Disseminated herpes simplex after total skin electron beam radiotherapy for mycosis fungoides

In mycosis fungoides, CD4+ T-cells localize to the skin, resulting in patches, plaques, tumours, and erythroderma. Superficial radiotherapy delivered with electrons to all skin surfaces is an important component of treatment in this disease. A theoretical risk of total skin radiotherapy is cutaneous immunosuppression.

CASE HISTORY

At age 76, a woman with a history of chronic lymphocytic leukaemia, hypothyroidism, recurrent herpes zoster, and cutaneous basal and squamous cell carcinomas developed mycosis fungoides involving the trunk and right shoulder. Despite treatment with multiple systemic and topical agents, the disease progressed and 4 years later she was referred to a radiation oncologist. At that time she had circular, deep pink, 1-6 cm patches and plaques on more than 10% of her body surface area localized primarily to the trunk, arms, and legs and with ulceration in the gluteal cleft and perineal region. There was no obvious adenopathy or hepatosplenomegaly.

Total skin radiotherapy was initiated with 6 megaelectronvolt electrons produced by a linear accelerator mounted on a dual-angle gantry. The patient was treated with 100 centigray (cGy) per day, 4 days per week, by a standard six-field technique.¹ After receiving 500 cGy she became severely fatigued and sought medical attention. On examination she had developed numerous 2-3 mm vesicles, pustules, yellow-crusted erosions, and haemorrhagic erosions, all of which were localized to the previously described plaques (Figure 1). A Tzanck smear gave an equivocal result but a direct immunofluorescence test for herpes simplex virus was positive. She was admitted to hospital and treated with intravenous aciclovir, 10 mg/kg every 8 hours for 24 hours then 5 mg/kg. By hospital day five, all of her lesions had encrusted. She was discharged on oral valaciclovir 1 g twice daily and has not resumed radiotherapy.

Figure 1.

A cluster of vesicles and erosions arising on a pre-existing cutaneous plaque

COMMENT

This patient developed Kaposi's varicelliform eruption (KVE), a disseminated vesicular eruption localized to plaques from a pre-existing lesion. KVE most frequently occurs in patients with atopic dermatitis, but has been reported in other skin diseases including mycosis fungoides.^2-4 Herpes simplex virus is the primary cause, but individuals with atopic dermatitis who receive the smallpox (variola) vaccine may develop an identical clinical syndrome.

Risk factors for development of KVE remain unclear. A report of two cases in patients with atopic dermatitis treated with topical tacrolimus suggests that downregulation of cutaneous cell-mediated immunity can increase the risk in susceptible individuals.⁵ A case report of KVE after sun exposure points to non-ionizing radiation as another possible trigger.⁶ In the present case, the direct cause of the disseminated herpes simplex eruption is uncertain. Clearly, the patient was already immunosuppressed by her chronic lymphocytic leukaemia and by the various immunomodulatory treatments for mycosis fungoides; therefore, it is quite possible that the temporal relation between initiation of total skin radiotherapy and occurrence of KVE arose solely by chance. Alternatively, the radiotherapy may have further suppressed cutaneous cell-mediated immunity and thus put the patient at risk of herpes infection.

Only one other group has documented KVE after total skin electron therapy. In this report, a woman of 39 with plaque stage mycosis fungoides developed KVE after receiving 4600 cGy to all skin surfaces.³ From serial samples of peripheral blood, the investigators detected a transient depression of natural killer cell activity that coincided with the start of radiotherapy and may have contributed to the development of KVE.

Our case report illustrates that KVE can occur even after small doses of external radiation. Radiation oncologists, dermatologists, and general practitioners should be aware that a vesicular eruption during the course of total skin radiotherapy may signify a life-threatening condition that requires immediate diagnosis and intravenous antiviral therapy. In view of the rarity of this complication, we do not advise routine antiviral prophylaxis during total skin radiotherapy.