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Introduction: Familial Mediterranean fever (FMF) is the most frequent monogenic auto-inflammatory disease worldwide responsible for episodes of fever, serositis and musculoskeletal symptoms. Inflammatory attacks are responsible for sedentary behavior and FMF patients may be at increased cardiovascular risk. Cardiorespiratory Fitness (CRF) and physical capacities during adolescence are associated with cardiovascular mortality in adulthood. In this study, we aimed to describe the physical fitness of FMF adolescents., Methods: A monocentric retrospective study at the Versailles Hospital between January 2020 and June 2023. All FMF patients over 14-year-old who had completed a routine physical test were included. Clinical and physical data including results of the 6-minute walking test, timed unipedal stance test, Ruffier-Dickson index, 30-seconds chair-stand test and sit-and-reach test were extracted from medical records. Results were compared with previously published normative reference values and criterion-referenced standards for healthy subjects., Results: Eighteen FMF patients (12 girls, 6 boys) were included. The median age was 16 years old [14-18]. Clinical history included joint symptoms (n = 11), chest pleuritis (n = 8), and leg pain (n = 11). Estimated VO2max was below the recommended thresholds in 13 patients, which predicts cardiovascular risk. Cardiovascular adaptation was poor in 11 patients. Low VO2max was associated with CRP > 5 mg/l on test day and history of joint symptoms., Conclusion: FMF patients displayed altered physical capacities compared to normative values of healthy subjects. History of musculoskeletal pain, systemic inflammation and sedentary behavior may participate in impaired physical abilities and promote cardiovascular diseases in adulthood. Specific exercise programs could benefit patients for disease control and cardiovascular risk reduction., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: Teledermatology has been widely deployed over the past decade in France, becoming an indispensable tool in daily practice. Pediatric dermatology is a subspecialty of dermatology limited to a small number of specialists. In 2013, the Argenteuil Hospital developed a structured store-and-forward (SAF) service that is particularly well-suited for the field of pediatric dermatology. We report on our 10-year experience using the SAF approach in pediatric dermatology, focusing on the acceptability and efficiency of the service., Method: All pediatric (<18 years) cases submitted to the SAF service from 2013 to 2022 were analyzed to evaluate SAF performance (refusals, response times, and information quality); patient demographics; pathologies (diagnostic certainty, types); and management., Results: A total of 922 cases, from eight centers (six hospitals, two penitentiaries, and one health center) and 52 physicians, were analyzed. An increase in requests was noted over the years. No families refused to use the service. In 83 % and 94 % of cases, the quality of the photos and information was considered good or very good, respectively. The median response time was 1.5 h. The mean age of the children was 5 years (sex ratio: 1:1), with 26 % of cases involving newborns (<1 month). The median disease duration was 6 days (48 % <5 days). In 65 % of cases, the diagnosis was "certain," whereas in 34 % of cases a "diagnostic hypothesis" was made. Examinations were recommended in 35 % of cases and treatment was proposed in 62 % of cases. Dermatological follow-up was proposed in 32 % of cases., Conclusion: Our 10-year review of the SAF network showed that this pediatric teledermatology service has been accepted by parents and physicians. The information transmitted was of high quality, although additional clarification requests were sometimes required. The service enabled rapid responses in the majority of cases, including a wide variety of situations: one-quarter of cases involved newborns and 48 % of cases involved recently developed dermatoses (<5 days) requiring urgent management. This pediatric dermatology SAF-based tele-expertise service was therefore shown to be efficient and very well accepted, and is currently being deployed among private practitioners., Competing Interests: Declaration of competing interest None to declare, (Copyright © 2024. Published by Elsevier Masson SAS.)

