Long term use of interleukin-1 inhibitors reduce flare activity in patients with fibrodysplasia ossificans progressiva.

OBJECTIVES: Fibrodysplasia ossificans progressiva (FOP) is one of the most catastrophic forms of genetic heterotopic ossification (HO). FOP is characterized by severe, progressive inflammatory flare-ups, that often lead to HO. The flare-ups are associated with increased inflammatory cytokine production, suggesting auto-inflammatory features driven by interleukin-1ß (IL-1ß). This study describes the short- and long-term responses of FOP patients to anti-IL-1 therapy. METHODS: Previously, we reported that a patient with FOP treated with anti-IL-1 agents showed dramatically lower rates of flare-ups, improved flare-up symptoms, decreased use of glucocorticoids, and apparently decreased size of residual lesions. Plasma analyses also showed marked elevation in IL-1ß levels during a FOP flare, further supporting a role of IL-1ß in the pathogenesis of FOP flares. Here, we report results from long-term therapy with IL-1 inhibitors in that patient, and describe 3 additional patients, from two medical centers. RESULTS: All 4 patients showed persistent improvement in flare activity during treatment with IL-1 inhibitors, with minimal formation of new HO sites. Two patients who stopped therapy experienced resurgence of flare activity that was re-suppressed upon re-initiation. These patients had IL-1ß levels comparable to those in IL-1ß-driven diseases. Child Health Assessment Questionnaires confirmed extensive subjective improvements in the pain and general health visual analogue scales. CONCLUSION: This case series demonstrates significant benefits from IL-1 inhibitors for reducing flare activity and improving the general health of patients with FOP. These data provide strong support for additional studies to better understand the function of IL-1 inhibition, primarily in reducing formation new HO. FUNDING: RH received support from the International FOP Association ACT grant; ECH received support from NIH/NIAMS R01AR073015 and the UCSF Robert Kroc Chair in Connective Tissue and Rheumatic Diseases III.

Influenza vaccine uptake in juvenile idiopathic arthritis: a multi-centre cross-sectional study.

While most countries provide safe and effective influenza vaccines for at-risk groups, influenza vaccine coverage among children with rheumatic diseases remains uncertain. This study investigated influenza vaccination rates in children with juvenile idiopathic arthritis (JIA) during the 2019-2020 season and assessed the knowledge and attitudes of caregivers of children with JIA regarding influenza vaccination. The secondary aims were to identify barriers to vaccination and explore strategies to improve vaccination rates. A multi-centre, cross-sectional anonymous survey was conducted in 7 countries during the 2019-2020 influenza season to assess the uptake history of influenza vaccination. Among 287 participants, only 87 (30%) children with JIA received the influenza vaccine during the 2019-2020 season. Children who were more likely to be vaccinated were those with systemic juvenile idiopathic arthritis (sJIA), a history of previous vaccination and those aware of the vaccination recommendations. Conversely, children who previously experienced adverse vaccine-related events reported the lowest uptake. The primary reason for non-vaccination was lack of awareness about the necessity of influenza vaccination.  Conclusion: Despite variations among countries, the uptake of influenza vaccines remains low in children with JIA. Improving awareness among families about the importance of influenza vaccination may increase vaccination rates in children with rheumatic diseases. What is Known: • Rheumatic children are at increased risk for influenza infection due to immunosuppressive therapy and immune dysregulation. • Influenza vaccine is formally recommended to children with rheumatic diseases. What is New: • This multicentre study showed that influenza vaccine uptake rates remain suboptimal among children with Juvenile Idiopathic Arthritis despite formal recommendations. • Factors like previous experience with vaccination and information provided by medical professionals via different ways play essential roles in increasing vaccination rates and can contribute to improved health outcomes for these vulnerable children.

[THE 12TH CONGRESS OF THE INTERNATIONAL SOCIETY OF SYSTEMIC AUTOINFLAMMATORY DISEASES (ISSAID) HELD ON 15-18 MAY 2023, TORONTO, CANADA].

INTRODUCTION: THE 12TH CONGRESS OF THE INTERNATIONAL SOCIETY OF SYSTEMIC AUTOINFLAMMATORY DISEASES (ISSAID) HELD ON 15-18 MAY 2023, TORONTO, CANADA.

