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.

Exploring factors for predicting colchicine responsiveness in children with PFAPA.

Periodic fever, aphthous stomatitis, pharyngitis, and cervical adenitis syndrome (PFAPA) are the most common autoinflammatory syndromes in children. This study aimed to evaluate the clinical and laboratory parameters that may predict colchicine responsiveness.This retrospective, multicenter, cross-sectional study involved nine pediatric rheumatology centers from our country., The patients diagnosed with PFAPA were compared on the basis of their responses to colchicine. In the 806 (42.3% female 57.7% male) patients, the most common clinical findings were fever (100%), exudative tonsillitis (86.5%), pharyngitis (80.9%), and aphthous stomatitis (50.5%). The mean attack frequency was 13.5 ± 6.8 attacks per year lasting for a mean of 3.9 ± 1.1 days. Colchicine treatment was attempted in 519 (64.4%) patients, with 419 (80.7%) showing a favorable response. In patients who underwent MEFV gene analysis (70.8%), the most common variant was M694V heterozygous (16.8%). The presence of pharyngitis (p = 0.03, 95% CI 0.885 to 0.994), the presence of arthralgia (p = 0.04, 95% CI 0.169 to 0.958), and having more frequent attacks (p = 0.001, 95% CI 0.028 to 0.748) were found to be associated with colchicine unresponsiveness, whereas the carriage of the M694V variant (p = 0.001, 95% CI 0.065 to 0.242) was associated with colchicine responsiveness. CONCLUSION: This study identified the presence of pharyngitis, arthralgia, and increased attack frequency in patients with PFAPA as factors predicting colchicine unresponsiveness, whereas the carriage of the M694V variant emerged as a predictor of colchicine responsiveness. Predicting colchicine response at disease onset may facilitate a more effective management of PFAPA. WHAT IS KNOWN: • Colchicine treatment can be used in the prophylaxis of PFAPA disease. • Having the MEFV variant is the most commonly known factor in predicting response to colchicine. WHAT IS NEW: • The presence of pharyngitis or arthralgia, and more frequent attacks in PFAPA disease were found to be independently associated with colchicine unresponsiveness. • Carrying the M694V variant was identified as the sole factor predicting colchicine responsiveness.

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.

The effect of temporomandibular joint dysfunction on the craniocervical mandibular system: A retrospective study.

BACKGROUND: Temporomandibular disorders are the most common condition affecting the orofacial region, resulting in pain and dysfunction. OBJECTIVE: This study aimed to elucidate the ambiguous association between cervical features and temporomandibular disorders by measuring the rotations between the skull-atlas, atlas-axis and mandible-atlas and examining the relationship between these rotations and temporomandibular disorders. METHODS: Cone-beam computed tomography (CBCT) images from 176 patients, 97 females and 79 males with an average age of 25.7 years were used in this study. The patients were divided into two groups: those with joint dysfunction (n = 88) and those without (n = 88). The study employed various methods to determine rotations in the skull-atlas, atlas-axis and mandible atlas based on anatomical landmarks and measurements. These methods include the use of specific planes, angles and distances to identify and measure rotation. Data analysis was performed using the TURCOSA statistical software (Turcosa Analytics Ltd Co, Turkey, www.turcosa.com.tr). RESULTS: The results showed that the degree of rotation between the skull and the atlas was higher in the TMD group than in the control group (p < .001). Similarly, Atlas-axis rotation was significantly higher in the TMD group (p < .001). However, no significant difference was found between mandible atlas rotations in the two groups (p = .546). The study also found a significant difference between the direction of rotation between the atlas and axis and the direction of mandible atlas rotation (p < .001) as well as between skull and atlas rotations and mandible-atlas rotations (p < .001). CONCLUSION: Overall, the study suggests that there is a relationship between the skeletal structures of the cranio-cervico-mandibular system and TMD. Skull-atlas and atlas-axis rotations may play an important role in the aetiology of TMD in individuals with TMD. Therefore, it is important to evaluate rotations in the skull-atlas-axis region for the treatment of TMD.

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.

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.

Anti-inflammatory and pro-regenerative effects of a monoterpene glycoside on experimental periodontitis in a rat model of diabetes.

