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.

Myelodysplasia cutis and VEXAS syndrome initially diagnosed as histiocytoid Sweet syndrome: A diagnostic pitfall.

Histiocytoid Sweet syndrome (H-SS) is a histopathological variant of Sweet syndrome (SS) defined by cutaneous infiltration of immature myeloid cells morphologically resembling histiocytes. The association of H-SS with underlying malignancy, particularly myelodysplastic syndromes, is well-established. Myelodysplasia cutis (MDS-cutis) has been proposed to describe cases historically diagnosed as H-SS but characterized by shared clonality of the myeloid infiltrate in skin and bone marrow. Therefore, identifying patients who might have MDS-cutis is critical for the management of the associated hematologic malignancy. VEXAS syndrome, an adult-onset autoinflammatory disease, should also be included in the histopathologic differential diagnosis of H-SS, as it shares clinical and pathologic features with MDS-cutis. Through the presentation of two cases, we aim to highlight the defining features and key clinical implications of MDS-cutis and VEXAS syndrome.

Standardized Protocols for Clinical and Histopathological Characterization of Hidradenitis Suppurativa Tissue Specimens.

Methods for describing and reporting the clinical and histologic characteristics of cutaneous tissue samples from patients with hidradenitis suppurativa (HS) are not currently standardized, limiting clinicians' and scientists' ability to uniformly record, report, and communicate about the characteristics of tissue used in translational experiments. A recently published consensus statement outlined morphological definitions of typical HS lesions, but no consensus has been reached regarding clinical characterization and examination of HS tissue samples. In this study, we aimed to establish a protocol for reporting histopathologic and clinical characteristics of HS tissue specimens. This study was conducted from May 2023 to August 2023. Experts in clinical care, dermatopathology, and translational research were recruited, and a modified Delphi technique was used to develop a protocol for histologic reporting and clinical characterization of submitted tissue specimens from patients with HS. A total of 27 experts participated (14 dermatologists, 3 fellowship-trained dermatopathologists, 3 plastic surgeons, 3 general surgeons, and 4 research scientists) in creating and reviewing protocols for the clinical and histopathological examination of HS tissue specimens. The protocols were formatted as a synoptic report and will help to consistently classify specimens in biobanks on the basis of histologic features and more accurately report and select samples used in translational research projects.

A case of diagnostic uncertainty: High-grade melanocytoma versus balloon cell melanoma in a pediatric patient.

An 11-year-old female was referred from an outside institution after a diagnostic biopsy and subsequent excision of a progressively enlarging reddish-brown nodule demonstrated features concerning for a balloon cell nevus with severe atypia versus a high-grade melanocytoma. Upon review of the initial biopsy specimen and molecular data, we favored the diagnosis to be consistent with a high-grade melanocytoma with balloon cell changes while considering the possibility of balloon cell melanoma due to concerning histopathologic and genetic abnormalities. In this case study, we discuss critical diagnostic considerations in this rare pediatric case and highlight important pathologic and clinical features of melanocytomas and balloon cell melanoma.

Systemic correlates of cutaneous manifestations of lupus erythematosus.

BACKGROUND: We aimed to investigate the prevalence of skin disease among patients with systemic lupus erythematosus (SLE) and determine whether LE skin disease had clinical or serologic correlates with SLE. METHODS: We reviewed records of 335 patients with SLE (seen at Mayo Clinic, Rochester, Minnesota, USA) and abstracted skin manifestations, fulfilled mucocutaneous SLE criteria, and clinical and serologic parameters. RESULTS: Of the 231 patients with skin manifestations, 57 (24.7%) had LE-specific conditions, 102 (44.2%) had LE-nonspecific conditions, and 72 (31.2%) had both. LE skin disease was associated with photosensitivity, anti-Smith antibodies, and anti-U1RNP antibodies (all P < 0.001). Patients without LE skin disease more commonly had elevated C-reactive protein levels (P = 0.01). Patients meeting 2-4 mucocutaneous American College of Rheumatology criteria less commonly had cytopenia (P = 0.004) or anti-double-stranded DNA antibodies (P = 0.004). No significant associations were observed for systemic involvement (renal, hematologic, neurologic, and arthritis) when comparing patients with or without LE skin involvement. LE skin involvement was not significantly associated with internal SLE disease flare, number of medications, or overall survival. CONCLUSIONS: LE skin disease commonly occurs in patients with SLE. The presence of LE skin disease had no mitigating impact on the severity of SLE sequelae, disease flares, number of medications, or overall survival.

Digital dermatopathology implementation: Experience at a multisite academic institution.

