Edoardo Marrani

Biological Treatments in Behçet's Disease: Beyond Anti-TNF Therapy

Behçets disease (BD) is universally recognized as a multisystemic inflammatory disease of unknown etiology with chronic course and unpredictable exacerbations: its clinical spectrum varies from pure vasculitic manifestations with thrombotic complications to protean inflammatory involvement of multiple organs and tissues. Treatment has been revolutionized by the progressed knowledge in the pathogenetic mechanisms of BD, involving dysfunction and oversecretion of multiple proinflammatory molecules, chiefly tumor necrosis factor- (TNF-) α, interleukin- (IL-) 1β, and IL-6. However, although biological treatment with anti-TNF-α agents has been largely demonstrated to be effective in BD, not all patients are definite responders, and this beneficial response might drop off over time. Therefore, additional therapies for a subset of refractory patients with BD are inevitably needed. Different agents targeting various cytokines and their receptors or cell surface molecules have been studied: the IL-1 receptor has been targeted by anakinra, the IL-1 by canakinumab and gevokizumab, the IL-6 receptor by tocilizumab, the IL12/23 receptor by ustekinumab, and the B-lymphocyte antigen CD-20 by rituximab. The aim of this review is to summarize all current experiences and the most recent evidence regarding these novel approaches with biological drugs other than TNF-α blockers in BD, providing a valuable addition to the actually available therapeutic armamentarium.

Serum amyloid-A in Behçet's disease.

Serum amyloid-A (SAA) is an acute phase protein, synthesized by the liver and previously investigated as a marker of disease activity in many rheumatologic disorders. Its significance in Behçet’s disease (BD), a chronic inflammatory disorder at the crossroad between autoimmune and autoinflammatory syndromes, is still unraveled. Our aim was to assess the role of SAA levels as a potential marker of disease activity in patients with BD. According to our findings, the occurrence of oral aphthosis, neurological impairment, and ocular disease is significantly associated with SAA serum levels higher than 30, 50, and 150 mg/L, respectively. We also suggest that increased SAA levels might identify a thrombotic risk in BD with previous or concurrent vascular involvement.

Glucocorticoids in the management of systemic juvenile idiopathic arthritis

Glucocorticoids have been the mainstay of treatment for many years in systemic-onset juvenile idiopathic arthritis (sJIA), causing important side effects and some difficulties in the management of this disease. Until the introduction of biologic agents, oral glucocorticoids were used to control fever and other systemic features for several months or even years if systemic manifestations persisted. Nowadays, clinicians have valid alternatives that have revolutionized the natural history of sJIA. Biologic agents, such as the interleukin-1 inhibitors anakinra and the more recent canakinumab, or the interleukin-6 inhibitor tocilizumab, have improved the prognosis of this debilitating disease. Glucocorticoids still have to be considered at the onset of disease when a non-steroidal anti-inflammatory drug therapy fails or when there are life-threatening complications such as severe anemia or pericarditis, or macrophage activation syndrome. Local (intra-articular) triamcinolone hexacetonide is the treatment of choice for arthritis limited to one joint or a few joints in patients without systemic activity. To date, there is still great heterogeneity in the management of sJIA patients, but in recent years there have been attempts to design algorithms and treatment protocols for glucocorticoids, disease-modifying anti-rheumatic drugs, and biologic agents. This review provides an overview of the current knowledge of glucocorticoid therapy in sJIA, comments on recently published recommendations, and gives practical support to the clinician for management of this disease.

Pediatric Osteoporosis: Diagnosis and Treatment Considerations

Osteoporosis is now increasingly recognized in children due to the increased prevalence of disorders associated with bone loss. Fragility fractures represent the cardinal clinical features of pediatric osteoporosis and children presenting with fragility fractures deserve an accurate assessment to rule out a secondary cause. Indeed, in the pediatric population, a low bone mass is often a consequence of a chronic disease or its treatment; genetic bone disorders represent the cause of only a small fraction of cases. The position statement of the International Society for Clinical Densitometry guides physicians in interpreting densitometric data and making diagnoses of osteoporosis in children. Once a diagnosis of osteoporosis has been made, the aim is to identify children in whom bone status may deteriorate if left untreated. To date, bisphosphonates have represented the mainstay of treatment for pediatric osteoporosis. However, due to the peculiar pathophysiology of osteoporosis in this age group, a pharmacological agent with an anabolic effect on bone may provide clinicians with other therapeutic options in children. Multicenter studies are needed to optimize treatments and define optimal clinical response in treated children.

