Association of age with survival in older patients with cutaneous melanoma treated with immune checkpoint inhibitors.

INTRODUCTION: Several types of immune checkpoint inhibitors (ICIs) are approved to treat advanced melanoma, but their effectiveness has not been compared in older patients treated outside of a clinical trial. Moreover, evidence suggests that a patient's response to ICI therapy may vary by age and type of ICI. The purpose of this study was to compare survival by ICI type in older patients with melanoma and to investigate treatment effect modification by age. MATERIALS AND METHODS: Using the SEER-Medicare database, we identified patients with cutaneous melanoma (2012-2015) treated with an ICI (CTLA-4, PD-1, or combination CTLA-4 + PD-1 inhibitors). Cox proportional hazards regression was used to estimate hazard ratios (HRs) with 95% confidence intervals (CI) for ICI types. We used an interaction term and stratified models to test for treatment effect modification by age. RESULTS: Of the 1435 patients included in our analysis, 790 (55.1%) received CTLA-4 inhibitors, 512 (35.7%) received PD-1 inhibitors, and 133 (9.3%) were treated with combination ICIs. Median survival ranged from 13.4 months (95%CI: 10.7-16.3) for CTLA-4 inhibitors to 23.5 months (95%CI: 16.2-30.0) for combination ICIs. In multivariable models, the risk of death was lower with PD-1 inhibitors compared to CTLA-4 inhibitors (HR = 0.78, 95%CI: 0.68-0.89). An age*ICI type interaction term was significant (p < 0.001), and survival gains were greater the older age group (≥80) compared to the younger group (65-79). DISCUSSION: In a population-based setting, we identified important differences in survival by ICI type in older patients with melanoma treated with ICIs, with prolonged survival associated with PD-1 inhibitors compared to CTLA-4 inhibitors.

Clinical and pathologic correlation of cutaneous COVID-19 vaccine reactions including V-REPP: A registry-based study.

BACKGROUND: Cutaneous reactions after COVID-19 vaccination have been commonly reported; however, histopathologic features and clinical correlations have not been well characterized. METHODS: We evaluated for a history of skin biopsy all reports of reactions associated with COVID-19 vaccination identified in an international registry. When histopathology reports were available, we categorized them by reaction patterns. RESULTS: Of 803 vaccine reactions reported, 58 (7%) cases had biopsy reports available for review. The most common histopathologic reaction pattern was spongiotic dermatitis, which clinically ranged from robust papules with overlying crust, to pityriasis rosea-like eruptions, to pink papules with fine scale. We propose the acronym "V-REPP" (vaccine-related eruption of papules and plaques) for this spectrum. Other clinical patterns included bullous pemphigoid-like (n = 12), dermal hypersensitivity (n = 4), herpes zoster (n = 4), lichen planus-like (n = 4), pernio (n = 3), urticarial (n = 2), neutrophilic dermatosis (n = 2), leukocytoclastic vasculitis (n = 2), morbilliform (n = 2), delayed large local reactions (n = 2), erythromelalgia (n = 1), and other (n = 5). LIMITATIONS: Cases in which histopathology was available represented a minority of registry entries. Analysis of registry data cannot measure incidence. CONCLUSION: Clinical and histopathologic correlation allowed for categorization of cutaneous reactions to the COVID-19 vaccine. We propose defining a subset of vaccine-related eruption of papules and plaques, as well as 12 other patterns, following COVID-19 vaccination.

Cutaneous reactions reported after Moderna and Pfizer COVID-19 vaccination: A registry-based study of 414 cases.

BACKGROUND: Cutaneous reactions after messenger RNA (mRNA)-based COVID-19 vaccines have been reported but are not well characterized. OBJECTIVE: To evaluate the morphology and timing of cutaneous reactions after mRNA COVID-19 vaccines. METHODS: A provider-facing registry-based study collected cases of cutaneous manifestations after COVID-19 vaccination. RESULTS: From December 2020 to February 2021, we recorded 414 cutaneous reactions to mRNA COVID-19 vaccines from Moderna (83%) and Pfizer (17%). Delayed large local reactions were most common, followed by local injection site reactions, urticarial eruptions, and morbilliform eruptions. Forty-three percent of patients with first-dose reactions experienced second-dose recurrence. Additional less common reactions included pernio/chilblains, cosmetic filler reactions, zoster, herpes simplex flares, and pityriasis rosea-like reactions. LIMITATIONS: Registry analysis does not measure incidence. Morphologic misclassification is possible. CONCLUSIONS: We report a spectrum of cutaneous reactions after mRNA COVID-19 vaccines. We observed some dermatologic reactions to Moderna and Pfizer vaccines that mimicked SARS-CoV-2 infection itself, such as pernio/chilblains. Most patients with first-dose reactions did not have a second-dose reaction and serious adverse events did not develop in any of the patients in the registry after the first or second dose. Our data support that cutaneous reactions to COVID-19 vaccination are generally minor and self-limited, and should not discourage vaccination.

