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BackgroundPediatric Inflammatory Multisystemic Syndrome associated to SARS-CoV2 (PIMS) happens 4 to 6 weeks after SARS-CoV2 infection1-2. Its early diagnostic recognition as well as its early management is important to avoid cardiac complications related to this pathology.ObjectivesTo highlight a frequent symptom in PIMS and improve its therapeutic care.MethodsThe JIR Cohort database, an international registry collecting data on patients with pediatric inflammatory diseases, was consulted to include patients between 03/15/20 and 12/31/2021.ResultsOf the 140 patients in whom a diagnosis of PIMS was retained, we present a series of 38 patients (27%) who presented at diagnosis or during evolution, febrile torticollis or painful cervical involvement. These patients were on average 8.2 years old (0.6-15.2). The proportion of boys was 14 out of 38 (37%). Twenty-four patients out of 33 (73%) were hospitalized in intensive care. Ten patients out of 38 (26%) underwent cervical imaging, 5 (50%) had abnormalities such as collection or infiltration of the soft tissues. At the therapeutic level, 27/38 patients (71%) received corticosteroid therapy, 33/38 (87%) immunoglobulins, and 26/38 (68%) antibiotic therapy.ConclusionPIMS is a pathology with significant clinical heterogeneity and severe consequences in case of delay in therapeutic management. In this epidemic context, it is important to consider PIMS in any patient with febrile torticollis, especially if he does not respond to antibiotics.References[1]Feldstein LR, Rose EB, Horwitz SM, Collins JP, Newhams MM, Son MBF, et al. Multisystem Inflammatory Syndrome in U.S. Children and Adolescents. N Engl J Med. 23 juill 2020.[2]Whittaker E, Bamford A, Kenny J, Kaforou M, Jones CE, Shah P, et al. Clinical Characteristics of 58 Children With a Pediatric Inflammatory Multisystem Syndrome Temporally Associated With SARS-CoV-2. JAMA. 8 juin 2020Disclosure of InterestsNone declared

BackgroundPaediatric inflammatory multisystem Syndrome (PIMS) is a new systemic inflammatory disease linked to SARS-CoV2 that affects children. It was first reported in may 2020 [1-2].ObjectivesThe objectives of this study were to describe patients with PIMS through the international JIR cohort registry and to compare the different profiles and treatments of these patients over the different waves.MethodsStudy patients with international PIMS criteria were included from March 2020 to June 2021. Patients were identified in the JIR cohort, an international registry collecting demographic, clinical and paraclinical data on patients with pediatric inflammatory diseases. Two groups were distinguished: from March 2020 to July 2020 for patients in the first wave, from July 2020 to June 2021 for patients in the 2nd and 3rd waves. These two groups were compared using a Fischer test for categorical data and a Mann-Whitney test for quantitative dataResults136 patients meeting the PIMS criteria were included (64 patients in the 1st wave, 72 patients after). Patients had less frequent myocarditis (51 patients in wave 1 vs. 36 patients after, p=0,0003) and respiratory distress (34 patients vs 10 patients, pConclusionThere was a decrease in the number of complications of PIMS, particularly cardiac and respiratory complications, and a decrease in the length of hospitalization over time. The treatment of PIMS has also evolved, with a clear increase in the use of corticosteroids and a decrease in the use of antibiotics.References[1]Riphagen S, Gomez X, Gonzalez-Martinez C, Wilkinson N, Theocharis P (2020) Hyperinflammatory shock in children during COVID-19 pandemic. Lancet 395:1607–1608.[2]Verdoni L, Mazza A, Gervasoni A, Martelli L, Ruggeri M, Ciuffreda M, Bonanomi E, D’Antiga L (2020) An outbreak of severe Kawasaki-like disease at the Italian epicentre of the SARS-CoV-2 epidemic: an observational cohort study. Lancet. 395:1771–1778AcknowledgementsAcknowldgements to the French Covid-19 Paediatric Inflammation Consortium.Disclosure of InterestsNone declared

