Elizabeth A. Quigley

Autoimmune Bullous Skin Disorders with Immune Checkpoint Inhibitors Targeting PD-1 and PD-L1

Bullous pemphigoid is a rare immune-related adverse event after anti–PD-1/PD-L1 immune checkpoint treatment and may be mediated by both T-cell and B-cell responses. Early referral to dermatology for accurate diagnosis and management is recommended. Monoclonal antibodies (mAb) targeting immune checkpoint pathways such as cytotoxic T-lymphocyte–associated protein 4 (CTLA-4) and programmed death 1 (PD-1) may confer durable disease control in several malignancies. In some patients, immune checkpoint mAbs cause cutaneous immune-related adverse events. Although the most commonly reported cutaneous toxicities are mild, a subset may persist despite therapy and can lead to severe or life-threatening toxicity. Autoimmune blistering disorders are not commonly associated with immune checkpoint mAb therapy. We report a case series of patients who developed bullous pemphigoid (BP), an autoimmune process classically attributed to pathologic autoantibody formation and complement deposition. Three patients were identified. Two patients developed BP while receiving the anti–PD-1 mAb nivolumab, and one while receiving the anti–PD-L1 mAb durvalumab. The clinicopathologic features of each patient and rash, and corresponding radiologic findings at the development of the rash and after its treatment, are described. Patients receiving an anti–PD-1/PD-L1 mAb may develop immune-related BP. This may be related to both T-cell– and B-cell–mediated responses. Referral to a dermatologist for accurate diagnosis and management is recommended. Cancer Immunol Res; 4(5); 383–9. ©2016 AACR.

Skin Cancer Education for Primary Care Physicians: A Systematic Review of Published Evaluated Interventions

ABSTRACTBACKGROUNDEarly detection of melanoma may provide an opportunity to positively impact melanoma mortality. Numerous skin cancer educational interventions have been developed for primary care physicians (PCPs) to improve diagnostic accuracy. Standardized training is also a prerequisite for formal testing of melanoma screening in the primary care setting.OBJECTIVEWe conducted a systematic review to determine the extent of evaluated interventions designed to educate PCPs about skin cancer, including melanoma.DESIGNRelevant studies in the English language were identified through systemic searches performed in MEDLINE, EMBASE, BIOSIS, and Cochrane through December 2010. Supplementary information was obtained from corresponding authors of the included studies when necessary.APPROACHStudies eligible for inclusion formally evaluated skin cancer education interventions and were designed primarily for PCPs. Excluded studies lacked a specified training intervention, used decision-making software, focused solely on risk factor identification, or did not directly educate or assess participants. Twenty studies met the selection criteria. Data were extracted according to intervention content and delivery format, and study outcomes.KEY RESULTSAll interventions included instructions about skin cancer diagnosis, but otherwise varied in content. Curricula utilized six distinct educational techniques, usually incorporating more than one. Intervention duration varied from 12 min to over 6 h. Eight of the 20 studies were randomized trials. Most studies (18/20, 90%) found a significant improvement in at least one of the following five outcome categories: knowledge, competence, confidence, diagnostic performance, or systems outcomes. Competence was most commonly measured; no study evaluated all categories. Variability in study design, interventions, and outcome measures prevented correlation of outcomes with intervention characteristics.CONCLUSIONSDespite the development of many isolated educational interventions, few have been tested rigorously or evaluated under sufficient standardized conditions to allow for quantitative comparison. Improved and rigorously tested skin cancer educational interventions for PCPs with outcome measures focusing on changes in performance are needed.

Developing an Interactive Web-Based Learning Program on Skin Cancer: the Learning Experiences of Clinical Educators

Web-based learning in medical education is rapidly growing. However, there are few firsthand accounts on the rationale for and development of web-based learning programs. We present the experience of clinical educators who developed an interactive online skin cancer detection and management course in a time-efficient and cost-efficient manner without any prior skills in computer programming or technical construction of web-based learning programs. We review the current state of web-based learning including its general advantages and disadvantages as well as its specific utility in dermatology. We then detail our experience in developing an interactive online skin cancer curriculum for primary care clinicians. Finally, we describe the main challenges faced and lessons learned during the process. This report may serve medical educators who possess minimal computer programming and web design skills but want to employ the many strengths of web-based learning without the huge costs associated with hiring a professional development team.

Technology and Technique Standards for Camera-Acquired Digital Dermatologic Images: A Systematic Review

IMPORTANCE Photographs are invaluable dermatologic diagnostic, management, research, teaching, and documentation tools. Digital Imaging and Communications in Medicine (DICOM) standards exist for many types of digital medical images, but there are no DICOM standards for camera-acquired dermatologic images to date. OBJECTIVE To identify and describe existing or proposed technology and technique standards for camera-acquired dermatologic images in the scientific literature. EVIDENCE REVIEW Systematic searches of the PubMed, EMBASE, and Cochrane databases were performed in January 2013 using photography and digital imaging, standardization, and medical specialty and medical illustration search terms and augmented by a gray literature search of 14 websites using Google. Two reviewers independently screened titles of 7371 unique publications, followed by 3 sequential full-text reviews, leading to the selection of 49 publications with the most recent (1985-2013) or detailed description of technology or technique standards related to the acquisition or use of images of skin disease (or related conditions). FINDINGS No universally accepted existing technology or technique standards for camera-based digital images in dermatology were identified. Recommendations are summarized for technology imaging standards, including spatial resolution, color resolution, reproduction (magnification) ratios, postacquisition image processing, color calibration, compression, output, archiving and storage, and security during storage and transmission. Recommendations are also summarized for technique imaging standards, including environmental conditions (lighting, background, and camera position), patient pose and standard view sets, and patient consent, privacy, and confidentiality. Proposed standards for specific-use cases in total body photography, teledermatology, and dermoscopy are described. CONCLUSIONS AND RELEVANCE The literature is replete with descriptions of obtaining photographs of skin disease, but universal imaging standards have not been developed, validated, and adopted to date. Dermatologic imaging is evolving without defined standards for camera-acquired images, leading to variable image quality and limited exchangeability. The development and adoption of universal technology and technique standards may first emerge in scenarios when image use is most associated with a defined clinical benefit.

Results of the 2016 International Skin Imaging Collaboration International Symposium on Biomedical Imaging challenge: Comparison of the accuracy of computer algorithms to dermatologists for the diagnosis of melanoma from dermoscopic images

Background Computer vision may aid in melanoma detection. Objective We sought to compare melanoma diagnostic accuracy of computer algorithms to dermatologists using dermoscopic images. Methods We conducted a cross‐sectional study using 100 randomly selected dermoscopic images (50 melanomas, 44 nevi, and 6 lentigines) from an international computer vision melanoma challenge dataset (n = 379), along with individual algorithm results from 25 teams. We used 5 methods (nonlearned and machine learning) to combine individual automated predictions into “fusion” algorithms. In a companion study, 8 dermatologists classified the lesions in the 100 images as either benign or malignant. Results The average sensitivity and specificity of dermatologists in classification was 82% and 59%. At 82% sensitivity, dermatologist specificity was similar to the top challenge algorithm (59% vs. 62%, P = .68) but lower than the best‐performing fusion algorithm (59% vs. 76%, P = .02). Receiver operating characteristic area of the top fusion algorithm was greater than the mean receiver operating characteristic area of dermatologists (0.86 vs. 0.71, P = .001). Limitations The dataset lacked the full spectrum of skin lesions encountered in clinical practice, particularly banal lesions. Readers and algorithms were not provided clinical data (eg, age or lesion history/symptoms). Results obtained using our study design cannot be extrapolated to clinical practice. Conclusion Deep learning computer vision systems classified melanoma dermoscopy images with accuracy that exceeded some but not all dermatologists.

Influence of time on dermoscopic diagnosis and management

Dermoscopy aids in clinical decision‐making. However, time pressure is a common reason precluding its use. We evaluated the effect of time on lesion recognition and management decisions utilising clinical and dermoscopic images.

Microinvasive melanoma: cutaneous pharmacotherapeutic approaches.

