ARTRITA JUVENILĂ IDIOPATICĂ – FACTORI DE RISC ŞI FORME CLINICE STUDIU CAZUISTIC

Obiectivul este de a stabili factorii de risc şi prevalenţa formelor clinice de AJI cu evidenţierea difi cultăţilor de încadrare la debut şi în evoluţie luând în studiu un lot semnifi cativ de bolnavi (169 cazuri). Formele clinice conturate (în ordinea frecvenţei) au fost: oligoarticulară (44, 17%), poliarticulară cu FR negativ (33,13), entezită (11,24%), sistemică (5,91%), poliarticulară cu FR pozitiv (2,95%) şi psoriazică (2,36%). Analiza individualizată a cazuisticii a scos în evidenţă durata de la debutul real al bolii până la diagnostic, cât şi factorii de risc pentru AJI (în ordinea frecvenţei): traumatici (9,46%), antecedente familiale pozitive (5,32%) şi infecţioşi (2,36%). De asemenea, a fost evidenţiată posibilitatea transformării unei forme clinice în alta chiar sub tratament adecvat

Opportunistic infections in immunosuppressed patients with juvenile idiopathic arthritis: analysis by the Pharmachild Safety Adjudication Committee

Background To derive a list of opportunistic infections (OI) through the analysis of the juvenile idiopathic arthritis (JIA) patients in the Pharmachild registry by an independent Safety Adjudication Committee (SAC). Methods The SAC (3 pediatric rheumatologists and 2 pediatric infectious disease specialists) elaborated and approved by consensus a provisional list of OI for use in JIA. Through a 5 step-procedure, all the severe and serious infections, classified as per MedDRA dictionary and retrieved in the Pharmachild registry, were evaluated by the SAC by answering six questions and adjudicated with the agreement of 3/5 specialists. A final evidence-based list of OI resulted by matching the adjudicated infections with the provisional list of OI. Results A total of 772 infectious events in 572 eligible patients, of which 335 serious/severe/very severe non-OI and 437 OI (any intensity/severity), according to the provisional list, were retrieved. Six hundred eighty-two of 772 (88.3%) were adjudicated as infections, of them 603/682 (88.4%) as common and 119/682 (17.4%) as OI by the SAC. Matching these 119 opportunistic events with the provisional list, 106 were confirmed by the SAC as OI, and among them infections by herpes viruses were the most frequent (68%), followed by tuberculosis (27.4%). The remaining events were divided in the groups of non-OI and possible/patient and/or pathogen-related OI. Conclusions We found a significant number of OI in JIA patients on immunosuppressive therapy. The proposed list of OI, created by consensus and validated in the Pharmachild cohort, could facilitate comparison among future pharmacovigilance studies

Vaccine breakthrough hypoxemic COVID-19 pneumonia in patients with auto-Abs neutralizing type I IFNs

Life-threatening `breakthrough' cases of critical COVID-19 are attributed to poor or waning antibody response to the SARS- CoV-2 vaccine in individuals already at risk. Pre-existing autoantibodies (auto-Abs) neutralizing type I IFNs underlie at least 15% of critical COVID-19 pneumonia cases in unvaccinated individuals; however, their contribution to hypoxemic breakthrough cases in vaccinated people remains unknown. Here, we studied a cohort of 48 individuals ( age 20-86 years) who received 2 doses of an mRNA vaccine and developed a breakthrough infection with hypoxemic COVID-19 pneumonia 2 weeks to 4 months later. Antibody levels to the vaccine, neutralization of the virus, and auto- Abs to type I IFNs were measured in the plasma. Forty-two individuals had no known deficiency of B cell immunity and a normal antibody response to the vaccine. Among them, ten (24%) had auto-Abs neutralizing type I IFNs (aged 43-86 years). Eight of these ten patients had auto-Abs neutralizing both IFN-a2 and IFN-., while two neutralized IFN-omega only. No patient neutralized IFN-ss. Seven neutralized 10 ng/mL of type I IFNs, and three 100 pg/mL only. Seven patients neutralized SARS-CoV-2 D614G and the Delta variant (B.1.617.2) efficiently, while one patient neutralized Delta slightly less efficiently. Two of the three patients neutralizing only 100 pg/mL of type I IFNs neutralized both D61G and Delta less efficiently. Despite two mRNA vaccine inoculations and the presence of circulating antibodies capable of neutralizing SARS-CoV-2, auto-Abs neutralizing type I IFNs may underlie a significant proportion of hypoxemic COVID-19 pneumonia cases, highlighting the importance of this particularly vulnerable population