BackgroundChronic recurrent multifocal osteomyelitis (CRMO) is a rare inflammatory disease of the skeleton characterized by chronic and recurrent episodes of osteo-articular inflammation. The median age of onset is 10 years old. Clinical manifestations include musculoskeletal symptoms that are well described (pain, tenderness, swelling). Sometimes, skin lesions or digestive manifestations occur. Whole body magnetic resonance imaging (MRI) is the gold standard for assessing the multifocal pattern of the CRMO. Treatment is still empirical and mainly relies on non-steroidal anti-inflammatory drugs (NSAIDs). Bisphosphonates and biologics are used as second-line treatments. To date, the focus has been set on bone involvement and very few data are available on extra-osseous manifestations in CRMO.ObjectivesThis study aims to further describe these extra-osseous clinical manifestations in CRMO.MethodsA historical cohort was designed using 61 CRMO patients at the Pediatric Rheumatology Department in a tertiary university hospital in Paris (Hôpital Bicêtre, France). All patients underwent a MRI that confirmed the diagnosis according to the criteria of Jansson. Skeletal involvement was characterized with 1/axial, 2/ peripheral, 3/ axial and peripheral lesions. Extra-osseous manifestations were divided into 1/ skin lesions, 2/ gastro-intestinal manifestations, 3/ enthesitis and 4/ others. Pain was evaluated thanks to the Visual Analog Scale (VAS, from 0 to 10). Treatments used were recorded. The study complied with ethical requirements.ResultsForty one patients were included in the study, with 31 females (75.6%). The mean ± SD age at onset was 79.1 ± 59.8 months, with a delay at diagnosis beyond six months (6.71 ± 6.96). Twenty-one patients had a familial history of inflammatory diseases (51.2%), with a majority of psoriasis or ankylosing spondylitis (n=13/21, 61.9%). At diagnosis, the level of pain was 5.71 ± 3.24. Eleven patients (42.3%) had blood inflammation. Bone lesions were reviewed thanks to whole body MRI: four patients had isolated axial involvement (10.0%), nine had peripheral involvement (22.5%) and 27 patients harbored both types of lesions (67.5%). The mean number of lesions was 6.65 ± 4.23. After 12 months of follow-up, all parameters regarding disease’s activity decreased (pain, blood inflammation, number of lesions). Regarding extra-osseous symptoms, fever occurred in seven patients (17.1%). Twenty-four patients had skin manifestations (58.5%) with palmoplantar lesions (n=3, 12.5%), acne (n=6, 25.0%), psoriasis (n=5, 20.8%) and aphthous (n=10, 41.7%). Four patients (9.76%) had gastro-intestinal symptoms and seven (17.1%) had enthesitis. One patient had uveitis. Almost all patients received NSAIDs (n=39/41, 95.1%) and half of the cohort were treated with bisphosphonates (n=21/41, 51.2%). Nine patients (22.0%) received biologics with a majority of TNF inhibitors. All patients that received TNF inhibitors had either a cutaneous involvement or digestive symptoms or enthesitis (Figure 1).ConclusionExtra-osseous manifestations have to be carefully searched in CRMO, especially in the presence of familial history of inflammatory diseases. While the severity of bone involvement can lead to use bisphosphonates, the introduction of biologics seems to rely on extra-osseous symptoms. These conclusions are drawn on a retrospective study and need to be confirmed in larger cohort.References[1]Wipff J, et al. A large national cohort of French patients with chronic recurrent multifocal osteitis. Arthritis Rheumatol 67, 1128-1137 (2015).[2]Jansson A, et al. Classification of Non-Bacterial Osteitis: Retrospective study of clinical, immunological and genetic aspects in 89 patients. Rheumatology 46, 154-160 (2006).Disclosure of InterestsNone declared

Conventional immunosuppressive drugs, anti-TNF alpha and other biotherapies used in clinical practice are capable of controlling non-infectious anterior uveitis, posterior uveitis and panuveitis. The present work has been led by a multidisciplinary panel of experts, internists, rheumatologists and ophthalmologists and is based on a review of the literature. In case of corticodependency or sight-threatening disease, conventional immunosuppressive drugs (methotrexate, azathioprine and mycophenolate mofetil) and/or anti-TNF alpha (adalimumab, infliximab) are used to achieve and maintain remission. Interferon is an efficient immunomodulatory treatment, as a second-line therapy, for some therapeutic indications (refractory macular edema, Behcet's vascularitis). Other biologics, especially tocilizumab, are showing promising results. Local treatments (corticosteroids, sirolimus etc.) are adjuvant therapies in case of unilateral inflammatory relapse. Therapeutic response must be evaluated precisely by clinical examination and repeated complementary investigations (laser flare photometry, multimodal imaging, perimetry, electroretinography measures).

