Enfortumab Vedotin Drug Eruption: Cutaneous Adverse Events and Histopathologic Findings.

ABSTRACT: Enfortumab is a monoclonal antibody directed against nectin-4 and, when combined with vedotin, is an antibody-drug conjugate approved for the treatment of locally advanced or metastatic urothelial cancers. A 75-year-old woman with stage IV papillary urothelial carcinoma of the bladder who completed cycle 2 of enfortumab vedotin (EV) infusions presented to our dermatology department for new-onset symmetric and painful dusky erythematous patches on the extremities and trunk without mucosal involvement. Two biopsies were obtained, which revealed an interface dermatitis with notable ring mitoses within the basal and suprabasal layers of the epidermis without epidermal necrosis. The patient was diagnosed with toxic erythema of chemotherapy and improved with application of triamcinolone 0.1% ointment twice daily without discontinuation of her EV infusions. Although a targeted therapy, EV commonly exhibits cutaneous side effects due to the expression of nectin-4 in the skin. Most cutaneous side effects are mild and can be managed symptomatically. However, severe drug-induced eruptions, such as toxic epidermal necrolysis, have been described. The histologic findings of EV associated skin eruptions can aid in correctly identifying the culprit drug and assist in management. This case provides insights for dermatologists by highlighting the common cutaneous side effects of EV and the associated histologic findings as this targeted therapy becomes increasingly utilized in the treatment of refractory neoplasms.

Critical Reflection to Investigate Medical Student Attitudes Toward Skin Tone in Their Preclinical Years.

INTRODUCTION: Implicit racial bias, defined as unreasoned judgement based solely on an individual's skin color, is a persistent barrier to quality medical care for people of color in the United States. Early, learner-centered intervention is crucial to establish cultural competence within health professional training programs. METHODS: Over 3 academic years, preclinical, second-year medical students were asked to submit an anonymous critical reflection regarding skin tone in medicine (n=794). Critical reflection is an instructional approach that encourages students to investigate their own thoughts and actions. Course credit was given based on the honor system. Reflection submission content and student feedback were analyzed quantitatively and qualitatively using constructivist thematic analysis. RESULTS: Most students completed the assignment (93.0%) and reported feeling comfortable expressing themselves honestly in the anonymous format (84.6%). Students' comfort level with honesty declined if they would have had to identify themselves (50.8%). Student comments indicated relief to have a place to process experiences and emphasized the importance of anonymity for value of this assignment. Thematic analysis identified 2 themes and 13 subthemes among student submissions. Submissions varied in format and typically contained multiple codes (4.08 ± 1.77 subthemes), indicating that students participated meaningfully in the assignment. CONCLUSIONS: Although some educators may hesitate to address these topics, students at our institution appreciated having a space to process their thoughts. This assignment structure is an effective way for educators to address a difficult, sensitive, and important topic in a meaningful way with students.

African American race is a risk factor for severe hidradenitis suppurativa.

BACKGROUND: African Americans face a disproportionate incidence and prevalence of hidradenitis suppurativa (HS) in the United States, but HS severity and outcomes across racial and ethnic groups have not been well-established while controlling for potentially confounding factors. In this retrospective cohort study, we investigated the associations of race and ethnicity with HS severity, emergency department (ED) visits, hospitalizations, and surgeries for HS while controlling for age, sex, body mass index (BMI), tobacco use, and insurance type. METHODS: We reviewed 1190 patients seen at the Medical College of Wisconsin with ≥3 encounters for HS between 1/1/2002 and 3/19/2019, excluding those without race data or an encounter in which HS was treated. RESULTS: A total of 953 patients were included; 470 patients were Black or African American non-Hispanic (49%), 39 Hispanic (4%), 418 White non-Hispanic (44%), and 26 other race or ethnicity (3%). Controlling for age, sex, BMI, tobacco use, and insurance type, Black patients had 2.8 times the odds of having Hurley stage III disease (95% CI 1.76-4.45, P < 0.001), 2.86 times the risk for experiencing an ED visit for HS (95% CI 2.12-3.88, P < 0.001), 2.25 times the risk for experiencing a hospitalization for HS (95% CI 1.42-3.56, P < 0.001), and 1.61 times the risk for experiencing a surgical encounter for HS (95% CI 1.34-1.95, P < 0.001) when compared to White patients. CONCLUSIONS: African Americans face significant disparities in HS severity, ED visits, hospitalizations, and surgeries. The causes of these disparities must be further investigated and addressed.

Racial disparities of delay in diagnosis and dermatologic care for hidradenitis suppurativa.

Hidradenitis suppurativa is a chronic, debilitating skin disease that disproportionately affects African Americans, and care-related factors may contribute to this disparity. In this study, we investigated delay in diagnosis and dermatologic care for HS at an urban Midwestern Academic Center. A retrospective chart review of 1,190 patients with 3 or more encounters for HS between 1/1/2002 and 3/19/2019 was conducted. A total of 953 patients were included in statistical analysis. A mean (standard deviation) delay in diagnosis was 4.1 ± 7.0 years. For white patients the delay in diagnosis was 3.2 ± 6.3 years, for Black patients 4.8 ± 7.0 years, for Hispanic patients 4.7 ± 5.8 years, and for other races 4.9 ± 7.4 years (p <0.001). Among the 932 patients with known specialist visit types, 500 (53.6%) had seen dermatology including 222 (47.8%) of Black patients, 242 (59.5%) of white patients, 24 (64.9%) of Hispanic patients, and 12 (50%) patients of other races (p=0.003).White patients and Hispanic patients saw a dermatologist an average of 3.0 years after first presentation of HS and Black patients saw a dermatologist on average 5.0 years after first presentation (p=0.004). Of the patients who did see dermatology, 44.9% of Black patients, 31.6% of white patients, 23.1% of Hispanic patients, and 30.8% of other races saw surgery before dermatology (p<.001). Our results indicate that non-white patients have a longer delay in diagnosis than their white counterparts and that Black patients do not see dermatology as early in their disease course as other racial groups. Black patients also see surgery more often than white patients before seeing dermatology, which could suggest greater disease severity at presentation and diagnosis or difficult access to dermatology.

Cutaneous Herpetiform Ulcerations as the Presenting Sign of an Acute Aortic Occlusion.

This case report describes a woman in her 40s with a 2-week history of abrupt painful ulcerations of the perineum.

Subepidermal calcified nodule on the periungual finger successfully treated with ablative carbon dioxide laser.

Subepidermal calcified nodules are lesions that primarily affect children and are most commonly located on the head. The current standard of treatment for these is surgical excision. However, surgical excision is not always possible and may not be cosmetically favorable. We describe the use of a CO2 laser as a successful treatment for a subepidermal calcified nodule of the finger.

A case of primary cutaneous Ewing sarcoma in a neutropenic patient.

Primary cutaneous Ewing sarcoma is a rare clinical presentation of Ewing sarcoma, usually occurring as a small, localized tumor on the extremities of young adults and associated with favorable prognosis. We report a case of primary cutaneous Ewing sarcoma, which presented on the sole of the foot of a 27-year-old patient with relapsed acute myeloid leukemia and neutropenia. Diagnosis was determined through histological features and staining, as well as fluorescence in situ hybridization and molecular testing. The patient underwent wide-local excision with plan to begin targeted chemotherapy, but unfortunately died from adenovirus pneumonia while neutropenic before targeted chemotherapy was initiated.

Loss of CENP-F results in distinct microtubule-related defects without chromosomal abnormalities.

Microtubule (MT)-binding centromere protein F (CENP-F) was previously shown to play a role exclusively in chromosome segregation during cellular division. Many cell models of CENP-F depletion show a lag in the cell cycle and aneuploidy. Here, using our novel genetic deletion model, we show that CENP-F also regulates a broader range of cellular functions outside of cell division. We characterized CENP-F(+/+) and CENP-F(-/-) mouse embryonic fibroblasts (MEFs) and found drastic differences in multiple cellular functions during interphase, including cell migration, focal adhesion dynamics, and primary cilia formation. We discovered that CENP-F(-/-) MEFs have severely diminished MT dynamics, which underlies the phenotypes we describe. These data, combined with recent biochemical research demonstrating the strong binding of CENP-F to the MT network, support the conclusion that CENP-F is a powerful regulator of MT dynamics during interphase and affects heterogeneous cell functions.

Isolation and physiological analysis of mouse cardiomyocytes.

Cardiomyocytes, the workhorse cell of the heart, contain exquisitely organized cytoskeletal and contractile elements that generate the contractile force used to pump blood. Individual cardiomyocytes were first isolated over 40 years ago in order to better study the physiology and structure of heart muscle. Techniques have rapidly improved to include enzymatic digestion via coronary perfusion. More recently, analyzing the contractility and calcium flux of isolated myocytes has provided a vital tool in the cellular and sub-cellular analysis of heart failure. Echocardiography and EKGs provide information about the heart at an organ level only. Cardiomyocyte cell culture systems exist, but cells lack physiologically essential structures such as organized sarcomeres and t-tubules required for myocyte function within the heart. In the protocol presented here, cardiomyocytes are isolated via Langendorff perfusion. The heart is removed from the mouse, mounted via the aorta to a cannula, perfused with digestion enzymes, and cells are introduced to increasing calcium concentrations. Edge and sarcomere detection software is used to analyze contractility, and a calcium binding fluorescent dye is used to visualize calcium transients of electrically paced cardiomyocytes; increasing understanding of the role cellular changes play in heart dysfunction. Traditionally used to test drug effects on cardiomyocytes, we employ this system to compare myocytes from WT mice and mice with a mutation that causes dilated cardiomyopathy. This protocol is unique in its comparison of live cells from mice with known heart function and known genetics. Many experimental conditions are reliably compared, including genetic or environmental manipulation, infection, drug treatment, and more. Beyond physiologic data, isolated cardiomyocytes are easily fixed and stained for cytoskeletal elements. Isolating cardiomyocytes via perfusion is an extremely versatile method, useful in studying cellular changes that accompany or lead to heart failure in a variety of experimental conditions.

Dermatology on Tumblr.

Tumblr broke into the social media scene in 2007 as a micro-blogging platform that hosts 169 million blogs, 75 billion total posts, and 111 million posts daily to date. This study aimed to determine the presence of dermatology-focused journals, organizations, and groups on Tumblr. These were entered into the Tumblr search query to identify affiliated Tumblr blogs and 'dermatology Tumblr' was searched on Google to determine the first four distinct results that were active within the last six months. None of the dermatology-focused journals, organizations, or groups maintained a Tumblr blog and three of the first four blogs on Google were maintained by private practices. In conclusion, Tumblr remains a social media domain that lacks a strong presence from dermatology journals and organizations, remaining an untapped resource for information dissemination and interaction with the public.