Efficacy of adalimumab in young children with juvenile idiopathic arthritis and chronic uveitis: A case series

Background: Juvenile idiopathic arthritis is a relatively common chronic disease of childhood, and is associated with persistent morbidity and extra-articular complications, one of the most common being uveitis. The introduction of biologic therapies, particularly those blocking the inflammatory mediator tumor necrosis factor-α, provided a new treatment option for juvenile idiopathic arthritis patients who were refractory to standard therapy such as non-steroidal anti-inflammatory drugs, corticosteroids and/or methotrexate. Case presentations. The first case was a 2-year-old girl with juvenile idiopathic arthritis and uveitis who failed to respond to treatment with anti-inflammatories, low-dose corticosteroids and methotrexate, and had growth retardation. Adalimumab 24 mg/m2 every 2 weeks and prednisone 0.5 mg/kg/day were added to methotrexate therapy; steroid tapering and withdrawal started after 1 month. After 2 months the patient showed good control of articular and ocular manifestations, and she remained in remission for 1 year, receiving adalimumab and methotrexate with no side effects, and showing significant improvement in growth. Case 2 was a 9-year-old boy with an 8-year history of juvenile idiopathic arthritis and uveitis that initially responded to infliximab, but relapse occurred after 2 years off therapy. After switching to adalimumab, and adjusting doses of both adalimumab and methotrexate based on body surface area, the patient showed good response and corticosteroids were tapered and withdrawn after 6 months; the patient remained in remission taking adalimumab and methotrexate. The final case was a 5-year-old girl with juvenile idiopathic arthritis for whom adalimumab was added to methotrexate therapy after three flares of uveitis. The patient had two subsequent episodes of uveitis that responded well to local therapy, but was then free of both juvenile idiopathic arthritis and uveitis symptoms, allowing methotrexate and then adalimumab to be stopped; the patient remained in drug-free remission. Conclusion: This report includes the first published case of the use of adalimumab in a child aged <3 years. Our clinical experience further supports the use of biologic therapy for the management of juvenile idiopathic arthritis and uveitis in children as young as two years of age. © 2014 La Torre et al.; licensee BioMed Central Ltd

Non-specific oral and cutaneous manifestations of Coronavirus Disease 2019 in children

Coronavirus Disease 2019 (COVID-19) seems to affect children only marginally, as a result, there is less knowledge of its manifestations in childhood. The purpose of this retrospective cross-sectional study was to investigate the oral and cutaneous manifestations in children affected by COVID-19. All the medical records of children with COVID-19 admitted to the Pediatric Clinic- ASST Spedali Civili of Brescia from March to April 2020 were reviewed. The following data were recorded: age, temperature, clinical presentation, oral mucosa lesions, taste alteration and cutaneous lesions. The medical records of twenty-seven pediatric patients (mean age 4,2 years + 1,7) were analyzed. The clinical presentation of the disease mainly included elevated body temperature and cough. The following oral lesions were recorded: oral pseudomembranous candidiasis (7.4 %), geographic tongue (3.7%), coated tongue (7.4 %) and hyperaemic pharynx (37 %). Taste alteration was reported by 3 patients. Six patients presented cutaneous flat papular lesions. As for our paediatric sample, COVID-19 resulted to be associated with non-specific oral and cutaneous manifestations

Stability of unfrozen whole blood DNA for remote genotypic analysis of HIV-1 coreceptor tropism

Maraviroc is an HIV-1 coreceptor antagonist that has shown good efficacy and tolerability in treatment-naive and treatment-experienced patients harboring CCR5-tropic virus. The use of Maraviroc in treatment simplification in patients with suppressed plasma HIV-1 RNA requires analysis of HIV-1 DNA. Coreceptor tropism testing is often performed remotely at reference laboratories. In this study paired whole blood stored at + 4 °C and at-20°C were compared as a source for genotypic coreceptor tropism testing

Condylar asymmetry in patients with juvenile idiopathic arthritis: Could it be a sign of a possible temporomandibular joints involvement?

