A case report of a novel compound heterozygous mutation in a Brazilian patient with deficiency of Interleukin-1 receptor antagonist (DIRA)

Autor: Jorge Kalil, Fabio Fernandes Morato Castro, Myrthes Toledo Barros, Isabella Ceccherini, Robson Aguiar de Oliveira, Francesco Caroli, Alessandra Pontillo, Marco Gattorno, Leonardo Oliveira Mendonça, Alice Grossi
Jazyk: angličtina
Rok vydání: 2020
Předmět:
lcsh:Diseases of the musculoskeletal system
medicine.drug_class
Interleukin-1beta
Deficiency of interleukin-1 receptor antagonist
Review
Compound heterozygosity
Antibodies
Monoclonal
Humanized
DIRA
03 medical and health sciences
0302 clinical medicine
Rheumatology
Adrenal Cortex Hormones
medicine
IL1RN
Immunology and Allergy
Humans
030212 general & internal medicine
Genetic Testing
Child
030203 arthritis & rheumatology
Anakinra
business.industry
Hereditary Autoinflammatory Diseases
Homozygote
lcsh:RJ1-570
Interleukin
lcsh:Pediatrics
Osteomyelitis
Receptor antagonist
Symptom Flare Up
Rash
Rilonacept
Radiography
Canakinumab
Interleukin 1 Receptor Antagonist Protein
Interleukin 1 receptor antagonist
Treatment Outcome
Antirheumatic Agents
Pediatrics
Perinatology and Child Health
Immunology
Mutation
lcsh:RC925-935
medicine.symptom
business
medicine.drug
Zdroj: Pediatric Rheumatology Online Journal
Pediatric Rheumatology Online Journal, Vol 18, Iss 1, Pp 1-5 (2020)
ISSN: 1546-0096
Popis: Background Deficiency of the natural antagonist of interleukin-1 was first described in 2009 and so far 20 patients has been reported. In Brazil just two cases have been reported both carrying the same homozygous 15 bp deletion. Blocking interleukin-1 has changed rate survival for DIRA patients. The use of anakinra and rilonacept has been reported safe and efficient, whereas the selective blockade of interleukin-1 beta, using the monoclonal antibody canakinumab has been reported in a single case only. Case presentation Here we report a case of a 7 years old Brazilian boy that presented with recurrent episodes of systemic inflammation with severe disabling osteomyelitis with mild pustular skin rash. A Next Generation Sequencing gene panel allowed to detect two pathogenic mutations in the IL1RN gene, described in compound heterozygosity. Corticosteroids was effective in controlling inflammation and anti-IL1 beta blocker triggered disease flare. Complete clinical control could be achieved using IL-1 receptor antagonist. Conclusions DIRA is a severe, life threatening autoinflammatory condition with low numbers of patients described all over the world. The mutation p.Asp72_Ile76del in IL1RN is presented in all Brazilian DIRA patients already described and p.Q45* (rs1019766125) is a new mutation affecting the IL1RN gene. Following the pathogenesis of DIRA, blocking both subunits of interleukin one as well as antagonizing the receptor using anakinra or rilonacept seems to be effective. There is just one report using canakinumab for the treatment of DIRA and this is the first report of disease flare using this drug.
Databáze: OpenAIRE
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