OBJECTIVE: Paeoniflorin (Pae) is a monoterpene glycoside with immune-regulatory effects. Several studies have already demonstrated the impact of Pae on periodontitis, but its effect on diabetic periodontitis is unclear. In this study, our aim was to test the hypothesis that Pae had a strong anti-inflammatory effect that prevented bone loss in diabetic periodontitis. METHODS: Thirty male Wistar albino rats were randomly divided into control (healthy, n = 10), periodontitis (PD) + diabetes (DM; n = 10), and PD + DM + Pae (n = 10) groups. Ligature-induced periodontitis was created by placing 4-0 silk ligatures around the lower first molars on both sides of the mandibulae. Experimental DM was created via an injection of 50 mg/kg and streptozotocin (STZ). Hyperglycemia was confirmed by the blood glucose levels of rats (>300 mg/dL). The bone mineral density (BMD), trabecular number, trabecular thickness, and bone loss were measured by micro-CT. The expression levels of IL-1ß, IL-6, and TNF-α were measured in tissue homogenates by ELISA. RESULTS: The PD + DM + Pae group had significantly less alveolar crest resorption when compared to the PD + DM group. There was also a significant difference between the PD + DM + Pae group compared to PD + DM group in trabecular thickness, BMD, and the number of trabeculae. Pae application led to a statistically significant decrease in IL-1ß, IL-6, and TNF-α levels in diabetic periodontitis. CONCLUSION: Systemic application of Pae suppressed inflammation caused by PD and DM, leading to reduced bone loss and enhanced bone quality.

The Effect of COVID-19 Pandemic on Foreign Body Aspiration.

BACKGROUND: This article evaluates the effect of coronavirus disease 2019 (COVID-19) pandemic on clinical course and management of cases that underwent bronchoscopy for suspected foreign body aspiration (FBA) in children. METHODS: The patients who underwent bronchoscopy with a presumptive diagnosis of FBA between July 2018 and December 2021 were evaluated for demographic features, clinical findings, management details, and outcomes. Patients were divided in two groups: before pandemic (group A) and during pandemic (group B). RESULTS: In total 79 cases with a median age of 5 years (4-5) in group A (n = 47) and 3 years (2-3) in group B (n = 32) were included (p < 0.05). The witnessed aspiration was significantly higher in group B (90.6%) when compared to group A (53%) (p < 0.05). Admission time was less than 48 hours in 30 cases (64%) in group A and 23 cases (72%) in group B (p = 0.002). The intervention time was less than 24 hours in 30 cases (64%) in group A, 9 cases (28%) in group B (p = 0.002). Bronchoscopy was performed after COVID-19 polymerase chain reaction (PCR) testing in all cases in group B. The positive FBA rate was 38% (n = 18) in group A, and 59% (n = 19) in group B (p = 0.067). CONCLUSION: During pandemics, bronchoscopy for FBA was performed in younger infants than before pandemic and witnessed aspiration was significantly more common in that period. The differences in age groups and symptoms may be explained by spending more time at home during pandemics. Waiting for the PCR test results causes delays in the intervention. However, this delay did not cause any respiratory distress.

The effect of different treatment protocols with diode laser on regeneration in axonetmesis injuries of the inferior alveolar nerve: an animal study.

The inferior alveolar nerve can be damaged during dental procedures, leading to symptoms, such as tingling, numbness, and reduced quality of life. Recovery depends on factors such as medications, surgery, and photobiomodulation therapy. Photobiomodulation therapy has shown the potential to improve nerve function and reduce regeneration time; however, there is no standard treatment protocol yet. This study aimed to examine the effect of diode lasers on nerve regeneration in patients with axonetmesis injuries. In this experiment on animals, Wistar rats' damaged sensory systems were treated with lasers to restore them. Animals were randomly divided into six groups: a sham group, a control group, and four laser treatment groups(1st group: performed every day, 10 sessions; 2nd group: performed every 2 days, 10 sessions; 3rd group: performed every day, 20 sessions; and 4th group: performed every 2 days, 20 sessions). Sensory function was determined using the Semmes-Weinstein monofilament test, which was repeated after the surgical procedure. The results showed that the 20-session group had the best improvement, most closely resembling the group without sensory test damage. The histomorphometric results showed that the number of axons was significantly lower in the group that received 10 daily sessions and in the control group than in the undamaged nerve. Axon diameter was lower in all groups than in the sham group. In conclusion, the remarkable aspect of this study is that consecutive-day 20-session laser treatment showed better improvement than the over-the-day 20-session treatment protocol.

