Pyoderma Gangrenosum: An Updated Literature Review on Established and Emerging Pharmacological Treatments

Abstract

Pyoderma gangrenosum is a rare inflammatory skin disease classified within the group of neutrophilic dermatoses and clinically characterized by painful, rapidly evolving cutaneous ulcers with undermined, irregular, erythematous-violaceous edges. Pyoderma gangrenosum pathogenesis is complex and involves a profound dysregulation of components of both innate and adaptive immunity in genetically predisposed individuals, with the follicular unit increasingly recognized as the putative initial target. T helper 17/T helper 1-skewed inflammation and exaggerated inflammasome activation lead to a dysregulated neutrophil-dominant milieu with high levels of tumor necrosis factor-α, interleukin (IL)-1β, IL-1α, IL-8, IL-12, IL-15, IL-17, IL-23, and IL-36. Low-evidence studies and a lack of validated diagnostic and response criteria have hindered the discovery and validation of new effective treatments for pyoderma gangrenosum. We review established and emerging treatments for pyoderma gangrenosum. A therapeutic algorithm based on available evidence is also provided. For emerging treatments, we review target molecules and their role in the pathogenesis of pyoderma gangrenosum.

Targeted interleukin‐12 inhibition in peristomal pyoderma gangrenosum

“…3 The use of the interleukin-12 (IL-12) and interleukin 23 (IL-23) inhibitor ustekinumab is increasing due to the importance of IL-23 inhibition in PG and IBD; however, the role of IL-12 remains overlooked. 4 Here, we report a patient with PPG and concomitant IBD unresponsive to TNF inhibition who showed IL-12B overexpression in the perilesional dermis successfully treated with ustekinumab.…”

Refractory Pyoderma Gangrenosum: Stabilized on Colchicine and Tumor Necrosis Factor (TNF) Inhibitor

“…Hence, it can be associated with systemic diseases like inflammatory bowel disease, arthritis, and hematological disorders, sometimes leading to choosing one medication over the other [ 6 , 7 ]. Treatment of PG remains challenging, and, to date, no guidelines have been established [ 2 , 8 ].…”

“…Additionally, PG may manifest with bullous, vegetative, peristomal, or extracutaneous lesions [ 1 ]. PG is an uncommon condition with an incidence between three and 10 per million individuals yearly [ 2 ]. The etiology, pathophysiology, and optimal treatment remain unclear.…”

“…As PG is considered an inflammatory process, systemic corticosteroid therapy is the first-line therapy. Unfortunately, there is a 40% risk of relapse after complete remission [ 2 ]. Consequently, tapering corticosteroids with a steroid-sparing agent have been shown to prevent relapse [ 4 ].…”

“…Consequently, tapering corticosteroids with a steroid-sparing agent have been shown to prevent relapse [ 4 ]. Colchicine has been shown to be effective in treating neutrophilic dermatoses, such as Sweet syndrome and Behcet's disease, making it a valuable option for controlling PG [ 2 ].…”