TERAPIA DURERII CRONICE DIN ARTRITA JUVENILĂ PRIN MIJLOACE COMPLEMENTARE ŞI ALTERNATIVE

În ultimii ani, utilizarea unor metode complementare şi alternative în pediatrie a crescut considerabil, în special pentru afecţiunile cronice precum artrita juvenilă idiopatică, în care durerea poate fi o problemă semnifi cativă. Interesul crescut în abordările medicinei complementare şi alternative pentru simptomele durerii la copii şi adolescenţi, precum şi la populaţia adultă, a concentrat atenţia asupra problemelor de siguranţă şi efi cacitate ale acestor metode. Urmărirea unor intervenţii sigure, efi ciente şi rentabile pentru durerea cronică la copiii care suferă de artrită juvenilă, folosite în locul sau împreună cu abordările medicale convenţionale, este un obiectiv valoros, care ar trebui să fie abordat cu cea mai mare rigoare ştiinţifi că. Trebuie să gândim creativ şi diferit în scopul de a educa cadrele medicale, precum şi publicul larg, pentru a le schimba atitudinea

TERAPIA CU AGENŢI BIOLOGICI ÎN SPONDILARTRITA ANKILOZANTĂ CU DEBUT JUVENIL

Spondilartrita anchilozantă este o boalǎ infl amatorie mediată imun, care include artrita axială şi periferică, infl amaţia locului unde tendoanele şi capsulele articulare se inseră pe os, precum şi degenerarea articulaţiilor sacro-iliace şi ale coloanei vertebrale, care conduce la fuziuni progresive ale vertebrelor. Introducerea în terapie a moleculelor imunomodulatoare, cu ţintă pe interleukine, cum ar fi pe factorul de necroză tumorală alfa, a fost considerată ca un progres major în tratamentul formelor severe de spondiliartrite ankilozante. Acest caz ilustrează evoluţia particulară a manifestărilor clinice în corelaţie cu traumatismul articular, infecţia digestivă şi consecinţele devastatoare ale spondilitei ankilozante active HLA-B27 pozitivă cu debut juvenil

Increased incidence of inflammatory bowel disease on etanercept in juvenile idiopathic arthritis regardless of concomitant methotrexate use

To describe risk factors for IBD development in a cohort of children with JIA

Increased incidence of inflammatory bowel disease on etanercept in juvenile idiopathic arthritis regardless of concomitant methotrexate use

Objectives: To describe risk factors for inflammatory bowel disease (IBD) development in a cohort of children with juvenile idiopathic arthritis (JIA). Methods: JIA patients who developed IBD were identified from the international Pharmachild register. Characteristics were compared between IBD and non-IBD patients and predictors of IBD were determined using multivariable logistic regression analysis. Incidence rates of IBD events on different disease-modifying anti-rheumatic drugs (DMARDs) were calculated, differences between therapies were expressed as relative risks (RR). Results: Out of 8,942 patients, 48 (0.05%) developed IBD. These were more often male (47.9% vs 32.0%) and HLA-B27 positive (38.2% vs 21.0%) and older at JIA onset (median 8.94 vs 5.33 years) than patients without IBD development. They also had more often a family history of autoimmune disease (42.6% vs 24.4%) and enthesitis-related arthritis (ERA) (39.6% vs 10.8%). The strongest predictors of IBD on multivariable analysis were ERA (OR: 3.68, 95% CI: 1.41-9.40) and a family history of autoimmune disease (OR: 2.27, 95% CI: 1.12-4.54). Compared with methotrexate monotherapy, the incidence of IBD on etanercept monotherapy (RR: 7.69, 95% CI: 1.99-29.74), etanercept with methotrexate (RR: 5.70, 95% CI: 1.42-22.77) and infliximab (RR: 7.61, 95% CI: 1.27-45.57) therapy was significantly higher. Incidence on adalimumab was not significantly different (RR: 1.45, 95% CI: 0.15-13.89). Conclusion: IBD in JIA was associated with ERA and a family history of autoimmune disease. An increased IBD incidence was observed for etanercept therapy regardless of concomitant methotrexate use