Pyogenic arthritis, pyoderma gangrenosum, and acne (PAPA) syndrome is a rare disease (OMIM #604416) that mainly affects the joints and skin and is caused by an autosomal dominant mutation of the Proline-Serine-Threonine Phosphatase-interacting Protein 1 (PSTPIP1). Studies have shown that the response to anti-IL-1 agents, such as anakinra, is variable, with anakinra exhibiting better effectiveness for joint manifestations than for cutaneous involvement. Instead, anti- tumor necrosis factor alpha (TNF) treatment is more effective in the treatment and prevention of pyoderma gangrenosum lesions. Here, we describe four cases of clinically suspected PAPA syndrome in patients from the same family, who were treated empirically with initial corticosteroid therapy combined with methotrexate to improve joint symptoms. The results were promising in terms of both efficacy and tolerance. We concluded that while biologics remain the ideal therapeutic option, methotrexate is an accessible and well-tolerated alternative that can offer significant clinical improvement in joint involvement, especially in early or mild cases. Further studies are needed to better define its place in the therapeutic arsenal for PAPA syndrome.
