The impact of comorbidity identification on outcomes in patients with pyoderma gangrenosum: A retrospective cohort study of previously hospitalized patients

Abstract

To the Editor: Pyoderma gangrenosum (PG) is a rapidly evolving neutrophilic dermatosis with underlying disease associations.1Maverakis E. Marzano A.V. Le S.T. et al.Pyoderma gangrenosum.Nat Rev Dis Primers. 2020; 6: 81Crossref PubMed Scopus (33) Google Scholar Inflammatory bowel disease (IBD)-associated PG confers improved hospital mortality.2Kaffenberger B.H. Hinton A. Krishna S.G. The impact of underlying disease state on outcomes in patients with pyoderma gangrenosum: a national survey.J Am Acad Dermatol. 2018; 79: 659-663Abstract Full Text Full Text PDF PubMed Scopus (14) Google Scholar This study evaluated whether the presence of an identified PG-associated condition affects outcomes, including wound closure, recurrence, and readmission, in PG patients. A retrospective cohort study of PG patients seen at the Ohio State University Wexner Medical Center was conducted. The PG patients were identified from an inpatient database of dermatology consultations at the Ohio State University Wexner Medical Center from 2011 to 2017. Fifty-five patients with a PARACELSUS score of ≥10, suggesting a likely PG diagnosis,3Jockenhöfer F. Wollina U. Salva K.A. Benson S. Dissemond J. The PARACELSUS score: a novel diagnostic tool for pyoderma gangrenosum.Br J Dermatol. 2019; 180: 615-620Crossref PubMed Scopus (64) Google Scholar were included. Their courses were analyzed. An assessment of the laboratory evaluation to examine predominant comorbidities and mimickers was performed for the following: (1) any of anti-Saccharomyces cerevisiae antibodies, fecal calprotectin, or colonoscopy; (2) rheumatoid factor; (3) antinuclear antibody; (4) any of antineutrophil cytoplasmic, antimyeloperoxidase, or anti-proteinase 3 antibodies; and (5) any of serum immunofixation, serum protein electrophoresis, or blood smear. PG-associated conditions were identified in 39 patients. PG was diagnosed prior to the comorbidity in 38.5% (15/39) of these patients (Table I). Because of a concomitant hematologic malignancy or the need to await testing results, initial systemic treatment was less common in patients with comorbidities than in those without (74.4% vs 100%, respectively, P = .025), and initial targeted local treatment only was more common in patients with comorbidities than in those without (20.5% vs 0%, respectively, P = .050). The standard initial dose for cyclosporine and prednisone was 2-5 mg/kg and ≤1 mg/kg, respectively. No significant statistical differences in treatments administered specifically for PG throughout the follow-up course were identified.Table IDemographic and clinical characteristics, mortality, and follow-up details of hospitalized patients with PG∗The χ2 test was performed for the comparison of proportions.CharacteristicStudy population (n = 55)Demographics Age at the time of index hospitalization (y), mean (SD)48.8 (17.2) Female, n (%)29 (52.7) White, n (%)49 (89.1) Black, n (%)6 (10.9)PARACELSUS score ≥ 10 (high likelihood of PG), n (%)3Jockenhöfer F. Wollina U. Salva K.A. Benson S. Dissemond J. The PARACELSUS score: a novel diagnostic tool for pyoderma gangrenosum.Br J Dermatol. 