Monogenic autoinflammatory disorders: beyond the periodic fever

Abstract

The past two decades have seen an exponential increase in the number of monogenic autoinflammatory disorders described, coinciding with improved genetic sequencing techniques. This group of disorders has evolved to be heterogeneous and certainly more complex than the original four ‘periodic fever syndromes’ caused by innate immune over‐activation. This review aims to provide an update on the classic periodic fever syndromes as well as introducing the broadening spectrum of clinical features seen in more recently described conditions.

Successful treatment of HIV‐associated lupus‐like glomerulonephritis with mycophenolic acid

“…While there was limited testing for periodic fever syndromes (the patient tested negative for familial Mediterranean fever), these entities would not account for the renal histopathological findings. 9 Given the lack of alternative explanation and the presence of established HIV infection, which preceded the initial presentation of febrile hematruic episodes, the patient's renal pathology was attributed to consequence of HIV rather than an alternative process. 10 Beyond empiric recommendations for renin-angiotensin system inhibition, there is limited data to guide treatment of patients with either HIV-associated lupus-like glomerulonephritis, or HIVICK more broadly.…”

“…Importantly, extensive testing for concurrent infection was persistently negative, as was other markers of autoimmune disorders. While there was limited testing for periodic fever syndromes (the patient tested negative for familial Mediterranean fever), these entities would not account for the renal histopathological findings 9 . Given the lack of alternative explanation and the presence of established HIV infection, which preceded the initial presentation of febrile hematruic episodes, the patient's renal pathology was attributed to consequence of HIV rather than an alternative process 10 …”

Systemic autoinflammatory diseases: Clinical state of the art

“…Some of the most well-known SAIDs are monogenic, the most common one being familial Mediterranean fever (FMF), while others have a more illdefined pathophysiology, such as Still's disease or Schnitzler syndrome (2)(3)(4). The framework of FMF has been constantly evolving in recent years thanks to advances in genetics and the discovery of new diseases associated with mutations in genes involved in innate immunity (5). Nevertheless, although approximately 60 genes have been associated with a monogenic SAID, it is still difficult in clinical practice to predict if a genetic analysis will detect a pathogenic mutation based only on the clinical phenotype and medical history (4,5).…”

“…The framework of FMF has been constantly evolving in recent years thanks to advances in genetics and the discovery of new diseases associated with mutations in genes involved in innate immunity (5). Nevertheless, although approximately 60 genes have been associated with a monogenic SAID, it is still difficult in clinical practice to predict if a genetic analysis will detect a pathogenic mutation based only on the clinical phenotype and medical history (4,5). Furthermore, a significant minority of patients are eventually labelled as "unclassified systemic autoinflammatory disease" or USAID (6).…”

“…SAIDs are generally caused by a disorder of innate immunity leading to inflammation via multiple effectors. (4,5) In Figure 1, we propose 7 main mechanisms for these diseases.…”