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.

BackgroundGranulomatosis with polyangiitis (GPA), formerly known as Wegener’s granulomatosis (WG), belongs to the group of ANCA-associated necrotizing vasculitides. This study describes the clinical picture of the disease in a large cohort of GPA paediatric patients.Children with age at diagnosis ≤ 18 years, fulfilling the EULAR/PRINTO/PRES GPA/WG classification criteria were extracted from the PRINTO vasculitis database. The clinical signs/symptoms and laboratory features were analysed before or at the time of diagnosis and at least 3 months thereafter and compared with other paediatric and adult case series (>50 patients) derived from the literature.FindingsThe 56 children with GPA/WG were predominantly females (68%) and Caucasians (82%) with a median age at disease onset of 11.7 years, and a median delay in diagnosis of 4.2 months. The most frequent organ systems involved before/at the time of diagnosis were ears, nose, throat (91%), constitutional (malaise, fever, weight loss) (89%), respiratory (79%), mucosa and skin (64%), musculoskeletal (59%), and eye (35%), 67% were ANCA-PR3 positive, while haematuria/proteinuria was present in > 50% of the children. In adult series, the frequency of female involvement ranged from 29% to 50% with lower frequencies of constitutional (fever, weight loss), ears, nose, throat (oral/nasal ulceration, otitis/aural discharge), respiratory (tracheal/endobronchial stenosis/obstruction), laboratory involvement and higher frequency of conductive hearing loss than in this paediatric series.ConclusionsPaediatric patients compared to adults with GPA/WG have similar pattern of clinical manifestations but different frequencies of organ involvement.

Data regarding the safety and efficacy of treatment regimens for juvenile dermatomyositis (JDM) tends to be from anecdotal, small, uncontrolled, non-randomized case series.

Factors that would predict treatment outcome for methotrexate (MTX) would be of great value to clinicians. Recent pharmacogenetic studies have reported associations between single nucleotide polymorphisms (SNP) in MTX transporters and treatment outcome in childhood acute lymphoblastic leukemia and in rheumatoid arthritis.

The conduct of Clinical Research in rare diseases, such as Juvenile Systemic Sclerosis (jssc) and Juvenile Localized Scleroderma (JLS), requires an adequate number of patients and a fruitful collaboration between international centers. The clinical management of young patients suffering from these diseases is also often difficult to achieve in an effective and shared matter.

Cervical spine arthritis is a well-recognized complication of juvenile idiopathic arthritis (JIA). It is usually present in patients with more severe disease.

Dysregulation of many inflammatory cytokines, utilizing STAT signaling pathways, has been found as important contributor in initiation, progression and maintenance of inflammation in patients with Systemic Lupus Erythematosus (SLE). FoxP3+CD4+ regulatory T cells (Tregs) are important mediators of peripheral immune tolerance and their perturbed homeostasis, including expansion of CD45RA-FoxP3lo non-Treg subpopulation was reported in adult patients with SLE. Type I and II interferons (IFN I and IFN II), which are implicated in SLE pathogenesis, were shown to perturb Treg homeostasis. Many IFN regulated genes are dependent on STAT1 for optimal transcription, and STAT1 protein expression is under control of IFNs.

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). In recent years, APS has been increasingly recognized in various pediatric autoimmune and nonautoimmune diseases, but the relatively low prevalence and heterogeneity of APS in childhood made it very difficult to study in a systematic way.

Catatonia is a rarely reviewed clinical feature of neuropsychiatric (NP) manifestation of pediatric systemic lupus erythematosus (pSLE). It is a state of neurogenic motor immobility, and behavioral abnormality manifested by stupor.

Takayasu arteritis (TA) is a rare chronic granulomatous vasculitis of large vessels. Initial symptoms and signs are usually non-specific, therefore a high index of suspicion is needed to make a timely and correct diagnosis.