Long-term evaluation of infliximab in the treatment of persistently active juvenile idiopathic arthritis refractory to conventional therapy

Objectives: To evaluate, in long-term open label prospective study, infliximab as therapeutic choice for Juvenile Idiopathic Arthritis (JIA) non responsive to conventional therapy. Methods: We enrolled to treat with infliximab 78 JIA patients (66 females, 12 males): the mean age was 20.7±7.1 years (median 20.9, range 5.4-34.9); mean JIA duration was 13.6±7.6 years (median 13.5, range 0.4-31.4). Infliximab, at dose of 3-10 mg/kg/infusion added to weekly subcutaneous Methotrexate or other previous DMARDs, was administered by intravenous infusions at weeks 0, 2, 6 and every 8 weeks thereafter. Chest X-ray, Mantoux's test, electrocardiogram were performed at baseline; laboratory tests and clinical evaluation were performed at each infusion. Response was evaluated according to ACR improvement criteria. Results: Mean treatment period was 21.6 months±18.8 (median 14.7, range 1.4-72.4). Just after first infusion most of patients reported significant improvement in pain, fatigue, morning stiffness. Infliximab is still successfully administered to 23 patients (29.5%); 55 (70.5%) patients suspended because of: inefficacy (7), infusion reactions (17), adverse events (9), disease flare-up after a period of effectiveness on synovitis, pain, and morning stiffness (19), remission (2), lack of compliance to treatment (1). Infusion reactions, like dyspnea, flushing, chills, headache, hypotension, anxiety, throat oedema, were observed in 29 patients (34.5%). Anti-DNA antibodies were present in 7 patients (none developed Systemic Lupus Eritematous). Conclusions: Infliximab showed impressive effectiveness treating refractory JIA, although most of patients had to discontinue treatment because of disease flare-up or adverse events. Infliximab may represent a good therapeutic choice in patients non-responders to Methotrexate

HIV replication leads to skewed maturation of CD8-positive T-cell responses in infected children

HIV-1 infection causes a severe T-cell impairment with alteration of immune response. However, in children the natural decline of lymphocytes and CD4 cells in early life makes it more difficult to monitor immunocompetence and progression of HIV-infection. Aim of this study was to characterize the CD8 response in non-vertically HIV-infected children exposed persistently to viremia and in HIV-infected children controlling efficiently viremia by ART, by analysing the effect of persistent viremia on CD4 and CD8 T-cells count, HIV-specific immune-response and naive/memory pattern of CD8 T-cell. Whereas, no differences of CD4 count between viremic patients and viral controllers were observed (1046.9 +/- 472.1 cells/microl vs 1101.3 +/- 415.4 cells/microl; p > 0.05), CD8 count was higher in the viremic patients (1080.6 +/- 652.1 cells/microl vs 747.5 +/- 389.9 cells/microl, p < 0.05). In viremic patients, HIV-specific CD8 T-cells correlated with viral load. However, in this group a loss of HIV-specific CD8 response was associated with a 7 fold decrease of naïve and increase of pre-effector CD8 T-cells (62.8% +/- 10.21% vs 10.37% +/- 7.91%, p < 0.03). Persistent exposure to viremia alters HIV-specific CD8 response possibly through a persistent immune activation process leading to exhaustion of naive CD8 T-cells and skewed maturation of memory subset. Therefore, memory CD8 T-cells might lose the ability to respond correctly and efficiently to HIV-antigen exposure

Temporomandibular joint involvement in juvenile idiopathic arthritis: treatment with an orthodontic appliance

Introduction and purpose: About 65% of children suffering from juvenile idiopathic arthritis (JIA) shows a more or less marked involvement of temporo-mandibular joint (TMJ) with altered mandibular growth, resorption of the condyles, occlusary instability, reduced chewing ability and facial dysmorphia. The purpose of our study is to prevent and to treat the progressive evolution of JIA on craniofacial growth and morphology with a functional appliance; surgery should be considered only in so far as the adequacy of TMJ movement is concemed. Methods: From 1992 until now 72 children with proved JIA and TMJ involvement have been treated (50 females, 22 males, aged 6 to 16 years old). TMJ involvement was bilateral in 61% and unilateral in 39% of patients. A diagnostic workup was carried out involving tomograms of TMJ and cephalometric radiograph and analysis. The authors used a bimaxillary activator in the attempt to modify the unfavourable growth pattern and provide a gradual ante-rotation of the jaw. Results: Almost all JIA patients showed satisfactory long term results, easing of pain, reduced skeletal discrepancy, increased function and good facial profile. Conclusions: The long term results of this study indicate that orthopaedic therapy might control the vicious circle of the malocclusion in children with JIA, preventing exacerbation of mandibular clockwise rotation. Surgical intervention for the improvement of TMJ function should be considered only if a severe restricted state is imminent

Anti-CD 20 monoclonal antibody (rituximab) treatment for inflammatory ocular diseases

Rituximab is a monoclonal antibody directed against the CD20 antigen expressed on B cells and widely used in the treatment of non-Hodgkin's lymphoma and rheumatoid arthritis. There is a growing amount of literature which suggests that rituximab may be useful for inflammatory ocular diseases and intraocular lymphoma. Few cases have been reported on treatment of refractory scleritis, peripherative ulcerative keratitis, uveitis and ocular surface inflammatory disorders. Rituximab may be effective in the treatment of ocular inflammatory diseases in particular the most aggressive, recalcitrant and sight-threatening forms of inflammation such as uveitis associated to juvenile idiopathic arthritis. We review the literature covering the use of Rituximab in these conditions and report our results on the efficacy of Rituximab in the treatment of 8 children with very severe and long-standing uveitis who failed to respond to one or more TNF blockers. Our patients showed improvement in activity of uveitis, reduction of concomitant corticosteroids and immunosuppressants after a mean follow-up time of 14.87 months on rituximab. No serious adverse events were encountered in our treated patients. Although further studies are needed for assessing the efficacy of rituximab and the exact dosing regimen, rituximab may be considered as a treatment alternative in patients with the most aggressive forms of inflammatory ocular diseases who fail to respond to conventional and anti-TNF immunosuppressive agent

Italian intersociety consensus on management of long covid in children

Background: Two sequelae of pediatric COVID-19 have been identified, the multisystem inflammatory syndrome in children (MIS-C) and the long COVID. Long COVID is much less precisely defined and includes all the persistent or new clinical manifestations evidenced in subjects previously infected by SARS-CoV-2 beyond the period of the acute infection and that cannot be explained by an alternative diagnosis. In this Intersociety Consensus, present knowledge on pediatric long COVID as well as how to identify and manage children with long COVID are discussed. Main findings: Although the true prevalence of long COVID in pediatrics is not exactly determined, it seems appropriate to recommend evaluating the presence of symptoms suggestive of long COVID near the end of the acute phase of the disease, between 4 and 12 weeks from this. Long COVID in children and adolescents should be suspected in presence of persistent headache and fatigue, sleep disturbance, difficulty in concentrating, abdominal pain, myalgia or arthralgia. Persistent chest pain, stomach pain, diarrhea, heart palpitations, and skin lesions should be considered as possible symptoms of long COVID. It is recommended that the primary care pediatrician visits all subjects with a suspected or a proven diagnosis of SARS-CoV-2 infection after 4 weeks to check for the presence of symptoms of previously unknown disease. In any case, a further check-up by the primary care pediatrician should be scheduled 3 months after the diagnosis of SARS-CoV-2 infection to confirm normality or to address emerging problems. The subjects who present symptoms of any organic problem must undergo a thorough evaluation of the same, with a possible request for clinical, laboratory and / or radiological in-depth analysis in case of need. Children and adolescents with clear symptoms of mental stress will need to be followed up by existing local services for problems of this type. Conclusions: Pediatric long COVID is a relevant problem that involve a considerable proportion of children and adolescents. Prognosis of these cases is generally good as in most of them symptoms disappear spontaneously. The few children with significant medical problems should be early identified after the acute phase of the infection and adequately managed to assure complete resolution. A relevant psychological support for all the children during COVID-19 pandemic must be organized by health authorities and government that have to treat this as a public health issue

Point of view of the Italians pediatric scientific societies about the pediatric care during the COVID-19 lockdown: What has changed and future prospects for restarting

Background: The coronavirus disease 2019 (COVID-19) is currently rare in children and they seem to have a milder disease course and better prognosis than adults. However, SARS-Cov-2 pandemic has indirectly caused problems in pediatric medical assistance. In view of this we wanted to draw a picture of what happened during health emergency and analyze future prospects for restarting. Methods: We involved the Italian pediatric scientific societies institutionally collected in the Italian Federation of Associations and Scientific Societies of the Pediatric Area (FIARPED); We sent a questionnaire to all scientific societies about the pediatric care activity during the COVID-19 emergency and future perspectives for the phase of post-containment. Results: The analysis of the questionnaires showed significant decrease of:admission, outpatient visits and specialist consultancy activities during the COVID-19 emergency, primarily linked to the fear of infection. Instead it was increased the serious degree of diseases admitted. Most of scientific societies maintained the relationship with chronic patients through some form of telemedicine, reporting a strong positive opinion about this modality. Finally showed the need to give life a new approach for hospitalizations and outpatient visits through a greater use of telemedicine, educational programs on families and a more decisive role of family pediatricians. Conclusions: Our study highlighted many aspects that can be improved in pediatric care. We think that It will be necessary a new shared strategy to improve the management and continuity of care for pediatric patients, primarily developing a network of collaboration between families, family pediatrician and hospitals and by enhancing the use of new methods of telecommunications

Side effects of anti-TNFa therapy in juvenile idiopathic arthritis

Aim of the study: To report adverse events registered in our population affected by JIA and treated with anti-TNFαblockers. Methods: Ninety-five patients were enrolled to be treated with Etanercept, median age 14 years (range 4-34); median duration of therapy 12 months (range 1-40). 19 patients were als treated with MTX (median dose 12.5 mg/week).Fifty-six patients were enrolled to be treated with Infliximab associated with MTX (median dose of MTX 8.8mg/week),median age 23.2 years (range 7.8-34.9); median duration of therapy 20.1 months (range 1.4-60.4). All adverse events were divided in definitely, probably and possibly related to the biologic agent. Results: Side effects definitely related to Infliximab were the reactions to infusions and the Anti-dsDNA positivity. Side effects definitely related to Etanercept were severe headache and thrombocytopenia. Side effects probably correlated to both the biological agents were behavioural modifications and pain amplification syndrome. Probably correlated to the treatment with Etanercept was the onset of Crohn’s disease in 3 patients. Possibly correlated to the biological agents were the new onset or flare-up of Chronic Iridocyclitis and single cases of thyroideal cancer, hypoglossal nerve paralysis and a severe Cytomegalovirus pulmonary infection. No case of tuberculosis infection was registered during this study. Conclusions: Treatment with a TNFαantagonist seems to be associated with various adverse events. Some of them,like onset of Crohn’s disease, behavioural modifications are unusual and others, like pain amplification syndrome were never described before. Children and young adults affected by JIA should be monitored very carefully so as to limit as much as possible the risk of serious side effects on anti-TNFα therapy

Multicentre Italian study of SARS-CoV-2 infection in children and adolescents, preliminary data as at 10 April 2020

Data on features of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in children and adolescents are scarce. We report preliminary results of an Italian multicentre study comprising 168 laboratory-confirmed paediatric cases (median: 2.3 years, range: 1 day\u201317.7 years, 55.9% males), of which 67.9% were hospitalised and 19.6% had comorbidities. Fever was the most common symptom, gastrointestinal manifestations were frequent; two children required intensive care, five had seizures, 49 received experimental treatments and all recovered