Rare Turner syndrome and lupus coexistence with insights from DNA methylation patterns.

Systemic lupus erythematosus (SLE or lupus) is a complex autoimmune disease that can affect multiple organs. While the exact disease etiology remains incompletely understood, there is a suggested influence of X-chromosome dosage in the pathogenesis of lupus. Here, we report a rare case of a female patient diagnosed with mosaic Turner syndrome and subsequently presenting with juvenile-onset SLE. DNA methylation patterns were analyzed in this patient and compared with age-matched female SLE controls, revealing higher methylation levels in interferon-regulated genes previously shown to be hypomethylated in SLE. These data provide a potential link between a gene-dose effect from the X-chromosome and the lupus-defining epigenotype. We hypothesize that the attenuated demethylation in interferon-regulated genes might provide a protective effect explaining the rarity of SLE in Turner syndrome.

Evaluation of pediatric rheumatologists' approach to rituximab use: a questionnaire study.

Rituximab (RTX) is a chimeric monoclonal antibody that targets the CD20 antigen on B cells and is used in various autoimmune disorders. In this study, we aimed to measure the awareness of pediatric rheumatologists about the use of RTX through a survey. Between February and March 2023, a 42-question survey was sent via email to pediatric rheumatology specialists in Turkey. The participants were questioned for which diagnoses and system involvement they preferred to use RTX, which routine tests they performed, vaccination policy, and adverse events that occurred during or after infusion. Forty-one pediatric rheumatologists answered the survey. They prescribed RTX most frequently for systemic lupus erythematosus (87.8%) and ANCA-associated vasculitis (9.8%). Prior to the administration of RTX, 95% of clinicians checked renal and liver function tests, as well as immunoglobulin levels. The most frequently tested hepatitis markers before treatment were HBsAg and anti-HBs antibody (97.6%), while 85.4% of rheumatologists checked for anti-HCV. Clinicians (31.4%) reported that they postpone RTX infusion 2 weeks following an inactivated vaccine. Sixty-one percent of rheumatologists reported starting RTX treatment 1 month after live vaccines, while 26.8% waited 6 months. The most frequent adverse events were an allergic reaction during RTX infusion (65.9%), hypogammaglobulinemia (46.3%), and rash (36.6%). In the event of hypogammaglobulinemia after RTX treatment, physicians reported that they frequently (58.5%) continued RTX after intravenous immunoglobulin administration. CONCLUSIONS: RTX has become a common treatment option in pediatric rheumatology in recent years. Treatment management may vary between clinician such as vaccination and routine tests. WHAT IS KNOWN: • During the course of rituximab therapy, clinicians should be attentive to specific considerations in pre-treatment, during administration, and in post-treatment patient monitoring. WHAT IS NEW: • There are differences in practice among clinicians in the management of RTX therapy. These practice disparities have the potential to impact the optimal course of treatment. • This study highlights that standardized guidelines are needed for RTX treatment in pediatric rheumatology, particularly for vaccination policies and routine tests.

Description of the Characteristics of the Nailfold Capillary Structure in Healthy Children: A Multi-Centric Study.

BACKGROUND: Nailfold videocapillaroscopy (NVC) is the primary diagnostic tool for the assessment of microcirculation in the pediatric population. OBJECTIVE: To define and standardize age-specific normal NVC patterns in healthy children and adolescents. METHODS: A cross-sectional observational multicentric study was conducted in 564 participants aged 5-17 years. Dino-Lite CapillaryScope 200 Pro Model MEDL4N Pro was performed at 200× magnification. Quantitative and qualitative NVC parameters were analyzed separately for each age group and divided into 4 groups based on age categories. RESULTS: Of the 564 healthy participants, 54.9% were female. A total of 1184 images and 3384 capillaries were analysed. Positive correlations were observed between age and capillary density (p < 0.001, R = 0.450, CI95% 0.398-0.503). There was also a positive correlation between age and arterial/venous, loop diameter and capillary length, whereas there was a weak negative correlation between intercapillary distance. However, no correlation was found between age and capillary width. In addition, capillary density was significantly lower in 5-7 age group compared to the other patient groups. Arterial limb diameter was lower in 5-7 age group, while venous limb diameter was significantly wider in 15-17 age group compared to the other patient groups. Dilated capillaries (8.7%), capillary tortuosity (14.4%), crossed capillaries (43.1%), micro-haemorrhages (2.7%), avascular area (4.8%) were present in all age groups. Excellent intra- and interobserver ICC values were obtained for all parameters. CONCLUSION: These findings hold potential significance for future studies, aiding in the analysis and differentiation of children suspected of rheumatological diseases with potential microangiopathy.

