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 1 interferonopathy. Our secondary goal was to identify the predictors of long-term morbidities or fatalities. METHODS: We included children with genetically confirmed type 1 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 (0.1-13.2). They were diagnosed at an average age of 6.8 ± 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 one permanent morbidity or died during follow-up; thus, they were included in the poor-outcome group. While younger age at disease onset, intracranial calcification (ICC), and lack of chilblains and elevated acute phase reactants (APRs) were significant in univariate logistic regression analysis, only ICC on MRI at admission (aOR, 19.69; 95% C.I.: 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 1 interferonopathy with a broad spectrum of subtypes. Furthermore, our study's unique patient characteristics can provide valuable insights into these extremely rare conditions.

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.

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.

Clinical characteristics of pediatric noninfectious uveitis and risk factors for severe disease: a single-center study.

OBJECTIVES: We aimed to present the demographic, clinical, laboratory, and treatment data of children with non-infectious uveitis and to evaluate the risk factors for the development of complications and the need for biological treatment. METHOD: Patients diagnosed with non-infectious uveitis in childhood and followed up for at least 1 year were included in the study. Demographic data, including age, gender, age at diagnosis, uveitis in first-degree relatives, and rheumatologic diseases, were obtained retrospectively from medical records. The presence of complications or the need for biologic therapy was considered a composite outcome suggesting severe disease. RESULTS: The study included 123 patients (female: n = 59, 48%). The mean age at diagnosis was 14.89 ± 4.86 years. Uveitis was symptomatic in 104 patients (84.6%). Approximately one-quarter of the patients had at least one rheumatic disease (n = 35, 28.5%), the most common being juvenile idiopathic arthritis. Thirty-three patients (26.8%) had anti-nuclear antibody positivity. Biologic agents were needed in 60 patients (48.8%). Complications developed in 14 patients (11.4%). Early age at disease onset (aOR, 0.875; 95% C.I. 0.795-0.965, p = 0.007) and female gender (aOR, 2.99; 95% C.I. 1.439-6.248, p = 0.003) were significantly associated with the need for biologic treatment, while Behçet's disease (BD) was strongly associated with uveitis-related complications (aOR, 14.133; 95% C.I. 2.765-72.231, p = 0.001). CONCLUSION: We suggest that among pediatric patients with non-infectious uveitis, females, those with an early age of disease onset, and those with BD need to be closely monitored due to a significantly increased risk of severe disease. Key Points • Limited data exist on the clinical course of non-infectious uveitis in children and the associated risk factors for severe disease. • Our study reveals that nearly a quarter of pediatric patients with non-infectious uveitis also have a rheumatic disease. • Among pediatric patients diagnosed with non-infectious uveitis, we observed an increased risk of severe disease in those with an earlier onset age, in female patients, and in those diagnosed with Behçet's disease.

COVID-19 vaccination rates and factors affecting vaccination in children with rheumatic disease.

Objectives: This study aimed to investigate coronavirus disease 2019 (COVID-19) vaccination rates and factors affecting vaccination in children with rheumatic diseases. Patients and methods: This multicenter cross-sectional survey-based study was conducted between July 2022 and September 2022. Four hundred seventy-four patients (256 females, 218 males; median age: 15 years; interquartile range, 13 to 16 years) were included in the patient group, and 211 healthy children (124 females, 87 males; median age: 15 years; interquartile range, 13 to 16 years) were included in the control group. A questionnaire was administered to the parents face-to-face during routine outpatient visits. Results: Of the patients, 220 were followed up with the diagnosis of autoinflammatory disease, 174 with juvenile idiopathic arthritis, 48 with connective tissue disease, 23 with vasculitis, eight with uveitis, and one with sarcoidosis. In the study group, 256 (54%) patients and 115 (54.5%) healthy children received at least one dose of COVID-19 vaccine. Parents' concern regarding potential side effects of the vaccine was the most common reason for COVID-19 vaccination hesitancy in both groups. The median patient age, follow-up period, colchicine treatment rates, childhood vaccination and influenza vaccination rates, median parental age, parental vaccination rate, and parental education level were higher in vaccinated patients (p<0.001). Conclusion: Parents' concerns about safety and side effects were found to be the most important factors affecting vaccination success. Identification of the underlying causes of parental vaccine hesitancy will facilitate the development of effective vaccination strategies for potential future outbreaks.

