Pyoderma Gangrenosum: An Update on Pathophysiology, Diagnosis and Treatment

Abstract

Pyoderma gangrenosum (PG) is a rare inflammatory neutrophilic disorder with prototypical clinical presentations. Its pathophysiology is complex and not fully explained. Recent information regarding the genetic basis of PG and the role of auto-inflammation provides a better understanding of the disease and new therapeutic targets. PG equally affects patients of both sexes and of any age. Uncontrolled cutaneous neutrophilic inflammation is the cornerstone in a genetically predisposed individual. Multimodality management is often required to reduce inflammation, optimize wound healing, and treat underlying disease. A gold standard for the management of PG does not exist and high-level evidence is limited. Multiple factors must be taken into account when deciding on the optimum treatment for individual patients: location, number and size of lesion/ulceration(s), extracutaneous involvement, presence of associated disease, cost, and side effects of treatment, as well as patient comorbidities and preferences. Refractory and rapidly progressive cases require early initiation of systemic therapy. Newer targeted therapies represent a promising pathway for the management of PG, and the main focus of this review is the management and evidence supporting the role of new targeted therapies in PG.

Epidemiology of pyoderma gangrenosum: Results from an Italian prospective multicentre study

“…There is no gold standard in the therapy of PG, but our findings mostly adapt to the indications of other authors . First, we underline the importance of using topical and/or intralesional corticosteroids (used in 54.7% of cases in our study): acting on the pathophysiology of the ulcer, they are particularly effective in treating the indolent, localised, and smaller forms of PG or, in association with systemic therapy, the progressive and malignant cases.…”

“…PG is associated with other conditions in 50% to 75% of patients; these conditions may occur prior to, concurrently with, or following the diagnosis of PG. The most frequent association is with inflammatory bowel disease (IBD) and less frequently with arthritis and haematological disorders . In a retrospective multicentre study, a significant association between PG and metabolic/endocrinological diseases is also described.…”

“…Subsequently, it was recognised as a neutrophilic dermatosis, primarily typified by aseptic neutrophilic infiltration and systemic inflammation . Current research suggests that neutrophil dysfunction, a clonal T expansion, elevated levels of inflammatory mediators (IL 17, IL 23), and genetic predisposition plays a role in PG progression . There are currently 4 widely recognised subtypes of PG: classic (ulcerative), bullous, pustular, and vegetative .…”

“…There is no gold standard for treatment of PG; it varies from patient to patient and even varies at different times for the individual patient. Optimal management may include: recognition and avoidance of triggers; appropriate wound care; adequate pain management; treatment of underlying conditions; discontinuation of the suspected drug in case of drug‐induced PG; and topical, systemic, and targeted immunomodulatory therapies …”

Old but Gold: The Importance of Medical History in Diagnosing Neutrophilic Dermatoses Characterized by Pathergy. A Case of Pyoderma Gangrenosum

“…Pyoderma Gangrenosum (PG) is a neutrophilic dermatosis which typically presents with painful exudating ulcers, with infiltrated and actively inflamed violaceous borders [1]. One helpful clinical feature for diagnosing active PG may be the presence of "pathergy" or the occurrence of lesions at sites of trauma, in up to 30% of the patients [2][3][4].…”