Macrophage activation syndrome in patients with systemic juvenile idiopathic arthritis on anti-interleukin-1 or -6 therapy.

OBJECTIVES: The aim of this study is to investigate the effect of anti-interleukin (IL)-1/-6 biologics on systemic juvenile idiopathic arthritis (sJIA)-associated macrophage activation syndrome (MAS). METHODS: Demographic, clinical, and laboratory data of patients followed up with a diagnosis of sJIA-associated MAS assessed from sixteen pediatric rheumatology centers across the country. The clinical and laboratory features of MAS developing while on biological drugs were compared with those without this treatment. RESULTS: One hundred and sixty-two patients were included in the study. 45 of the MAS events were detected under the effect of anti-IL-1/-6 biologics, while the patients experiencing the remaining 155 events have not received biological treatment in the last three months. Platelet count [128 (72-232) vs 199 (130-371) 109/l], ferritin level on admission [1107 (676-2050) vs 2863 (1193-9562) ng/ml], C-reactive protein level [15.4 (2.9-56) vs 90 (32-160) mg/l], erythrocyte sedimentation rate [13 (3-36) vs 43.5 (13-77) mm/h] and fever duration [5 (4-7.5) vs 10 (7-14.3) days] were found lower in the group under the impact of anti-IL-1/-6 biologics. Among patients treated with biologics, 26.6% did not meet the published 2016 MAS classification criteria at presentation. The rates of hepatomegaly and splenomegaly were relatively lower in the canakinumab-treated group when compared with those receiving other biologicals or to patients, not on biologicals. CONCLUSION: Anti-IL-1/-6 therapies can mask the clinical and laboratory features of MAS, and proposed guidelines for MAS classification criteria may not be met.

Comparison of EULAR/PRINTO/PReS Ankara 2008 and 2022 ACR/EULAR Classification Criteria for Granulomatosis with Polyangiitis in Children.

OBJECTIVE: Granulomatosis with polyangiitis (GPA) is an antineutrophil cytoplasmic antibody-associated vasculitis. The 2022 American College of Rheumatology/European Alliance of Associations for Rheumatology (ACR/EULAR)-endorsed classification criteria for GPA was derived using data only from adult patients. We aimed to assess the performance of the ACR/EULAR classification criteria for GPA in pediatric patients and compare it with the EULAR/Pediatric Rheumatology International Trials Organization (PRINTO)/Pediatric Rheumatology European Society (PReS)-endorsed Ankara 2008 criteria for GPA. METHODS: Retrospective data of pediatric patients with GPA in 20 centers from 9 countries were evaluated. The diagnosis of GPA was made according to the expert opinion. The sensitivity, specificity, positive predictive value, and negative predictive value of the criteria sets were evaluated. RESULTS: The study included 77 patients with GPA and 108 controls (immunoglobulin A vasculitis (n = 44), Takayasu's arteritis (n = 20), microscopic polyangiitis (n = 16), polyarteritis nodosa (n = 14), Behçet's disease (n = 12), eosinophilic granulomatosis with polyangiitis (n = 1), and Cogan's syndrome (n = 1)) with a median age of 17.8 and 15.2 years, respectively. Of patients with GPA, constitutional symptoms (85.7%) and ear-nose-throat involvement (79.2%) were the most common presentations. In the GPA group, 73 patients fulfilled the Ankara 2008 criteria and 69 the ACR/EULAR classification criteria. Sensitivities of the Ankara 2008 criteria and the ACR/EULAR classification criteria were 94.8% and 89.6%, while specificities were 95.3% and 96.3%, respectively. No significant difference was found between sensitivities and specificities of both classification criteria (p= 0.229 and p= 0.733, respectively). CONCLUSION: In children, both the ACR/EULAR and EULAR/PRINTO/PReS Ankara 2008 classification criteria for GPA perform well and similarly.

Not easy-peasy to diagnose: familial Mediterranean fever unaccompanied by fever.