Objectives: A new form of systemic juvenile idiopathic arthritis (SJIA) with associated lung disease (SJIA-LD) has recently been described. Multiple lines of treatment have failed to yield satisfactory results for this disorder. JAK inhibitors (JAKis) have recently been approved for the treatment of JIA, but clinical evidence of their efficacy in SJIA-LD is still weak. Here we describe and assess real-life experience of SJIA-LD treatment with JAKis in France., Methods: This is a retrospective study based on information gathered from patients' medical records. Systemic and pulmonary symptoms, biological data including CRP, ferritin, IL18, chest CT scan, and functional respiratory tests were collected., Results: Eight patients with SJIA-LD were identified in French pediatric rheumatology centers. All received at least one JAKi (baricitinib, ruxolitinib, and/or tofacitinib). Complete disease control was obtained in four patients. Steroids were tapered in four patients and stopped in two. Three patients presented an episode of MAS shortly after anti-IL1s were stopped when JAKis were introduced. Two patients had other serious side effects (viral reactivation-EBV, BK virus, cytopenia). At last follow-up, one patient had died from severe MAS, two patients had undergone hematopoietic stem cell transplantation, four were in complete response (two of them free of steroids), and one in partial response with JAKis. Lung response to JAKi was not clearly linked to disease duration., Conclusion: JAKis offer another therapeutic option for patients with SJIA-LD. However, the risk of MAS argues for caution about stopping anti-IL1s when introducing JAKis. Tolerance needs careful monitoring in larger studies., (© The Author(s) 2024. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Background: Transitioning from pediatric to adult care is a critical step for individuals with autoinflammatory diseases, requiring effective programs to ensure continuity of care and disease management. Despite various recommendations, the effectiveness of transition programs, particularly in monogenic autoinflammatory diseases, remains understudied., Methods: A single-center medical records review study was conducted at the French National Reference Center for Adult Autoinflammatory Diseases in Tenon Hospital from 2017 to 2023. All patients who had consulted for the first time between the ages of 15 and 30 years and had received care for an autoinflammatory disease during childhood were included. The patients were classified according to whether they had undergone a transition, defined as either no transition, simple transition (referral letter), or joint transition (pediatrician and adult physician consultation)., Results: One hundred eleven patients (median age, 18 years) were included. Patients who consulted without transition started adult follow-up and were followed up less regularly than those who underwent the transition process ( p < 0.001 and p = 0.028). In patients with familial Mediterranean fever, the absence of a formal transition was associated with poorer disease control at baseline ( p = 0.019). The type of transition did not impact disease control during follow-up., Conclusions: Participation in a transition program is associated with earlier and more regular follow-up in adulthood. Although transition type did not significantly impact disease control during follow-up in familial Mediterranean fever, the potential benefit of joint consultation extends beyond consultation frequency and disease outcomes, encompassing patient perspectives and self-management abilities. This study highlights the significance of collaborative transition programs in AIDs., Competing Interests: The authors declare no conflict of interest., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Several studies reported that Familial Mediterranean Fever (FMF) diagnosis may be missed or delayed even in countries with a high FMF prevalence. Our aim was to study on a large cohort of European FMF patients the frequency and associated factors of diagnosis delay. Clinical data were extracted from the Juvenile Inflammatory Rheumatism (JIR)-cohort. All FMF patients fulfilled Livneh Criteria and had been sequenced for MEFV exon 10. FMF-diagnostic delay (d-FMF) was defined as the duration between the onset of the symptoms and the diagnosis of more than 10 years. 960 FMF patients were enrolled: delayed diagnosis (d-FMF) was noted in 200 patients (20%). d-FMF patients were significantly older compared to non d-FMF with a median age of 46.4 years old vs. 15.5 (p < 0.0001). Women displayed more d-FMF compared to men (56 vs. 47%, p = 0.03). Clinical presentation during attacks was not statistically significant except for erysipelas-like erythema, which was higher among d-FMF patients (33 vs. 22%, p = 0.0003). The presence of one or two pathogenic MEFV mutation was not different between patients. Compared to other FMF, d-FMF patients displayed significantly more AA amyloidosis (10 vs. 2.6%, p < 0.0001) and received more biotherapy (18 vs. 3.8%, p < 0.0001). Twenty percent of FMF patients had a diagnostic delay >10 years, including more women. The differential diagnosis of abdominal attacks with menstrual pain may be an explanation, and erysipelas-like erythema may not be recognized as FMF by all practitioners., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Autoinflammatory diseases (AIDs) are conditions characterized by dysfunction of innate immunity, causing systemic inflammation and various clinical symptoms. The field of AIDs has expanded due to improved comprehension of pathophysiological mechanisms and advancements in genomics techniques. A new emerging category of AIDs is characterized by a significant increase in interleukin 18 (IL-18), a pro-inflammatory cytokine synthesized in macrophages and activated by caspase 1 via various inflammasomes. IL-18 plays a role in the regulation of innate and adaptive immunity. IL-18 is involved in various functions, such as the proliferation, survival, and differentiation of immune cells, tissue infiltration of immune cells, polarization of immune responses, and production of other pro-inflammatory cytokines. This review analyzes the literature on IL-18 regarding its functions and its implications in the diagnosis and treatment of AIDs. IL-18-associated AIDs comprise Still's disease and diseases associated with mutations in NLRC4, XIAP, CDC42, and PSTPIP1, as well as IL-18BP deficiencies. With the exception of PSTPIP1-associated diseases, these conditions all carry a risk of macrophagic activation syndrome. Measuring IL-18 levels in serum can aid in the diagnosis, prognosis, and monitoring of these diseases. Therapies targeting IL-18 and its signaling pathways are currently under investigation., (Copyright © 2024 Société Nationale Française de Médecine Interne (SNFMI). Published by Elsevier Masson SAS. All rights reserved.)

