Unveiling Cardiac Involvement in Juvenile Dermatomyositis Through Speckle-Tracking Echocardiography.

Early detection of cardiac involvement in Juvenile Dermatomyositis (JDM) is difficult due to the absence of clinical signs and symptoms, with systolic dysfunction often emerging in late stages and associated with a poor prognosis. This study aimed to employ two-dimensional speckle-tracking echocardiography (STE) for subclinical assessment of left ventricular (LV) systolic failure in JDM and explore potential associations between impaired LV systolic function (LV-GLS) and disease activity. A prospective study enrolled 20 healthy volunteers and 26 JDM patients (< 18 years old) without cardiac symptoms. Clinical data were collected from medical records, and echocardiograms were conducted by a pediatric cardiologist. Our study cohort demonstrated similar age to controls (13.5 ± .6 vs. 13.8 ± 4.7; p = 0.465). Median illness duration at echocardiography was 5 (1.5-17.5) years, and conventional echocardiography indicated normal LV ejection fraction (> 55%) in all participants. However, STE revealed lowered LV GLS in JDM patients (- 22.2 ± 4.1% vs. - 26.5 ± 5.3% p = 0.022). Pulse steroid users displayed lower GLS average values compared to non-users (ß = 4.99, 95% CI 1.34-8.64, p = 0.009). Negative correlations existed between LV-GLS and age at diagnosis (r = - 0.499; p = 0.011), diastolic parameters (E/E' ratio) and age at diagnosis (r = - 0.469; p = 0.018), as well as RV global strain and age at diagnosis (r = - 0.443; p = 0.024). Employing STE in JDM patients facilitated the identification of preclinical cardiac dysfunction. Given JDM patients' younger age, early myocardial damage detection through STE may impact treatment decisions and long-term cardiovascular prognosis.

Exploring cardiovascular implications of juvenile dermatomyositis: Insights from aortic stiffness analysis and 3D echocardiography.

OBJECTIVE: Our goal was to use three dimensional (3D) strain analysis to evaluate myocardial function and ascending aorta elasticity changes in juvenile dermatomyositis (JDM). METHODS: Between 2019 and 2021, 23 JDM patients and 20 healthy volunteers participated. Both groups underwent 2D and 3D strain analysis, assessing aortic stiffness using aortic distensibility, stiffness index, strain, and elastic modulus. RESULTS: JDM patients had a median age of 13.3 ± 5.2 years, while controls had a median age of 13.8 ± 4.76 years. 3D strain analysis revealed significantly lower global longitudinal (GLS) and circumferential strain (GCS) in JDM patients compared to controls. Specifically, 3D GLS was notably reduced in patients (-28.1% vs. -31%, p = .047) compared to controls, and 3D GCS was also lower in patients (-27.5% vs. -30.5%, p = .019) compared to controls. Aortic strain and elastic modulus were significantly lower in JDM patients, while aortic stiffness index and distensibility showed no significant differences. Correlation analyses within the JDM group revealed a negative correlation between 3D GLS and age at diagnosis (r = -.561, p = .04), as well as a positive correlation between 3D GLS and both aortic strain (r = .514, p = .0001) and elastic modulus (r = .320, p = .03) in JDM patients. CONCLUSION: Our study demonstrated a trend towards lower ejection fraction and strain in patients with JDM, along with increased aortic stiffness using 3D echocardiography. These findings suggest potential cardiovascular involvement in juvenile dermatomyositis, emphasizing the importance of comprehensive cardiac assessments in these patients.

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

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

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.

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.

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 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.

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.

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.

Pediatric mixed connective tissue disease versus other overlap syndromes: a retrospective multicenter cohort study.

Pediatric mixed connective tissue disease (MCTD) is a subgroup of overlap syndromes. We aimed to compare the characteristics and outcomes in children with MCTD and other overlap syndromes. All MCTD patients met either Kasukawa or Alarcon-Segovia and Villareal criteria. The patients with other overlap syndromes had the features of ≥ 2 autoimmune rheumatic diseases but did not meet MCTD diagnostic criteria. Thirty MCTD (F/M = 28/2) and thirty (F/M = 29/1) overlap patients were included (disease onset < 18 years). The most prominent phenotype at disease onset and the last visit was systemic lupus erythematosus (SLE) in the MCTD group; juvenile idiopathic arthritis and dermatomyositis/polymyositis, respectively, in the overlap group. At the last visit, systemic sclerosis (SSc) phenotype was more frequent among MCTD than overlap patients (60% vs. 33.3%; p = 0.038). The frequency of the predominant SLE phenotype had decreased (60% to 36.7%), while predominant SSc phenotype had increased (13.3% to 33.3%) during follow-up in MCTD patients. Weight loss (36.7% vs. 13.3%), digital ulcers (20% vs. 0), swollen hands (60% vs. 20%), Raynaud phenomenon (86.7% vs. 46.7%), hematologic involvement (70% vs. 26.7%), and anti-Sm positivity (29% vs. 3.3%) were more common, while Gottron papules (16.7% vs. 40%) were less frequent among MCTD than overlap patients (p < 0.05). A higher percentage of overlap patients achieved complete remission than MCTD patients (51.7% vs. 24.1%; p = 0.047). The disease phenotype and outcome differ between pediatric MCTD and other overlap syndromes where MCTD may be regarded as a more severe disease. Analyzing these patients could pave the way for early and effective treatment.

