title: Histologic and Immunohistochemical Features of the Skin Lesions in CANDLE Syndrome.
abstract: Chronic atypical neutrophilic dermatosis with lipodystrophy and elevated temperature (CANDLE) syndrome is a newly characterized autoinflammatory disorder, caused by mutations in PSMB8. It is characterized by early-onset fevers, accompanied by a widespread, violaceous, and often annular cutaneous eruption. Although the exact pathogenesis of this syndrome is still obscure, it is postulated that the inflammatory disease manifestations stem from excess secretion of interferons. Based on preliminary blood cytokine and gene expression studies, the signature seems to come mostly from type I interferons, which are proposed to lead to the recruitment of immature myeloid cells into the dermis and subcutis. In this study, we systematically analyzed skin biopsies from 6 patients with CANDLE syndrome by routine histopathology and immunohistochemistry methods. Skin lesions showed the presence of extensive mixed dermal and subcutaneous inflammatory infiltrate, composed of mononuclear cells, atypical myeloid cells, neutrophils, eosinophils, and some mature lymphocytes. Positive LEDER and myeloperoxidase staining supported the presence of myeloid cells. Positive CD68/PMG1 and CD163 staining confirmed the existence of histiocytes and monocytic macrophages in the inflammatory infiltrate. CD123 staining was positive, demonstrating the presence of plasmacytoid dendritic cells. Uncovering the unique histopathological and immunohistochemical features of CANDLE syndrome provides tools for rapid and specific diagnosis of this disorder and further insight into the pathogenesis of this severe life-threatening condition.
authors.affiliation: *Department of Dermatology, Hospital del Niño Jesús, Madrid, Spain; †Paediatric Histopathology Department, Birmingham Children's Hospital, Birmingham, United Kingdom; ‡Department of Dermatology, Fundación Jiménez Díaz, Madrid, Spain; §Department of Dermatology, Northwestern University, Chicago, IL; ¶Department of Dermatology and the Center for Genetic Diseases of the Skin and Hair, Hadassah-Hebrew University Medical Center, Jerusalem, Israel; ‖Laboratory of Pathology, Center for Cancer Research, NCI, NIH, Bethesda, MD; **Department of Dermatology, Hospital Carlos Haya, Málaga, Spain; ††Translational Autoinflammatory Disease Section, NIAMS, NIH, Bethesda, MD; and ‡‡Dermatohistopathologisches Gemeinschaftslabor, Friedrichshafen, Germany.
authors.forename: Antonio
authors.initials: A
authors.lastname: Torrelo
authors.forename: Isabel
authors.initials: I
authors.lastname: Colmenero
authors.forename: Luis
authors.initials: L
authors.lastname: Requena
authors.forename: Amy S
authors.initials: AS
authors.lastname: Paller
authors.forename: Yuval
authors.initials: Y
authors.lastname: Ramot
authors.forename: Chyi-Chia
authors.initials: CC
authors.lastname: Richard Lee
authors.forename: Angel
authors.initials: A
authors.lastname: Vera
authors.forename: Abraham
authors.initials: A
authors.lastname: Zlotogorski
authors.forename: Raphaela
authors.initials: R
authors.lastname: Goldbach-Mansky
authors.forename: Heinz
authors.initials: H
authors.lastname: Kutzner
mesh_terms: D015703:Antigens, CD / Q000032:analysis; D015214:Antigens, Differentiation, Myelomonocytic / Q000032:analysis; D002908:Chronic Disease; D003713:Dendritic Cells / Q000737:chemistry / Q000473:pathology; D004804:Eosinophils / Q000473:pathology; D005334:Fever / Q000378:metabolism / Q000473:pathology; D006644:Histiocytes / Q000737:chemistry / Q000473:pathology; D006801:Humans; D007150:Immunohistochemistry; D053650:Interleukin-3 Receptor alpha Subunit / Q000032:analysis; D008060:Lipodystrophy / Q000378:metabolism / Q000473:pathology*; D008214:Lymphocytes / Q000473:pathology; D008264:Macrophages / Q000737:chemistry / Q000473:pathology; D022423:Myeloid Cells / Q000737:chemistry / Q000473:pathology; D009504:Neutrophils; D009195:Peroxidase / Q000032:analysis; D011956:Receptors, Cell Surface / Q000032:analysis; D012871:Skin Diseases / Q000378:metabolism* / Q000473:pathology*; D013577:Syndrome; D000098902:CD163 Antigen; D000097382:CD68 Molecule
chemical_list: D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D053650:Interleukin-3 Receptor alpha Subunit; D009195:Peroxidase; D011956:Receptors, Cell Surface; D000098902:CD163 Antigen; C067980:CD68 antigen, human; D000097382:CD68 Molecule; C115022:IL3RA protein, human