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.

Superficial Atypical Lipomatous Tumor With Pleomorphic Features: Case Report and Discussion of the Literature.

ABSTRACT: Among liposarcomas, well-differentiated liposarcoma and dedifferentiated liposarcoma are the most common. The majority of these tumors are found in deep retroperitoneum or extremities. When found outside the retroperitoneum, these adipose-derived tumors are known as atypical lipomatous tumors (ALT). Superficial ALT are particularly rare; thus, little is known about their clinical presentation, genomic status, and management. Here, we present the case of a 54-year-old man with an intermittently bothersome, slowly growing mass on his left upper back for over 2 years, which was incidentally diagnosed as ALT. This patient's ALT, however, showed a profound degree of pleomorphism with MDM2 and control centromere 12 (CEP12) coamplification and negative CD34 and S100 and RB1 expression, unlike most other ALT described in the literature. This case report details the diagnostic workup and histopathological findings for adipose tumors and summarizes the different subtypes, including atypical spindle cell/pleomorphic lipomatous tumor, pleomorphic liposarcoma, and spindle cell/pleomorphic lipoma, with brief discussion on management.

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.

Microcystins: Biogenesis, Toxicity, Analysis, and Control.

Microcystins are cyclic peptide toxins formed by cyanobacteria. These toxins are recognized for their association with algal blooms, posing a significant threat to ecosystems and drinking water quality. Due to the growing environmental concerns they raise, a comprehensive review on microcystins' genesis, toxicity, and analytical methods for their quantitative determination is outlined. Genes, including the mcyABC cluster, regulate microcystin biogenesis. Bioanalytical experiments have identified key environmental factors, such as temperature and nitrogen availability, that promote microcystin production. Microcystin toxicity is explored based on its modulatory effects on protein phosphatases 1 and 2A in specific tissues and organs. Additionally, biochemical mechanisms of chelation, transportation, resultant oxidative stress, and tumor promotion abilities of microcystins are also discussed. Various analytical methods to separate, detect, and quantify microcystins, including the quantitative real-time polymerase chain reaction, enzyme-linked immunosorbent assay, nuclear magnetic resonance spectroscopy, and chromatographic platforms-linked tandem mass spectrometry (LC-MS) for unequivocal structural identification, are also reviewed. Since control of microcystins in water is of great necessity, both water treatment and mechanisms of abiotic transformation and microbial degradation are also discussed.

Structural basis for lipid binding and mechanism of the Mycobacterium tuberculosis Rv3802 phospholipase.

The Mycobacterium tuberculosis rv3802c gene encodes an essential enzyme with thioesterase and phospholipase A activity. Overexpression of Rv3802 orthologs in Mycobacterium smegmatis and Corynebacterium glutamicum increases mycolate content and decreases glycerophospholipids. Although a role in modulating the lipid composition of the unique mycomembrane has been proposed, the true biological function of Rv3802 remains uncertain. In this study, we present the first M. tuberculosis Rv3802 X-ray crystal structure, solved to 1.7 Å resolution. On the basis of the binding of PEG molecules to Rv3802, we identified its lipid-binding site and the structural basis for phosphatidyl-based substrate binding and phospholipase A activity. We found that movement of the α8-helix affords lipid binding and is required for catalytic turnover through covalent tethering. We gained insights into the mechanism of acyl hydrolysis by observing differing arrangements of PEG and water molecules within the active site. This study provides structural insights into biological function and facilitates future structure-based drug design toward Rv3802.

The Case for Advocacy Curricula and Opportunities in Medical Education: Past Examples to Inform Future Instruction.

ABSTRACT: With recent advances in understanding racial, socioeconomic, and mental health issues in medicine and their relation to policy and legislation, medical professionals are increasingly involved in local and national advocacy efforts. At the frontlines of these initiatives are medical students who, in addition to completing required coursework and clinical training, devote themselves to serving patients through civic participation. The burgeoning evidence concerning health care disparities and inequity, along with greater awareness of racial and socioeconomic discrimination, have made advocacy an essential aspect of many students' medical training. Every year, thousands of medical students join national medical advocacy organizations, in addition to regional, state, and local groups. Despite the rich history of medical student involvement in advocacy, there remains much speculation and skepticism about the practice as an essential component of the medical profession. From early initiatives pushing for national health insurance after World War II to encouraging antidiscrimination policies and practices, medical students have been collectively working to create change for themselves and their patients. Through efforts such as banning smoking on airplanes, creating safe syringe programs, and protesting against police brutality, many medical students work tirelessly in advocacy despite minimal educational support or guidance about the advocacy process. Given that medical student advocacy continues to grow and has shown measurable successes in the past, the authors believe that these efforts should be rewarded and expanded upon. The authors examine historical examples of medical student advocacy to suggest ways in which advocacy can be integrated into core medical school curricula and activities. They call attention to opportunities to support students' development of knowledge and skills to facilitate legislative change, expansion of interprofessional collaborations and credit, and curricular updates to promote social and health equity.

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.

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.

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.

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.

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.

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.