Dear Editor,
Pyoderma gangrenosum (PG) is a neutrophilic ulcerative dermatosis marked by increased healthcare utilization and delayed healing outcomes.1 Our previous research has shown that a history of thromboembolism prolongs healing time among PG patients.2 However, despite PG’s recognized association with other systemic diseases, the impact of these comorbidities on PG-related healing outcomes remains unexplored. In this single-center case-control study, we evaluate the relative healing concerning all comorbidities associated with PG and delayed wound healing.
This study was reviewed and approved by the OHSU IRB #16753. Data was prospectively collected between December 2019 and February 2024. Inclusion criteria was defined as patients with classic, ulcerative PG with a PARACELSUS score of ≥10 from the OHSU PYGAS Registry.3 Data on patient demographics and subsequent wound size reduction at 6-months, 9-months, and 1-year were collected. PG-related and wound healing comorbidities were confirmed with additional chart review. PG-related comorbidities were defined as having a history of autoimmune or inflammatory disorders, rheumatoid arthritis, psoriatic arthritis, inflammatory bowel disease (IBD), and hidradenitis suppurativa.4 Wound healing comorbidities included a history of smoking, diabetes mellitus, deep-vein thrombosis, obesity, peripheral artery insufficiency (PAI), and venous insufficiency (VI).4 Chi-squared tests were utilized to compare demographic data amongst groups with and without various comorbidities. Logistic regression and Kaplan-Meier survival analysis were applied to assess the impact of having up to two PG-associated or wound healing associated comorbidities on healing outcomes. Combinations of comorbidities were limited to two, since most patients had 0–2 PG-related comorbidities (117 patients, 100%) and 0–2 wound healing comorbidities (102 patients, 87%).
In total, 117 patients met inclusion criteria, and 144 total ulcers were analyzed. The mean presenting age was 53 (SD +/− 17), with a majority being female (88 patients, 75%) (Table I). The most common PG-related comorbidities were a history of IBD (26 patients, 22%) and history of autoimmune or inflammatory disorder (9 patients, 7.7%) (Table I). The most common wound healing comorbidities were a history of smoking (51 patients, 44%) and obesity (69 patients, 59%) (Table I). 87 (60%) ulcers were healed at 6-months, 111 (77%) ulcers were healed at 9-months, and 121(84%) ulcers were healed at the 1-year mark.
Table I.
Participant demographics and comorbidities.
| Participant characteristic | N (%) |
|---|---|
| Sex | |
| Male | 29 (25%) |
| Female | 88 (75%) |
| Reported Ancestry and Ethnicity | |
| White | 72 (62%) |
| Black or African American | 2 (1.7%) |
| Hispanic or Latino | 3 (2.6%) |
| Asian | 1 (0.9%) |
| Unreported | 39 (33%) |
| PG-related comorbidities | |
| History of Autoimmune/Inflammatory Disorders | 9 (7.7%) |
| History of Rheumatoid Arthritis | 4 (3.4%) |
| History of Psoriatic Arthritis | 2 (1.7%) |
| History of Inflammatory Bowel Disease | 26 (22%) |
| History of Hidradenitis suppurativa | 4 (3.4%) |
| Wound-healing comorbidities | |
| History of Smoking | 51 (44%) |
| History of Diabetes Mellitus | 17 (15%) |
| History of Deep-vein Thrombosis | 15 (13%) |
| History of Obesity | 69 (59%) |
| History of Peripheral Artery Insufficiency | 2 (1.7%) |
| History of Venous Insufficiency | 7 (6.0%) |
| Number of PG-related comorbidities | |
| 0 | 80 (68%) |
| 1 | 29 (25%) |
| 2 | 8 (6.8%) |
| Number of Wound-healing comorbidities | |
| 0 | 18 (15%) |
| 1 | 55 (47%) |
| 2 | 29 (25%) |
| 3 | 12 (10%) |
| 4 | 3 (2.6%) |
Logistic regression at 6-months, 9-months, and 1-year demonstrated significantly decreased odds of healing at all 3 time points in patients with ≥2 wound healing comorbidities (P = .031). Kaplan-Meier survival analysis also demonstrated that at all 3 time points, patients with ≥2 wound healing comorbidities had significantly longer healing intervals (P = .02) (Figure 1). Patients with only 1 wound healing comorbidity and patients with 1 or 2 PG-associated comorbidities did not have significantly impacted healing. Confounders that may have influenced healing time such as treatment strategy were also adjusted for and were not found to significantly impact healing time.
Figure 1.
Kaplan-Meier curve showing a statistically significant difference in wound healing outcomes at 6 months, 9 months, and 1 year in patients with ≥ 2 wound healing comorbidities.
These novel findings demonstrate that wound healing comorbidities affect healing outcomes in PG patients and may be even more clinically relevant than PG-associated comorbidities.5 Such findings underscore the need to incorporate comorbidity screenings into clinical evaluations and clinical trials to identify PG patients at greater risk of failing medical interventions. While further efforts are needed to establish standardized methods for detecting and addressing underlying conditions that might affect healing outcomes in PG, our results emphasize the need for implementing proactive comorbidity management along with therapeutic interventions in improving treatment outcomes.
Funding Statement:
Dr. Alex Ortega-Loayza is supported by NIAMS R01AR083110. Other authors have no funding support.
Disclosures:
Dr. Alex Ortega-Loayza has served in advisory boards for Janssen, BMS, and Behringer Ingelheim, and as a consultant for Genentech and Guidepoint. He has also received research grants from Eli Lilly Company, OHSU School of Medicine Gerlinger research award, and Medical Research Foundation of Oregon. Other authors have no interests to disclose. He is supported by NIAMS R01AR083110.
Footnotes
Ethical Approval Statement: Reviewed and approved by Oregon Health & Science University IRB; approval #16753
Ethics Statement: This investigation was part of the Pyoderma Gangrenosum Study at OHSU (IRB 16753), for which identifiable information required written informed consent.
Availability of data:
The data that support the findings of this study are available from the corresponding author upon reasonable request.
References:
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Data Availability Statement
The data that support the findings of this study are available from the corresponding author upon reasonable request.