Pyrin associated autoinflammation with neutrophilic dermatosis (PAAND)

PAAND is a rare monogenic autoinflammatory disease that shares clinical features with Familial Mediterranean Fever (FMF).

Genetics

 

This form of an inflammatory disease is due to mutations in the MEFV gene (that codes for pyrin) which is also associated FMF, leading to high serum IL-1β levels during febrile episodes. So far, all reported cases of PAAND have been associated with a dominant p.S242R mutation in the MEFV gene.

Unlike FMF, it is an inherited autosomal-dominant gene mutation disease and clinically presents during childhood with longer fever episodes (several weeks). Only a single copy of the mutation is needed to cause disease, meaning it affects half the children of patients, unlike the mutations that cause FMF, which often skip generations.

Symptoms

PAAND is characterized by sterile skin abscesses, long episodes of high fever, myalgia, myositis, fatigue and unlike FMF it is not characterized by serositis or amyloidosis. Clinical cutaneous manifestations evoked a closer resemblance to PAPA (pyogenic arthritis, pyoderma gangrenosum, and acne), with a lack of pyogenic arthritis. Other patients have also reported maculo-papular and pustular skin rash on the perioral region and upper and lower extremities, perineal mucosal inflammatory lesions, abdominal pain, failure to thrive, developmental delay, episodic myalgias and arthralgias. Elevated APRs and anemia are normally present among these patients.

Treatment

Colchicine, an effective treatment for FMF, has showed promising results in the treatment of PAAND. Therapy targeting IL-1β has also been successful in other patients, resolving pyrin-associated autoinflammation with neutrophilic dermatosis.

 

Sources:

Moghaddas F, Llamas R, De Nardo D, et al. A novel Pyrin-Associated Autoinflammation with Neutrophilic Dermatosis mutation further defines 14-3-3 binding of pyrin and distinction to Familial Mediterranean Fever. Annals of the Rheumatic Diseases 2017; 76: 2085-2094.

http://dx.doi.org/10.1136/annrheumdis-2017-211473

Shahrokh, Shabman et al. “410 Pyrin-associated auto-inflammation with neutrophilic dermatosis (PAAND): Novel autosomal recessive MEFV mutation and successful treatment with colchicine.” Journal of Investigative Dermatology May 2019; Volume 139, Issue 5, Supplement, Page S71.

https://doi.org/10.1016/j.jid.2019.03.486

Seth L. Masters et al. Familial autoinflammation with neutrophilic dermatosis reveals a regulatory mechanism of pyrin activation. Science Translational Medicine 30 Mar 2016: Vol. 8, Issue 332, pp. 332ra45

http://dx.doi.org/10.1126/scitranslmed.aaf1471

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