Ancient friends, revisited: Systematic review and case report of pyoderma gangrenosum-associated autoinflammatory syndromes

Abstract

In the last decade, new scientific findings significantly improved our understanding of the molecular pathogenesis of autoinflammation and have resulted in the identification and definition of several pyoderma gangrenosum-associated autoinflammatory syndromes (PGAAIS) as new and distinct clinical entities. These different clinical entities include PAPA (pyogenic arthritis, pyoderma gangrenosum and acne conglobata), PASH (pyoderma gangrenosum, acne and suppurative hidradenitis), PAPASH (pyoderma gangrenosum, acne, suppurative hidradenitis and pyogenic arthritis), PsAPASH (pyoderma gangrenosum, acne, suppurative hidradenitis and psoriatic arthritis), PASS (pyoderma gangrenosum, acne conglobata, suppurative hidradenitis, and axial spondyloarthritis) and PAC (pyoderma gangrenosum, acne and ulcerative colitis), which can be distinguished by their clinical presentation and the presence or absence of mutations in several genes, such as the genes encoding proline-serine-threonine phosphatase-interacting protein 1 (PSTPIP1), nicastrin (NCSTN), Mediterranean fever (MEFV) and nucleotide-binding oligomerization domain-containing protein (NOD). In this systematic review, we summarize the present knowledge of this rapidly developing hot topic and provide a guide to enable the easy diagnosis of these syndromes in everyday clinical practice. Moreover, we report a rare case of PASS syndrome demonstrating successful treatment with adalimumab and another case of a previously unreported combination of symptoms, including psoriatic arthritis, pyoderma gangrenosum, suppurative hidradenitis and Crohn’s disease (newly coined PsAPSC), as examples. Because of the identification of similar genetic and pathogenic mechanisms of PGAAIS, we think the wide variety of seemingly different syndromes may represent distinct phenotypes of one disease.

IL-1 and autoinflammatory disease: biology, pathogenesis and therapeutic targeting

“…The pathogenesis of hidradenitis suppurativa is thought to be due to a combination of genetic and environmental factors, although a positive family history is present in nearly 30% of patients, suggesting an autosomal-dominant inheritance 97 . More recently, hidradenitis suppurativa has been linked to a spectrum of autoinflammatory syndromes including pyoderma gangrenosum, acne, suppurative hidradenitis and ankylosing spondylitis (PASS) 98 ; pyoderma gangrenosum, acne, and suppurative hidradenitis (PASH); pyogenic arthritis, pyoderma gangrenosum, acne and suppurative hidradenitis (PAPASH); and psoriatic arthritis, pyoderma gangrenosum, acne, suppurative hidradenitis (PsAPASH) 99 . Although all of these syndromes share the sterile neutrophilic inflammatory lesions of hidradenitis suppurativa, the varied joint manifestations are consistent with a complex aetiology.…”

Successful Treatment of Coexistent Acne Fulminans and Severe Hidradenitis Suppurativa with Adalimumab

“…Their impact on patients' quality of life is usually significant, as marked visible lesions have a negative impact on body image [4,5]. Their coexistence together with the presence of seronegative spondyloarthropathy could either represent a potential new syndrome or be related to PASS syndrome (pyoderma gangrenosum, acne, suppurative hidradenitis, and spondyloarthritis), as it is already known that pyoderma gangrenosum can appear at any point after the development of HS lesions [6]. Antibiotics are commonly used to treat flares of HS, as secondary bacterial infections occur.…”

Role of the F-BAR Family Member PSTPIP2 in Autoinflammatory Diseases

“…There is growing evidence that mutations in different genes associated with autoinflammation are associated with other "neutrophilic diseases" (108)(109)(110). Pyoderma gangrene (PG) is a rare inflammatory neutrophilic skin disease that may occur in the context of PAPA (pyogenic sterile arthritis with PG and acne) and SAPHO syndromes as well as PASH (pyoderma gangrenosum, acne and pyogenic hidradenitis) syndromes (108). Two mutations encoding PSTPIP1 gene (A230T and E250Q) were found in PAPA patients (111), and the absence of PSTPIP2 triggers SAPHO syndromes (91).…”