Adult-onset systemic autoinflammatory disorders: a clinical approach

Abstract

Autoinflammatory disorders (AIDs) are a subgroup of immune-mediated syndromes that result from a primary dysfunction of the innate immune system. AIDs can be either monogenic or polygenic diseases. Unlike organspecific AIDs, systemic AIDs are characterized by fever and/or elevation of acute-phase reactants. This review aims to describe the most common adult-onset systemic AIDs, focusing mostly on polygenic and mixed-pattern diseases which are expected to be more prevalent in adult patients than monogenic AIDs overall. The literature was searched in Medline database. Organ-specific or childhood-onset systemic AIDs were excluded. AIDs were divided in three distinct groups: mixed-pattern, polygenic and adult-onset monogenic AIDs. Most adult-onset AIDs are polygenic but late-onset disease is not rare among monogenic AIDs such as familial Mediterranean fever (FMF). The diagnosis of systemic AIDs in adults is often delayed due to several factors and sometimes it is only established when amyloidosis or other complications are present. Therefore, it probably makes sense to primarily exclude common AIDs in adult patients with fever of unknown origin (and probably different presentations such as polyserositis) since a high prevalence of adult-onset Still’s disease or FMF is usually expected. Colchicine, nonsteroidal anti-inflammatory drugs, steroids, immunosuppressive agents, interleukin-1 inhibitors and tumor necrosis factor antagonists constitute common therapeutic options for systemic AIDs.

A young woman with fever and polyserositis caused by familial Mediterranean fever

“…Familial Mediterranean fever is the most common monogenic autoinflammatory disorder; it is characterized by self-limited episodes of fever, polyserositis and elevated inflammatory markers. [1][2][3][4] The condition is associated with gain-of-function sequence variations in the MEFV gene that encodes for the pyrin protein, and results in uncontrolled production of interleukin-1β and an exaggerated inflammatory response. 1,2,4 The disease manifests as recurrent bouts of fever, abdominal pain and chest pain that start abruptly and peak soon after onset, last for 1-4 days and then resolve spontaneously.…”

“…[1][2][3][4] The condition is associated with gain-of-function sequence variations in the MEFV gene that encodes for the pyrin protein, and results in uncontrolled production of interleukin-1β and an exaggerated inflammatory response. 1,2,4 The disease manifests as recurrent bouts of fever, abdominal pain and chest pain that start abruptly and peak soon after onset, last for 1-4 days and then resolve spontaneously. Patients typically have no symptoms between attacks.…”

Transient and Recurrent Pulmonary Infiltrations Associated with Familial Mediterranean Fever

“…In monogenic autoinflammatory disease, where the association between genetic abnormalities and pathological conditions is clear, nonsteroidal anti-inflammatory drugs (NSAIDs) or steroids are generally effective, but not colchicine. Exceptionally, however, colchicine is effective against FMF, while NSAIDs/steroids are not ( 12 ). Second- and third-line therapeutic options for colchicine-resistant FMF are interleukin-1 (IL-1) inhibitors and tumor necrosis factor-α inhibitors (or immunosuppressive agents), respectively ( 12 ).…”

“…Exceptionally, however, colchicine is effective against FMF, while NSAIDs/steroids are not ( 12 ). Second- and third-line therapeutic options for colchicine-resistant FMF are interleukin-1 (IL-1) inhibitors and tumor necrosis factor-α inhibitors (or immunosuppressive agents), respectively ( 12 ). In Japan, human anti-IL-1β monoclonal neutralizing antibody (canakinumab) is covered by health insurance for such patients ( 13 ).…”

The Clinical Chameleon of Autoinflammatory Diseases in Children

“…Although many classification criteria have been developed to help diagnose rare monogenic ADs, patients with recurrent fevers and inflammatory symptoms experience a general delay in identification of the disease, which can lead to further morbidities and dreadful complications, such as AA-amyloidosis [ 8 , 9 ]. The repertoire of ADs was expanded to include inflammatory diseases such as Behçet’s disease, gout and idiopathic recurrent pericarditis, all of which have autoinflammatory-mediated mechanisms and a presumed polygenic basis [ 10 ]. Identification of the causative genes has also allowed for the confirmation of the clinical diagnosis in familial Mediterranean fever (FMF); tumor necrosis factor receptor-associated periodic syndrome (TRAPS); cryopyrin-associated periodic syndrome (CAPS), which includes familial cold-induced autoinflammatory syndrome (FCAS), Muckle-Wells syndrome (MWS) and chronic infantile neurological cutaneous articular (CINCA) syndrome; mevalonate kinase deficiency (MKD); pyogenic diseases including pyogenic arthritis/pyoderma gangrenosum/acne (PAPA) syndrome, Majeed syndrome (MS) and deficiency of the IL-1 receptor antagonist (DIRA); Blau syndrome (BS); OTULIN-related autoinflammatory syndrome (ORAS) and proteasome-associated autoinflammatory syndromes (PRAAS).…”