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.

A cursed goodbye kiss from severe acute respiratory syndrome-coronavirus-2 to its pediatric hosts: multisystem inflammatory syndrome in children.

PURPOSE OF REVIEW: We aimed to summarize a novel disease called multisystem inflammatory syndrome in children (MIS-C), which develops several weeks after a severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) illness. RECENT FINDINGS: Given the rarity of the disease, the question of why a minority of children develop MIS-C is not known. Certain intrinsic susceptibility factors in the host have been described. In addition to hyperinflammation induced by the innate and acquired immune cells, evidence of molecular mimicry was presented for the disease pathogenesis. As there is an increasing number of infected individuals and mass vaccination schedules, concerns regarding the usefulness of the existing diagnostic criteria sets raised. SUMMARY: Although children are likely to have a milder COVID-19 course compared with adults, MIS-C as a postinfectious and life-threatening complication was reported in the pediatric age. After 2 years of the disease definition, optimal treatment regimes, effective preventive measures, and long-term outcomes are still debated.

Long-term efficacy of tonsillectomy/adenotonsillectomy in patients with periodic fever aphthous stomatitis pharyngitis adenitis syndrome with special emphasis on co-existence of familial Mediterranean fever.

Periodic fever, aphthous stomatitis, pharyngitis, adenitis (PFAPA) syndrome is one of the most common autoinflammatory fever disorders in the childhood which may co-exists with familial Mediterranean fever (FMF) causing treatment complexity. As the role of surgery in PFAPA syndrome is still controversial, in this paper, our aim is to present our results of tonsillectomy/adenotonsillectomy in the treatment of PFAPA syndrome. Archives of a tertiary care hospital were investigated for patients who underwent tonsillectomy or adenotonsillectomy due to PFAPA Syndrome between 2010 and 2020. 344 patients were found but only 281 of them were accessible. Through phone call interview and chart review methods, preoperative and postoperative the number and severity of the attacks and general satisfaction after the operation were recorded and analyzed. Also, patients with concomitant FMF were analyzed separately. A total of 281 patients were included in the study. There was no improvement in 10 (3.55%) patients. Eight (2.84%) patients showed mild improvement, 29 (10.32%) patients had moderate improvement and 234 (83.27%) patients had full recovery after tonsillectomy. There were 266 PFAPA patients without FMF. No improvement, mild improvement, moderate improvement, and full recovery in this patient group were 5 (1.9%), 6 (2.3%), 25 (9.4%) and 230 (86.5%), respectively. FMF was present in 5.33% (15/281) of the patients. In PFAPA + FMF group 5 patients had no improvement (33.3%), 2 had mild improvement (13.3%), 4 had moderate improvement (26.7%) and 4 had full recovery (26.7%). Benefit of tonsillectomy was significantly lower in the patients with concomitant FMF when compared to the patients who did not have FMF (p < 0.001). Age of diagnosis, age of operation, severity of the disease, type of operation, and gender were found to have no significant relationship with the benefit from surgery (p < 0.05). According to the findings of this study, tonsillectomy is an effective long-term treatment for PFAPA syndrome with success rate of 83.27%. Also, preoperatively FMF should be considered in these patients, which dramatically reduces surgical efficacy.

An overview of the relationship between juvenile idiopathic arthritis and potential environmental risk factors: Do early childhood habits or habitat play a role in the affair?

