Vemurafenib‐induced interface dermatitis manifesting as radiation‐recall and a keratosis pilaris‐like eruption

Vemurafenib is a specific inhibitor of the V600E mutated BRAF protein kinase used for the treatment of unresectable or metastatic melanoma harboring this mutation. Multiple predictable side effects have been described with use of this targeted therapy, and implicate BRAF and mitogen activated protein kinase (MAPK) signaling pathways in their pathogenesis. Herein, we report the novel finding of an interface dermatitis in radiation recall and a keratosis pilaris‐like clinical reaction in a patient treated with vemurafenib.     

Docetaxel‐induced photo‐recall phenomenon

Photo‐recall phenomenon is a phototoxic eruption occurring on areas of previous ultraviolet‐induced solar erythema following a systemic administration of a drug. It has been mostly described with methotrexate but remains rare with other antineoplastic drugs. We describe a case of docetaxel‐induced photo‐recall skin rash in a woman treated for a non‐small‐cell lung cancer. Although the patient has refused to receive a second infusion, chemotherapy can be carried on with photoprotection and the use of topical and/or systemic corticosteroids. In contrast, radiation recall is a well‐known reaction by oncologists, most of them may not be aware of a similar phenomenon called photo‐recall phenomenon. Recognizing this entity may avoid misdiagnosing a drug allergy and should avoid inappropriate decisions of drug discontinuation.     

Drug eruption secondary to aciclovir with recall phenomenon in a dermatome previously affected by herpes zoster

Classically, recall dermatitis refers to chemotherapy-induced reactivation of skin damage caused by radiotherapy months, or even years, earlier. The concept of recall dermatitis has now been extended to include radiation recall dermatitis induced by other drugs, ultraviolet radiation, extravasation of drugs, and allergic contact dermatitis. We now describe recall dermatitis along the residual cutaneous lesions of a previous thoracic herpes zoster in a patient who developed a drug eruption after oral administration of aciclovir. The most striking feature consisted of confluent linear erythema along the dermatomes previously involved by the herpes zoster episode. Histopathologic study demonstrated small foci of spongiosis, vacuolar changes involving the basal layer of the epidermis and single necrotic keratinocytes scattered within the epidermis. The papillary dermis appeared oedematous and with dilated blood capillaries surrounded by a sparse inflammatory infiltrate composed mainly of lymphocytes. Serial sections failed to demonstrate cytologic changes of herpes varicella zoster infection. We interpreted this case as an example of recall dermatitis because the widespread cutaneous eruption secondary to aciclovir was more intense in skin previously compromised by herpes varicella zoster infection. To the best of our knowledge, recall dermatitis has not been described before at the site of previous involvement by herpes zoster.     

E‐cadherin mediates ultraviolet radiation‐ and calcium‐induced melanin transfer in human skin cells

Skin pigmentation is directed by epidermal melanin units, characterized by long‐lived and dendritic epidermal melanocytes (MC) that interact with viable keratinocytes (KC) to contribute melanin to the epidermis. Previously, we reported that MC:KC contact is required for melanosome transfer that can be enhanced by filopodi, and by UVR/UVA irradiation, which can upregulate melanosome transfer via Myosin X‐mediated control of MC filopodia. Both MC and KC express Ca²⁺‐dependent E‐cadherins. These homophilic adhesion contacts induce transient increases in intra‐KC Ca²⁺, while ultraviolet radiation (UVR) raises intra‐MC Ca²⁺ via calcium‐selective ORAI1 ion channels; both are associated with regulating melanogenesis. However, how Ca²⁺ triggers melanin transfer remains unclear. Here we evaluated the role of E‐cadherin in UVR‐mediated melanin transfer in human skin cells. MC and KC in human epidermis variably express filopodia‐associated E‐cadherin, Cdc42, VASP and β‐catenin, all of which were upregulated by UVR in human MC in vitro. Knockdown of E‐cadherin revealed that this cadherin is essential for UVR‐induced MC filopodia formation and melanin transfer. Moreover, Ca²⁺ induced a dose‐dependent increase in filopodia formation and melanin transfer, as well as increased β‐catenin, Cdc42, Myosin X and E‐cadherin expression in these skin cells. Together, these data suggest that filopodial proteins and E‐cadherin, which are upregulated by intracellular (UVR‐stimulated) and extracellular Ca²⁺ availability, are required for filopodia formation and melanin transfer. This may open new avenues to explore how Ca²⁺ signalling influences human pigmentation.