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.

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Familial Mediterranean fever (FMF) is the most common monogenic autoinflammatory disease manifesting phenotypic heterogeneity. It is a clinically diagnosed disease supported by MEditerranean FeVer (MEFV) gene mutation analysis. However, the phenotype-genotype correlation is not yet established clearly. We aimed to determine the clinical findings, phenotype-genotype correlation, and treatment outcomes within a large pediatric FMF cohort. The medical charts of children with FMF who were diagnosed and followed up at the eight pediatric rheumatology units were reviewed retrospectively. All patients in the cohort were analyzed for sequence variants in exon 2,3,5 and 10 of the MEFV gene. Patients without any mutations or with polymorphisms including R202Q were excluded. A total of 3,454 children were involved in the study. The mean ± standard deviation of current age, age at symptom onset, and age at diagnosis were 12.1 ± 5.2, 5.1 ± 3.8, and 7.3 ± 4.0 years, respectively. Of 3,454 patients, 88.2% had abdominal pain, 86.7% had fever, 27.7% had arthritis, 20.2% had chest pain, 23% had myalgia, and 13.1% had erysipelas-like erythema. The most common MEFV mutation patterns were homozygous (32.5%) and heterozygous (29.9%) mutations of exon 10. Homozygous M694V was present in 969 patients (28.1%). Allele frequencies of common mutations were M694V (55.3%), M680I (11.3%), V726A (7.6%), and E148Q (7.2%). Children carrying homozygous or compound heterozygous exon 10 mutations had an earlier age of disease onset (4.6 vs. 5.6 years, p = 0.000) and a higher number of attacks per year (11.1 vs. 9.6, p = 0.001). Although 8% of the patients had a family history of amyloidosis, 0.3% (n = 11) had the presence of amyloidosis. M694V homozygosity was detected in nine patients who developed amyloidosis. Colchicine resistance was present in 4.2% of our patients. In this largest pediatric cohort reviewed and presented to date, patients with exon 10 mutations, particularly the M694V homozygous mutation, have been demonstrated earlier disease onset, annual attack count, and more frequent colchicine-resistant cases. Although E148Q is considered as a polymorphism in some populations, it was identified as a disease-causing mutation in our cohort. Secondary amyloidosis is still happening in adults however, it is extremely rare among children, presumably due to increased awareness, tight control, and the availability of anti-IL1 agents in colchicine-resistant cases.

Spondyloenchondrodysplasia (SPENCD) is a rare skeletal dysplasia characterized with platyspondyly and metaphyseal lesions of the long bones mimicking enchondromatosis, resulting in short stature. SPENCD often coexists with neurologic disorders and immune dysregulation. Spasticity, developmental delay and intracranial calcification are main neurologic abnormalities. Large spectrum of immunologic abnormalities may be seen in SPENCD, including immune deficiencies and autoimmune disorders with autoimmune thrombocytopenia and systemic lupus erythematosus as the most common phenotypes. SPENCD is caused by loss of tartrate-resistant acid phosphatase (TRAP) activity, due to homozygous mutations in ACP5, playing a role in non-nucleic acid-related stimulation/regulation of the type I interferon pathway. We present two siblings, 13-year-old girl and 25-year-old boy with SPENCD, from consanguineous parents. Both patients had short stature, platyspondyly, metaphyseal changes, spastic paraparesis, mild intellectual disability, and juvenile-onset SLE. The age at disease-onset was 2 years for girl and 19 years for boy. Both had skin and mucosa involvement. The age at diagnosis of SLE was 4 years for girl, and 19 years for boy. The clinical diagnosis of SPENCD was confirmed by sequencing of ACP5 gene, which revealed a homozygous c.155A > C (p.K52T), a variant reported before as pathogenic. Juvenile-onset SLE accounts for about 15-20% of all SLE cases. But, the onset of SLE before 5-years of age and also monogenic SLE are rare. Our case report and the literature review show the importance of multisystemic evaluation in the diagnosis of SPENCD and to remind the necessity of investigating the monogenic etiology in early-onset and familial SLE cases.