The impact of the COVID-19 pandemic on pediatric rheumatology practice: an international, cross-sectional survey study.

OBJECTIVE: The COVID-19 pandemic has affected patient care in general. We aimed to analyze the impact of the pandemic on pediatric rheumatology practice. METHODS: An online survey including 22 questions was created by the representatives of the Emerging RheumatoloGists and rEsearchers (EMERGE) group of the Pediatric Rheumatology European Society (PReS) on SurveyMonkey. The descriptive analysis of the responses was performed on SurveyMonkey. RESULTS: Overall, 469 pediatric rheumatologists (F/M: 2.9) from 70 countries completed the survey. The practice of drug prescription is not affected by the pandemic, according to 65.3 % of the respondents, while 24.3 % and 16.5 % are prescribing biologic drugs and corticosteroids less often, respectively. Over 40 % of the respondents have seen an increased number of patients with vasculitis or chilblains during the pandemic. One-third of the respondents stated no adjustments in their clinical practice after 2.5 years of COVID-19 pandemic. The rest indicated implementing various changes, with an emphasis on incorporating telemedicine. Telemedicine constitutes ≥10 % of the clinical practice for one-third of the participants. Nonetheless, 35.5 % agree that there are still delays in patient care due to the pandemic. However, most (∼90 %) think our practice is returning to the pre-pandemic routine. CONCLUSION: The findings of our study indicate a significant alteration in pediatric rheumatology practice due to the pandemic. This includes increased caution when prescribing anti-rheumatic drugs, a transition towards telemedicine utilization, delays in routine care, and a rise in COVID-19-related inflammatory conditions. It is imperative to address these aspects in order to improve patient care in pediatric rheumatology.

Gender differences in juvenile systemic sclerosis patients: Results from the international juvenile scleroderma inception cohort.

Objective: To compare organ involvement and disease severity between male and female patients with juvenile onset systemic sclerosis. Methods: Demographics, organ involvement, laboratory evaluation, patient-reported outcomes and physician assessment variables were compared between male and female juvenile onset systemic sclerosis patients enrolled in the prospective international juvenile systemic sclerosis cohort at their baseline visit and after 12 months. Results: One hundred and seventy-five juvenile onset systemic sclerosis patients were evaluated, 142 females and 33 males. Race, age of onset, disease duration, and disease subtypes (70% diffuse cutaneous) were similar between males and females. Active digital ulceration, very low body mass index, and tendon friction rubs were significantly more frequent in males. Physician global assessment of disease severity and digital ulcer activity was significantly higher in males. Composite pulmonary involvement was also more frequent in males, though not statistically significantly. After 12 months, they are the pattern of differences changed female patients had significantly more frequent pulmonary involvement. Conclusion: In this cohort, juvenile onset systemic sclerosis had a more severe course in males at baseline and but the pattern changed after 12 months. Some differences from adult findings persisted, there is no increased signal of pulmonary arterial hypertension or heart failure in male pediatric patients. While monitoring protocols of organ involvement in juvenile onset systemic sclerosis need to be identical for males and females.

Safety and Immunogenicity Following the Second and Third Doses of the BNT162b2 mRNA COVID-19 Vaccine in Adolescents with Juvenile-Onset Autoimmune Inflammatory Rheumatic Diseases: A Prospective Multicentre Study.

