title: Caveats and truths in genetic, clinical, autoimmune and autoinflammatory issues in Blau syndrome and early onset sarcoidosis.
abstract: Blau syndrome (BS) and early onset sarcoidosis (EOS) are, respectively, the familial and sporadic forms of the pediatric granulomatous autoinflammatory disease, which belong to the group of monogenic autoinflammatory syndromes. Both of these conditions are caused by mutations in the NOD2 gene, which encodes the cytosolic NOD2 protein, one of the pivotal molecules in the regulation of innate immunity, primarily expressed in the antigen-presenting cells. Clinical onset of BS and EOS is usually in the first years of life with noncaseating epithelioid granulomas mainly affecting joints, skin, and uveal tract, variably associated with heterogeneous systemic features. The dividing line between autoinflammatory and autoimmune mechanisms is probably not so clear-cut, and the relationship existing between BS or EOS and autoimmune phenomena remains unclear. There is no established therapy for the management of BS and EOS, and the main treatment aim is to prevent ocular manifestations entailing the risk of potential blindness and to avoid joint deformities. Nonsteroidal anti-inflammatory drugs, corticosteroids and immunosuppressive drugs, such as methotrexate or azathioprine, may be helpful; when patients are unresponsive to the combination of corticosteroids and immunosuppressant agents, the tumor necrosis factor-α inhibitor infliximab should be considered. Data on anti-interleukin-1 inhibition with anakinra and canakinumab is still limited and further corroboration is required. The aim of this paper is to describe BS and EOS, focusing on their genetic, clinical, and therapeutic issues, with the ultimate goal of increasing clinicians' awareness of both of these rare but serious disorders.
authors.affiliation: Research Center of Systemic Autoinflammatory Diseases and Behçet's Disease Clinic, Department of Medical Sciences, Surgery and Neurosciences, University of Siena, Siena, Italy; Rheumatology Unit, Department of Medicine DIMED, University of Padua, Padua, Italy.
authors.forename: Francesco
authors.initials: F
authors.lastname: Caso
authors.affiliation: Rheumatology Unit, Department of Clinical Medicine and Surgery, University Federico II, Naples, Italy.
authors.forename: Luisa
authors.initials: L
authors.lastname: Costa
authors.affiliation: Institute of Pediatrics, Policlinico "A. Gemelli", Università Cattolica Sacro Cuore, Rome, Italy.
authors.forename: Donato
authors.initials: D
authors.lastname: Rigante
authors.affiliation: Research Center of Systemic Autoinflammatory Diseases and Behçet's Disease Clinic, Department of Medical Sciences, Surgery and Neurosciences, University of Siena, Siena, Italy.
authors.forename: Antonio
authors.initials: A
authors.lastname: Vitale
authors.affiliation: Department of Pediatrics, Rheumatology Unit, Anna Meyer Children's Hospital and University of Florence, Florence, Italy.
authors.forename: Rolando
authors.initials: R
authors.lastname: Cimaz
authors.affiliation: Research Center of Systemic Autoinflammatory Diseases and Behçet's Disease Clinic, Department of Medical Sciences, Surgery and Neurosciences, University of Siena, Siena, Italy.
authors.forename: Orso Maria
authors.initials: OM
authors.lastname: Lucherini
authors.affiliation: Rheumatology Unit, Department of Medicine DIMED, University of Padua, Padua, Italy.
authors.forename: Paolo
authors.initials: P
authors.lastname: Sfriso
authors.affiliation: Periodic Fever Research Center, Department of Internal Medicine, Policlinico "A. Gemelli", Università Cattolica Sacro Cuore, Rome, Italy.
authors.forename: Elena
authors.initials: E
authors.lastname: Verrecchia
authors.affiliation: Ophthalmology Unit, Department of Neurosciences, University of Padua, Padua, Italy.
authors.forename: Sofia
authors.initials: S
authors.lastname: Tognon
authors.affiliation: Research Center of Systemic Autoinflammatory Diseases and Behçet's Disease Clinic, Department of Medical Sciences, Surgery and Neurosciences, University of Siena, Siena, Italy.
authors.forename: Vittoria
authors.initials: V
authors.lastname: Bascherini
authors.affiliation: Research Center of Systemic Autoinflammatory Diseases and Behçet's Disease Clinic, Department of Medical Sciences, Surgery and Neurosciences, University of Siena, Siena, Italy.
authors.forename: Mauro
authors.initials: M
authors.lastname: Galeazzi
authors.affiliation: Rheumatology Unit, Department of Medicine DIMED, University of Padua, Padua, Italy.
authors.forename: Leonardo
authors.initials: L
authors.lastname: Punzi
authors.affiliation: Research Center of Systemic Autoinflammatory Diseases and Behçet's Disease Clinic, Department of Medical Sciences, Surgery and Neurosciences, University of Siena, Siena, Italy. Electronic address: cantariniluca@hotmail.com.
authors.forename: Luca
authors.initials: L
authors.lastname: Cantarini
mesh_terms: D000818:Animals; D001168:Arthritis; D001327:Autoimmune Diseases / Q000188:drug therapy / Q000235:genetics / Q000276:immunology*; D003389:Cranial Nerve Diseases / Q000188:drug therapy / Q000235:genetics / Q000276:immunology*; D004338:Drug Combinations; D020022:Genetic Predisposition to Disease; D006801:Humans; D007249:Inflammation / Q000188:drug therapy / Q000235:genetics; D012507:Sarcoidosis / Q000188:drug therapy / Q000235:genetics / Q000276:immunology*; D013585:Synovitis / Q000188:drug therapy / Q000235:genetics / Q000276:immunology*; D014605:Uveitis / Q000188:drug therapy / Q000235:genetics / Q000276:immunology*; D056660:Hereditary Autoinflammatory Diseases
chemical_list: D004338:Drug Combinations
keywords: Blau syndrome; Early onset sarcoidosis; Pediatric granulomatous autoinflammatory disease