Introduction: Familial Mediterranean fever (FMF) is the most common monogenic autoinflammatory disease characterized by recurrent fever and serosal inflammation. Although colchicine is the primary treatment, around 10% of FMF patients do not respond to it, necessitating alternative therapies. Biologic treatments, such as interleukin-1β (IL-1β), TNF-α, and interleukin-6 (IL-6) inhibitors, have been considered. However, the accessibility and cost of IL-1β inhibitors may limit their use in certain regions. Tocilizumab (TCZ), an IL-6 receptor inhibitor, offers an alternative, but its efficacy in FMF is not well-documented., Objective: To evaluate the efficacy and safety of tocilizumab in the treatment of FMF., Methods: Following PRISMA guidelines, we identified 237 articles on the use of TCZ in FMF., Results: After selection, 14 articles were included: 2 double-blind RCTs, 2 retrospective studies, and 10 case reports. Multicentre double-blind RCTs reported mixed results in FMF patients without AA amyloidosis due to genetic/classification heterogeneity of the available studies, possible misdiagnosed FMF patients and study design. Retrospective studies suggest that TCZ may benefit FMF patients with established renal AA amyloidosis, potentially preventing progression and managing flares more effectively. TCZ showed a safe profile with no specific adverse events, but data on its use during pregnancy or breastfeeding are lacking. There was no available data on the use of TCZ in pediatric FMF., Conclusion: This review summarizes the current state of research, safety and efficacy of TCZ in FMF. While IL1β inhibitors remain the first choice for colchicine-resistant or intolerant FMF patients, TCZ might be of interest in some selected FMF patients with established AA amyloidosis and resistance to colchicine and interleukin 1 inhibitors., (© The Author(s) 2024. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

A20 Haploinsufficiency (HA20) is a monogenic autoinflammatory disease associated with an autosomal dominant mutation in the TNFAIP3 gene. It induces a defect in the inactivation of the pro-inflammatory NF-κB pathway. Less than 200 cases have been described worldwide. The clinical picture of the disease is essentially based on the association of recurrent fever and/or biologic inflammatory syndrome, aphtosis, often bipolar, and cutaneous folliculitis. However, the clinical spectrum of HA20 is very broad, including gastrointestinal (mainly colonic ulceration), articular, cutaneous, pericardial and lymph node involvement, as well as frequent association with organ-specific or non-specific autoimmune manifestations and/or autoantibodies, including antinuclear antibodies and anti-dsDNA. As a result, the diagnosis of a number of systemic or organic disorders, most notably Behçet's disease, Crohn's disease, and sometimes even systemic lupus, has been corrected to HA20 by molecular research for a heterozygous mutation with functional deficiency of TNFAIP3. Although the first signs of the disease often appear in the first years of life, the diagnosis is often made in adulthood and requires the involvement of both paediatric and adult physicians. Treatment for HA20 is not codified and relies on conventional or biological immunomodulators and immunosuppressants adapted to the patient's symptomatology. This review highlights the enormous diagnostic challenges in this autoinflammatory disease., (Copyright © 2023 Société Nationale Française de Médecine Interne (SNFMI). Published by Elsevier Masson SAS. All rights reserved.)

A20 haploinsufficiency is an autoinflammatory disease caused by defective inactivation of the NF-κB pathway. We conducted a systematic literature review of articles reporting patients with TNFAIP3 sequence variants from 2016 to August 2023 following PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines. Data from 177 patients from 65 articles were retrieved (108 women). The principal features were mucosal ulcers (n = 129); fever (n = 93) followed by gastrointestinal (n = 81); skin features (n = 76); autoimmunity (n = 61), including thyroiditis (n = 25) and lupus (n = 16); and joint involvements (n = 54). Five patients had died at the time of publication. In 54 of 63 patients, CRP was significantly elevated during flares, with a median of 51 mg/l. The most commonly used treatment included corticosteroids and nonsteroidal anti-inflammatory drugs (n = 32), TNF blockers (n = 29), colchicine (n = 28), and methotrexate (n = 14). TNFAIP3 variants impacted the ovarian tumor domain in 92 cases and a Zinc finger domain in 68 cases. Geographic origin, reported sex, and variant type significantly impacted phenotype. A better understanding of the wide A20 haploinsufficiency phenotype could facilitate the diagnosis process. Much remains to be elucidated about pathogenesis and treatment to improve outcome in patients with A20 haploinsufficiency., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Systemic autoinflammatory disorders (SAIDs) represent a growing spectrum of diseases characterized by dysregulation of the innate immune system. The most common pediatric autoinflammatory fever syndrome, Periodic Fever, Aphthous Stomatitis, Pharyngitis, Adenitis (PFAPA), has well defined clinical diagnostic criteria, but there is a subset of patients who do not meet these criteria and are classified as undefined autoinflammatory diseases (uAID). This project, endorsed by PRES, supported by the EMERGE fellowship program, aimed to analyze the evolution of symptoms in recurrent fevers without molecular diagnosis in the context of undifferentiated AIDs, focusing on PFAPA and syndrome of undifferentiated recurrent fever (SURF), using data from European AID registries., Methods: Data of patients with PFAPA, SURF and uSAID were collected from 3 registries including detailed epidemiological, demographic and clinical data, results of the genetic testing and additional laboratory investigations with retrospective application of the modified Marshall and PRINTO/Eurofever classification criteria on the cohort of PFAPA patients and preliminary SURF criteria on uSAID/SURF patients., Results: Clinical presentation of PFAPA is variable and some patients did not fit the conventional PFAPA criteria and exhibit different symptoms. Some patients did not meet the criteria for either PFAPA or SURF, highlighting the heterogeneity within these groups. The study also explored potential overlaps between PFAPA and SURF/uAID, revealing that some patients exhibited symptoms characteristic of both conditions, emphasizing the need for more precise classification criteria., Conclusions: Patients with recurrent fevers without molecular diagnoses represent a clinically heterogeneous group. Improved classification criteria are needed for both PFAPA and SURF/uAID to accurately identify and manage these patients, ultimately improving clinical outcomes., (© 2024. The Author(s).)