OBJECTIVES: The aim of the study was to evaluate the condylar and ramal asymmetry of the mandible in patients with juvenile idiopathic arthritis (JIA) using orthopantomographies (OPTs). METHODS: A total of 30 JIA patients with confirmed diagnosis of JIA and a routine OPT, seeking for orthodontic therapy, free of specific symptoms of temporomandibular joint involvement, and 30 normal matched subjects with OPT were comprised in the study. The method of Habets et al. was used to compare the condyles and rami in OPT. The significance of between-group differences were assessed using Mann-Whitney test. RESULTS: The results showed a high significant difference in the range of asymmetry of the condyle, being the patient group highly asymmetrical (P < 0.0001). No differences were found in the range of asymmetry of the ramus between groups (P = 0.47). The intra-group comparison between males and females showed a difference in the patient group (P = 0.04), being the females more asymmetric. CONCLUSIONS: Knowing that the temporomandibular joint (TMJ) is highly susceptible to inflammatory alterations during growth, even in absence of symptomatology, and being the OPT a cost-benefit favorable imaging tool widespread in the dental field, the latter could be used as a first screening examination in JIA patients to calculate the condylar asymmetry index. The use of this screening tool will help the physicians in addressing the patients that should undergo a more detailed TMJ imaging to early detect TMJ abnormalities and to early set up a targeted therapy of the related cranial growth alteration

Longitudinal analysis of HIV-1 coreceptor tropism by single and triplicate HIV-1 RNA and DNA sequencing in patients undergoing successful first-line antiretroviral therapy

Objectives: Maraviroc has been shown to be effective in patients harbouring CCR5-tropic HIV-1. While this CCR5 antagonist has initially been used in salvage therapy, its excellent safety profile makes it ideal for antiretroviral treatment simplification strategies in patients with suppressed plasma viraemia. The aim of this study was to compare HIV-1 tropism as detected in baseline plasma RNA and peripheral blood mononuclear cell (PBMC) DNA prior to first-line therapy and to analyse tropism evolution while on successful treatment. Methods: HIV-1 tropism was determined using triplicate genotypic testing combined with geno2pheno[coreceptor] analysis at a 10% false positive rate in 42 patients. Paired pre-treatment plasma RNA and PBMC DNA and two subsequent PBMC DNA samples (the first obtained after reaching undetectable plasma HIV-1 RNA and the second after at least 2 years of suppression of plasma viraemia) were evaluated. Results: Coreceptor tropism was completely concordant in paired pre-treatment RNA and DNA, with 26.2% of HIV-1 sequences predicted to be non-CCR5-tropic. During follow-up, coreceptor tropism switches were detected in 4 (9.5%) patients without any preferential direction. Although false positive rate discrepancies within triplicates were common, the rate of discordance of coreceptor tropism assignment among triplicate results in this mostly CCR5-tropic dataset was only 2.1%, questioning the added value of triplicate testing compared with single testing. Conclusions: HIV-1 coreceptor tropism changes during virologically successful first-line treatment are infrequent. HIV-1 DNA analysis may thus support the choice of a CCR5 antagonist in treatment switch strategies; however, maraviroc treatment outcome data are required to confirm this option

Switch to maraviroc with darunavir/r, both QD, in patients with suppressed HIV-1 was well tolerated but virologically inferior to standard antiretroviral therapy: 48-Week results of a randomized trial