Comparing ultraviolet light A photo(chemo)therapy with Methotrexate protocol in childhood localized Scleroderma: Evidence from systematic review and meta-analysis approach

OBJECTIVE Localized scleroderma is a skin fibrosing disorder that, if untreated, may result in severe disability. The purpose of this systematic review is to compare the present evidence concerning the effectiveness of Methotrexate versus phototherapy, alone or associated with Psoralen, in childhood localized scleroderma. METHOD A systematic search between January 1996 and May 2017 was performed to identify studies investigating the efficacy of Methotrexate (MTX) or phototherapy (UVA) for treating localized scleroderma with onset ≤18 years. Due to a lack of validated clinical criteria, four clinical response criteria were used to assess the treatment efficacy as primary outcome. We determined a combined estimate of the proportion of children responding to MTX and UVA. RESULTS A total of 19 studies was included (8 MTX; 11 UVA). In the methotrexate group, 193 children were included in the analysis; in the phototherapy group, a total of 48 treated children. For both groups age, disease subtype, glucocorticoids (GCs) use, and side effects of treatment were also analyzed. The meta-analysis suggested that UVA and MTX protocols have both a favorable effect in active lesions of childhood localized scleroderma. However, MTX resulted significantly superior to UVA, with or without Psoralen. CONCLUSION Our study supports the combination of MTX and GCs in patients with a high risk of complication. Phototherapy with UVA1 could represent a therapeutic option in patients with limited scleroderma, where lesions do not cross joints and they do not lead to potential cosmetic changes.

“Brucellupus” in a boy: challenging sle diagnosis in childhood

Systemic Lupus Erythematosus (SLE) is the prototype of systemic autoimmune disorders. Several infectious diseases can mimic autoimmune disorders , eg. Mycobacterium tubercolosis), Parvovirus B19), and Leishmania. Brucella infection has been rarely reported in such differential.

Kawasaki shock syndrome: a case report

Kawasaki disease is the second most common systemic vasculitis of childhood and may result in life-threatening coronary artery abnormalities in up to 25% of untreated patients. Adolescents often present with an atypical/incomplete presentation of KD with a delayed diagnosis. Kawasaki Shock syndrome (KDSS) is a rare KD presentation and has been recently defined as the presence of any of the following conditions: systolic hypotension ( 20% or clinical signs of poor perfusion with accompanying features of KD [1].

Joint pain management in children and adolescents

In children, joint pain is common complaint and it proves challenging for primary care physicians. The possible differential diagnoses include a wide range of disorders, from the common and benign ones to serious and even life-threating conditions. An accurate work-up of these patients is needed, with thorough patient history and a systematic physical examination as essential tools. Clarifying the nature, the site, and the duration of the pain is fundamental as well as identifying systemic symptoms such as fever, weight loss, and night sweating. We will provide a description of the different clinical presentations of such disorders, and suggest how to approach a targeted patient history and a complete physical examination, which may lead to the appropriate investigation and consequently to the correct diagnosis.

Sensorineural hearing loss: a new manifestation of neonatal lupus erythematosus?

Neonatal lupus erythematosus (NLE) is a rare acquired autoimmune disease, characterized by the transplacental passage of maternal antibodies (anti-SSA/Ro and/or anti-SSB/La) into the fetal circulation system, inducing clinical manifestation in the neonate. The most serious clinical manifestation of NLE is a nonreversible complete congenital heart block (CHB), and other common manifestation included skin rash, hepatobiliary and hematologic abnormalities, which are usually reversible.

Localized scleroderma in a cohort of juvenile idiopathic arthritis children.

Juvenile idiopathic arthritis (JIA) is the most common chronic rheumatic disease in childhood. Localized scleroderma also known as morphea is an inflammatory, fibrosing skin disorder that leads to sclerosis of the dermis and eventually of the underlying tissues. The prevalence is estimated at around 1-9/100,000 with the onset before 10 years of age in 2% of patients.The association between different autoimmune diseases is well described, but few studies have been performed to investigate the relationship between JIA and other autoimmune diseases, in particular very little is written about the possible association between arthritis and morphea. In these cases articular involvement in terms of arthralgia, impaired joint mobility, or joint contracture, may be related to a mechanical etiology secondary to the contracture of the overlying skin.