BACKGROUND: To explore the long-term safety and dynamics of the immune response induced by the second and third doses of the BNT162b2 mRNA COVID-19 vaccine in adolescents with juvenile-onset autoimmune inflammatory rheumatic diseases (AIIRDs) compared with healthy controls. METHODS: This international prospective study included adolescents with AIIRDs and controls vaccinated with two (AIIRDs n = 124; controls n = 80) or three (AIIRDs n = 64; controls n = 30) doses of the BNT162b2 vaccine, evaluated for vaccine side-effects, disease activity, COVID-19 breakthrough infection rates and severity, and anti-spike S1/S2 IgG antibody titers in a sample from both groups. RESULTS: The vaccination safety profile was favorable, with most patients reporting mild or no side-effects. The rheumatic disease remained stable at 98% and 100% after the second and third doses, respectively. The two-dose vaccine induced comparable seropositivity rates among patients (91%) and controls (100%), (p = 0.55), which declined within 6 months to 87% and 100%, respectively (p = 0.3) and increased to 100% in both groups after the third vaccine dose. The overall post-vaccination COVID-19 infection rate was comparable between patients and controls, 47.6% (n = 59) and 35% (n = 28), respectively; p = 0.5278, with most infections occurring during the Omicron surge. In relation to the last vaccination, time-to-COVID-19 infection was similar between patients and controls, at a median of 5.5 vs. 5.2 months, respectively (log-rank p = 0.1555). CONCLUSION: The safety profile of three doses of the BNT162b2 mRNA vaccine was excellent, with adequate humoral response and similar efficacy among patients and controls. These results support the recommendation for vaccinating adolescents with juvenile-onset AIIRDs against COVID-19.

COVID-19-related anxiety trajectories in children, young people and adults with rheumatic diseases.

Objectives: Uncertainty regarding the risk of coronavirus disease 2019 (COVID-19), its complications and the safety of immunosuppressive therapies may drive anxiety among adults and parents of children and young people (CYP) with rheumatic diseases. This study explored trajectories of COVID-related anxiety in adults and parents of CYP with rheumatic diseases. Methods: Adults and parents of CYP participating in the international COVID-19 European Patient Registry were included in the current study if they had enrolled in the 4 weeks following 24 March 2020. COVID-related anxiety scores (0-10) were collected weekly for up to 28 weeks.Group-based trajectory models explored COVID-related anxiety clusters in adult and parent populations, with optimal models chosen based on model fit, parsimony and clinical plausibility. Demographic, clinical and COVID-19 mitigation behaviours were compared between identified clusters using univariable statistics. Results: In 498 parents of CYP and 2640 adults, four common trajectory groups of COVID-related anxiety were identified in each cohort: persistent extreme anxiety (32% and 17%), persistent high anxiety (43% and 41%), improving high anxiety (25% and 32%) and improving moderate anxiety (11% and 10%), respectively. Few characteristics distinguished the clusters in the parent cohort. Higher and more persistent anxiety clusters in the adult cohort were associated with higher levels of respiratory comorbidities, use of immunosuppressive therapies, older age and greater self-isolation. Conclusions: COVID-19-related anxiety in the rheumatic disease community was high and persistent during the COVID-19 pandemic, with four common patterns identified. In the adult cohort, higher COVID-related anxiety was related to perceived risk factors for COVID-19 morbidity and mortality.

Obstacles in Early Diagnosis of Children With Juvenile Idiopathic Arthritis: A Nationwide Israeli Retrospective Study.

OBJECTIVE: Characterization of the stages that patients with juvenile idiopathic arthritis (JIA) pass until they are diagnosed, and analysis of the different causes that lead to a delay in JIA diagnosis in Israel. METHODS: This is a retrospective cohort study conducted in 8 pediatric rheumatology centers in Israel. All patients diagnosed with JIA between October 2017 and October 2019 were included in the study. Demographic, clinical, and data regarding the referring physicians were collected from hospital and community medical charts. RESULTS: Of 207 patients included in the study, 201 cases were analyzed, 71.1% of the population were female. Patients, on average, were evaluated during the diagnostic process by 3.1 different physicians. In most cases, they initially met with a pediatrician in the community setting (61.2%), and later, most commonly referred to a rheumatologist by the community pediatrician (27.9%). The median time until diagnosis was 56.0 days (range: 1.0-2451.0 days). Patients diagnosed with polyarticular and spondyloarthritis/enthesitis-related arthritis (SpA/ERA) JIA subtypes had the longest period until diagnosis (median: 115.5 and 112.0 days, respectively). Younger age correlated with a quicker diagnosis, and females were diagnosed earlier compared to males. Fever at presentation significantly shortened the time to diagnosis (P < 0.01), whereas involvement of the small joints/sacroiliac joints significantly lengthened the time (P < 0.05). CONCLUSION: This is the first nationwide multicenter study that analyzes obstacles in the diagnosis of JIA in Israel. Raising awareness about JIA, especially for patients with SpA/ERA, is crucial in order to avoid delays in diagnosis and treatment.

