title: Interleukin-1 receptor antagonist deficiency with a novel mutation; late onset and successful treatment with canakinumab: a case report.
abstract: BACKGROUND
  Interleukin-1 receptor antagonist deficiency is a rare autoinflammatory disease involving neonatal onset of pustulosis, periostitis, and sterile osteomyelitis. The underlying genetic abnormality involves a recessive mutation in IL1RN, which encodes interleukin-1 receptor antagonist. In this case report, we describe a case of a 12-year-old Turkish girl who initially was presented at 1 year of age, older than previously reported children with interleukin-1 receptor antagonist deficiency, and with a novel mutation, p.R26X, in ILR1N.
  
  
  METHODS
  Our patient developed pustular cutaneous lesions at 1 year of age. At the age of 12 years, she was hospitalized for arthralgia of her knees, elbows, and ankles and arthritis of the left knee, with simultaneous pustular cutaneous lesions. She was admitted to the intensive care unit because of septicemia and respiratory insufficiency during follow-up. A skin biopsy of hyperpigmented lesions demonstrated neutrophil infiltration in the epidermis and subepidermal pustular dermatosis. Interleukin-1 receptor antagonist deficiency was suspected, and genetic analysis revealed a homozygous mutation (p.R26X) in IL1RN, which led to a diagnosis of interleukin-1 receptor antagonist deficiency. Treatment with canakinumab (recombinant human anti-human interleukin-1β monoclonal antibody) 150 mg subcutaneously once every 6 weeks was initiated. Our patient did not experience further cutaneous lesions or arthritis. Her post-treatment inflammatory markers were normal; she gained weight; and she was able to walk independently.
  
  
  CONCLUSIONS
  In this case report, we describe a patient with interleukin-1 receptor antagonist deficiency who responded excellently to canakinumab treatment. We believe more awareness is warranted for interleukin-1 receptor antagonist deficiency in children. It is possible that the mutation in our patient was a founder mutation that may lead to diagnosis of additional cases in Turkey.
authors.affiliation: Department of Pediatrics, Ege University Faculty of Medicine, Izmir, Turkey. ezgiulusoy13@hotmail.com.
authors.forename: Ezgi
authors.initials: E
authors.lastname: Ulusoy
authors.affiliation: Department of Pediatrics, Ege University Faculty of Medicine, Izmir, Turkey. neslihanedeer@gmail.com.
authors.forename: Neslihan Edeer
authors.initials: NE
authors.lastname: Karaca
authors.affiliation: Qatar Biomedical Research Institute, Medical Genetics Center, Doha, Qatar. helshanti@qf.org.qa.
authors.forename: Hatem
authors.initials: H
authors.lastname: El-Shanti
authors.affiliation: Department of Pediatrics, Ege University Faculty of Medicine, Izmir, Turkey. erhankilicoglumd@gmail.com.
authors.forename: Erhan
authors.initials: E
authors.lastname: Kilicoglu
authors.affiliation: Department of Pediatrics, Ege University Faculty of Medicine, Izmir, Turkey. guzideaksu@gmail.com.
authors.forename: Guzide
authors.initials: G
authors.lastname: Aksu
authors.affiliation: Department of Pediatrics, Ege University Faculty of Medicine, Izmir, Turkey. necil.kutukculer@ege.edu.tr.
authors.forename: Necil
authors.initials: N
authors.lastname: Kutukculer
mesh_terms: D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized; D002648:Child; D005260:Female; D056660:Hereditary Autoinflammatory Diseases / Q000188:drug therapy* / Q000235:genetics*; D006801:Humans; D053590:Interleukin 1 Receptor Antagonist Protein / Q000235:genetics*; D009154:Mutation / Q000235:genetics*; D016896:Treatment Outcome; D014421:Turkey
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; C507763:IL1RN protein, human; D053590:Interleukin 1 Receptor Antagonist Protein; C541220:canakinumab