Comparison of Three Diagnostic Frameworks for Pyoderma Gangrenosum

Pyoderma gangrenosum (PG) is an inflammatory condition characterized by chronic cutaneous ulcerations. There are three proposed PG diagnostic frameworks (Su, PARACELSUS, Delphi); however, they lack consensus, and their performance has not yet been validated in a well-defined cohort of patients with PG. In this cross-sectional retrospective study, we sought to evaluate compare the concordance these within single-institution were 47 from initial 76 identified International Classification Diseases-9 and/or Diseases-10 codes, where two experts agreed diagnosis on basis clinical descriptions, photographs, pathology. This group was which evaluated frameworks. The PARACELSUS score highest proportion (89% [42 patients]), followed Delphi Su criteria, each at 74% (35 patients). Assessment multirater agreement found that criteria diagnoses for 72% (95% confidence interval = 60–85%); chance-adjusted determined be 0.44 0.16–0.68, Fleiss’ kappa). Future research should seek refine identify targeted methods testing reduce rates misdiagnosis patient misclassification trials. neutrophilic dermatosis presence painful ulcerations (Ruocco et al., 2009Ruocco E. Sangiuliano S. Gravina A.G. Miranda A. Nicoletti G. gangrenosum: updated review.J Eur Acad Dermatol Venereol. 2009; 23: 1008-1017Crossref PubMed Scopus (332) Google Scholar). Diagnostic have unproven performance. dermatology setting, combined absence specific laboratory or histopathological markers, places high risk delayed mismanagement (Weenig 2002Weenig R.H. Davis M.D. Dahl P.R. W.P. Skin ulcers misdiagnosed as pyoderma gangrenosum.N Engl J Med. 2002; 347: 1412-1418Crossref (292) Among various PG, 2004Su Weenig Powell F.C. Perry H.O. clinicopathologic correlation criteria.Int Dermatol. 2004; 43: 790-800Crossref (401) Scholar (Table 1) most frequently cited reports publications related (Bhat, 2012Bhat R.M. update.Indian Online J. 2012; 3: 7-13Crossref Scholar, Gameiro 2015Gameiro Pereira N. Cardoso J.C. Gonçalo M. challenges solutions.Clin Cosmet Investig 2015; 8: 285-293Crossref (73) framework requires satisfying major minimum minor criteria. However, its formally assessed setting (Su Scholar).Table 1Comparison between Three Major Criteria: Criteria, Score, Consensus CriteriaSu ScholarPARACELSUS Score (2018)Delphi Criteria (2018)Diagnosis both least criteriaDiagnosis highly likely >10 pointsDiagnosis meeting criterion four eight criteriaMajor CriteriaMajor (three points)Major CriterionRapid progression painful, necrolytic ulcer irregular, violaceous, undermined borderProgressive course diseaseBiopsy infiltrateOther causes ulceration excludedAbsence relevant differential diagnosesReddish-violaceous wound borderMinor CriteriaMinor (two points)Minor CriteriaHistory suggestive pathergy finding cribriform scarringAmelioration due immunosuppressantExclusion infection histologySystemic diseases associated PGCharacteristically bizarre shapePathergyHistopathological findings (sterile dermal neutrophilia, ± mixed inflammation, lymphocytic vasculitis)Extreme pain > 4 (VAS)Personal history IBD arthritisTreatment response (rapid systemic steroid treatment)Localized phenomenonPapule, pustule, vesicle rapidly ulceratesAdditional (one point)Peripheral erythema, undermining border, tenderness site ulcerationSuppurative inflammation histopathologyMultiple (at one occurring anterior lower leg)Undermined marginCribriform wrinkled paper scars healed sitesAssociated diseaseDecrease size after immunosuppressive treatmentAbbreviations: IBD, bowel disease; gangrenosum; VAS, visual analog scale pain. Open table new tab Abbreviations: Two 2018, including score, based point system diagnosis, well consensus require fulfillment (Jockenhöfer 2019Jockenhöfer F. Wollina U. Salva K.A. Benson Dissemond score: novel tool gangrenosum.Br 2019; 