Background: Our study aimed to provide real-world evidence on the treatment patterns, effectiveness and safety of canakinumab in France in Familial Mediterranean Fever (FMF), Mevalonate Kinase Deficiency (MKD), and Tumor necrosis factor Receptor Associated Periodic Syndrome (TRAPS)., Methods: This study used the JIR cohort, a multicentre international registry created in 2013 to collect data on patients with juvenile inflammatory rheumatic diseases. French patients diagnosed with FMF, MKD or TRAPS and treated with canakinumab were included in this study., Results: 31 FMF, 26 MKD and 7 TRAPS patients received canakinumab during the study period. Most of them initiated canakinumab at the recommended dose of 2 mg/kg or 150 mg, but less than half of FMF and MKD patients initiated it at the recommended frequency (every 4 weeks). Two years after initiation, the rate of patients still on treatment was 78.1% in FMF, 73.7% in MKD, and 85.7% in TRAPS patients. While the dose per injection remained globally the same over the course of the treatment, some adjustments of the dose intervals were observed. Six patients had a severe adverse event reported. Of those, three were possibly related to canakinumab., Conclusion: This interim analysis showed a good maintenance of canakinumab treatment 2 years after initiation and confirmed its safety profile in real-life practice in France in patients diagnosed with FMF, MKD and TRAPS. The high variety of dose and interval combinations observed in canakinumab treated patients let suppose that physicians adapt the posology to individual situations rather than a fixed treatment plan., (© 2024. The Author(s).)

Objective: Juvenile systemic lupus erythematosus (j-SLE) is a rare chronic auto-immune disease involving several organs. Neuropsychiatric (NP) SLE (NPSLE) is frequent in j-SLE and associated with increased morbidity/mortality. Although NPSLE classification criteria exist, attributing NP features to j-SLE remains a major challenge. The study objective is to thoroughly describe j-NPSLE patients and assist in their diagnosis., Methods: This is a 4-year retrospective monocentric study of j-SLE patients. NP events were attributed to j-SLE using standardised diagnostic criteria and multidisciplinary paediatric clinical expertise. Clinical features, brain magnetic resonance imaging (MRI)s and samples analysis including cerebrospinal fluid were assessed. A risk of j-NPSLE score was developed based on multivariable logistic regression analysis., Results: Of 39 patients included, 44% were identified as having j-NPSLE. J-NPSLE diagnosis was established at the onset of j-SLE in 59% of patients. In addition to frequent kidney involvement (76%) and chilblains (65%), all j-NPSLE patients displayed psychiatric features: cognitive symptoms (82%), hallucinations (76%), depressed mood (35%), acute confused state (18%) and catatonia (12%). Neurological involvement was often mild and nonspecific, with headache (53%) in about half of the patients. The main features reported on brain MRI were nonspecific T2/FLAIR white matter hyperintensities (65%), and cerebral atrophy (88%). Upon immunosuppressive treatment, clinical improvement of NP features was observed in all j-NPSLE patients. The score developed to attribute j-NPSLE probability, guide further investigations and appropriate treatments is based on hallucinations, memory, sleep and renal involvement (Sensitivity: 0.95 Specificity: 0.85). Cerebrospinal fluid (CSF) neopterin assessment increases the score sensitivity and specificity., Conclusion: Physicians should carefully and systematically assess the presence of NP features at diagnosis and early stages of j-SLE. For j-NPSLE patients with predominant psychiatric features, a multidisciplinary collaboration, including psychiatrists, is essential for the diagnosis, management and follow-up., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.