Classical attacks of familial Mediterranean fever (FMF) are often accompanied by fever, but some of the patients have attacks without fever. This study aimed to compare the characteristics of FMF patients with and without fever during their attacks and draw attention to the different clinical presentations of FMF in children. Medical files of patients aged 0-18 years who were followed up with the diagnosis of FMF in two reference pediatric rheumatology centers were reviewed retrospectively. The patients were divided into two groups: children who had had no fever in any of their attacks were assigned as group 1, and those who had fever during their attacks were classified as group 2. Out of 2003 patients evaluated, 191 (9.53%) patients had attacks not accompanied by fever and their median age at onset of symptoms (7.0 vs. 4.0 years, p < 0.001) and the median age at diagnosis (8.6 vs. 6.0 years, p < 0.001) were significantly higher; however, group 2 had a delay in diagnosis. The annual number of attacks and abdominal attacks were more common in group 2; arthritis, arthralgia, erysipelas-like rash, exercise-induced leg pain, and myalgia were more common in group 1.    Conclusion: The data from the assessment of children with FMF attacks not accompanied with fever were presented for the first time. Children with late age onset of FMF and dominance of musculoskeletal features may display attacks not accompanied with fever. What is Known: • Familial Mediterranean fever (FMF) is the most common inherited auto-inflammatory disease, characterized by recurrent attacks of fever, serositis, and musculoskeletal symptoms. • Although fever is the most common symptom, few studies have reported attacks without fever. What is New: • The aim of this study was to identify patients with FMF but without fever during attacks and to demonstrate their distinctive presentations. • We found that 7% of our patients had afebrile attacks with predominant musculoskeletal symptoms and were diagnosed earlier than patients with febrile attacks, probably due to early referral to pediatric rheumatology clinics.

Pediatric mixed connective tissue disease versus other overlap syndromes: a retrospective multicenter cohort study.

Pediatric mixed connective tissue disease (MCTD) is a subgroup of overlap syndromes. We aimed to compare the characteristics and outcomes in children with MCTD and other overlap syndromes. All MCTD patients met either Kasukawa or Alarcon-Segovia and Villareal criteria. The patients with other overlap syndromes had the features of ≥ 2 autoimmune rheumatic diseases but did not meet MCTD diagnostic criteria. Thirty MCTD (F/M = 28/2) and thirty (F/M = 29/1) overlap patients were included (disease onset < 18 years). The most prominent phenotype at disease onset and the last visit was systemic lupus erythematosus (SLE) in the MCTD group; juvenile idiopathic arthritis and dermatomyositis/polymyositis, respectively, in the overlap group. At the last visit, systemic sclerosis (SSc) phenotype was more frequent among MCTD than overlap patients (60% vs. 33.3%; p = 0.038). The frequency of the predominant SLE phenotype had decreased (60% to 36.7%), while predominant SSc phenotype had increased (13.3% to 33.3%) during follow-up in MCTD patients. Weight loss (36.7% vs. 13.3%), digital ulcers (20% vs. 0), swollen hands (60% vs. 20%), Raynaud phenomenon (86.7% vs. 46.7%), hematologic involvement (70% vs. 26.7%), and anti-Sm positivity (29% vs. 3.3%) were more common, while Gottron papules (16.7% vs. 40%) were less frequent among MCTD than overlap patients (p < 0.05). A higher percentage of overlap patients achieved complete remission than MCTD patients (51.7% vs. 24.1%; p = 0.047). The disease phenotype and outcome differ between pediatric MCTD and other overlap syndromes where MCTD may be regarded as a more severe disease. Analyzing these patients could pave the way for early and effective treatment.

Cardiac involvement in multisystem inflammatory syndrome in children: single-centre experience.

