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CANDLE syndrome: chronic atypical neutrophilic dermatosis with lipodystrophy and elevated temperature—a rare case with a novel mutation

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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.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Clovis Artur Silva.

Ethics declarations

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.

Conflict of interest

The authors declare that they have no competing interests.

Fundings

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.

Additional information

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

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