A cohort study of personal and family history of skin cancer in relation to all-cause and cancer-specific mortality.

PURPOSE: Even though the fatality rate from skin cancers is low, evidence from a few cohort studies has raised the possibility that people with a personal history of skin cancer may have a higher all-cause mortality rate compared with those without a personal history of skin cancer. The purpose of the present study was to investigate the potential links between a personal history or family history of skin cancer and all-cause and cancer-specific mortality METHODS: A prospective cohort (n = 8,622) was assembled within the NHANES I follow-up study. Cox Proportional Hazard Regression analysis was used to estimate the hazard ratios (HR) and 95% confidence intervals (CI) for the association for personal and family history of skin cancer and all-cause and cancer-specific mortality. RESULTS: After adjustment for several potential confounding variables, a personal history of skin cancer was associated with decreased risk for all-cause mortality (HR 0.72, 95% CI 0.61-0.85), whereas the results for cancer-specific mortality were consistent with a null association (HR 0.97, 95% CI 0.74-1.27). A family history of skin cancer was not significantly associated with all-cause mortality (HR 0.97, 95% CI 0.76-1.24) or cancer-specific mortality (HR 0.69, 95% CI 0.38-1.24). CONCLUSION: The results of the present study do not support the hypothesis that a personal history or family history of skin cancer is associated with an increased risk of all-cause or cancer-specific mortality. The high prevalence of skin cancer adds to the public health significance of this question, providing a strong rationale for further research to resolve this question.

Sebaceous Carcinoma of the Eyelid: A Systematic Review and Meta-Analysis.

BACKGROUND: Sebaceous carcinoma (SC) of the eyelid is a rare, aggressive malignancy associated with high rates of recurrence, metastasis, and tumor-related mortality. OBJECTIVE: Provide a collective analysis of clinical presentations, management techniques, and outcomes, and compare outcomes of common treatment methods. METHODS AND MATERIALS: Observational studies reporting management and outcomes of SC of the eyelid were included. Patient and clinical data were extracted, and meta-analysis of proportions was performed. RESULTS: One thousand three hundred thirty-three subjects were included with a mean age of 65.2 years and 803 (60.2%) women. Of 647 initial diagnoses reported, 277 (42.8%) were correct, and the mean diagnostic delay was 14.7 months (range 8.5-34.8). The tumor location was reported in 1,246 subjects and involved the upper eyelid in 780 (62.6%), lower eyelid in 409 (32.8%), and 57 (4.8%) involved both. Overall rates of recurrence, metastasis, and tumor-related mortality were 15.9%, 12.1%, and 6.2%, respectively. There were no statistically significant differences in wide local excision (WLE) versus Mohs micrographic surgery (MMS) outcomes. CONCLUSION: Sebaceous carcinoma of the eyelid is more common in women, on the upper eyelid, and is frequently misdiagnosed initially. Rate of recurrence, metastasis, and tumor-related mortality were similar in subjects managed with WLE versus MMS.

Immune checkpoint inhibitors retain effectiveness in older patients with cutaneous metastatic melanoma.

