Erythema dyschromicum perstans-like eruptions induced by epidermal growth factor receptor inhibitors in patients with lung cancer.

INTRODUCTION: Cutaneous adverse reactions to epidermal growth factor receptor inhibitors (EGFRi) are some of the most common side effects that patients experience. However, cutaneous adverse reactions that cause dyspigmentation in patients have been rarely reported. Erythema dyschromicum perstans (EDP) is a rare pigmentary condition that causes ashy-grey hyperpigmented macules and patches, with a few cases reported from EGFRi in the literature. The disfiguration caused by this condition may negatively impact patients' quality of life. Our study aimed to describe the clinical characteristics of EDP induced by EGFRi to better recognize and manage the condition. METHODS: We conducted a multicenter retrospective review at three academic institutions to identify patients with EDP induced by EGFRi from 2017 to 2023 and included sixteen patients in our study. RESULTS: The median age of patients was 66 years old, with 63% female and 37% male (Table 1). The majority of our patients were Asian (88%). All patients had non-small cell lung cancer and most patients received osimertinib. Median time to EDP was 6 months. The most common areas of distribution were the head/neck region, lower extremities, and upper extremities. Various topical ointments were trialed; however, approximately less than half had improvement in their disease and most patients had persistent EDP with no resolution. All patients desired treatment except one with EDP on the tongue, and there was no cancer treatment discontinuation or interruption due to EDP. Table 1 Patient demographics and clinical characteristics of 16 patients with EDP induced by EGFRi Case no Demographics: age, race, and sex Fitzpatrick skin type Cancer type EGFR therapy Concomitant photosensitive drug(s) Time to EDP (months) Clinical features Distribution Symptoms Treatments and clinical course EDP status from most recent follow up 1 47 y/o Asian male III Stage IV NSCLC Erlotinib None Unknown Brown-blue-gray hyperpigmented patches Bilateral shins Left thigh Xerosis Pruritus Triamcinolone 0.1% ointment for 4 months, improvement of blue discoloration Tacrolimus 0.1% BID for 9 months, improvement but no resolution Ongoing 2 62 y/o Asian female IV Stage IV NSCLC Osimertinib None 4 Gray-brown hyperpigmented patches Bilateral arms Back Forehead Neck Right shin None Tacrolimus 0.1% ointment for 1 year with minor improvement Ongoing 3 69 y/o Asian female IV Stage IV NSCLC Osimertinib None 4 Gray-brown macules and patches Chest Face Forehead Bilateral legs None Tacrolimus 0.1% ointment for 10 months, no improvement Ongoing 4 79 y/o White male II Stage IV NSCLC Osimertinib None 15 Mottled grey-blue hyperpigmented patches and plaques with mild scaling Bilateral arms Back Forehead Neck None Photoprotection, no improvement Ongoing 5 69 y/o Asian female III Stage IV NSCLC Osimertinib Ibuprofen 4 Blue-grey hyperpigmented macules and patches Abdomen Bilateral arms None Tacrolimus 0.1% ointment for 7 months, no improvement Ongoing 6 65 y/o Asian male III Stage IV NSCLC Osimertinib None 20 Hyperpigmented blue gray macules and patches Helix Bilateral shins None Photoprotection, no improvement Ongoing 7 66 y/o Asian female IV Stage IV NSCLC Erlotinib TMP-SMX 6 Ashy grey-brown thin plaques Back Forehead None 2.5% hydrocortisone ointment for 8 months, resolved Resolved 8 82 y/o Asian male III Stage III NSCLC Erlotinib Simvastatin 20 Ash-grey hyperpigmented patches Dorsal feet Forehead Scalp None Photoprotection Ongoing 9 57 y/o Asian female III Stage II NSCLC Erlotinib None 1 Bue-grey discoloration Tongue None No intervention Ongoing 10 51 y/o Asian female III Stage IV NSCLC Osimertinib None 9 Blue-grey hyperpigmented macules and patches Bilateral arms Axillae Groin Neck Trunk None 2.5% hydrocortisone ointment, triamcinolone 0.1% ointment, photoprotection with mild improvement Ongoing 11 67 y/o Asian male III Stage IV NSCLC Osimertinib None 7 Gray-blue macules and patches with mild background erythema and scaling Bilateral arms Ears Face Bilateral shins None Triamcinolone 0.1% ointment, protection for 6 months with mild improvement Ongoing 12 75 y/o Asian female IV Stage III NSCLC Osimertinib TMP-SMX 3 Gray-blue hyperpigmented patches Bilateral arms Abdomen Back Face Bilateral shins Pruritus Triamcinolone 0.1% and betamethasone 0.01% with relief of pruritus, lesions unchanged Triluma cream 6 months, mild improvement Ongoing 13 42 y/o Asian male IV Stage IV NSCLC Afatinib TMP-SMX 24 Grey-brown hyperpigmented patches Back Face None Hydroquinone 4% cream for 2 years with mild improvement Ongoing 14 74 y/o White female III Stage II NSCLC Osimertinib Atorvastatin 4 Grey-brown hyperpigmented patches Bilateral legs Trunk None Photoprotection Ongoing 15 64 y/o Asian female IV Stage IV NSCLC Osimertinib None 3 Gray-brown hyperpigmentation Abdomen Bilateral arms Back Bilateral legs Pruritus Triamcinolone 0.1% cream; No change, minimal concern to patient Ongoing 16 52 y/o Asian female IV Stage IV NSCLC Osimertinib None 42 Gray hyperpigmented patches with digitate shape Abdomen Bilateral flanks None Triamcinolone 0.1% cream Ongoing NSCLC, non-small cell lung cancer, TMP-SMX, Trimethoprim/Sulfamethoxazole CONCLUSIONS: We highlight the largest case series describing EDP from EGFR inhibitors, which mostly affected Asian patients with lung malignancy and on EGFR tyrosine kinase inhibitors. Clinicians should be able to recognize this condition in their patients and assess how it is affecting their quality of life, and refer to dermatology to help with management.

