Disseminated cutaneous herpes zoster complicated by acyclovir nephrotoxicity and successfully treated with brivudin

ARTICLE

Auteur(s) : Berna Aksoy^1,2, Asli Altaykan-Hapa³, Abdülkadir Cengiz⁴, Hasan Mete Aksoy⁵, Nilgun Atakan³

¹TDV 29 Mayis Private Ankara Hospital, Dermatology Clinic, Ankara, Turkey
²Private Konak Hospital, Dermatology Clinic, Kocaeli, Turkey
³Hacettepe University Faculty of Medicine, Department of Dermatology, Ankara, Turkey
⁴TDV 29 Mayis Private Ankara Hospital, Internal Medicine Clinic, Ankara, Turkey
⁵Private Konak Hospital, Plastic and Reconstructive Surgery Clinic, Kocaeli, Turkey

Acyclovir is a highly effective antiviral agent available for treatment of varicella zoster virus (VZV) infection. Adverse effects of acyclovir are injection site reactions, neutropenia, Stevens-Johnson syndrome, neurotoxicity and nephrotoxicity. Neurotoxicity usually presents with hallucinations, delirium, tremors, ataxia, seizures and even coma [1]. Acute renal failure from intravenous use of high doses is also a well known complication and its estimated incidence is 12-49%. Suggested risk factors for renal failure are rapid bolus injection, high dose administration and inadequate hydration, all of which increase the concentration of acyclovir in renal tissue. Due to its narrow therapeutic index, baseline renal function tests are recommended before the initiation of therapy [2].

A 70-year-old man was admitted for vesicular lesions involving the cervical dermatomes C6, C7, C8 and 45 additional lesions located on the left forearm, right arm, trunk, face and scalp. He had a past medical history of rheumatoid arthritis and hypertension. The most recent therapy for rheumatoid arthritis was methotrexate, which had ended 6 months previously. Disseminated VZV infection was diagnosed, and acyclovir with a slow intravenous infusion of 2,250 mg/day in 3 divided doses (10 mg/kg/dose) was initiated. He had no laboratory abnormalities, including renal function tests, at the beginning of the therapy. On the third day of acyclovir therapy, the patient developed nausea, vomiting and lethargy. Laboratory examination was remarkable for blood urea nitrogen of 36.4 mg/dL (4.7-23) and serum creatinine of 3 mg/dL (0.5-1.3). Serum electrolyte levels were within normal limits except sodium levels of 129.6 mEq/L (135-150) and acidosis never developed. The diagnosis was acute renal failure due to acyclovir therapy and the treatment was discontinued. Renal function tests gradually decreased to normal levels with oral and intravenous hydration and diuretics in the following 10 days. After the discontinuation of acyclovir, brivudin at a dosage of 125 mg peroral once daily was started for 7 days. Herpetic lesions resolved during therapy with brivudin and no deterioration of renal function tests was observed.

Disseminated cutaneous herpes zoster is defined as more than 20 lesions outside the area of primary and adjacent dermatomes. This form of herpes zoster is usually observed in immunocompromised persons. However, it has rarely been described in healthy individuals [3]. Patients with dissemination have a high risk of visceral involvement. Therefore, appropriate and timely treatment is important and intravenous acyclovir is recommended [4]. Immunosuppressive therapy given 6 months previously may be the reason for dissemination in our patient, as well as age-related depression of cellular immunity.

Brivudin is an oral antiviral drug which is effective in the treatment of herpes zoster. The most common side effects are nausea and headache. A unique advantage of brivudin is its convenient once daily dosing frequency. In contrast to acyclovir, brivudin dosage need not be altered in patients with renal and hepatic failure. However, its major disadvantage is the lethal drug interaction with thymidine analogues such as 5-fluorourasil and tegafur, due to fatal accumulation of these drugs. There are reports suggesting significant advantages for brivudin over acyclovir for termination of vesicle formation and acceleration of healing of the herpetic lesions [5].

When side effect profiles and dose regimens are taken into consideration, brivudin may be an alternative therapy for patients presenting with disseminated herpes zoster and especially for patients who experience nephrotoxicity during acyclovir treatment.

Acknowledgements

References

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4 Diaz-Ramon JL, Diaz-Perez JL. Herpes simplex and zoster. Eur J Dermatol 2008; 18: 108-11.

5 Clercq E, De. Discovery and development of BVDU (brivudin) as a therapeutic for the treatment of herpes zoster. Biochem Pharmacol 2004; 68: 2301-15.