EULAR/PRES recommendations for vaccination of paediatric patients with autoimmune inflammatory rheumatic diseases: update 2021.

OBJECTIVES: Recent insights supporting the safety of live-attenuated vaccines and novel studies on the immunogenicity of vaccinations in the era of biological disease-modifying antirheumatic drugs in paediatric patients with autoimmune/inflammatory rheumatic diseases (pedAIIRD) necessitated updating the EULAR recommendations. METHODS: Recommendations were developed using the EULAR standard operating procedures. Two international expert committees were formed to update the vaccination recommendations for both paediatric and adult patients with AIIRD. After a systematic literature review, separate recommendations were formulated for paediatric and adult patients. For pedAIIRD, six overarching principles and seven recommendations were formulated and provided with the level of evidence, strength of recommendation and Task Force level of agreement. RESULTS: In general, the National Immunisation Programmes (NIP) should be followed and assessed yearly by the treating specialist. If possible, vaccinations should be administered prior to immunosuppressive drugs, but necessary treatment should never be postponed. Non-live vaccines can be safely given to immunosuppressed pedAIIRD patients. Mainly, seroprotection is preserved in patients receiving vaccinations on immunosuppression, except for high-dose glucocorticoids and B-cell depleting therapies. Live-attenuated vaccines should be avoided in immunosuppressed patients. However, it is safe to administer the measles-mumps-rubella booster and varicella zoster virus vaccine to immunosuppressed patients under specific conditions. In addition to the NIP, the non-live seasonal influenza vaccination should be strongly considered for immunosuppressed pedAIIRD patients. CONCLUSIONS: These recommendations are intended for paediatricians, paediatric rheumatologists, national immunisation agencies, general practitioners, patients and national rheumatology societies to attain safe and effective vaccination and optimal infection prevention in immunocompromised pedAIIRD patients.

Effectiveness of the BNT162b2 mRNA COVID-19 vaccine among adolescents with juvenile-onset inflammatory rheumatic diseases.

OBJECTIVES: The effectiveness of the BNT162b2 mRNA COVID-19 vaccine for adolescents with juvenile-onset inflammatory or immune rheumatic diseases (IRDs) is unknown. Several studies have suggested attenuated immunogenicity in patients with IRD. This study evaluated the effectiveness of the BNT162b2 mRNA COVID-19 vaccine in preventing COVID-19 infection in adolescents with juvenile-onset IRD compared with controls without immune rheumatic disease. METHODS: We used data from Clalit Health Services, the largest health-care organization in Israel, to conduct an observational cohort study from February to December 2021, involving 12-18 year-old adolescents diagnosed with IRD. Study outcomes included documented COVID-19 infection in relation to vaccination status and immunomodulatory therapy. We estimated vaccine effectiveness as one minus the risk ratio. Adolescents aged 12-18 years without immune rheumatic disease served as controls. RESULTS: A total of 1639 adolescents with IRD (juvenile idiopathic arthritis, SLE, or familial Mediterranean fever) were included and compared with 524 471 adolescents in the same age range without IRD. There was no difference in COVID-19 infection rates after the second dose of vaccine between those with IRD and controls (2.1% vs 2.1% respectively, P = 0.99). The estimated vaccine effectiveness for adolescents with IRD was 76.3% after the first dose, 94.8% after the second and 99.2% after the third dose. CONCLUSION: We found that the BNT162b2 mRNA vaccine was similarly effective against COVID-19 infection in adolescents with and without IRD. Immunomodulatory therapy did not affect its effectiveness. These results can encourage adolescents with IRD to get vaccinated against COVID-19.

Approaches to SARS-CoV-2 and other vaccinations in children with a history of multisystem inflammatory syndrome (MIS-C): An international survey.