Health conditions of first-degree relatives of children with familial Mediterranean fever.

BACKGROUND: Given the strong genetic background of familial Mediterranean fever (FMF), the frequently reported co-existing diseases in children with FMF should also be investigated in other family members. Therefore, we aimed to examine the medical conditions of first-degree relatives (FDRs) of our pediatric patients with FMF in the present study. METHODS: Chronic diseases of FDRs of pediatric 449 FMF, 147 juvenile idiopathic arthritis (JIA) patients and 93 healthy controls (HC) were questioned during their routine clinical visits for 9 consecutive months. RESULTS: A total of 1975 FDRs of 449 FMF, 690 FDRs of 147 JIA patients, and 406 FDRs of 93 HC were included into the study. The most common medical conditions were non-atopic asthma (n=71, 3.6%), type 2 DM (n=14, 2%), and tonsillectomy history (n=12, 2.95%) in the FMF, JIA, and HC groups, respectively. Atopic diseases (FMF vs. JIA: p=0.013; FMF vs. HC: p=0.014), rheumatic diseases (FMF vs. JIA: p=0.030; FMF vs. HC: p=0.017), and surgical histories (FMF vs. JIA: p<0.01; FMF vs. HC: p=0.026), including adenoidectomy, tonsillectomy, and appendectomy, were significantly more common in the FMF group than in other groups. CONCLUSIONS: Our novel findings may contribute to understanding the hereditary burden of co-existing diseases in children with FMF and encourage further studies involving genetic screenings.

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.

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.

Ovarian reserve in children with juvenile idiopathic arthritis using biologic disease-modifying anti-rheumatic drugs.

BACKGROUND/OBJECTIVES: The aim of the study is to assess the effect of juvenile idiopathic arthritis (JIA) and biologic disease-modifying anti-rheumatic drugs (bDMARDs) on ovarian reserve in children. MATERIALS AND METHODS: A cross-sectional study was performed from March 2021 to March 2022 and included 81 patients with JIA and 49 healthy children. Serum anti-Mullerian hormone (AMH), follicle-stimulating hormone (FSH), luteinizing hormone (LH), and estradiol levels were analyzed using electrochemiluminescence methods. RESULTS: The mean of current age (13.5 ± 3.2 vs. 14.4 ± 2.4 years), height standard deviation score (SDS) (- 0.35 ± 1.18 vs. - 0.44 ± 0.94), body mass index SDS (0.12 ± 1.33 vs. 0.25 ± 1.28), and the median weight SDS (- 0.13 (- 2.27-3.23) vs. - 0.52 (- 3.4-3.3)) were similar in JIA patients and controls (p > 0.05). Patients with JIA were divided into two groups according to their treatment regimens: treated with methotrexate (MTX) (biologic naive) (n = 32) and treated with MTX plus bDMARDs (n = 49). No significant differences were detected between the 3 groups regarding menarche age, menstrual cycle length, and flow duration (for all p > 0.05). The median serum concentration of AMH was 2.94 (1.12-7.88) ng/ml in the control group, 3.02 (0.36-8.54) ng/ml in the biologic naïve group, and 3.01 (0.99-8.26) ng/ml in the MTX plus bDMARD group. There were no significant differences between 3 groups according to serum AMH, FSH, LH, and estradiol levels (p > 0.05). CONCLUSION: Biologic DMARDs are reassuring in terms of ovarian reserve in girls with JIA and demonstrate that AMH is unaffected by treatment. Prospective studies with larger sample sizes are needed to confirm our findings and to evaluate the impact on the future fertility of patients. Key Points • Although biologic disease-modifying anti-rheumatic drugs (bDMARDs) are being game-changing treatment options in juvenile idiopathic arthritis, their effect on fertility and ovarian reserve is one of the most discussed issues. • In addition to treatment used, autoimmune diseases might also have a negative effect on fertility. • In this cross-sectional study, we found that anti-Mullerian hormone level of patients who were on bDMARDs, patients who were on methotrexate, and healthy controls were similar. • Our results suggest that bDMARDs are reassuring in terms of ovarian reserve in girls with JIA and demonstrate that AMH is unaffected by treatment.

