Şengül Çağlayan

Objectives: With advances in genetic testing, monogenic lupus is increasingly recognized, yet disease-specific classification criteria are lacking. We compared all three classification criteria sets in the same monogenic lupus cohort and, for the first time, evaluated their performance across distinct genetic pathways. Methods: This national multicentre study included 88 genetically confirmed monogenic lupus patients from 22 paediatric rheumatology centres across Türkiye. Fulfilment of the AmericanCollege of Rheumatology (ACR)-1997, Systemic Lupus International Collaborating Clinics (SLICC)-2012 and European League Against Rheumatism (EULAR)/ACR-2019 criteria and pathway-based differences in classification performance were assessed. Results: Overall, 74% (n = 65) fulfilled ACR-1997, 70.5% (n = 62) SLICC-2012 and EULAR/ACR-2019 criteria, and 62.5% (n = 55) met all three, whereas 17% (n = 15) met none. Agreement was substantial (κ = 0.63–0.73), with no significant differences between criteria (P > 0.05). Classification performance differed significantly across genetic pathways (P < 0.05), with the highest fulfilment performances in complement deficiencies and the lowest in nucleic acid metabolism and type I interferon pathway defects. Most patients who did not fulfil any classification criteria had nucleic acid metabolism and clearance defects (13/15, 86.7%). Domain-level analyses showed that classification success was mainly driven by mucocutaneous, immunologic and renal domains. Complement and immune-regulation defects showed a more classical lupus phenotype, with most fulfilling all three criteria (78.6%, 22/28 and 77.8%, 14/18), whereas the proportion was lower in type I interferon pathway and nucleic acid metabolism and clearance defects (33.3%, 2/6 and 47.2%, 17/36). No classification criteria were superior within genetic pathways. Conclusion: One-third of genetically confirmed monogenic lupus patients remained unclassified, particularly those with interferon-related and nucleic acid metabolism defects, highlighting pathway-dependent limitations of current classification criteria.

Background: This study evaluated the efficacy, safety, and drug retention of anakinra and canakinumab in paediatric patients with colchicine-resistant familial Mediterranean fever (cr-FMF) within a real-world cohort. Methods: This retrospective cohort study was conducted from June 2016 to April 2024, including 86 patients diagnosed with cr-FMF. Clinical and laboratory parameters, including attack frequency, C-reactive protein, serum amyloid A, and autoinflammatory disease activity index (AIDAI) scores, were recorded at baseline and during follow-up. Results: A total of 86 patients (50 females, 36 males) were included in the study. All carried exon 10 MEFV mutations, with 69 patients (80.2%) having the M694V/M694V genotype. Anakinra was initiated in 36 patients (41.9%), and canakinumab in 50 patients (58.1%). The median treatment duration was significantly longer for canakinumab (48 months) compared to anakinra (7 months) (P < .001). Both treatments significantly reduced attack frequency, AIDAI scores, C-reactive protein, and serum amyloid A levels compared to baseline (P < .001). While the reduction in attack frequency was comparable between the groups, patients treated with canakinumab achieved significantly lower mean AIDAI scores at 12 months compared to the anakinra group (P = .021). Anakinra provided a more rapid onset of symptom control but was commonly discontinued due to injection site reactions (44.4%). Canakinumab was associated with sustained long-term disease control with fewer local side effects. However, rare serious events, including acute myeloid leukaemia and inflammatory bowel disease, were observed, though causality with treatment could not be established. Conclusions: In this paediatric cohort of cr-FMF patients, both anakinra and canakinumab were effective in reducing disease activity and inflammation. Anakinra offered rapid symptom relief but had frequent injection site reactions. Canakinumab provided sustained control with fewer local side effects but required monitoring for rare complications. Key points:

Objectives: Anti-interleukin-1 therapies are effective for colchicine-resistant familial Mediterranean fever (FMF), yet data on optimal duration in pediatric patients remain limited. A previous multicentre study showed favorable outcomes with a standardized canakinumab dose extension protocol, though follow-up was short. This study aimed to assess the long-term outcomes of this protocol. Methods: The protocol, developed via a multicentre Delphi consensus in Turkey, recommends doubling the canakinumab dosing interval after six attack-free months and tripling it after one year of continued remission. This retrospective study included colchicine-resistant FMF patients treated according to the protocol, with data extracted from medical records. Results: Forty-five patients initiated monthly canakinumab. The median follow-up after starting canakinumab was 47 months (range 35–78). After six months, intervals were extended to every two months. During bimonthly dosing, 7 patients (15.6%) experienced attacks and reverted to monthly dosing. Of the 38 patients (84.4%) whose interval was further extended to every three months, 11 returned to bimonthly dosing due to attacks. Among 10 patients who achieved remission with three-month intervals, treatment was discontinued; 5 remained attack-free, while 5 had attacks. Seventeen patients continued three-monthly dosing, one was lost to follow-up, and 16 (35.6%) remained attack-free at a median follow-up of 33 months (IQR: 6.5). Clinical and laboratory findings were similar between patients with and without attacks, except splenomegaly, which was absent in the attack-free group (p= 0.006). Conclusion: The dose extension protocol shows promising long-term outcomes in colchicine-resistant FMF. Larger, prospective studies are warranted to optimize treatment strategies.

Background. The aim of this study was to investigate whether a short exon screening consisting of selected variants could confirm the diagnosis in patients with a preliminary diagnosis of familial Mediterranean fever (FMF), thus providing a cost-saving alternative to a comprehensive MEditerranean FeVer (MEFV) gene sequence analysis test. Methods. This observational study on pediatric patients focused on clinically suspected FMF cases without prior genetic analysis. Participants met the Turkish pediatric FMF criteria. They underwent short exon screening for M694V, M680I, V726A, and E148Q variants. Those who were heterozygous or negative on short exon screening received further MEFV gene sequence analysis. Results. The study involved 1557 patients. Pathogenic variants in both alleles of the MEFV gene were found in 611 patients (39.2%), and a high-penetrance variant in heterozygosity or an E148Q variant on the other allele was found in 643 patients (41.3%). A further 189 patients (12.1%) had one or two E148Q variants. Short-exon screening was negative in 114 patients (7.6%). Of the 876 patients who underwent MEFV gene sequence analysis, additional variants were found in 72 of the 762 initially heterozygous patients. Of the 114 initially negative patients, 34 had homozygous or compound heterozygous variants, and 74 had heterozygous variants. Ultimately, only 6 patients yielded negative results in the MEFV gene sequence analysis. Conclusion. The short exon screening for common MEFV mutations offers a practical and cost-saving alternative to comprehensive MEFV gene sequence analysis in populations with a high prevalence of FMF.

The aim of this study was to assess the efficacy and safety of etanercept (ETA) use in juvenile idiopathic arthritis (JIA). The 24-month data of patients with JIA on etanercept in a single center were evaluated retrospectively. Response to treatment was assessed according to 10-joint Juvenile Arthritis Disease Activity Score (JADAS10), and JIA-American College of Rheumatology (ACR) improvement criteria. Safety assessments were based on adverse event (AE) reports. The study included 152 patients with JIA. The mean age at diagnosis of JIA was 8.5 ± 4.4 years, and treatment with ETA started at a mean age of 11.1 ± 4.4 years. The mean duration of ETA use was 16 ± 11.1 months. The mean JADAS10 score at baseline was 18.5 ± 5.9. By the third month, it had reduced to 8.6 ± 6.6 and by the sixth month to 5.7 ± 6. By the twelfth month, the JADAS10 score was 4.9 ± 6.7, and by the twenty-fourth month, it worsened to 7.3 ± 7.8. ACR50 response, was achieved in 79.6% of patients at three months, 67.1% at six months, 79.3% at twelfth months, 70.7% at twenty-fourth months. During ETA treatment, 10 patients required hospitalization for serious infections. Etanercept is a safe and effective option for patients with JIA. However, variations in response between JIA subtypes highlight the need for individualized treatment strategies.

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

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.

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.