Toxic epidermal necrolysis-like cutaneous toxicity following chimeric antigen receptor T-cell therapy in recurrent large B-cell lymphoma.

Chimeric antigen receptor (CAR) T-cell therapy has demonstrated remarkable success in treating various B-cell malignancies, redirecting T-cell cytotoxicity toward cancer cells. Despite its efficacy, CAR-T therapy is associated with potential risks, including cytokine release syndrome (CRS) and cytopenia. We present a case of a 69-year-old man with diffuse large B-cell lymphoma treated with axicabtagene-ciloleucel CAR-T therapy, who developed a rare and severe cutaneous toxicity resembling toxic epidermal necrolysis (TEN). The patient exhibited persistent fevers, CRS, and subsequent development of a widespread erythematous macular eruption, progressing to vesiculation with bullae. Notably, allopurinol-induced TEN was considered with the patient's recent exposure to allopurinol, although the onset and minimal mucosal involvement did not align with typical presentations of allopurinol-induced cases. The cutaneous reaction, distinct from typical SJS/TEN, showed minimal mucosal involvement and coincided with the cytokine release storm, differing from allopurinol-induced TEN. Despite the absence of guidelines, the patient was managed with systemic steroids, achieving significant improvement. This case expands the spectrum of CAR-T therapy-related cutaneous toxicities, highlighting the need for early recognition of histopathology and tailored management by dermatologists. Further understanding of these reactions is crucial for optimizing the safety profile of this groundbreaking immunotherapy.

Eczema exacerbation following herpes zoster infection in an immunocompetent patient: A case report.

This case report highlights a severe eczematous rash manifesting broadly across the scalp, face, and neck of a 54-year-old female following a resolved herpes zoster infection. Notably, such cutaneous reactions post-varicella zoster virus infection, which may present weeks to years after the acute phase, have been documented but remain poorly understood in their pathogenesis. This patient exhibited a blistering rash diagnosed as shingles with overlying cellulitis, initially treated with valacyclovir and cefalexin. Upon returning with a diffuse rash post-treatment, further examination and tests led to a differential diagnosis that most closely aligned with eczema exacerbation with superimposed bacterial infection, confirmed by the presence of methicillin-resistant Staphylococcus aureus. Treatment encompassed intravenous vancomycin, ciprofloxacin eye drops, topical hydrocortisone, betamethasone lotion, and gabapentin, leading to substantial improvement. This case underscores the complexity of diagnosing and managing cutaneous reactions post-varicella zoster virus infection and suggests a multimodal treatment approach may yield favorable outcomes.

Topical Ruxolitinib in the Treatment of Necrobiosis Lipoidica: A Prospective, Open-Label Study.

Necrobiosis lipoidica (NL) is a rare granulomatous disease. There are few effective treatments for NL. We sought to investigate the efficacy and safety of the Jak1/2 inhibitor, ruxolitnib, in the treatment of NL and identify the biomarkers associated with the disease and treatment response. We conducted an open-label, phase 2 study of ruxolitinib in 12 patients with NL. We performed transcriptomic analysis of tissue samples before and after treatment. At week 12, the mean NL lesion score decreased by 58.2% (SD = 28.7%, P = .003). Transcriptomic analysis demonstrated enrichment of type I and type II IFN pathways in baseline disease. Weighted gene coexpression network analysis demonstrated post-treatment changes in IFN pathways with key hub genes IFNG and signal transducer and activator of transcription 1 gene STAT1. Limitations include small sample size and a study group limited to patients with <10% body surface area. In conclusion, ruxolitinib is an effective treatment for NL and targets the key pathogenic mediators of the disease.

Oral Baricitinib in the Treatment of Cutaneous Lichen Planus.

Background: Cutaneous lichen planus (LP) is a recalcitrant, difficult-to-treat, inflammatory skin disease characterized by pruritic, flat-topped, violaceous papules on the skin. Baricitinib is an oral Janus kinase (JAK) 1/2 inhibitor that interrupts the signaling pathway of interferon (IFN)-γ, a cytokine implicated in the pathogenesis of LP. Methods: In this phase II trial, twelve patients with cutaneous LP received baricitinib 2 mg daily for 16 weeks, accompanied by in-depth spatial, single-cell, and bulk transcriptomic profiling of pre-and post-treatment samples. Results: An early and sustained clinical response was seen with 83.3% of patients responsive at week 16. Our molecular data identified a unique, oligoclonal IFN-γ, CD8+, CXCL13+ cytotoxic T-cell population in LP skin and demonstrate a rapid decrease in interferon signature within 2 weeks of treatment, most prominent in the basal layer of the epidermis. Conclusion: This study demonstrates the efficacy and molecular mechanisms of JAK inhibition in LP. Trial Registration Number : NCT05188521.