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.

Temporary Thyroid Dysfunction and Catecholamine Excess Due to Mercury Poisoning in 6 Cases.

OBJECTIVE: Mercury poisoning is a condition with multiple-organ dysfunction that has effects on the central nervous system, gastrointestinal system, cardiovascular system, skin, lungs, and kidneys. It can be fatal or may result in sequelae such as neurological disturbances, if treated late or left untreated. The endocrinological effects of mercury exposure are not well-known. We aimed to evaluate patients with mercury poisoning. MATERIALS AND METHODS: A total of 6 cases of mercury poisoning from 3 families were included in the study. Clinical, laboratory, and follow-up data were recorded. RESULTS: Thyroid dysfunction was presented as high thyroid hormones and normal thyrotropin level (unsuppressed) in 5 cases (83.3%). On the other hand, pheochromocytoma-like syndrome was detected in 5 cases (83.3%) with hypertension. The 4 cases were the first to use methimazole for mercury poisoning due to tachycardia and hypertension despite antihypertensive treatment due to catecholamine excess and thyroid dysfunction. Hyponatremia was detected in 3 cases (50%). CONCLUSION: Mercury poisoning is difficult to diagnose because it is rare and presents with nonspecific physical and laboratory findings. Early diagnosis and providing appropriate treatment are essential in order to prevent sequelae. Mercury poisoning should be considered in patients with unexplained hypertension and tachycardia suggesting the involvement of thyroid hormones and catecholamines.

The impact of COVID-19 on clinical course and treatment among patients with juvenile systemic sclerosis.

Objectives: This study aimed to explore the influence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic among patients with juvenile systemic sclerosis (JSS). Patients and methods: Twenty-seven patients (22 females, 5 males; mean age: 20 years; range, 17 to 22 years) diagnosed with JSS and followed up at the department of pediatric rheumatology were included in the cross-sectional study. A web-based survey was performed by focusing on patients' complaints, accessibility to health care, and compliance with routine treatment from January 1, 2021, to January 10, 2021. Results: Five (18.5%) patients had deterioration of the disease, while six (22.2%) patients reported irregular usage of their routine scleroderma treatment during the last six months. Nine (33.3%) patients had missed their routine clinic control since the proclamation of the SARS-CoV-2 pandemic. Seven (25.9%) patients had household contact with coronavirus disease 2019 (COVID-19). Four (14.8%) patients were diagnosed with COVID-19, and only one (3.7%) was hospitalized. Nine patients were under biological treatment (tocilizumab); however, only one of them was diagnosed with COVID-19. Conclusion: The COVID-19 pandemic has not significantly disrupted the medical care of JSS patients. Telemedicine could be an acceptable option for JSS patients disenabled to come to the hospital.

Gray zone in the spectrum of autoinflammatory diseases: familial Mediterranean fever accompanying periodic fever, aphthous stomatitis, pharyngitis, and adenitis syndrome: single-center experience.