BACKGROUND: This study aimed to evaluate electrocardiographic and echocardiographic findings, Holter recordings of the multisystem inflammatory syndrome in children, and to identify prognostic factors for cardiac involvement. METHODS: We retrospectively reviewed demographic characteristics, medical data, laboratory findings, electrocardiogram and echocardiographic findings, 24-hour Holter recordings, need for an ICU, and extracorporeal membrane oxygenation in multisystem inflammatory syndrome in children. Acute left ventricular systolic dysfunction was defined as left ventricular ejection fraction (EF) ≤%55 on echocardiography. RESULTS: Sixty-seven children were included in the study. 24-hour Holters were recorded in 61.2% of the patients and 49.2% were normal. On echocardiographic examination, 14.9% of the patients had systolic dysfunction (EF ≤ 55%). While 32.8% of patients had mild mitral regurgitation, 3% had moderate mitral regurgitation, and 6% had mild aortic regurgitation. There was no statistically significant difference in EF values between the group with arrhythmia in Holter and the group with normal Holter results (p ≥ 0.05). B-type natriuretic peptide was positively correlated with C-reactive protein, ferritin, and fibrinogen. Significant effectivity of the B-type natriuretic peptide value was observed in the differentiation of those with EF ≤ and > 55%. Extracorporeal membrane oxygenation support was needed for three (4.5%) patients. One patient who died had systemic juvenile idiopathic arthritis. CONCLUSIONS: Neutrophil/lymphocyte ratio, C-reactive protein, D-dimer, ferritin, troponin, and B-type natriuretic peptide were found to be significantly higher in patients with systolic dysfunction. Also, the cut-off value of 1700 pg/ml for B-type natriuretic peptide was significantly effective. These parameters may indicate the severity of the disease but should be supported by prospective studies.

PREDICT-crFMF score: A novel model for predicting colchicine resistance in children with familial Mediterranean fever.

OBJECTIVES: To develop a novel scoring system to predict colchicine resistance in Familial Mediterranean fever (FMF) based on the initial features of the patients. METHODS: The medical records of patients were analyzed prior to the initiation of colchicine. After generating a predictive score in the initial cohort, it was applied to an independent cohort for external validation of effectiveness and reliability. RESULTS: Among 1418 patients with FMF, 56 (3.9%) were colchicine resistant (cr) and 1312 (96.1%) were colchicine responsive. Recurrent arthritis (4 points), protracted febrile myalgia (8 points), erysipelas-like erythema (2 points), exertional leg pain (2 points), and carrying M694V homozygous mutation (4 points) were determined as the parameters for predicting cr-FMF in the logistic regression model. The cut-off value of 9 was 87% sensitive and 82% specific to foresee the risk of cr-FMF in the receiver operating characteristic. Validation of the scoring system with an independent group (cr-FMF = 107, colchicine responsive = 1935) revealed that the cut-off value was 82% sensitive and 79% specific to identify the risk of cr-FMF. CONCLUSIONS: By constructing this reliable and predictor tool, we enunciate that predicting cr-FMF at the initiation of the disease and interfering timely before the emergence of complications will be possible.

Differences and similarities of multisystem inflammatory syndrome in children, Kawasaki disease and macrophage activating syndrome due to systemic juvenile idiopathic arthritis: a comparative study.

To compare the clinical and laboratory findings of multisystem inflammatory syndrome in children (MIS-C), patients with Kawasaki disease (KD) and with macrophage activating syndrome due to systemic juvenile idiopathic arthritis (sJIA-MAS) on real-life data. Patients diagnosed with MIS-C, KD, and sJIA-MAS from 12 different centers in Turkey who were followed for at least 6 months were included in the study. Demographic, clinical, and laboratory findings of all patients were analyzed. A total of 154 MIS-C, 59 KD, and 31 sJIA-MAS patients were included. The median age of patients with MIS-C were higher than those with KD while lower than those with sJIA-MAS (8.2, 3, 12 years, respectively). Myalgia (39.6%), cardiac (50.6%), gastrointestinal (72.7%), and neurological (22.1%) involvements were more common in patients with MIS-C compared to others. MIS-C patients had lower levels of lymphocyte (950 vs 1700 cells/µl) and thrombocyte (173,000 vs 355,000 cells/µl) counts and higher pro-BNP (1108 vs 55 pg/ml) levels than KD. Ferritin levels were higher in patients with MIS-C compared to patients with KD while they were lower than patients with sJIA-MAS (440, 170, 10,442 ng/ml, respectively). Patients with MIS-C had a shorter duration of hospitalization than sJIA-MAS (p = 0.02) while they required intensive care unit admission more frequently (55 vs 8 patients, p < 0.001). The median MAS/sJIA score of MIS-C patients was - 1.64 (- 5.23 to 9.68) and the median MAS/sJIA score of sJIA-MAS patients was -2.81 ([- 3.79] to [- 1.27]). MIS-C patients displayed certain differences in clinical and laboratory features when compared to KD and sJIA-MAS. Definition of the differences and similarities between MIS-C and the other intense inflammatory syndromes of childhood such as KD and MAS will help the clinicians while making timely diagnosis.