Nails as Dynamic, Not Static, Entities-Rethinking the Approach to Nail Disorders.

This Viewpoint discusses the need for a broader approach to nail pathology, in which infectious, inflammatory, systemic, and structural factors are considered.

Clinical features of drug-induced hypersensitivity syndrome to BRAF inhibitors with and without previous immune checkpoint inhibition: a review.

PURPOSE: Cutaneous reactions to BRAF inhibitors are common, but severe reactions resembling or consistent with drug-induced hypersensitivity syndrome (DIHS)/drug reaction with eosinophilia and systemic symptoms (DRESS) are relatively rare. Several reports suggest that cutaneous reactions including DRESS/DIHS to BRAF inhibitors are more frequent and severe in the setting of previous immune checkpoint inhibition (ICI). METHODS: To characterize existing literature on these reports, we queried the PubMed/MEDLINE database for cases of DIHS/DRESS to BRAF inhibitors. RESULTS: We identified 23 cases of DIHS to BRAF inhibitors following checkpoint inhibition and 14 cases without prior checkpoint inhibitor therapy. In both cohorts, DIHS occurred relatively early, with median time to onset from drug exposure of 8-10 days. Patients who received prior ICI were less likely to have peripheral eosinophilia (26% vs 71%), atypical lymphocytes (9% vs 50%), renal involvement (61% vs 79%), hepatic involvement (52% vs 86%), and lymphadenopathy (9% vs 43%) compared to patients who did not receive prior ICI. Thrombocytopenia was more common with prior ICI (17% vs 7%). Only patients who received prior ICI experienced hypotension (26%) during the course of their DIHS. All cases of BRAF-induced DIHS generally improved on systemic steroids/supportive care, and no cases of death were identified. CONCLUSION: Dermatologists should consider a diagnosis of DIHS following BRAF inhibitor initiation, particularly in the setting of past checkpoint inhibition, with atypical features including relatively rapid onset and steroid responsiveness, lack of peripheral eosinophilia, lymphocytosis, or lymphadenopathy, and increased risk of thrombocytopenia and hypotension.

Using art to improve visual diagnosis: a review.

BACKGROUND: Elective visual arts-based courses for trainees in the health professions may, amongst other things, help improve visual diagnostic skills. An emphasis on the careful observation of visual art and medical images and the co-teaching of such courses by both medical faculty members and local art educators seem to be particularly important elements for the successful implementation of such courses. LITERATURE REVIEW: At least 12 studies to date suggest that guided observation of visual art (e.g. paintings and photography) can enhance the quality and/or quantity of visual observations. More research is needed regarding optimal course structure and assessment, but existing evidence supports the development of visual arts-based coursework for health care trainees using strategies such as 'visual thinking skills' and engagement and processing in groups. TAKE-HOME MESSAGE: The arts or 'medical humanities' are increasingly used in the education of health professionals, and growing evidence exists that visual arts-based coursework, in particular, can enhance the observation skills of participants. Notably, the expertise and experience of trainees in specific disciplines are likely to influence specific learning goals and course structure in each context; however, unique arts-based teaching strategies (e.g. 'visual thinking skills') can be used across all settings. There is no more difficult art to acquire than the art of observation … William Osler, 19031.

