PFAPA syndrome is the most common autoinflammatory disorder in childhood with unknown etiology. The aim of our study was clinical evaluation of PFAPA patients from a single tertiary care center and to determine whether variations of AIM2, MEFV, NLRP3, and MVK genes are involved in PFAPA pathogenesis. Clinical and laboratory data of consecutive patients with PFAPA syndrome followed up at the University Children's Hospital, Ljubljana, were collected from 2008 to 2014. All four genes were PCR amplified and directly sequenced. Eighty-one patients fulfilled criteria for PFAPA syndrome, 50 (63%) boys and 31 (37%) girls, with mean age at disease onset of 2.1 ± 1.5 years. Adenitis, pharyngitis, and aphthae were present in 94%, 98%, and 56%, respectively. Family history of recurrent fevers in childhood was positive in 78%. Nineteen variants were found in 17/62 (27%) patients, 4 different variants in NLRP3 gene in 13 patients, and 6 different variants in MEFV gene in 5 patients, and 2 patients had 2 different variants. No variants of clinical significance were found in MVK and AIM2 genes. Our data suggest that PFAPA could be the result of multiple low-penetrant variants in different genes in combination with epigenetic and environmental factors leading to uniform clinical picture.

BackgroundRheumatic diseases in children are associated with significant morbidity andpoor health-related quality of life (HRQOL). There is no health-relatedquality of life (HRQOL) scale available specifically for children with lesscommon rheumatic diseases. These diseases share several features withsystemic lupus erythematosus (SLE) such as their chronic episodic nature,multi-systemic involvement, and the need for immunosuppressive medications.HRQOL scale developed for pediatric SLE will likely be applicable tochildren with systemic inflammatory diseases.FindingsWe adapted Simple Measure of Impact of Lupus Erythematosus in Youngsters(SMILEY©) to Simple Measure of Impact of Illness in Youngsters(SMILY©-Illness) and had it reviewed by pediatric rheumatologists forits appropriateness and cultural suitability. We tested SMILY©-Illnessin patients with inflammatory rheumatic diseases and then translated it into28 languages.Nineteen children (79% female, n=15) and 17 parents participated. The meanage was 12±4 years, with median disease duration of 21 months (1-172months). We translated SMILY©-Illness into the following 28 languages:Danish, Dutch, French (France), English (UK), German (Germany), German(Austria), German (Switzerland), Hebrew, Italian, Portuguese (Brazil),Slovene, Spanish (USA and Puerto Rico), Spanish (Spain), Spanish(Argentina), Spanish (Mexico), Spanish (Venezuela), Turkish, Afrikaans,Arabic (Saudi Arabia), Arabic (Egypt), Czech, Greek, Hindi, Hungarian,Japanese, Romanian, Serbian and Xhosa.ConclusionSMILY©-Illness is a brief, easy to administer and score HRQOL scale forchildren with systemic rheumatic diseases. It is suitable for use acrossdifferent age groups and literacy levels. SMILY©-Illness with itsavailable translations may be used as useful adjuncts to clinical practiceand research.

Childhood-onset systemic lupus erythematosus (cSLE) is a rare multisystem autoimmune disease that often leads to significant morbidity. Evidence-based guidelines are sparse and management is mostly based on physician’s experience. Consequently, treatment regimens differ throughout Europe. In 2012, a European initiative called SHARE (Single Hub and Access point for paediatric Rheumatology in Europe) was launched to optimize and disseminate diagnostic and management regimens in Europe for children and young adults with rheumatic diseases such as cSLE.

Childhood-onset systemic lupus erythematosus (cSLE) represents 15-20% of all SLE cases and is in general associated with a more aggressive disease course and more rapid damage accrual than adult-onset SLE. Disease expression varies according to ethnicity, with more severe disease course in non-Caucasian ethnic groups. The majority of patients with cSLE develop damage within 5-10 years of disease onset, most frequently involving the musculoskeletal, ocular, renal and central nervous systems. Premature atherosclerosis and osteoporosis have become increasingly prevalent comorbidities in cSLE patients. Treatment of cSLE is challenging and is further complicated by an unpredictable disease course, adolescent noncompliance and long requirement for therapy. New therapeutic regimens combining immunosuppressive agents and targeted B-cell depletion often provide improved disease control and follow the oncologic model of remission induction and maintenance therapy. Management of children with SLE must include also prevention of medication side effects on growth, delayed puberty, development and fertility. Optimal management of an adolescent with SLE should take into account also patient’s quality of life, psychosocial development and organization of successful transition from pediatric to adult care. The antiphospholipid antibody syndrome (APS) is a multisystemic autoimmune disease characterized by thromboembolic events, pregnancy morbidity, hematologic, dermatologic, neurologic and other manifestations in the presence of elevated titers of antiphospholipid antibodies (aPL). APS may occur as an isolated clinical entity (primary APS) or in association with autoimmune diseases, infections and malignancies. Multiple pathogenic mechanisms have been proposed by which aPL may predispose to thrombosis including interaction between aPL and endothelial cells, platelets, monocytes, activation of the complement system, and interaction with the proteins involved in the regulation of the coagulation cascade. Management in all patients with APS include avoidance of additional risk factors for thrombosis. Patients with persistently positive aPL, in particular those with lupus anticoagulants (LA), have a high risk for recurrent thrombosis and should receive long-term anticoagulation with warfarin. The standard treatment in APS patients with venous or non-cerebral arterial thromboembolism consist of oral anticoagulation at a target INR of 2.0-3.0. However, it is essential to individualize treatment according to the presence of additional thrombophilic risk factors and the aPL profile (multiple aPL antibodies, high titers of aCL and/or anti-β2GPI, presence of LA). An improved understanding of the pathogenic mechanisms by which aPL induce thrombosis has suggested some innovative treatments such as new anticoagulant and antiplatelet drugs, hydroxychloroquine, statins, complement inhibitors, rituximab and other targeted therapies.