Are the nutritional status and growth parameters of children with juvenile idiopathic arthritis akin to their healthy peers? A single-center experience.

OBJECTIVE: Proper nutrition is a significant contributor to growth achievement in patients with juvenile idiopathic arthritis (JIA). In this study, the aim was to analyze the growth parameters and nutritional status of children with JIA and then compare them with their healthy peers. METHODS: A cross-sectional study was conducted with 54 patients with JIA and the same number of healthy peers. Growth parameter z-scores and nutrient distributions were analyzed and compared with a control group and among disease subgroups. RESULTS: While the average height in the control group was significantly greater than in the patient group, there was similarity in terms of body weight and body mass index (BMI) (P < 0.001, P = 0.33, P = 0.14, respectively). Body weight and BMI z-scores of patients with high disease activity at the most recent visit were significantly lower (P = 0.03, P = 0.01, respectively). Both groups had similar energy and protein requirement-meeting percentages (P = 0.62, P = 0.51). JIA atients had higher carbohydrate intake (P = 0.04), and fat intake was higher in controls (P = 0.02). Energy obtained from junk food was higher in patients with entesitis-related arthritis (ERA) compared to oligoarticular JIA and polyarticular JIA (P = 0.03). Micronutrient intake in the ERA group was significantly lower for vitamin E, C, and folate (P = 0.02, P = 0.03, P < 0.001). CONCLUSION: In our cohort, patients had a lower height score. As they have a diet characterized by adequate energy/protein, carbohydrate, and high fat intake, this may be a reflection of disease activity. Although some of the micronutrient intakes were less than normal in both groups, significant deficiencies were identified in the ERA group.

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.

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.

The assessment of fatigue and sleep quality among children and adolescents with familial Mediterranean fever: A case-control and correlation study.

To evaluate the sleep quality and fatigue levels in children with familial Mediterranean fever (FMF) in comparison to healthy children. The Pediatric Quality of Life Multidimensional Fatigue Scale (PedsQL-MFS) and the Pittsburgh Sleep Quality Index (PSQI) were the instruments utilized to assess fatigue and sleep quality in children with FMF and controls, respectively. Spearman's rank coefficient was decisive in determining the association between patient-reported outcome measures and disease-related features. Two hundred twenty-five (59.3% female) patients and 182 (51.6% female) healthy counterparts were enrolled in the study. In PSQI, where high scores indicate sleep disturbance, the median score was significantly higher in the patient group (5; 3-6) than the control group (3; 2-4) (p < 0.001). PEDsQL-MFS demonstrated significantly lower fatigue levels in the control group than patients (p = 0.01). The level of fatigue in the patient group was found to increase in correlation with sleep problems (r: - 0.750, p < 0.001). Additionally, a high correlation was present between the PSQI/PedsQL-MFS scores and the number of attacks in the last year (r: - 0.645, p < 0.001/r: 0.721, p < 0.001, respectively). There was no difference in terms of fatigue and sleep disorders between mutations (homozygous, heterozygous, or compound heterozygous) in the MEFV gene (p > 0.05).    Conclusion: High disease activity has a significant negative impact on the sleep quality and fatigue levels of patients with FMF. This study emphasizes the importance of assessing fatigue and sleep quality with objective outcome tools periodically in FMF patients throughout the disease course. What is Known: • Fatigue is a common matter that often accompanies rheumatic diseases and causes disability. • Chronic rheumatic diseases often experience poor sleep quality. What is New: • In high correlation with the disease severity of familial Mediterranean fever, sleep quality decreases and fatigue level increases significantly. • In familial Mediterranean fever patients, a negative correlation is present between age and the general fatigue and sleep/rest related fatigue scores (low scores indicating greater fatigue) and sleep quality is poorer in the adolescent age group.

Rhupus syndrome in children: A multi-center retrospective cohort study and literature review.

