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

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

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.

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.

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.

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.

Periodic Fever, Aphthous Stomatitis, Pharyngitis, and Adenitis Syndrome: A Single-Center Experience.

OBJECTIVE: The purpose of this study is to share our experience about clinical findings, natural course, and treatment response rates of a large cohort of patients with periodic fever, aphthous stomatitis, pharyngitis, and adenitis (PFAPA) syndrome. MATERIALS AND METHODS: Medical records of patients who were diagnosed with PFAPA syndrome between January 2010 and May 2021 at Istanbul University-Cerrahpasa Cerrahpasa Medical Faculty pediatric rheumatology department were reviewed retrospectively. RESULTS: A total of 607 patients (females: 277, males: 330) with PFAPA syndrome were included. The median duration of episodes was 3 (1-15; interquartile range (IQR) 3-5) days, and the median interval between episodes was 20 days (5-120; IQR 15-30). The median age at the last attack and median disease duration were 66 (24-168; IQR 48-84) months and 40 (4-132; IQR 27.5-60) months, respectively. Fever (100%) was the most common clinical finding, followed by pharyngitis/exudative tonsillitis in 594 (97.9%), aphthous stomatitis in 308 (50.7%), cervical lymphadenopathy in 278 (45.8%), abdominal pain in 249 (41%), and arthralgia in 228 (37.6%) of the patients. Among the clinical findings, there was no statistical difference according to gender, except for cervical lymphadenitis being higher in males (P < .001). Of the patients who were given steroids during attacks, 94.6% were responsive. Colchicine was effective in 93 (63.7%) patients. The disease episodes ceased in 313 (95.4%) of patients who had tonsillectomy/adenoidectomy. CONCLUSIONS: Clinicians should be alert for additional symptoms such as abdominal pain, arthralgia, and headache apart from the cardinal signs. Although tonsillectomy is highly effective, its use is controversial. Colchicine may be a good alternative for prophylaxis.

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.

Specific early signs and long-term follow-up findings of progressive pseudorheumatoid dysplasia (PPRD) in the Turkish cohort.

OBJECTIVES: Progressive pseudorheumatoid dysplasia (PPRD) is a spondyloepiphyseal dysplasia caused by biallelic variants in CCN6. This study aimed to describe the early signs and follow-up findings in 44 Turkish PPRD patients. METHODS: The patients with progressive stiffness of multiple joints, characteristic wide metaphysis of interphalangeal (IP) joints and platyspondyly were clinically diagnosed with PPRD. Fifteen patients who had first symptoms under 3 years of age were grouped as early-onset, while others were grouped as classical. CCN6 sequencing was performed in 43 patients. RESULTS: Thirteen pathogenic/likely pathogenic variants were identified, five were novel. c.156C>A(p.Cys52*) variant was found in 53.3% of the families. The initial symptom in the early-onset group was genu varum deformity, while it was widening of IP joints in the classical group. The median age of onset of symptoms and of diagnosis was 4 and 9.7 years, respectively. The mean follow-up duration was 5.6 years. The median age of onset of IP, elbow, knee and hip stiffness, which became progressive with growth was 5, 9, 9 and 12.2 years, respectively. Waddling gait occurred in 97.7% of the patients. A total of 47.7% lost independent walking ability at the median age of 12 years. In the early-onset group, waddling gait occurred earlier than in classical group (P < 0.001). Two patients had atypical presentation with late-onset and mild or lack of IP involvement. CONCLUSION: We observed that genu varum deformity before the age of 3 years was an early sign for PPRD and almost half of the patients lost walking ability at the median age of 12 years.

A fatal interstitial lung disease in an anti-melanoma differentiation-associated gene 5 (anti-MDA5) antibody negative patient with juvenile dermatomyositis.

