Published in:
01-11-2019 | Adalimumab | Letter to Editor
Successful Treatment of PAPA Syndrome with Dual Adalimumab and Tacrolimus Therapy
Authors:
Amika K. Sood, Diana B. McShane, Paul B. Googe, Eveline Y. Wu
Published in:
Journal of Clinical Immunology
|
Issue 8/2019
Login to get access
Excerpt
Pyogenic arthritis, pyoderma gangrenosum, and acne (PAPA) syndrome is a rare autosomal dominant disorder with variable expressivity [
1] and results from mutations in the
PSTPIP1 gene. The PSTPIP1 protein is a cytoskeletal protein within hematopoietic cells that serves as a scaffold for the binding of other cellular proteins, such as pyrin, protein tyrosine phosphatases, c-Abl, CD2, and WASP. Through these interactions, PSTPIP1 regulates several cellular functions including IL-lβ release, cytoskeleton organization, cell migration, and T cell activation [
2,
3]. Depending on the mutation location within the
PSTPIP1 gene and consequent alterations in protein-protein interactions, a spectrum of autoinflammatory disorders may result and are collectively referred to as
PSTPIP1-associated inflammatory diseases (PAID). While the underlying pathogenesis is not completely understood, the PAID spectrum is characterized by dysregulated IL-lβ release and neutrophil responses [
4], and clinically manifests as recurrent bouts of untriggered inflammation involving various organ systems [
5]. PAPA syndrome is only one entity within the PAID spectrum and classically presents with sterile pyogenic arthritis, pyoderma gangrenosum (PG), and cystic acne. Due to heterogeneous presentations, delays in diagnosis and misdiagnoses as autoimmune or immunodeficiency conditions are common. …