OBJECTIVE: In this study, we aimed to evaluate the characteristics of pediatric rhupus patients including all the related series in the literature. METHODS: Thirty pediatric patients with rhupus syndrome from 12 different centers in Turkey were included in this study. The literature was also reviewed for pediatric patients with rhupus syndrome. RESULTS: The most prominent phenotype of these 30 patients was juvenile idiopathic arthritis (JIA) (60%) at the disease onset and SLE (73.3%) at the last visit. Major SLE-related organ involvements were skin (80%), hematological system (53.3%), and kidney (23.3%). Arthritis was polyarticular (73.3%), asymmetric (66.7%), and erosive (53.3%) in most patients. Hydroxychloroquine (100%), glucocorticoids (86.7%), and mycophenolate mofetil (46.7%) were mostly used for SLE, while glucocorticoids (76.6%), methotrexate (73.3%), and nonsteroidal anti-inflammatory drugs (NSAIDs) (57.6%) were mainly preferred for JIA. Our literature search revealed 20 pediatric patients with rhupus syndrome (75% were RF positive). The most prominent phenotype was JIA (91.7%) at the disease onset and SLE (63.6%) at the last visit. Major SLE-related organ involvements were skin (66.7%), hematological system (58.3%), and kidney (58.3%). Arthritis was polyarticular (77.8%), asymmetric (63.6%), and erosive (83.3%) in most patients. Glucocorticoid (100%), hydroxychloroquine (76.9%), and azathioprine (46.2%) were mostly used for SLE, while methotrexate (76.9%) and NSAIDs (46.2%) were mainly preferred for the JIA phenotype. CONCLUSION: Our study is the largest cohort in the literature evaluating pediatric rhupus cases. Most of the pediatric patients had polyarticular, asymmetric, and erosive arthritis, as well as organ involvements associated with SLE, including the skin, hematological system, and kidney.

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.

Evaluation of clinical outcomes in systemic juvenile idiopathic arthritis patients treated with biological agents in Turkey: the TURSIS study.

OBJECTIVES: Biological drugs are one of the most effective treatment methods for systemic juvenile idiopathic arthritis (SJIA) and can significantly prevent morbidity and mortality. This study aimed to evaluate the efficacy and safety of biologics in patients with SJIA and provide real-life data that might help improve the outcomes. METHODS: TURSIS was a retrospective multicentre study carried out in patients with SJIA for whom a biological treatment had been initiated between 1st March 2013 and 30th December 2018. Data include patients' characteristics, laboratory-clinical results, outcomes, and safety-related variables. The 24-month follow-up data of the patients and the efficacy and safety of biological drugs were evaluated. RESULTS: 147 patients were enrolled. The clinical course of the disease was as follows; it was monocyclic in 38.1%, polycyclic in 49%, and persistent in 12.9% of patients. First-choice biologics were interleukin (IL)-1 blockers in the majority of patients (56.5%), followed by the anti-IL-6 (25.2%) and anti-TNF-alpha drugs (18.4%). Anakinra was the most preferred biologic agent in patients with macrophage activation syndrome (MAS), and tocilizumab was used more frequently in patients with persistent type (p=0.000 and p=0.003). The most frequent switch rate was seen in patients receiving anakinra (n=40/68, 58.8%), and it was most frequently switched to canakinumab (n=32/40, 80%). Better physician's global assessment scores were achieved in patients treated with anakinra in Month 3, compared to other treatments (p=0.04). CONCLUSIONS: The results of our study support the efficacy of biological drugs in particular anti-IL-1 and anti-IL-6 drugs, in the treatment of SJIA. These treatments resulted in improvement in activity of disease and provide a considerable decrease in the frequency of MAS.

A score for predicting colchicine resistance at the time of diagnosis in familial Mediterranean fever: data from the TURPAID registry.

OBJECTIVES: Colchicine forms the mainstay of treatment in FMF. Approximately 5-10% of FMF patients are colchicine resistant and require anti-IL-1 drugs. We aimed to compare the characteristics of colchicine-resistant and colchicine-responsive patients and to develop a score for predicting colchicine resistance at the time of FMF diagnosis. METHODS: FMF patients (0-18 years) enrolled in the Turkish Paediatric Autoinflammatory Diseases (TURPAID) registry were included. The predictive score for colchicine resistance was developed by using univariate/multivariate regression and receiver operating characteristics analyses. RESULTS: A total of 3445 FMF patients [256 (7.4%) colchicine-resistant and 3189 colchicine-responsive) were included (female:male ratio 1.02; median age at diagnosis 67.4 months). Colchicine-resistant patients had longer, more frequent attacks and were younger at symptom onset and diagnosis (P < 0.05). Fever, erysipelas-like erythema, arthralgia, arthritis, myalgia, abdominal pain, diarrhoea, chest pain, comorbidities, parental consanguinity and homozygosity/compound heterozygosity for exon 10 MEFV mutations were significantly more prevalent among colchicine-resistant than colchicine-responsive patients (P < 0.05). Multivariate logistic regression analysis in the training cohort (n = 2684) showed that age at symptom onset, attack frequency, arthritis, chest pain and having two exon 10 mutations were the strongest predictors of colchicine resistance. The score including these items had a sensitivity of 81.3% and a specificity of 49.1%. In the validation cohort (n = 671), its sensitivity was 93.5% and specificity was 53.8%. CONCLUSION: We developed a clinician-friendly and practical predictive score that could help us identify FMF patients with a greater risk of colchicine resistance and tailor disease management individually at the time of diagnosis.

