Pyoderma Gangrenosum: An Update on Pathophysiology, Diagnosis and Treatment

Afsaneh Alavi; Lars E. French; Mark D. Davis; Alain Brassard; Robert S. Kirsner

Disclosures

Am J Clin Dermatol. 2017;18(3):355-372. 

In This Article

Abstract and Introduction

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.

Introduction

Pyoderma gangrenosum (PG) is a prototypic autoinflammatory neutrophilic dermatosis characterized by a spectrum of clinical presentations with variable courses, and has an increased cytokine and chemokine expression in lesional skin.[1,2] PG is considered a 'diagnosis of exclusion' due to the lack of definitive laboratory or histopathological diagnostic criteria and is thus frequently misdiagnosed.[3] Several factors contribute to the pathophysiology of PG. The patient's genetic background likely alters the immune response affecting both innate and adaptive immune systems, and the aberrant activation of innate-immune complexes termed 'inflammasomes' leads to increased levels of cytokines that contribute to neutrophilic tissue infiltration. Evidence-based management of patients with PG is limited by the paucity of randomized controlled trials to support treatment outcomes. Treatment options are therefore largely based on expert opinion and anecdotal data from available case reports, small case studies, and a handful of randomized clinical trials (RCTs).[4,5] Emerging evidence, coupled with improved understanding of PG pathophysiology, suggest potential targets for therapy. This review provides an update on the clinical presentation, complex pathophysiology, and diagnosis and management of PG.

Comments

3090D553-9492-4563-8681-AD288FA52ACE

processing....