Autoinflammatory syndromes associated with hidradenitis suppurativa and/or acne

Abstract

Autoinflammatory syndromes associated with hidradenitis suppurativa (HS) and/or acne are rare but potentially debilitating disorders if not diagnosed and treated correctly. They share a common pathogenesis involving a dysregulated innate immune system with abnormal interleukin (IL)-1 signaling leading to sterile neutrophilic inflammation. The clinical features are recurrent episodes of fever, painful arthritis, and skin lesions consistent with HS, acne, and pyoderma gangrenosum (PG) accompanied by elevated systemic inflammatory markers in blood. So far, several clinically different syndromes have been reported in the literature including pyoderma gangrenosum, acne, and pyogenic arthritis (PAPA), pyoderma gangrenosum, acne, and hidradenitis suppurativa (PASH), pyoderma gangrenosum, acne, and spondyloarthritis (PASS), pyoderma gangrenosum, acne, pyogenic arthritis, and hidradenitis suppurativa (PAPASH), psoriatic arthritis, pyoderma gangrenosum, acne, and hidradenitis suppurativa (PsAPASH), and pyoderma gangrenosum, acne, and ulcerative colitis (PAC). The rarity of the syndromes complicates the establishment of evidence-based treatment guidelines. Furthermore, treatment can be challenging due to lack of response to standard treatment modalities. Therefore, it is important to increase the awareness about these diseases in order to optimize disease management and ultimately improve the quality of life of patients.

PAPASH , Ps APASH and PASS autoinflammatory syndromes: phenotypic heterogeneity, common biological signature and response to immunosuppressive regimens

“…The clinical phenotypes of these AIS are ill‐defined, and unlike PASH (Pyoderma gangrenosum, Acne, Suppurative Hidradenitis) or PAPA (Pyogenic Arthritis, Pyoderma gangrenosum, Acne) syndromes, still lack any biological or genetic marker. Moreover, their optimal therapeutic management remains unclear . We report an in‐depth description of the clinicopathological, radiological, immunobiological features and treatment outcomes in a series of nine patients diagnosed with PAPASH ( n = 2), PsAPASH ( n = 1) or PASS ( n = 6), in three tertiary care centres between 2014 and 2016.…”

A new link between autoinflammation and hidradenitis suppurativa?

“…Recent reports suggest perturbations in the skin microbiome rather than primary infections in patients with HS, and several observations support a dysregulation of the innate immune response. Indeed, HS can coexist with other inflammatory pathologies such as acne, inflammatory bowel disease (IBD) and pyoderma gangrenosum (PG) and is an integral disease component of certain complex autoinflammatory syndromes …”

The immunological disease continuum of inflammation against self as an explanation for the lack of association between hidradenitis suppurativa and autoimmune thyroid disease

“…However, evidence suggests that HS is an autoinflammatory disease (AID) rather an autoimmune disease (AD) . Monogenic autoinflammatory disorders, including pyoderma gangrenosum (PG), acne, pyogenic arthritis (PAPA) syndrome and related syndromes, including PASH (PG, acne and HS), PAPASH (PG, acne, pyogenic arthritis and HS), PASS (PG, acne and spondyloarthritis), PsAPASH (psoriatic arthritis, pyoderma gangrenosum, acne and HS) and PAC (PG, acne and ulcerative colitis) .…”

“…However, evidence suggests that HS is an autoinflammatory disease (AID) rather an autoimmune disease (AD) . Monogenic autoinflammatory disorders, including pyoderma gangrenosum (PG), acne, pyogenic arthritis (PAPA) syndrome and related syndromes, including PASH (PG, acne and HS), PAPASH (PG, acne, pyogenic arthritis and HS), PASS (PG, acne and spondyloarthritis), PsAPASH (psoriatic arthritis, pyoderma gangrenosum, acne and HS) and PAC (PG, acne and ulcerative colitis) . From a pathogenetic point of view, all these conditions share common mechanisms, including overactivation of the innate immune system, beginning with increased production of interleukin (IL)‐1 family members and other cytokines, and sterile neutrophil‐rich cutaneous inflammation in the absence of circulating autoantibodies and autoreactive T‐cells.…”

“…From a pathogenetic point of view, all these conditions share common mechanisms, including overactivation of the innate immune system, beginning with increased production of interleukin (IL)‐1 family members and other cytokines, and sterile neutrophil‐rich cutaneous inflammation in the absence of circulating autoantibodies and autoreactive T‐cells. From a genetic point of view, several mutations, most notably in PSTPIP2 , which affect proteins of the inflammasome complex or proteins that regulate the inflammasome and innate immune cell function, have been described in these disorders . By contrast, Hashimoto thyroiditis represents a prototype of AD characterized by autoantibodies that pre‐date target organ damage …”