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Rash after a single injection of T‐VEC

Talimogene laherparepvec (Imlygic ® ) has been approved since 2015 for intralesional injection in patients with advanced melanoma without hepatic, pulmonary or cerebral metastases. Talimogene laherparepvec (T-VEC) is a genetically modifi ed human herpesvirus (HSV) type 1 that selectively replicates in tumor cells and subsequently leads to tumor lysis. T-VEC carries deletions in the sequences encoding the regulatory infected cell protein (ICPs) genes 34.5 and 47. As a result, this herpes virus lacks the ability to replicate in healthy cells and to evade immunological detection by blocking antigen presentation. Instead, T-VEC contains two copies of the gene coding for the human granulocyte-macrophage colony-stimulating factor (GM-CSF). Gene Dendritic cells are stimulated both by the GM-CSF production thus triggered and by the release of antigens caused by tumor lysis. This indirectly leads to an increased T-cell response against tumor cells and explains why there is an effect on non-injected metastatic lesions as well. T-VEC therapy is generally well tolerated. Typical adverse effects at the beginning of treatment include local erythema and warmth at the injection sites as well as general symptoms such as fever and chills [ 1 ] . These usually resolve after the fi rst or second injection and do not recur with subsequent injections. We report on a 74-year-old patient who was diagnosed with BRAF wild-type melanoma on his right lower leg in June 2017. He underwent complete excision with appropriate surgical margins (in accordance with guidelines) and – given the tumor thickness – sentinel lymph node biopsy, which showed a micrometastasis (2 mm). By December 2017, a total of about 25 satellite metastases (up to 5 mm in diameter) had developed on the medial aspect of the right lower leg (Figure 1 a). Given that imaging studies (CT of the chest, abdomen and pelvis as well as cranial MRI and ultrasound of the lymph nodes) provided no evidence of further metastases, the case was discussed in an interdisciplinary tumor board. It was decided to attempt treatment with T-VEC. After the fi rst injection of T-VEC (a total of 2.5 mL at a concentration of 10 6 PFU/mL) into several of the larger cutaneous metastases, the patient not only experienced the expected side effects (subfebrile temperatures, chills and fatigue) but he also developed a rash over his entire right leg (Figure 2 ) after fi ve days. Clinical exam showed disseminated erythematous papules and papulovesicles (1–2 mm in size), except for an area on the proximal thigh that was spared (Figure 2 ). All laboratory tests were normal. While we considered these fi ndings to be a drug reaction, we did want to rule out disseminated herpesvirus infection. PCR testing of a swab and histology of a biopsy taken from one of the papulovesicles showed no virologic or histologic evidence of such an infection. A false-negative PCR result was ruled out using a gel control. Given that UL30 DNA polymerase is not affected by the above-mentioned genetic modifi cations, T-VEC can be detected with standard HSV1 PCR probes [ 2 ] . Histological examination revealed superfi cial and deep, perivascular and interstitial lymphocytic dermatitis with vacuolar interface dermatitis and central epidermal necrosis; there were no cytopathic changes characteristic of herpesvirus infection (Figure 3 a, b). Immunohistochemistry using HSV and varicella-zoster virus antibodies was likewise negative. Topical therapy with prednicarbate cream for two weeks resulted in complete resolution. At that time, the cutaneous metastases already showed slight regression (Figure 1 b). Cutaneous side effects of T-VEC primarily include local injection site reactions associated with erythema and edema but also pruritus and vitiligo. One case of psoriasis and