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.

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.

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.

Acquired acrodermatitis enteropathica after gastric bypass surgery responsive to IV supplementation.

Nutritional deficiency is rare in developed countries, but can be acquired from decreased nutrient intake, reduced absorption, and increased gastrointestinal excretion. We report a patient with acquired acrodermatitis enteropathica (AE) who exhibited low plasma zinc levels and concurrent nutritional deficiencies (pyridoxine, selenium and fatty acids). Our patient had undergone Roux-en-Y gastric bypass 13 years prior to presentation. The rash, consistent with AE clinically and histologically, nearly resolved one week after starting IV zinc supplementation, total parenteral nutrition, and micronutrient supplements. This case highlights the importance of long-term post-operative follow-up for gastric bypass patients who are at high risk for micronutrient and macronutrient deficiencies and illustrates the potential for rapid improvement with IV supplementation.

Introduction to Skin Cancer: A Video Module.

INTRODUCTION: This introductory skin cancer video module engages novice health care professionals to make histological-clinical correlations for the three most common skin cancers: basal cell carcinoma (BCC), squamous cell carcinoma (SCC), and melanoma. The goal of this video module is to engage novice health care professionals (e.g., allied health, medical, nursing students) to go beyond the all-too-common phenomenon of memorizing gross and histological features of skin cancers without reference to the relationship between these features. METHODS: By explicitly highlighting underlying histological-clinical correlations for BCC, SCC, and melanoma, this video module helps learners build a deeper and lasting knowledge of these common diseases. Materials in this module include a learner guide with instructions on how to complete the module; four chalk-talk videos that discuss classification of skin cancers, histological-clinical correlations for BCC, SCC, and melanoma, and how to distinguish among benign nevi, dysplastic nevi, and melanoma (total viewing time 54 minutes, 22 seconds); annotated slides used in the videos; and 10 multiple-choice self-assessment questions. RESULTS: This module was successfully incorporated into the first-year flipped classroom curriculum for medical and dental students at Harvard Medical School. Written comments from students revealed that they enjoyed watching short concept videos to prepare for in-class, case-based discussions of BCC, SCC, and melanoma. DISCUSSION: By illustrating histological-clinical correlations and reducing cognitive load of the material through use of cartoons and prototypical clinical images, this video module is an accessible initial resource for an emerging generation of millennial health care professionals to learn about common skin cancers.