Delayed allergy to acyclovir revealed by lymphocyte proliferation test

Acyclovir (Acycloguanosine) is an antiviral drug commonly used in the management of the Herpes virus infections. Indeed, acyclovir has the unique property of inhibiting viral DNA polymerases and, thereby, decreasing the production of viral particles. Acyclovir can be administered by a topical, oral or intravenous route, depending on clinical circumstances. Importantly, in the case of haematological malignancies, acyclovir can be used after either chemotherapy or stem cell transplantation, in order to prevent Herpes virus reactivation [1]. So far, immediate allergic reactions to acyclovir have been described [2]. In contrast, delayed allergy to acyclovir remains anecdotal [3].
Here we report a case of an adult patient diagnosed with non-Hodgkin lymphoma who developed severe delayed hypersensitivity to oral acyclovir administration. The adverse reaction was revealed using a non-radioactive lymphocyte proliferation test (LPT).
A 62-year-old man was diagnosed with non-Hodgkin lymphoma in 2014. In May 2016, he underwent autologous haematopoietic stem cell transplantation, followed by an oral acyclovir treatment course (1200 mg/day, for 7 days), to prevent Herpes virus reactivation (IgG anti-Herpes simplex 1–2 29.1 U/ml; IgG anti-Epstein Barr virus 30.4 U/ml). This treatment was well tolerated.
In November 2016, due to a relapse of the non-Hodgkin lymphoma, the patient started treatment with bendamustine and rituximab. This treatment was followed by an oral acyclovir course at the same dosage as above. However, after 10 days, the patient developed a generalized cutaneous rash characterized by erythematous, long-lasting and intensively itchy lesions (Figure 1 A). For this reason, the treatment with acyclovir was stopped and treatment with prednisone 5 mg/day and fexofenadine hydrochloride 180 mg b.i.d. was established.
In December 2016, the patient underwent another treatment course with bendamustine and rituximab; however no antiviral treatment was administered following this latter treatment course. Importantly, the patient did not develop any adverse reactions.
Thereby, based on the clinical symptoms manifested, the time of onset of the adverse reaction and the resolution of the clinical condition upon treatment withdrawal and steroid treatment, we postulated the diagnosis of delayed hypersensitivity to acyclovir.
Thus, the case was further investigated using both patch tests and LPT. The patch tests performed with a 25...


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