Teaching and Learning Tips 12: Peer observation of teaching.

Challenge: How can clinical teachers continually improve their teaching skills? In addition to student feedback, peer and expert opinion can also provide valuable formative and evaluative feedback to guide self-improvement efforts. Here, we discuss ways to structure peer observation of teaching in dermatological settings and offer tips on how to optimize the learning experience for both the educator and peer observer.

Teaching & Learning Tips 11: Teaching a procedure.

Challenge: Balancing patient-centered clinical care with learner-centered teaching in a clinical setting becomes particularly challenging when it comes to teaching procedures to trainees (e.g. biopsies, excisions, etc.). How can procedures be taught in a way that reinforces repetition and mastery without compromising patient safety, care, and comfort?

Factors Influencing Patient Decisions Regarding Treatments for Skin Growths: A Cross-Sectional Study.

Variations in treatment modalities for skin growths contribute substantially to overall healthcare spending within dermatology. However, little is known regarding factors impacting patient decision-making when choosing a treatment modality. In this survey-based, cross-sectional study (n = 375, 81.9% response rate), we asked patients to rate the importance of different treatment parameters for a nonfacial skin growth, further classified into five domains: efficacy, appearance, financial impact, visit duration, and productivity. Although patients generally prioritized treatment efficacy when selecting a treatment modality, they emphasized different aspects of the treatment experience as a function of age, gender, race, insurance status, and history of malignancy. Patients over age 50 were less likely to consider treatment impact on finances as being "important", but more so efficacy and visit duration. Women were more likely to value efficacy and appearance. Patients without private insurance were more likely to cite efficacy and impact on productivity as being "important". While the underlying reasons for these variations differ across patients, these findings help explain variations in treatment selection among patients choosing between treatments for skin growths and may ultimately lead to improved shared decision-making.

Teaching & Learning Tips 10: Interspecialty teaching through inpatient dermatology consults.

Medical students and residents often have little experience in placing or responding to dermatologic consults in the inpatient setting when they first begin training. Trainees often learn what and how to communicate through observation or trial and error. We propose that dermatologists can play an active role in facilitating interspecialty education and improving patient outcomes by teaching in a systematic fashion.

Teaching & Learning Tips 9: Case-based teaching with patients.

Challenge: "Case-based teaching" is a buzzword for engaging clinical teaching through cases, but how can it be implemented effectively in practice? We review popular case-based teaching methods (i.e., one-minute preceptor, SNAPPS, and the "Aunt Minnie method") for use during traditional one-on-one clinical preceptorships in the ambulatory dermatological setting.

Teaching & Learning Tips 8: Preparing to teach in ambulatory settings.

Challenge: Clinical teaching in dermatology largely occurs in the outpatient setting. Herein, we review common barriers to teaching in the ambulatory setting and discuss strategies preceptors can take to "teach on the run" during clinic sessions.

Teaching & Learning Tips 7: small-group discussion.

Challenge: The success of a small-group discussion depends in large part on the effectiveness of the facilitator or small-group tutor. How can a facilitator successfully manage diverse views and knowledge bases of participants while also contributing as a member of the group? Herein, we provide tips for managing small-group discussions that can be applied widely in dermatology didactics.

Teaching & Learning Tips 6: The flipped classroom.

Challenge: The "flipped classroom" is a pedagogical model in which instructional materials are delivered to learners outside of class, reserving class time for application of new principles with peers and instructors. Active learning has forever been an elusive ideal in medical education, but the flipped class model is relatively new to medical education. What is the evidence for the "flipped classroom," and how can these techniques be applied to the teaching of dermatology to trainees at all stages of their medical careers?

Teaching & Learning Tips 4: Motivation and emotion in learning.

Challenge: Trainees' motivational and emotional states can influence their learning and career decisions, but historically these "affective" learning factors have received little attention in medical education. In this "Tips" piece, we outline strategies to positively influence trainees' intrinsic motivation and emotion toward their training to ultimately enhance their overall learning experience.