NOD2 mutation, 9 the p.R334Q and 11 various other NOD2 missense mutations; 20 patients were sporadic and 11 from five BS pedigrees. Median disease duration was 12.8 years (1.1-57). Arthritis, documented in all but one patient, was oligoarticular in 7, polyarticular in 23. The median active joint count was 21. Functional capacity was normal in 41%, mildly impaired in 31% and moderate-severe in 28% of patients. The most frequently involved joints at presentation were wrists, ankles, knees and PIPs. On radiographs, a symmetrical non-erosive arthropathy was shown. Previously unknown dysplastic bony changes were found in two-thirds of patients. Ocular disease was documented in 25 of 31 patients, with vitreous inflammation in 64% and moderate-severe visual loss in 33%. Expanded manifestations (visceral, vascular) beyond the classic clinical triad were seen in 52%. CONCLUSION: BS is associated with severe ocular and articular morbidity. Visceral involvement is common and may be life-threatening. Bone dysplastic changes may show diagnostic value and suggest a previously unknown role of NOD2 in bone morphogenesis. BS is resistant to current drugs, suggesting the need for novel targeted therapies.

Registries in rheumatological and musculoskeletal conditions. Paediatric Behçet's disease: an international cohort study of 110 patients. One-year follow-up data.

OBJECTIVE: To set-up an international cohort of patients suspected with Behçet's disease (BD). The cohort is aimed at defining an algorithm for definition of the disease in children. METHODS: International experts have defined the inclusion criteria as follows: recurrent oral aphthosis (ROA) plus one of following-genital ulceration, erythema nodosum, folliculitis, pustulous/acneiform lesions, positive pathergy test, uveitis, venous/arterial thrombosis and family history of BD. Onset of disease is <16 years, disease duration is ≤3 years, future follow-up duration is ≥4 years and informed consent is obtained. The expert committee has classified the included patients into: definite paediatric BD (PED-BD), probable PED-BD and no PED-BD. Statistical analysis is performed to compare the three groups of patients. Centres document their patients into a single database. RESULTS: At January 2010, 110 patients (56 males/54 females) have been included. Mean age at first symptom: 8.1 years (median 8.2 years). At inclusion, 38% had only one symptom associated with ROA, 31% had two and 31% had three or more symptoms. A total of 106 first evaluations have been done. Seventeen patients underwent the first-year evaluation, and 36 had no new symptoms, 12 had one and 9 had two. Experts have examined 48 files and classified 30 as definite and 18 as probable. Twenty-six patients classified as definite fulfilled the International Study Group criteria. Seventeen patients classified as probable did not meet the international criteria. CONCLUSION: The expert committee has classified the majority of patients in the BD group although they presented with few symptoms independently of BD classification criteria.

Immunomodulatory treatment and surgical management of idiopathic uveitis and juvenile idiopathic arthritis-associated uveitis in children: a French survey practice.

BACKGROUND: Surgeries for idiopathic uveitis and juvenile idiopathic arthritis-associated uveitis in children are complex because of the high risk of inflammatory postoperative complications. There is no consensus about treatment adaptation during the perioperative period. The objectives of this study are to report the therapeutic changes made in France and to determine whether maintaining or stopping immunosuppressive therapies is associated with an increased risk of surgical site infection or an increased risk of uveitis or arthritis flare-up. METHODS: We conducted a retrospective cohort study between January 1, 2006 and December 31, 2018 in six large University Hospitals in France. Inclusion criteria were chronic idiopathic uveitis or chronic uveitis associated with juvenile idiopathic arthritis under immunosuppressive therapies at the time of the surgical procedure, operated before the age of 16. Data on perioperative treatments, inflammatory relapses and post-operative infections were collected. RESULTS: A total of 76 surgeries (42% cataract surgeries, 30% glaucoma surgeries and 16% posterior capsule opacification surgeries) were performed on 37 children. Adaptation protocols were different in the six hospitals. Immunosuppressive therapies were discontinued in five cases (7%) before surgery. All the children in the discontinuation group had an inflammatory relapse within 3 months after surgery compared to only 25% in the other group. There were no postoperative infections. CONCLUSIONS: The results of this study show varying practices between centres. The benefit-risk balance seems to favour maintaining immunosuppressive therapies during surgery. Further studies are needed to determine the optimal perioperative treatments required to limit post-operative inflammatory relapses.

Orofacial manifestations of SAPHO syndrome: a systematic review of case reports.

