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In this study, we demonstrate the utility of whole-slide CyCIF (tissue-based cyclic immunofluorescence) imaging for characterizing immune cell infiltrates in immune checkpoint inhibitor (ICI)-induced dermatologic adverse events (dAEs). We analyzed six cases of ICI-induced dAEs, including lichenoid, bullous pemphigoid, psoriasis, and eczematous eruptions, comparing immune profiling results obtained using both standard immunohistochemistry (IHC) and CyCIF. Our findings indicate that CyCIF provides more detailed and precise single-cell characterization of immune cell infiltrates than IHC, which relies on semi-quantitative scoring by pathologists. This pilot study highlights the potential of CyCIF to advance our understanding of the immune environment in dAEs by revealing tissue-level spatial patterns of immune cell infiltrates, allowing for more precise phenotypic distinctions and deeper exploration of disease mechanisms. By demonstrating that CyCIF can be performed on friable tissues, such as bullous pemphigoid, we provide a foundation for future studies to examine the drivers of specific dAEs using larger cohorts of phenotyped toxicity and suggest a broader role for highly multiplexed tissue imaging in phenotyping the immune mediated disease that they resemble.

Immune checkpoint inhibitors (ICI) may cause eruptions resembling cutaneous autoimmune diseases. There are six cases of immunotherapy-associated subacute cutaneous lupus erythematosus (SCLE) in the literature. We present details of five patients referred to the Skin Toxicity Program at the Dana-Farber Cancer Institute/Brigham and Women's Cancer Center who developed de novo immunotherapy-associated SCLE-like eruptions, along with clinicopathological correlation and highlight potential mechanistic features and important diagnostic points. Two patients were maintained on topical corticosteroids, antihistamines and photoprotection. One had complete clearance and two had improvement with addition of hydroxychloroquine. Four patients continued their immunotherapy uninterrupted, while one had immunotherapy suspended for a month before restarting at full dose. Histopathologically, this series illustrates the temporal evolution of ICI-induced immune cutaneous reactions with SCLE subtype. Looking beyond the universally present lichenoid infiltrate, features of evolving SCLE were evident. We hypothesize that programmed death-1 blockade may induce immunological recognition of previously immunologically tolerated drug antigens, leading to epitope spreading and the SCLE phenotype.

Introduction To evaluate the use of inaccurate terminology used by dermatology practices to describe the training and qualifications of their nonphysician clinicians (NPCs) when new patients are booking appointments. Methods Clinics were randomly selected and called to determine the first available appointment for a new patient with a new and changing mole. If the receptionist confirmed the first-offered appointment was with an NPC, the encounter was included in this study. If receptionists used inaccurate terminology to describe the NPCs and their qualifications, this instance was recorded along with the specific language that they used. Results A total of 344 unique dermatology clinics were contacted on February 27, 2020, in 25 states. Phone calls at 128 clinics (37.2%) met our inclusion criterion. Inaccurate language was used to describe NPCs at 23 (18%) unique clinic locations across 12 states, with "dermatologist," "doctor," "physician," and "board-certified" being used to describe NPCs as the most common inaccurate terms. Conclusion These findings demonstrate that front office staff at dermatology clinics use inaccurate and potentially misleading terminology to refer to NPCs working in their clinics. While we cannot establish whether this is intentional or due to a lack of training, additional focus should be placed on accurately representing provider qualifications to patients.

Langerhans cell histiocytosis (LCH) limited to the skin is rare in adult patients. Given the challenges of prospective clinical trials for this rare disease, there is paucity in data to guide the management of cutaneous LCH. Topical nitrogen mustard is a possible treatment for cutaneous LCH with positive responses in five known adult cases in the literature. In this report, we present two adult patients with recalcitrant cutaneous LCH and no evidence of systemic involvement who had rapid and complete response on topical nitrogen mustard therapy. We provide support for topical nitrogen mustard as a treatment option for primary cutaneous LCH which may spare patients from requiring systemic immunosuppressive treatments. J Drugs Dermatol. 2020;19(8):803-805. doi:10.36849/JDD.2020.4943.