Characteristics of Matched vs Nonmatched Dermatology Applicants.

Dermatology residency continues to be one of the most competitive specialties, with a match rate of 84.7% in 2019. We surveyed 475 dermatology applicants who applied to the Mayo Clinic in Scottsdale, Arizona, during the 2018-2019 application cycle and 629 dermatology applicants who applied to the Mayo Clinic in Scottsdale; Rochester, Minnesota; and Jacksonville, Florida, during the 2019-2020 application cycle. The initial survey obtained application and demographic information. The follow-up survey obtained match data. The initial 2019 and 2020 surveys were completed by 149 and 142 dermatology applicants, respectively, and 112 and 124 applicants completed the respective follow-up surveys. Our survey finds that factors associated with matching included a higher US Medical Licensing Examination (USMLE) Step 1 score, having a home dermatology program, and a higher number of interviews offered and attended. Some demographics had varying USMLE Step 1 scores but similar match rates.

Characteristics of ulcerated and non-ulcerated necrobiosis lipoidica.

BACKGROUND: Necrobiosis lipoidica (NL) is complicated by ulceration in up to 35% of cases. METHODS: Retrospective study of patients with NL seen at our institution between January 1, 1992, and May 25, 2021, was conducted. Ulcerated NL (UNL, n = 83) and non-ulcerated NL (NUNL, n = 233) groups were compared. RESULTS: Twenty-six percent (83/316) of patients with NL experienced ulceration. UNL was significantly more likely to be painful (52% vs. 36%, P = 0.01), was more likely to have a lesion-associated cutaneous malignancy (7% vs. 0%, P < 0.001), and had a larger median size (7 vs. 5 cm, P = 0.004) compared to NUNL. Vascular studies were performed on a subset of patients and revealed transcutaneous oxygen pressure (TcPO2) < 40 mm Hg in 53% and venous insufficiency in 62% with no significant differences between UNL and NUNL groups. In patients with unilateral ulceration, mean TcPO2 values (39.7 vs. 46.6 mm Hg), regional perfusion index <0.6 (29% vs. 14%), and TcPO2 < 40 mm Hg (43% vs. 14%) were worse in the ulcerated leg compared to the non-ulcerated leg, but these differences were not statistically significant. CONCLUSIONS: UNL was more likely to be painful, develop lesion-associated malignancy, and be larger in size compared to NUNL. There were no statistically significant differences in venous insufficiency, arterial Doppler/ankle brachial index, or TcPO2 values between UNL and NUNL patients, however, a significant portion of the cohort demonstrated abnormal vascular studies, particularly on TcPO2 and venous insufficiency testing.

Secukinumab for the treatment of adult-onset pityriasis rubra pilaris: a single-arm clinical trial with transcriptomic analysis.

BACKGROUND: The pathogenesis of pityriasis rubra pilaris (PRP) is not completely understood, but interleukin (IL)-17 has been shown to play a critical role. There are no reliable immunomodulatory agents to treat PRP. We conducted an open-label, single-arm clinical trial of secukinumab, a monoclonal antibody that inhibits IL-17A, for the treatment of PRP. OBJECTIVES: To evaluate the clinical efficacy of secukinumab and define the transcriptomic landscape of PRP and its response to IL-17A blockade. METHODS: Twelve patients with PRP were recruited for an open-label trial of secukinumab. Patients received a 24-week course of secukinumab. The primary endpoint was a ≥ 75% reduction in Psoriasis Area and Severity Index (PASI 75) from baseline to week 28. Secondary endpoints included PASI 90, change in Physician's Global Assessment (PGA), and change in Dermatology Life Quality Index (DLQI). RNA sequencing was performed on lesional and nonlesional skin biopsies obtained at baseline and week 2. Sample groups were compared to identify differential gene expression and pathway enrichment. This trial was registered with ClinicalTrials.gov: 'Cosentyx (secukinumab) for the treatment of adult onset pityriasis rubra pilaris' - NCT03342573. RESULTS: At week 28, six of 11 patients (55%) achieved PASI 75, and three patients (27%) achieved PASI 90. PGA (P = 0.008) and DLQI scores (P = 0.010) showed significant improvement with treatment. No serious treatment-related adverse events were encountered. Treatment with secukinumab normalized transcriptional differences between lesional and nonlesional skin. Transcriptomic data from nonresponsive patients suggest that overactivity of innate immune pathways may be driving resistance to secukinumab. CONCLUSIONS: Secukinumab appears to be an effective treatment for PRP and warrants further investigation. PRP is a transcriptionally heterogeneous disease, reflecting its variable response to therapy. Agents targeting other IL-17 isoforms and innate immune mediators should be considered for future clinical trials. What is already known about this topic? The pathogenesis of pityriasis rubra pilaris is incompletely understood. Successful treatment has been reported with a variety of immunomodulatory agents, but disease is often refractory to therapy. Interleukin (IL)-17 is thought to drive keratinocyte proliferation and vascular dysfunction in this disease. A previous trial demonstrated efficacy of the anti-IL-17A drug ixekizumab for pityriasis rubra pilaris. What does this study add? Herein we describe the findings of a clinical trial of secukinumab, an anti-IL-17A monoclonal antibody, for the treatment of pityriasis rubra pilaris. Secukinumab was effective in treating pityriasis rubra pilaris. Our transcriptomic data give new insight into the expressional changes that occur in response to secukinumab and suggest mechanisms of treatment resistance.

