Cryopyrin-Associated Periodic Fever Syndrome and the Nervous System

Abstract

Purpose of reviewThe purpose of this review is to highlight the molecular and clinical characteristics of the cryopyrin-associated periodic fever syndrome (CAPS) and its management. CAPS is an autosomal dominantly inherited autoinflammatory disorder associated with mutations in the NLRP3 gene, which ultimately lead to excessive production of interleukin-1β (IL-1β) and systemic inflammation. Typical systemic features include fever, urticarial rash and arthralgia, and ultimately amyloidosis. There are also multiple neurological manifestations including, but not restricted to, headache, sensorineural hearing loss, aseptic meningitis, myalgia and optic nerve involvement.Recent findingsSince the recognition of CAPS as a single disease entity and discovery of the underlying causative gene, there has been a major breakthrough in terms of its treatment by pharmacological IL-1β inhibition. Highly targeted therapies against IL-1 have been shown to be remarkably effective in the treatment of CAPS and make early diagnosis of this condition crucial. It is hoped that starting pharmacological intervention in a timely manner will prove neuroprotective. There are three drugs licensed for treatment of CAPS; canakinumab, anakinra and rilonacept. The former two are widely used: canakinumab is a fully humanised anti-IL-1β monoclonal antibody administered as a subcutaneous injection once every 8 weeks starting at a dose of 150 mg in patients weighing more than 40 kg. Anakinra is a recombinant form of the IL-1 receptor antagonist and the adult daily dose is 100 mg subcutaneously.SummaryCAPS is a highly debilitating disorder characterised by unregulated IL-1β production driven by autosomal dominantly inherited mutations in the NLRP3 gene. Effective therapies targeted against IL-1 are now available and are vital to prevent long-term complications.

Associations between Monocyte and T Cell Cytokine Profiles in Autism Spectrum Disorders: Effects of Dysregulated Innate Immune Responses on Adaptive Responses to Recall Antigens in a Subset of ASD Children

“…Given the role of IL-1β in TI, excessive, dysregulated production of IL-1β is likely to cause maladapted TI, and resultant pathogenic consequences. Patients with gene mutations that lead to the over-production of IL-1β are known to reveal inflammatory symptoms involving multiple organs including the brain [22,42]. Moreover, chronic inflammatory conditions, including neuropsychiatric conditions have been implicated with maladapted TI [29,43].…”

Innate Immunity and Neuroinflammation in Neuropsychiatric Conditions Including Autism Spectrum Disorders: Role of Innate Immune Memory

“…Given the role of IL-1β in trained immunity, excessive, dysregulated production of IL-1β is likely to cause maladapted trained immunity and resultant pathogenic consequences. This may be observed in patients with autoinflammatory syndromes associated with gene mutation that lead to overproduction of IL-1β, including cryopyrin associated periodic syndrome (CAPS) [38,42]. On the other hand, impaired induction of trained immunity can also cause detrimental effects.…”

Tolosa Hunt Syndrome: Current Diagnostic Challenges and Treatment

“…It is compulsatory to perform thoughtful evaluation of the associated systemic symptoms, as presence of fevers, hives rash, hearing loss, red eyes, joint pain following history of unilateral PO and diplopia is likely to be cryopyrin-associated periodic fever syndrome rather than THS hence confirmatory genetic testing for the (Q703K) mutation of the cryopyrin/NLRP3 gene and inflammatory markers should be considered [36] [37]. By the same token, pyrexia of unknown origin and nosebleed which may mistakenly thought to be a common cold, when followed with symptoms/signs of CS syndrome mimicking THS such as PO, diplopia, 3rd and 6th CN palsy unilaterally, is convincingly a metastases of a rare but fatal malignant lymphoma, the Extranodal NK/T-cell lymphoma which is prevalent in Mexico, Asia, South America, therefore unexceptionable evidence for the existence of abnormal, focal lesions should be sought from the PET-CT and MRI, as early treatment is associated with good prognosis [38].…”