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Kawasaki disease (KD) is one of the most common vasculitides of childhood and the main cause of acquired heart disease in developed countries. Intravenous immunoglobulin (IVIG) in association with aspirin represents the main treatment for KD. However, 10–20% of patients fail to respond to standard treatment and have an increased risk of cardiac complications. There is currently no accepted protocol for treatment of resistant cases. Several authors highlighted the role of interleukin-1 (IL-1) as a mediator of inflammation in KD and suggested the possibility of using IL-1 or its receptor as a target of therapy. The use of IL-1 inhibitors in patients with KD has been reported in the scientific literature, but data are largely limited to individual case reports and small case series. We summarized the scientific literature related to the use of anakinra, analyzing preclinical and clinical data. Thirty-eight patients have been described so far, most of them with KD-related complications. Twenty-two were described in case reports and case series, while 16 were patients from the completed KAWAKINRA phase IIa study. Almost all patients received clinical benefit, and no relevant side effects were noted. Based on this evidence, in our opinion, anakinra may be considered as an option after the failure of the first IVIG infusion, especially in patients with coronary involvement.

Background Tinea amiantacea is a papulo-squamous condition of the scalp that can lead to scalp fibrosis and subsequent permanent hair loss. It is thought to represent a reaction pattern to inflammatory skin disease as psoriasis or seborrheic dermatitis (1). Objectives To highlight an adverse reaction which involved the skin in the disease course of a young JIA (juvenile idiopathic arthritis) patient, during treatment with adalimumab. Methods A 16-month-old female patient presented to our clinic with a 4-week history of knee swelling, associated with functional limitation and morning stiffness. Family history was unremarkable, while past medical history revealed atopic dermatitis in the first year of life. The baby was initially treated with NSAIDs, but one month later, due the persistence of arthritis and the appearance of uveitis, subcutaneous methotrexate was started (15 mg/m2/weekly). However 5 months later, given the persistence of uveitis and the onset of a severe hypertransaminasemia, methotrexate was interrupted and adalimumab (24 mg/m2 every 2 weeks) was introduced with a prompt and stable control of ocular and articular disease and a gradual normalization of transaminases. One year later the patient developed dry, itchy, red and cracked skin behind her ears, with fissuringin the lower attachment of the ear lobe, and presented right parietal yellowish scalp lesions which were pruriginous, thick, and scaly, attached both to the scalp and to the proximal hair shafts. A first diagnosis of pityriasis amiantacea secondary to atopic dermatitis was made. A paradoxical cutaneous reaction to the anti-TNF therapy was later hypothesized (2), and 7 months later adalimumab was interrupted with quick resolution of the dermatologic lesions. However, both arthritis and uveitis rapidly recurred, showing an inadequate response to a six month cycle of abatacept treatment (10 mg/kg/month). Adalimumab was than reintroduced with a rapid improvement. Results Currently, after 16 months of adalimumab treatment, the patient still shows complete disease control, without any new dermatologic lesions up to now. Conclusion TNF antagonist-induced tinea amiantacea is a rare adverse reaction that may require the drug discontinuation. Although the exact pathogenetic mechanism is unclear, an imbalance in the cytokine milieu with a selective overexpression of type I interferon has been hypothesized. References [1] F. Osorio, F. Magro, C. Lisboa, S. Lopes, G. Macedo, H. Bettencourt, F. Azevedo, S. Magina, Anti-TNF-Alpha induced psoriasiform eruptions with severe scalp involvement and alopecia: report of five cases and review of the literature. Dermatology. 2012;225(2):163-7. doi: 10.1159/000342503 [2] J. Ettler, D.A. Wetter, M.R. Pittelkow. Pityriasis amiantacea: a distinctive presentation of psoriasis associated with tumour necrosis factor-α inhibitor therapy. Clin Exp Dermatol. 2012Aug;37(6):639-41. doi: 10.1111/j.1365-2230.2011.04286.x. Disclosure of Interests Maria Costanza Caparello: None declared, Francesca Tirelli: None declared, Gabriele Simonini Grant/research support from: Abbvie, Speakers bureau: Abbvie, Rolando Cimaz: None declared, Teresa Giani: None declared

