Cryopyrin-associated periodic syndromes: development of a patient-reported outcomes instrument to assess the pattern and severity of clinical disease activity

Hoffman, Hal M.; Wolfe, Frederick; Belomestnov, Pavel; Mellis, Scott

doi:10.1185/03007990802297495

Cited by 20 publications

(12 citation statements)

References 26 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Based on the collected evidence for excessive contact system activation in FACAS, we initiated a short treatment course over 4 consecutive days with the bradykinin B2 receptor antagonist icatibant in the index patient (patient #1). Individual symptoms were assessed by a patient-reported standardized daily health assessment form that was adapted from a validated tool for CAPS 23 . Within 30 min after the first administration of 30 mg icatibant, the generalized urticarial rash and systemic symptoms improved.…”

Section: Characteristicmentioning

confidence: 99%

Cold-induced urticarial autoinflammatory syndrome related to factor XII activation

et al. 2020

View full text Add to dashboard Cite

Hereditary autoinflammatory diseases are caused by gene mutations of the innate immune pathway, e.g. nucleotide receptor protein 3 (NLRP3). Here, we report a four-generation family with cold-induced urticarial rash, arthralgia, chills, headache and malaise associated with an autosomal-dominant inheritance. Genetic studies identify a substitution mutation in gene F12 (T859A, resulting in p.W268R) which encodes coagulation factor XII (FXII). Functional analysis reveals enhanced autocatalytic cleavage of the mutated protein and spontaneous FXII activation in patient plasma and in supernatant of transfected HEK293 cells expressing recombinant W268R-mutated proteins. Furthermore, we observe reduced plasma prekallikrein, cleaved high molecular weight kininogen and elevated plasma bradykinin. Neutrophils are identified as a local source of FXII. Interleukin-1β (IL-1β) is upregulated in lesional skin and mononuclear donor cells exposed to recombinant mutant proteins. Treatment with icatibant (bradykinin-B2-antagonist) or anakinra (interleukin-1-antagonist) reduces disease activity in patients. In conclusion, our findings provide a link between contact system activation and cytokine-mediated inflammation.

show abstract

Section: Characteristicmentioning

confidence: 99%

Cold-induced urticarial autoinflammatory syndrome related to factor XII activation

et al. 2020

View full text Add to dashboard Cite

show abstract

“…Because of the variable nature of symptoms and severity in CAPS, it is often difficult to accurately assess the quality of life of CAPS patients. Daily health assessment forms have been developed that reliably capture disease severity or symptoms and can be used to measure treatment efficacy [77]. …”

Section: Treatmentmentioning

confidence: 99%

Cryopyrin-Associated Periodic Syndrome: An Update on Diagnosis and Treatment Response

Leslie

2010

Curr Allergy Asthma Rep

115

View full text Add to dashboard Cite

Cryopyrin-associated periodic syndrome (CAPS) is a rare hereditary inflammatory disorder encompassing a continuum of three phenotypes: familial cold autoinflammatory syndrome, Muckle-Wells syndrome, and neonatal-onset multisystem inflammatory disease. Distinguishing features include cutaneous, neurological, ophthalmologic, and rheumatologic manifestations. CAPS results from a gain-of-function mutation of the NLRP3 gene coding for cryopyrin, which forms intracellular protein complexes known as inflammasomes. Defects of the inflammasomes lead to overproduction of interleukin-1, resulting in inflammatory symptoms seen in CAPS. Diagnosis is often delayed and requires a thorough review of clinical symptoms. Remarkable advances in our understanding of the genetics and the molecular pathway that is responsible for the clinical phenotype of CAPS has led to the development of effective treatments. It also has become clear that the NLRP3 inflammasome plays a critical role in innate immune defense and therefore has wider implications for other inflammatory disease states.

show abstract

“…This study demonstrated clear clinical and laboratory responses similar to those observed with daily anakinra 105 and was the foundation for the first randomized, placebo-controlled trial in 44 patients with FCAS and MWS 18 using a novel, validated, self-reporting daily diary to derive a key symptom score that was the primary clinical end point of the study. 106 Significant differences were observed between active drug and placebo in key symptom scores, number of flares, and CRP and SAA concentrations in both the treatment and withdrawal phase of this 2-part multicenter study in the United States. The primary side effect noted was injection-site reactions in the treatment group that never resulted in drug discontinuation.…”

Section: Newer Il-1-targeted Therapies In Patients With Capsmentioning

confidence: 79%

Therapy of autoinflammatory syndromes

2009

Journal of Allergy and Clinical Immunology

View full text Add to dashboard Cite

The therapy of autoinflammatory syndromes is an excellent example of the power of translational research. Recent advances in our understanding of the molecular and immunologic basis of this newly identified classification of disease have allowed for the application of novel, effective, targeted treatments with life-changing effects on patients. Although colchicine and TNF-α inhibitors are important therapies for specific autoinflammatory syndromes, the novel IL-1-targeted drugs are particularly effective for many of these diseases. Recently, the pharmaceutical industry has adopted a strategy of confirming the efficacy of new targeted drugs in often-ignored patients with orphan diseases, and US Food and Drug Administration policies have allowed for accelerated approval of these drugs, creating a win-win situation for patients and industry. This article reviews the general approach to the therapy of autoinflammatory diseases, focusing on current approved therapies and novel approaches that might be used in the future. Keywords Autoinflammatory; IL-1; inflammasomeThe traditional clinical classification of immune-mediated diseases, including allergy, immunodeficiency, and autoimmunity, is based on differences in immunologic mechanisms and clinical symptomatology and has defined the medical specialties caring for patients with immune-mediated illnesses for more than 60 years. However, in the last 10 years, a new category of immunologic disease, known as autoinflammatory diseases, has been created to account for disorders that did not fit well into the classical disease groups. 1 Although patients with these disorders can present with classic rheumatologic symptoms, including inflammation involving the joints, skin, muscles, and eyes, the underlying inflammatory mechanisms do not involve autoantibodies or antigen-specific T cells. 2 Some patients also display episodic or precipitated symptoms, including urticaria and conjunctivitis, similar to those seen in allergic patients, but there is no evidence of IgE-mediated inflammation. Recurrent fever is a common feature of both autoinflammatory disorders and infections caused by immune deficiency. However, insufficient immune response to pathogens is not an immunologic characteristic of autoinflammatory diseases.Reprint requests: Hal M. Hoffman, MD, University of California at San Diego, School of Medicine, 9500 Gilman Dr, La Jolla, CA 92093-0635. hahoffman@ucsd.edu. HHS Public Access Author Manuscript Author ManuscriptAuthor Manuscript Author ManuscriptThe autoinflammatory disorders are characterized by dysregulation of innate immunity, the arm of the immune system considered to be more primitive and less specific. Instead of lymphocyte or antibody responses to specific antigens based on a memory of prior exposure, innate immune cells, such as macrophages and dendritic cells, sense conserved pathogenassociated molecular patterns. The primary effectors of the innate immune response are myeloid cells, such as neutrophils and monocytes, and proinflammatory cytokines...

show abstract

Cryopyrin-associated periodic syndromes: development of a patient-reported outcomes instrument to assess the pattern and severity of clinical disease activity

Cited by 20 publications

References 26 publications

Cold-induced urticarial autoinflammatory syndrome related to factor XII activation

Cold-induced urticarial autoinflammatory syndrome related to factor XII activation

Cryopyrin-Associated Periodic Syndrome: An Update on Diagnosis and Treatment Response

Therapy of autoinflammatory syndromes

Contact Info

Product

Resources

About