180: 615-620Crossref (64) Scholar; Maverakis 2018Maverakis Ma C. Shinkai K. Fiorentino D. Callen J.P. al.Diagnostic ulcerative international experts.JAMA 2018; 154: 461-466Crossref (194) using 60 leg seen tertiary centers specializing care, control composed 50 venous 10 20 possible points indicates likelihood Scores seven can described unlikely because all scored study reported sensitivity specificity 100% attained when applied groups tested 113 case reports, 65 cases 48 mimickers drawn (Maverakis validation performed met criteria—biopsy edge demonstrating infiltrate—and 8 86% 90% attained. To best our knowledge, comparison another, only patients. aim diagnosed single institution. Su, cohort. 89% (42 47) [CI] 77–95). CI 60–85). Figure 1 shows (present absent) criterion. Multirater estimated 0.16–0.68) kappa, indicating moderate agreement. Examining pairwise assessments lowest (Cohen’s kappa: 0.38, 95% 0.07–0.68) 0.52, 0.23–0.81). Table 2 overall results detail.Table 2Diagnostic Agreement among CriteriaAgreement StatisticsEstimate Confidence Interval)Proportion observed agreement72.3% (59.6%–85.1%)Fleiss’ kappa0.44 (0.16–0.68)Pairwise Cohen’s kappa versus score0.52 (0.23–0.81) consensus0.44 (0.15–0.73) consensus0.38 (0.07–0.68) poses significant challenge practice, even those who specialize management. dermatologists, recent survey examining characteristics considered making revealed (Al Ghazal 2014Al P. Klode dermatologic Germany.J Dtsch Ges. 2014; 12: 1129-1131PubMed published frameworks; there no previous comparisons relative many variations components make up frameworks, especially regard delineation addition, physical examination medical history, introduces bias through subjective interpretation. may contributed interrater study. For example, required rapid border Similar clinical, observation-based, descriptions categorize papule, ulcerates peripheral different lists progressive disease reddish‒violaceous characteristically shape extreme margin least-weighted additional category. slight but important distinction use description pain, implying milder than respectively. sometimes used help differentiate several such large basal cell carcinoma blastomycosis, tends mild One striking differences importance consistent Whereas consider biopsy (least weighted) criterion, classify infiltrate authors describe how originally before being reclassified necessary potential issue requiring mainly acute stages PG; might other (e.g., lymphohistiocytic infiltrate). chart review 2011 demonstrated 7% (8 103) had characteristic findings, defined early abscess formation (Binus 2011Binus A.M. Qureshi A.A. Li V.W. Winterfield L.S. characteristics, comorbidities therapy 103 patients.Br 2011; 165: 1244-1250Crossref (226) cohort, 11% (5 showed formation. Moreover, infectious organisms stimulates neutrophil production migration, could misleading interpreting sterile neutrophilia samples. utmost pretest probability high. approach ruling out PG-mimicking another difference exclusion; thus, rely upon excluded, respectively Common include vascular occlusive stasis ulcers, vasculitides, infections, malignancies vast rule-out improves tools. performing workup rule would time-consuming, costly, clinically indicated, placing negative health outcomes while waiting establish diagnosis. attempt simplify histology establishing more practical, negligible effects specificity. microbiological cultures still gold standard managing skin soft tissue infections. As tools continues improve, molecular microbiology assist differentiating infections necrotizing infections) incorporated into routine If presents overlapping features fasciitis blood empiric antibiotics surgical consultation advisable given progression. high, always necessary, intervention approached caution owing pathergy. Clinical treatment following days will dictate further action. It evident