BACKGROUND: Technology has revolutionized not only direct patient care but also diagnostic care processes. This study evaluates the transition from glass-slide microscopy to digital pathology (DP) at a multisite academic institution, using mixed methods to understand user perceptions of digitization and key productivity metrics of practice change. METHODS: Participants included dermatopathologists, pathology reporting specialists, and clinicians. Electronic surveys and individual or group interviews included questions related to technology comfort, trust in DP, and rationale for DP adoption. Case volumes and turnaround times were abstracted from the electronic health record from Qtr 4 2020 to Qtr 1 2023 (inclusive). Data were analyzed descriptively, while interviews were analyzed using methods of content analysis. RESULTS: Thirty-four staff completed surveys and 22 participated in an interview. Case volumes and diagnostic turnaround time did not differ across the institution during or after implementation timelines (p = 0.084; p = 0.133, respectively). 82.5% (28/34) of staff agreed that DP improved the sign-out experience, with accessibility, ergonomics, and annotation features described as key factors. Clinicians reported positive perspectives of DP impact on patient safety and interdisciplinary collaboration. CONCLUSIONS: Our study demonstrates that DP has a high acceptance rate, does not adversely impact productivity, and may improve patient safety and care collaboration.

Plexiform neurofibroma masquerading as a giant congenital melanocytic nevus.

A 4-month-old male presented for a large, hypertrichotic brown patch on the upper back with several scattered 0.5-1.5 cm, round to oval, brown macules and patches on the trunk and extremities. The lesion was initially diagnosed as a giant congenital melanocytic nevus based on clinical exam and histopathology with immunohistochemical stains. The patient was later diagnosed with neurofibromatosis type 1, and the lesion on the back developed a "bag of worms" texture consistent with a plexiform neurofibroma and found to harbor a pathogenic variant in the NF1 gene. This case highlights the diagnostic challenge of differentiating these lesions and their overlapping clinical and histopathological features.

What can we learn about skin of color in dermatopathology?

As the US population becomes increasingly diverse, more patients of color seek dermatologic care and often have concerns that are unique to their skin color. Therefore, it is critically important that the knowledge gap in skin of color dermatology be urgently addressed. In addition to addressing the clinical gap in recognizing dermatologic disease in patients of color, the role of dermatopathology in bridging this gap remains unaddressed. Given the impact that skin color can have on the presentation and subsequent management of dermatologic diseases, understanding the current knowledge of the unique structural and histologic characteristics in skin of color may help give us insight on the role skin color should play in histopathologic diagnosis. In this paper, we bring insights into the role dermatopathology plays in addressing our knowledge of cutaneous disease in patients with skin of color. After we highlight issues to consider, we can begin to identify gaps in knowledge that still exist within dermatopathology that need to be addressed to ensure patients of all backgrounds receive equitable dermatologic care.

Teledermatology in practice: Report of Mayo Clinic experience.

Background: Delivery of dermatologic care through telemedicine was accelerated by the COVID-19 pandemic. We sought to analyze the teledermatology experience across Mayo Clinic's health care system to identify strengths and limitations of teledermatology. Methods: Electronic health records of dermatology televisits were reviewed from multiple U.S. Mayo Clinic sites from January 2020 through January 2021. Results: A total of 13,181 dermatology televisits were conducted in 6468 unique patients. Patients were primarily female (60.2%), and mean age of all patients was 34.1 years. Synchronous / live video conferencing visits were the most common (40.0%) telecare modality. Synchronous / live audio conferencing and asynchronous / store-and-forward visits comprised 33.0% and 27.0% of appointments. In total, 3944 televisits (29.9%) were successfully concluded via a single appointment. An in-person appointment was needed for 1693 patients (26.2%) after their initial televisit. For patients with a single televisit, synchronous / live video conferencing was the most common virtual modality (58.0% vs 32.2% of patients with multiple visits, p < 0.001). Patients needing in-person follow-up visits were slightly older than those who did not (mean [SD], 38.8 [22.3] vs 35.0 [23.6] years; p < 0.001) but without any sex-based difference. Around one-third of patients needed an in-person follow-up visit after their initial asynchronous / store-and-forward visit which was higher when compared with synchronous / live audio and video conferencing. Conclusion: Single dermatology televisits effectively managed nearly one-third of patients who did not require in-person follow-up. An initial synchronous / live video conferencing was more likely to yield a single clinical encounter, whereas asynchronous / store-and-forward visits required more in-person follow-up. Future studies are required that focus on dermatology-specific cost, diagnoses, access, quality of care, and outcomes.

Neutrophilic Urticarial Dermatosis.

