A developing portrait of hereditary periodic fevers in childhood

ABSTRACT

Introduction: Hereditary periodic fevers (HPFs) are inherited errors of the innate immunity which, although individually uncommon, collectively have set up a novel emerging and developing chapter of pediatrics.

Areas covered: A careful analysis and identification of diseases globally known as HPFs is essential to prompt an effective treatment and improve survival and quality of life of these children. This review provides a detailed summary of the main monogenic autoinflammatory disorders appearing with recurrent fevers in childhood with the final aim to help pediatricians in a correct recognition and discrimination of hereditary causes of fever.

Expert opinion: Challenges associated with the management of monogenic autoinflammatory disorders in childhood have been increasingly tantalized by the different treatment options available and by the recently accessible genetic investigation techniques, which have led to identify a growing number of rare causes of periodic fevers. In addition, as new mechanisms underlying the regulation of innate immunity are discovered and more pathogenetic therapeutic approaches are adopted, the next decade promises a progress in the knowledge of HPFs and a potential genomically-based therapeutic approach. Actually, the inhibition of interleukin (IL)-1 represents the most incisive treatment for patients with HPFs who do not respond to standard therapies or for whom the administration of canonical drugs is unsuitable and characterized by secondary effects.

KEYWORDS:

• Autoinflammatory disease
• inflammation
• child

Article highlights

• The innate immune system acts as an immune surveillance keeper that patrols healthy host tissue, discriminates among apoptotic cells, chromatin-modifiers or transcription factors and mediates the detection of infectious agents in the human body;

• Monogenic autoinflammatory disorders are a growing family of heterogeneous diseases characterized by periodic fevers and apparently inexplicable recurrence of multi-organ inflammation in the absence of autoreactive T-lymphocytes, auto-antibodies, and causative infectious agents, which globally involve the innate immune system;

• All these conditions are caused by dysregulation of the inflammasome, a large intracellular multiprotein platform that plays a pivotal role in innate immunity and leads to overproduction of proinflammatory cytokines, namely interleukin-1β and other chemokines;

• Biochemical investigation during and outside febrile episodes can support the diagnosis of these diseases by excluding other causes of fever of unknown origin in children, but decisions about specific genetic testing should be guided by the integration of clinical and familiar data;

• Genotype-phenotype correlations for the monogenic autoinflammatory disorders might help pediatricians in a correct recognition of multi-organ inflammatory manifestations combined with periodic fevers in children and in the most proper and poised judgement of genetic test results.

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Declaration of interest

The author has no affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in this manuscript, including employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending and royalties. Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This paper was not funded