INTRODUCTION: Immune checkpoint inhibitors (ICIs) have dramatically changed the treatment landscape for advanced melanoma, but their use in older patients remains understudied. An age-related decline in immune function is of concern when treating older patients because host immune factors can influence clinical outcomes with immunotherapy. Therefore, we aimed to evaluate the effectiveness of ICIs in patients 65 years and older. METHODS: Using the SEER-Medicare data, we evaluated survival by first systemic treatment type in a retrospective cohort study of patients aged 65 years and older who were diagnosed with stage IV cutaneous melanoma between 2012 and 2015. Cox proportional hazards regression was used to estimate hazard ratios (HR) and their corresponding 95% confidence intervals. RESULTS: A total of 541 patients were included in this study. Median survival differed significantly between groups (p < 0.0001) and was longest in patients treated with PD-1 inhibitors (34.0 months), followed by CTLA-4 inhibitors (16.8 months), targeted therapy (9.7 months), chemotherapy (7.1 months), and no systemic therapy (3.6 months). The ICI survival benefit persisted after adjusting for age, sex, comorbidities, M stage, the presence of brain metastases, and evaluation at an NCI-designated cancer center. Hazard ratios comparing ICIs to no systemic therapy were 0.35 (95% CI: 0.24-0.52) for PD-1 inhibitors and 0.48 (95% CI: 0.37-0.63) for CTLA-4 inhibitors. We did not observe a difference in ICI effectiveness by age group (65-74 vs ≥75). CONCLUSIONS: In a nationally representative cohort of patients with advanced melanoma, ICI therapy delivered in a real world setting significantly improved survival in patients aged 65 years and older.

The spectrum of COVID-19-associated dermatologic manifestations: An international registry of 716 patients from 31 countries.

BACKGROUND: Coronavirus disease 2019 (COVID-19) has associated cutaneous manifestations. OBJECTIVE: To characterize the diversity of cutaneous manifestations of COVID-19 and facilitate understanding of the underlying pathophysiology. METHODS: Case series from an international registry from the American Academy of Dermatology and International League of Dermatological Societies. RESULTS: The registry collected 716 cases of new-onset dermatologic symptoms in patients with confirmed/suspected COVID-19. Of the 171 patients in the registry with laboratory-confirmed COVID-19, the most common morphologies were morbilliform (22%), pernio-like (18%), urticarial (16%), macular erythema (13%), vesicular (11%), papulosquamous (9.9%), and retiform purpura (6.4%). Pernio-like lesions were common in patients with mild disease, whereas retiform purpura presented exclusively in ill, hospitalized patients. LIMITATIONS: We cannot estimate incidence or prevalence. Confirmation bias is possible. CONCLUSIONS: This study highlights the array of cutaneous manifestations associated with COVID-19. Many morphologies were nonspecific, whereas others may provide insight into potential immune or inflammatory pathways in COVID-19 pathophysiology.

Pernio-like skin lesions associated with COVID-19: A case series of 318 patients from 8 countries.

BACKGROUND: Increasing evidence suggests pernio-like lesions are cutaneous manifestations of coronavirus infectious disease 2019 (COVID-19). OBJECTIVE: To describe clinical and pathologic findings of pernio-like lesions in patients with confirmed or suspected COVID-19. METHODS: An international dermatology registry was circulated to health care providers worldwide through the American Academy of Dermatology, International League of Dermatologic Societies, and other organizations. RESULTS: We documented 505 patients with dermatologic manifestations associated with COVID-19, including 318 (63%) with pernio-like lesions. Patients with pernio-like lesions were generally young and healthy, with relatively mild COVID-19. Of 318 patients with confirmed or suspected COVID-19 by providers, 23 (7%) were laboratory-confirmed COVID-19 positive, and 20 others (6%) were close contacts of patients with confirmed COVID-19. Given current testing criteria, many patients lacked COVID-19 testing access. For 55% of patients, pernio-like lesions were their only symptom. In patients with other COVID-19 symptoms, pernio-like lesions typically appeared after other symptoms. Pernio-like lesions lasted a median of 14 days (interquartile range, 10-21 days). LIMITATIONS: A case series cannot estimate population-level incidence or prevalence. In addition, there may be confirmation bias in reporting. We cannot exclude an epiphenomenon. CONCLUSIONS: Pernio-like skin changes of the feet and hands, without another explanation, may suggest COVID-19 infection and should prompt confirmatory testing.

A cohort study of personal and family history of skin cancer in relation to future risk of non-cutaneous malignancies.

PURPOSE: Skin cancer has repeatedly been observed to be a marker of increased risk for developing an internal malignancy. The purpose of our study was to further investigate this association while also characterizing the potential role of family history of skin cancer in relation to risk for non-cutaneous malignancies. METHODS: Our study used data from 8,408 participants from the NHANES I epidemiological follow-up study. Cox-proportional hazards models were used to estimate the risk for developing an internal cancer associated with a personal history and family history of skin cancer during follow-up. RESULTS: A personal history of skin cancer was associated with significantly increased risk of developing an internal cancer in adjusted models [hazard ratio (HR) 1.33, 95% confidence interval (CI) 1.09-1.61] but a family history of skin cancer was not associated with increased risk (HR 0.80, 95% CI 0.58-1.11). CONCLUSIONS: Consistent with prior reports, a personal history of skin cancer was associated with increase of developing internal malignancies, but this did not hold true for a family history of skin cancer. Further research is needed to understand why a personal history of skin cancer acts as a marker for increased risk for internal cancer.