Despite the advanced knowledge concerning autoinflammatory diseases (AID), more data regarding the optimal treatment options and outcomes of the children who met the criteria of more than one AID are required. This study aimed to describe the demographic and clinical characteristics of children from familial Mediterranean fever (FMF)-endemic countries who meet both the FMF and the periodic fever, aphthous stomatitis, pharyngitis, and adenitis (PFAPA) syndrome criteria. Moreover, we aimed to measure the response rates to colchicine and tonsillectomy and evaluate the factors affecting the colchicine response in these patients. The study was conducted at pediatric rheumatology tertiary centre. A total of 131 patients (58 females; 73 males) who met both the modified Marshall and pediatric FMF criteria were included. The median age at onset was 18 months (1-77 months), and the mean age at diagnosis was 47 ± 21.88 months. The median interval between episodes was 21 (7-90) days. The median disease duration was 46 (6-128) months. Consanguineous marriage was detected in 17 (13%) of the patients. The most common clinical finding was fever (100%), followed by exudative pharyngitis (88.5%), abdominal pain (86.3%), arthralgia (61.8%), stomatitis (51.1%), adenitis (42%), myalgia (28.7%), chest pain (16%), maculopapular rash (12.2%), arthritis (8.4%), and erysipelas-like rash (4.6%). MEFV gene variants were identified in 106 (80.9%) patients. The most common variants were M694V heterozygous (29%). We found that patients with tonsillopharyngitis, aphthous stomatitis, and PFAPA family history were more likely to be colchicine-resistant and tonsillectomy responsive, while those with exon 10 MEFV gene mutations were more prone to have a favorable response to colchicine.     Conclusion: PFAPA syndrome patients with exon 10 MEFV gene mutation, showing typical FMF symptoms, should be treated with colchicine, even after tonsillectomy. In multivariate analysis, PFAPA family history and lack of exon 10 MEFV gene mutations were independent risk factors for colchicine resistance. Thus, tonsillectomy may be recommended as a possible treatment option for these patients. It has yet to be clarified when colchicine treatment will be discontinued in patients whose attacks ceased after tonsillectomy that was performed due to colchicine unresponsiveness. What is Known: • A certain number of patients with periodic fever, aphthous stomatitis, pharyngitis, and adenitis (PFAPA) syndrome concomitantly fulfill the familial Mediterranean fever (FMF) criteria. • While colchicine is proposed as a first treatment choice in familial Mediterranean fever (FMF), corticosteroids are recommended as a first-line treatment in PFAPA syndrome patients. What is New: • In patients with concomitant PFAPA syndrome and FMF, PFAPA family history and lack of exon 10 MEFV gene mutation are predictive factors of colchicine resistance. • The presence of exon 10 MEFV gene mutations in patients with concomitant FMF and PFAPA syndrome has a favourable effect on response to colchicine treatment.

The efficacy of a single-dose anakinra injection during disease attack in pediatric familial Mediterranean fever.

The aim of this retrospective study is to evaluate the efficacy of a single-dose anakinra during familial Mediterranean fever (FMF) attacks and its effect on the duration, severity, and frequency of attacks. The patients with FMF who had disease episode and received a single-dose anakinra during disease episode between December 2020 and May 2022 were included. Demographic characteristics, MEFV gene variants detected, concomitant medical conditions, demographics of recent and previous episodes, laboratory findings and length of hospital stay were recorded. A retrospective analysis of medical records revealed 79 attacks from 68 patients who met inclusion criteria. The patients had a median age of 13 (2.5-25) years. All patients reported that the average duration of their previous episodes lasted longer than 24 h. When the recovery time of attacks after subcutaneous anakinra application at the disease attack was examined, it was observed that 4 attacks (5.1%) ended in 10 min; 10 attacks (12.7%) in 10-30 min; 29 attacks (36.7%) in 30-60 min; 28 attacks (35.4%) in 1-4 h; 4 attacks (5.1%) in 24 h; and 4 attacks (5.1%) ended in more than 24 h. There was no patient who did not recover from their attack after a single dose of anakinra. Although the efficacy of a single-dose anakinra administration during FMF attacks in children needs to be confirmed by prospective studies, our results suggest that use of a single-dose anakinra during FMF attacks is effective in reduction of severity and duration of disease attacks.

Type I Interferonopathies in Childhood.

