Abstract
We described herein a patient with chronic atypical neutrophilic dermatosis with lipodystrophy and elevated temperature (CANDLE) syndrome and a novel mutation in PSMB8 gene. This patient had multiple visceral inflammatory involvements, including rare manifestations, such as Sweet syndrome and pericarditis. A 3-year-old male, Caucasian, was born to consanguineous healthy parents. At the age of 11 months, he presented daily fever (temperature >40 °C), irritability, hepatomegaly, splenomegaly; and tender and itching, erythematous papular and edematous plaque lesions. Echocardiogram showed mild pericarditis. Skin biopsy revealed a neutrophil infiltrate without vasculitis suggesting Sweet syndrome. Mutational screening of PSMB8 gene revealed homozygous c.280G>C, p.A94P mutation. He responded partially to high doses of oral glucorticoid and intravenous methylprednisolone. Colchicine, azathioprine, methotrexate, cyclosporine, and intravenous immunoglobulin were not efficacious. At the age of 3 years and 1 month, tocilizumab was administered resulting in remission of daily fever and irritability. However, there was no improvement of the skin tenderness and itching lesions.
Conclusion: A new mutation in a CANDLE syndrome patient was reported with pericarditis and mimicking Sweet syndrome. The disease manifestations were refractory to immunosuppressive agents and partially responsive to tocilizumab therapy.
What is Known: • Proteasome-associated autoinflammatory syndromes (PRAAS) include four rare diseases. • Chronic atypical neutrophilic dermatosis with lipodystrophy and elevated temperature (CANDLE) syndrome was seldom reported. |
What is New: |
• We described a Brazilian patient with CANDLE syndrome possessing a novel mutation in the PSMB8 gene. • This patient had multiple visceral inflammatory involvements, including rare manifestations, such as pericarditis and mimicking Sweet syndrome. |
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Abbreviations
- ANA:
-
Antinuclear antibodies
- CANDLE:
-
Chronic atypical neutrophilic dermatosis with lipodystrophy and elevated temperature
- CAPS:
-
Cryopyrin associated periodic syndromes
- CRP:
-
C-reactive protein
- ESR:
-
Erytrocyte sedimentation rate
- FMF:
-
Familial Mediterranean fever
- JAK:
-
Janus kinase
- JASL:
-
Japanese autoinflammatory syndrome with lipodystrophy
- JMP:
-
Joint contractures, muscle atrophy, microcytic anemia and panniculitis-induced lipodystrophy
- MKD:
-
Mevalonate kinase deficiency
- NNS:
-
Nakajo-Nishimura syndrome
- PRAAS:
-
Proteasome-associated autoinflammatory syndromes
- PSMB8:
-
Proteasome subunit beta type 8
- TRAPS:
-
TNF receptor associated periodic syndrome
- WBC:
-
White blood cell
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Acknowledgments
We would like to thank Dr Ilana Halpern, Pediatric Department, Faculdade de Medicina da Universidade São Paulo to review the skin biopsy and the Fig. 2.
Authors’ contributions
Acquisition of data: Cavalcante, Brunelli, Miranda, Novak, Malle, Aikawa, Jesus, and Silva.
Manuscript preparation: Cavalcante, Brunelli, Miranda, Novak, Malle, Aikawa, Jesus, and Silva.
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This study was approved by the Local Ethics Committee of our University Hospital and a written informed consent was obtained from all individual participants included in the study.
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The authors declare that they have no competing interests.
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This study was funded by Conselho Nacional do Desenvolvimento Científico e Tecnológico (CNPQ-grant 302724/2011-7 to CAS), by Federico Foundation to CAS, by Núcleo de Apoio à Pesquisa “Saúde da Criança e do Adolescente” da USP (NAP-CriAd) and was funded by the NIAMS Intramural Research program (IRP) NIH, the Clinical Center, and NIAMS.
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Communicated by Beat Steinmann
Louise Malle and Adriana A. Jesus contributed equally to this work.
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Cavalcante, M.P.V., Brunelli, J.B., Miranda, C.C. et al. CANDLE syndrome: chronic atypical neutrophilic dermatosis with lipodystrophy and elevated temperature—a rare case with a novel mutation. Eur J Pediatr 175, 735–740 (2016). https://doi.org/10.1007/s00431-015-2668-4
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DOI: https://doi.org/10.1007/s00431-015-2668-4