Use of dermal injection of activated protein C for treatment of large chronic wounds secondary to pyoderma gangrenosum

Kapila, Shivam; Reid, Ian A.; Dixit, Shreya; Fulcher, Greg; March, Lyn; Jackson, Chris; Cooper, Alan

doi:10.1111/ced.12361

Cited by 18 publications

(14 citation statements)

References 20 publications

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“…A notable example is activated protein C (APC), which was first discovered for its more well-known activities in anticoagulation but has since demonstrated potent pleiotropic anti-inflammatory and cytoprotective properties [83]. A number of preclinical and pilot clinical trials have demonstrated very promising results to support APC’s use in chronic wounds [84,85,86,87,88,89,90,91]. …”

Section: Future Prospectsmentioning

confidence: 99%

Inflammation in Chronic Wounds

Zhao

Liang

Clarke

et al. 2016

IJMS

797

589

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Non-healing chronic wounds present a major biological, psychological, social, and financial burden on both individual patients and the broader health system. Pathologically extensive inflammation plays a major role in the disruption of the normal healing cascade. The causes of chronic wounds (venous, arterial, pressure, and diabetic ulcers) can be examined through a juxtaposition of normal healing and the rogue inflammatory response created by the common components within chronic wounds (ageing, hypoxia, ischaemia-reperfusion injury, and bacterial colonisation). Wound bed care through debridement, dressings, and antibiotics currently form the basic mode of treatment. Despite recent setbacks, pharmaceutical adjuncts form an interesting area of research.

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Section: Future Prospectsmentioning

confidence: 99%

Inflammation in Chronic Wounds

Zhao

Liang

Clarke

et al. 2016

IJMS

797

589

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“…More recently, intralesional activated protein C and timolol gel, already used in chronic venous and diabetic ulcers, showed promising results. 49,50 It is important to highlight the equal importance of treating the inflammatory state, balanced with optimized wound care. 51 Therefore, wound dressing is particularly important, since most ulcers show heavy exudates.…”

Section: Topical Treatmentmentioning

confidence: 99%

Pyoderma gangrenosum: challenges and solutions

Gameiro¹,

Pereira²,

Cardoso³

et al. 2015

OTT

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Pyoderma gangrenosum (PG) is a rare disease, but commonly related to important morbidity. PG was first assumed to be infectious, but is now considered an inflammatory neutrophilic disease, often associated with autoimmunity, and with chronic inflammatory and neoplastic diseases. Currently, many aspects of the underlying pathophysiology are not well understood, and etiology still remains unknown. PG presents as painful, single or multiple lesions, with several clinical variants, in different locations, with a non specific histology, which makes the diagnosis challenging and often delayed. In the classic ulcerative variant, characterized by ulcers with inflammatory undermined borders, a broad differential diagnosis of malignancy, infection, and vasculitis needs to be considered, making PG a diagnosis of exclusion. Moreover, there are no definitively accepted diagnostic criteria. Treatment is also challenging since, due to its rarity, clinical trials are difficult to perform, and consequently, there is no "gold standard" therapy. Patients frequently require aggressive immunosuppression, often in multidrug regimens that are not standardized. We reviewed the clinical challenges of PG in order to find helpful clues to improve diagnostic accuracy and the treatment options, namely topical care, systemic drugs, and the new emerging therapies that may reduce morbidity.

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“…In another case report, a woman, who had previously developed anaphylaxis following intravenous treatment with TNFα antibodies, showed complete resolution of PG lesions with topical application of infliximab gel . Intralesional administration of triamcinolone acetonide and activated protein C both resulted in a clinical response in two patients.…”

Section: Topical and Intralesional Treatment Optionsmentioning

confidence: 95%

Treatment options for pyoderma gangrenosum

Quist

Kraas

2017

J Deutsche Derma Gesell

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SummaryPyoderma gangrenosum (PG) is an orphan disease. While research on such disorders is based on only few randomized multicenter as well as retrospective studies, most of the data comes from case series of small patient groups. Apart from topical and intralesional therapeutic options for early stages and mild disease courses, treatment predominantly involves systemic therapeutic agents. Besides systemic corticosteroids and cyclosporine A (CsA), options also include intravenous immunoglobulins (IVIG) and biologics such as the TNF α inhibitors infliximab, adalimumab, and etanercept; the interleukin (IL) 12/23 antibody ustekinumab; the IL-1 receptor antagonist anakinra; and the IL-1 β antibody canakinumab. The best evidence-based study data is available for CsA, prednisolone, and infliximab; the latter especially in patients with concomitant ulcerative colitis or Crohn's disease. A response to IVIG and canakinumab has been reported in smaller case series. First described by Brocq almost 100 years ago, it was soon recognized that PG did in fact require treatment. To this day, however, such treatment remains a clinical challenge. Despite the severe -albeit rare -clinical picture, improvement in therapeutic options may be expected in the future, primarily due to further clinical studies -especially with a greater number of patients, a better understanding of the etiopathogenesis, as well as the use of modern targeted therapies with higher efficacy and a lower rate of side effects than conventional immunosuppressants such as prednisolone and CsA.

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Use of dermal injection of activated protein C for treatment of large chronic wounds secondary to pyoderma gangrenosum

Abstract: Although this study has limited because of its small sample size and lack of a true placebo group, it does indicate that APC has potential as a therapeutic option for patients with chronic skin ulcers from PG.

Cited by 18 publications

References 20 publications

Inflammation in Chronic Wounds

Inflammation in Chronic Wounds

Pyoderma gangrenosum: challenges and solutions

Treatment options for pyoderma gangrenosum

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