Background: Following the Coronavirus Disease-19 (COVID-19) pandemic outbreaks, the hyperinflammatory condition termed Multisystem Inflammatory Syndrome in Children (MIS-C) became a healthcare issue worldwide. Since December 2020 the mRNA vaccine against SARS-CoV-2 has become available with a good safety profile. However, evidence regarding safety and vaccination strategies in children with previous MIS-C is still lacking. The aim of our study was to investigate the current approach of international centers to anti-SARS-CoV-2 and other vaccinations in children with a history of MIS-C. Methods: Physicians who care for patients with MIS-C were invited to anonymously complete a 15-question, web-based survey. The survey was open from October 6 to December 31, 2021. Results: A total of 290 replies from 236 centers in 61 countries were collected. Most respondents (86%) were pediatric rheumatologists. The anti-SARS-CoV-2 vaccine was available in 85% of the countries. Sixty-seven centers (28%) in 22 countries already vaccinated MIS-C patients without adverse reactions in most cases (89%). Six reported complications: 2 not specified, 3 mild symptoms and 1 reported a MIS-C-like reaction. Most centers (84%) favored vaccinating MIS-C patients against SARS-CoV-2, after 3-6 months (40%), 6-12 months (52%) or >12 months (8%). The survey revealed broad heterogeneity of responses among healthcare providers within the same country and within the same center. The variable with the greatest impact on the decision not to vaccinate MIS-C patients was the current lack of evidence (51%), followed by patient/parent objection (40%). The most relevant parameters in the vaccination strategy were time from MIS-C episode (78%), immunosuppressive treatment (35%), SARS-CoV-2 serologic status (32%), and MIS-C features (31%). Almost all centers favored continuing regular vaccination with non-live (99%) and live (93%) vaccines; however, with high variability in suggested timelines. Conclusion: To date, the experience of the international pediatric rheumatology community in vaccinating MIS-C patients against SARS-CoV-2 is overall reassuring. However, lack of evidence causes broad heterogeneity in vaccination strategy worldwide.

Measuring the knowledge of juvenile idiopathic arthritis among Israeli paediatricians and paediatric orthopaedic surgeons: what needs to be improved?

OBJECTIVES: Approximately 1 child in 1,000 is affected by juvenile idiopathic arthritis (JIA). Persistent, undiagnosed JIA with high disease activity interferes with daily life and carries a risk of irreversible physical and psychosocial damage. Due to its relative rarity, primary care physicians often do not recognise it. Consequently, diagnosis and referral to paediatric rheumatologists are delayed. We aimed to evaluate the knowledge of Israeli paediatricians and paediatric orthopaedic surgeons regarding the epidemiology, clinical manifestations, laboratory parameters and treatment of JIA. METHODS: An 11-item, online questionnaire regarding JIA was sent to Israeli paediatricians and paediatric orthopaedic surgeons. The questionnaire was completed by 318 paediatricians and 30 paediatric orthopaedic surgeons (total response rate 22.5%). RESULTS: The average score was 67/100 points and the pass rate was 70.1% (set at 60 points). Several factors were associated with better overall scores: paediatric residents compared to senior physicians, exposure to rheumatology during residency, and seeing more patients with JIA in the past 5 years. No significant difference was found between paediatricians and paediatric orthopaedic surgeons. The true incidence of JIA was underestimated by 40% of participants, 30-45% were not familiar with its clinical presentation (age of onset, pain characteristics, chronic uveitis symptoms), and 60% were not familiar with up-to-date treatments. CONCLUSIONS: Paediatricians and paediatric orthopaedic surgeons in Israel have gaps in knowledge regarding JIA. This could result in delayed referral and treatment, which might affect outcomes. The results of this study highlight the need for better education and exposure to a rheumatologist, to improve knowledge and recognition of JIA.

Efficacy, Immunogenicity and Safety of Vaccination in Pediatric Patients With Autoimmune Inflammatory Rheumatic Diseases (pedAIIRD): A Systematic Literature Review for the 2021 Update of the EULAR/PRES Recommendations.