High Levels of Gadolinium Deposition in the Skin of a Patient With Normal Renal Function.

OBJECTIVE: The aim of this study was to assess gadolinium deposition in the skin of a patient with normal renal function, based on estimated glomerular filtration rate values greater than 59 mL/min/1.73 m(2) after exposure to large cumulative doses of gadolinium-based contrast agents (GBCAs). MATERIALS AND METHODS: The patient underwent 61 contrasted brain MRI scans over the course of 11 years. Skin biopsies from the forearm and lower extremity were analyzed with inductively coupled plasma mass spectrometry (ICP-MS), laser ablation ICP-MS, and hydrophilic interaction liquid chromatography ICP-MS. RESULTS: The ICP-MS demonstrated high levels of gadolinium deposition (14.5 ± 0.4 µg/g), similar to previously reported gadolinium levels within the skin of patients with nephrogenic systemic fibrosis. The laser ablation ICP-MS demonstrated deposition of gadolinium within the deep layers of skin. Speciation analysis using hydrophilic interaction liquid chromatography ICP-MS demonstrated the presence of intact gadolinium-chelate species, although most of the gadolinium present could not be further characterized. Light microscopy demonstrated increased CD34 immunoreactivity in the connective tissue septations of the subcutaneous adipose tissue. The patient had no history of skin disorders and did not have a history of nephrogenic systemic fibrosis but did have severe joint contractures of unknown etiology. CONCLUSIONS: Our results, in contradiction to published literature, suggest that in patients with normal renal function, exposure to GBCAs in extremely high cumulative doses can lead to significant gadolinium deposition in the skin. This finding is in line with more recent reports of gadolinium deposition in the brain of patients with normal renal function. Future studies are required to address possible clinical consequences of gadolinium deposition in the skin, brain, and potentially other organs in patients with normal renal function. We recommend, in addition to following current US Food and Drug Administration and American College of Radiology guidelines based on estimated glomerular filtration rate values, that caution be used when administering large cumulative doses of GBCAs and that total cumulative dose of each agent administered is recorded in the patient's medical record.

Automatic diagnosis of melanoma using machine learning methods on a spectroscopic system.

BACKGROUND: Early and accurate diagnosis of melanoma, the deadliest type of skin cancer, has the potential to reduce morbidity and mortality rate. However, early diagnosis of melanoma is not trivial even for experienced dermatologists, as it needs sampling and laboratory tests which can be extremely complex and subjective. The accuracy of clinical diagnosis of melanoma is also an issue especially in distinguishing between melanoma and mole. To solve these problems, this paper presents an approach that makes non-subjective judgements based on quantitative measures for automatic diagnosis of melanoma. METHODS: Our approach involves image acquisition, image processing, feature extraction, and classification. 187 images (19 malignant melanoma and 168 benign lesions) were collected in a clinic by a spectroscopic device that combines single-scattered, polarized light spectroscopy with multiple-scattered, un-polarized light spectroscopy. After noise reduction and image normalization, features were extracted based on statistical measurements (i.e. mean, standard deviation, mean absolute deviation, L1 norm, and L2 norm) of image pixel intensities to characterize the pattern of melanoma. Finally, these features were fed into certain classifiers to train learning models for classification. RESULTS: We adopted three classifiers - artificial neural network, naïve bayes, and k-nearest neighbour to evaluate our approach separately. The naive bayes classifier achieved the best performance - 89% accuracy, 89% sensitivity and 89% specificity, which was integrated with our approach in a desktop application running on the spectroscopic system for diagnosis of melanoma. CONCLUSIONS: Our work has two strengths. (1) We have used single scattered polarized light spectroscopy and multiple scattered unpolarized light spectroscopy to decipher the multilayered characteristics of human skin. (2) Our approach does not need image segmentation, as we directly probe tiny spots in the lesion skin and the image scans do not involve background skin. The desktop application for automatic diagnosis of melanoma can help dermatologists get a non-subjective second opinion for their diagnosis decision.