Nasal Symptoms During Isotretinoin Therapy Can Be a Sign of Herpes Simplex Virus Infection

Abstract

To the Editor: Isotretinoin (13-cis-retinoic acid)—a derivative of vitamin A—is a commonly used effective treatment for acne vulgaris that is also, but less frequently, used to treat a wide range of additional dermatological conditions, including other pilosebaceous disorders, granulomatous diseases, disorders of keratinization, scarring alopecia, cutaneous lupus erythematosus, photoaging, and nonmelanoma skin cancer prophylaxis.1 The most common adverse effects of systemic isotretinoin administration are mucocutaneous dryness, epistaxis, and cheilitis.2 Cutaneous herpes simplex virus (HSV) infection is common, chronic, and recurrent, and is caused by HSV type 1 (HSV-1) and type 2 (HSV-2). According to World Health Organization, 67% of the world's population is infected with HSV-1. Herpes simplex virus type 1 infection is usually asymptomatic; however, the virus is shed frequently and subclinically. Clinically apparent HSV-1 infection manifests in most cases as orolabial herpes lesions, which generally have a benign and self-limiting course. Reports on the relationship between vitamin A derivatives and HSV infection are inconsistent. Vitamin A derivatives are known to have virucidal activity, and isotretinoin has been used for the treatment of recurrent HSV infection with encouraging results3,4; however, in recent years, prolonged or recurrent HSV infection has been observed in patients during isotretinoin treatment.5–7 Herein, we present a patient that had recurrent nasal mucosa HSV-1 infection during isotretinoin treatment. CASE REPORT A 46-year-old woman presented with an acute painful vesicular eruption in the nasal mucosa. She reported that she had taken isotretinoin a single dose of 10 mg 7 days before the onset of the eruption. She also reported that she had experienced a similar eruption in the same area after taking another single dose of isotretinoin 3 weeks earlier. She began taking isotretinoin on an irregular basis because of keratosis pilaris approximately 1 month before presentation. The patient had a history of herpes labialis but reported not having had intranasal herpes infection before using isotretinoin. Dermatological examination showed grouped coalescing vesicles and pustules in the left nasal mucosa. The patient was not atopic, systemically ill, or immunocompromised. Polymerase chain reaction analysis was performed from the base of a fresh vesicular lesion and HSV-1 was identified. Systemic valacyclovir 500 mg twice a day was initiated, and 5 days later, the lesions were completely healed. At the 6-month follow-up, the patient reported that she had not had any HSV infections after discontinuing isotretinoin. The presented patient's frequent recurrence of HSV-1 infections after use of isotretinoin suggests that isotretinoin was a predisposing agent. The connection between isotretinoin and HSV-1 infection has been previously described.5–7 Isotretinoin-induced HSV infection is thought to be associated with mucocutaneous dryness, photosensitivity, atopy, reduced stratum corneum thickness, and a decrease in cutaneous integrity. In addition, retinoids are known to modulate immune response via their effect on T-cell differentiation and function,8 and because they decrease the number and activity of natural killer cells and cytokines.9 Although the interferon signal pathway is the most important line of host defense against HSV-1, replication or reactivation of HSV in ganglia is controlled by cells of the innate immune system.10 It is difficult to determine whether HSV reactivation is due to isotretinoin-induced mucocutaneous dryness, an immunological mechanism, or a combination of both; however, in the presented case, we think that it was most likely due to mucosal dryness, as the symptoms of infection manifested sooner than a single dose of isotretinoin is expected to affect the immune system. Intranasal HSV infection can easily be overlooked, as it mimics the symptoms of nasal dryness, a common adverse effect of isotretinoin. Dermatologists should be aware that isotretinoin can trigger intranasal HSV infection—a potentially life-threatening condition in immunosuppressed patients. Basak Yalici-Armagan, MD Department of Dermatology and Venereology Hacettepe University Faculty of Medicine Ankara, Turkey [email protected]Sibel Ersoy-Evans, MD Department of Dermatology and Venereology Hacettepe University Faculty of Medicine Ankara, Turkey