Cluster analysis of paediatric Behçet's disease: Data from The Pediatric Rheumatology Academy-Research Group.

OBJECTIVES: Behçet's disease (BD) is a systemic vasculitis affecting many organ systems, with the involvement of all-sized arteries and veins. The study aims to determine the main characteristics of paediatric BD patients and also analyse the clustering phenotypes. METHODS: Demographic data, clinical manifestations, laboratory features, treatment schedules, and disease outcomes were achieved from patients' charts retrospectively. A cluster analysis was performed according to the phenotype. RESULTS: A total of 225 (109 male/116 female) patients with BD were enrolled in the study. The median ages of disease onset and diagnosis were 131 (36-151) and 156 (36-192) months, respectively. According to cluster analysis, 132 (58.6%) patients belonged to the mucocutaneous-only cluster (C1), while 35 (15.6%) patients fitted to articular type (C2), 25 (11.1%) were in the ocular cluster (C3), 26 (11.6%) were in the vascular cluster (C4), and 7(3.1%) belonged to the gastrointestinal cluster (C5). Ocular and vascular clusters were more common in boys (p < .001), while girls usually presented with the mucocutaneous-only cluster. The disease activity at the diagnosis and the last control was higher in ocular, vascular, and gastrointestinal clusters. CONCLUSIONS: These identified juvenile BD clusters express different phenotypes with different outcomes Our analysis may help clinicians to identify the disease subtypes accurately and to arrange personalized treatment.

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

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

Clinical characteristics and predictors for recurrence in chronic nonbacterial osteomyelitis: a retrospective multicenter analysis.

Background/aim: Chronic nonbacterial osteomyelitis (CNO) is a rare disease of unknown etiology and most commonly occurs during childhood or adolescence. The purpose of this study is to collect data on the clinical features, outcomes, and management of the disease and to identify the factors affecting recurrence. Materials and methods: This is a retrospective multicenter cross-sectional study of pediatric patients diagnosed with CNO. A total of 87 patients with a diagnosis of CNO followed for at least 6 months in 8 pediatric rheumatology centers across the country between January 2010 and December 2021 were included in this study. Results: The study included 87 patients (38 girls, 49 boys; median age: 12.5 years). The median follow-up time was 20 months (IQR: 8.5-40). The median time of diagnostic delay was 9.9 months (IQR: 3-24). Arthralgia and bone pain were the most common presenting symptoms. Multifocal involvement was detected in 86.2% of the cases and a recurrent course was reported in one-third of those included in the study. The most commonly involved bones were the femur and tibia. Vertebrae and clavicles were affected in 19.5% and 20.6% of cases, respectively. The erythrocyte sedimentation rate (ESR) values of 60.9% of the patients were above 20 mm/h and the C-reactive protein values of 44.8% were above 5 mg/L. The remission rate was 13.3% in patients using nonsteroidal antiinflammatory drugs and 75.0% in those using biological drugs. Vertebral and mandibular involvement and high ESR values at the time of diagnosis were associated with recurrence. Conclusion: In this multicenter study, CNO with vertebral and mandibular involvement and high ESR at diagnosis were associated with recurrence.

Adherence to best practice consensus guidelines for familial Mediterranean fever: a modified Delphi study among paediatric rheumatologists in Turkey.

BACKGROUND: Although not validated fully, recommendations are present for diagnosis, screening and treatment modalities of patients with familial Mediterranean fever (FMF). OBJECTIVE: To review the current practices of clinicians regarding FMF and reveal their adherence to consensus guidelines. METHODS: Fifteen key points selected regarding the diagnosis and management of FMF were assessed by 14 paediatric rheumatologists with a three-round modified Delphi panel. RESULTS: Consensus was reached on the following aspects: genetic analysis should be ordered to all patients when clinical findings support FMF, but its result is not decisive alone. In the absence of clinical features, colchicine should be commenced when two pathogenic alleles and family history of amyloidosis are present. Serum amyloid A testing at each visit is recommended in patients resistant to colchicine, with subclinical inflammation and family history of amyloidosis. Consensus was reached on both the definition of colchicine resistance and starting biologic in resistant cases. Cost, efficiency, ease of use, treatment adherence, accessibility and emergence of adverse events are the factors affecting the choice of biologic agents. In patients without any attack and evidence of subclinical inflammation within the last 6 months following initiation of biologics, treatment dose intervals can be prolonged. CONCLUSION: A consensus was achieved regarding the routine diagnosis and screening and treatment of FMF patients. The definition of colchicine resistance was made and a protocol was created for prolongation of treatment intervals of biologic agents. We anticipate that the results of the study reveal real-life data on the approach to patients in clinical practice.

