Comment
Skin biopsies and tissue cultures were strongly recommended (>90% survey respondents) for the initial evaluation of lesions suspected to be PG to evaluate for typical histopathologic changes that appear early in the disease, to rule out PG mimickers such as infectious or vascular causes, and to prevent the detrimental effects of inappropriate treatment and delayed diagnosis.5
Suspected PG warrants a reasonable search for related conditions because more than 50% of PG cases are associated with comorbidities such as rheumatoid arthritis, inflammatory bowel disease, and hematologic disease/malignancy.6,7 A complete blood cell count and comprehensive metabolic panel were recommended by most respondents, aiding in the preliminary screening for hematologic and infectious causes as well as detecting liver and kidney dysfunction associated with systemic conditions. Additionally, exclusion of infection or malignancy may be particularly important if the patient will undergo systemic immunosuppression. In challenging PG cases when initial findings are inconclusive and the clinical presentation does not direct workup (eg, colonoscopy to evaluate gastrointestinal tract symptoms), serum protein electrophoresis, hepatitis panel, rheumatoid factor, antinuclear antibodies, and antineutrophilic antibody tests also were frequently ordered by respondents to further evaluate for underlying or associated conditions.
This consensus regarding skin biopsies and certain ancillary tests is consistent with the proposed diagnostic criteria for classic ulcerative PG in which the absence or exclusion of other relevant causes of cutaneous ulcers is required based on the criteria.8 The importance of ensuring an accurate diagnosis is paramount, as a 10% misdiagnosis rate has been documented in the literature.5
Importantly, a stepwise diagnostic workup for PG is proposed based on survey results, which may limit unnecessary testing and the associated costs to the health care system (Figure 1). Selection of additional testing is guided by initial test results and features of the patient’s clinical presentation, including age, review of systems, and associated comorbidities. Available data suggest that underlying inflammatory bowel disease is more frequent in PG patients who are younger than 65 years, whereas those who are 65 years and older are more likely to have inflammatory arthritis, cancer, or an underlying hematologic disorder.9
Figure 1. Proposed stepwise algorithm of classic ulcerative pyoderma gangrenosum workup. H&E indicates hematoxylin and eosin; SPEP, serum protein electrophoresis; ANA, antinuclear antibody; ANCA, antineutrophilic antibody; ESR, erythrocyte sedimentation rate; CRP, C-reactive protein; HIV, human immunodeficiency virus. Asterisk indicates ≥80% of respondents reported routinely ordering; dagger, 60%–79% of respondents; double dagger, 40%–59% of respondents.
Treatment of PG should address both the inflammatory and wound components of the disease (Figure 2).7 In our survey results, systemic corticosteroids were identified as an important first-line therapy supported by reasonable evidence and were favored for their rapid response and minimal cost.1,10,11 Many respondents endorsed the use of systemic therapy in combination with topical steroids or calcineurin inhibitors. Combination therapy may provide more immediate control of rapidly progressing disease while minimizing adverse effects of long-term systemic corticosteroid use. A survey of German wound experts similarly endorsed frequent use of topical calcineurin inhibitors and combination systemic and topical glucocorticoid therapy as common therapeutic approaches.1
Figure 2. Proposed stepwise algorithm for the treatment of classic ulcerative pyoderma gangrenosum. IBD indicates inflammatory bowel disease. Asterisk indicates ≥90% of respondents reported routinely ordering; dagger, 60%–89% of respondents reported routinely ordering; double dagger, 40%–59% of respondents; section, 30%–39% of respondents.
Importantly, treatments may vary depending on patient characteristics, comorbidities, and underlying disease, which underscores the need for individualized treatment approaches. Alternative first-line systemic treatments favored by respondents were cyclosporine, biologic medications, and antineutrophilic agents such as dapsone. Cyclosporine has demonstrated comparable efficacy to systemic glucocorticoids in one RCT and is considered an important steroid-sparing alternative for PG treatment.2 Biologic agents, especially tumor necrosis factor inhibitors, may be effective in treating cases of refractory PG or for concomitant inflammatory bowel disease management, as demonstrated by a small RCT documenting improvement of PG following infliximab infusion.3
Respondents strongly recommended petrolatum-impregnated gauze and other nonadhesive dressings, including alginate and hydrocolloid dressings, as part of PG wound care. Topical antimicrobials and compression stockings also were recommended by respondents. These practices aim to promote moist environments for healing, avoid maceration, prevent superinfection, optimize wound healing, and minimize damage from adhesive injury.12 Wound debridement and grafting generally were not recommended. However, pathergy is not a universal phenomenon in PG, and wounds that are no longer in the inflammatory phase may benefit from gentle debridement of necrotic tissue and/or grafting in select cases.10
Conclusion
An approach to modifying PG management based on clinical presentation and the practice of combination therapy with multiple systemic agents in refractory PG cases was not addressed in our survey. The low response rate is a limitation; however, the opinions of 51 medical dermatologist experts who regularly manage PG (in contrast to papers based on individualized clinical experience) can provide important clinical guidance until more scientific evidence is established.
Acknowledgments
We would like to thank the SDH and RDS membership for their participation in this survey. We especially acknowledge the other members of the SDH Scientific Task Force for their feedback: Misha Rosenbach, MD (Philadelphia, Pennsylvania); Robert G. Micheletti, MD (Philadelphia, Pennsylvania); Karolyn Wanat, MD (Milwaukee, Wisconsin); Amy Chen, MD (Cromwell, Connecticut); and A. Rambi Cardones, MD (Durham, North Carolina).