Surgical excision is the treatment of choice for primary melanomas and radiation therapy is the accepted alternative for the subset of lesions not amenable to surgery. With the recent rise in melanoma incidence, especially in the elderly, there are a growing number of cases that are neither amenable to surgery nor radiation therapy. In this article, we review pharmacotherapeutic approaches to microinvasive melanoma (invasive radial growth phase melanoma) that might be considered in such circumstances. There are no approved drugs for the treatment of primary melanoma and randomized controlled trials with 5 or more years of follow-up have not been performed. The limited studies and numerous case series in the literature on pharmacologic treatment of primary melanoma have focused on topical therapies. Accordingly, we provide a review of the potential pharmacotherapeutic agents in the treatment of microinvasive melanoma by extrapolating from the available limited literature on the use of fluorouracil, azelaic acid, retinoic acid derivatives, interferon (IFN)-α, imiquimod, and other agents for melanoma in situ, invasive melanoma, and epidermotropic melanoma metastases. Our review indicates that topical fluorouracil and tretinoin are not effective as single agents. The efficacy of azelaic acid, tazarotene, cidofovir, and intralesional IFN-α, interleukin-2, and IFN-β is undefined. Imiquimod is the most studied and promising agent; however, optimal dosage, therapeutic regimen, and survival rates are unknown. In the face of a growing demand for non-surgical treatments, formal clinical trials are needed to ascertain the role of pharmacotherapeutic agents in the treatment of microinvasive melanoma.

A Firm Red-Brown Plaque on the Arm—Quiz Case

A 61-year-old white woman with a history of melanoma presented with an enlarging and asymptomatic lesion on her left arm for several months. Physical examination of the left deltoid revealed a 1.9 0.7-cm asymmetric, erythematous, and faintly brown plaque that was partially firm (Figure 1). Under dermoscopy, a patchy network and dotted blood vessels were observed. An excisional biopsy was performed for diagnosis (Figure 2 and Figure 3). What is your diagnosis?

Erythematous patches and plaques on the chest with induration of the breasts

A 57-year-old woman presented with a 1-month history of an erythematous eruption involving the breasts and chest. The eruption initially manifested on the mid-chest and gradually spread to involve both breasts. It was asymptomatic, with the exception of mild, intermittent pruritus. Her medical history was notable for metastatic papillary renal cell carcinoma (RCC) treated with temsirolimus, which was diagnosed 3 months prior to presentation, and papillary thyroidcarcinoma(multifocal follicularvariant) treatedwith total thyroidectomy 2 years prior. Her family medical history was unremarkable. Bilateral breast ultrasonography and mammography, performed as part of metastatic disease workup, revealed benign findings. Physical examination revealed numerous erythematous patches, thin plaques, telangiectasias, and peau d’orange appearance of the skin on the breasts (Figure1). The inferior aspects of the breasts were indurated (Figure 2). The patient was afebrile and there were no cutaneous leiomyomas. Punch biopsies of left upper chest and left breast were performed (Figure3). What is your diagnosis?

Erythematous patches and plaques on the chest with induration of the breasts. Metastatic papillary RCC in dermal lymphatics.

A 57-year-old woman presented with a 1-month history of an erythematous eruption involving the breasts and chest. The eruption initially manifested on the mid-chest and gradually spread to involve both breasts. It was asymptomatic, with the exception of mild, intermittent pruritus. Her medical history was notable for metastatic papillary renal cell carcinoma (RCC) treated with temsirolimus, which was diagnosed 3 months prior to presentation, and papillary thyroidcarcinoma(multifocal follicularvariant) treatedwith total thyroidectomy 2 years prior. Her family medical history was unremarkable. Bilateral breast ultrasonography and mammography, performed as part of metastatic disease workup, revealed benign findings. Physical examination revealed numerous erythematous patches, thin plaques, telangiectasias, and peau d’orange appearance of the skin on the breasts (Figure1). The inferior aspects of the breasts were indurated (Figure 2). The patient was afebrile and there were no cutaneous leiomyomas. Punch biopsies of left upper chest and left breast were performed (Figure3). What is your diagnosis?