Type 1 interferonopathy is a novel context reflecting a group of inborn disorders sharing common pathway disturbances. This group of diseases is characterized by autoimmunity and autoinflammation caused by an upregulation of type 1 interferons (IFN)s due to certain genetic mutations. Several features are common in most of the diseases in this group, such as vasculitic skin changes, including chilblains, panniculitis, interstitial lung disease, basal ganglion calcifications, neuromotor impairments, epilepsy, stroke, and recurrent fever. Family history and consanguineous marriage are also common. IFN signature is a useful diagnostic tool and is positive in almost all patients with type 1 interferonopathies. Although IFN signature is a sensitive test, its specificity is relatively low. It can also be positive in viral infections and several connective tissue diseases. Therefore, next-generation sequence methods, whole exome sequencing (WES) in particular, are required for the ultimate diagnosis. The optimal treatment regime is still under debate due to a lack of clinical trials. Although high-dose steroids, anti-IL-1 and anti-IL-6 treatments, and reverse transcriptase inhibitors are used, JAK inhibitors are highly promising. Additionally, monoclonal antibodies against IFN-alpha and interferon-α receptor (IFNAR) are currently underway.

Neuropsychiatric involvement in juvenile-onset systemic lupus erythematosus: A multicenter study.

INTRODUCTION: Neuropsychiatric (NP) involvement is a restricted area in juvenile-onset systemic lupus erythematosus (jSLE). AIM: To investigate the prevalence, demographic and clinical features, and outcomes of the neurological involvement in the Turkish jSLE population. METHODS: This study was based upon 24 referral centers' SLE cohorts, multicenter and multidisciplinary network in Turkey. Patient data were collected by a case report form which was standardized for NP definitions according to American Collage of Rheumatology (ACR). Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index (SDI) neuropsychiatric part was used to determine NP damage. Variables were evaluated Ward's hierarchical clustering analyses, univariate, and multivariate logistic regression analyses. RESULTS: A hundred forty-nine of 1107 jSLE patients had NP involvement (13.5%). The most common NPSLE findings were headache (50.3%), seizure (38.3%), and acute confusional state (33.6%). Five clusters were identified with all clinical and laboratory findings. The first two clusters involved neuropathies, demyelinating diseases, aseptic meningitis, and movement disorder. Cluster 3 involved headache, activity markers and other SLE involvements. Idiopathic intracranial hypertension, cerebrovascular disease, cognitive dysfunction, psychiatric disorders and SLE antibodies were in the fourth, and acute confusional state was in the fifth cluster. In multivariate analysis, APA positivity; OR: 2.820, (%95CI: 1.002-7.939), P: 0,050, plasmapheresis; OR: 13.804 (%95CI: 2.785-68.432), P: 0,001, SLEDAI scores; OR: 1.115 (%95CI: (1.049-1.186), P: 0,001 were associated with increased risk for neurologic sequelae. CONCLUSION: We detected the prevalence of juvenile NPSLE manifestations in Turkey. We have identified five clusters that may shed light pathogenesis, treatment and prognosis of NP involvements. We also determined risk factors of neurological sequelae. Our study showed that new definitions NP involvements and sequelae for childhood period are needed.

Non-Rheumatic Chronic Comorbidities in Children with Juvenile Idiopathic Arthritis.