AIM: The current study was undertaken to evaluate the influence of breastfeeding on the development and outcome measures of juvenile idiopathic arthritis (JIA). The second aim was to determine the consequences of particular sociodemographic and sociocultural characteristics and nutritional behavior of early childhood on JIA. METHODS: The study includes the patients diagnosed with JIA and regularly followed up at the Department of Pediatric Rheumatology in Istanbul University-Cerrahpasa. The comparison group consisted of healthy subjects and patients with juvenile systemic lupus erythematosus (jSLE). A face-to-face survey method was conducted with the parents of the participants between February 1, 2021, and September 1, 2021. RESULTS: The mean age of the JIA cohort (n = 324) was 12.2 ± 4.7 years, with a female ratio of 64.8%. The breastfeeding rate differed from the control groups (253 healthy subjects and 88 patients with jSLE) but was higher with a value of 94.8%. There was no difference between the groups (P = .097, P = .064) or within the subgroups of JIA (P = .12) regarding breastfeeding duration. Cow's milk introduction time (P = .02, P = .0001), household pet-keeping (P = .001), income level (P = .0001), maternal literacy (P = 0.013) made a statistical difference vs the control groups. CONCLUSION: No relationship was established between the rate or duration of breastfeeding and the development or severity of JIA. The early introduction of cow's milk was found to be higher in the patient cohorts. The income level and maternal literacy appeared to be relevant with the high disability and damage scores, and frequent relapse rates. Secondhand smoking, higher in JIA, may prompt the basis of primary preventable strategies in JIA.

An evaluation of sleep habits and childhood-onset systemic lupus erythematosus.

OBJECTIVES: Systemic lupus erythematosus (SLE) is a multisystem autoimmune disease, known for its heterogeneous clinical presentation. Although it is rarer in children, a more severe clinical course can be seen than in adults. It is known that sleep has physiological and developmental importance in children, and there are many studies on sleep quality in adult SLE patients. The aims of this study are to evaluate the sleep habits of children and adolescents with SLE and to compare them with their healthy peers. METHODS: The study included 48 children and adolescents with SLE and 64 healthy peers as a control group. The Children's Sleep Habits Questionnaire was used to evaluate the sleep characteristics of children. RESULTS: The age and gender of the children were similar across groups. The bedtime resistance and night waking scores of SLE patients were significantly higher than those of the control group. Total sleep score was higher in patients with SLE than in the control group, but there was no significant difference (47.13±7.63 vs 44.61±8.17; p=0.051). Similarly, the rate of sleep disorders in the patient group (75%) was higher than that of the control group (61%), though the differences were not statistically significant (p = 0.156). There was no correlation between disease severity and sleep problems. CONCLUSION: This research demonstrated that sleep disorders tend to increase in children and adolescents with SLE. Therefore, clinicians should pay attention to sleep disorders during the follow-up sessions of children and adolescents with SLE. Key Points • Sleep disorders tend to increase in children and adolescents with SLE. • Disease severity is not associated with sleep problems.

Comparisons of Clinical Features and Outcomes of COVID-19 between Patients with Pediatric Onset Inflammatory Rheumatic Diseases and Healthy Children.

(1) Background: We aimed to describe the clinical features and outcomes of coronavirus disease-2019 (COVID-19) in children and late adolescents with inflammatory rheumatic diseases (IRD) and to measure their severity risks by comparing them with healthy children. (2) Methods: Among children and late adolescents found to be severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) positive via polymerase chain reaction (PCR) test, IRD patients with an at least six-months follow-up duration, and healthy children were included in the study. Data were obtained retrospectively. (3) Results: A total of 658 (339 (51.5%) females) (healthy children: 506, IRD patients: 152) subjects were included in the study. While 570 of 658 (86.6%) experienced COVID-19-related symptoms, only 21 (3.19%) required hospitalization with a median duration of 5 (1-30) days. Fever, dry cough, and fatigue were the most common symptoms. None of evaluated subjects died, and all recovered without any significant sequelae. The presence of any IRD was found to increase the risk of both hospitalization (OR: 5.205; 95% CI: 2.003-13.524) and symptomatic infection (OR: 2.579; 95% CI: 1.068-6.228). Furthermore, increasing age was significantly associated with symptomatic infection (OR: 1.051; 95% CI: 1.009-1.095). (4) Conclusions: Our study emphasizes that pediatric rheumatologists should monitor their patients closely for relatively poor COVID-19 outcomes.

Early experience of COVID-19 vaccine-related adverse events among adolescents and young adults with rheumatic diseases: A single-center study.

OBJECTIVE: Considering the concerns regarding the coronavirus disease-2019 (COVID-19) vaccine safety among pediatric patients with inflammatory rheumatic diseases (IRD) due to a lack of data, an urgent need for studies evaluating safety profiles of vaccines emerged. METHODS: Among participants vaccinated by CoronaVac inactive SARS-CoV-2 or BNT162b2 messenger RNA (mRNA) COVID-19 (Pfizer-BioNTech) vaccine, healthy children under 18 and patients under 21 with an at least 1-year follow-up period in our department for a childhood-onset rheumatic disease were included into this cross-sectional study. RESULTS: Overall, 246 subjects (141 [57.3%] females) (biologic group: 43, non-biologic group: 180, healthy control group: 23) were eligible for the study. The median age was 15.34 (12.02-20.92) years. The most common adverse events were fatigue (n = 68, 27.6%), headache (n = 44, 17.9%), myalgia (n = 38, 15.4%), arthralgia (n = 38, 15.4%), and fever (n = 35, 14.2%). Only 3 subjects (2 patients with familial Mediterranean fever, and one healthy child) were considered to experienced serious adverse events, since they required hospitalization. Local reactions were seen in 20 (8.13%), and 27 patients (12.1%) had disease flares within 1 month after the vaccines. Although it was significantly higher in those who received the BNT162b2 mRNA vaccine (P < .001), there was no significant relationship between adverse event frequency and age, gender, the existing diseases, ongoing treatment regimens and pre-vaccination COVID-19 histories. CONCLUSION: Although immunogenicity studies for efficacy of the vaccines and long-term follow-up studies for adverse events monitoring are required, our study indicates an acceptable safety profile of COVID-19 vaccines and encourages children with IRD to be vaccinated.