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

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H enoch-Schönlein purpura (HSP), also known as IgA vasculitis, is the most common form of systemic vasculitis in children [1]. HSP is grouped under the rubric of small vessel vasculitis and typically involves skin, joints, kidneys and gut. The clinical spectrum may range from mild skin rash and arthralgia to severe gastrointestinal (GI) and renal involvement [1, 2]. All of the patients have a purpuric rash typically located on the legs and buttocks. The rash may also extend to the arms and face [1-3]. Sometimes, GI manifestations, such as abdominal pain or join manifestations like arthralgia or arthritis, may precede the development of a purpuric rash in less than 5% of the patients [3]. Other manifestations are low-grade fever, lethargy, myalgia, orchitis, sub-ABSTRACT OBJECTIVE: This retrospective observational study aims to demonstrate initial signs and symptoms of Henoch-Schönlein purpura (HSP), search for risk factors for gastrointestinal and renal involvement and give short term follow-up results. METHODS: The files of newly diagnosed HSP patients from two pediatric rheumatology centers in the southeastern part of the country were retrospectively analyzed in this study. Demographic, clinical features and laboratory results were recorded from the files. RESULTS: The cohort consisted of 323 children (males: 53.6%, females: 46.4%). Median age at the time of diagnosis was 7.5 (1.8-17.3) years and the median duration of follow-up was six (3-22) months. The rash was present in all cases but was not the first symptom in 22.9% of the cases. Arthritis and abdominal pain before the development of rash were the initial symptoms in 11.8% and 11.1% of the cases, respectively. Other manifestations were subcutaneous edema (63.2%), arthralgia (57.6%), arthritis (27.6%), myalgia (17.6%), lethargy (10.2%), orchitis (7.5%) and fever (5.3%). Gastrointestinal involvement was seen in 53.3% and renal involvement in 23.5% of the cases. None of the patients developed renal impairment during the follow-up. Older age at diagnosis, necrotic rash, subcutaneous edema, abdominal pain, lethargy, myalgia, arthralgia and arthritis were significantly higher in patients with renal involvement, but none of the demographic, clinical and laboratory features was an independent risk factor for renal or gastrointestinal involvement. CONCLUSION: Abdominal pain, arthritis may be the first manifestation of HSP. Having constitutional symptoms, such as fever, myalgia and lethargy at the time of diagnosis, may be warning signs of a more aggressive course with gastrointestinal and renal involvement.

Objectives Behçet’s Disease (BD) is a systemic vasculitis affecting many organ systems with the involvement of all sized arteries and veins. Patients with BD may present with varying features. The study aims to determine the main characteristics of pediatric BD patients and also analyze the clustering phenotypes in a large multicentric cohort. Methods Demographic data, clinical manifestations, laboratory features, treatment schedules, and disease outcomes were achieved from patients’ charts retrospectively. A cluster analysis was performed according to phenotype. Results A total of 225 (109 male/ 116 female) patients with BD were enrolled in the study. The median age of disease onset and diagnosis was 131 (36-151) and 156 (36-192) months, respectively. The median time between the onset of symptoms and diagnosis was 23.5 (0-45) months. According to cluster analysis; 132 (58.6%) patients belonged to the mucocutaneous-only cluster (C1) while 35 (15.6%) patients fitted to articular type (C2), 25 (11.1%) %) were in ocular cluster (C3), 26 (11.6%) were in vascular cluster (C4) and 7 (3.1%) belonged to the gastrointestinal cluster (C5). Ocular and vascular clusters were more common in boys (p&lt;0.001), while girls usually presented with the mucocutaneous-only cluster. The clusters had comparable ages upon diagnosis. The disease activity at the diagnosis and the last control was higher in ocular, vascular, and gastrointestinal clusters. Conclusions We identified five different subtypes in juvenile BD patients. These subtypes express different phenotypes with different outcomes. Our analysis may help clinicians to identify the disease subtypes accurately and to arrange personalized treatment.