OBJECTIVE: Juvenile idiopathic arthritis is a heterogeneous group of disorders and is the most common rheumatic condition in childhood. There are scarce data regarding all comorbidities in juvenile idiopathic arthritis patients. MATERIALS AND METHODS: We aimed to identify the non-rheumatic comorbidities in our juvenile idiopathic arthritis patients. Data were obtained cross-sectionally from the medical records and the face-to-face interviews for 6 consecutive months. Those with more than 1 rheumatic disease were excluded, and conditions that were highly related to the disease, such as uveitis, were not taken into account. RESULTS: The study included 459 patients with female dominance (62.1%, n = 285). The median age of the patients was 12.87 (1.53-20.95) years. One hundred fifty patients (32.7%) had at least 1 comorbidity (5 patients had 3 comorbidities, and 24 patients had 2 comorbidities). The most common 3 non-rheumatic accompanying medical conditions in our patients were allergic rhinitis (n = 37, 8.1%), attention-deficit hyperactivity disorder (n = 35, 7.6%), and atopic dermatitis (n = 28, 6.1%). None of our patients with systemic JIA had any autoimmune disease. All the patients with primary immune deficiencies had anti-nuclear antibody positivity. CONCLUSION: Almost one-third of our patients had at least one comorbidity. This finding might be very helpful to us in planning our multi-disciplinary approach to our patients.

Risk factors for coronary arterial involvement in Turkish children with Kawasaki disease: a multicenter retrospective study.

BACKGROUND: Coronary arterial lesions (CALs) are the major component of Kawasaki disease (KD), associated with significant morbidity, which affect a substantial proportion of patients despite proper treatment. The aim of this study was to define the risk factors for CALs in Turkish children with KD. METHODS: Medical records of 399 KD patients from five pediatric rheumatology centers in Turkey were reviewed retrospectively. Demographic, clinical (including duration of fever before intravenous immunoglobulin [IVIG] and resistance to IVIG), laboratory and echocardiographic data were noted. RESULTS: The patients with CALs were younger, had a higher male ratio and a longer duration of fever before IVIG. They also had higher lymphocyte and lower hemoglobin values before the initial treatment. Multiple logistic regression analyses defined the following three criteria as independent risk factors for predicting CALs in Turkish children with KD: age ≤12 months, male gender and duration of fever before IVIG ≥9.5 days. High sensitivity rates of elevated risk of CALs up to 94.5% were calculated despite specificity values falling to 16.5%, depending on which of these three parameters are taken into account. CONCLUSIONS: Based on the demographic and clinical features, we established an easily applicable risk-scoring system for predicting CALs in Turkish children with KD. This may be useful for choosing appropriate treatment and follow-up for KD to prevent coronary artery involvement. Further studies will show whether these risk factors can be used in other Caucasian populations as well.

NLRP3 gene variants and serum NLRP3 levels in periodic fever, aphthous stomatitis, pharyngitis, and adenitis (PFAPA) syndrome.

OBJECTIVES: Although most of the autoinfammatory disorders have a confirmed genetic cause, periodic fever, aphthous stomatitis, pharyngitis, and cervical adenitis (PFAPA) syndrome still has an unknown genetic background. However, familial cases of PFAPA syndrome have been reported suggesting a genetic its basis. PFAPA syndrome may also be considered an infammasome disorder as variants in infammasome-associated genes such as CARD8, NLRP3, and MEFV have been reported to contribute to the disease. METHODS: Polymerase chain reaction (PCR)/Sanger sequencing analysis was performed for the detection of the variations in 71 PFAPA patients and 71 healthy controls. NLRP3 concentrations in serum were measured in 71 PFAPA patients and 71 healthy controls. RESULTS: No statistically significant differences were observed in the allele or genotype frequencies of the NLRP3 polymorphisms between the controls and patients (P > 0.05). We found no significant differences for NLRP3 serum levels between PFAPA patients and controls (p > 0.05). Mutations in the MEFV gene were detected in 32.5% of our patients (13/40). CONCLUSIONS: It seems that the synergistic effect of different genes plays a role in the formation of PFAPA syndrome. For this reason, it may be useful to examine the presence of mutations in genes such as NLRP3, MEFV, and CARD8 together while investigating the genetics of PFAPA syndrome. Key points • Familial cases of PFAPA syndrome have been reported suggesting a genetic basis for this syndrome. • Elevated serum or plasma levels of IL-1ß, IL-6, and IL-18 have been demonstrated during PFAPA flares in several studies. • It seems that the synergistic effect of different genes plays a role in the formation of PFAPA syndrome.