Emerging treatments for pyoderma gangrenosum

ABSTRACT

Introduction: Pyoderma gangrenosum (PG) is a chronic inflammatory neutrophilic skin disorder with a mortality of up to 22%. In at least one third of patients, PG is associated with comorbidities.

Areas covered: This review covers clinical features of PG, current understanding of its etiology, established first and second line treatments and the potential of interleukin (IL)-1 antagonists, drugs interacting with the Th17/Treg balance, and phosphodiesterase-4 (PDE-4) antagonists for patients recalcitrant to these treatment options. Methodology: Published studies using PubMed® database 2000 – 2014 have been analyzed. The terms ‘pyoderma gangrenosum’, ‘treatment’, ‘interleukin-1 antagonists’, ‘Th17/Treg’, and ‘phosphodiesterase-4ʹ were used. Results: First line treatment of PG includes systemic corticosteroids and/or ciclosporin A. Second-line options are tumor necrosis factor-alfa antagonists. PG tends to develop drug resistance and becomes recalcitrant to available drug therapies. Antagonists to IL-1 seem to be a promising alternative. Antagonists to IL-12/IL-23 and IL-17 interfere with the Th17/Treg balance, with ustekinumab showing efficacy in PG. Recently, phosphodiesterase-4 (PDE-4) inhibitor apremilast was used successfully to treat PG.

Expert opinion: Targeted therapies with antagonists to IL-1, IL-12/IL-23 antagonists or PDE-4 seem to be promising. IL-17 antagonists are of potential interest as well, but clinical data are still missing for PG.

KEYWORDS:

• Pyoderma gangrenosum
• therapy
• chronic inflammatory bowel disease
• inflammasome
• interleukin-I
• Th17/Treg
• phosphodiesterase-4

Article highlights

• Pyoderma gangrenosum (PG) is a potentially life-threatening disease with major morbidity.

• Treatment of PG has to consider the major comorbidities such as chronic inflammatory bowel disease, malignancies, rheumatologic disorders, and endocrinopathies.

• PG often runs a chronic or chronic relapsing course and tends to become treatment resistant to drug therapy.

• New insights in etiopathogenesis of PG underline the activation of inflammasome(s).

• Emerging treatment are targeted therapies (such as interleukin 1 antagonists) and immunomodulating therapies (such as Th17/T_reg balance modulating drugs).

This box summarizes key points contained in the article.

Declaration of Interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Additional information

Funding

This paper was not funded.