Pyoderma gangrenosum, acne and ulcerative colitis in a patient with a novel mutation in thePSTPIP1gene

Abstract

We describe a novel mutation in PSTPIP1 resulting in pyoderma gangrenosum, acne and ulcerative colitis. This novel constellation of clinical manifestations, which we term 'PAC syndrome', suggests the need to regroup all PSTPIP1-associated phenotypes under one aetiological group.

Anti-Inflammatory Chromatinscape Suggests Alternative Mechanisms of Glucocorticoid Receptor Action

“…Activation of CLEC5A, such as by direct binding of dengue virus, leads to TNF-α and NO production in myeloid cells, which induces lethal shock (Chen et al, 2008; Cheung et al, 2011). Several mutations in Pstpip1 have been implicated in the pathogenesis of autoinflammatory pyogenic arthritis, pyoderma gangrenosum, and acne (PAPA) (Smith et al, 2010; Wise et al, 2002; Zeeli et al, 2015), and the mutant proteins bind to components of the inflammasome, causing constitutive assembly and activation of the complex (Shoham et al, 2003; Yu et al, 2007). In summary, our analysis reveals a small cohort of highly inflammatory genes among those that are apparently controlled more effectively by a late Dex treatment (in the LPS-activated macrophages) in comparison to Dex given early.…”

Autoinflammatory syndromes associated with hidradenitis suppurativa and/or acne

“…The dermatologic manifestations of PASH syndrome can be accompanied by either pyogenic arthritis in PAPASH syndrome or psoriatic arthritis (PsA) in PsAPASH syndrome . PAC syndrome consisting of PG, acne, and ulcerative colitis have also been described . PSTPIP1 mutations have been identified in PAPASH and PAC syndrome but not yet in PsAPASH .…”

“…PAC syndrome consisting of PG, acne, and ulcerative colitis have also been described . PSTPIP1 mutations have been identified in PAPASH and PAC syndrome but not yet in PsAPASH . Both anakinra and adalimumab have led to good clinical control of symptoms in these syndromes (Table ) …”

“…Acne and hidradenitis suppurativa (HS) are chronic inflammatory skin disorders with central pathophysiological events involving follicular occlusion of the pilosebaceous unit and a dysregulated innate immune response . HS and acne can be essential components of autoinflammatory syndromes of which several have been reported in the literature . These include the well‐described monogenic pyoderma gangrenosum, acne, and pyogenic arthritis (PAPA) syndrome consisting of pyoderma gangrenosum (PG), acne, and pyogenic sterile arthritis as well as other less well‐defined syndromes combining the triad of PG, acne, and HS, clinically differentiated by their arthritis component; pyoderma gangrenosum, acne, and hidradenitis suppurativa (PASH) with no arthritis, pyoderma gangrenosum, acne, pyogenic arthritis, and hidradenitis suppurativa (PAPASH), and pyoderma gangrenosum, acne, and spondyloarthritis (PASS), Recently added to the spectrum are the syndromes psoriatic arthritis, pyoderma gangrenosum, acne, and hidradenitis suppurativa (PsAPASH), and pyoderma gangrenosum, acne, and ulcerative colitis (PAC) where all three coexist …”

Postoperative pyoderma gangrenosum (PG): The Mayo Clinic experience of 20 years from 1994 through 2014

“…25 Patients with autoinflammatory syndromes, such as pyogenic arthritis, PG, and acne syndrome have been reported to carry the proline-serine-threonine phosphatase interacting protein 1 gene, also called CD2 antigen-binding protein-1. [26][27][28] However, the likely cause of postoperative PG is a multifactorial response in a predisposed individual.…”