Resume La maladie de Kawasaki, bien connue des pediatres, est une vascularite multisystemique aigue touchant les vaisseaux de moyens calibres avec une predilection pour les arteres coronaires. Dans les pays developpes, cette maladie est la premiere cause de cardiopathie acquise chez l’enfant. La physiopathologie de cette maladie est actuellement toujours inconnue, mais il est communement admis qu’un ou plusieurs agents infectieux induisent une reponse inflammatoire inappropriee chez un sujet genetiquement predispose. Le diagnostic est clinique et doit etre evoque chez des enfants presentant une fievre prolongee de plus de cinq jours avec un syndrome inflammatoire biologique. Des criteres cliniques d’inflammation cutaneomuqueuse ont ete definis par l’American Heart Association en 2004 afin d’etablir le diagnostic. Cependant, certains enfants peuvent presenter des formes incompletes de la maladie surtout lorsque la maladie apparait a un âge inhabituel. Les symptomes sont proches de certaines pathologies infectieuses de l’enfant comme la scarlatine ou une infection virale rendant le diagnostic difficile. Par ailleurs, un retard au diagnostic ou l’absence de traitement majore le risque de developper des anevrismes coronaires. Les immunoglobulines polyvalentes constituent le traitement de premiere ligne, avec un taux de succes de l’ordre de 80 %. En cas de non-reponse a cette premiere ligne de traitement, le recours aux corticoides peut etre propose, en association a une deuxieme cure d’immunoglobulines, surtout dans les formes de mauvais pronostic. D’autres therapeutiques comme les anti-tumor necrosis factor alpha ou certains immunosuppresseurs peuvent aussi etre employees en cas de resistance aux immunoglobulines, mais doivent etre discutees avec une equipe specialisee.

Background:Familial Mediterranean Fever (FMF) is a hereditary autoinflammatory disease associated with mutations in theMEFVgene. Colchicine is the cornerstone of current therapy for FMF; however, a subset of patients are resistant or intolerant to it. Previously published results from the CLUSTER trial [NCT02059291] demonstrated that canakinumab, a fully human anti-interleukin-1β monoclonal antibody, was effective in controlling and preventing flares in patients with colchicine-resistant familial Mediterranean fever (crFMF).1Objectives:To evaluate the long-term efficacy and safety of canakinumab to treat patients with crFMF during Epoch 4 of the CLUSTER study.Methods:Patients with active crFMF (baseline flare) were enrolled in the CLUSTER study. During Epoch 4 (weeks 40 to 113), patients received open-label canakinumab 150 or 300 mg, every 4 or 8 weeks (q4w or q8w). Patients started Epoch 4 on the same regimen that they were receiving at the end of Epoch 3, and stepwise up-titration of canakinumab was allowed in patients who experienced a flare, to a maximum dose of 300 mg q4w. We evaluated disease activity every 8 weeks using the physician global assessment of disease activity (PGA), counting the number of flares (defined as PGA ≥2 and CRP >30 mg/L), and measuring serum concentrations of C reactive protein (CRP) and serum amyloid A (SAA). Safety was assessed by the determination and classification of adverse events (AEs). We analysed safety and efficacy separately in two subgroups of patients receiving a cumulative dose of canakinumab lower than 2700 mg, or equal or higher than 2700 mg.Results:Of the 61 patients with active crFMF who started the CLUSTER study, 60 entered Epoch 4 and 57 completed it. During the 72-week period, 35/60 (58.3%) patients experienced no flares, and 23/60 (38.3%) had one single flare, as compared with a median of 17.5 flares per year reported at baseline. The incidence of flares was similar in the two cumulative dose groups. PGA scores indicated no disease activity for the majority of patients throughout the study, in both cumulative dose groups. 23/57 (40%) of patients remained in the lower dosing group (150 mg q8w) until study end, whereas 9/57 (16%) required the highest dose allowed (300 mg q4w). Patients with higher body weight had an increased probability to require up-titration of canakinumab to control disease activity. Median CRP concentrations were lower than 10 mg/L at every time point in both cumulative dose groups, while median SAA concentrations remained in the 16-70 mg/L range, and were higher in the group receiving ≥2700 mg canakinumab (Figure 1). No opportunistic infections, renal disease caused by amyloidosis, new or unexpected AEs were reported.Figure 1.SAA and CRP blood levels in Epoch 4 of the CLUSTER study, in two subgroups of patients treated with a cumulative dose of canakinumab Conclusion:Patients with crFMF treated with canakinumab during 72 weeks experienced a minimal incidence of flares and good control of clinical disease activity, with no new safety signals reported.References:[1]De Benedetti F et al.N Engl J Med2018;378:1908–19.Disclosure of Interests:Seza Özen Consultant of: Novartis, Pfizer, Speakers bureau: SOBI, Novartis, Eldad Ben-Chetrit Speakers bureau: Novartis, Ivan Foeldvari Consultant of: Novartis, Gil Amarilyo Grant/research support from: Novartis, Speakers bureau: Novartis, Huri Ozdogan: None declared, Steven Vanderschueren: None declared, Katherine Marzan Grant/research support from: Novartis, J Michelle Kahlenberg Grant/research support from: Celgene, BMS, Consultant of: Eli Lilly, AstraZeneca, BMS, Boehringer Ingleheim, Elise Dekker Employee of: Novartis, Fabrizio De Benedetti Grant/research support from: AbbVie, Pfizer, Novartis, Novimmune, Sobi, Sanofi, Roche, Speakers bureau: AbbVie, Novartis, Roche, Sobi, Isabelle Koné-Paut Consultant of: Novartis, Chugai, Pfizer, LFB, AbbVie, Novimmune, SOBI

Conventional immunosuppressive drugs, anti-TNF alpha and other biotherapies used in clinical practice are capable of controlling non-infectious anterior uveitis, posterior uveitis and panuveitis. The present work has been led by a multidisciplinary panel of experts, internists, rheumatologists and ophthalmologists and is based on a review of the literature. In case of corticodependency or sight-threatening disease, conventional immunosuppressive drugs (methotrexate, azathioprine and mycophenolate mofetil) and/or anti-TNF alpha (adalimumab, infliximab) are used to achieve and maintain remission. Interferon is an efficient immunomodulatory treatment, as a second-line therapy, for some therapeutic indications (refractory macular edema, Behçet's vascularitis). Other biologics, especially tocilizumab, are showing promising results. Local treatments (corticosteroids, sirolimus etc.) are adjuvant therapies in case of unilateral inflammatory relapse. Therapeutic response must be evaluated precisely by clinical examination and repeated complementary investigations (laser flare photometry, multimodal imaging, perimetry, electroretinography measures).

Familial Mediterranean Fever (FMF) is the most frequent monogenic auto-inflammatory disease. FMF is an autosomal recessive disease, which affects populations from Mediterranean origin and is associated with MEFV gene mutations encoding for the protein pyrin. Pyrin activation enhances the secretion of interleukin 1 by myelo-monocytic cells. Main features of the disease are acute attacks of serositis mainly located on the abdomen, less frequently on chest and joints, accompanied by fever and biological inflammatory markers elevation. Usually attacks last 1 to 3 days and spontaneously stop. A daily oral colchicine intake of 1 to 2mg/day is able to prevent attack's occurrence, frequency, intensity and duration among most patients. Colchicine is also able to prevent the development of inflammatory amyloidosis, the most severe complication of FMF. This state of the art article will focus on the diagnosis of FMF, the treatment and an update on the pathophysiology including the recent described dominant form of MEFV-associated new auto-inflammatory diseases.

Mevalonate kinase deficiency is a rare, autosomal recessive, auto-inflammatory disease. This results from mutations in the gene MVK coding for the enzyme mevalonate kinase. This enzyme is involved in cholesterol and isoprenoids synthesis. Depending partially of the residual activity of the mevalonate kinase, the clinical spectrum realizes a continuum which extends from the mild phenotype of the hyperimmunoglobulinemia D and periodic fever syndrome (HIDS) to a lethal form of mevalonic aciduria. The HIDS is characterized by recurrent episodes of fever with an intense inflammatory syndrome, accompanied with lymphadenopathy, abdominal pain, diarrhea, arthralgia, hepatomegaly, splenomegaly and skin rash. The first attack more frequently takes place in the first year of life, even during the neonatal period, where it can be confused with a maternofetal infection. There is furthermore in mevalonate aciduria a psychomotor retardation, a failure to thrive, a cerebellar ataxia, a dysmorphic syndrome and a reduction of the visual acuity. The diagnosis is based on the mevalonic aciduria during febrile attack. Genetics confirm the diagnosis in more than 80 % of the cases. The dosage of IgD, low sensitive and specific, has no interest. There is no reference treatment. The less severe forms can be treated by non-steroidal anti-inflammatory drugs or steroids during febrile attacks. The most severe patients can be treated by biotherapy: antagonists of IL-1, TNF-α and IL-6.

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

Resume L’osteoporose correspond a une rarefaction de la matrice proteique osseuse secondaire a un trouble de l’homeostasie (ou turnover ) entrainant un processus de destruction exageree. Le systeme RANK-L/RANK/OPG est au centre du systeme de regulation du remodelage osseux. Les osteoporoses juveniles peuvent etre primitives ou secondaires. Leurs causes principales sont d’une part, les fragilites osseuses constitutionnelles et d’autre part, les causes secondaires aux maladies inflammatoires chroniques ou a la corticotherapie prolongee. Leur diagnostic essentiellement clinique est souvent fait trop tardivement devant des complications. L’osteodensitometrie est un moyen sensible et non invasif de mesurer la densite minerale osseuse chez l’enfant, mais son interpretation est delicate du fait des variations induites par l’âge, le sexe, le stade pubertaire et la taille des pieces osseuses. Le traitement de l’osteoporose est essentiellement preventif, reposant sur des mesures hygienodietetiques, dont une supplementation vitaminocalcique et une activite physique maintenue. Les biphosphonates sont utilises pour traiter les osteoporoses symptomatiques (fracturaires). Leur utilisation doit etre prudente du fait de la meconnaissance actuelle de leurs effets secondaires a long terme. De nouvelles molecules aux effets antiresorbants et d’autres stimulant la formation osseuse sont utilisees avec succes chez l’adulte. Elles n’ont pas encore fait l’objet d’etudes chez l’enfant.

Behcet's disease (BD) occurs occasionally in children and is recognized at a median age of 14 years. The onset is insidious and the course is recurrent. Oral ulcers and fever of unknown origin are frequent at onset. The diagnosis is challenging and made only on a clinical basis with exclusion of other conditions comprising recurrent oral ulceration. Male patients are at a high risk of developing severe ocular, neurological, and vascular involvement. Large-vessel vasculitis is the leading cause of death. Drugs used in BD are aimed to target inflammation. They include NSAIDs, colchicine, and steroids as well as immunosuppressive agents. The use of biological treatments has increased for severe organ manifestations and two new medications have been recently approved by the FDA and EMA, for use in adults with severe recurrent aphthosis: Apremilast, and severe cortico-dependant uveitis; gevokizumab. The use of anticoagulants in vascular BD is not recommended.

We have conducted a segregation analysis in order to characterise the transmission of Behcet Disease (BD), a multifactorial condition with a strong genetic component. Complete information about BD status and pedigree was obtained on 104 probands from our database. We used the criteria of the International Study Group for BD (ISBD) to delineate the clinical status of the sibs: possible BD (patients meeting two criteria), or ascertained BD (patients meeting at least three criteria). A proband was defined as "paediatric" when he/she completed ISBD criteria before/by the age of 16 years. Families were distinguished as paediatric (n = 67) (ascertained through a paediatric proband), and non-paediatric (n = 37) ones. An Expectation Maximization (EM) algorithm was used to estimate the Mendelian segregation ratio P in nuclear families (two parents and their offspring). The maximum likelihood estimate: Pcirc; = 0.248, calculated in the paediatric data set, was consistent with the theoretical value of P = (1/4) for autosomal recessive inheritance, whereas the Pcirc; value was 0.08 when using the non-paediatric data set. Our work provides the first evidence of genetic heterogeneity in BD, and of the existence of a Mendelian entity in the paediatric BD subgroup. Previous studies failed to show any simple mode of inheritance in BD, probably because they were performed on the whole BD population.

Biphosphonates are synthetic analogs of the natural pyrophosphate molecule, introduced primarily for the treatment of Paget disease of bone. Their main mechanism of action consisting in an inhibition of osteoclastic activity is critical for treatment of disorders including an increased bone resorption. In childhood osteoporosis (especially osteogenesis imperfecta), hypercalcemia and heterotopic calcifications are the three main situations in which they have been successfully used, with however few follow-up and no controlled studies. The evolution of these compounds generating more potent products, given orally, with limited effect on bone mineralization should allow an extension of their use in pediatric patients. Multicentric studies are now necessary to specify their efficacy and guidelines for use in children.

Resume Objectif de l’etude. – Analyser les donnees epidemiologiques du syndrome de Raynaud chez l’enfant. Patients et methodes. – Nous avons mene une etude retrospective sur une periode de neuf ans, des enfants de moins de 17 ans ayant consulte pour un syndrome de Raynaud. Les dossiers ont ete retrouves a partir des consultations de pediatrie, de dermatologie et egalement a partir du registre des capillaroscopies. Un questionnaire type a ete etabli et les donnees manquantes ont ete completees apres entretien telephonique avec les parents. Resultats. – Un diagnostic definitif de syndrome de Raynaud a ete retenu chez 23 enfants avec une nette predominance feminine ( sex-ratio : 0,27). Les facteurs declenchant essentiels etaient le froid et les emotions. L’âge moyen au moment du diagnostic etait de 11 ans (cinq a 16 ans) avec un debut apres l’âge de dix ans dans 65 % des cas. Onze de ces syndromes de Raynaud se sont reveles secondaires dont dix a une connectivite, huit sont restes apparemment primaires et quatre ont ete juges comme suspects d’etre secondaires. Discussion. – Cette serie de syndromes de Raynaud pediatriques etait consequente compte tenu des donnees actuelles de la litterature sur le sujet. Elle a mis en evidence les difficultes du diagnostic qui reste exclusivement clinique et la forte representation des causes secondaires notamment des connectivites. Une enquete etiologique est donc imperative devant tout syndrome de Raynaud chez un enfant. Le caractere sensible (78 %) et specifique (80 %) de la capillaroscopie pour le diagnostic des connectivites dans le cadre de notre etude, a retenu notre attention ; sa valeur pronostique merite d’etre evaluee sur un plus grand echantillon de patients.