IMPORTANCE: In the 15 years since dermatology access was last investigated on a national scale, the practice landscape has changed with the rise of private equity (PE) investment and increased use of nonphysician clinicians (NPCs). OBJECTIVE: To determine appointment success and wait times for patients with various insurance types at clinics with and without PE ownership. DESIGN, SETTING, AND PARTICIPANTS: In this study, PE-owned US clinics were randomly selected and matched with 2 geographically proximate clinics without PE ownership. Researchers called each clinic 3 times over a 5-day period to assess appointment/clinician availability for a fictitious patient with a new and changing mole. The 3 calls differed by insurance type specified, which were Blue Cross Blue Shield (BCBS) preferred provider organization, Medicare, or Medicaid. MAIN OUTCOMES AND MEASURES: Appointment success and wait times among insurance types and between PE-owned clinics and control clinics. Secondary outcomes were the provision of accurate referrals to other clinics when appointments were denied and clinician and next-day appointment availability. RESULTS: A total of 1833 calls were made to 204 PE-owned and 407 control clinics without PE ownership across 28 states. Overall appointment success rates for BCBS, Medicare, and Medicaid were 96%, 94%, and 17%, respectively. Acceptance of BCBS (98.5%; 95% CI, 96%-99%; P = .03) and Medicare (97.5%; 95% CI, 94%-99%; P = .02) were slightly higher at PE-owned clinics (compared with 94.6% [95% CI, 92%-96%] and 92.8% [95% CI, 90%-95%], respectively, at control clinics). Wait times (median days, interquartile range [IQR]) were similar for patients with BCBS (7 days; IQR, 2-22 days) and Medicare (7 days; IQR, 2-25 days; P > .99), whereas Medicaid patients waited significantly longer (13 days; IQR, 4-33 days; P = .002). Clinic ownership did not significantly affect wait times. Private equity–owned clinics were more likely than controls to offer a new patient appointment with an NPC (80% vs 63%; P = .001) and to not have an opening with a dermatologist (16% vs 6%; P

In the United States, the process of obtaining initial medical licensure for international medical graduates (IMGs) is state and/or territory dependent. Hence, it is important to be meticulous about state- or territory-specific requirements, time lines, and notable exceptions. In this chapter, we first lay out the process for IMGs to become eligible to enter into Accreditation Council for Graduate Medical Education (ACGME) residency programs in three steps: (1) application for Educational Commission for Foreign Medical Graduates (ECFMG) certification, (2) medical licensing examinations including the United States Medical Licensing Examination Sequence (USMLE) Step 1, Step 2 Clinical Knowledge, and Step 2 Clinical Skills exams, and (3) medical education credential requirements. We then discuss the process of obtaining initial medical licensure for IMGs, which includes the successful completion of USMLE Step 3 and postgraduate residency training, with certain limits specific to each state or territory. Only after completion of these requirements are physicians able to successfully practice medicine in the United States.

Introduction To evaluate the impact of Sars-Cov-2 infection on mortality and immune checkpoint inhibitor (ICI) toxicity in patients with cancer receiving ICIs compared to those not receiving ICIs. Methods We conducted a retrospective matched cohort study of 25 patients receiving ICIs within 1 year of coronavirus disease 2019 (COVID-19) diagnosis between March 20, 2020, and June 3, 2020, at the Dana-Farber Cancer Institute/Mass General Brigham. Cases were matched 1:1 with controls based on age, sex, and anticancer therapy within the prior 6 months. Results Seven of 25 (28%) patients receiving ICIs died from COVID-19 as compared with nine of 25 (36%) controls. Through multivariable analysis adjusting for age, sex, and anticancer therapy, ICI use was not associated with increased risk for COVID-19 death (OR [odds ratio] 0.36, 95% CI 0.07–1.87). Determinants of mortality included age (OR 1.14, 95% CI 1.03–1.27) and chronic obstructive pulmonary disease (OR 12.26, 95% CI 1.76–85.14). Statin use was protective against mortality (OR 0.08, 95% CI 0.01–0.63). Two patients experienced persistent immune-related adverse events (irAEs) (hypophysitis); one had new-onset irAE (hypothyroidism) during their COVID-19 course. Patients with ICIs had significantly higher platelet (p = 0.017) and D-dimer (p = 0.037) levels. Elevated troponin levels (p = 0.01) were associated with COVID-19 death in patients using ICI. Conclusion There is insufficient evidence to conclude COVID-19–related outcomes are associated with ICIs, and we did not observe an increased risk of COVID-19–related death associated with ICIs. The potential protective effect of statin therapy and role of laboratory biomarkers warrant further investigation.

