Pyrin-associated autoinflammation with neutrophilic dermatosis D71

Pyrin-associated autoinflammation with neutrophilic dermatosis (PAAND) is an autosomal dominant inherited autoinflammatory disease caused by mutations in the MEFV gene, the same gene responsible for familial Mediterranean fever (FMF).

This is caused by mutations in the MEFV gene that codes for S242R and E244K. The mutated proteins lead to activation of the pyrin inflammasome (Masters SL et al. 2016).

PAAND occurs in childhood.

PAAND is characterized by recurrent fever attacks lasting several weeks, accompanied by arthralgia, myalgia and inflammatory skin changes. Dermatological manifestations: Severe neutrophilic dermatoses characterize the clinical picture of PAAND. The following have been described: severe pustular acne, pyoderma gangrenosum, recurrent sterile skin abscesses, neutrophilic vasculitis of the small vessels, severe hidradenitis suppurativa and neutrophilic panniculitis (Moghaddas F et al. 2017; Masters SL et al. 2016).

During seizures, acute phase reactions and circulating proinflammatory cytokines (IL-1β, IL-6, TNF-α and IL-1Ra) are increased (Moghaddas F et al.2017).

The histopathology shows dense dermal neutrophil infiltrates both interstitially and perivascularly (Masters SL et al. 2016).

Treatment with IL-1 blockers leads to rapid control of clinical and laboratory abnormalities. Infliximab and adalimumab were used in anakinra-resistant patients (Moghaddas F et al.2017)

1. Figueras-Nart I et al. (2019) Dermatologic and Dermatopathologic Features of Monogenic Autoinflammatory Diseases. Front Immunol. 10:2448.
2. Masters SL et al. (2016) Familial autoinflammation with neutrophilic dermatosis reveals a regulatory mechanism of pyrin activation. Sci Transl Med 8: 332
3. Moghaddas F et al.(2017) A novel pyrin -associated autoinflammation with nuetrophilic dermatosis mutation further defines 14-3-3 binding of pyrin and distinction to familial Mediterranean fever. Ann Rheum Dis 76: 2085-2094).