Low disease activity state in juvenile-onset systemic lupus erythematosus.

OBJECTIVES: To determine the rate of achieving The Lupus Low Disease Activity State (LLDAS) in children with systemic lupus erythematosus (SLE) for tracing pertinent treatment modalities. METHODS: A total of 122 juvenile-onset SLE (jSLE) patients from six pediatric rheumatology centers in Turkey were enrolled in the study. LLDAS-50 was defined as encountering LLDAS for at least 50% of the observation time. According to the achievement of LLDAS-50, clinical features, immunological profiles, and treatments of patients with jSLE have been revealed. RESULTS: LLDAS of any duration was achieved by 82% of the cohort. Although only 10.8% of the patients achieved remission, 68.9% reached LLDAS-50. A significant difference was found between patients who reached LLDAS-50 and those who did not, in terms of the time to reach low-dose corticosteroid treatment (p = 0.002), the presence of subacute cutaneous findings (p = 0.007), and the presence of proteinuria (p = 0.002). Both of the groups were under similar treatment approaches. However, the number of patients being treated with corticosteroids at the last visit was found to be significantly higher in patients who achieved LLDAS-50 (p<0.001). CONCLUSION: Targeting LLDAS in jSLE, even with long-term, low-dose corticosteroid use, seems to be an achievable goal in clinical practice.

The cultural differences in transition assessment: Evaluation of TRANSITION-Q and STARx scales on Turkish rheumatic patients.

Objectives: This study aimed to assess the readiness of our patient population for the transfer to adult care and the applicability of the TRANSITION-Q and STARx scales to the Turkish adolescent patient population. Patients and methods: A total of 153 patients (92 males, 61 females; mean age: 15.5±1.9 years; range, 12 to 18 years) were included in the study between September 15, 2021, and December 15, 2021. The patients were divided into two groups according to age groups: 12 to 15 years old and 16 to 18 years old. The patients were also divided into four groups according to their diagnosis: connective tissue diseases, juvenile idiopathic arthritis, vasculitis, and autoinflammatory diseases. The TRANSITION-Q and STARx scales were administered face-to-face by a nurse and a doctor. The transition readiness of the patients was evaluated according to their scores. Results: Sixty-nine (45%) patients were in the 12 to 15 age group, and 84 (55%) were in the 16 to 18 age group. Eight-four (54.9%) patients had juvenile idiopathic arthritis, 47 (30.7%) patients had an autoinflammatory disease, 14 (9.2%) patients had vasculitis, and eight (5.2%) patients had a connective tissue disease. There was no significant difference in the scale scores according to disease groups and sexes in both scales. Considering the age of the patients, the mean scores of the patients in the 16 to 18 age group were found to be significantly higher compared to the 12 to 15 age group for both the TRANSITION-Q (74.3±13.3 vs. 65.4±9.6, p<0.001) and STARx scales (51.8±8.1 vs. 44.8±9.1, p<0.001). Cronbach's alpha score was 0.71 for the STARx scale and 0.79 for the TRANSITION-Q scale. Conclusion: TRANSITION-Q and STARx scales could guide the Turkish patient population in determining the pretransition needs of patients in planning individualized transition processes.

Evaluation of childhood malignancies presenting with musculoskeletal manifestations from two different divisions: a multicenter study.

