Disease course and treatment effects of a JAK inhibitor in a patient with CANDLE syndrome

Autor: Sophie Hambleton, M. Boyadzhiev, Violeta Iotova, L. Marinov, Ivona Aksentijevich, Veselin Boyadzhiev
Rok vydání: 2019
Předmět:
Male
lcsh:Diseases of the musculoskeletal system
Lipodystrophy
Case Report
Dermatitis
Disease
Immunoproteasome
0302 clinical medicine
Interferon
CANDLE syndrome
Immunology and Allergy
030212 general & internal medicine
Family history
Child
Sulfonamides
lcsh:RJ1-570
Syndrome
Treatment Outcome
Failure to thrive
Autoinflammation
medicine.symptom
medicine.drug
Proteasome Endopeptidase Complex
medicine.medical_specialty
Neutropenia
Fever
Nephrolithiasis
Autoimmune Diseases
03 medical and health sciences
Rheumatology
Internal medicine
medicine
Humans
Janus Kinase Inhibitors
Loss function
030203 arthritis & rheumatology
JAK inhibitors
business.industry
lcsh:Pediatrics
medicine.disease
Dermatology
Purines
Chronic Disease
Pediatrics
Perinatology and Child Health
Azetidines
Pyrazoles
Kidney stones
lcsh:RC925-935
business
Zdroj: Pediatric Rheumatology Online Journal, Vol 17, Iss 1, Pp 1-7 (2019)
Pediatric Rheumatology Online Journal
ISSN: 1546-0096
DOI: 10.1186/s12969-019-0322-9
Popis: Background CANDLE syndrome (an acronym for Chronic Atypical Neutrophilic Dermatosis with Lipodystrophy and Elevated Temperature) is a recently described rare autosomal recessive disorder charaterized by systemic autoinflammation. Clinical manifestations include presentation in the first year of life, episodes of fever accompanied by erythematous skin lesions, progressive lipodystrophy, violaceous periorbital swelling and failure to thrive. This syndrome is caused by loss of function mutations and malfunction of the immunoproteasome complex. Most patients have biallelic mutations in the PSMB8 gene that encodes the β5i catalytic subunit of the immunoproteasome. Examples of digenic inheritance have been also described in CANDLE. CANDLE patients have strong type I interferon gene expression signature and they are responsive to treatment with JAK inhibitors. However, possible serious side-effects remain a concern. Here, we report another patient with CANDLE whose disease activity was well controlled by the treatment with baricitinib. Case presentation We report a Bulgarian patient of the Turkish ancestry who carries biallelic mutations in the PSMB8 gene: p.Ala92Val and p.Lys105Gln. The pathogenic variant p.Ala92Val has not been previously described in patients with CANDLE. We also comment on the unusual feature in this patient, nephrolithiasis, that has not been described in other patients, however it might be related to the positive family history for kidney stones. We have treated the patient with the JAK inhibitor baricitinib for the past year and we observed a significant amelioration of his inflammatory episodes, skin and joint manifestations, and improvements in physical activities and growth. The treatment with glucocorticoids (GC) was completely discontinued. No side effects have been observed, however they remain in consideration for a life-long therapy of this disease. Conclusions CANDLE should be suspected in patients with early-onset systemic inflammatory disease and prominent skin manifestations. Molecular testing can confirm the clinical diagnosis and is very important in guiding therapies. Treatment with JAK inhibitors is highly efficacious and appears to be safe in children with CANDLE and other intereforonopathies.
Databáze: OpenAIRE
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