A clinical overview of paediatric sarcoidosis: Multicentre experience from Turkey.

OBJECTIVES: We aimed to outline the demographic data, clinical spectrum, and treatment approach of sarcoidosis in a large group of patients and sought to figure out the variations of early-onset (EOS) and late-onset paediatric sarcoidosis (LOS). METHODS: The study followed a retrospective-descriptive design, with the analysis of medical records of cases diagnosed as paediatric sarcoidosis. RESULTS: Fifty-two patients were included in the study. The median age at disease onset and follow-up duration were 83 (28.2-119) and 24 (6-48) months, respectively. Ten (19.2%) cases had EOS (before 5th birthday) and 42 (80.7%) cases had LOS. The most common clinical findings at the time of the disease onset were ocular symptoms (40.4%) followed by joint manifestation (25%), dermatological symptoms (13.5%), and features related to multi-organ involvement (11.5%). Anterior uveitis was the most common (55%) one among ocular manifestations. Patients with EOS displayed joint, eye, and dermatological findings more commonly than patients with LOS. The recurrence rate of disease in patients with EOS (5.7%) and LOS (21.1%) were not statistically different (P = .7). CONCLUSIONS: Patients with EOS and LOS may present with variable clinical features and studies addressing paediatric sarcoidosis cases in collaboration between disciplines will enhance the awareness of this rare disease among physicians and assist early diagnosis with lesser complications.

Addressing the unmet needs of transitional care in juvenile idiopathic arthritis.

OBJECTIVES: We aimed to comprehensively analyse the available literature to identify the unmet requirements in transitional programs tailored specifically for patients diagnosed with JIA. METHODS: According to published guidance on narrative reviews, a systematic review of the literature on transitional care in rheumatology was conducted. Pertinent documents were collected from reputable databases, such as Web of Science, Scopus, and MEDLINE/PubMed. The search encompassed literature published from the inception of each database until January 2023. RESULTS: In this study, a comprehensive analysis of the findings of 34 studies was conducted. Among these, 12 studies focused on assessing the readiness of adolescents and young adults diagnosed with JIA. Additionally, 18 studies examined the effectiveness of structured transition programs in terms of adherence and satisfaction. Finally, 4 studies investigated disease-related outcomes in this population. CONCLUSION: The need for transitioning children with rheumatic diseases to adult rheumatology services for continued care is clearly evident. However, the absence of established best practice guidelines presents a challenge in facilitating this transition effectively. Although several scoring systems have been proposed to ensure organized and seamless transfers, a consensus has not yet been reached. Furthermore, the socio-economic and cultural variations across countries further complicate the development of universal guidelines for transitioning children with rheumatic diseases. To address these concerns, our objective in conducting this literature review was to emphasize the significance of this issue and identify the specific requirements based on the unmet needs in the transition process.

Inflammatory comorbidities in the largest pediatric Familial Mediterranean fever cohort: a multicenter retrospective study of Pediatric Rheumatology Academy (PeRA)-Research Group (RG).

AIM: The aim of this study was to investigate the frequency and type of FMF-associated inflammatory diseases in a large FMF pediatric patients and to compare them to those FMF patients without concomitant inflammatory diseases. MATERIALS AND METHODS: Familial Mediterranean fever patients enrolled in the Pediatric Rheumatology Academy (PeRA)-Research Group (RG) were included. The patients were divided into two groups according to concomitant inflammatory disease as FMF patients who had a concomitant inflammatory disease (group 1) and FMF patients who did not have a concomitant inflammatory disease (group 1). The clinical findings and treatments were compared between the two groups. RESULTS: The study group comprised 3475 patients with FMF. There were 294 patients (8.5%) in group 1 and 3181 patients (91.5%) in group 2. Juvenile idiopathic arthritis (n = 136) was the most common accompanying inflammatory disease. Arthritis, M694V homozygosity, and the need for biological therapy were more frequently observed in Group 1 (p < 0.05). Fever and abdominal pain were more frequently detected in Group 2 (p < 0.05). FMF patients with concomitant inflammatory diseas more frequently demonstrated colchicine resistance. There were no significant differences in the median attack frequency, chest pain, amyloidosis, erysipelas-like erythema, or family history of FMF between the two patient groups. CONCLUSION: To the best of our knowledge, this is the largest pediatric cohort reviewed to date. FMF patients may have different clinical profiles and colchicine responses if they have with concomitant inflammatory diseases. Key points • FMF is associated with some inflammatory comorbidities diseases. • To the best of our knowledge, this is the largest cohort evlauated pediatric FMF associated inflammatory comorbidities diseases reviewed to date.

The safety of canakinumab in systemic juvenile idiopathic arthritis and autoinflammatory diseases in pediatric patients: a multicenter study.

OBJECTIVE: To evaluate the safety of canakinumab using real-world data in patients with systemic juvenile idiopathic arthritis (sJIA) and autoinflammatory diseases (AID). RESEARCH DESIGN AND METHODS: This was a cross-sectional observational, multicenter study. Patients diagnosed with AID and sJIA treated with canakinumab were included in the study. The participating 13 centers retrospectively collected their patients' data. RESULTS: A total of 335 patients were involved in the study. Among these patients, 280 were in the AID group and 55 were in the sJIA group. Canakinumab was administered at a median dose of 3 (2.5-4) mg/kg. The median total exposure time to canakinumab was 1.9 (0.8-3.2) years, corresponding to 759.5 patient-years. Seven hundred and seventy-nine total adverse events (AE) were identified. The total incidence of AE, and serious adverse events (SAE) throughout the study period was 1.02 per patient-years. The upper respiratory tract infection rate was 0.7 per patient-years, while the other infection rate was 0.13 per patient-years. While no death was observed in any patient, SAE were observed in 8 patients. Interstitial lung disease, anaphylaxis, or anaphylactoid reactions were not observed in any patient. CONCLUSIONS: Real-life data from a large cohort of patients suggests that canakinumab is as safe as claimed in clinical trials.

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.

Vaccination coverage of children with rheumatic diseases compared with healthy controls: a retrospective case-control study.

OBJECTIVE: To reveal the vaccination status of patients with pediatric rheumatic disease (PedRD) and to compare this with healthy controls. METHODS: The electronic health records of the Ministry of Health regarding the vaccination status of children with PedRD followed in a tertiary hospital were analyzed cross-sectionally and compared with their healthy controls. The missing vaccines were reported according to individual, age-appropriate schedule and causes of skipped vaccines in both groups were investigated with an online survey. RESULTS: The vaccination rate of patients in the last examination was 71.4% (90/126) and 95.7% (110/115) in healthy controls (p < 0.001). Measles-mumps-rubella vaccine, diphtheria, the administration rates of the second dose of tetanus-acellular pertussis-inactivated polio and Haemophilus influenzae type B, chickenpox, and hepatitis A vaccines were significantly lower in patients than in controls (p values 0.004, 0.02, 0.01, 0.013, respectively). The pre-diagnosis incomplete vaccination proportion was significantly higher in the patient group (16.6%) than in healthy controls (4.3%) (p = 0.002). In the patient group, the proportion of incomplete live-attenuated vaccines after diagnosis (25%) was more than pre-diagnosis (61.1%) (p = 0.04), while the proportion of incomplete non-live vaccines before and after diagnosis was similar (47.2% and 50%, respectively) (p = 0.73). The major reasons for missed vaccines were physicians' recommendations (15.6%), the presence of PedRD diagnosis (12.5%), and the drugs used (12.5%). CONCLUSION: Vaccination coverage of PedRD patients has been shown to lag behind the routine vaccination schedule (71.4%). In addition to new recommendations, electronic health system records for vaccination may be appropriate for the follow-up of these patients, and the addition of reminder alerts may be useful to reduce the rate of missed vaccinations.

Do the features of juvenile psoriatic arthritis change according to age? A comprehensive evaluation of the PeRA Research Group Registry.