SAPHO (synovitis, acne, pustulosis, hyperostosis, and osteitis) syndrome is a poorly known disease with cutaneous and osteo-articular manifestations requiring a multidisciplinary care. The aim of this study was to review the case reports that have described oral manifestations in patients suffering for this syndrome. A systematic review of case reports was performed on PubMed and Science Direct on January 2020 among all the articles dealing with the disease. In vitro, preclinical, and clinical studies have not been included to select only the case reports. Eighteen articles, published between 1999 and 2019, were included. All the patients presented mandibular osteomyelitis or sclerosis, associated with various other symptoms such as trismus, temporomandibular joint arthritis, or dysphagia. The data highlight the high variability in the disease's manifestations between people and also in the treatments applied. Knowing the orofacial signs of the SAPHO syndrome, the dental surgeon has a crucial role in the diagnosis procedure and must take place in the multidisciplinary medical team involved in the patient following. Some care adaptations are needed for oral interventions in these patients, depending on their treatments and their handicap. Key Points • Orofacial manifestations of SAPHO syndrome mainly occur on the mandible. • In cases of mandible sclerosis, decorticalization surgeries may be performed. • Oral care are encouraged, especially the preventive treatments to limit the necessity of surgeries. • The complexity in the management of patients suffering for a SAPHO syndrome concerns the oral manifestations, the patient general health and the treatments he has to take every day.

Epidemiology of admissions in a pediatric resuscitation room.

OBJECTIVE: Describe the epidemiology of a pediatric resuscitation room (PRR). METHODS: A prospective study was performed in a pediatric emergency department (PED) from June 17, 2004 to March 19, 2006. Collected data were date and time of admission in the unit and, in the PRR, age and sex, geographical origin, mode of transportation, PED referral mode, diagnosis, evolution, and resuscitation techniques. Statistical analysis included a univariate analysis of hypothetical links between variables and their relation to the risk of death or transfer to the pediatric intensive care unit, then a multivariate analysis by logistical regression where the dependant variable was this risk. RESULTS: Three hundred sixty-one patients totaled 370 admissions. The male-female ratio was 1.3. Mean (SD) age was 5.5 (5.2) years. A quarter of the population was recommended for admission by a physician. Main causes were cardiocirculatory (32%), neurological (26%), respiratory (23%), and traumas (18%), and 17% were hospitalized in an intensive care unit and 4 died. Sixteen technical resuscitation procedures were performed. Children from 0 to 2 years old were more often admitted for cardiocirculatory insufficiency (P < 0.001). The children who were at higher risk for pediatric intensive care unit transfer or death were children from 0 to 2 years old (P < 0.001), an admission for respiratory insufficiency (P < 0.001), and an arrival by medicalized transport (P = 0.003). CONCLUSIONS: In addition to national guidelines for PRR management, the teaching and knowledge of the different diagnosis admitted in the PRR and their resuscitation technical procedures warranty a serener approach of those stressful situations.

Etanercept concentration and immunogenicity do not influence the response to Etanercept in patients with juvenile idiopathic arthritis.

OBJECTIVE: To investigate the relationship of clinical response of Juvenile Idiopathic Arthritis (JIA) to etanercept (ETN) with ETN levels, and the presence of anti-drug antibodies to ETN (ADAb). METHODS: Prospective study of JIA patients under 18 years old. Clinical and pharmacological data were collected at two visits. JIA clinical inactivity and activity were assessed according to the Wallace criteria and to the Juvenile Arthritis Disease Activity Score (JADAS). ETN and ADAb serum levels assessments were determined using ELISA-based assays. RESULTS: 126 patients were enrolled. The median duration of ETN treatment at inclusion was 569 days (range 53-2340). ADAb were undetectable (<10 ng/ml) in 171/218 (78%) samples and were > 25 ng/mL in 2/218 samples. No significant relationship between ETN concentration and the clinical inactivity status and JIA activity was found using either univariate logistic regression or multiple logistic regression analysis, adjusted on one individual descriptors, time since diagnosis, time of sampling, use of corticosteroids or methotrexate and classification of JIA. No correlation was found between the remission status and the detection of ADAb. CONCLUSION: This study did not demonstrate any correlation between JIA activity and circulating ETN levels in a large population of patients with JIA previously treated with ETN for at least 1.5 months. As described for adults, our study confirms that ETN is marginally immunogenic in pediatric patients. These results do not support the clinical usefulness of a monitoring of ADAb or ETN concentrations for the management of this group of JIA patients if they fail to achieve clinical inactive disease.

