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Pyrin-associated autoinflammation with neutrophilic dermatosis
Other Resources UpToDate PubMed

Pyrin-associated autoinflammation with neutrophilic dermatosis

Contributors: Ruth Wang PhD
Other Resources UpToDate PubMed

Synopsis

Pyrin-associated autoinflammation with neutrophilic dermatosis (PAAND) is a monogenic autoinflammatory condition that presents with features of systemic inflammation and rash. PAAND is due to a mutation of the Mediterranean fever (MEFV) gene that encodes pyrin, a protein that responds to pathogen signals and disruptions in cellular homeostasis by forming an inflammasome complex that activates the secretion of the proinflammatory cytokine interleukin-1β (IL-1β). The causative mutations have been found to be a serine-to-arginine substitution mutation at position 242 of MEFV (S242R) and a glutamate-to-lysine substitution mutation at position 244 (E244K). These mutations trigger pyrin inflammasome overactivation and excess IL-1β production.

First described in a family of Belgian ancestry spanning 3 generations, PAAND has since been identified in 6 additional families / individuals of Spanish, Japanese, and Iranian-Azeri ancestry, and from the United Kingdom, France, and Lebanon. As a rare disease, the populations affected by PAAND are still being characterized, but current studies have shown equal distributions between sexes, with the majority of disease onset during childhood, although a few cases of adult onset have been noted. The predominant mode of inheritance is autosomal dominant with incomplete penetrance, but one study identified an autosomal recessive mode of inheritance as well in a family of first-cousin consanguineous parents.

PAAND most commonly presents with recurrent neutrophilic dermatoses (severe acne, sterile skin abscesses, pyoderma gangrenosum, hidradenitis suppurativa, and cutaneous neutrophilic small-vessel vasculitis) and periodic fevers that last several weeks. Some patients experience a distinct exanthematous and pustular eruption that can be widespread or limited to the perioral region, upper and lower extremities, and perineal mucosa. Cutaneous eruptions are often the first manifestations of PAAND and can often persist or undergo a cyclical pattern. Patients will often have multiple cutaneous manifestations, with almost all patients experiencing acne, folliculitis, and pyoderma gangrenosum. Other common manifestations include arthralgia; myalgia / myositis; oligoarthritis / polyarthritis; abdominal pain accompanied by diarrhea, nausea, and vomiting; gastrointestinal (GI) inflammation; and anemia. Developmental delay is seen in patients with childhood onset. Rare manifestations include reported occurrence of dilated cardiomyopathy in a patient aged 13 years that evolved into chronic cardiac decompensation necessitating cardiac transplantation at age 20. Symptoms usually increase in severity with age.

Codes

ICD10CM:
M04.8 – Other autoinflammatory syndromes

SNOMEDCT:
724834006 – Neutrophilic dermatosis

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Last Reviewed:03/19/2022
Last Updated:03/20/2022
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Pyrin-associated autoinflammation with neutrophilic dermatosis
A medical illustration showing key findings of Pyrin-associated autoinflammation with neutrophilic dermatosis (Dermatologic )
Copyright © 2022 VisualDx®. All rights reserved.