BACKGROUND: The aim of the study was to evaluate the approaches of pediatric rheumatologists and pediatric hematologists to patients with similar musculoskeletal (MSK) complaints and to highlight the differences that general pediatricians should consider when referring patients to these specialties. METHODS: This is a cross-sectional study involving the patients who applied to pediatric rheumatology centers with MSK complaints and were diagnosed with malignancy, as well as patients who were followed up in pediatric hematology centers with a malignancy diagnosis, and had MSK complaints at the time of admission. RESULTS: A total of 142 patients were enrolled in the study. Of these patients, 83 (58.4%) applied to pediatric rheumatology centers, and 59 (41.6%) applied to pediatric hematology centers. Acute lymphoblastic leukemia (ALL) was the most common diagnosis among the patients who applied to both centers, with 80 cases (56.3%). The median age of diagnosis was 87 (interquartile range, IQR: 48-140) months. The most common preliminary diagnosis in pediatric rheumatology centers was juvenile idiopathic arthritis (JIA), with 37 cases (44.5%). MSK involvement was mainly seen as arthralgia, and bone pain. While arthralgia (92.7%) was the most common complaint in rheumatology centers, bone pain (88.1%) was more common in hematology centers. The most frequently involved joints were the knee (62.9%), ankle (25.9%), hip (25%), and wrist (14%). The most common laboratory abnormalities were high lactate dehydrogenase (LDH), high C-reactive protein (CRP), anemia, and high erythrocyte sedimentation rate (ESR). Thrombocytopenia, neutropenia, and high LDH were statistically significantly more frequent in patients admitted to hematology centers than in patients admitted to rheumatology centers (p < 0.001, p=0.014, p=0.028, respectively). Patients who applied to rheumatology clinics were found to have statistically significantly higher CRP levels (p=0.032). CONCLUSIONS: Malignancies may present with only MSK system complaints in childhood. Therefore, malignancies should be included in the differential diagnosis of patients presenting with MSK complaints.

Towards a standardized program of transitional care for adolescents with juvenile idiopathic arthritis for Turkey: a national survey study.

BACKGROUND: Juvenile idiopathic arthritis (JIA) is a prevalent childhood chronic arthritis, often persisting into adulthood. Effective transitional care becomes crucial as these patients transition from pediatric to adult healthcare systems. Despite the concept of transitional care being recognized, its real-world implementation remains inadequately explored. This study aims to evaluate the thoughts and practices of healthcare providers regarding transitional care for JIA patients. METHODS: A cross-sectional survey was conducted among pediatric and adult rheumatologists in Turkey. Based on the American Academy of Pediatrics' six core elements of transitional care, the survey included 86 questions. The respondents' demographic data, attitudes towards transitional care, and practical implementation were assessed. RESULTS: The survey included 48 rheumatologists, with 43.7% having a transition clinic. The main barriers to establishing transition programs were the absence of adult rheumatologists, lack of time, and financial constraints. Only 23.8% had a multidisciplinary team for transition care. Participants agreed on the importance of coordination and cooperation between pediatric and adult healthcare services. The timing of the transition process varied, with no consensus on when to initiate or complete it. Participants advocated for validated questionnaires adapted to local conditions to assess transition readiness. CONCLUSIONS: The study sheds light on the challenges and perspectives surrounding transitional care for JIA patients in Turkey. Despite recognized needs and intentions, practical implementation remains limited due to various barriers. Cultural factors and resource constraints affect the transition process. While acknowledging the existing shortcomings, the research serves as a ground for further efforts to improve transitional care and ensure better outcomes for JIA patients transitioning into adulthood.

Withdrawal of biologic therapy in juvenile idiopathic arthritis due to remission: predictors of flare and outcomes.

OBJECTIVES: To investigate patients who flared after discontinuation of biological disease-modifying anti-rheumatic agents (bDMARDs) and identify risk factors associated with flare. METHODS: A multicenter study evaluating systemic and non-systemic juvenile idiopathic arthritis (sJIA and non-sJIA) patients whose bDMARDs were ceased after remission. RESULTS: A total of 101 patients whose bDMARDs were ceased after remission was evaluated. Children with sJIA had the lowest risk of flare and 11.1% of 36 sJIA patients experienced flare after a median of 9 (4-24) months of bDMARDs cessation with three of them flaring in the first year. High leukocyte counts in sJIA patients were associated with inactive disease at 1-year after the start of treatment (p = 0.004). In the non-sJIA group, 46.1% patients experienced flare after a median of 7 (1-32) months of biologic cessation, and of these, 25 flared in the first year. Antinuclear antibody positivity (p = 0.02), earlier disease onset (p = 0.03), long disease duration (p = 0.01), and follow-up (p = 0.02) and extended time from diagnosis to first biological onset (p = 0.03) were more common among patients with flare. CONCLUSIONS: When considering discontinuation of bDMARDs, it should be kept in mind that the risk of exacerbation requiring re-initiation therapy is quite significant within the first year after discontinuation of therapy.

A pediatric case of Takayasu's arteritis with anti-neutrophil cytoplasmic antibody-associated vasculitis triggered by COVID-19 infection.

