Disease course and treatment effects of a JAK inhibitor in a patient with CANDLE syndrome
Abstract 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 yea...
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| Format: | Article |
| Language: | English |
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BMC
2019-05-01
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| Series: | Pediatric Rheumatology Online Journal |
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| Online Access: | http://link.springer.com/article/10.1186/s12969-019-0322-9 |
| _version_ | 1818241143209459712 |
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| author | M. Boyadzhiev L. Marinov V. Boyadzhiev V. Iotova I. Aksentijevich S. Hambleton |
| author_facet | M. Boyadzhiev L. Marinov V. Boyadzhiev V. Iotova I. Aksentijevich S. Hambleton |
| author_sort | M. Boyadzhiev |
| collection | DOAJ |
| description | Abstract 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. |
| first_indexed | 2024-12-12T13:24:39Z |
| format | Article |
| id | doaj.art-8155a5f66ad549c0beabb079b053a94a |
| institution | Directory Open Access Journal |
| issn | 1546-0096 |
| language | English |
| last_indexed | 2024-12-12T13:24:39Z |
| publishDate | 2019-05-01 |
| publisher | BMC |
| record_format | Article |
| series | Pediatric Rheumatology Online Journal |
| spelling | doaj.art-8155a5f66ad549c0beabb079b053a94a2022-12-22T00:23:12ZengBMCPediatric Rheumatology Online Journal1546-00962019-05-011711710.1186/s12969-019-0322-9Disease course and treatment effects of a JAK inhibitor in a patient with CANDLE syndromeM. Boyadzhiev0L. Marinov1V. Boyadzhiev2V. Iotova3I. Aksentijevich4S. Hambleton5Department of Pediatrics, Medical UniversityDepartment of Pediatrics, Medical UniversityDepartment of Pediatrics, Medical UniversityDepartment of Pediatrics, Medical UniversityNational Human Genome Research Institute, National Institutes of HealthInstituste of Cellular Medicine, Newcastle UniversityAbstract 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.http://link.springer.com/article/10.1186/s12969-019-0322-9AutoinflammationCANDLE syndromeImmunoproteasomeJAK inhibitorsNephrolithiasis |
| spellingShingle | M. Boyadzhiev L. Marinov V. Boyadzhiev V. Iotova I. Aksentijevich S. Hambleton Disease course and treatment effects of a JAK inhibitor in a patient with CANDLE syndrome Pediatric Rheumatology Online Journal Autoinflammation CANDLE syndrome Immunoproteasome JAK inhibitors Nephrolithiasis |
| title | Disease course and treatment effects of a JAK inhibitor in a patient with CANDLE syndrome |
| title_full | Disease course and treatment effects of a JAK inhibitor in a patient with CANDLE syndrome |
| title_fullStr | Disease course and treatment effects of a JAK inhibitor in a patient with CANDLE syndrome |
| title_full_unstemmed | Disease course and treatment effects of a JAK inhibitor in a patient with CANDLE syndrome |
| title_short | Disease course and treatment effects of a JAK inhibitor in a patient with CANDLE syndrome |
| title_sort | disease course and treatment effects of a jak inhibitor in a patient with candle syndrome |
| topic | Autoinflammation CANDLE syndrome Immunoproteasome JAK inhibitors Nephrolithiasis |
| url | http://link.springer.com/article/10.1186/s12969-019-0322-9 |
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