2019; 180: 615-620Crossref PubMed Scopus (64) Google Scholar55 (100)PG subtype Ulcerative, n (%)49 (89.1) Pustular, n (%)1 (1.8) Bullous, n (%)2 (3.6) Peristomal, n (%)3 (5.5)Pathergy, n (%)33 (60)PG-associated condition identified (n = 39)No PG-associated condition identified (n = 16)P value (α = 0.05)PG-associated condition†Two patients had 2 PG-associated conditions. The first patient had both a solid-organ malignant neoplasm and monoclonal gammopathy of undetermined significance, and the second patient had both hidradenitis suppurativa and hematologic malignancy. IBD, n (%)20 (51.3) Hidradenitis suppurativa, n (%)5 (12.8) Hematologic malignancy, n (%)4 (10.3) Other hematologic diseases, n (%)5 (12.8)Monoclonal gammopathy of undetermined significance, n (%)4 (10.3)Myelodysplastic syndrome, n (%)1 (2.6) Solid-organ malignant neoplasm, n (%)3 (7.7) Inflammatory arthritis, n (%)2 (5.1) Hepatitis C, n (%)1 (2.6) Primary biliary cholangitis, n (%)1 (2.6)PG diagnosed before a PG-associated condition, n (%)15 (38.5)Death during index hospitalization, n (%)01 (6.3).115Death due to a PG complication noted in the OSUWMC EMR, n (%)2 (5.1)2 (12.5).339No follow-up details in the OSUWMC system, n (%)3 (7.7)2 (12.5).573EMR, Electronic medical record; IBD, inflammatory bowel disease; OSUWMC, The Ohio State University Wexner Medical Center; PG, pyoderma gangrenosum.∗ The χ2 test was performed for the comparison of proportions.† Two patients had 2 PG-associated conditions. The first patient had both a solid-organ malignant neoplasm and monoclonal gammopathy of undetermined significance, and the second patient had both hidradenitis suppurativa and hematologic malignancy. Open table in a new tab EMR, Electronic medical record; IBD, inflammatory bowel disease; OSUWMC, The Ohio State University Wexner Medical Center; PG, pyoderma gangrenosum. For 50 patients with follow-up details in the Ohio State University Wexner Medical Center system, the presence of an identified comorbidity was associated with greater ulcer resolution within 1 year (55.6% vs 21.4%, P = .030), greater ulcer resolution throughout the entire follow-up period (66.7% vs 35.7%, P = .047), lower PG recurrence after ulcer resolution (25% vs 80%, P = .019), and less frequent PG-related readmissions (27.8% vs 64.3%, P = .017). Patients with IBD-associated PG also experienced greater ulcer resolution throughout the entire follow-up period than those with other comorbidities (83.3% vs 50%, respectively, P = .034) and those with no identified comorbidities (83.3% vs 35.7%, respectively, P = .006). No significant differences in age, sex, race, or follow-up duration were found between the groups (Table II). Of note, 56% of the patients without an identified comorbidity did not undergo the broad mimicker and comorbidity assessments.Table IICharacteristics and outcomes of hospitalized PG patients with follow-up in the OSUWMC EMR based on the identification of an associated condition∗Statistical analysis: The t test or analysis of variance was used for normally distributed continuous data, Wilcoxon rank-sum test for continuous data with a skewed distribution, and χ2 or Fisher's exact test for proportions. Bold values indicate P ≤ .05.DemographicsPG-associated condition identified (n = 36)No PG-associated condition identified (n = 14)P value (α = 0.05)Age at diagnosis (y), mean (SD)49.6 (18.1)42.1 (14.2).134Female, n (%)20 (55.6)7 (50).723White, n (%)34 (94.4)11 (78.6).093Black, n (%)2 (5.6)3 (21.4)Initial ulcer number (n = 31), median (IQR)1 (1)1 (1).883Ulcer resolution During hospitalization, n (%)00†No P value reported due to insufficient sample size to determine statistical significance. During time in the OSUWMC system, n (%)24 (66.7)5 (35.7).047 Within 30 d from initial presentation, n (%)2 (5.6)0.368 Within 365 d from initial presentation, n (%)20 (55.6)3 (21.4).030 Time to ulcer resolution (d), median (IQR)111 (167)283 (531).051PG recurrence after resolution (n = 29), n (%)6 (25)4 (80).019PG resolution to recurrence time (d), median (IQR)108 (330.8)86.5 (580.8)†No P value reported due to insufficient sample size to determine statistical significance.PG-related readmission, n (%)10 (27.8)9 (64.3).017Time to readmission (d), median (IQR)84 (561)76 (378).621Follow-up