New Therapeutic Developments for Pyoderma Gangrenosum and Hidradenitis Suppurativa
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- The pathogenesis of pyoderma gangrenosum and hidradenitis suppurativa involves numerous cytokines and immune pathways. The authors review current evidence regarding medications targeting elevated levels of TNF-α, IL-1, IL-17, IL-12, and IL-23, JAK inhibitors, and PDE-4 inhibitors for the treatment of these neutrophilic conditions.
- Given the complex pathogenesis of pyoderma gangrenosum and hidradenitis suppurativa, medications targeting a variety of cytokines seem to be effective, and a multimodal treatment may be necessary.
abstract
This abstract is available on the publisher's site.
Access this abstract nowPyoderma gangrenosum (PG) and hidradenitis suppurativa (HS) are stubborn inflammatory skin diseases categorized as neutrophilic hypodermal dermatoses. These conditions exhibit connections with other autoinflammatory disorders driven by immune responses. Their pathogenesis is complex, rooted in significant imbalances in both innate and adaptive immune systems, particularly featuring elevated levels of tumor necrosis factor-α (TNF-α), interleukin (IL)-1, IL-8, IL-17, and IL-23. Studies involving skin tissue pathology and serology have indicated that targeting specific cytokines can bring therapeutic benefits. Indeed, many patients in clinical settings have responded positively to such interventions. Yet, given the diverse cytokines in play, focusing on a single one with antibody therapy might not always be effective. When resistance to biologics emerges, a combined approach targeting multiple overactive cytokines with immunosuppressants, for example cyclosporine and Janus kinase inhibitors, could be an option. In the current review, we explore recent therapeutic developments for PG and HS.
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Additional Info
New treatment of pyoderma gangrenosum and hidradenitis suppurativa: A review
J Dermatol 2023 Nov 27;[EPub Ahead of Print], K YamanakaFrom MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
Pyoderma gangrenosum (PG) and hidradenitis suppurativa (HS) are challenging conditions routinely managed by medical dermatologists. Physicians have historically been limited to using rapidly acting immunosuppressants, such as corticosteroids and cyclosporine, to treat patients acutely. Improved understanding of the molecular drivers of PG and HS has opened the door to targeted therapeutics. This review summarizes the common inflammatory pathways implicated in both PG and HS, highlighting novel potential therapies for these complex patients.
Unfortunately, clinicians and researchers use a variety of tools to grade HS disease severity, and PG lacks a standardized, objective severity scoring instrument altogether. This can make it challenging to compare treatments and grade therapeutic responses. The continued development of these tools and their universal implementation will allow for stronger studies to support the use of targeted therapies.
In patients with PG or HS with comorbidities such as inflammatory bowel disease (IBD), TNF-alpha inhibitors are an excellent first-line treatment. Both adalimumab and infliximab treat the comorbid disease (eg, IBD) and generally lead to rapid improvement in PG. Head-to-head studies comparing adalimumab and infliximab for PG are lacking. In patients with HS, evidence suggests infliximab may be superior to adalimumab. Infliximab is also preferred in patients where compliance may be a concern. Etanercept seems less effective than adalimumab or infliximab in the treatment of PG or HS.
The author comments on the use of interleukin-1α/β inhibitors, anakinra and canakinumab. Anecdotally, there seems to be a specific subset of patients with PG who benefit the most from this therapy, with many patients exhibiting only a limited response. This also holds true in the HS literature with early improvements in severity scores that are not maintained over time. Notably, anakinra is a daily injection, which may impact patient compliance.
The use of interleukin-17 (IL-17) inhibitors has been recently reported in patients with PG and HS, with positive outcomes for both conditions. Caution should be used with IL-17 inhibitors in patients with IBD. I recommend screening for IBD in patients with PG/HS, in whom an IL-17 inhibitor is being considered with a thorough history, review of systems, and fecal calprotectin in select individuals.
The rapid development of targeted medications makes it an exciting time to be a medical dermatologist. Not only do these therapies provide an expanded treatment armamentarium for our patients, but also they teach us about the inflammatory conditions themselves.