Background: In 2011, the first European League Against Rheumatism (EULAR) vaccination recommendations for pediatric patients with autoimmune inflammatory rheumatic diseases (pedAIIRD) were published. The past decade numerous new studies were performed to assess the safety, efficacy and immunogenicity of vaccinations in pedAIIRD. A systematic literature review (SLR) was therefore performed to serve as the basis for the updated 2021 EULAR/PRES recommendations. Methods: An SLR was performed according to the standard operating procedures for EULAR-endorsed recommendations. Primary outcomes were efficacy, immunogenicity and safety of vaccination in pedAIIRD. The search was performed in Medline, Embase and the Cochrane Library and included studies published from November 2010 until July 2020. Results: The SLR yielded 57 studies which were included for critical appraisal and data extraction. Only 8 studies described the occurrence of vaccine-preventable infections after vaccination (efficacy), none of these studies were powered to assess efficacy. The majority of studies assessed (humoral) immune responses as surrogate endpoint for vaccine efficacy. Studies on non-live vaccines showed that these were safe and in general immunogenic. Biologic disease-modifying antirheumatic drugs (bDMARDs) in general did not significantly reduce seroprotection rates, except for B-cell depleting therapies which severely hampered humoral responses. Four new studies on human papilloma virus vaccination showed that this vaccine was safe and immunogenic in pedAIIRD. Regarding live-attenuated vaccinations, level 1 evidence of the measles mumps rubella (MMR) booster vaccination became available which showed the safety of this booster for patients treated with methotrexate. In addition, level 3 evidence became available that suggested that the MMR and varicella zoster virus (VZV) vaccination for patients on low dose glucocorticosteroids and bDMARDs might be safe as well. Conclusions: The past decade, knowledge on the safety and immunogenicity of (live-attenuated) vaccines in pedAIIRD significantly increased. Data on efficacy (infection prevention) remains scarce. The results from this SLR are the basis for the updated EULAR/PRES vaccination recommendations in pedAIIRD.

Outcomes of SARS-CoV-2 infection among children and young people with pre-existing rheumatic and musculoskeletal diseases.

OBJECTIVES: Some adults with rheumatic and musculoskeletal diseases (RMDs) are at increased risk of COVID-19-related death. Excluding post-COVID-19 multisystem inflammatory syndrome of children, children and young people (CYP) are overall less prone to severe COVID-19 and most experience a mild or asymptomatic course. However, it is unknown if CYP with RMDs are more likely to have more severe COVID-19. This analysis aims to describe outcomes among CYP with underlying RMDs with COVID-19. METHODS: Using the European Alliance of Associations for Rheumatology COVID-19 Registry, the Childhood Arthritis and Rheumatology Research Alliance (CARRA) Registry, and the CARRA-sponsored COVID-19 Global Paediatric Rheumatology Database, we obtained data on CYP with RMDs who reported SARS-CoV-2 infection (presumptive or confirmed). Patient characteristics and illness severity were described, and factors associated with COVID-19 hospitalisation were investigated. RESULTS: 607 CYP with RMDs <19 years old from 25 different countries with SARS-CoV-2 infection were included, the majority with juvenile idiopathic arthritis (JIA; n=378; 62%). Forty-three (7%) patients were hospitalised; three of these patients died. Compared with JIA, diagnosis of systemic lupus erythematosus, mixed connective tissue disease, vasculitis, or other RMD (OR 4.3; 95% CI 1.7 to 11) or autoinflammatory syndrome (OR 3.0; 95% CI 1.1 to 8.6) was associated with hospitalisation, as was obesity (OR 4.0; 95% CI 1.3 to 12). CONCLUSIONS: This is the most significant investigation to date of COVID-19 in CYP with RMDs. It is important to note that the majority of CYP were not hospitalised, although those with severe systemic RMDs and obesity were more likely to be hospitalised.

Safety and immunogenicity of BNT162b2 mRNA COVID-19 vaccine in adolescents with rheumatic diseases treated with immunomodulatory medications.