OBJECTIVES: To describe the clinical features and treatment outcomes of children with juvenile psoriatic arthritis (JPsA) and to compare the distinct patterns of the disease between early-onset and late-onset age groups. METHODS: Patients with JPsA followed regularly for at least 6 months between 2010-2020 in 7 pediatric rheumatology centers in Turkey were included in the study. The demographic features, clinical manifestations, treatment strategies, and outcomes of the patients were evaluated retrospectively. RESULTS: Eighty-seven (46 male/41 female) patients were included in the study. The mean age at diagnosis was 11.9 ± 4.5. Fifty-seven (65.5%) patients had psoriasis at the time of diagnosis, arthritis preceded psoriasis in 10 (11.5%) patients. Thirty (34.5%) patients had dactylitis, 28 (32.2%) had nail pitting, 36 (41.4%) had involvement of the small joints, 20 (23%) had enthesitis. Sacroiliitis was detected in 11 (12.6%) patients by magnetic resonance imaging. Anti-nuclear antibodies (ANA) were positive in 35 (40.2%) patients. Twelve children (%13.8) were in the early-onset (<5 years) group. Uveitis and ANA positivity were more common in the early-onset group. Active joint counts and activity scores of our patients showed significant improvement at 6th month and at the last control compared with baseline. CONCLUSION: About one-third of patients with JPsA do not have psoriasis at the time of diagnosis. In some patients, no skin lesion is seen during the course of the disease. Children with psoriatic arthritis seem to display two different phenotypes. Younger children have female predominance, ANA positivity, and uveitis, while older children have more axial involvement.

How common is remission in rheumatoid factor-positive juvenile idiopathic arthritis patients? The multicenter Pediatric Rheumatology Academy (PeRA) research group experience.

OBJECTIVE: Rheumatoid factor (RF)-positive polyarthritis is the least common type of juvenile idiopathic arthritis (JIA). Functional disability in RF-positive polyarthritis patients is much more severe than in patients with other subtypes; but data on this subtype alone is limited. This study aimed to analyze clinical features, long-term follow-up, treatment response, and remission status in a large multicenter cohort of RF-positive polyarthritis patients. METHODS: This retrospective study included RF-positive polyarthritis patients that were followed up for ≥ 6 months between 2017 and 2022 by the Pediatric Rheumatology Academy (PeRA)-Research Group (RG). Data on patient demographics, clinical and laboratory characteristics were obtained from medical charts. JIA treatments and duration of treatment were also recorded. The patients were divided into 2 groups based on methotrexate (MTX) response, as follows: group 1: MTX responsive, group 2: MTX unresponsive. Clinical and laboratory findings were compared between the 2 groups. RESULTS: The study included 56 (45 female and 11 male) patients. The median age at onset of RF-positive polyarthritis was 13.2 years [(interquartile range) (IQR): 9.0-15.0 years] and the median duration of follow-up was 41.5 months (IQR: 19.5-75.7 months). Symmetrical arthritis affecting the metacarpophalangeal and proximal interphalangeal joints of the hands was commonly observed. Subcutaneous MTX was the preferred initial treatment; however, it was ineffective in 39 (69.6%) of the patients. Of 25 patients followed for 24 months, 56% still had active disease at 24 months. CONCLUSION: During 2 years of treatment, 44% of RF-positive polyarthritis patients have inactive disease, and they should be considered as a distinct and important clinical entity requiring aggressive and early treatment.

Initial manifestations and risk factors for calcinosis in juvenile dermatomyositis: A retrospective multicenter study.

OBJECTIVE: This study aimed to look for the initial manifestations of juvenile dermatomyositis (JDM), give follow-up results, and search for risk factors for the development of calcinosis. METHODS: The files of children with JDM diagnosed between 2005 and 2020 were reviewed retrospectively. RESULTS: The study included 48 children, 33 girls and 15 boys. The mean age at the onset of the disease was 7.6±3.6 years. The median duration of follow-up was 35 (6-144) months. Twenty-nine patients (60.4%) had monocyclic, 7 (14.6%) patients had polycyclic, and 12 (25%) patients had chronic persistent disease course. At the time of enrollment, 35 (72.9%) patients were in remission, while 13 (27.1%) patients had active disease. Calcinosis developed in 11 patients (22.9%). Children having myalgia, livedo racemosa, skin hypopigmentation, lower alanine aminotransferase (ALT) levels, and higher physician visual analog scores at the time of diagnosis had a higher risk for calcinosis. Calcinosis was also more common in children with diagnostic delay and chronic persistent disease course. None of these parameters remained independent risk factors for calcinosis in multivariate logistic regression analysis. CONCLUSION: The rate of mortality has decreased dramatically over decades in JDM, but the rate of calcinosis has not changed proportionately. Long duration of active, untreated disease is accepted as the main risk factor for calcinosis. We have seen that calcinosis was more common in children having myalgia, livedo racemosa, skin hypopigmentation, lower ALT levels, and higher physician visual analog scores at the time of diagnosis.