Neutrophil extracellular traps formation in the lesional skin of various types of pyoderma gangrenosum

Pyoderma gangrenosum (PG) is a chronic neutrophilic disorder characterized by recurrent painful ulcers. Aseptic inflammation by neutrophils plays an essential role, and neutrophil extracellular traps (NETs) formation can contribute to the pathogenesis of PG. Seventy-five patients were diagnosed as having PG in our department, among which 58 ulcerative, 4 bullous, 3 pustular and 10 vegetative type. We examined the 20 skin biopsy specimens (11 ulcerative, 3 bullous, 2 pustular and 4 vegetative type), and local NETs formation in various types of PG was compared among each type. The biopsied specimens were double labelled for myeloperoxidase, citrullinated histone H3. Immunofluorescent images indicated that the histopathologic location and depth of NETs formation in PG varied by the clinical subtypes. In ulcerative PG, NETs formation was observed in the upper to deep dermis. In bullous PG, NETs formation was mainly observed in the epidermis. Pustular type showed NETs formation in the epidermis near the pustules, and in vegetative type, showed NETs formation mainly in the upper dermis. These results indicate that NETting neutrophils play an important role in the pathogenesis of various forms of PG, although the location and depth of NETs formation in the skin lesion of PG differ depending on each type. Further studies are necessary to examine what factors identify different clinical features of PG.