DIRECTIONS in RESIDENCY boards fodder A Publication of the American Academy of Dermatology | Association -specific cutaneous reactions by Parin Pearl Rimtepathip, MD, Janna Vassantachart, MD, and G. Alden Holmes, MD Most commonly Cutaneous reaction Clinical description Special notes associated drug Acral reactions Erythematous papules and Neutrophilic -Most notable in treatment of AML, plaques on extremities and eccrine hidradenitis Hodgkin , and solid tumors trunk Acral erythema, -Grade 1: Mild erythema without dyse- Prodrome of pain and dyses- 5-FU, Hand-foot syn- sthesia thesia followed by symmetric, drome (HFS), or -Grade 2: Erythema, pain, and dyses- sharply demarcated erythema > , Palmar-plantar thesia of palms and soles (diffuse) Cytarabine erythrodysesthesia -Grade 3: Blistering, pain, and impaired function Similar findings to HFS but on Atypical Hand-foot -Treatment: High-potency steroids, the DORSAL surface of hands, syndrome (HFS) moisturizers with keratinolytic proper- Achilles tendons, and malleoli ties, and possible cessation of therapy Parin Pearl -Grade 1: Absence of pain Rimtepathip, Less severe acral dysestheisa -Grade 2: Mild to moderate pain and swelling compared to Multi-kinase -Grade 3: Severe pain MD, is a 3rd year Hand foot skin HFS with prominent hyper- inhibitors, BRAF -Treatment: High-potency steroids, dermatology resident reaction (HFSR) at Loma Linda keratotic plaques on frictional inhibitors topical /urea, , and University areas ONLY temporary chemotherapy dose reduc- tion  chemotherapy cessation -Most notable in patients with andro- Affects entire skin but exag- Sticky skin Doxorubicin with gen-independent gerated effect on acral sur- syndrome simultaneously receiving ketoconazole faces and doxorubicin Truncal reactions -Grade 1: Topical antibiotics, antiseptic creams, and low-potency corticoste- Monomorphic, folliculocen- roids tric papulopustular eruption EGFR inhibitors, Acneiform rash -Grade 2/3: Doxycycline and/or low- distributed on the face, scalp, BRAF inhibitors dose systemic isotretinoin chest, and back Janna Mieko -Avoid topical benzoyl peroxide and Vassantachart, retinoids due to severe irritation MD, is a 3rd year -Treatment: slowing infusion  densiti- Typically appear after multiple dermatology resident Hypersensitivity zation  chemotherapy cessation infusions. Flushing/rash  Platinum agents at Loma Linda reaction - testing is not needed prior to anaphylaxis-like reaction University chemotherapy initiation -Has been observed to improve with Sclerodermoid , chemotherapy cessation and course of changes Taxanes high-dose steroids Reactions predominantly noted on extremities Fissuring and easy bruis- -Treatment: Avoiding dehydrating skin ing commonly observed on EGFR inhibitors, Xerosis practices, moisturization, and antihis- extremities contributing to MEK inhibitors tamines pain and pruritus BRAF inhibitors, Generalized folliculocentric -Treatment: Topical retinoids, urea, KP-like reaction Multi-kinase keratotic, pruritic papules alpha-hydroxy acids, or salicylic acid inhibitors G. Alden -Most common cause of drug-induced Holmes, MD is a Dermatomyositis (>50%) with latency Lichenoid/DM-like Overlying joints with PIH Hydroxyurea 1st year dermatology period of 60 months on average, longer resident at Loma than non-hydroxyurea induced DM Linda University -Risk factors include pre-existing Pseudocellulitis, lower extremity edema and impaired Erysipeloid lymphatic drainage

p. 1 • Fall 2019 www.aad.org/DIR boards fodder Chemotherapy-specific cutaneous reactions by Parin Pearl Rimtepathip, MD, Janna Vassantachart, MD, and G. Alden Holmes, MD

Most commonly Cutaneous reaction Clinical description Special notes associated drug Dyschromia

