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Recurrent febrile syndromes—what a rheumatologist needs to know

Abstract

Rheumatologists are likely to be asked to evaluate patients with recurrent febrile syndromes, so it is important that they are familiar with the clinical and diagnostic features, pathophysiology and therapeutic options for these rare autoinflammatory disorders. These syndromes are all characterized by recurrent episodes of fever and systemic inflammation; however, some syndromes have unique historical and physical features that can help with making a diagnosis. The primary associated morbidity is systemic amyloidosis, usually with renal involvement. Diagnostic testing is mostly limited to genetic testing. NSAIDs, colchicine and corticosteroids have roles in the treatment of some of these disorders, but biologic drugs that target interleukin-1β are emerging as consistently effective therapies.

Key Points

  • The autoinflammatory disorders are diseases of innate immune dysregulation

  • The recurrent febrile syndromes are characterized by episodes of systemic and tissue inflammation

  • The recurrent febrile syndromes present a diagnostic challenge

  • The primary long-term morbidity of the inherited recurrent febrile syndromes is systemic amyloidosis

  • Advances in the understanding of the genetics and pathogenesis of these disorders have led to improved diagnostic ability and therapy, including the development of biologic therapies that target interleukin-1β

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Figure 1: Pathophysiology of hereditary recurrent febrile syndromes.
Figure 2: Patterns of fever seen in recurrent febrile syndromes.
Figure 3: Diagnostic features and differential diagnosis of recurrent febrile syndromes.

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Acknowledgements

H. M. Hoffman is supported by the National Institute of Allergy and Infectious Diseases and the Ludwig Institute of Cancer Research. A. Simon is supported by a ZonMW VENI grant.

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Correspondence to Hal M. Hoffman.

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Hal Hoffman is a consultant for Regeneron pharmaceuticals and Novartis pharmaceuticals, who make rilonacept and canakinumab, respectively.

A. Simon has declared no competing interests.

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Hoffman, H., Simon, A. Recurrent febrile syndromes—what a rheumatologist needs to know. Nat Rev Rheumatol 5, 249–256 (2009). https://doi.org/10.1038/nrrheum.2009.40

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