OBJECTIVES: Adolescents with juvenile-onset autoimmune inflammatory rheumatic diseases (AIIRDs) could be at risk for disease flare secondary to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection or to withholding anti-inflammatory therapy. While vaccination can protect against coronavirus disease 2019 (COVID-19), safety and immunogenicity data regarding anti-SARS-CoV-2 vaccines among adolescents with AIIRDs are limited. This international, prospective, multicentre study evaluated the safety and immunogenicity of the BNT162b2 anti-SARS-CoV-2 vaccine among adolescents and young adults with juvenile-onset AIIRDs, 80% of whom are on chronic immunomodulatory therapy. METHODS: Vaccine side effects, disease activity and short-term efficacy were evaluated after 3 months in 91 patients. Anti-spike S1/S2 IgG antibody levels were evaluated in 37 patients and 22 controls 2-9 weeks after the second dose. RESULTS: A total of 91 patients and 40 healthy controls were included. The safety profile was good, with 96.7% (n = 88) of patients reporting mild or no side effects and no change in disease activity. However, three patients had transient acute symptoms: two following the first vaccination (renal failure and pulmonary haemorrhage) and one following the second dose (mild lupus flare vs viral infection). The seropositivity rate was 97.3% in the AIIRD group compared with 100% among controls. However, anti-S1/S2 antibody titres were significantly lower in the AIIRD group compared with controls [242 (s.d. 136.4) vs 387.8 (57.3) BAU/ml, respectively; P < 0.0001]. No cases of COVID-19 were documented during the 3 month follow-up. CONCLUSION: Vaccination of juvenile-onset AIIRD patients demonstrated good short-term safety and efficacy and a high seropositivity rate but lower anti-S1/S2 antibody titres compared with healthy controls. These results should encourage vaccination of adolescents with juvenile-onset AIIRDs, even while on immunomodulation.

The impact of the Eurofever criteria and the new InFevers MEFV classification in real life: Results from a large international FMF cohort.

INTRODUCTION: New Eurofever/PRINTO classification criteria (EPCC) for Familial Mediterranean Fever (FMF) and other recurrent fevers have been recently developed, together with the classification of the pathogenicity of MEFV variants. OBJECTIVES: To evaluate the impact in real life of both the EPCC and INSAID pathogenicity classification of MEFV variants in the large international Eurofever FMF cohort. METHODS: Baseline demographic, genetic and clinical data of FMF patients included in the Eurofever registry were evaluated. The EPCC and the 2018 INSAID classification for MEFV variants were applied in all eligible FMF patients. RESULTS: Since November 2009, clinical information was available for 1012 FMF (532 males/480 females, 827 children/185 adults) from 119 centres. Complete data were available for 887 patients in whom 623 (70.2%) satisfied EPCC (EPCC+), while 264 (29.8%) did not (EPCC-). The majority of the EPCC- patients (172, 65.1%) displayed negative or non-informative genetics (monoallelic or biallelic benign variants, monoallelic variant of unknown significance). At baseline, colchicine was used in most of EPCC+ patients (88%) and in a lower percentage of EPCC- patients (69%, p < 0.0001), who were treated in a higher proportion with steroid or NSAID on demand (p = 0.003 and 0.008, respectively). Four percent of patients received Anti-IL-1 treatment. CONCLUSIONS: The combination of EPCC and the 2018 INSAID classification of MEFV variants is able to identify two distinct groups of patients, which differ in clinical characteristics, therapeutic approach and response to treatment. EPCC+ patients displayed the typical features of FMF, while EPCC- patients had a more variable phenotype with a lower percentage of response to colchicine.

Magnetic resonance findings may aid in diagnosis of protracted febrile myalgia syndrome: a retrospective, multicenter study.

BACKGROUND: Protracted febrile myalgia syndrome (PFMS) is a rare complication of Familial Mediterranean fever (FMF). The diagnosis is based on clinical symptoms and is often challenging, especially when PFMS is the initial manifestation of FMF. The aim of this report was to describe the magnetic resonance imaging (MRI) findings in pediatric patients with PFMS. RESULTS: There were three girls and two boys ranging in age from 6 months to 16 years, all of Mediterranean ancestry. Three had high-grade fever, and all had elevated inflammatory markers. MRI of the extremities yielded findings suggestive of myositis, which together with the clinical picture, normal CPK levels, and supporting family history of FMF, suggested the diagnosis of PFMS. Out of most common MEFV mutations tested, one patient was homozygous for M694V mutation, three were heterozygous for M694V mutation, and one was compound heterozygous for the M694V and V726A mutations. CONCLUSIONS: MRI may serve as an auxiliary diagnostic tool in PFMS.