The clinical course of SARS-CoV-2 infection among children with rheumatic disease under biologic therapy: a retrospective and multicenter study.

The effects of biological disease-modifying antirheumatic drugs (bDMARDs) in the clinical course of COVID-19 on children with underlying rheumatologic diseases have not been fully demonstrated. To evaluate the course of COVID-19 infection in patients with rheumatic disease receiving bDMARD treatment. This was a retrospective, multicenter study conducted in pediatric patients infected by SARS-CoV-2 and under bDMARDs therapy. The study population consisted of 113 patients (72 female/41 male). The mean age of the patients was 12.87 ± 4.69 years. The primary diagnosis of the cohort was as follows: 63 juvenile idiopathic arthritis, 35 systemic autoinflammatory diseases, 10 vasculitides, and five cases of connective tissue diseases. The mean duration of the primary disease was 4.62 ± 3.65 years. A total of 19 patients had additional comorbid diseases. Thirty-five patients were treated with canakinumab, 25 with adalimumab, 18 with etanercept, 10 with infliximab, nine with tocilizumab, six with rituximab, four with anakinra, three with tofacitinib, and one with abatacept. The median exposure time of the biological drug was 13.5 months. Seventy-one patients had symptomatic COVID-19, while 42 were asymptomatic. Twenty-four patients required hospitalization. Five patients presented with MIS-C. The hospitalized patients were younger and had a shorter duration of rheumatic disease compared to ambulatory patients, although the difference was not statistically significant. Steroid usage, presence of fever, and dyspnea were more common among the hospitalized patients. A worsening in the course of both COVID-19 and current disease was not noticed under bDMARDs, however, to end with a strong conclusion multicentric international studies are required.

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

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

The analysis of genotype-phenotype correlation in familial Mediterranean fever.

BACKGROUND: Familial Mediterranean fever (FMF) is the most common monogenic autoinflammatory disease manifesting with phenotypic heterogeneity. It is a clinically diagnosed disease supported by Mediterranean fever gene mutation analysis. This medical record review study aimed to make a new interpretation of clinical features in FMF patients by grouping genetic results based on the classification proposed by the Eurofever/ Paediatric Rheumatology International Trials Organisation. METHODS: The medical charts of pediatric FMF patients who were diagnosed and followed up regularly at the two pediatric rheumatology units were reviewed. Genetic analysis results were classified as confirmatory and nonconfirmatory as defined in the new Eurofever/ Paediatric Rheumatology International Trials Organisation classification criteria, and they were compared with clinical findings. RESULTS: A total of 216 FMF patients were involved in the study. Group 1 was composed of 133 (61.6%) patients with a confirmatory mutation and group 2 included 83 (38.4%) patients with a nonconfirmatory mutation. All clinical findings were compared, and in terms of fever (P = 0.027), abdominal pain (P = 0.016), arthritis (P = 0.008) and erysipelas-like erythema (ELE; P = 0.003) incidence, there was a significant difference between the two groups. The most common Mediterranean fever gene mutation patterns were homozygous (33.8%) and heterozygous (17.1%) mutations of M694V. The frequency of arthritis and ELE in patients with M694V homozygous mutations was significantly higher than in the other patients (P = 0.002 and P <0.001, respectively). CONCLUSIONS: The most frequently observed clinical features of FMF (i.e., fever and abdominal pain) are both observed in patients with confirmatory and nonconfirmatory mutations, ELE and arthritis are more commonly observed in patients with confirmatory mutations.

Peri-implant bone microstructural analysis and comparison of resonance frequency analysis before prosthetic placement: a retrospective study.

