title: Novel evidences of atypical manifestations in cryopyrin-associated periodic syndromes.
abstract: OBJECTIVE
  Cryopyrin-associated periodic syndromes (CAPS) usually start during infancy as an urticarial-like rash and a marked acute phase response, with additional manifestations appearing during its evolution. The aim of this study was to expand the clinical diversity of CAPS by the description of novel atypical features.
  
  
  METHODS
  Clinical data were collected from patients' medical charts. Sanger sequencing analyzed NLRP3. Response to anti-IL-1 blockade was evaluated by clinical assessments and by measurements of laboratory parameters.
  
  
  RESULTS
  Seventeen patients from two families (A and B), carrying the p.Ala439Thr and p.Arg260Trp NLRP3 mutations respectively, were enrolled. The disease was unexpectedly atypical in all members of Family A, with a 16-year-old asymptomatic carrier, and onset in adulthood associated with absence of skin lesions in four affected members. Surprisingly, one patient from each family suffered from severe haemorrhagic cystitis due to AA amyloidosis in the urinary bladder. Members of Family B displayed a classical phenotype, with two patients suffering from olfactive disorders.
  
  
  CONCLUSIONS
  Our evidence suggests that CAPS may occasionally be presented as a late-onset, recurrent inflammatory disease without urticarial-like rash. In some patients, AA amyloidosis in strange locations like urinary bladder may complicate the clinical course. The response to IL-1 blockade in these atypical CAPS was similar to that described in classical forms. Consequently, we suggest that CAPS should be included in the differential diagnosis of adult patients with unexplained, recurrent inflammatory diseases, and once confirmed, the early initiation of anti-IL-1 blockade will probably prevent the development of life-threatening complications.
authors.affiliation: Department of Internal Medicine, Hospital Vall Hebron, Barcelona, Spain.
authors.forename: Segundo
authors.initials: S
authors.lastname: Bujan-Rivas
authors.affiliation: Department of Allergy, Hospital Universitari Germans Trias i Pujol, Badalona, Barcelona, Spain.
authors.forename: Maria
authors.initials: M
authors.lastname: Basagaña
authors.affiliation: Department of Internal Medicine, Hospital Verge de la Cinta, Tortosa, Spain.
authors.forename: Francisca
authors.initials: F
authors.lastname: Sena
authors.affiliation: Department of Paediatrics, Hospital Universitari Germans Trias i Pujol, Badalona, Barcelona, Spain.
authors.forename: Maria
authors.initials: M
authors.lastname: Méndez
authors.affiliation: Department of Allergy, Hospital Municipal de Badalona, Spain.
authors.forename: Maria Teresa
authors.initials: MT
authors.lastname: Dordal
authors.affiliation: Department of Immunology-CDB, Hospital Clínic-IDIBAPS, Barcelona, Spain.
authors.forename: Eva
authors.initials: E
authors.lastname: Gonzalez-Roca
authors.affiliation: Department of Immunology-CDB, Hospital Clínic-IDIBAPS, Barcelona, Spain.
authors.forename: Estibaliz
authors.initials: E
authors.lastname: Ruiz-Ortiz
authors.affiliation: Department of Immunology-CDB, Hospital Clínic-IDIBAPS, Barcelona, Spain.
authors.forename: Anna
authors.initials: A
authors.lastname: Mensa-Vilaró
authors.affiliation: Department of Immunology-CDB, Hospital Clínic-IDIBAPS, Barcelona, Spain.
authors.forename: Susana
authors.initials: S
authors.lastname: Plaza
authors.affiliation: Department of Paediatric Rheumatology, Hospital Vall Hebron, Barcelona, Spain.
authors.forename: Consuelo
authors.initials: C
authors.lastname: Modesto
authors.affiliation: Department of Internal Medicine, Hospital Vall Hebron, Barcelona, Spain.
authors.forename: Josep
authors.initials: J
authors.lastname: Ordi-Ros
authors.affiliation: Department of Immunology-CDB, Hospital Clínic-IDIBAPS, Barcelona, Spain.
authors.forename: Jordi
authors.initials: J
authors.lastname: Yagüe
authors.affiliation: Department of Internal Medicine, Hospital Vall Hebron, Barcelona, Spain.
authors.forename: Ferrán
authors.initials: F
authors.lastname: Martínez-Valle
authors.affiliation: Department of Immunology-CDB, Hospital Clínic-IDIBAPS, Barcelona, Spain. jiaroste@clinic.ub.es.
authors.forename: Juan Ignacio
authors.initials: JI
authors.lastname: Aróstegui
mesh_terms: D000293:Adolescent; D017668:Age of Onset; D000368:Aged; D000686:Amyloidosis / Q000188:drug therapy / Q000209:etiology* / Q000235:genetics / Q000276:immunology; D058070:Asymptomatic Diseases; D056587:Cryopyrin-Associated Periodic Syndromes / Q000150:complications* / Q000188:drug therapy / Q000235:genetics / Q000276:immunology; D003556:Cystitis / Q000188:drug therapy / Q000209:etiology* / Q000235:genetics / Q000276:immunology; D005260:Female; D020022:Genetic Predisposition to Disease; D006417:Hematuria / Q000209:etiology; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D007375:Interleukin-1 / Q000037:antagonists & inhibitors / Q000276:immunology; D007674:Kidney Diseases / Q000188:drug therapy / Q000209:etiology* / Q000235:genetics / Q000276:immunology; D008297:Male; D009154:Mutation; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein / Q000235:genetics; D010375:Pedigree; D010641:Phenotype; D016896:Treatment Outcome
chemical_list: D007166:Immunosuppressive Agents; D007375:Interleukin-1; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; C453881:NLRP3 protein, human