Cryopyrinopathies: update on pathogenesis and treatment

  title={Cryopyrinopathies: update on pathogenesis and treatment},
  author={B{\'e}n{\'e}dicte Neven and Anne Marie Prieur and Pierre Quartier dit Maire},
  journal={Nature Clinical Practice Rheumatology},
Cryopyrinopathies are a group of rare autoinflammatory diseases that includes familial cold autoinflammatory syndrome, Muckle–Wells syndrome and chronic infantile neurologic cutaneous articular syndrome (also termed neonatal-onset multisystemic inflammatory disease). These syndromes were initially considered to be distinct disease entities despite some clinical similarities; however, mutations of the same gene have since been found in all three cryopyrinopathies. These diseases, therefore, are… 

[Cryopyrin-associated periodic syndromes].

Pharmacological treatment options for cryopyrin-associated periodic syndromes

This review covers pharmacokinetic, pharmacodynamic and safety aspects of the approved drugs and the potential utility of IL-1β blockers in a wide range of other conditions with an autoinflammatory component.

Interleukin-1β inhibitors for the treatment of cryopyrin-associated periodic syndrome

  • Eugen Dhimolea
  • Medicine, Biology
    The application of clinical genetics
  • 2011
Cryopyrin-associated periodic syndrome comprises a group of rare, but severe, inherited autoinflammatory disorders associated with aberrant secretion of interleukin (IL)-1, and evidence supporting the clinical value of IL-1β in CAPS has been provided from the complete response of patients after treatment withIL-1 blocking agents.

Cryopyrin-associated periodic syndrome.

CAPS is a rare autoinflammatory disease associated with mutations in the NLRP3 gene that result in overactivation of the inflammasome, increased secretion of IL-1beta and IL-18, and systemic

Bridging the Gap between the Clinician and the Patient with Cryopyrin-Associated Periodic Syndromes

Cryopyrin-associated periodic syndromes are categorized as a spectrum of three autoinflammatory diseases, namely familial cold auto-inflammatory syndrome, Muckle-Wells syndrome and chronic infantile neurological cutaneous articular syndrome, justifying the need to facilitate early diagnosis and thus avoid irreversible negative consequences for tissues and organs.

Diagnosis and Management of the Cryopyrin-Associated Periodic Syndromes (CAPS): What Do We Know Today?

This review summarizes the current evidence in diagnosis and management of patients with cryopyrin-associated periodic syndromes and suggests a targeted anti-IL-1 therapy should be started as soon as possible.

Síndromes autoinflamatórias hereditárias na faixa etária pediátrica

Pediatricians must recognize the clinical features of the most prevalent autoinflammatory syndromes, namely familial Mediterranean fever; TNF receptor associated periodic syndrome; the cryopyrinopathies; mevalonate kinase deficiency; pediatric granulomatous arthritis; pyogenic arthritis, pyoderma gangrenosum and acne syndrome; Majeed syndrome; and deficiency of interleukin 1 receptor antagonist.

A rare hereditary disease: Muckle-Wells syndrome

A 58-year-old male, who had migratory joint pains, daily urticaria, chills, and episodic conjunctivitis since childhood and hearing loss in his 20s with a family history of similar symptoms was diagnosed with MWS and successfully treated with canakinumab.

Canakinumab for the treatment of adult and pediatric cryopyrin‐associated periodic syndromes (CAPS)

A promising new medication, canakinumab, is a recombinant, human anti‐human‐IL‐1β monoclonal antibody that has been effective in treating adult and pediatric CAPS.

Rilonacept in the management of cryopyrin-associated periodic syndromes (CAPS)

Rilonacept is the first us Food and Drug Administration-approved treatment for familial cold autoinflammatory syndrome and Muckle–Wells syndrome and the first in a new line of drugs designed for longer-acting IL-1 blockade, associated with a decrease in disease activity, high-sensitivity C-reactive protein (hsCRP) and serum amyloid A (SAA) in the treatment of CAPS.



Spectrum of clinical features in Muckle-Wells syndrome and response to anakinra.

The remarkable response of MWS to anakinra suggests that IL-1beta has a fundamental role in the pathogenesis of inflammation associated with mutations in the NALP3 gene, and supports study of IL- 1 inhibition in patients with NOMID/CINCA syndrome or FCAS.

The clinical continuum of cryopyrinopathies: novel CIAS1 mutations in North American patients and a new cryopyrin model.

Investigation of the structural effect of disease-causing mutations on cryopyrin provides insight into potential molecular mechanisms by which cryopyrsin mutations can inappropriately activate an inflammatory response.

Familial autoinflammatory diseases: genetics, pathogenesis and treatment

Advances in molecular genetics extend the ability to recognize and treat patients with systemic autoinflammatory diseases and inform the understanding of the regulation of innate immunity in humans.

A variant Muckle-Wells syndrome with a novel mutation in CIAS1 gene responding to anakinra

The resolution of inflammatory symptoms, normalization of serological values, and improvement in hearing was noted with anakinra treatment, and Interleukin 1B blockade may be therapeutic for this syndrome.

Arthropathy of neonatal onset multisystem inflammatory disease (NOMID/CINCA)

These findings suggest that the arthropathy of NOMID is the result of abnormal endochondral bone growth, and whether this deformity is triggered by inflammation early in development or by CIAS1 mutations causing abnormal chondrocyte apoptosis is needed to determine.

Hearing improvement in a patient with variant Muckle-Wells syndrome in response to interleukin 1 receptor antagonism

The confirmed improvement in hearing after initiation of interleukin 1 receptor antagonism corroborates previous reports that specific blockade of this single cytokine reverses most of the symptoms of this group of CIAS1/NALP3 related autoinflammatory conditions, including the sensorineural deafness, which has not been previously reported.

The clinical course of a child with CINCA/NOMID syndrome improved during and after treatment with thalidomide

It is proposed that thalidomide can be beneficial in select patients with CINCA syndrome and a 17‐year‐old girl with CinCA for whom numerous medication trials had been unsuccessful is described.

A cryopyrin-associated periodic syndrome with joint destruction.

A previously unreported form of CAPS with atypical neurological signs, joint destruction and livedo is described, extending the clinical spectrum associated with CIAS1 mutations.

A large kindred with familial cold autoinflammatory syndrome.

Response to IL‐1‐Receptor Antagonist in a Child with Familial Cold Autoinflammatory Syndrome

This is the first report of successful treatment with anakinra in a young child with familial cold auto‐inflammatory syndrome, and several authors have reported successful use of this agent in children with chronic infantile neurologic, cutaneous, articular syndrome.