title: CANDLE syndrome: chronic atypical neutrophilic dermatosis with lipodystrophy and elevated temperature-a rare case with a novel mutation.
abstract: We described herein a patient with chronic atypical neutrophilic dermatosis with lipodystrophy and elevated temperature (CANDLE) syndrome and a novel mutation in PSMB8 gene. This patient had multiple visceral inflammatory involvements, including rare manifestations, such as Sweet syndrome and pericarditis. A 3-year-old male, Caucasian, was born to consanguineous healthy parents. At the age of 11 months, he presented daily fever (temperature >40 °C), irritability, hepatomegaly, splenomegaly; and tender and itching, erythematous papular and edematous plaque lesions. Echocardiogram showed mild pericarditis. Skin biopsy revealed a neutrophil infiltrate without vasculitis suggesting Sweet syndrome. Mutational screening of PSMB8 gene revealed homozygous c.280G>C, p.A94P mutation. He responded partially to high doses of oral glucorticoid and intravenous methylprednisolone. Colchicine, azathioprine, methotrexate, cyclosporine, and intravenous immunoglobulin were not efficacious. At the age of 3 years and 1 month, tocilizumab was administered resulting in remission of daily fever and irritability. However, there was no improvement of the skin tenderness and itching lesions.
  
  
  CONCLUSIONS
  A new mutation in a CANDLE syndrome patient was reported with pericarditis and mimicking Sweet syndrome. The disease manifestations were refractory to immunosuppressive agents and partially responsive to tocilizumab therapy.
  
  
  BACKGROUND
  • Proteasome-associated autoinflammatory syndromes (PRAAS) include four rare diseases. • Chronic atypical neutrophilic dermatosis with lipodystrophy and elevated temperature (CANDLE) syndrome was seldom reported. What is New: • We described a Brazilian patient with CANDLE syndrome possessing a novel mutation in the PSMB8 gene. • This patient had multiple visceral inflammatory involvements, including rare manifestations, such as pericarditis and mimicking Sweet syndrome.
authors.affiliation: Pediatric Rheumatology Unit, Pediatric Department, Hospital Geral de Fortaleza, Ceará, Brazil.|Pediatric Rheumatology Unit, Pediatric Department, Faculdade de Medicina da Universidade São Paulo, São Paulo, Brazil.
authors.forename: Miria Paula V
authors.initials: MP
authors.lastname: Cavalcante
authors.affiliation: Pediatric Rheumatology Unit, Pediatric Department, Faculdade de Medicina da Universidade São Paulo, São Paulo, Brazil.
authors.forename: Juliana B
authors.initials: JB
authors.lastname: Brunelli
authors.affiliation: Pediatric Rheumatology Unit, Pediatric Department, Faculdade de Medicina da Universidade São Paulo, São Paulo, Brazil.
authors.forename: Clarissa C
authors.initials: CC
authors.lastname: Miranda
authors.affiliation: Pediatric Rheumatology Unit, Pediatric Department, Faculdade de Medicina da Universidade São Paulo, São Paulo, Brazil.
authors.forename: Glaucia V
authors.initials: GV
authors.lastname: Novak
authors.affiliation: National Institutes of Health, National Institute of Arthritis and Musculoskeletal and Skin Diseases, Bethesda, USA.
authors.forename: Louise
authors.initials: L
authors.lastname: Malle
authors.affiliation: Pediatric Rheumatology Unit, Pediatric Department, Faculdade de Medicina da Universidade São Paulo, São Paulo, Brazil.|National Institutes of Health, National Institute of Arthritis and Musculoskeletal and Skin Diseases, Bethesda, USA.
authors.forename: Nadia E
authors.initials: NE
authors.lastname: Aikawa
authors.affiliation: National Institutes of Health, National Institute of Arthritis and Musculoskeletal and Skin Diseases, Bethesda, USA.
authors.forename: Adriana A
authors.initials: AA
authors.lastname: Jesus
authors.affiliation: Pediatric Rheumatology Unit, Pediatric Department, Hospital Geral de Fortaleza, Ceará, Brazil. clovisaasilva@gmail.com.|, Av. Dr. Eneas Carvalho Aguiar, 647 - Cerqueira César, São Paulo - SP, Brazil, 05403-000. clovisaasilva@gmail.com.
authors.forename: Clovis Artur
authors.initials: CA
authors.lastname: Silva
mesh_terms: D001831:Body Temperature; D002675:Child, Preschool; D002908:Chronic Disease; D004247:DNA / Q000235:genetics*; D004252:DNA Mutational Analysis; D005334:Fever / Q000209:etiology* / Q000503:physiopathology; D006801:Humans; D008060:Lipodystrophy / Q000235:genetics* / Q000378:metabolism; D008285:Major Histocompatibility Complex; D008297:Male; D009154:Mutation; D046988:Proteasome Endopeptidase Complex / Q000235:genetics* / Q000378:metabolism; D016463:Sweet Syndrome / Q000235:genetics* / Q000503:physiopathology
chemical_list: D004247:DNA; C077436:LMP7 protein; D046988:Proteasome Endopeptidase Complex
keywords: CANDLE syndrome; PSMB8 gene; Sweet syndrome; Tocilizumab