Cryopyrin-associated periodic syndrome is a rare hereditary periodic fever syndrome for which, the genetic mechanism, mutation in the NLRP3 gene, has allowed to gather 3 clinical phenotypes (familial cold urticaria [FCAS], Muckle-Wells syndrome [MWS], and chronic infantile neurological cutaneous and articular syndrome [CINCA]) initially described independently, and to discover the NLRP3 inflammasome, a key receptor of the innate immunity, which regulates the interleukine-1β secretion into the mononuclear cells. The clinical manifestation of CAPS : urticaria-like skin rash, eyes redness, myalgia and sensory deafness are not specific, if considered separately, and that often leads to a wandering diagnosis through a complex medical journey including various specialists. The diagnostic delay is deleterious to patients compromising their quality of life and exposing them to neurosensory complications and renal failure by secondary amyloidosis. The paediatric onset of disease, the family history, the trigger of symptoms by the cold, and the recognition of the skin rash as neutrophilic are important clues before diagnostic confirmation by genetic testing. Interleukine-1 blockade is the only effective treatment of CAPS symptoms which often may stabilize (rarely regression) the sensory involvement and in some cases may allow the regression of secondary amyloidosis.

Tocilizumab (TCZ) is an anti-interleukin-6-receptor antibody. The blockade of IL-6 is used as a strategy for the treatment of systemic juvenile idiopathic arthritis (S-JIA) and multicentric Castleman disease (MCD). In this study, we describe the tolerability profile of tocilizumab in eight children followed in a pediatric rheumatology department. Six patients were treated for S-JIA and two for a MCD. They received doses of TCZ between 8 and 12mg/kg of body weight depending on their disease. Infusions were received every 2-4 weeks. The mean duration of treatment was 32.9 months (14 months to 4.5 years). Clinical adverse events were all mild or moderate. No cases of macrophage activation syndrome and no anaphylactic reactions were reported. TCZ was never stopped for a clinical adverse event. Neutropenia was the most common biological adverse event, sometimes requiring dose adjustments. Thrombopenia, lymphopenia, and increased liver enzymes were reported as well, but treatment was not modified. All these biological adverse events were not complicated by any clinical manifestation. In conclusion, TCZ had a good tolerability profile in these eight patients with partial or total efficacy. Despite this advantageous profile, TCZ should be closely monitored because of the potential severity of adverse events. Moreover, long-term safety has still not been assessed.

Resume Le syndrome KID est un syndrome rare associant keratite, ichtyose et surdite (deafness), probablement du a une anomalie congenitale de l'ectoderme affectant la cornee, la peau et l'oreille interne. Des manifestations cliniques associees telles que la sensibilite aux infections et l'atteinte des phaneres peuvent aider a poser le diagnostic. Il n'y a pas d'anomalies biologiques specifiques. La plupart des cas sont sporadiques mais il a ete decrit des cas familiaux dont le mode de transmission reste mal precise. Le traitement des atteintes cutanees, ophtalmologiques et auditives est decevant. La prise en charge passe donc essentiellement par le depistage precoce des complications

Chronic recurrent multifocal osteomyelitis (CRMO) is a rare autoinflammatory disease in children. Pathological vertebral fracture may be the first symptom revealing this disease. We describe the case of a 14-year-old boy, with no significant past medical history, who had a sudden dorsal pain after carrying a friend on his back. Plain radiographs and MRI showed fractures of the superior endplate of T5 and T6 associated with a mild degree of kyphosis. MRI allowed ruling out discitis. The diagnostic hypotheses raised were cancer (lymphoma, leukemia), Langerhans cell histiocytosis, osteogenesis imperfecta, and CRMO. A whole-body MRI (wbMRI) was performed and disclosed several clinically silent signal abnormalities in key sites of CRMO (pelvic bone and tibial metaphyses). We point out that CRMO should be systematically added to the list of possible diseases in case of vertebral fracture. In this perspective, wbMRI is a major noninvasive tool to assess the diagnosis of CRMO, and allows avoiding a bone biopsy in most cases.