Takayasu's arteritis (TA) is a rare chronic granulomatous vasculitis characterized by large-vessel involvement. The aorta and its main branches are most commonly involved. Although pulmonary artery involvement is common, hemoptysis or respiratory findings are rarely seen. Herein, we present a case of TA who developed anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis with diffuse alveolar hemorrhage after coronavirus disease 2019 (COVID-19) infection. A 17-year-old female patient with the diagnosis of TA presented with cough, bloody vomiting, and diarrhea. In follow-up, she developed tachypnea and dyspnea and was transferred to the pediatric intensive care unit. The findings on the chest computed tomography were compatible with acute COVID-19 infection, but the SARS-CoV2 reverse transcription-polymerase chain reaction test was negative, but SARS-CoV2 immunoglobulin (Ig) G and IgM antibody tests were positive. The patient was not vaccinated against COVID-19. The bronchoscopy showed bronchial mucosal fragility, bleeding foci, and mucosal bleeding. The broncoalveolar lavage hemosiderin-laden macrophages were seen in the histopathologic examination. The indirect immunofluorescence assay-ANCA test became 3 (+) with myeloperoxidase (MPO)-ANCA of 125 RU/ml (normal: <20). Cyclophosphamide and pulse steroid treatment were started. After immunosuppressive therapy, the patient condition improved and did not have hemoptysis again. The successful response was obtained by applying balloon angioplasty to the patient with bilateral renal artery stenosis. Types of post-COVID vasculitis include thromboembolic events, cutaneous vasculitis, Kawasaki-like vasculitis, myopericarditis, and ANCA-associated vasculitis. It is thought that COVID-19 may impair immune tolerance and trigger autoimmunity with cross-reaction. To the best of our knowledge, the third pediatric case was reported with MPO-ANCA-positive COVID-associated ANCA vasculitis.

Real-life data on efficacy and safety of original Adalimumab and biosimilar Adalimumab (ABP 501) in pediatric rheumatic diseases.

BACKGROUND: We aimed to compare the efficacy and safety of the original product (OP) and biosimilar product (BP) of adalimumab in pediatric rheumatic diseases. RESEARCH DESIGN AND METHODS: The study group consisted of patients who had received original or biosimilar adalimumab (ABP 501) therapy for at least 3 months. The patients were divided into uveitis and arthritis groups based on the indication of adalimumab treatment. Assessment of disease activity was performed by Juvenile Arthritis Disease Activity Score in patients with juvenile idiopathic arthritis, and by standardization of uveitis nomenclature criteria in patients with uveitis. RESULTS: The study included 140 patients, of which 87 were treated with OP and 53 with BP. In the arthritis group, 26 (63.4%) and 20 (57.1%) patients reached inactive disease according to JADAS-27 in the original and biosimilar adalimumab groups, respectively. In the uveitis group the mean number of exacerbations throughout the treatment period was 0.84 ± 1.07 in the OP group, and 0.58 ± 0.79 in the BP group. There were 71 treatment-emergent adverse events in the OP group and 38 in the BP group. CONCLUSION: There was no significant difference between the biosimilar and the original product in efficacy and safety.

The assessment of autoinflammatory disease classification criteria (Eurofever/PRINTO) in a real-life cohort.

OBJECTIVE: The aim of the study was to determine the sensitivity and specificity rates of Eurofever/PRINTO autoinflammatory recurrent fever classification criteria with real-life data in patients with an autoinflammatory disease. METHODS: A total of 119 patients were included in the study. Based on clinical symptoms, they were divided into four subgroups: cryopyrin-associated periodic syndromes (CAPS), TNF receptor-associated periodic syndrome (TRAPS), mevalonate kinase deficiency (MKD), and syndrome of undifferentiated recurrent fever (SURF) using the Eurofever/PRINTO clinical classification criteria. In the last step, the patients were re-evaluated in the light of genetic results and their final diagnosis was reached. RESULTS: A total of 119 patients, including 37 CAPS, 13 TRAPS, 8 MKD, 39 SURF, 14 NLRP12-related autoinflammatory disease (NLRP12-AID), and 8 familial Mediterranean fever (FMF) patients were evaluated in the study. While the sensitivity of the new clinical Eurofever/PRINTO criteria was 48% for CAPS, 77% for TRAPS, 87.5%for MKD, and the specificity of the clinical criteria was 86% for CAPS, 85% for TRAPS, and 60% for MKD. The sensitivity of the new mixed (genetic plus clinical variables) Eurofever/PRINTO criteria was 27% for CAPS, 61% forTRAPS, 85% for MKD, and the specificity of the mixed criteria for each group was 100%. CONCLUSION: We found the sensitivity of the Eurofever/PRINTO classification criteria to be low as genotypic changes between populations cause phenotypic differences. For this reason, we think that patient-based evaluation is correct rather than standard classification criteria in real life. Key-points • In systemic autoinflammatory diseases, common variants in the populations may alter the phenotype, and making it difficult to classify some patients with the current classification criteria. • In populations with common genetic variants, the classification criteria should be modified according to the clinical phenotype.