Histopathologic features of necrobiosis lipoidica.

BACKGROUND: Necrobiosis lipoidica (NL) is an uncommon granulomatous dermatosis that can occur in patients with or without associated diabetes mellitus (DM). Prior studies have attempted to determine distinctive histopathologic features of NL in patients with and without DM. METHODS: A retrospective review of 97 patients with NL was performed to determine the similar and distinctive histopathologic features in patients with DM and without DM. RESULTS: Of the 97 patients, 32% (n = 31) had DM. Epidermal acanthosis was seen more commonly in diabetics than nondiabetics (32.3% vs. 12.1%; p = 0.017). Naked (sarcoidal/tuberculoid) granulomas were more frequently observed in nondiabetics than diabetics (22.7% vs. 3.2%; p = 0.016). Eosinophils were more common in nondiabetics than diabetics (38.5% vs. 9.7%; p = 0.004), while neutrophilic infiltration was more common in diabetics than nondiabetics (45.2% vs. 17.5%; p = 0.004). CONCLUSIONS: This study corroborates well-documented histopathologic features of NL and shows distinctive histopathologic features of NL among patients with DM-I, DM-II, and without DM. These results support the hypothesis that there are different underlying drivers of NL between diabetics and nondiabetics.

The role of race and ethnicity in the dermatology applicant match process.

OBJECTIVE: The field of dermatology is one of the least racially diverse specialties. We aimed to identify ways in which minorities become underrepresented within dermatology. METHODS: We surveyed dermatology applicants who applied to Mayo Clinic in Scottsdale, AZ during the 2018-2019 application cycle and Mayo Clinic in Rochester, Scottsdale, and Jacksonville during the 2019-2020 application cycles. Underrepresented minorities (URM) were defined as Latino/Latina, African American, American Indian/Alaska Native, or Native Hawaiian/Pacific Islander. RESULTS: In total, 149 and 142 dermatology applicants completed the initial 2019 and 2020 surveys, 112 and 124 completed the follow-up surveys. The racial breakdown was 69.9% Caucasian, 23.7% Asian, 5.4% African American, 0.4% American Indian/Alaska Native, and 0.7% Native Hawaiian/Pacific Islander. Eight percent identified as Hispanic/Latino. Median Step 1 scores were lower for URM (p<0.01). URM had more publications (p=0.01). There were no observed differences in away rotations or interviews attended. URM were less likely to match (76.7%) vs. Whites (88.4%) and Asians (96.0%; p=0.03). CONCLUSION: URM are taking out more loans, pursuing research fellowships more often than their White counterparts, publishing more, completing the same number of away rotations and interviews, yet have lower match rates leading to underrepresentation in the field. It is important to realize how Step scores might reflect and reproduce disparities between different racial/ethnic backgrounds, in turn influencing the racial composition of dermatology residency programs.

The role research gap years play in a successful dermatology match.

