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.

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.

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.

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.

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.

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.

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.

A case of juvenile systemic sclerosis and congenital pulmonary airway malformation related mucinous adenocarcinoma of the lung: paraneoplastic syndrome or just a coincidence?

BACKGROUND: Juvenile systemic sclerosis (JSS) is an extremely rarely seen auto-immune disease characterized by the increased fibrosis of skin and internal organs. Congenital pulmonary airway malformation (CPAM) is a developmental disorder of the lung, characterized by atypical cell hyperplasia which creates the ground for lung adenocarcinoma. In general, CPAM is diagnosed in early childhood, due to recurrent respiratory symptoms including cough, hemoptysis and respiratory infections. Although rare, there are some sporadic asymptomatic cases of CPAM that have been reported. We present a case with a coincidental presence of two rare diseases: JSS and CPAM. CASE: An adolescent female patient was admitted to hospital due to clinical signs of JSS. During the followup, the patient had been diagnosed with cystic adenoid malformation of the lung complicated by mucinous adenocarcinoma. The patient was previously healthy with an unremarkable history, including lack of respiratory symptoms. Left inferior lobectomy was performed. Considering the small size of malignant loci, the total resection of the tumor and absence of any sign for metastasis disease, adjuvant therapy was not scheduled. We haven`t found a pediatric case of CPAM associated adenocarcinoma of the lung presented by signs of JSS in the literature. In this case, the clinical signs of JSS possibly represent part of the paraneoplastic syndrome related to adenocarcinoma of the lung. CONCLUSIONS: Internal organ involvement, including respiratory system, should not be omitted even in asymptomatic patients with JSS. Auto-antibody negativity represents a clue for the possible underlying condition. Further studies with a higher number of patients would reveal more relevant data.

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.

Pediatric Takayasu Arteritis: A Review of the Literature.

Takayasu arteritis (TA) is the third most common vasculitis of childhood and is extremely rare. It is mainly characterized by chronic, autoimmune, and granulomatous inflammation of the aorta and its major branches. Women under 40 years of age are mostly affected. It occurs for the first time in childhood in about 30% of affected individuals. Initially, it presents nonspecific constitutional findings. Since there is no specific laboratory finding, diagnosis is challenging. The gold standard imaging method for diagnosis is conventional angiography. Delay in diagnosis can cause devastating consequences. Therefore, in cases presenting with nonspecific findings, with hypertension and high acute phase reactants, the diagnosis should be suspected and confirmed with appropriate imaging method, and treatment should be started immediately. Immunosuppressive agents are the mainstay of the treatment. Biological agents are successful in refractory cases, and endovascular revascularization methods are used in the treatment of complications.