BACKGROUND: Juvenile dermatomyositis associated interstitial lung disease, rarely seen in pediatric age groups, has adverse effects on survival. Anti-melanoma differentiation associated gene 5, one of the identified autoantibodies in juvenile dermatomyositis, preferentially affects the lung tissue and may cause rapidly progressive interstitial lung disease. It is a major cause of mortality in juvenile dermatomyositis. In this case report, we present a pediatric patient diagnosed with juvenile dermatomyositis without anti-melanoma differentiation associated gene 5 antibody positivity. CASE: A six-year-old male patient admitted to the Pediatric Intensive Care Unit with symptoms of respiratory failure, 1.5 months after the diagnosis of juvenile dermatomyositis. Thorax computed tomography examination revealed pneumomediastinum, a trace of left-sided pneumothorax, atelectasis on the left posterior lung region, ground-glass opacity, minimal subpleural patchy consolidation, and subcutaneous emphysema especially on the sides of the chest wall. Broad-spectrum antibiotics were started. His nasal swab sample was positive in terms of influenza B; therefore, oseltamivir was added to the treatment. Autoimmune myositis antibodies panel was examined but all of them including anti-melanoma differentiation associated gene 5 antibody resulted as negative. There was no notable reduction in lung infiltrations with the patient`s current treatment regimen. On the 12 < sup > th < /sup > day of Pediatric Intensive Care Unit admission, thorax computed tomography scan revealed progressed radiological lung findings compatible with rapidly progressive interstitial lung disease secondary to juvenile dermatomyositis. Despite intensive medical and extracorporeal treatments such as pulse steroid, intravenous immunoglobulin, methotrexate, cyclophosphamide, rituximab, therapeutic plasma exchange and, extracorporeal membrane oxygenation, the patient died on the 35 < sup > th < /sup > day. CONCLUSIONS: Juvenile dermatomyositis patients should be carefully monitored for the development of interstitial lung disease. Rapidly progressive interstitial lung disease with a high mortality may develop shortly after diagnosis, even if the anti-melanoma differentiation associated gene 5 antibody is negative.

Frequency of juvenile idiopathic arthritis and associated uveitis in pediatric rheumatology clinics in Turkey: A retrospective study, JUPITER.

BACKGROUND: Juvenile idiopathic arthritis (JIA), is the most common pediatric rheumatologic disorder with unknown etiology. Currently, no population-based data are available regarding the distribution of categories and frequency of uveitis in patients with JIA in Turkey. The purpose of this study was to evaluate the frequency of JIA-associated uveitis (JIAU) and distribution of JIA categories in a Turkish JIA cohort. METHODS: This was a retrospective study of 500 randomized patients in four pediatric rheumatology clinics in Turkey. RESULTS: Oligoarticular JIA (oJIA) was the most common JIA disease category in this study cohort (38.8%). The frequencies of the other categories were as follows: enthesitis-related arthritis (ERA), 23.2%; rheumatoid factor (RF)-negative polyarthritis, 15.6%; systemic arthritis, 12.2%; juvenile psoriatic arthritis, 5.2%; undifferentiated arthritis, 2.8%; and RF-positive polyarthritis, 2.2%. JIA-associated uveitis was observed in 6.8% of patients at a mean (Standard Deviation, SD) age of 9.1 (3.8) years over a mean JIA disease duration of 4 (1.9) years. Uveitis developed after joint disease, with a mean (SD) duration of 1.8 (1.9) years. Patients with oJIA had the highest rate of uveitis (12.9%) followed by patients with ERA (5.2%) and polyarticular RF-negative disease (3.8%). Compared with persistent oJIA, the extended oJIA category had a > 3-fold higher risk of uveitis (11.3% vs 27.7%; odds ratio, 3.38 [95% Confidence Interval, 1.09-10.4]). The most frequently administered drug after development of uveitis was tumor necrosis factor-alpha inhibitors (38.2%). Five patients (14.7%) had uveitis-related complications that required surgical intervention. CONCLUSIONS: Turkish pediatric patients with JIA experience a lower frequency of oJIA and higher frequency of ERA than their white European counterparts; the occurrence of uveitis is also somewhat lower than expected. Geographic and ethnic factors may affect these differences and need further investigation.

Clinical features and outcomes of 76 patients with COVID-19-related multi-system inflammatory syndrome in children.

