Abstract
Monogenic autoinflammatory diseases are rare conditions caused by genetic abnormalities affecting the innate immunity. Previous therapeutic strategies had been mainly based on results from retrospective studies and physicians' experience. However, during the last years, the significant improvement in their genetic and pathogenic knowledge has been accompanied by a remarkable progress in their management. The relatively recent identification of the inflammasome as the crucial pathogenic mechanism causing an aberrant production of interleukin 1β (IL-1β) in the most frequent monogenic autoinflammatory diseases led to the introduction of anti–IL-1 agents and other biologic drugs as part of the previously limited therapeutic armamentarium available. Advances in the treatment of autoinflammatory diseases have been favored by the use of new biologic agents and the performance of a notable number of randomized clinical trials exploring the efficacy and safety of these agents. Clinical trials have contributed to increase the level of evidence and provided more robust therapeutic recommendations. This review analyzes the treatment of the most frequent monogenic autoinflammatory diseases, namely, familial Mediterranean fever, tumor necrosis factor receptor–associated periodic fever syndrome, hyperimmunoglobulin D syndrome/mevalonate kinase deficiency, and cryopyrin-associated periodic syndromes, together with periodic fever with aphthous stomatitis, pharyngitis, and cervical adenitis syndrome, which is the most common polygenic autoinflammatory disease in children, also occurring in adult patients. Finally, based on the available expert consensus recommendations and the highest level of evidence of the published studies, a practical evidence-based guideline for the treatment of these autoinflammatory diseases is proposed.
Highlights
Over the past 20 years, pathogenic insights into the mechanisms of autoinflammation completely changed treatment and prognosis of many inherited autoinflammatory diseases, known as “hereditary periodic fever syndromes,” a group of rare diseases characterized by difficult diagnostic and therapeutic approaches
This study provided relevant information about dosage variability of anakinra to control cryopyrin-associated periodic syndromes (CAPS) activity
Because most patients will require a biologic agent to control the disease activity, glucocorticoids may be reserved as initial treatment to prove response or may be administered in a continuous or on-demand modality for mild/non-severe cases
Summary
Over the past 20 years, pathogenic insights into the mechanisms of autoinflammation completely changed treatment and prognosis of many inherited autoinflammatory diseases, known as “hereditary periodic fever syndromes,” a group of rare diseases characterized by difficult diagnostic and therapeutic approaches. The more recent knowledge of other autoinflammatory mechanisms, such as the activation of nuclear factor κB (NF-κB) and type I interferon (IFN) pathways, provided new therapeutic options, such as anti-TNF and Janus kinase (JAK) inhibitors agents, directed to the specific blockade of cytokines and molecules involved in these novel inflammatory mechanisms [5,6,7,8,9]. During the last years, the vast improvement in their genetic and pathogenic knowledge has been accompanied by a great effort in improving their management In this sense, a remarkable number of randomized clinical trials exploring the efficacy and safety of new biologic agents in autoinflammatory diseases have been conducted, and therapeutic recommendations can be based on higher evidence levels
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