Pyoderma gangrenosum with increased levels of serum cytokines

Abstract

A 66-year-old woman presented after an episode of accidental trauma with a painful ulcer on her scalp which rapidly enlarged in size, accompanied by central necrosis and undermining ulceration. The patient's past history was negative for underlying systemic disease, although she had had a similar post-traumatic intractable leg ulcer 3 years prior, which was unresponsive to surgical management but successfully treated with systemic steroids. A biopsied specimen from the scalp showed marked neutrophilic infiltrates in the dermis, compatible with a diagnosis of pyoderma gangrenosum (PG). The large ulcerative lesion responded very well to oral steroid therapy, showing rapid epithelialization. Serum levels of granulocyte colony-stimulating factor and interleukin-6 were significantly elevated prior to treatment, with decrease to normal levels after treatment. Serum tumor necrosis factor (TNF)-α and granulocyte macrophage colony-stimulating factor levels were within normal limits. The significance and pathogenic role of cytokine burst in PG is reviewed and discussed.

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

“…G‐CSF has also been identified to be elevated in the serum of a patient with PG, which could explain increased activation and prolonged survival of neutrophils seen in this condition, 26 although further mechanistic data are required. Interestingly, there have been reports of patients who have developed PG after receiving G‐CSF as part of their chemotherapy treatment for malignancies, thus supporting the role of G‐CSF in the pathogenesis of PG 27,28 …”

“…Furthermore, an increased expression of genes involved in the complement pathway has been identified within the perilesional dermis of patient with PG, 24 with C5a in particular being purported to function through self-amplification of neutrophil activity. 25 G-CSF has also been identified to be elevated in the serum of a patient with PG, which could explain increased activation and prolonged survival of neutrophils seen in this condition, 26 although further mechanistic data are required. Interestingly, there have been reports of patients who have developed PG after receiving G-CSF as part of their chemotherapy treatment for malignancies, thus supporting the role of G-CSF in the pathogenesis of PG.…”

Pyoderma Gangrenosum: A Current Problem as Much as an Unknown One

“…Several immune-mediates abnormalities have been proposed, including complement deficiencies, 11 deposition of immunoglobulins in the dermal blood vessels with monoclonal or polyclonal hyperglobulinemia, 12,13 aberrant neutrophil trafficking through overexpression of cell surface integrins CR3 and CR4, 14 increased serum levels of interleukin-8 (IL-8), granulocyte colony-stimulating factor, and IL-6. 15-17 IL-23, already associated with Crohn’s disease, may also play a critical role, as confirmed by good results with anti-IL-23 monoclonal antibody ustekinumab. 18,19 Recently, as adjunctive pathogenic mechanism, it has been observed an overexpression of chemokine receptors associated to lymphocytes Th1 (CCR5+) and Th17 (CCR6+) with a downregulation of Th2 (CCR4+).…”

Pyoderma gangrenosum preceding the onset of extranodal natural killer/T-cell lymphoma

“…Some authors have suggested that increased levels of serum cytokines and chemoattractants have a role in the pathogenesis of PG in the setting of underlying hematological diseases. [ 10 , 11 ] Masuda et al reported that increased production of interleukin (IL)-8 by the tumor cells of anaplastic large cell lymphoma may be a potent activator of neutrophils and may cause neutrophilic inflammation contributing to the pathogenesis of PG. [ 11 ] Furthermore, the production of IL-8 and other chemoattractants by tumor cells in the serum of patients with PG was reported.…”