Postoperative Bleeding Complications Associated With Novel Oral Anticoagulants in Mohs Micrographic Surgery.

BACKGROUND: Novel oral anticoagulants (NOACs) are commonly prescribed, recently developed anticoagulants, but limited data exist on NOAC-related bleeding complications in Mohs micrographic surgery (MMS). OBJECTIVE: To assess the risk of postoperative bleeding in patients taking NOACs compared with patients taking no antithrombotic medications. METHODS/MATERIALS: A 5-year retrospective chart review of all MMS cases performed by a single surgeon was conducted. Patient and surgery characteristics, anticoagulant use, and bleeding complications were recorded. RESULTS: Two thousand one hundred eighty-one MMS cases in 1,545 patients were included. There were 696/2,181 cases in which patients were taking at least 1 antithrombotic medication, with 149 on NOAC monotherapy and 15 on NOAC and aspirin combination therapy. Bleeding complications occurred in 22/2,181 cases. Patients on NOAC monotherapy did not have an increased risk of bleeding complications compared with patients on no antithrombotic medications (odds ratio [OR]:1.70, 95% confidence interval [CI]: 0.36-7.97, p = .50). In contrast, patients on NOAC and aspirin combination therapy exhibited an increased bleeding risk (OR: 20.5, 95% CI: 3.99-105.7, p < .001). CONCLUSION: Novel oral anticoagulant use alone during MMS was not associated with an increased postoperative bleeding risk, supporting the safety of continuing NOAC therapy during MMS. However, NOAC and aspirin combination therapy was associated with a high postoperative bleeding risk. Nonetheless, these bleeding events did not lead to adverse long-term outcomes.

Febrile Ulceronecrotic Mucha-Habermann Disease Associated With Hemophagocytic Lymphohistiocytosis: A Case Report and Review of the Literature.

ABSTRACT: Mucha-Habermann disease (MHD) is an inflammatory skin disease characterized by polymorphous eruptions of erythematous, necrotic macules that have been reported for similarities to cutaneous T-cell lymphoma. Febrile ulceronecrotic MHD (FUMHD) represents a severe variant of MHD, marked by ulcers, hemorrhagic bullae, and systemic symptoms. Herein, we report a case of a severely atypical lymphomatoid expression of FUMHD associated with hemophagocytic lymphohistiocytosis (HLH). A previously healthy 21-year-old woman was admitted to the hospital with a rapidly progressive necrotic papular rash. Physical examination revealed right orbital swelling, bilateral hemorrhagic auricular bullae, and multiple ulcerative purpuric papulonodules on the trunk, face, and extremities. Biopsy indicated a dermal and subcutaneous infiltrate of atypical CD8 + lymphocytes with loss of CD5 and reduction in CD7 expression, along with features of lymphomatoid vasculitis. A diagnosis of a severely atypical lymphomatoid expression of FUMHD was made. The patient also met 7 of 9 HLH-2004 criteria, leading to a diagnosis of HLH. Positron emission tomography/computed tomography, flow cytometry, and rheumatologic workup were unremarkable. Treatment with an eight-week course of etoposide and dexamethasone for HLH led to rapid clinical improvement. Over time, her skin lesions regressed and eventually scabbed over to leave hyperpigmented scars, confirming the diagnosis of MHD. She has remained stable, off therapy for 4 years. Although potentially fatal, FUMHD often exhibits favorable outcomes and may resolve without recurrence, as in our patient. FUMHD should be considered in the differential diagnosis for patients presenting with cutaneous CD8 + necrotizing angiocentric lymphoproliferative disease complicated by HLH.

Extragenital lichen sclerosus et atrophicus-morphea overlap as an initial presentation of genital lichen sclerosus.

Lichen sclerosus et atrophicus (LSA) is a chronic inflammatory disorder, most often characterized by atrophic skin plaques located on female genitalia. Infrequently, LSA may present extragenitally; however, much is unknown about the temporal relationship between genital and extragenital LSA. Morphea, also known as localized scleroderma, is a rare inflammatory skin condition characterized by sclerotic plaques. Investigators debate whether LSA and morphea exist on the same spectrum of disease, with LSA representing a superficial variant of morphea involving genitalia, or if they are distinct but coincidental entities. Although researchers have described LSA and morphea occurring in different locations on the same patient, few reports describe LSA and morphea occurring in the same lesion and in the inguinal folds. Herein, we report a case of a 62-year-old woman with extragenital LSA-morphea overlap in the inguinal folds, who three months later developed genital LSA. Extragenital LSA-morphea in the same plaque, with no signs of genital lesions on initial exam, with later development of genital LSA, is especially uncommon. The temporal progression of extragenital LSA-morphea overlap to genital LSA over a three-month period is an important contribution to the literature, as the temporal relationship between extragenital and genital LSA is not previously discussed.

Cutaneous type IV hypersensitivity reaction following tebentafusp treatment for uveal melanoma.

Tebentafusp is a bispecific protein that recently underwent FDA approval for the treatment of metastatic uveal melanoma that functions by redirecting cytotoxic T cells to glycoprotein-100, a protein highly expressed in melanoma. Although clinical trials have demonstrated that rashes are common in the first few days of treatment, little is known about skin reactions that develop later in the treatment course. Herein, we describe a type IV hypersensitivity reaction and vitiligo-like depigmentation that developed six weeks into treatment and discuss the possible mechanisms underlying these reactions. The type IV hypersensitivity reaction resolved without intervention within seven weeks of onset, suggesting that tebentafusp can be safely continued in select patients who develop this cutaneous reaction.

DNA Area and NETosis Analysis (DANA): a High-Throughput Method to Quantify Neutrophil Extracellular Traps in Fluorescent Microscope Images.

BACKGROUND: Neutrophil extracellular traps (NETs), extracellular structures composed of decondensed chromatin and antimicrobial molecules, are released in a process called NETosis. NETs, which are part of normal host defense, have also been implicated in multiple human diseases. Unfortunately, methods for quantifying NETs have limitations which constrain the study of NETs in disease. Establishing optimal methods for NET quantification holds the potential to further elucidate the role of NETs in normal and pathologic processes. RESULTS: To better quantify NETs and NET-like structures, we created DNA Area and NETosis Analysis (DANA), a novel ImageJ/Java based program which provides a simple, semi-automated approach to quantify NET-like structures and DNA area. DANA can analyze many fluorescent microscope images at once and provides data on a per cell, per image, and per sample basis. Using fluorescent microscope images of Sytox-stained human neutrophils, DANA quantified a similar frequency of NET-like structures to the frequency determined by two different individuals counting by eye, and in a fraction of the time. As expected, DANA also detected increased DNA area and frequency of NET-like structures in neutrophils from subjects with rheumatoid arthritis as compared to control subjects. Using images of DAPI-stained murine neutrophils, DANA (installed by an individual with no programming background) gave similar frequencies of NET-like structures as the frequency of NETs determined by two individuals counting by eye. Further, DANA quantified more NETs in stimulated murine neutrophils compared to unstimulated, as expected. CONCLUSIONS: DANA provides a means to quantify DNA decondensation and the frequency of NET-like structures using a variety of different fluorescent markers in a rapid, reliable, simple, high-throughput, and cost-effective manner making it optimal to assess NETosis in a variety of conditions.

Cutaneous lymphoproliferative disorders after COVID-19 vaccination: clinical presentation, histopathology, and outcomes.

Individual reports described lymphoproliferative disorders (LPDs) after COVID-19 vaccination; however, the relationship between cases is unexamined. We aim to determine if there are cases of cutaneous LPDs associated with COVID-19 vaccination and their outcomes. We present a review of world literature, vaccine registries, and two unreported cases of LPDs after COVID-19 vaccination. Review of the medical literature, VAERS, and our two cases reveal predominance of Pfizer-BioNTech vaccine, younger patients, and males. All cases resulted in favorable outcomes. Approximately 84% of cases demonstrated CD30+ positivity in their skin biopsies, suggesting that an antigenic trigger may lead to a type IV adaptive immune response, with clonal expansion of CD30+ T-cells and subsequent oncogenic mutational hits eventuating in transient LPDs. LPDs after COVID-19 vaccination appear in the context of the same vaccines (proportionally to their global market shares), share clinical and pathological findings, and have indolent, self-limited character.

Gammopathic dermopathy: characterization of cutaneous MGUS.

Monoclonal Gammopathy of Undetermined Significance (MGUS) is a clonal plasma cell disorder that is considered preneoplastic, asymptomatic, and only requiring observation. However, MGUS may result in cutaneous complications, which are poorly understood, causing treatment delays and patient suffering. We present 30 patients with cutaneous findings associated with MGUS, characterizing clinical presentations, isoforms, treatments, and outcomes. These included: MGUS-associated 'rashes' (pruritic eczematous rashes), reactive and mucin-depositional conditions (pyoderma gangrenosum, scleromyxedema), M-protein-related deposition disorders (POEMS syndrome, Waldenstrom macroglobulinemia), and cutaneous lymphomas. Twelve of 30 (40%) patients received multiple myeloma drugs (MMDs). Eleven (92%) patients improved, and those not receiving MMDs rarely improved, suggesting that MMDs have efficacy for cutaneous manifestations of MGUS. Therefore, trialing MMDs may be warranted for patients with MGUS not responding to other therapies. Moreover, evaluation for monoclonal gammopathy in elderly patients with intractable pruritus or other chronic skin conditions that are non-responsive to skin-directed therapies should be considered.

Exploring cutaneous lymphoproliferative disorders in the wake of COVID-19 vaccination.

Background: Individual reports have described lymphoproliferative disorders (LPDs) and cutaneous lymphomas emerging after administration of the COVID-19 vaccine; however, the relationship between reactions and vaccine types has not yet been examined. Objective: Determine if there are cases of cutaneous LPDs associated with certain COVID-19 vaccines and their outcomes. Methods: We analysed PubMed, the Vaccine Adverse Events Reporting System (VAERS), and our database for instances of biopsy-proven LPDs following COVID-19 vaccines. Results: Fifty cases of biopsy-proven LPDs arising after COVID-19 vaccination were found: 37 from medical literature, 11 from VAERS and two from our institution. Geographical distribution revealed the most cases in the United States, Italy, and Greece, with single cases in Spain, Colombia, Canada, Japan, and Romania. The average age of patients was 53; with a slight male predominance (male-to-female ratio of 1.5:1). The Pfizer-BioNTech vaccine was associated with LPDs in 36/50 (72%) cases, aligning with its 70% share of the global vaccine market. Histopathology revealed CD30+ in 80% of cases. The most prevalent form of LPD was lymphomatoid papulosis (LyP, 30%). All reported cases produced favourable outcomes (either complete or near-complete remission). Therapeutic approaches ranged from observation to treatment with steroids, methotrexate, or excision. Conclusion: LPDs after COVID-19 vaccination appear in the context of the same vaccines (proportionally to their global market shares), share clinical and pathological findings, and have indolent, self-limited character.

From Molecules to Microbes: Tracing Cutaneous T-Cell Lymphoma Pathogenesis through Malignant Inflammation.

The etiology of CTCL is a subject of extensive investigation. Researchers have explored links between CTCL and environmental chemical exposures, such as aromatic hydrocarbons (eg, pesticides and benzene), as well as infectious factors, including various viruses (eg, human T-lymphotropic virus [HTLV]-I and HTLV-II) and bacteria (eg, Staphylococcus aureus). There has been growing emphasis on the role of malignant inflammation in CTCL development. In this review, we synthesize studies of environmental and infectious exposures, along with research on the aryl hydrocarbon receptor and the involvement of pathogens in disease etiology, providing insight into the pathogenesis of CTCL.

Current status of artificial intelligence methods for skin cancer survival analysis: a scoping review.

Skin cancer mortality rates continue to rise, and survival analysis is increasingly needed to understand who is at risk and what interventions improve outcomes. However, current statistical methods are limited by inability to synthesize multiple data types, such as patient genetics, clinical history, demographics, and pathology and reveal significant multimodal relationships through predictive algorithms. Advances in computing power and data science enabled the rise of artificial intelligence (AI), which synthesizes vast amounts of data and applies algorithms that enable personalized diagnostic approaches. Here, we analyze AI methods used in skin cancer survival analysis, focusing on supervised learning, unsupervised learning, deep learning, and natural language processing. We illustrate strengths and weaknesses of these approaches with examples. Our PubMed search yielded 14 publications meeting inclusion criteria for this scoping review. Most publications focused on melanoma, particularly histopathologic interpretation with deep learning. Such concentration on a single type of skin cancer amid increasing focus on deep learning highlight growing areas for innovation; however, it also demonstrates opportunity for additional analysis that addresses other types of cutaneous malignancies and expands the scope of prognostication to combine both genetic, histopathologic, and clinical data. Moreover, researchers may leverage multiple AI methods for enhanced benefit in analyses. Expanding AI to this arena may enable improved survival analysis, targeted treatments, and outcomes.

Racial and ethnic disparities in the perception of respect from physicians among skin cancer patients in the United States.

Background: Racial and ethnic minority groups are at increased risk of poor skin cancer outcomes. Successful patient-physician communication is linked to better health outcomes, but it is unknown whether disparities in perceived care exist among skin cancer patients. Objective: To investigate whether there are racial and ethnic disparities in the perception of physicians showing respect, listening, and explaining during clinical encounters. Methods: A cross-sectional study was conducted using data from participants with a self-reported skin cancer history from the 2008 to 2017 and 2019 Medical Expenditure Panel Survey. Race and ethnicity were self-identified. Results: Of 5570 participants, 5263 were non-Hispanic White and 307 were racial and ethnic minority individuals. Racial and ethnic minority participants were less likely to report that their doctors show them respect, listen to, and explain to them than non-Hispanic White participants, even when adjusting for age, sex, insurance type, health status, and survey year. Among racial and ethnic minority participants, perceptions of physicians listening and explaining were strongly associated with perceived respect. Limitations: Lack of disaggregated racial and ethnic subgroup analysis. Conclusions: Our findings suggest racial and ethnic disparities in perceived care among skin cancer patients. Future research is warranted to determine whether such perceptions contribute to disparities in skin cancer care and/or outcomes.

Decision Paralysis: Recognition and Patient-Centered Discourse.

Decision paralysis (DP) can be defined as a patient's inability to commit to a physician and/or initiate appropriate treatment for their condition. An incessant search for greater physician opinions often leads to treatment delay, disease progression, and initiation of care at more advanced stages. Despite the harms associated with DP, a dearth of research on the issue remains. There are no guidelines that assist in both recognition and rectification of DP, leaving patients with chronic illnesses and diagnoses without well-characterized treatment algorithms especially vulnerable. This paper analyzes why patients are inclined toward DP and the clinical implications. Review of the literature affirms that the patient-physician relationship holds considerable influence; physicians identifying DP can improve therapeutic outcomes for their patients. Using these findings, we then propose a framework for broaching this topic with a method that supports patients while respecting their autonomy. A practical approach to both recognition and patient-centered discourse is introduced, providing a foundation for physicians to host these conversations and understand their patients' perspectives. This approach toward recognition and discourse on DP holds clinical importance, given that there is a paucity of established guidance. A future uniform approach may generate optimal patient care recommendations, which will hold far-reaching impact on both the patient-physician relationship and overall patient outcomes.

Topical Mechlorethamine for the Treatment of Psoriasis: A Report of Two Cases and Literature Review.

INTRODUCTION: Psoriasis is a common inflammatory skin disease that significantly impacts patients' psychosocial wellbeing. Despite increasingly effective treatment options, the recurrence of plaques after discontinuation of therapy in many patients highlights the need for additional therapies. METHODS: We report two cases of patients with concurrent psoriasis and mycosis fungoides who were treated with topical mechlorethamine (MCH). A literature review was performed by searching PubMed using the keywords psoriasis, mechlorethamine, chlormethine, and nitrogen mustard. RESULTS: Both patients had significant improvement in their psoriasis following treatment with topical MCH gel, which was well tolerated and maintained clearance after 1 and 3 years of follow-up. Seven prospective cohort studies investigating the use of topical MCH were identified through literature review. Out of five studies reporting clinical outcomes by patient, 68 of 77 patients (88%) experienced an improvement in their psoriasis, with 47 of 77 (61%) achieving complete or near-complete clearance. The remaining two studies reported clinical outcomes by lesion, demonstrating improvement in 40 of 45 lesions (88%) and complete or near-complete clearance in 32 of 42 lesions (76%). Contact dermatitis was the most frequent adverse effect, observed in 56 of 125 patients (45%). CONCLUSIONS: Topical MCH may be an option for patients with psoriasis who fail or have incomplete responses to other treatments. Published studies are limited by lack of standardized treatment regimens and well-defined outcome measures, highlighting the need for prospective clinical trials to better understand the utility of this topical agent in psoriasis.

Clusters, crop dusters, and myth busters: a scoping review of environmental exposures and cutaneous T-cell lymphoma.

INTRODUCTION: Cutaneous T-cell lymphoma (CTCL) is a heterogenous group of non-Hodgkin lymphomas. Similar presentation to benign conditions, significant genetic variation, and lack of definitive biomarkers contributes to diagnostic delay. The etiology of CTCL is unknown, and environmental exposures, such as geographic, occupational, chemicals, sunlight, and insects have been investigated. EVIDENCE ACQUISITION: Review of the literature for CTCL and exposures was performed in PubMed and Google Scholar in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) Extension for Scoping Reviews. This search yielded 193 total results, which were initially screened with defined inclusion and exclusion criteria. The 45 remaining articles were reviewed and classified by exposure type. EVIDENCE SYNTHESIS: The most frequently investigated CTCL exposure type was geographic (13/45 articles, 29%). Chemical exposures were commonly discussed (10/45 articles, 22%), along with occupational (10/45 articles, 22%). Insect exposures (6/45, 13%) and sun exposure (3/45, 7%) were also reviewed, along with articles describing multiple exposure types (3/45, 7%). Article types ranged from cases to systematic reviews and case-control studies. Evidence linking CTCL and these exposures was mixed. Limitations of this investigation include reliance on patient reporting and frequent speculation on disease association versus causality. CONCLUSIONS: This investigation synthesizes the current literature on exposures potentially implicated in the pathogenesis of CTCL, while offering guidance on patient history-taking to ensure potential exposures are captured. Awareness of these possible associations may improve understanding of disease pathogenesis and diagnosis. Moreover, these insights may help with public health decision-making and disease mitigation.

Accessibility and readability of online patient education on cutaneous lymphomas.

Background: Patients facing a cutaneous lymphoma diagnosis frequently turn to the internet for information but finding patient-accessible education may be a challenge. Objective: To investigate accessibility and readability of patient-oriented online education on cutaneous lymphomas, including cutaneous T-cell and B-cell lymphoma subtypes. Methods: This study queried a search engine for 11 cutaneous lymphoma terms, resulting in 1083 webpages. Webpages were screened using defined inclusion/exclusion criteria; literature directed to physicians and scientists was excluded. Webpages were stratified by academic/nonacademic and dermatology/nondermatology hosts and assessed by order of appearance. Readability, including text complexity, was analyzed for grade level understanding using 5 established calculators. Overall readability was assessed by Flesch-Kincaid Reading Ease. Results: Academic webpages had earlier order of appearance. There was a dearth in dermatology-hosted webpages. Rarer cutaneous lymphomas yielded fewer patient-accessible results. Search term readability significantly exceeded the American Medical Association-recommended sixth grade level (P < .001∗), with higher grade levels for cutaneous T-cell lymphoma subtype webpages than cutaneous B-cell lymphoma subtypes. Limitations: Webpage quality, accuracy, and language were not assessed. Conclusion: Current online education for cutaneous lymphomas exceeds the American Medical Association's maximum readability recommendation. There is a need for more patient-accessible education amidst predominance of scientific literature, greater dermatology host websites, and enhanced readability of existing online education.

Disordered Antigens and Epitope Overlap Between Anti-Citrullinated Protein Antibodies and Rheumatoid Factor in Rheumatoid Arthritis.

OBJECTIVE: Anti-citrullinated protein antibodies (ACPAs) and rheumatoid factor (RF) are commonly present in rheumatoid arthritis (RA) without a clear rationale for their coexistence. Moreover, autoantibodies develop against proteins with different posttranslational modifications and native proteins without obvious unifying characteristics of the antigens. We undertook this study to broadly evaluate autoantibody binding in seronegative and seropositive RA to identify novel features of reactivity. METHODS: An array was created using a total of 172,828 native peptides, citrulline-containing peptides, and homocitrulline-containing peptides derived primarily from proteins citrullinated in the rheumatoid joint. IgG and IgM binding to peptides were compared between cyclic citrullinated peptide (CCP)-positive RF+, CCP+RF-, CCP-RF+, and CCP-RF- serum from RA patients (n = 48) and controls (n = 12). IgG-bound and endogenously citrullinated peptides were analyzed for amino acid patterns and predictors of intrinsic disorder, i.e., unstable 3-dimensional structure. Binding to IgG-derived peptides was specifically evaluated. Enzyme-linked immunosorbent assay confirmed key results. RESULTS: Broadly, CCP+RF+ patients had high citrulline-specific IgG binding to array peptides and CCP+RF- and CCP-RF+ patients had modest citrulline-specific IgG binding (median Z scores 3.02, 1.42, and 0.75, respectively; P < 0.0001). All RA groups had low homocitrulline-specific binding. CCP+RF+ patients had moderate IgG binding to native peptides (median Z score 2.38; P < 0.0001). The highest IgG binding was to citrulline-containing peptides, irrespective of protein identity, especially if citrulline was adjacent to glycine or serine, motifs also seen in endogenous citrullination in the rheumatoid joint. Highly bound peptides had multiple features predictive of disorder. IgG from CCP+RF+ patients targeted citrulline-containing IgG-derived peptides. CONCLUSION: Disordered antigens, which are frequently citrullinated, and common epitopes for ACPAs and RF are potentially unifying features for RA autoantibodies.