Behçet's disease is a chronic multisystem vasculitis of unknown etiology. The disease is commonly described in young adults but can occur in childhood. Diagnosis is based on clinical manifestations since there are no pathognomonic laboratory findings. Early diagnosis in children is challenging due to the insidious nature of the disease and the low sensitivity of adult criteria in the pediatric population. The purpose of this review is to describe the demographic and clinical features of Behçet's disease in childhood, its complications and recent advances in therapeutics highlighting differences with the adult onset disease.

Resume Le syndrome hypoglossie-hypodactylie associant une reduction congenitale des membres, une hypoglossie et une micrognathie est exceptionnellement associe a une ankylose glossopalatine et a une fente palatine. Observation. — Une jumelle issue d'une grossesse monochoriale presentait une hypoglossie et une micrognathie avec synostose maxillomandibulaire antericure, ankylose glossopalatine et fente palatine. Son pied gauche etait ampute apres l'astragale et le calcaneum; le pied droit n'avait qu'une phalange. La deuxieme phalange du deuxieme doigt etait hypoplasique a la main droite. La main gauche etait sans anomalie. Sa sceur n'est pas atteinte. La fussion maxillomandibulaire a ete sectionnee le deuxieme jour de vie. L'enfant a pu teter le dixieme jour. Des apnees obstructives ont ete constatees sur l'enregistrement cardiorespiratoire et l'enfant a pu beneficier d'un monitorage a domicile. Conclusion. — Cette observation suggere que des perturbations hemodynamiques entrainees par les anastomoses placentaires multiples des grossesses monochoriales ont provoque les lesions d'origine ischemique de l'hypoglossie-hypodactylie. D'autres malformations et des signes de dysfonctionnement du trone cerebral doivent etre recherches.

Joint swelling is common in childhood. The pattern of presentation, the duration and the location may reveal sometimes monoarthritis. A detailed clinical history, thorough clinical examination, and sometimes complementary tests are needed to reach the correct diagnosis. The single most important investigation in a child with acute monoarthritis is joint aspiration to rule out septic arthritis that may destroy the joint within few hours. Serum inflammatory markers, antinuclear antibody, tuberculosis testing, and imaging (in specific cases) play an important role in making the diagnosis. This article presents the clinical approach to the diagnosis of monoarthritis as well as the different causes of monoarthritis in children.

Cat scratch disease is the most common zoonosis in humans and its typical expression is a persistent benign regional adenopathy. In some rare cases, mono- or multifocal osteomyelitis is described. In this paper, we report the case of bone lesions in a 13-year-old girl infected with cat scratch disease. We have also undertaken a literature review and analyzed 60 other such cases. The manifestation of a bone lesion associated with cat scratch disease was characterized by a mono- or multifocal infectious osteomyelitis, fever, and a general alteration of the patient's health. The most frequent location of osteomyelitis was in the spine. Magnetic resonance imaging appeared the most sensitive test to highlight the bone lesions. Serological findings help reinforce the diagnosis of cat scratch disease caused by Bartonella henselae infection. Osteomyelitis in cat scratch disease is rare but not exceptional. Therefore, it is essential to think about this hypothesis in case of osteomyelitis associated with a general alteration of the patient's health, especially if the lesions are multifocal and if there is a known history of cat contact.

According to the French national health authority guidelines, the diagnosis of childhood pneumonia is based on clinical suspicion and radiological confirmation. The chest radiography is an expensive procedure, and potentially deleterious by its radiating character. We have attempted to clarify its diagnostic value in community acquired pneumonia in children through a literature review using the Pubmed search engine with the following keywords: "pneumonia, child, radiograph".The indication of chest radiography in severe pneumonia achieved unanimity among the various scientific societies. In contrast, in mild forms, tendency of the available data is to not recommend the routine use of chest radiography; further randomised and prospective studies are necessary to confirm this trend. Finally, because of the frequency of atypical presentations in children, chest radiography retains all its usefulness in the etiologic diagnosis of fever of unknown origin.

Introduction: Behcet disease (BD) is a systemic vasculitis which can affect the neurological system. Neuro-Behcet's disease (NBD) is not well described in children. Objective: Our study aimed to analyse the clinical patterns of paediatric NBD and to describe their repercussions on children's schooling. Methods: We performed a retrospective chart review of 12 NBD children and a phone interview of patients and their physicians to investigate their last physical and schooling status. Results: In 40 BD patients reviewed, 12 (sex ratio 8M/4F) had neurological involvement. The mean age of onset was 11 years. In 4 cases, neurological symptoms were the initial presentation. In other cases, NBD occurred within a mean time of 10 months after BD was diagnosed. Cerebral venous thromboses were frequent (5/12) as compared to recurrent meningoencephalitis (2/12), rhombencephalitis (2/12), transverse myelitis (1/12), peripheral neuropathy (1/12) or psychiatric disturbances (1/12). 9 patients had sequelae and 8 had difficulties in learning. 6 stopped at middle school level. For the other patients, an arrangement of the teaching environment was needed due to visual, auditory and concentration disorders. Conclusion: Neurological involvement is frequent in BD children and its consequences could be severe. Timely accommodations are required to facilitate their ability to follow the normal curriculum.