Autoimmune diseases affect up to 10% of the world's population and, as a whole, they are far more common in females, although differences exist according to the single disease and also in different age groups. In childhood-onset autoimmune diseases, the sex bias is generally less evident than in adults, probably for the different hormonal milieau, being estrogens strongly implicated in the development of autoimmunity. Still, some rheumatic conditions, such as juvenile idiopathic arthritis (JIA), show a strong predilection for girls (F:M = 3-6.6:1), and differences may coexist between males and females regarding disease outcome. For example, chronic anterior uveitis associated with JIA affects more commonly girls but boys tend to have a more severe course. Systemic lupus erythematosus predominantly affects girls and women (F:M = 3-5:1 in children, F:M = 10-15:1 in adults). Behςet's disease has been reported to be more prevalent in adult males (F:M = 1:1-4); in children, there are no differences. The sex ratio is equal in children and adults for Henoch-Schönlein purpura (F:M = 1:1). A higher male-to-female ratio exists for Kawasaki disease (F:M = 1:1.1-1.6 in children, F:M = 1:1,5 in adults). Juvenile dermatomyositis (F:M = 2-5:1), systemic sclerosis (F:M = 4:1 in children, F:M = 6:1 in adults), and Takayasu arteritis (F:M = 2:1 in children, F:M = 7-9:1 in adults) are more common in girls and women then in boys and men. There is no gender bias for acute rheumatic fever in children, while in adults, the F:M ratio is 2:1. Given that estrogen levels are not different between genders during childhood, pediatric rheumatic diseases could represent good models to study other mechanisms related to the development of autoimmunity. Recently, the levels of miRNA expression, and their variation according to sex chromosomes, have been linked to the development of autoimmune diseases, with different impact among sexes. This review will focus not only on the sex bias reported in the more common rheumatic conditions of childhood, focusing on differences in incidence, but also on outcome and trying to depict the mechanisms underlying those differences.

Juvenile idiopathic arthritis (JIA) may affect natural growth. The aim of the study has been to assess auxological parameters of JIA patients, receiving different anti-rheumatic treatments.This is a retrospective study; JIA patients were recruited from the Rheumatology Unit of Anna Meyer Children's University Hospital of Florence, Italy from March 1996 to June 2016.Two hundred and thirty-two patients were included in the current study. The best result in terms of catch-up growth occurred in systemic JIA patients. All JIA categories showed standard deviation score (SDS) gain for height except those belonging to enthesitis related arthritis category. Patients treated with disease-modifying anti-rheumatic drugs (DMARDs) only maintained constant growth during study follow-up. Patients who needed biologic therapy showed an impaired growth during pre-DMARDs treatment and an increased growth velocity mostly during biologic therapy. Body mass index (BMI) decreased in almost all JIA categories. The best BMI reduction was observed among patient receiving biologic drugs.Patients with JIA followed in our centre had a gain of height SDS and lost BMI SDS in 5 years of follow-up. We observed a stable and good pattern of growth in patients treated with DMARDs and an increased growth velocity during biologic treatment.

TNF-receptor-associated periodic syndrome is an autoinflammatory disorder caused by mutations in TNF receptor superfamily 1A gene. The molecular pathogenesis of TRAPS remains unclear; it is known that a key role is played by mutations in TNFRSF1A that induce the hypersecretion of pro-inflammatory cytokines as well as IL-1β, resulting in uncontrolled inflammatory reactions. Furthermore, TNFRSF1A gene mutations result in intracellular stress ultimately leading to increased production of interleukin-1β, but the exact mechanism referred to in the connection between TNFRSF1A mutation and increased release of IL-1β, is still under study. This explains why IL-1 inhibition treatment can be effective in treating TRAPS patients. The purpose of this review is to discuss the safety and efficacy of canakinumab, a high-affinity human monoclonal anti IL-1β antibody. Areas covered: The data obtained from case reports, case series, Phase II study and a phase III randomized, double-blind, placebo controlled trial have been analyzed. Efficacy and safety profiles of canakinumab are discussed. Expert commentary: Was discussed an overview of treatment options in TRAPS patients. The understanding of pathogenesis of TNF-receptor-associated periodic syndrome led to realize why TRAPS patients respond to IL-1 inhibition. Canakinumab became approved for the treatment in TRAPS patients very recently.