Juvenile Idiopathic arthritis (JIA) is the most common chronic rheumatic disease in childhood. The diagnosis is based on the underlying symptoms of arthritis with an exclusion of other diseases Biologic agents are increasingly used on the side of disease-modifying anti-rheumatic drugs (DMARD) in JIA treatment. The aim of this meta-analysis was to investigate the observed infections in JIA children during tumor necrosis factor (TNF)-alpha inhibitor therapy. A systematic search of three databases (Medline via PubMed, Embase, Cochrane Library) was carried out up to May 2018. Published trials that evaluated the infectious adverse events in patients receiving TNF-alpha inhibitor vs. a control group were included in the analysis. Full-text data extraction was carried out independently by the investigators from ten relevant publications. 1434 patients received TNF-alpha inhibitor therapy; the control group consisted of 696 subjects. The analysis presented the risk of infection in the active treatment group (OR = 1.13; 95% CI: 0.76–1.69; p = 0.543). The majority of infections were upper respiratory tract infections (URTIs). Furthermore, the subgroup analysis demonstrated a higher infection rate in the observed localization. Anti-TNF therapy slightly but not significantly increases the incidence of infection in JIA children compared to other therapies (GRADE: moderate evidence). The most common infections reported were mild URTIs. Further studies with larger patients number with a strong evidence level are crucially needed to finalize the answer whether anti-TNF therapy elevates and if yes on what extent the incidence of infection in JIA children. Prospero: CRD42017067873 .

Raynaud’s phenomenon (RP) is a functional vascular disease, presenting with recurrent episodes of ischemia of extremities in response to cold and emotional stress. Investigating cutaneous microcirculation is an important tool in understanding the complex neuro-immuno-vascular interactions in its pathophysiological mechanisms. Since there is no available data on vascular responsiveness in RP in the paediatric population, we investigated skin perfusion and heat-induced hyperaemia in comparison with clinical severity and laboratory parameters of the disease. Fifty two adolescents (27 patients with primary RP and 25 age-matched healthy controls) were investigated in the study. Patients were divided into two groups according to the symptoms existing within the previous 2 months. Following baseline microcirculation measurement with Laser Doppler flowmetry (Periflux 5000 system), all subjects underwent local heating test at 42 °C and 44 °C. Besides routine laboratory parameters, immune-serological tests and the vasoactive sensory neuropeptides somatostatin and pituitary adenylate-cyclase activating polypeptide (PACAP) were measured. Baseline perfusion measured in perfusion units (PU) at 32 °C was significantly lower in symptomatic RP patients (97.6 ± 22.4 PU) compared with both healthy volunteers (248.3 ± 23.5 PU, p < 0.001) and RP patients without symptoms (187.4 ± 24.9 PU, p < 0.05). After local heating to 42 °C maximum blood flow was significantly reduced in primary RP participants with current symptoms (358.6 ± 43.9 PU, p < 0.001), but not in asymptomatic ones (482.3 ± 28.7 PU, p > 0.05) when compared with healthy subjects (555.9 ± 28.2 PU). Both the area under the response curve and the latency to reach the maximum flow were significantly increased in both RP groups (symptomatic 164.6 ± 7.4 s, p < 0.001, asymptomatic 236.4 ± 17.4 s, p < 0.001) when compared with the control group (101.9 ± 4.7 s). The heat-induced percentage increase from baseline to maximal blood flow was significantly greater in symptomatic RP adolescents in comparison with healthy ones. Laboratory parameters and neuropeptide plasma levels were not altered in any groups. To our knowledge this is the first study in paediatric population to show altered heat-induced cutaneous hyperaemia responses in relation with the clinical severity and symptomatology.

Autoinflammatory diseases are disorders of the innate immune system characterized by recurrent systematic inflammation and serious complications. Dysregulation of inflammasome and overproduction of interleukin-1 play a major role in the pathogenesis of autoinflammatory diseases. The diagnosis of these rare conditions rely on recognising the pattern of presentation and differential diagnosis. Manifestations may include fever, rash, serositis (pleuritis and peritonitis), arthritis, meningitis and uveitis. Secondary amyloidosis may complicate longstanding disease. Advances in our understanding of the molecular and pathophysiological basis of the autoinflammatory diseases have resulted in new treatment strategies. Early diagnosis and effective therapy are critical to prevent irreversible organ damage. The purpose of this review is to describe the major clinical, genetic, and therapeutic features of the most common autoinflammatory syndromes. Orv Hetil. 2018; 159(23): 898–907.

This is the first report describing a severe form of cold agglutinin-induced acrocyanosis with cutaneous necrosis after Mycoplasma infection in a 9-year-old patient without any other severe symptoms and laboratory alterations. We also present the results ...

Introduction: Natural autoantibodies (nAAbs) contribute to immune homeostasis and may be altered in patients with autoimmune diseases. While anti-heat shock protein (Hsp) antibodies have been previously described in juvenile idiopathic arthritis (JIA), their relationship with disease severity and treatment effects during remission remains unclear. This study aimed to measure the serum levels of IgM and IgG nAbs against heat shock protein (Hsp) 60 and Hsp70 in children with JIA in remission (mean age: 7.41 years, range:1.27-14.54 years) and to explore their associations with disease subtype, severity, and treatment. Methods: Serum samples from 47 children with JIA in remission and 22 apparently healthy controls (HC) were analyzed. Patient groups were stratified according to the treatment regimen (methotrexate monotherapy versus methotrexate plus adalimumab) and disease subtype and severity. Anti-Hsp60 and anti-Hsp70 IgM and IgG antibodies were measured u s ing an in-house indirect ELISA. Results: No significant differences in anti-Hsp60 or anti-Hsp70 nAAb levels were observed between patients with JIA and apparently healthy controls or between treatment groups. However, severity-based analyses revealed significantly lower anti-Hsp60 and anti-Hsp70 IgM levels in patients with polyarticular JIA than in those with milder oligoarticular forms and in apparently healthy controls. No significant differences were observed in the anti-Hsp60 or anti-Hsp70 IgG levels. Conclusion: Reduced levels of natural IgM autoantibodies against Hsp60 and Hsp70 are associated with more severe JIA phenotypes during remission, supporting the potential immunoregulatory and protective roles of natural IgM autoantibodies in JIA.