duration (y), mean (SD)4.2 (2.9)3.1 (2.4).180PG-associated IBD (n = 18)Other PG-associated condition identified (n = 18)No PG-associated condition identified (n = 14)P value (α = 0.05)Demographics Age at diagnosis (y), mean (SD)44.6 (18.7)54.6 (16.4)42.1 (14.2).085 Female, n (%)10 (55.6)10 (55.6)7 (50).939 White, n (%)17 (94.4)17 (94.4)11 (78.6).297 Black, n (%)1 (5.6)1 (5.6)3 (21.4)Initial ulcer number (n = 31), median (IQR)1 (1)2 (1)1 (1).626Ulcer resolution During hospitalization, n (%)000†No P value reported due to insufficient sample size to determine statistical significance. During time in the OSUWMC system, n (%)15 (83.3)9 (50)5 (35.7).006 15 (83.3)9 (50)5 (35.7).034 Within 30 d, n (%)2 (11.1)00.324 Within 365 d, n (%)11 (61.1)9 (50)3 (21.4).075 Ulcer resolution time (d), median (IQR)105.5 (270)119 (95)283 (531).150PG recurrence after resolution (n = 29), n (%)5 (33.3)1 (11.1)4 (80).023Time from PG resolution to recurrence (d), median (IQR)110 (381.5)106 (0)86.5 (580.8)†No P value reported due to insufficient sample size to determine statistical significance.PG-related readmission, n (%)3 (16.7)7 (38.9)9 (64.3).006Time to readmission (d), median (IQR)78 (585)174 (688.3)76 (378).738Follow-up duration (y), mean (SD)4.7 (2.4)3.7 (3.3)3.1 (2.4).270EMR, Electronic medical record; IBD, inflammatory bowel disease; IQR, interquartile range; OSUWMC, The Ohio State University Wexner Medical Center; PG, pyoderma gangrenosum.∗ Statistical analysis: The t test or analysis of variance was used for normally distributed continuous data, Wilcoxon rank-sum test for continuous data with a skewed distribution, and χ2 or Fisher's exact test for proportions. Bold values indicate P ≤ .05.† No P value reported due to insufficient sample size to determine statistical significance. Open table in a new tab EMR, Electronic medical record; IBD, inflammatory bowel disease; IQR, interquartile range; OSUWMC, The Ohio State University Wexner Medical Center; PG, pyoderma gangrenosum. The improved PG outcomes in patients with comorbidities may have been due to the concomitant treatment of the comorbidity, implying potential benefits in identifying PG-associated conditions.4Ashchyan H.J. Butler D.C. Nelson C.A. et al.The association of age with clinical presentation and comorbidities of pyoderma gangrenosum.JAMA Dermatol. 2018; 154: 409-413Crossref PubMed Scopus (64) Google Scholar For example, patients with IBD may additionally benefit from the treatment of their comorbid IBD through improved PG outcomes. Therefore, a thorough history and appropriate evaluations4Ashchyan H.J. Butler D.C. Nelson C.A. et al.The association of age with clinical presentation and comorbidities of pyoderma gangrenosum.JAMA Dermatol. 2018; 154: 409-413Crossref PubMed Scopus (64) Google Scholar in patients without identified comorbidities are warranted. The small cohort size from a single center and the inability to analyze the effect of treatments for comorbid conditions on PG patients might have limited the interpretation and generalizability of the conclusions. However, the study benefited from the granular outcomes and assessments, which are not generally available in larger databases. The identification of comorbidities may be associated with higher wound closure and lower wound recurrence rates. However, testing for underlying diseases in patients without diagnosed comorbidities is still not ideal. Further work is necessary to develop standard comorbidity assessments to identify and address underlying conditions. Dr Kaffenberger is an investigator for AnaptysBio Inc, Biogen, InflaRx, Onquality Pharmaceuticals, and Eli Lilly Co and is funded by the Dermatology Foundation . Drs Trinidad and Spaccarelli and Author Ravi have no conflicts of interest to declare.