OBJECTIVES: Fractal analysis is a mathematical method used for the calculation of bone trabeculation and lacunarity. This study aims to evaluate the relationship between resonance frequency analysis (RFA) and fractal dimension (FD) of peri-implant bone to determine the preload stability of implants. MATERIALS AND METHODS: In this study, the results of the fractal analysis calculated from the resonance frequency analysis results taken in the 3rd month of the patients who underwent 2-stage implant by the same doctor and the radiographs taken in the same session were evaluated. A hundred implants in 20 patients were applied in this study. The implant stability quotient (ISQ) values of the implants and fractal dimension values of the peri-implant bone were calculated. RESULTS: The findings showed that the ISQ1 (p = 0.008), ISQ2 (p = 0.038), ROI2 (p = 0.013), and ROI3 (p < 0.001) values were statistically significantly higher in men than women. The ISQ1 (p = 0.003), ISQ2 (p = 0.013), ROI1 (p = 0.011), and ROI3 (p < 0.001) of the mandible were statistically higher than the maxilla. The fractal dimension cut-off value to assess prosthetic loading was found 1.198. CONCLUSION: Fractal analysis is a non-invasive method that can be used in conjunction with clinical examination in the prosthetic loading decision of implants. It is a valuable parameter that can be used without the need for an extra device when it is necessary to reduce the clinical study time. CLINICAL RELEVANCE: Calculating the fractal dimension of the peri-implant bone is a practical, economical, and applicable method for clinicians. FD calculated from panoramic radiographs used for diagnosis in routine treatments in clinics where access to the necessary devices for ISQ measurement is not available will contribute to clinical practice.

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

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

The feasibility of withdrawing canakinumab in paediatric colchicine-resistant familial Mediterranean fever patients.

OBJECTIVES: To determine the feasibility of withdrawing canakinumab (CAN) in a large cohort of paediatric patients with colchicine-resistant familial Mediterranean fever (crFMF). METHODS: This retrospective observational cohort study included paediatric crFMF patients that received CAN treatment for ≥6 months. Patient data were recorded at treatment onset (baseline), and at 1, 3, 6, 12, 18, and 24 months after initiation of treatment. RESULTS: The study included 114 patients that were followed-up for 2736 person-months. During the 24-month follow-up period, the CAN dose interval remained unchanged in 44 patients. The dose interval was extended in 58 patients within a median 6 months (range: 3-18 months) of treatment initiation. In all, 4 of these 58 patients had a new attack of crFMF after the dose interval was extended. CAN was withdrawn in 12 patients (in 5 at month 12 month and in 7 at month 18), of which 2 had a new attack within 3 months of withdrawal. In these 2 patients CAN was re-initiated with a dose interval of 8 weeks. The remaining 10 patients in which CAN was withdrawn did not report any symptoms throughout the remainder of the 24-month follow-up period. The median attack-free period in those treated with CAN was 669 d (95% CI: 644-696). CONCLUSIONS: The present findings show that it may be feasible to withdraw CAN or extend its dose interval in paediatric crFMF patients. Based on the present findings, we think that as the quantity of real-life data increases, standard CAN protocols may be developed.

Protracted febrile myalgia syndrome as the first manifestation of familial Mediterranean fever in children: case-based review.

Protracted febrile myalgia syndrome (PFMS) is one of the rare conditions characterized by long standing severe myalgia and fever in familial Mediterranean fever (FMF) patients. Laboratory studies show elevated values of inflammatory markers and normal creatinine phosphokinase (CPK) levels. Rarely, PFMS may be the first manifestation of FMF and this makes the diagnosis of FMF and PFMS challenging. The aim of this report was to describe case series of PFMS patients without previous diagnosis of FMF and discuss with other pediatric PFMS cases described in the literature. Six patients with PFMS as the first manifestation of FMF from two Pediatric Rheumatology clinics were presented. The male: female ratio was 1:1. The median (min-max) age at diagnosis was 7.05 (5.5-15.5) years. All patients had severe myalgia. No fever was detected in two patients. Only one patient had rash. Markedly elevated acute phase reactants were observed in all patients. CPK levels were normal in all patients. Also, we searched the PubMed/MEDLINE, Google Scholar, Web of Science and Scopus databases from inception to May 2020, using the keywords 'familial Mediterranean fever, protracted febrile myalgia, child' and 52 pediatric PFMS were found. In the literature, three patients did not have fever, and nineteen patients were not previously diagnosed with FMF as our patients. As a conclusion, PFMS may be the first manifestation of FMF. It should be suspected in cases with prolonged severe myalgia with or without fever, and high acute phase reactants.