OBJECTIVES: Multi-system inflammatory syndrome in children (MIS-C) is a less understood and a rare complication of coronavirus disease-2019 (COVID-19). Given the scarce data regarding this novel disease, we aimed to describe the clinical features and outcomes of our patients with MIS-C and to evaluate the associated factors for the pediatric intensive care unit (PICU) admission. METHODS: The MIS-C patients under 18 years old diagnosed and treated in three referral centers between July 2020 and March 2021 were included. Data of the patients were retrospectively obtained from their medical records. RESULTS: Overall, 76 subjects (24 females) with a mean age of 8.17 ± 4.42 years were enrolled. Twenty-seven (35.5%) patients were admitted to the PICUs. The two most common systemic involvement patterns were cardiac and gastrointestinal. There was only one lethal outcome in a patient with underlying acute lymphoblastic leukemia. Those with higher procalcitonin levels at admission were found to stay longer in the hospital (r = 0.254, p = 0.027). The risk of PICU admission increased with age (aOR: 1.277; 95% CI: 1.089-1.498; p = 0.003) and with decreased initial serum albumin levels (aOR: 0.105; 95% CI: 0.029-0.378; p = 0.001). CONCLUSION: Although there is a wide clinical variability among the patients with MIS-C, we suggest that those with older age and lower initial serum albumin levels merit close monitoring due to their higher risk for PICU admission. Key Points • Although there is a wide variability regarding the management process among clinicians, MIS-C is a rare, severe, less understood complication of COVID-19 that may cause rapid clinical deterioration in the patients. • Clinicians should be aware of this condition in children with persistent fever and a family history of COVID-19. • Older age and low serum albumin levels are the independent predictors for the pediatric intensive care unit admission among MIS-C patients.

Biologics in juvenile idiopathic arthritis-main advantages and major challenges: A narrative review.

Juvenile idiopathic arthritis (JIA) is the most common rheumatic disease in childhood. The disease is divided in different subtypes based on main clinical features and disease course. Emergence of biological agents targeting specific pro-inflammatory cytokines responsible for the disease pathogenesis represents the revolution in the JIA treatment. Discovery and widespread usage of biological agents have led to significant improvement in JIA patients' treatment, with evidently increased functionality and decreased disease sequel. Increased risk of infections remains the main discussion topic for years. Despite the slightly increased frequency of upper respiratory tract infections reported in some studies, the general safety of drugs is acceptable with rare reports of severe adverse effects (SAEs). Tuberculosis (TBC) represents the important threat in regions with increased TBC prevalence. Therefore, routine screening for TBC should not be neglected when prescribing and during the follow-up of biological treatment. Malignancy represents a hypothetical complication that sometimes causes hesitations for physicians and patients in its prescription and usage. On the other hand, current reports from the literature do not support the increased risk for malignancy among JIA patients treated with biological agents. A multidisciplinary approach including a pediatric rheumatologist and an infectious disease specialist is mandatory in the follow- up of JIA patients. Although the efficacy and safety of biological agents have been proven in different studies, there is still a need for long-term, multicentric evaluation providing relevant data.

Tocilizumab therapy in juvenile systemic sclerosis: a retrospective single centre pilot study.

To evaluate the efficacy and safety of anti-interleukin (IL)-6 receptor antibody tocilizumab (TCZ) as a treatment option of juvenile systemic sclerosis (JSS). Nine JSS patients were assigned to a TCZ, additionally to conventional treatment (steroids, methotrexate, mycophenolate-mofetil). The modified Rodnan skin score (mRSS), carbon-monoxide diffusion capacity (DLCO), thorax high-resolution tomography (HRCT), patient global assessment (PGA) and Juvenile Systemic Sclerosis Severity (J4S) score were used to explore the efficacy of treatment. Nine JSS patients were treated with TCZ with a median treatment duration of 10 (1-21) months. Nine patients (77.8%) had radiologically confirmed improvement on thorax HRCT, 7 (77.8%) had decreased PGA (mean pre-treatment PGA 3.7 vs. 2.3 post-treatment PGA 2), 6 (66.7%) had increased DLCO (mean pre-treatment DLCO 69.14% vs. post-treatment DLCO 79.50%) after the TCZ treatment. In all patients mRSS and the J4S decreased: 26.1 vs. 19.7 and 8.2 vs. 4.7, respectively. Changes in mRSS, DLCO, PGA and J4S were statistically significant: p = 0.012, 0.04, 0.026 and 0.007, respectively. All patients tolerated well TCZ treatment. JSS is a rare condition characterized with skin fibrosis and internal organ involvement. Tocilizumab represents a potential treatment option for patients unresponsive to conventional treatment. Long-term prospective studies with higher number of patients are needed to provide more relevant data.