currently available emphasizes distinct aspects disease. Despite differences, identifying interpretation objective markers validate improve utility. Ultimately, yield simplified method main strength independent expert investigators determine final it recently suggested reliability Diseases (ICD) code alone poor (Lockwood 2018Lockwood S.J. D.G. Butler Tsiaras W. Joyce Mostaghimi validity electronic database.Br 179: 216-217Crossref (12) We also against population general clinics during inpatient hospital admission. Limitations nature fact conducted site, relatively small size. limited diagnosing relied judgment rather any diagnoses. conclusion, useful now unique populations derived—general patients, respectively, care reports. additionally highlights existing refinement ability competing literature compromises cohorts trial data. Collaborative efforts directed toward developing testing. Advancements lead accurate timely reducing morbidity mortality entity. academic center January 2012 March 2017. A total 143 record search ICD-9 ICD-10 codes Inclusion aged 18 years above classic, type Exclusion less years; atypical forms vegetative, bullous, pustular, peristomal variants; biopsy-proven Institutional Review Board approval obtained (STUDY00016969). Patient consent review. 38 initially excluded exclusion 30 insufficient information charts confirm resulting 75 remaining presumed (Figure 2). experts, investigator (AGOL) B (JK), discussion resolve discordant cases. exercised diagnoses, opposed scoring system, reflecting current practices. Utilizing notes, dermatopathology data, appearance lesions, scarring, commonly diseases, response, typical features, findings. When blinded other, 56 (74.7%) (kappa 0.44, 0.24–0.64). unblinded, came removal 29 cases, alternate included factitial dermatitis. referred 3). All biopsies some degree suppurative infiltrate. Only 5 evidence Patients designated present absent criteria: then evaluated.Table 3Baseline Characteristics CohortCategoryLevelOveralln47Age, y, mean (SD)55.38 (16.33)Sex, n (%)Female31 (66.0)Male16 (34.0)Race, (%)Asian2 (4.3)Black1 (2.1)Latino1 (2.1)White43 (91.5)WBC, ×109/l, median (IQR)1Data 42 patients.10.85 (8.00, 13.38)Platelets, patients.291.00 (222.50, 369.75)Hemoglobin, gm/dl, (SD)1Data patients.11.99 (2.20)BUN, mg/dl, (IQR)2Data patients.17.00 (13.25, 23.75)Creatinine, patients.0.81 (0.68, 1.02)AST, IU/l, patients.16.50 (14.00, 31.50)ALT, patients.27.00 (19.00, 36.75)ALP, U/l, (SD)2Data patients.82.26 (32.58)Albumin, g/dl, patients.3.42 (0.59)Abbreviations: ALP, alkaline phosphatase level; ALT, alanine aminotransferase; AST, aspartate BUN, urea nitrogen; IQR, interquartile range; l, liter; WBC, white cell.1 Data patients.2 cell. Descriptive statistics (mean SD continuous variables; frequencies percentages categorical variables) (n 47). ratings (i.e., diagnoses) treated independent. bootstrap CIs (Zapf 2016Zapf Castell Morawietz L. Karch Measuring inter-rater nominal data – coefficients intervals appropriate?.BMC Med Res Methodol. 2016; 16: 93Crossref (122) pair Statistical analysis R: Language Environment Computing. datasets generated analyzed corresponding author reasonable request. Carter Haag: http://orcid.org/0000-0003-4250-0591 Trevor Hansen: http://orcid.org/0000-0002-0520-3750 Tamar Hajar: http://orcid.org/0000-0003-0246-1487 Emile Latour: http://orcid.org/0000-0002-7749-7217 Jesse Keller: http://orcid.org/0000-0002-0872-4594 Kanade Shinkai: http://orcid.org/0000-0003-0384-1158 Alex Ortega-Loayza: http://orcid.org/0000-0001-5028-9269 state conflict interest. AGOL supported Gerlinger Research Endowment Medical Foundation Oregon. Conceptualization: CH, TrH, TaH, JK, KS, AGOL; Curation: EL; Formal Analysis: Investigation: Methodology: EL, Project Administration: Resources: Supervision: Validation: Visualization: Writing - Original Draft Preparation: Editing: