Search

Sarah L Becker,1,* Rose Velasco,2,* Alex G Ortega-Loayza1 1Department of Dermatology, Oregon Health & Science University, Portland, OR, USA; 2University of Illinois College of Medicine, Chicago, IL, USA*These authors contributed equally to this workCorrespondence: Alex G Ortega-Loayza, Department of Dermatology, Oregon Health & Science University, 3303 S Bond Ave Building 1, 16th Floor, Portland, OR, 97239, USA, Tel +1 503-418-3376, Fax +1 503-494-6968, Email ortegalo@ohsu.eduAbstract: Pyoderma gangrenosum (PG) is a rare, autoinflammatory disease leading to aseptic ulcers which carries a significant disease burden and is often difficult to treat, with many patients failing first-line treatment and requiring additional therapies. Such cases are typically referred to in the literature as “recalcitrant”, “refractory”, or “resistant”, though little is known about the clinical characteristics of such cases. We performed a narrative literature review to characterize patient demographics and clinical course associated with difficult to treat pyoderma gangrenosum cases in order to identify trends to guide future clinical management and therapeutic innovation. We identified 148 cases with clinical manifestations and associated patient demographics stratified by ulcer and patient features. Consistent with previous work, a greater prevalence of PG was observed among female patients and those with a history of inflammatory bowel disease, however interestingly despite an aggressive course to their PG, few patients had comorbidities complicating their disease course. Additionally, despite the requirement of three or more treatments for most patients’ disease to resolve, the majority healed within the typical window observed in previous clinical studies with low rates of recurrence. Biologics were the most common medication patients were on at time of remission. Collectively, our results suggest a potential benefit for a reduced threshold for biologic initiation in PG patients and a need for standardization of language in the field to facilitate treatment outcomes comparisons and interventions.Keywords: pyoderma gangrenosum, recalcitrant, refractory, resistant, biologics

Willy Ramos,1,2 Alex G Ortega-Loayza,3 Jesús Díaz,4 Jhony A De La Cruz-Vargas,1 Mercedes Tello,5 Gerardo Ronceros,2 Manuel Loayza,1 Ericson L Gutierrez1 1Instituto de Investigaciones en Ciencias Biomédicas (INICIB), Universidad Ricardo Palma, Lima, Peru; 2Instituto de Investigaciones Clínicas, Universidad Nacional Mayor de San Marcos, Lima, Peru; 3Department of Dermatology, Oregon Health and Science University, Portland, OR, USA; 4Universidad Católica Santo Toribio de Mogrovejo, Chiclayo, Peru; 5Universidad Nacional Mayor de San Marcos, Lima, PeruCorrespondence: Ericson L Gutierrez, Instituto de Investigaciones en Ciencias Biomédicas (INICIB), Universidad Ricardo Palma, Av. Alfredo Benavides 5440, Santiago de Surco, Lima, 15039, Peru, Email eringunza@yahoo.esObjective: To characterize the epidemiology and clinical manifestations of arsenicism from chronic exposure to mine tailings in people with lesions on their skin and/or annexes in two mining districts in the highlands of Peru.Materials and Methods: In this case series study, we included 17 people that presented arsenical lesions in skin and annexes which were identified in two prior studies. We evaluated age, occupation, place of exposure, time of exposure, time of disease, manifestations on skin and annexes, location of lesions, severity, and 24-hour urine clearance of arsenic.Results: The average time of exposure was 16.5 ± 14.7 years, and the average length of disease was 9.8 ± 8.1 years. In this study, 70.6% were men, 41.2% were farmers and 17.6% were underage. The most frequent main manifestations in skin and annexes were plantar keratosis (23.5%), palmar (11.8%), palmoplantar (11.8%) and thoracic keratosis (5.9%). Other manifestations were palmoplantar keratosis with thoracic hyperpigmentation (17.6%), Mees’ lines (17.6%) and hyper/hypopigmentation in thorax and back (11.8%). With relation to the severity of lesions, 35.3% were grade 1 (mild), 29.4 % were grade 0 (asymptomatic), 29.4 % were grade 2 (moderate), and 5.9% were grade 3 (severe). The median of 24-hour urine clearance of arsenic was 55 μg/L/24 hours. No cases of skin cancer were presented.Conclusion: The studied cases of arsenicism with lesions on skin and/or annexes by exposure to mine tailings present with differential characteristics in comparison to other forms of arsenicism such as less severity, lower urine clearance of arsenic, and absence of skin cancer cases.Keywords: arsenicism, mine tailings, Peru

Competing Interests: Conflict of interest Dr Loayza is President of the Pacific Dermatology Association and serves as an associate editor for Dermatology (Karger). Additionally, he is a consultant for Genentech and Guidepoint and an advisor to Bristol Meyer Squibb, Boehringer Ingelheim, and Janssen. Dr Foster is a consultant for Arcutis Pharmaceuticals. Authors Chan and Choe have no conflicts of interest to declare.

Livedoid vasculopathy (LV) is a rare condition affecting the lower extremities, often linked to hypercoagulable states or vascular disorders, and despite increasing treatment options, patients frequently experience suboptimal outcomes. Our systematic review of 44 studies, involving 216 patients, found that Rivaroxaban was the most common treatment, with complete (n=18, 31%) or partial (n=40, 68%) ulcer healing and complete pain resolution in the 19% reported, while IVIG also showed promise, though results were mixed. The review highlights the need for further research to identify optimal treatments for LV and establish a standard of care for future clinical trials., (© The Author(s) 2024. Published by Oxford University Press on behalf of British Association of Dermatologists. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Background: Cutaneous (or "Metastatic") Crohn disease (CCD) is a rare and underrecognized disease characterized by cutaneous granulomatous inflammation. We describe patient demographics, clinical characteristics, histology, and treatment of 89 pediatric cases of CCD, including 78 previously reported and 11 new cases seen at four academic institutions. We emphasize the efficacy of biologic mono- and dual therapy., Methods: PubMed identified cases using keywords including "metastatic Crohn disease" and "cutaneous Crohn disease". Patients were identified by retrospective review of the electronic health record including histopathologic diagnosis consistent with CCD. Chart review collected demographic, clinical, and histologic data., Results: Most pediatric patients with CCD are male 55% (49/89), present with edema (73/89, 82%) and erythema (47/89, 53%) of the genitals (33/49, 67%), and have intestinal Crohn disease (69/89, 78%). Oral corticosteroids (53/75, 71%) and metronidazole (29/75, 39%) are the most frequently prescribed medications. Of the 17 patients treated with tumor necrosis factor (TNF)-blockade, 94% (16/17) had partial or total clearance. Ustekinumab resulted in clearance of cutaneous disease in two patients (2/3, 67%) and partial clearance in one patient (1/3, 33%). Two cases achieved total clearance with the use of dual biologic therapy defined as the use of two biologic therapies with differing mechanisms of action or the use of a biologic therapy and small molecule inhibitor., Conclusions: TNF blockade is an effective treatment for pediatric CCD, and interleukin-12/23 inhibitors may be similarly effective. Consideration of dual biologic therapy may be useful in pediatric patients requiring discordant therapies for their intestinal and cutaneous CD., (© 2024 The Author(s). Pediatric Dermatology published by Wiley Periodicals LLC.)

Background and Objective: Pyoderma gangrenosum (PG) is a rare ulcerative neutrophilic dermatosis that can be associated with primary immunodeficiency. The pathogenesis of PG has not yet been elucidated, although contributions from dysregulation of the immune system in patients with apparent genetic predispositions have been postulated. We conducted a Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA)-guided systematic review with the objective of identifying inborn errors of immunity in the presence of PG as well as their clinical characteristics of severity including number of PG lesions and anatomic areas affected, and treatment outcomes., Methods: A literature search was performed using PubMed/MEDLINE, Embase, Cochrane Library, and Web of Science through August 24, 2023, for studies published in English using the search terms: "pyoderma gangrenosum," "inborn error of immunity," "immune defect*," and a list of genetic mutations potentially associated with PG., Results: Seventy-four cases of PG associated with inborn errors of immunity were identified. The results demonstrate an association of PG with a variety of inborn errors of immunity, including genetic mutations not classically associated with the condition. Genetic mutations such as BTK, IL1RN, ITGB2, LPIN2, MEFV, NFkB1, NLRP3, NLRP12, NOD2, PSMB8, PLCG2, PSTPIP1, RAG1, TTC37, and WDR1, as well as complement component 2/complement component 4 (C2/C4) and complement component 7 (C7) deficiencies were identified in the presence of either idiopathic or syndromic PG. Of note, mutations in genes such as PSMB8, NLRP3, and IL1RN were found to be associated with a more severe and atypical course of PG, whereas mutations in RAG1 as well as those causing a C2/C4 deficiency were associated with the mildest clinical presentations of PG. Mutations in NFkB1, ITGB2, and PSTPIP1 were associated with the most heterogeneous clinical presentations., Conclusions: Human inborn errors of immunity may be implicated in the genetic predisposition to PG and may influence the clinical presentation. Due to the rarity of these diseases, further work must be done to describe the association between inborn errors of immunity and PG. Identifying inborn errors of immunity that may contribute to the development of PG may assist in further elucidating the mechanism of PG, guiding targeted treatment, and improving clinical outcomes for these patients., (© 2024. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Competing Interests: Conflicts of interest Dr Ortega-Loayza reports consultancy/advisory boards disease-relevant honoraria from Genentech, Boehringer-Ingelheim, Bristol Mayer-Squibb, and Janssen; also reports research grants from Lilly, Pfizer, and Janssen; and is also supported by NIAMS NIH R01AR083110. Authors Haddadin, Drs Erickson, Latour, and Sisley have no conflicts of interest to declare.

Abstract: Pyoderma gangrenosum is an inflammatory skin disease that presents with rapidly progressive ulcers with violaceous, undermined borders. Despite most commonly affecting the lower extremities, pyoderma gangrenosum can rarely present in the genital, anal, and perineal regions. We describe 2 cases and report a review of published cases., Competing Interests: Conflict of Interest and Sources of Funding: A.G.O.L. serves as an associate editor for Dermatology ( Karger ). In addition, he is a consultant for Genentech and Guidepoint and an advisor to Bristol Meyer Squibb, Boehringer Ingelheim, and Janssen. Dr. Ortega-Loayza has received research grants from the Lilly, Janssen, Incyte, and Pfizer. He is supported by NIH NIAMS R01 AR083110. Authors S.C., A.S., S.K., M.V., A.H., and J.R.D. have no conflicts of interest to disclose., (Copyright © 2024 American Sexually Transmitted Diseases Association. All rights reserved.)

The heterogeneity of atypical wounds can present diagnostic and therapeutic challenges; however, as the prevalence of atypical wounds grows worldwide, prompt and accurate management is increasingly an essential skill for dermatologists. Addressing the underlying cause of an atypical wound is critical for successful outcomes. An integrated approach with a focus on pain management and patient engagement is recommended to facilitate enduring wound closure. Advances in treatment, in addition to further research and clinical training, are necessary to address the expanding burden of atypical wounds., (© 2024. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Inpatient hospitalization of individuals with hidradenitis suppurativa (HS) has increased. Inpatient services may not be familiar enough with this disease to understand how to manage severe HS and/or HS flares. It would be beneficial to the inpatient medical community to establish consensus recommendations on holistic inpatient care of patients with HS. A survey study was developed and distributed by Wake Forest University School of Medicine (Winston-Salem, North Carolina). A total of 26 dermatologists participated in the Delphi process, and the process was conducted in 2 rounds. Participants voted on proposal statements using a 9-point scale (1=very inappropriate; 9=very appropriate). Statements were developed using current published guidelines for management of HS and supportive care guidelines for other severe inpatient dermatologic diseases. A total of 50 statements were reviewed and voted on between the 2 rounds. Consensus was determined using the RAND/UCLA Appropriateness Method. Twenty-six dermatologists completed the first-round survey, and 24 completed the second-round survey. The 40 consensus recommendations generated through these surveys can serve as a resource for providers caring for inpatients with HS.

At present, there are no standardized guidelines for determining patient eligibility for pyoderma gangrenosum (PG) clinical trials. Thus, we aim to determine which clinical features, histopathological features, or laboratory features should be included in active ulcerative PG clinical trial eligibility criteria for treatment-naïve patients and patients already treated with immunomodulating medications (treatment-exposed patients). This study employed 4 rounds of the Delphi technique. Electronic surveys were administered to 21 international board-certified dermatologists and plastic surgeon PG experts (June 2022-December 2022). Our results demonstrated that for a patient to be eligible for a PG trial, they must meet the following criteria: (i) presence of ulcer(s) with erythematous/violaceous undermining wound borders, (ii) presence of a painful or tender ulcer, (iii) history/presence of rapidly progressing disease, (iv) exclusion of infection and other causes of cutaneous ulceration, (v) biopsy for H&E staining, and (vi) a presence/history of pathergy. These criteria vary in importance for treatment-naïve versus treatment-exposed patients. Given the international cohort, we were unable to facilitate live discussions between rounds. This Delphi consensus study provides a set of specific, standardized eligibility criteria for PG clinical trials, thus addressing one of the main issues hampering progress toward Food and Drug Administration approval of medications for PG., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Peristomal pyoderma gangrenosum is an uncommon subtype of pyoderma gangrenosum mainly affecting stoma sites of patients with inflammatory bowel disease. While surgical treatments are often used to assist healing, little is known about the relationship between surgical interventions and the rate of recurrence of peristomal pyoderma gangrenosum. The aim of this study was to identify patient and clinical factors associated with peristomal pyoderma gangrenosum recurrence following surgical intervention. A multi-institutional retrospective case series and literature review was conducted to evaluate patient characteristics and perioperative treatment. Patients of any age with peristomal pyoderma gangrenosum undergoing surgical operations related to their pyoderma gangrenosum or due to another comorbidity were included. Descriptive statistics were used to characterize demographic information. Associations were evaluated using Wilcoxon's rank-sum test for continuous variables and Fisher's exact test for categorical data. Thirty-seven cases were included, 78.3% of which had a history of inflammatory bowel disease. Overall, 13 (35.1%) cases experienced recurrence at 30 days. There was no significant association identified between patient demographics, stoma location, surgical intervention, or perioperative treatment with rate of recurrence at 30 days post-operation. While no clinical risk factors or treatments were associated with recurrence, our work underscores the importance of a multidisciplinary approach to this disease to address gastrointestinal, dermatologic, and surgical components of treatment., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

In this CME, we review two specific categories of ulcers: inflammatory (where inflammation is the primary pathologic process leading to ulceration) and vaso-occlusive (where occlusion is the primary process). Inflammatory ulcers include pyoderma gangrenosum and vasculitides, whereas livedoid vasculopathy, calciphylaxis and Martorell ulcers are vaso-occlusive ulcers. Determining the causes of ulcers in these conditions may require laboratory evaluation, biopsy and imaging., (Copyright © 2024. Published by Elsevier Inc.)

Background: Pyoderma gangrenosum (PG) is a rare ulcerative skin condition with no current standardized outcomes or outcome measures. With a rich investigational therapeutic pipeline, standardization of outcomes and improvement of data quality and interpretability will promote the appropriate and consistent evaluation of potential new therapies. Core outcome sets (COS) are agreed, standardized sets of outcomes that represent the minimum that should be measured and reported in all clinical trials of a specific condition., Objectives: To identify and reach a consensus on which domains (what to be measured) should be included in the Understanding Pyoderma Gangrenosum: Review and Analysis of Disease Effects (UPGRADE) core domain set for clinical trials in PG., Methods: Collaborative discussions between patients and PG experts, and a systematic review of the literature identified items and prospective domains. A three-round international eDelphi exercise was performed to prioritize the domains and refine the provisional items (consensus: ≥ 70% of participants rating a domain as 'extremely important' and < 15% of participants voting 'not important'), followed by an international meeting to reach consensus on the core domain set (consensus: < 30% disagreement). Item-generation discussions and consensus meetings were hosted via online videoconferences. The eDelphi exercise and consensus voting were performed using Qualtrics survey software. Participants were adults with PG, healthcare professionals, researchers and industry representatives., Results: Collaborative discussions and systematic reviews yielded 115 items, which were distilled into 15 prospective domains. The eDelphi exercise removed the three lowest-priority domains ('laboratory tests', 'treatment costs' and 'disease impact on family') and ranked 'pain', 'quality of life' and 'physical symptoms' as the highest-priority prospective domains. Consensus was reached on the domains of 'pain', 'quality of life' and 'clinical signs'. The domain of 'disease course/disease progression' narrowly failed to reach consensus for inclusion in the core set (32% of participants voted 'no'). Refinement of this domain definition will be required and presented for consideration at future consensus meetings., Conclusions: The UPGRADE core domain set for clinical trials in PG has been agreed by international multistakeholder consensus. Future work will develop and/or select outcome measurement instruments for these domains to establish a COS., Competing Interests: Conflicts of interest M.E.J. reports membership of the Harmonising Outcomes Measures for Eczema (HOME) Executive Committee. L.A.A.G. reports membership of the HOME Executive Committee and membership of the board of directors of the CHORD COUSIN Collaboration (C3). A.V.M. reports consultancy/advisory boards disease-relevant honoraria from AbbVie, Boehringer-Ingelheim, Novartis, Pfizer, Sanofi and UCB. D.M.C. reports employment with Genentech. J.D. reports consultations, lectures and/or studies for Aurealis, B. Braun, Biomonde, Coloplast, Convatec, Draco, Engelhardt, Flen Pharma, Lohmann & Rauscher, Mölnlycke, Smith & Nephew and Urgo; and also reports membership of the board of the following professional societies: Initiative Chronische Wunden, AG Wunde of the German Society of Dermatology, WundDACH. K.S.T. reports membership of the HOME Executive Committee and membership of the methods group for C3. A.G.O.-L. reports consultancy/advisory boards disease-relevant honoraria from Genentech, Boehringer-Ingelheim, Bristol Meyers Squibb and Janssen; reports research grants from Lilly, Pfizer and Janssen; and is also supported by NIAMS R01AR083110. J.W.R., W.B., L.J.G., D.L.O., T.Y., K.S., B.N. and D.L. declare no conflicts of interest., (© The Author(s) 2023. Published by Oxford University Press on behalf of British Association of Dermatologists. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Competing Interests: S. N. Tolkachjov is a speaker/investigator for CASTLE Biosciences and Bioventus/LifeNet. The remaining authors declare no conflicts of interest.

Introduction: Pyoderma gangrenosum (PG) is a rare, inflammatory dermatologic disease that, as a diagnosis of exclusion with nonspecific histologic features, is difficult to diagnose. As pharmaceutical interest in potential treatments for PG increases, the need for standardized diagnostic criteria to ensure reproducibility, comparability, and external validity of PG research is required. In this study, we aim to characterize the inclusion and exclusion criteria used in the diagnosis of PG in clinical research studies as well as the eligibility of PG in clinical trials., Methods: A systematic review was conducted to characterize the PG inclusion and exclusion criteria in research studies. An additional search of the USA and international clinical trials databases was conducted as well to capture eligibility criteria for PG trials., Results: Our study revealed a broad range of inclusion and exclusion criteria used to establish the presence or absence of PG. Based on eight distinct categories used to characterize inclusion criteria for research studies, diagnosis by a dermatologist (n = 25, 31.6%), no inclusion criteria listed (n = 21, 26.6%), and clinical and histopathologic features consistent with PG (n = 20, 25.3%) were most common. For current clinical trials, six categories were used to characterize inclusion criteria, of which clinical and histopathologic features consistent with PG (n = 5, 31.3%), identification based on diagnosis of PG (n = 4, 25.0%), and clinical features consistent with PG (n = 3, 18.8%) were the most common., Conclusion: This systematic literature review highlights the range of heterogeneity in diagnostic and eligibility criteria used in PG-directed clinical research and current clinical trials and illustrates the need for the development of consensus guidelines and a rigorous framework to enable high-quality future trials for PG., (© 2023 S. Karger AG, Basel.)

Introduction: Neutrophilic dermatoses (NDs) often occur secondary to inflammatory conditions, medication exposure, and hematologic malignancy. While malignancy-associated NDs (MA-NDs) have been well reported among those with hematologic cancers, little is known about drug-induced NDs (DI-NDs) within this population. The objective of this study was to compare the presentations and outcomes of patients with hematologic malignancies who developed MA-NDs and DI-NDs., Methods: Cases of ND occurring between 2013 and 2023 among those with hematologic malignancies were identified from the electronic medical records of our institution. Patient characteristics, recent medication exposures, cancer mutations, and disease outcomes were reviewed. Patients were categorized with DI-ND if they were recently exposed to one of four medications known to be commonly associated with ND or were otherwise categorized with MA-ND. We report a descriptive analysis of cases of DI-ND and MA-ND., Results: We identified 52 patients with ND and co-occurring hematologic malignancy including 16 cases of DI-ND (30.8%) and 36 cases of MA-ND (69.2%). The most common ND in both groups was Sweet's syndrome. Chronic underlying conditions including solid tumors, inflammatory disorders, chronic viral infection, and tobacco use were more common among those with MA-ND. Among those with DI-ND, tyrosine kinase inhibitors were the most commonly associated drugs (43.8%). The most common cancer mutation among those with DI-ND was FLT3 (43.8%), while the most common mutation among those with MA-ND was TP-53 (19.4%). Among those who had died at the time of data collection, 90.0% of those with DI-ND and 66.7% of those with MA-ND died within 1 year of ND diagnosis., Conclusion: Most cases of ND occurring with hematologic malignancies develop secondary to cancer rather than drug exposure. Different cancer mutations may predispose to DI-ND and MA-ND. Further research is needed to establish diagnostic criteria for DI-ND and to determine the pathogenic role of specific cancer mutations, particularly FLT3, in the development of ND., (© 2024 S. Karger AG, Basel.)

Pyoderma gangrenosum (PG) is a rare ulcerative neutrophilic dermatosis that is occasionally associated with primary immunodeficiency. Though contributions from dysregulation of the innate immune system, neutrophil dysfunction and genetic predisposition have been postulated, the precise pathogenesis of PG has not yet been elucidated. This article reviews reported cases of coexisting PG and primary immunodeficiency in order to gain insight into the complex pathophysiology of PG. Our findings suggest that variations in genes such as RAG1, ITGB2, IRF2BP2 and NFκB1 might play a role in genetically predisposing patients to develop PG. These studies support the feasibility of the role of somatic gene variation in the pathogenesis of PG which warrants further exploration to guide targeted therapeutics., (© 2023 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Pyoderma gangrenosum (PG) is a rare inflammatory condition with an immense disease burden that remains understudied. With limited approved treatments and low-quality clinical evidence, PG continues to have poor patient outcomes. Unfortunately, improvement in PG treatments and patient care is based on additional research endeavors that can only be developed from existing high-quality data. The following protocol outlines the development of the Minimum Data Set for Treatment Effectiveness in Pyoderma gangrenosum (MIDSTEP), a core set of domains and domain items for the Pyoderma Gangrenosum Treatment Effectiveness (PyGaTE) international registry. The outcomes and benefits are focused on providing real-world data for physicians to improve their clinical decisions on PG treatment and inform clinical trial design, promoting clinical research among the international scientific community. MIDSTEP is a multi-phase project. The first phase will produce a domain item list from a literature review to take into the second phase which would finalize the core data set by an e-Delphi exercise. There will be a single stakeholder group participating together in the e-Delphi consisting of PG experts (healthcare providers, researchers, methodologists, industry representatives, and regulators), ulcerative PG patients, and PG patient advocates. The methodology outlined in the protocol is a systematic method based on several guidelines through COMET and established dermatologic registries and outcome sets with systematic methodologies of their own. The third phase will identify the instruments for the items, the 'when to measure' the items, and the platform for the registry. The last phase is the implementation and continued maintenance of the international registry PyGaTE. By solidifying a consensus on standardized outcomes and collecting information on PG treatment effectiveness in a centralized database, existing treatments can be compared more systematically and analyzed with increased evidence. MIDSTEP and the PyGaTE international registry will have the ambitious goal to generate and disseminate real-world data that can be used by all stakeholders to improve health outcomes for PG patients. Future potential for the outcome of this project includes the development of a gold-standard PG treatment., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Pyoderma gangrenosum is a rare neutrophilic dermatosis that leads to exceedingly painful ulcerations of the skin. Although the exact pathogenesis is not yet fully understood, various auto-inflammatory phenomena with increased neutrophil granulocyte activity have been demonstrated. Despite the limited understanding of the pathogenesis, it is no longer a diagnosis of exclusion, as it can now be made on the basis of validated scoring systems. However, therapy remains a major multidisciplinary challenge. Various immunosuppressive and immunomodulatory therapies are available for the treatment of affected patients. In addition, concomitant topical pharmacologic therapy, wound management and pain control should always be addressed. Corticosteroids and/or cyclosporine remain the systemic therapeutics of choice for most patients. However, in recent years, there has been an increasing number of studies on the positive effects of biologic therapies such as inhibitors of tumour necrosis factor-α; interleukin-1, interleukin-17, interleukin-23 or complement factor C5a. Biologics have now become the drug of choice in certain scenarios, particularly in patients with underlying inflammatory comorbidities, and are increasingly used at an early stage in the disease rather than in therapy refractory patients., (© 2023. The Author(s).)

Background: Endemic pemphigus foliaceus and endemic pemphigus vulgaris are autoimmune dermatologic disorders endemic to the Peruvian Amazon., Objective: To determine the ultrastructural skin alterations of three healthy subjects with anti DSG-1 antibodies in areas endemic to pemphigus foliaceus and pemphigus vulgaris in the Peruvian Amazon., Patients and Methods: Case series carried out from data of three clinically healthy subjects positive to anti DSG-1 antibodies, from Peru. This study consists of a sub-analysis of data gathered in a previous study., Results: Ultrastructural results are presented from the skin biopsies of three clinically healthy patients positive to anti -desmoglein 1 (DSG-1) antibodies. High Resolution Optical Microscopy (HROM) showed the absence of acantholysis. Transmission Electron Microscopy (TEM) showed the widening of intercellular space between keratinocytes, the presence of vacuoles in intercellular space with granular material and cytoplasmic vacuolization, loss of desmosome structure, loss of normal distribution among tonofilaments and lateral separation among cells in the stratum basale., Conclusion: According to our results, healthy subjects that present anti -desmoglein 1 antibodies can develop ultrastructural alterations that are visible through transmission electron microscopy but not through conventional optical microscopy., Competing Interests: The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© 2023 Published by Elsevier B.V.)

Importance: Scoring systems for Stevens-Johnson syndrome and epidermal necrolysis (EN) only estimate patient prognosis and are weighted toward comorbidities and systemic features; morphologic terminology for EN lesions is inconsistent., Objectives: To establish consensus among expert dermatologists on EN terminology, morphologic progression, and most-affected sites, and to build a framework for developing a skin-directed scoring system for EN., Evidence Review: A Delphi consensus using the RAND/UCLA appropriateness criteria was initiated with a core group from the Society of Dermatology Hospitalists to establish agreement on the optimal design for an EN cutaneous scoring instrument, terminology, morphologic traits, and sites of involvement., Findings: In round 1, the 54 participating dermatology hospitalists reached consensus on all 49 statements (30 appropriate, 3 inappropriate, 16 uncertain). In round 2, they agreed on another 15 statements (8 appropriate, 7 uncertain). There was consistent agreement on the need for a skin-specific instrument; on the most-often affected skin sites (head and neck, chest, upper back, ocular mucosa, oral mucosa); and that blanching erythema, dusky erythema, targetoid erythema, vesicles/bullae, desquamation, and erosions comprise the morphologic traits of EN and can be consistently differentiated., Conclusions and Relevance: This consensus exercise confirmed the need for an EN skin-directed scoring system, nomenclature, and differentiation of specific morphologic traits, and identified the sites most affected. It also established a baseline consensus for a standardized EN instrument with consistent terminology.

Introduction: Pyoderma gangrenosum (PG) can represent a diagnostic challenge, leading to missed or delayed diagnosis. With prolonged immunosuppressive therapy, the risk of infections is elevated, predisposing patients to receive anti-infective treatments and, in serious cases, amputations. Limb amputations have been reported as complication of PG misdiagnosis but can also occur as a complication of long-standing PG ulcers., Methods: We aimed to describe the clinical characteristics of patients with PG leading to limb amputation through a multicenter retrospective case series between 2010 and 2020 including patients with PG who underwent limb amputation. We report a descriptive analysis of these patients' clinical course and outcome., Results: Ten patients with PG who underwent at least one limb amputation were identified. Six were male (60%). Mean age was 65 years. All patients had ulcerative PG on the lower extremities, with a mean PG ulcer duration of 30.6 months. Six patients had PG-related comorbidities such as ulcerative colitis, myelodysplasia, and inflammatory arthritis. Other significant comorbidities included diabetes mellitus (DM) (five patients), coronary artery disease (five patients), and chronic kidney disease (two patients). The majority of patients (8/10) were correctly diagnosed with PG prior to amputation, whereas two patients were misdiagnosed with necrotizing soft tissue infections (NSTIs). All patients received intravenous antibiotics without substantial improvement. Eight patients developed sepsis and shock-like symptoms and the diagnosis of NSTIs was considered. Below-knee amputation was performed in six patients and above-knee amputation in four. Four patients had amputation performed twice because of recurrent NSTIs. Conclusion This multicenter case series sheds light on practice gaps for physician assessing patients with PG, in that limb amputation may result from PG misdiagnosis or complications thereof. Elderly patients (above 65 years) with coexisting lower extremity PG, DM, and/or chronic cardiac or renal disease should be managed with particular care toward preventing infection/NSTIs to prevent further complications such as limb amputations., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Ulcers of mixed etiology are diagnostically elusive and challenging to treat, especially when rare conditions are superimposed. Pyoderma gangrenosum (PG) is an autoinflammatory, ulcerative skin disease that is difficult to diagnose. Diagnostic criteria exist but there are no specific clinical tests to identify it. We discuss a case of PG initially diagnosed as venous ulcer in the setting of peripheral artery disease, complicated by superinfection, refractory to standard wound care, multiple surgical debridements, revascularization, negative pressure therapy, and parenteral antibiotics. Findings differentiating PG from other wound etiologies are explored, with the aim of improving clinical recognition of this condition.

Competing Interests: Dr Alex Ortega-Loayza has served in advisory boards for Janssen, BMS, and Boehringer 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. Dr Mostaghimi reports no conflicts of interest relevant to this manuscript. He has received consulting fees from Pfizer, hims, Digital Diagnostics, Concert, Lilly, Abbvie, Equillium, Boehringer, Ingelheim, LEO, ACOM, and Digital Diagnostics.

Introduction: Pyoderma gangrenosum (PG) is a rare neutrophilic dermatosis that affects approximately 0.3-6 out of every 100,000 people worldwide. Clinical trials are scarce but there is growing interest in using newer and more targeted therapeutics to achieve disease remission. However, there are no standardized instruments to measure outcomes in PG and, therefore, future clinical trials are hampered by the absence of established and accurate means of assessment and comparison. Therefore, we aim to produce an internationally accepted core outcome set (COS) that will overcome this obstacle. This protocol outlines our intended approach to achieve the first part of this process, establishing a core outcome domain set., Methods: An international team of PG stakeholders, consisting of physicians, wound care nurses, patients, scientists and industry representatives, has been assembled for the purpose of building a comprehensive and universally established set of core outcome domains. During the first step, we will generate items of relevance using a nominal process from all stakeholders. Items will be distilled and collapsed into potential domains and subdomains. A systematic review of current methods for reporting PG has already been published and domains identified in this work will be considered in the generation of the core domains set. During the second step, after the potential domains and subdomains are identified, stakeholders will participate in an e-Delphi exercise to rate the importance of (sub)domains. A final consensus meeting will be organized with the goal of establishing a core domain set., Conclusion: Pyoderma gangrenosum lacks an established COS and previously published clinical trials have used inconsistent measures established from similarly inconsistent domains. As a first step this study seeks to create a core domain set within the COS, to build the foundation for future core outcome work for PG., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Competing Interests: Conflicts of interest A.A. is a consultant for AbbVie, Boehringer Ingelheim, Inflarx, Novartis, UCB, and is an investigator for Boehringer Ingelheim and Processa. W.W.H. is a consultant for Genentech. A.M. reports no conflicts of interest relevant to this manuscript. He has received consulting fees from Pfizer, Hims, Digital Diagnostics, Concert, Lilly, AbbVie, Equillium, Boehringer Ingelheim and equity from Hims, Figure 1 and Acome Seebe. He has also received licensing/royalties from Pfizer, Concert and Lilly. A.M. participates in medical advisory boards for Hims, Figure 1 and Digital Diagnostics, and has conducted clinical trials with Lilly and Concert. He is an Associate Editor for Journal of the American Medical Association Dermatology. C.A.N. has received a research grant from Boehringer Ingelheim for work outside of this manuscript. M.H.N. has received research grants from Boehringer Ingelheim for work unrelated to this manuscript. A.G.O.-L. has received consulting fees from Genentech and research grants from Pfizer, Janssen and Lilly. He has participated in advisory boards for the following companies: Janssen, Boehringer Ingelheim and Bristol Myers Squibb. He is a Section Editor for Dermatology (Karger).

Sweet syndrome (SS), the prototypical neutrophilic dermatosis, is characterized by abrupt onset of tender plaques and nodules, classically accompanied by fever and leukocytosis. While management mainly relies on systemic corticosteroids, inadequate response can be seen in some patients that necessitates exploring other treatment options. Early diagnosis of malignancy-associated SS (MA-SS) along with detection of concomitant malignancy is crucial for improving patients' outcomes. Data regarding various clinical manifestations, extracutaneous associations, treatment, and outcomes are poorly characterized in the literature. We aimed to review all published case reports and case series to portray clinical features of SS including extracutaneous manifestations. We also describe reported treatment options and their outcomes to draw attention toward unmet therapeutic needs in the management of SS. In addition, for clinical and practical purposes, we attempted to delineate the distinction between MA-SS and nonmalignant subtypes of SS., (© 2023 S. Karger AG, Basel.)

Competing Interests: Conflicts of interest Dr Ortega-Loayza has served on advisory boards for Janssen, BMS, and Boehringer Ingelheim and as a consultant for Genentech and Guidepoint; he has also received research grants from Eli Lilly and Company, OHSU School of Medicine Gerlinger research award, and Medical Research Foundation of Oregon. Dr Kaffenberger has received research funding from the Dermatology Foundation, Eli Lilly and Company, and InflaRx. Dr Mostaghimi has received consulting fees from Pfizer, hims, Digital Diagnostics, Concert, Eli Lilly and Company, AbbVie, and Bioniz. He has served on medical advisory boards for and holds equity in hims and Figure 1. Dr Mostaghimi has received licensing/royalties from Pfizer and Concert and has participated in clinical trials by Eli Lilly and Company and Concert. Additionally, he serves as an associate editor for JAMA Dermatology. Dr Seminario-Vidal has had advisory board relationships with Novartis, Boehringer Ingelheim, Helsinn, Kyowa Kirin, Regeneron, and Blueprint. She or her institution received research funding from Eli Lilly and Company, Soligenix, Helsinn, Eisai, Boehringer Ingelheim, Novartis, AbbVie, BMS, Celgene, Glenmark, Kyowa Kirin, Amgen, AnaptysBio, and Innate Pharma. Dr Seminario-Vidal has also been a speaker for Helsinn and Kyowa Kirin. Authors Reese and Latour and Drs Gupta, Loyo, Creadore, and Rick have no conflicts of interest to declare.

Objective: To review the litigation literature related to patients with pyoderma gangrenosum (PG) to characterize the legal issues they face., Data Sources: Data sources include law databases Casetext and Lexis Nexis., Study Selection: All disability and medical liability claims directly involving patients with PG were included., Data Extraction: Data extraction came directly from Casetext and Lexis Nexis. All cases extracted came from September 1965 to December 2020. This resulted in 32 cases, 18 of which were excluded because they did not mention the plaintiff having a diagnosis of PG (n = 14)., Data Synthesis: The review found a total of six medical liability cases in which adverse health outcomes were reported, including prolonged suffering (2/6 cases), unnecessary treatments or procedures (2/6), exacerbation of disease (1/6 cases), and permanent scarring (1/6 cases). Despite this, two plaintiffs won their case and only one of them received any monetary award. Similarly, of the eight disability claims in the review, four were ruled in the favor of the plaintiffs and only two resulted in immediate awarding of benefits. Half of medical liability cases occurred in correctional facilities after the denial of appropriate care., Conclusions: The findings demonstrate a need for access to specialty care in incarcerated populations. Cases that occurred in a hospital setting also stress the importance of initiatives such as telemedicine to efficiently increase access to care in a cost-effective manner. Further, PG has been recognized as a severe impairment in disability claims despite patients being denied because they were deemed able to perform other work., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Pyoderma gangrenosum is a rare inflammatory skin disease classified within the group of neutrophilic dermatoses and clinically characterized by painful, rapidly evolving cutaneous ulcers with undermined, irregular, erythematous-violaceous edges. Pyoderma gangrenosum pathogenesis is complex and involves a profound dysregulation of components of both innate and adaptive immunity in genetically predisposed individuals, with the follicular unit increasingly recognized as the putative initial target. T helper 17/T helper 1-skewed inflammation and exaggerated inflammasome activation lead to a dysregulated neutrophil-dominant milieu with high levels of tumor necrosis factor-α, interleukin (IL)-1β, IL-1α, IL-8, IL-12, IL-15, IL-17, IL-23, and IL-36. Low-evidence studies and a lack of validated diagnostic and response criteria have hindered the discovery and validation of new effective treatments for pyoderma gangrenosum. We review established and emerging treatments for pyoderma gangrenosum. A therapeutic algorithm based on available evidence is also provided. For emerging treatments, we review target molecules and their role in the pathogenesis of pyoderma gangrenosum., (© 2022. The Author(s).)

Hidradenitis suppurativa/acne inversa (HS) is a chronic inflammatory disease of the pilosebaceous unit leading to formation of painful, inflammatory nodules, abscesses and tunnels in apocrine gland-bearing areas of the skin. Pain and drainage are the most important symptoms associated with reduction of quality of life in HS. On the other hand, an overlooked symptom in quality of life studies is itch, despite the fact that several studies have reported its importance. Various theories have tried to explain the pathogenesis of itch in HS, such as the presence of mast cells in the cell infiltrates and elevated Ig E levels in the lesional skin. Smoking and advanced stage of disease have been found to be associated with increased intensity of itch. A PUBMED search was conducted to perform a systematic literature review using the term "hidradenitis suppurativa" [all fields], the keywords "pruritus", "itching", "itch" [all fields] and with "AND" as operator. Mast cells and mTor signaling were found to be raised in both lesional and perilesional skin. Itch as a presenting symptom has been found in 35-82.6% of patients across multiple studies. It often co-presents with pain and may be misinterpreted as burning, stinging, tickling, tweaking, prickling, etc. The presence of itch is associated with reduced quality of life, depression and impairment of social life. Brodalumab, a monoclonal antibody against IL-17A receptor, produced significant improvements in itch, pain, QoL and depression in patients with moderate to severe HS. Statins have shown some reduction in itch intensity score. Further studies are required to gain a better understanding of the etiopathogenesis and optimal therapeutic modalities for itch in HS that will allow clinicians to better address issue and reduce its impact on quality of life.