Determination of tuberculin skin test for isoniazid prophylaxis in BCG vaccinated children who are using anti-TNF agents for rheumatologic diseases.

OBJECTIVE: The use of tumor necrosis factor inhibitors (anti-TNF) has a risk of activating latent tuberculosis infection (LTBI). This study was performed to investigate LTBI according to tuberculin skin test (TST) size and to determine the frequency of tuberculosis (TB) in bacillus Calmette-Guerin (BCG)-vaccinated children receiving anti-TNF treatment for rheumatological disease. MATERIALS AND METHODS: The study consisted of 559 children. Information on demographics, anti-TNF agents, TST size, and isoniazid (INH) prophylaxis was recorded. Patients (n = 254) with TST size ≥5 mm were divided into three groups according to TST size and INH prophylaxis: group 1, TST size 5 to 9 mm and no INH prophylaxis; group 2, TST size 5 to 9 mm with INH prophylaxis; and group 3, TST size ≥10 mm with INH prophylaxis. RESULTS: The 559 patients comprised 314 (56.3%) females and 245 (43.6%) males; they had a mean age of 13.1 ± 4.1 years. The mean TST size in all patients was 4.2 ± 4.7 mm. Group 1 consisted of 76 (29.9%) patients, group 2 consisted of 88 (34.6%) patients, and group 3 consisted of 90 (35.4%) patients. The mean TST sizes for the three groups were 6.8 ± 3.1 mm, 7.2 ± 3.2 mm, and 13.9 ± 2.8 mm, respectively. New TB was diagnosed in only two (0.35%) patients. Both of them were in group 3. CONCLUSIONS: A TST size of ≥10 mm in BCG-vaccinated children receiving anti-TNF treatment may distinguish children at high risk for reactivation of LTBI.

Epstein-Barr virus, cytomegalovirus and BK polyomavirus burden in juvenile systemic lupus erythematosus: correlation with clinical and laboratory indices of disease activity.

OBJECTIVES: Clinical and laboratory investigations have revealed that Epstein-Barr virus (EBV) is involved in altered immunological response of systemic lupus erythematosus (SLE). Higher seroprevalence rates of anti-EBV antibodies and increased viral load are demonstrated in adult SLE patients. The prevalence of BK polyomavirus (BKV) reactivation is also suggested to be higher in SLE. Herein, we aimed to evaluate the immune response of children with SLE to EBV antigens in addition to EBV and BKV DNA. We also tried to evaluate whether these serological results differ from another connective tissue disease - juvenile systemic sclerosis (jSS) - and healthy individuals. METHODS: Serum levels of EBV early antigen diffuse (EA-D) IgG, EBV nuclear antigen-1 IgG, EBV viral capsid antigen (VCA), cytomegalovirus (CMV) IgG, EBV DNA, CMV DNA and urinary BKV DNA were evaluated in healthy controls and in patients with a diagnosis of juvenile SLE (jSLE) and jSS. RESULTS: A total of 70 jSLE patients, 14 jSS patients and 44 sex-matched healthy individuals were involved in the study. EBV VCA was positive in 84.2% of jSLE patients, 85.7% of jSS patients and 36.3% of healthy controls. EBV EA-D IgG positivity was significantly higher in jSLE patients compared to jSS patients and healthy controls (20% vs. 7.1% and 0%, p = 0.005). EBV VCA positivity was associated with malar rash and immunological disorder, but there was no statistical significance in other antibody positivity in terms of clinical and haemogram findings and autoantibody positivity. CMV DNA positivity was present in only 2.8% of jSLE patients. None of the jSS patients or the healthy controls had CMV DNA positivity. EBV DNA and BKV DNA were also negative in all three groups. CONCLUSION: The results of our study assume a relationship between SLE and EBV, but we could not demonstrate an association between CMV and BKV. The negative DNA results in contrast to serological positivity can be interpreted as an altered and impaired immune system and increased viral susceptibility. These results suggest that EBV contributes to disease continuity, even if it does not directly cause development.