Objectives Primary study outcome was absence of treatment failure (virological failure, VF, or treatment interruption) per protocol at week 48. Methods Patients on 3-drug ART with stable HIV-1 RNA &lt;50 copies/mL and CCR5-tropic virus were randomized 1:1 to maraviroc with darunavir/ritonavir qd (study arm) or continue current ART (continuation arm).Results In June 2015, 115 patients were evaluable for the primary outcome (56 study, 59 continuation arm). The study was discontinued due to excess of VF in the study arm (7 cases, 12.5%, vs 0 in the continuation arm, p = 0.005). The proportion free of treatment failure was 73.2% in the study and 59.3% in the continuation arm. Two participants in the study and 10 in the continuation arm discontinued therapy due to adverse events (p = 0.030). At VF, no emergent drug resistance was detected. Co-receptor tropism switched to non-R5 in one patient. Patients with VF reported lower adherence and had lower plasma drug levels. Femoral bone mineral density was significantly improved in the study arm. Conclusion Switching to maraviroc with darunavir/ritonavir qd in virologically suppressed patients was associated with improved tolerability but was virologically inferior to 3-drug therap

Factors Associated With Severe Gastrointestinal Diagnoses in Children With SARS-CoV-2 Infection or Multisystem Inflammatory Syndrome

Importance Severe gastrointestinal (GI) manifestations have been sporadically reported in children with COVID-19; however, their frequency and clinical outcome are unknown. Objective To describe the clinical, radiological, and histopathologic characteristics of children with COVID-19 presenting with severe GI manifestations to identify factors associated with a severe outcome. Design, Setting, and Participants A multicenter retrospective cohort study (February 25, 2020, to January 20, 2021) enrolled inpatient and outpatient children (aged &lt;18 years) with acute SARS-CoV-2 infection, confirmed by positive real-time reverse-transcriptase–polymerase chain reaction on nasopharyngeal swab or fulfilling the US Centers for Disease Control and Prevention criteria for multisystem inflammatory syndrome in children (MIS-C). The study was conducted by pediatricians working in primary care or hospitals in Italy participating in the COVID-19 Registry of the Italian Society of Pediatric Infectious Diseases. Main Outcomes and Measures The occurrence of severe GI manifestations, defined by a medical and/or radiological diagnosis of acute abdomen, appendicitis (complicated or not by perforation and/or peritonitis), intussusception, pancreatitis, abdominal fluid collection, and diffuse adenomesenteritis requiring surgical consultation, occurring during or within 4 to 6 weeks after infection with SARS-CoV-2 infection. Logistic regression was used to estimate odds ratios (ORs) with 95% CIs of factors potentially associated with severe outcomes. Results Overall, 685 children (386 boys [56.4%]; median age, 7.3 [IQR, 1.6-12.4] years) were included. Of these children, 628 (91.7%) were diagnosed with acute SARS-CoV-2 infection and 57 (8.3%) with MIS-C. The presence of GI symptoms was associated with a higher chance of hospitalization (OR, 2.64; 95% CI, 1.89-3.69) and intensive care unit admission (OR, 3.90; 95% CI, 1.98–7.68). Overall, 65 children (9.5%) showed severe GI involvement, including disseminated adenomesenteritis (39.6%), appendicitis (33.5%), abdominal fluid collection (21.3%), pancreatitis (6.9%), or intussusception (4.6%). Twenty-seven of these 65 children (41.5%) underwent surgery. Severe GI manifestations were associated with the child’s age (5-10 years: OR, 8.33; 95% CI, 2.62-26.5; &gt;10 years: OR, 6.37; 95% CI, 2.12-19.1, compared with preschool-age), abdominal pain (adjusted OR [aOR], 34.5; 95% CI, 10.1-118), lymphopenia (aOR, 8.93; 95% CI, 3.03-26.3), or MIS-C (aOR, 6.28; 95% CI, 1.92-20.5). Diarrhea was associated with a higher chance of adenomesenteritis (aOR, 3.13; 95% CI, 1.08-9.12) or abdominal fluid collection (aOR, 3.22; 95% CI, 1.03-10.0). Conclusions and Relevance In this multicenter cohort study of Italian children with SARS-CoV-2 infection or MIS-C, 9.5% of the children had severe GI involvement, frequently associated with MIS-C. These findings suggest that prompt identification may improve the management of serious complications