Neutrophilic urticarial dermatosis (NUD) is a rare form of dermatosis that is poorly understood. It was first described by Kieffer and colleagues as an urticarial eruption that is histopathologically characterized by a perivascular and interstitial neutrophilic infiltrate with intense leukocytoclasia and without vasculitis or dermal edema. NUD clinically presents as a chronic or recurrent eruption that consists of nonpruritic macules, papules, or plaques that are pink to reddish and that resolve within 24 hours without residual pigmentation. NUD is often associated with systemic diseases such as Schnitzler syndrome, lupus erythematosus, adult-onset Still's disease, and cryopyrin-associated periodic syndromes.

High-risk adverse drug reactions: consideration of limited dialysis therapy for toxic epidermal necrolysis (TEN).

Toxic epidermal necrolysis (TEN) is a rare but often lethal drug reaction involving the skin. Treatment is often centered around suppurative care, and the mortality rate remains unacceptably high, although the clinical and epidemiological features of TEN have been well documented for decades. Recent studies have placed an emphasis on certain medications in the pathophysiology of severe TEN, and our colleagues previously reported several cases of clinical improvement in TEN patients following hemodialysis. Here, we discuss the major considerations for initiating dialysis in TEN patients. By doing so, we hope to encourage others to explore this potential avenue for treating TEN, one of the most serious medical emergencies in the field of dermatology.

Diagnosis and Management of Bullous Disease.

Bullous diseases are a group of dermatoses primarily characterized by the presence of vesicles (0.1-0.9 cm) or bullae (>1 cm). There are various categories of bullous disease: allergic, autoimmune, infectious, mechanical, and metabolic. These diseases affect individuals in all decades of life, but older adults, age 65 and older, are particularly susceptible to bullous diseases of all etiologies. The incidence of these disorders is expected to increase given the advancing age of the general population. In this comprehensive review, we will outline the common bullous diseases affecting older individuals and provide an approach to evaluation and management.

Dense Lichenoid Inflammation in Paget Disease: A Diagnostic Pitfall.

ABSTRACT: Mammary Paget disease is a rare form of breast cancer, which typically presents as an eczematous plaque on the nipple or surrounding skin. It is often a clinical diagnosis that is confirmed with skin biopsy. Histologic hallmarks of mammary Paget disease include large, pleomorphic, malignant, ductal epithelial cells within the epidermis. Chronic lichenoid inflammation may be seen in the papillary dermis but is not diagnostic. Because mammary Paget disease often overlies ductal carcinoma in situ or invasive carcinoma of the breast, prompt bilateral mammography is warranted. We report a case of Paget disease of the nipple with negative breast imaging that was originally misdiagnosed due to a dense lichenoid infiltrate obscuring the neoplasm.

Health Disparities, Clinical Trials, and the Digital Divide.

In the past few years, there have been rapid advances in technology and the use of digital tools in health care and clinical research. Although these innovations have immense potential to improve health care delivery and outcomes, there are genuine concerns related to inadvertent widening of the digital gap consequentially exacerbating health disparities. As such, it is important that we critically evaluate the impact of expansive digital transformation in medicine and clinical research on health equity. For digital solutions to truly improve the landscape of health care and clinical trial participation for all persons in an equitable way, targeted interventions to address historic injustices, structural racism, and social and digital determinants of health are essential. The urgent need to focus on interventions to promote health equity was made abundantly clear with the coronavirus disease 2019 pandemic, which magnified long-standing social and racial health disparities. Novel digital technologies present a unique opportunity to embed equity ideals into the ecosystem of health care and clinical research. In this review, we examine racial and ethnic diversity in clinical trials, historic instances of unethical research practices in biomedical research and its impact on clinical trial participation, and the digital divide in health care and clinical research, and we propose suggestions to achieve digital health equity in clinical trials. We also highlight key digital health opportunities in cardiovascular medicine and dermatology as exemplars, and we offer future directions for development and adoption of patient-centric interventions aimed at narrowing the digital divide and mitigating health inequities.

Eruptive Papules as a Cutaneous Manifestation of Metastatic Prostate Adenocarcinoma.

ABSTRACT: Cutaneous metastasis from prostate cancer is a rare manifestation, occurring in less than 1% of all cases of prostate cancer. Prostate cancer metastasis occurs most often in lymph nodes and bones. In this study, we present the case of a 55-year-old man with prostate adenocarcinoma and progressive papules on his left chest that developed shortly after androgen deprivation therapy was initiated. This case emphasizes the significance of considering cutaneous metastasis in the diagnostic differential when assessing patients with a history of cancer and the need to thoroughly evaluate these cases.