Croitoru, Kenneth

ABSTRACT Background Pyoderma gangrenosum (PG) is a rare neutrophilic dermatosis highly associated with systemic comorbidities. Accurate diagnosis and treatment remain challenging due to its rarity and clinical mimickers. Objectives To evaluate demographic, clinical features and treatment outcomes in patients referred with suspected PG at a tertiary wound care centre. Methods A prospective observational study was conducted of patients referred for suspected PG between April 2021 and June 2023. Demographic, clinical and laboratory data, including biopsies and tissue cultures, were collected. Patients were categorised as having PG vs alternative diagnoses based on diagnostic criteria from Su, Maverakis and the PARACELSUS score. Results Of 60 patients (female, 51.7%; mean [SD] age 52.9 [14.0] years), 44 (73.3%) met at least one published diagnostic criterion for PG. The most common comorbidity was IBD (63.6%), followed by inflammatory arthritis (25.0%) and monoclonal gammopathy of undetermined significance (MGUS) (4.5%). Systemic corticosteroids were used by 40.9% of patients before referral, but steroid‐sparing agents and biologics were the primary treatments after consultation. Biologics and steroid‐sparing agents were associated with significant improvement in disease activity using the PGA score (average score decreased from 2.3 to 1.5, p < 0.005), with 40.9% achieving complete remission. Elevated serum inflammatory markers and faecal calprotectin were observed in PG patients but absent in non‐PG cases. Conclusions These prospective data support previously published rates of association between PG and systemic comorbidities. Steroid‐sparing anti‐neutrophilic and targeted therapies are effective steroid‐sparing strategies in managing PG. Small sample size and referral bias may limit generalisability.

Abstract Background Biomarkers for predicting the development of Ulcerative Colitis (UC) and disease-related complications are lacking. Anti-integrin αvβ6 IgG autoantibodies (anti-αvβ6) have been recently described in patients diagnosed with UC. Here, we sought to determine if anti-αvβ6 autoantibodies predate UC development and to study associations between anti-αvβ6 and disease outcomes in newly diagnosed UC patients. Methods In a unique pre-clinical IBD cohort from the PRoteomic Evaluation and Discovery in an IBD Cohort of Tri-service Subjects (PREDICTS), anti-αvβ6 were measured in longitudinal pre-diagnosis serum samples from 82 subjects who later developed UC as well as in 82 matched subjects that did not develop IBD (HC). Sample A was at the time of UC diagnosis, Sample B was at a median of 2 years before Sample A, Sample C was at a median of 4 years before Sample A and Sample D was at a median of 10 years before Sample A. In a distinct, external validation cohort (the Crohn’s and Colitis Canada Genetics Environment Microbial (GEM) Project), we tested samples from 12 subjects who later developed UC and compared those with 49 matched subjects who remained asymptomatic. Further, anti-αvβ6 were measured in 2 incident IBD cohorts (COMPASS, n=55 and OSCCAR, n=104 UC subjects) and associations between anti-αvβ6 and adverse UC-outcomes were defined using Cox proportional-hazards model. Results Anti-αvβ6 were significantly higher in the PREDICTS cohort among individuals who developed UC compared to HC up to 10 years prior to diagnosis (Figure 1A). The anti-αvβ6 seropositivity was 12.2% 10 years before diagnosis and increased to 52.4% at the time of diagnosis in subjects who developed UC compared with 2.7% in controls across the 4 timepoints. Additionally, the predictive performance of anti-αvβ6 autoantibodies as assessed via area under the receiver operator curves (AUROC) with 10-fold cross validation was at least 0.8 up to 10 years before diagnosis (Figure 1B). Elevated levels of anti-αvβ6 in pre-clinical UC samples were further validated in the GEM cohort (Figure 1C). Finally, high anti-αvβ6 were associated with a composite of adverse UC-outcomes including hospitalization, disease extension, colectomy, systemic steroid use and/or escalation to biologic therapy in both incident cohorts (Figure 1D). Conclusion Anti-integrin αvβ6 autoantibodies precede the clinical diagnosis of UC by up to 10 years and are associated with adverse UC-related outcomes.