Background: To evaluate the presence of endothelial dysfunction in Slovak children with juvenile psoriatic arthritis in the absence of classic cardiovascular risk factors in order to assess its relationship to the disease activity and disability. Methods: 25 juvenile psoriatic arthritis patients (JPSA) and 25 healthy controls aged 6–19 years were enrolled into this study. In all subjects vascular measurements over a period of three years (January 2013 – January 2016) were performed, in accordance with the guidelines for ultrasonographic evaluation of FMD% (flow-mediated endothelial dependent vasodilatation) of the brachial artery. The measured items were compared to the variables reflecting the disease activity and disability. Results: Significantly lower FMD% values in patients with JPSA when compared to healthy controls {mean(SD), median, range: 5.49% (3.77), 3.55, 0.3–13.0 vs. 9.28% (1.72), 9.3, 6.4–13.1} (p < 0.001) have been documented. Strong correlations between FMD% values and disease duration (p < 0.01), non-specific inflammatory markers levels (p < 0.001) or functional disability (p < 0.01) have been observed. Significantly lower FMD% values in patients with an early disease onset (JPSA onset < 5 years of age) when compared to the rest of JPSA group {mean (SD), median, range: 4.39% (2.47), 4.45, 0.9–13.2 vs. 6.38% (1.42), 6.3, 3.2–12.1} (p < 0.01) have also been detected. Conclusion: Study is the only one addressing endothelial dysfunction development in Slovak children with psoriatic arthritides. We state that endothelial dysfunction is present in these patients even during childhood and in the absence of classic cardiovascular risk factors. Its development seems to be related to an early disease onset as well as to the increased disease activity and disability. Potential genetic predictors have also been identified.

Tumor necrosis factor alpha (TNF alpha) inhibitors are widely and effectively used for inflammatory and autoimmune diseases in rheumatology, gastroenterology, and dermatology. Adalimumab, etanercept, and infliximab are indicated for the treatment of patients with moderate to severe chronic plaque psoriasis. This target treatment is very effective and lead to control the most severe cases, which were formerly fatal. Biologic treatment is strictly monitored. These large molecules, even with the same mechanism of action in the form of inhibiting TNF alpha, may act differently, and they may have other adverse effects. Skin complications of anti-TNF alpha treatment include a wide range of manifestations which can be divided into four groups: infections, reactions directly associated with drug administration, immune-mediated skin reaction, and malignancy. This chapter describes currently available information regarding the occurrence of individual complications and defines possible therapeutic options in case of individual adverse reactions.

Background Site reactions are the most common but the least serious events of biological treatment. However, the first signs of the serious adverse events may be skin manifestations. Objectives The aim of the prospective study was to evaluate the skin manifestations in children treated with anti-TNF drugs in the center for biological treatment of rheumatic and skin diseases in Eastern Slovakia. Methods A group of thirty one pediatric patients receiving anti-TNF treatment (etanercept or adalimumab) for juvenile idiopathic arthritis (JIA) or psoriasis was evaluated in the period from May 2006 to December 2011. Patients were recruited primarily from the rheumatology department (15 girls and 11 boys). Parameters of efficacy and safety were evaluated every 3 months after therapy initiation. The mean age at initiation was 14.1 years (SD ± 3.9). Average duration of treatment was 3.04 years (range 0.32 – 5.67), 94.24 patient-years in total. Results In the subgroup of JIA patients, four patients developed five different skin manifestations more than 1 year after the initiation. All patients were confirmed for polyarticular seronegative form and ACR-Ped70 responders to etanercept.All underwent a dermatological examination. Three cases were assessed as adverse events. The first patient developed a HPV infection, the second one Varicella and the third one developed both Varicella and mycotic lesions on the face and neck. After temporary discontinuation of anti-TNF drug, skin lesions healed with systemic and topical treatment. All patients continued with anti-TNF treatment thereafter. One case was assessed as a serious adverse event. 13 year-old girl developed Henoch-Schönlein purpura 14 months after initiation of anti-TNF treatment. Although a causative relationship could not be confirmed, anti-TNF treatment was stoped. In the subgroup of psoriasis patients skin-manifested adverse event was observed as well. 15 year-old boy developed histologically verified scleroderma-like lesions 13 months after initiation of etanercept with excellent therapeutic response to the underlying disease. It was assessed as serious adverse event and therefore, anti-TNF treatment was stoped. Conclusions Immunologically mediated cutaneous manifestations could be considered as potential serious adverse events of the anti-TNF treatment although a clear causative relationship can not be confirmed. Careful monitoring of the patients and close cooperation of pediatric rheumatologist and dermatologist is a prerequisite for an early recognition of any infectious or non-infectious skin-manifested complications of anti-TNF drugs and for its treatment. More data possibly from national and international pharmacovigilance registries are necessary to evaluate the actual risk of complications in patients on anti-TNF treatment. Disclosure of Interest None Declared