Remission rates and risk factors for relapse in pediatric morphea: a multicenter retrospective study of Pediatric Rheumatology Academy (PeRA)-Research Group (RG).

AIM: Morphea, also known as localized scleroderma, is an immune-mediated disease and the most common form of scleroderma in children. It is a localized sclerosing disease of the skin, but can also involve such adjacent tissues as the fascia, muscle, bone, and underlying tissues. This multicenter study aimed to evaluate Turkish pediatric morphea patients, regarding demographics, treatments, and response to treatment. MATERIALS AND METHODS: The study was performed by the Pediatric Rheumatology Academy and included pediatric morphea patients from 6 Turkish pediatric rheumatology centers who were followed up for ≥6 months. Demographic, clinical, and laboratory findings and treatment modalities were analyzed. The patients were divided into 3 groups according to treatment response, as follows: group 1: topical treatment response, group 2: methotrexate response, and group 3: methotrexate resistance. Clinical findings were compared between the 3 groups. RESULTS: The study included 76 patients, of which 53 (69.7%) were female. Mean age at diagnosis of morphea was 9.7 ± 4.3 years and mean duration of follow-up was 3.2 ± 2.9 years. Linear morphea was the most common form, accounting for 43.4% (n = 33) of the patients. Extracutaneous features were noted in 17 patients (22.4%) and anti-nuclear antibody positivity was noted in 32 (42.1%). In all, 14.4% of the patients received topical treatment only, whereas 86.6% received both topical and systemic treatment. The methotrexate response rate was 76.9% in the patients that received systemic immunosuppressive therapy. The overall relapse rate while under treatment was 19.7%. CONCLUSION: In this study, most of the pediatric morphea patients responded well to methotrexate. Bilateral lesions were more common in the methotrexate-resistant group. Multiple involvement, and bilateral lesions, were more common in relapsed patients than in non-relapsed patients. Key points • Most of the pediatric morphea patients respond well to MTX. • Multiple involvement, and bilateral involvement, were more common in relapsed patients than in non-relapsed patients. • Presence of extracutaneous findings in patients increased relapse rate 5.7 times.

Is it possible to extend the dose interval of canakinumab treatment in children with familial Mediterranean fever? PeRA group experience.

BACKGROUND: There is no clear data on the optimal duration of treatment with anti-interleukin-1 drugs in colchicine-resistant familial Mediterranean fever patients, as well as on the dose interval. This study aimed to assess patients whose canakinumab dose interval was adjusted according to a specific protocol, with the objective of evaluating the effectiveness of implementing this protocol for the patient care. METHODS: The files of 45 patients whose canakinumab treatment interval was opened with a standard protocol previously determined by the Delphi method were retrospectively reviewed. RESULTS: Canakinumab treatment was initiated once a month for all patients. In the sixth month of canakinumab treatment, a dose interval extension was introduced; however, 7 patients (15.5%) experienced an attack, and consequently, no further interval extension was administered to them. For 29 patients, the dose interval was successfully extended to once every three months, as they remained attack-free for a year after the first interval extension. Nine patients continued receiving the drug every 2 months, as they had not yet completed one year since the first extension. The study found no significant correlation between experiencing an attack during the dose interval extension protocol and the number, duration of attacks, or autoinflammatory diseases activity index score. CONCLUSION: Extending treatment intervals with canakinumab in colchicine-resistant familial Mediterranean fever shows promise for favorable outcomes.