BACKGROUND: A new trend includes taking a dedicated year away from medical school to complete a research fellowship. There is minimal data on the benefit of a gap year. We aimed to identify if a gap year makes a dermatology applicant more successful in The Match. METHODS: Dermatology applicants who applied to Mayo Clinic Arizona for the 2018-2019 application cycle and Mayo Clinic Rochester, Arizona, and Florida for the 2019-2020 application cycle were surveyed. RESULTS: In total, 291 dermatology applicants completed the initial survey, and 236 completed the follow-up survey. Ninety applicants took a gap year, 198 applicants did not. There was no significant difference in match rates. When comparing match rates at top dermatology residency programs, 40.6% of gap-year applicants matched to these residencies versus 19.0% of no gap-year applicants (P < 0.01). CONCLUSION: Applicants should weigh the opportunity costs before pursuing research gap years as they may not be universally helpful. Applicants who want to match at a top dermatology program may benefit from a research gap year. This data may have limited generalizability outside of the United States.

A Mathematical Model of the Dynamics of Cytokine Expression and Human Immune Cell Activation in Response to the Pathogen Staphylococcus aureus.

Cell-based mathematical models have previously been developed to simulate the immune system in response to pathogens. Mathematical modeling papers which study the human immune response to pathogens have predicted concentrations of a variety of cells, including activated and resting macrophages, plasma cells, and antibodies. This study aims to create a comprehensive mathematical model that can predict cytokine levels in response to a gram-positive bacterium, S. aureus by coupling previous models. To accomplish this, the cytokines Tumor Necrosis Factor Alpha (TNF-α), Interleukin 6 (IL-6), Interleukin 8 (IL-8), and Interleukin 10 (IL-10) are included to quantify the relationship between cytokine release from macrophages and the concentration of the pathogen, S. aureus, ex vivo. Partial differential equations (PDEs) are used to model cellular response and ordinary differential equations (ODEs) are used to model cytokine response, and interactions between both components produce a more robust and more complete systems-level understanding of immune activation. In the coupled cellular and cytokine model outlined in this paper, a low concentration of S. aureus is used to stimulate the measured cellular response and cytokine expression. Results show that our cellular activation and cytokine expression model characterizing septic conditions can predict ex vivo mechanisms in response to gram-negative and gram-positive bacteria. Our simulations provide new insights into how the human immune system responds to infections from different pathogens. Novel applications of these insights help in the development of more powerful tools and protocols in infection biology.

COVID-19 Impact on the Doctor-Patient Relationship: Patient Perspectives on Emergency Physician Empathy and Communication.

OBJECTIVE: To investigate in how the current COVID-19 pandemic affects patient's perceptions of emergency physician empathy and communication. METHODS: Patients cared for by Emergency Department physicians with the lowest satisfaction scores were surveyed within one week of discharge via phone. Using questions from the Consultation and Relational Empathy (CARE) survey, patients rated their satisfaction with their Emergency provider's empathy and communication on a scale of 1 to 5 and provided feedback on how the patient-provider interaction could be improved. Demographic data and patient responses to CARE survey questions were compared between pre-COVID-19 and during COVID-19 time. Patient's open-ended responses were analyzed for themes related to the impact of COVID-19 on the patient-provider relationship. RESULTS: Patient median quantitative scores were 5 (4-5) across all five questions of pre-COVID-19 and 5 (4-5) during COVID-19 for all questions except two (showing care and compassion), median 5(5-5). Female patients rated provider empathy and communication lower than mens. There was no differences across age strata. A shift in provider focuses to COVID-19 only care (N=3), and an understanding of the stress on healthcare processes (N=13) from open-ended responses themes emerged of patients who want to minimize interactions within the emergency department (N=3). CONCLUSIONS: The external factor of the current pandemic did not negatively impact patient's satisfaction scores. Many patients express leniency and gratitude for emergency providers during this challenging time. Their responses seem to mirror current societal views of frontline healthcare workers.

Patient Suggestions to Improve Emergency Physician Empathy and Communication.

Emergency physician empathy and communication is increasingly important and influences patient satisfaction. This study investigated if there is a need for improvement in provider empathy and communication in our emergency department and what areas could be targeted for future improvement. Patients cared for by emergency physicians with the lowest satisfaction scores were surveyed within 1 week of discharge. Patients rated their emergency provider's empathy and communication and provided feedback on the patient-provider interaction. Compared to survey responses nationally, our providers fell between the 10th and 25th percentiles for all questions, except question 5 (making a plan of action with [the patient]) which was between the 5th and 10th percentile. Areas most frequently cited for improvement were "wanting to know why" (N = 30), "time is short" (N = 15), and "listen to the patient" (N = 13). Survey percentiles and open-ended suggestions demonstrate a need for providers to give thorough explanations, spend more time with the patient, and demonstrate active listening. These themes can be used to strengthen the provider-patient relationship.