Blau Syndrome-Associated Uveitis: Preliminary Results From an International Prospective Interventional Case Series.

PURPOSE: Provide baseline and preliminary follow-up results in a 5-year longitudinal study of Blau syndrome. DESIGN: Multicenter, prospective interventional case series. METHODS: Baseline data from 50 patients from 25 centers worldwide, and follow-up data for patients followed 1, 2, or 3 years at the end of study enrollment. Ophthalmic data were collected at baseline and yearly visits by means of a standardized collection form. RESULTS: Median age at onset of eye disease was 60 months and duration of eye disease at baseline 145 months. At baseline 38 patients (78%) had uveitis, which was bilateral in 37 (97%). Eight patients (21%) had moderate to severe visual impairment. Panuveitis was found in 38 eyes (51%), with characteristic multifocal choroidal infiltrates in 29 eyes (39%). Optic disc pallor in 9 eyes (12%) and peripapillary nodules in 9 eyes (12%) were the commonest signs of optic nerve involvement. Active anterior chamber inflammation was noted in 30 eyes (40%) at baseline and in 16 (34%), 17 (57%), and 11 (61%) eyes at 1, 2, and 3 years, respectively. Panuveitis was associated with longer disease duration. At baseline, 56 eyes (75%) were on topical corticosteroids. Twenty-six patients (68%) received a combination of systemic corticosteroids and immunomodulatory therapy. CONCLUSIONS: Blau uveitis is characterized by progressive panuveitis with multifocal choroiditis, resulting in severe ocular morbidity despite continuous systemic and local immunomodulatory therapy. The frequency and severity of Blau uveitis highlight the need for close ophthalmologic surveillance as well as a search for more effective therapies.

Severe global inflammatory involvement of ocular segments and optic disc swelling in a 12-year-old girl with Kawasaki disease.

PURPOSE: Pediatric Kawasaki ocular involvement is dominated by bulbar conjunctival injection and mild, self-limited anterior uveitis. Posterior segment involvement is rare. METHODS/RESULTS: Case Report. Despite early efficient treatment including aspirin and intravenous immunoglobulins, a 12-year-old girl developed a severe bilateral global inflammatory ocular involvement including punctuated keratitis, retrodescemetic precipitates, anterior uveitis, vitritis, and bilateral optic disc swelling with papillitis. DISCUSSION: This is the first description of severe bilateral global inflammatory involvement of the eyes in Kawasaki disease (KD). Usually subclinical and self-limited, eye involvement in KD can lead to severe visual impairment. CONCLUSIONS: Inflammation of both anterior and posterior segments does not seem to respond to KD-specific treatment and could justify a specific ophthalmologic therapeutic approach.

Neuroblastoma in adolescents.

BACKGROUND: Less than 5% of neuroblastomas are diagnosed in adolescent patients. Previous studies of patients who were treated with less intensive chemotherapy regimens relative to currently available regimens suggested that adolescents survived longer than younger children, and this finding was related to a lack of myc-N amplification. Those reports prompted the authors to study a cohort of adolescent patients who had been included in more recent trials. METHODS: The authors investigated the presentation, treatment, and outcome in 28 adolescent patients who were enrolled in studies of the French Society of Pediatric Oncology during the period from 1987 to 1999 and who were older than age 10 years at the time they were diagnosed with neuroblastoma. The results were used to compare this subpopulation with a control group of children. RESULTS: None of the six patients with Stage I-II disease either developed recurrent disease or died. At 5 years, disease progression was high (progression-free survival [PFS], 28%) for the 9 adolescents with Stage III disease, but so was survival (overall survival [OS], 86%). The 13 adolescent patients with metastatic neuroblastoma had very poor outcomes (PFS, 18%; OS, 27%). Despite intensive therapy, advanced neuroblastoma appeared to carry a poorer prognosis in adolescent patients compared with children, although patients with Stage III disease had a more indolent course. No difference was found between adolescent patients and children regarding the clinical presentation, treatment schedule, or doses and tolerance of chemotherapy. The incidence of elevated urinary catecholamine metabolite secretion was lower in adolescents compared with children. CONCLUSIONS: Adolescent patients with advanced neuroblastoma had less favorable outcomes compared with children, even if survival in adolescents with Stage III disease seemed longer.