Pyoderma gangrenosum: A systematic review of the molecular characteristics of disease

Abstract

Pyoderma gangrenosum is a painful recurrent ulcerative neutrophilic dermatosis in which the pathogenesis is incompletely defined. Current evidence suggests that PG is associated with dysregulation of components of both the innate and adaptive immune system with dysregulation of neutrophil function and contribution of the Th17 immune axis. PG can be present in numerous heterogeneous clinical presentations and be associated with multiple inflammatory conditions including rheumatoid arthritis, inflammatory bowel disease and hidradenitis suppurativa. However, no critical evaluation of the observed molecular characteristics in PG studies in association with their clinical findings has been assessed. Additionally, emerging evidence suggests a potential role for other cell types and immune pathways including B cells, macrophages, autoantibodies and the complement system in PG, although these have not yet been integrated into the pathogenesis of disease. This systematic review aims to critically evaluate the current molecular observations regarding the pathogenesis of PG and discuss associations with clinical characteristics as well as the evidence supporting novel cell types and immune pathways in PG.

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

“…A broad autoantibody response, also against neutrophil extracellular traps, has been documented in serum and skin from patients with hidradenitis suppurativa, associating with immune complex generation and macrophage activation [ 133 ]. Similar mechanisms may occur in PG [ 21 ]. Rituximab is a monoclonal antibody that targets CD20, an antigen expressed at most stages of B-cell development.…”

“…Unsurprisingly, trauma (i.e., pathergy) is among the best documented trigger factors of PG, as it entails the release of PG-driving cytokines such as IL-36 and IL-8 from keratinocytes, an event that may be sufficient in the setting of concurrent genetic predisposition [ 1 ]. Complement system, and particularly neutrophil-attractant anaphylatoxin C5a [ 18 , 19 ], NETosis, regulatory T-cell unbalance [ 20 ], B cells as well as fibroblasts and monocytes/macrophages all add to the multi-layered pathophysiology of PG [ 21 ].…”

Pioderma gangrenoso y colitis ulcerativa. Reporte de Caso

“…Históricamente se ha contemplado que hasta la mitad de los pacientes con pioderma gangrenoso pueden cursar con otra patología asociada, siendo la enfermedad inflamatoria intestinal la más descrita, seguido por la artropatía inflamatoria, vasculitis y patologías hematológicas (5) . En la revisión realizada por Flora A et al, de los pacientes que cursaron con comorbilidad inflamatoria, 50,8% corresponden a enfermedad inflamatoria intestinal 11,8% artritis reumatoide, 6,7% fibrosis quística, 16% con alteraciones hematológicas (6) .…”

“…También, contribuye la respuesta anormal mediada por neutrófilos, inducida por activación de Th17 y sobreproducción de Interleucina 1β (IL-1β) inducida por inflamosomas, concordando con los hallazgos histopatológicos de infiltrado de neutrófilos y clínicamente con lesiones que progresan rápida a ulceración (8) . En biopsias de lesiones de pioderma gangrenoso se encontró mayor nivel de Interleucina 8 (IL8 o CXCL8) y factor de necrosis tumoral, IL8 es un agente quimiotáctico de neutrófilos, que puede ser secretado por múltiples células incluyendo fibroblastos dérmicos, células endoteliales, linfocitos T y macrófagos (6). También se han encontrado niveles séricos altos de factor de crecimiento de colonias de granulocitos (G-CSF) en pacientes con pioderma gangrenoso activo y también se han descrito casos de pioderma en pacientes que han recibido G-CSF como parte de tratamiento de alteraciones hematológicas, que desarrollan lesiones de pioderma posterior a la administración, considerándose el G-CSF como parte de la patogenia (9) .…”

“…A pesar de la existencia de criterios clínicos diagnósticos, no existe un estándar de oro para el diagnóstico, considerándose un diagnóstico de exclusión al haber descartado otras causas de úlceras cutáneas (6,14) .…”