The Impact of Different MEFV Genotypes on Clinical Phenotype of Patients with Familial Mediterranean Fever: Special Emphasis on Joint Involvement.

Familial Mediterranean Fever (FMF) is the most common monogenic autoinflammatory disease worldwide. In this retrospective cohort study, we aimed to assess the effects of various MEFV genotypes on the clinical characteristics of the patients, with a special focus on the joint involvement. In total, 782 patients with FMF were categorized into 3 groups according to the MEFV mutation; Group 1: Patients homozygous for M694V; Group 2: Patients carrying other pathogenic MEFV variants in exon 10 in homozygous or compound heterozygous states; and Group 3: FMF patients with other variants or without mutations. Clinical and demographic findings were compared between groups. Among the 782 FMF patients, total frequency of arthritis was 237 (30.3%): 207 (26.4%) were acute monoarthritis and 67 (8.5%) were chronic arthritis. Both the frequency of arthritis (acute and/or chronic) (40.4% vs. 24.8% vs. 26.7%; p:0.001) and acute monoarthritis (35.4% vs. 20% vs. 23.7%; p:0.001) were significantly higher in Group 1 than in the other groups. FMF patients with chronic arthritis showed a distinct juvenile idiopathic arthritis (JIA) distribution pattern with a more frequent enthesitis-related arthritis (ERA) subtype (43.2%). HLA-B27 was positive in 24% of the ERA patients.Conclusion: Homozygous M694V mutation is associated with a more frequent and longer acute monoarthritis comparing to other MEFV genotypes. In addition, the risk of chronic arthritis seems not related to the MEFV mutations. However, FMF patients with chronic arthritis show a distinct ILAR JIA distribution pattern with a more frequent ERA and undifferentiated arthritis subtype. What is known: • Homozygous M694V mutation is associated with a more frequent and longer acute monoarthritis What is new: • FMF patients with chronic arthritis show a distinct ILAR JIA distribution pattern with a more frequent ERA subtype • ERA patients with negative HLA-B27 antigen should also be assessed for polyserositis episodes of FMF, especially in countries with high FMF carrier frequency.

Children With Type 1 Interferonopathy: Commonalities and Diversities in a Large Patient Cohort.

OBJECTIVE: This study aimed to provide a comprehensive overview of the clinical features, laboratory and screening results, treatment options, and outcomes of patients with type I interferonopathy. Our secondary goal was to identify the predictors of long-term morbidity or mortality. METHODS: We included children with genetically confirmed type I interferonopathies, with a follow-up duration of > 1 year. Data were obtained retrospectively from medical records. RESULTS: Of the 40 eligible patients for the study, 52.5% were female, with a median age of disease onset of 1.5 years (range 0.1-13.2 yrs). They were diagnosed at an average age of 6.8 (SD 4.6) years. Aicardi-Goutières syndrome was the most common diagnosis (n = 15, 37.5%). The central nervous system was the most frequently affected system (n = 27, 67.5%). Janus kinase inhibitors were administered to 17 (42.5%) patients. Twenty-five patients (62.5%) developed at least 1 permanent morbidity or died during follow-up; thus, they were included in the poor outcome group. Although younger age at disease onset, intracranial calcification (ICC), and lack of chilblains and elevated acute-phase reactants were significant in univariate logistic regression analysis, only ICC on magnetic resonance imaging at admission (adjusted odds ratio 19.69, 95% CI 1.08-359.05, P = 0.04) was found to be a significant predictor of poor outcomes in multivariate logistic regression analysis. CONCLUSION: For the first time, we evaluated the predictors of poor outcomes in patients with type I interferonopathy with a broad spectrum of subtypes. Further, our study's unique patient characteristics can provide valuable insights into these extremely rare conditions.

Evaluation of thyroid dysfunction in childhood-onset systemic lupus erythematosus: Risk factors for Hashimoto's thyroiditis.

OBJECTIVE: Increased frequency of autoimmune thyroid disease, particularly Hashimoto's thyroiditis (HT) was reported several studies in the literature, in individuals with childhood-onset systemic lupus erythematosus (cSLE). Our study aimed to investigate the prevalence and contributing factors of thyroid dysfunction and HT among cSLE patients. METHODS: Thyroid function tests were obtained cross-sectionally from cSLE patients. Demographic, clinical, and laboratory characteristics and activity scores were collected from medical records. Patients diagnosed with cSLE were compared to the healthy control group for the frequency of thyroid dysfunction. The Mann-Whitney U, independent samples t test, and the Chi-square or Fisher's exact test were used to compare study groups. A p-value below 0.05 was considered statistically significant. RESULTS: Out of 73 cSLE patients, 14 (19.1%) had subclinical hypothyroidism, 9 (12.3%) had clinical hypothyroidism, 12 (16.4%) were diagnosed with HT, and 12 (16.4%) had a family history of HT. Thyroid USG was performed in 5 euthyroid patients and 1 borderline subclinical hypothyroid patient with positive thyroid autoantibody and reported as diffuse heterogeneous echogenicity enlargement in the thyroid gland. There were no significant differences in clinical and laboratory data or medication used between the groups with and without HT; however, patients with HT had a higher frequency of clinical hypothyroidism and family history of HT. Cumulative prednisolone dose was significantly lower in patients diagnosed with HT. The frequency of HT was considerably higher in patients with cSLE compared to the healthy control group. CONCLUSION: The results demonstrate an increased incidence of HT in cSLE patients, even if they are euthyroid, and recommend that cSLE patients be screened more frequently.

Long-term safety profile and secondary effectiveness of canakinumab in pediatric rheumatic diseases: a single-center experience.

BACKGROUND: To demonstrate the long-term safety profile of canakinumab over a nine-year period by documenting adverse events in patients with various pediatric rheumatic diseases. RESEARCH DESIGN AND METHODS: This retrospective observational study was conducted at the Pediatric Rheumatology Department of Istanbul University Cerrahpasa between 2015 and 2023. The analysis concerned individuals who had been administered canakinumab treatment for at least six months. The exposure-adjusted event rates were calculated as adverse events per 100 patient days and were compared among three groups based on the cumulative canakinumab dose of <35 mg/kg, 35-70 mg/kg, and >70 mg/kg. RESULTS: Among 189 patients, the median exposure time to canakinumab was 2.9 (1.5-4.1) years, corresponding to 573.4 patient years. The median cumulative dose of canakinumab was 2205 (1312-3600) mg. The most common adverse event was upper respiratory tract infection (0.76), followed by urinary tract infection (0.02), pneumonia (0.009), latent tuberculosis (0.009) and lymphadenitis (0.004). A total of 55 serious adverse events (0.025) were reported, 12 (0.006) of which led to drug discontinuation. The event rate of macrophage activation syndrome and disease exacerbation was statistically higher in patients receiving <35 mg/kg cumulative canakinumab dose (p < 0.05). CONCLUSIONS: An increase in side effect was not observed with the increasing cumulative doses of canakinumab. Canakinumab demonstrated long-term safety with appropriate indication and monitoring.

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.