Genetic screening of early-onset patients with systemic lupus erythematosus by a targeted next-generation sequencing gene panel.

OBJECTIVE: In this study, we aimed to screen 31 genes (C1QA, C1QB, C1QC, C1R, C1S, C2, C3, TREX1, RNASEH2A, RNASEH2B, RNASEH2C, SAMHD1, ADAR, DNASE1, DNASE1L3, PRKCD, ACP5, SLC7A7, IFIH1, TMEM173, ISG15, CYBB, FAS, FASLG, KRAS, NRAS, MAN2B1, PEPD, PTPN11, RAG2, and SHOC2), that we have categorized under the umbrella term "monogenic lupus" using a targeted next-generation sequencing (NGS) panel in 24 individuals with early-onset (≤10 years of age) systemic lupus erythematosus (SLE) and in 24 patients with late-onset (>10 years of age) disease. METHODS: A total of 48 SLE patients (24 with disease onset ≤10 years of age and 24 with disease onset >10 years of age) were included. Patients with late-onset disease have been used as patient controls. Sequencing was carried out using 400 bp kit on the Ion S5 system. RESULTS: Among the 48 patients, three had one pathogenic variant and 45 patients had at least one rare variant classified as benign, likely benign or variant of unknown significance (VUS). In all three patients with a pathogenic variant, the onset of disease was before 10 years of age. Two patients (they were siblings) carried C1QA homozygote pathogenic allele (p.Gln208Ter, rs121909581), and one patient carried PEPD heterozygote pathogenic allele (p.Arg184Gln, rs121917722). CONCLUSION: We demonstrated a pathogenic variant in our target gene panel with a frequency of 9.52% in patients with a disease onset ≤10 years of age. All patients with early-onset SLE phenotype, irrespective of a positive family history for SLE or parental consanguinity, should be scanned for a single-gene defect by a targeted gene panel sequencing. With the discovery of many single-gene defects and ongoing efforts to identify novel genes in SLE, similar gene panels including even more genes will possibly become more necessary and practical in the future.

Comparing the novel microstream and the traditional mainstream method of end-tidal CO2 monitoring with respect to PaCO2 as gold standard in intubated critically ill children.

The objective of this study was to evaluate a novel microstream method by comparison with PaCO2 and the more standard mainstream capnometer in intubated pediatric patients. We hypothesized that the novel microstream method would superior compared to the traditional mainstream method in predicting PaCO2. This was a prospective single-center comparative study. The study was carried out on 174 subjects with a total of 1338 values for each method. Data were collected prospectively from mainstream and microstream capnometer simultaneously and compared with PaCO2 results. Although both mainstream PetCO2 (mainPetCO2) and microstream PetCO2 (microPetCO2) were moderately correlated (r = 0.63 and r = 0.68, respectively) with PaCO2 values, mainPetCO2 was in better agreement with PaCO2 in all subjects (bias ± precision values of 3.8 ± 8.9 and 7.3 ± 8.2 mmHg, respectively). In those with severe pulmonary disease, the mainPetCO2 and microPetCO2 methods were highly correlated with PaCO2 (r = 0.80 and r = 0.81, respectively); however, the biases of both methods increased (14.8 ± 9.1 mmHg and 16.2 ± 9.0 mmHg, respectively). In cases with increased physiologic dead space ventilation, the agreement levels of mainPetCO2 and microPetCO2 methods became distorted (bias ± precision values of 20.9 ± 11.2 and 25.0 ± 11.8 mm Hg, respectively) even though mainPetCO2 and microPetCO2 were highly correlated (r = 0.78 and r = 0.78, respectively). It was found that the novel microstream capnometer method for PetCO2 measurements provided no superiority to the traditional mainstream method. Both capnometer methods may be useful in predicting the trend of PaCO2 due to significant correlations with the gold standard measurement in cases with severe pulmonary disease or increased physiological dead space -despite reduced accuracy.