PAPA syndrome is caused by
The mutated gene produces a hyperphosphorylated protein that binds excessively to pyrin, thus restricting pyrin’s anti-inflammatory activity, which possibly involves inhibiting neutrophil activation and chemotaxis by blocking activation of inflammasomes.
Arthritis begins in the first decade of life and is progressively destructive. Episodes of mild trauma may trigger the arthritis. Poorly healing ulcers with undermined edges may appear, often at sites of injury (eg, at vaccination sites). Acne is usually nodulocystic and, if untreated, causes scarring. By puberty, arthritis tends to subside, and cutaneous symptoms predominate.
Diagnosis of PAPA syndrome is based on clinical findings and a family history. The ulcers may be biopsied. Biopsy shows superficial ulceration and neutrophilic inflammation.
Treatment of PAPA syndrome with etanercept or anakinra (100 mg subcutaneously once a day) may be useful. Acne is treated with oral tetracycline or isotretinoin.