Generalized (Addison-like) -May also have pulmonary fibrosis , Intertriginous/occlusive areas Serpentine supravenous Fluorouracil -Distributed over infused veins -Skin and lungs susceptible to bleomycin toxicity due to absence of Linear, flagellate, or whipped- Bleomycin > bleomycin hydrolase like patches on trunk Docetaxel Hyperpigmentation -Similar findings with raw shiitake mushroom consumption Palmar creases, skin over Bleomycin, joints Doxorubicin Capecitabine, Acral and mucosal , , -Increases both melanocytes as well Site of topical application as melanin in keratinocytes Localized to diffuse effect -Caused by an inhibition of c- inhibitors ranging from hypopigmenta- -More commonly observed in patients (), Multi- Hypopigmentation tion to depigmentation that with darker skin kinase inhibitors, can affect the skin, nails, hair, -Course typically reverses with dose Imiquimod, PD-1 and oral mucosa reduction or chemotherapy cessation Inhibitors Yellow discoloration intensi- Multi-kinase Yellow skin, white fies with treatment duration -Spontaneously resolves with chemo- inhibitors (specifi- hair typically sparing mucous therapy cessation cally ) membranes and sclera Other -TKI: Dose-dependent response Tyrosine kinase -EGFRI/Vismodegib: Typically inhibitors, EGFR reversible Anagen effluvium inhibitors, -Treatment: Topical minoxidil shortens Vismodegib, Multi- hair loss duration, dose reduction/ kinase inhibitors chemotherapy cessation Busulfan, Hair effects Nonreversible alopecia Docetaxel Excessive growth (tricho- -Treatment: Eye lash trimming, megaly, hypertrichosis of EGFR inhibitors depilatory creams, laser epilation, upper lip) interruption of treatment Flag sign (alternating bands MTX of dark/light hair) -Treatment: Warm compresses, anti- Pitting and onycholysis  nail EGFR inhibitors, bacterial soaks, topical corticosteroids, loss, paronychia, discoloration Taxanes and/or systemic

Melanonychia Doxorubicin > Nail effects Subungual splinter Multi-kinase -Spontaneous resolution with therapy hemorrhages inhibitors cessation -Most notable in treatment of breast Exudative hyponychial derma- Docetaxel, cancer titis (pain with hemorrhage) Capecitabine -Chemotherapy cessation if severe

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Most commonly Cutaneous reaction Clinical description Special notes associated drug Other -Aphthae treatment: Topical steroids, including antiseptic washes, and palifermin aphthae, xerostomia, and geo- EGFR inhibitors (recombinant human keratinocyte graphic tongue. Rarely vulvo- ). vaginitis/balanitis Mucosal effects -Typically resolves within 3 weeks Mucocutaneous hemorrhage Anti-angiogenesis -Therapy should be reconsidered in (epistaxis and/or cutaneous agents existing hemorrhage hemorrhage) Oral leukoplakia resembling Palifermin flat warts Inflammation of AKs and Fluorouracil, DSAP Capecitabine Cytarabine, Inflammation of SKs Taxanes Eruptive nevi Multi-kinase -Spontaneous resolution with therapy Reactions Involving inhibitors cessation Skin Lesions Keratotic lesions including -Regular dermatologic follow-up with Acantholytic dermatosis, BRAF inhibitors, excision of malignancies. SKs, Verrucous keratosis, Vismodegib -Vismodegib is more specifically Hypertrophic AKs, KAs, and associated with SCC and KA Cutaneous SCC Scrotal erythema (with pain) Sunitinib Scrotal reactions Scrotal eczema (without pain) Fluorouracil, -Treatment: Sun protective measures EGFR inhibitors, -EGFR inhibitors: hyperpigmentation Photosensitivity with hyper- BRAF Inhibitors, and telangiectasias fade with pigmentation, telangiectasias, Radiation-related MTX, Hydroxyurea, chemotherapy cessation and photosensitive reactions reactions Docetaxel, -BRAF inhibitors: increased susceptibility to UVA Sunburn recall and Radiation MTX recall Extravasation reaction with ulceration or indurating red Fluorouracil, plaques at chemotherapy administration site EGFR inhibitors, MTX, Multi-kinase Pyogenic granuloma -EGFRI lesions are found on the great inhibitors (spe- toes Ulcerative reactions cifically Sunitinib), Capecitabine -Inhibits DNA synthesis by disrupting the of the resulting Lower extremity foot ulcers in basal keratinocyte damage and Hydroxyurea hindered collagen production -Treatment: Wound care, chemotherapy cessation if severe

References: 1. Cutaneous reactions to chemotherapeutic drugs and targeted therapies for cancer. Reyes-Habito, Claire Marie et al. Journal of the American Academy of Dermatology, Volume 71, Issue 2, 203.e1 - 203.e12. 2. Cutaneous adverse effects of targeted therapies. Macdonald, James B. et al. Journal of the American Academy of Dermatology, Volume 72, Issue 2, 203 – 218. 3. Cutaneous adverse effects of targeted therapies. Macdonald, James B. et al. Journal of the American Academy of Dermatology, Volume 72, Issue 2, 221 – 236.

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