The hyperimmunoglobulinemia D syndrome (HIDS) is a well-defined entity resembling familial Mediterranean fever. HIDS is a systemic inflammatory disease associated with stimulation of T-cell-mediated immunity. These patients are at low risk for amyloidosis and are not known to develop nephropathy. We report a boy of Mediterranean ancestry who exhibited typical HIDS and end-stage renal failure. Kidney biopsy revealed pauci-immune crescentic glomerulonephritis (cGN). We hypothesized that the glomerular involvement was secondary to the cytokine network activation observed in HIDS. Thus, cGN should be considered as part of the syndrome, and kidney biopsy should be performed early in the course of the renal disease in patients with HIDS.

Retroperitoneal fibrosis (RF) is a rare disease in children. We report the case of a 15-year-old boy who presented with a 2-month history of dorsal pain and a 2-week history of fever. The erythrocyte sedimentation rate and serum C-reactive protein value were high. Magnetic resonance imaging revealed a large heterogeneous retroperitoneal mass, suggestive of RF. Percutaneous biopsy of inguinal lymph node provided the diagnosis of anaplastic large cell lymphoma. This is the first report of RF revealing malignancy in childhood. It emphasizes that malignancy must be carefully searched for in children with unexplained RF.

The outcome of acute osteomyelitis in children has been modified by the use of potent antibiotics. However, treatment management remains unclear. The aim of this study was to investigate the current management of acute osteomyelitis in children in France.A questionnaire regarding the choice and the duration of antibiotics was sent to French pediatricians and pediatric orthopedists.Ninety-four centers answered the questionnaire: 72 pediatricians and 22 pediatric orthopedists. The response rate was 51% and the median number of children hospitalized per year for osteomyelitis was 4 in each center. The radiologic procedures most often used for diagnosis were X-rays (99%) and bone scintigraphy (82%). Two intravenous antibiotics schemes were used by 80% of centers: either an association of 3rd-generation cephalosporin plus fosfomycin or an association of penicillin M and aminoglycoside, followed by oral penicillin M or pristinamycin. Intravenous therapy lasted 7 to 14 days in 72% of the centers. The total duration of antibiotic therapy was 6 weeks for 55% of centers. In 83% of cases, immobilization was prescribed. The decision for treatment withdrawal was based on clinical, biological or empirical findings for 59, 75 and 60% of departments, respectively.In spite of controversies and lack of consensus, regarding both the diagnostic procedures and treatment management, 2 main antibiotic therapy schemes emerged from our survey. However, the treatment duration appeared more variable. Reaching a consensus for acute-osteomyelitis care in children remains a critical issue.

Osteoporosis is induced by a disorder of the bone turnover that generates an accelerated destruction process and leads to the rarefaction of the protein matrix. The RANK-L/RANK/OPG system is the main actor of the bone remodelling regulation. Juvenile osteoporoses may have primary or secondary aetiologies. The main causes include constitutional bone fragilities, and osteoporoses, which are secondary to chronic inflammatory diseases and sustained steroid treatment. Etiologic diagnosis relies on a clinical basis, and is often made too lately when complications occur. Osteodensitometry is a sensitive and noninvasive tool for measuring mineral bone density in children. The reliability of results is limited by the variations due to patients' age, gender, pubertal stage, and by the length of bone pieces. The optimal treatment of osteoporosis is preventive, and includes accurate nutritional diet, D vitamin-calcium supplementation and regular physical activity. Biphosphonates are used for treatment of symptomatic osteoporoses. Careful utilization is required in childhood because their late potential secondary effects are still unknown. New antiresorptive drugs and other that stimulate osteoformation are successfully used in adults. Their effects have not been studied in the paediatric population.

International audience

Childhood-onset systemic lupus erythematosus (SLE) is often severe and has a serious long-term morbidity. Pediatric guidelines about its management do not exist. The French study group of childhood-onset SLE proposes recommendations about the investigation which are needed at diagnosis and during follow-up of SLE, in order to adjust the treatment according to the severity of the disease and to avoid unnecessary investigations.