Background There are conflicting data regarding the vulnerability of cancer patients receiving immune checkpoint inhibitors (ICIs) to COVID-19 infection.1–3 In addition, immune-related adverse events (irAEs) driven in part by cytokine dysregulation could parallel the cytokine storm implicated in COVID-19. We sought to evaluate the impact of COVID-19 infection on irAEs and mortality in cancer patients receiving ICIs. Methods We performed a retrospective matched cohort study of 25 patients receiving ICIs within one year of a confirmed COVID-19 diagnosis between March 20, 2020 and June 3, 2020 at the Dana-Farber Cancer Institute/Mass General Brigham network. Cases were matched 1:1 with controls without ICI use based on age, sex, and use of non-ICI anti-cancer therapy within 6 months prior to COVID-19 diagnosis. The primary outcome was death due to COVID-19, and potential covariates (patient comorbidities, concomitant medications, ICI therapy, other anti-cancer therapy) were explored using multivariable logistic regression models. Results We reviewed the records of 611 patients with prior ICI use who were evaluated at our institutions. The final study population included 25 patients who tested positive for COVID-19. The median age was 72 years (range 45–83) and 11 patients (44%) were female (table 1). Seven of 25 (28%) patients on ICIs died from COVID-19 compared to 9 of 25 (36%) controls (figure 1). In multivariable analysis, determinants of mortality included age (OR 1.14, 95% CI 1.03–1.27) and chronic obstructive pulmonary disease (OR 12.26, 95% CI 1.76–85.14), while concomitant statin use was protective against mortality (OR 0.08, 95% CI 0.01–0.63). After adjusting for age, sex, and anti-cancer therapy, ICI use was not associated with increased risk for COVID-19 death (OR 0.36, 95% CI 0.07–1.87, figure 2). Two patients experienced persistent irAEs (hypophysitis) and one patient had new onset irAE (hypothyroidism) during their COVID-19 course. Patients with ICI use presented with significantly higher platelet (p = 0.017) and D-dimer (p = 0.037) levels compared to controls (figure 3A). Elevated troponin levels (p = 0.01) were associated with COVID-19 death in patients using ICI but not in controls (figure 3B). Conclusions In our study, ICI use was not associated with increased risk of COVID-19 related death. We observed low rates of new or persistent irAEs within our small sample. The potential protective effect of statin therapy and predictive role of laboratory biomarkers warrants further investigation. Our findings are promising for the continuation of immunotherapy in cancer patients with COVID-19. Acknowledgements K.T. and A.N.B. contributed equally. N.R.L. and O.E.R. contributed equally.The authors would like to acknowledge the DFCI Oncology Data Retrieval System (OncDRS) for the aggregation, management, and delivery of the clinical and operational research data used in this project. The content is solely the responsibility of the authors. Ethics Approval This project was approved by the Partners Healthcare Institutional Review Board (#2020P000851). References Robilotti EV, Babady NE, Mead PA, et al. Determinants of COVID-19 disease severity in patients with cancer. Nature Medicine 2020. In press. Luo J, Rizvi H, Egger JV, Preeshagul IR, Wolchok JD, Hellmann MD. Impact of PD-1 blockade on severity of COVID-19 in patients with lung cancers. Cancer Discov 2020. In press. Lee LYW, Cazier JB, Starkey T, Turnbull CD, Kerr R, Middleton G. COVID-19 mortality in patients with cancer on chemotherapy or other anticancer treatments: a prospective cohort study. Lancet 2020;395(10241):1919–1926.

CHEK2 mutations have been linked with an increased risk of breast cancer. A unique challenge for oncodermatologists and oncologists is in the monitoring and counselling of patients regarding skin cancer risk due to CHEK2 mutation carrier status. In this review, we highlight current information in the literature on the risk of melanoma and non-melanoma skin cancers in CHEK2 mutation carriers. On the molecular level, CHEK2 is a cell cycle regulator that has been linked to cancer pathogenesis, though evidence from clinical studies regarding skin cancer risk has been inconsistent and conflicting. For melanoma, one study has demonstrated a statistically significant twofold risk of melanoma in individuals with CHEK2 mutations, particularly the CHEK2*1100delC variant. Five other studies did not show an association. For non-melanoma skin cancer, fewer data exist, with one prevalence study of CHEK2 mutations in a cohort of patients with basal cell carcinomas. Although there are currently no known studies of CHEK2 and cutaneous squamous cell carcinoma (SCC), data from other disciplines associating CHEK2 with head and neck SCCs are emerging. Overall, while there is currently not enough evidence to make conclusive statements regarding increased risk of melanoma and non-melanoma skin cancers in CHEK2 carriers, a molecular mechanism associating the mutation with cutaneous malignancy pathogenesis is evident, and further work is needed. Patient with CHEK2 mutations may benefit from screening dermatologic examinations with particular attention to skin cancers.