Kawasaki Disease (KD) and Henoch Schonlein Purpura (HSP) are paediatric vasculitides that can lead to significant morbidity. Evidence-based guidelines are sparse and management is mostly based on physician experience. Consequently, treatment regimens differ throughout Europe. In 2012, a European initiative called SHARE (Single Hub and Access point for paediatric Rheumatology in Europe) was launched to optimize and disseminate guidelines for diagnosis and management for children and young adults with paediatric rheumatic diseases (PRD) such as KD and HSP within Europe.

Single nucleotide polymorphisms (SNPs) are common (1%) variations in DNA sequence, that can be the reason for individual variability in drug efficacy and drug safety.

Results We report the patient characteristics at time point 0, 6 and 12 months of their follow up. We present date on 25 patients. The mean follow up of the patients in the cohort are 3.5 years. No patient died during the follow up. Eighteen of the 25 patients were female. The mean age of the onset of Raynaud symptomatic was 10.4 years, the youngest patient was 2.0 years of age. The mean age at the onset of the non-Raynaud symptomatic were 11.0 years. 19 of the 25 have diffuse subtype, 6 of them have an overlap symptomatic, two of them associated with diffuse subtype. ANA positive were 20, and 8 of them were antiScl 70 positive. None of them was anticentromere positive The mean modified Rodnan Skin Score was at timepoint 0, 6 and 12 month 18.1, 15.1 (n=21) and 15.1. (n=17). Raynaud ́s Phenomen occurred in 22/25 at time point 0 and 16 of 21 at time point 6 months and 12 of 17 at 12 months. 18 of 25 of them had capillary changes already at time point 0. 7 of them had already ulcerations at time point zero, 9 of 21 at month 6 and 4 of 17 at months 12. 15 of them had cardiopulmonary involvement, at time point zero already, 9 of them had interstitial lung disease. 6 of 21 have cardiopulmonary involvement at month 6 and 7 of 17 at month 12 of follow up. Two of them have renal involvement at time point 0 and 3 at time point 6 and 12 months. 9 of 25 had gastrointestinal involvement, and 5 of them oesophageal involvement at time point zero, 3 from 21 at month 6 and 5 of 17 at 12 months. 22 of 25 have musculoskeletal involvement 19 of 21 at month 6 and 16 of 17 at 12 months.

Macrophage activation syndrome (MAS) is a potentially fatal complication of systemic juvenile idiopathic arthritis (sJIA), whose prompt recognition and treatment are critical. However, early diagnosis of MAS is often challenging and none of the current diagnostic criteria is satisfactory. An international project aimed to develop a new set of classification criteria for MAS was recently started.

PFAPA syndrome is the most common autoinflammatory fever disorder in childhood, characterized by recurrent fever, aphthous stomatitis, pharyngitis and adenitis. Mutations in the MEFV and NLRP3 genes are known to cause syndromes with PFAPA overlapping symptoms (Familial Mediterranean Fever and Cryopyrin-Associated Periodic Syndrome), which are rarely reported in patients from Slovenia.

Varicella infection is a highly contagious disease which can have a complicated course especially in immunocompromised children and children receiving immunomodulatory therapy.

Antiphospholipid syndrome (APS), either primary or secondary to other paediatric rheumatic diseases, is rare in children, but it can lead to significant morbidity. Evidence-based guidelines are sparse and management is mostly based on physician’s experience. Consequently, treatment regimens differ throughout Europe. In 2012, a European initiative called SHARE (Single Hub and Access point for paediatric Rheumatology in Europe) was launched to optimize and disseminate diagnostic and management regimens in Europe for children and young adults with rheumatic diseases such as APS.

Juvenile Localized Scleroderma (JLS) and Juvenile Systemic Sclerosis (JSSc) form a group of rare pediatric diseases that can lead to significant morbidity. Evidence-based guidelines are sparse and management is mostly based on physician’s experience. Consequently, treatment regimens differ throughout Europe. In 2012, a European initiative called SHARE (Single Hub and Access point for pediatric Rheumatology in Europe) was launched to optimize and disseminate diagnostic and management regimens in Europe for children and young adults with rheumatic diseases.