Tratamientos sistemáticos para Pioderma Gangrenoso.

Effectiveness of Systemic Treatments for Pyoderma Gangrenosum

The British Journal of Dermatology

TAKE-HOME MESSAGE

• The authors of this review of 41 studies evaluated systemic treatments for pyoderma gangrenosum. Similar efficacy for corticosteroids, cyclosporine, and infliximab was found in two randomized controlled studies. In other observational studies it was found that systemic steroids in combination with dapsone, cyclosporine, clofazimine, and cyclophosphamide, as well as adalimumab, canakinumab, and azathioprine were effective.

• Systemic corticosteroids, cyclosporine, and infliximab are the most studied treatments for pyoderma gangrenosum and have similar efficacy.

  – Anna Wile, MD

 Dermatology

Written by

 

 

David Fivenson MD

Pyoderma gangrenosum (PG) is an uncommon, painful, neutrophilic dermatosis that is characterized by rapidly enlarging ulcers with rolled violaceous borders. It is most often associated with inflammatory bowel disease (IBD), collagen vascular diseases (CTDs), monoclonal gammopathies (MGUS, myeloma), and underlying malignancy; however, many cases have no associated etiology. This article by Partridge et al is a systematic review of multiple databases designed to characterize the relative efficacy of therapies reported as useful in PG. They have analyzed 6130 citations and whittled these down to 375 reports, ranging from case series with a minimum of 5 patients, to larger retrospective and prospective series, to randomized controlled trials (RCTs). The authors' stated goals were to describe which therapies were associated with the best healing times, rates of adverse events (AEs), pain control, quality-of-life (QOL) effects, and recurrence rates.

Their key findings are in the capsule summary, "Systemic corticosteroids, cyclosporine, infliximab and canakinumab had the strongest evidence in treating pyoderma gangrenosum, although overall there are few high-quality studies," The only subgroup analysis was PG in IBD patients, where it seemed that cyclosporin was a little better than corticosteroids compared with other PG presentations. No subgroups of CTD, MGUS, or malignancy patients were reported.

This study is helpful to practicing dermatologist by breaking down the myriad therapies reported for PG, and it helps highlight the overall apparent efficacy of systemic steroids, cyclosporine, infliximab, and the emerging role for IL-1 inhibitors such as canakinumab. The biggest limitations in this review are that many of the patients in the case series had multiple prior or simultaneous therapies and the lack of a standardized tool to quantify disease activity (beyond surface area), such as the PASI in psoriasis and the EASI in atopic dermatitis. There are also no good quality-of-life tools specific for PG.

Curiously, these authors describe PG with a characteristic "undermined and gun metal grey border," whereas most of us learn to recognize PG by its painful, rolled, violaceous borders. This distinction is not trivial, as classic wounds due to dermal processes with secondary epidermal necrosis and ulceration are undermined as the deeper process expands (bottom-up damage). PG is a disease with epidermal and superficial dermal necrosis followed closely by dermal necrosis (top-down damage); thus, it is not usually undermined at the leading edges. The leading edge of a PG lesion is where such things as topical and intralesional steroids work, and systemic inhibitors of IL-1 and TNF-alpha may also target. When this inflammation is gone, the remaining ulcer can often heal with primary wound care while immunosuppressives are tapered or even stopped.

This review also underscores the dearth of RCTs in PG. We should all encourage our colleagues in pharma to pursue RCTs in PG, as it is considered an orphan disease due to its rarity. Unfortunately, one of the few such studies was abruptly terminated recently when the study drug (gevokizumab, an IL-1 inhibitor) was purchased by another company who "killed" further development for PG (ClinicalTrials.gov Identifier: NCT02315417 and NCT02326740).

The British Journal of Dermatology

Effectiveness of Systemic Treatments for Pyoderma Gangrenosum: A Systematic Review of Observational Studies and Clinical Trials

Br J Dermatol 2018 Feb 25;[EPub Ahead of Print], ACR Partridge, JW Bai, CF Rosen, SR Walsh, WP Gulliver, P Fleming 

Abstract

BACKGROUND

Pyoderma gangrenosum (PG) is a neutrophilic dermatosis with substantial morbidity. Currently, there is no consensus on gold-standard treatments.

OBJECTIVES

Our primary objective was to review the effectiveness of systemic therapy for PG.

METHODS

We searched Cochrane Central, Cochrane DSR, EMBASE, MEDLINE, PubMed, and Web of Science for 24 systemic therapies for PG. Primary outcomes were complete healing and clinical improvement; secondary outcomes were time-to-healing and adverse effects.

RESULTS

We found 3,326 citations, of which 375 articles underwent full-text review, and 41 studies met inclusion criteria. There were 704 participants amongst 26 retrospective cohort studies, 3 prospective cohort studies, 7 case series, 1 case-control study, 2 open-label trials, and 2 randomized controlled trials (RCT). Systemic corticosteroids were the most studied (n=32 studies), followed by cyclosporine (n=21), biologics (n=16), and oral dapsone (n=11). One RCT (STOP-GAP, n=121) showed that prednisolone and cyclosporine were similar, with 15-20% complete healing at 6-weeks and 47% at 6-months. Another RCT (n=30) found that infliximab was superior to placebo at 2-weeks (46% vs. 6% response), with 21% complete healing rate at 6-weeks. Two uncontrolled trials showed 60% and 37.5% healing in four months with canakinumab and infliximab, respectively; other data suggest that patients with concurrent IBD may benefit from biologics. The remaining studies were of poor quality and small sample sizes, though supported the use of corticosteroids, cyclosporine, and biologics.

CONCLUSIONS

Systemic corticosteroids, cyclosporine, infliximab, and canakinumab had the most evidence in treating PG. However, current literature is limited to small and lower-quality studies with substantial heterogeneity.