ABSTRACT
INTRODUCTION: 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-1ß, resulting in uncontrolled inflammatory reactions. Furthermore, TNFRSF1A gene mutations result in intracellular stress ultimately leading to increased production of interleukin-1ß, but the exact mechanism referred to in the connection between TNFRSF1A mutation and increased release of IL-1ß, 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-1ß 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.
Subject(s)
Anti-Inflammatory Agents/therapeutic use , Antibodies, Monoclonal/therapeutic use , Fever/therapy , Hereditary Autoinflammatory Diseases/therapy , Immunotherapy/methods , Interleukin-1beta/immunology , Antibodies, Monoclonal, Humanized , Clinical Trials as Topic , Drug Approval , Fever/genetics , Fever/immunology , Hereditary Autoinflammatory Diseases/genetics , Hereditary Autoinflammatory Diseases/immunology , Humans , Mutation/genetics , Receptors, Tumor Necrosis Factor, Type I/geneticsABSTRACT
BACKGROUND: Chronic recurrent multifocal osteomyelitis (CRMO) is a rare condition that commonly affects the clavicle and pelvis. CASE PRESENTATION: We report here a case a 12 years old girl with CRMO arising with recurrent episodes of left supraorbital headache, followed by the appearance of a periorbital dyschromia. Magnetic resonance imaging (MRI) of the skull and orbits revealed an important subacute inflammatory process. Few months after, the child presented a painful swelling of the left clavicle; the histological examination of the related biopsy allowed to establish the diagnosis of CRMO. CONCLUSION: CRMO presenting as acute headache involving neurocranium is rare; to our knowledge this is the first recognized case in the world literature. This pathological condition is frequently misdiagnosed as infection or neoplasm and needs a deep investigation for the differential diagnosis. The physical, laboratoristic and instrumental diagnostic investigations of the patient and the treatment employed are described in detail.
