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  • Review Article
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A clinical guide to autoinflammatory diseases: familial Mediterranean fever and next-of-kin

Nature Reviews Rheumatology volume 10, pages 135–147 (2014)Cite this article

Subjects

Key Points

  • Monogenic autoinflammatory diseases can be classified on the basis of their dominating clinical feature (for example, periodic fever) or their pathogenesis (for example, as IL-1 or NFκB activation disorders)

  • Among the monogenic autoinflammatory diseases, clinical diagnostic criteria have already been suggested for familial Mediterranean fever (FMF), and we suggest a flowchart to guide requests for mutation analysis of the associated gene

  • FMF is an autosomal recessive disease; however, a single mutation, or a clear disease-causing mutation together with a variant with low penetrance, can be associated with the clinical phenotype

  • Clinical classification criteria and flowcharts to guide physicians in decision-making and asking for specific genetic testing are also needed for other autoinflammatory diseases

  • Anti-IL-1 treatment has shown promising results in many of the autoinflammatory diseases

Abstract

Autoinflammatory diseases are associated with abnormal activation of the innate immune system, leading to clinical inflammation and high levels of acute-phase reactants. The first group to be identified was the periodic fever diseases, of which familial Mediterranean fever (FMF) is the most common. In FMF, genetic results are not always straightforward; thus, flowcharts to guide the physician in requesting mutation analyses and interpreting the findings are presented in this Review. The other periodic fever diseases, which include cryopyrin-associated periodic syndromes (CAPS), TNF receptor-associated periodic syndrome (TRAPS) and mevalonate kinase deficiency/hyperimmunoglobulin D syndrome (MKD/HIDS), have distinguishing features that should be sought for carefully during diagnosis. Among this group of diseases, increasing evidence exists for the efficacy of anti-IL-1 treatment, suggesting a major role of IL-1 in their pathogenesis. In the past decade, we have started to learn about the other rare autoinflammatory diseases in which fever is less pronounced. Among them are diseases manifesting with pyogenic lesions of the skin and bone; diseases associated with granulomatous lesions; diseases associated with psoriasis; and diseases associated with defects in the immunoproteasome. A better understanding of the pathogenesis of these autoinflammatory diseases has enabled us to provide targeted biologic treatment at least for some of these conditions.

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Figure 1: A schematic showing a simplified view of the pathogenesis of the main monogenic autoinflammatory syndromes.
Figure 2: A flowchart to guide requests for MEFV mutation analysis.
Figure 3: Algorithm to guide diagnosis and treatment decisions after MEFV genotype analysis.
Figure 4: Differential diagnosis in a child referred with fever.
Figure 5
Figure 6

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Acknowledgements

We thank I. Aksentijevich for her comments.

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  1. Department of Paediatric Rheumatology, Hacettepe University Faculty of Medicine, 06100, Ankara, Turkey

    Seza Ozen & Yelda Bilginer

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Both authors contributed to writing the article. In addition, S. Ozen decided on the content of the article and reviewed the manuscript before submission, and Y. Bilginer researched data for the article.

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Correspondence to Seza Ozen.

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S. Ozen declares that she has received a consultancy fee from Novartis and speaker honouraria from Biovitrium. Y. Bilginer declares no competing interests.

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Ozen, S., Bilginer, Y. A clinical guide to autoinflammatory diseases: familial Mediterranean fever and next-of-kin. Nat Rev Rheumatol 10, 135–147 (2014). https://doi.org/10.1038/nrrheum.2013.174

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