Diagnosis: Herpes simplex labialis

A diagnosis of herpes simplex labialis (HSL) was made based on a history of recurrent labial lesions presenting classically as vesiculation (blisters) with subsequent crusting and ulceration. The diagnosis of HSL is generally straightforward with a history and physical examination. Patients typically present with a history of intermittent grouped papules, vesicles, and ulcerated lesions located on the lips, perioral skin, nose, or cheeks.1 Fever, fatigue, myalgias, and headache often accompany the primary herpes simplex virus (HSV) infection. Prodromal symptoms (i.e., focal tenderness, burning, tingling) prior to lesion appearance are common and help differentiate HSL from allergic stomatitis.1

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HSL is a common, incurable disease that persists throughout the patient’s lifetime, often in latent form,1,2 and is most often caused by HSV-1 and occasionally by HSV-2. HSL can be painful and cosmetically disfiguring and sometimes associated with embarrassment, decreased self-esteem, anger, guilt, and negative social implications.

HSV-1 is transmitted through direct exposure of mucous membranes or abraded skin to lesions or mucosal secretions of an individual with active infection. It may also be spread by respiratory droplets or exposure to mucocutaneous secretions of an asymptomatic person shedding the virus.1 Nearly 70% of patients with HSL are reported to have HSV-1 on their hands. Because HSV-1 may remain viable on skin, clothing, or plastic, close contact may facilitate transmission.1

Recurrence of HSL is commonly preceded by prodromal symptoms at the site of the future lesion, followed by development of multiple vesicles that coalesce and rupture, forming tender, superficial erosions that rapidly crust over. The ulcerative stage of lesion progression is particularly embarrassing to patients, many of whom may pursue all available means to avoid this stage. Lesions generally heal without scarring. Lesion duration is variable and can range from several days to up to two weeks. A variety of triggers (e.g., UV light, stress, facial procedures, common cold) may precede an outbreak. Sun-induced HSL, which is common, tends to be more severe with larger lesions, higher viral titers, longer healing time, and longer duration of pain.3

The current treatment approach targets prevention of transmission, suppression of recurrence, and palliation and healing of lesions.1 Clinicians need to be able to distinguish among the available and emerging treatments, taking into account individual patient preferences and level of discomfort.

Topical and oral antiviral agents inhibit viral replication and subsequent epithelial damage.2 However, maximum benefit may be attained only if treatment is started early, since most viral replication occurs during the first 48 hours of recurrence. Patients must be vigilant in recognizing initial signs and symptoms of an outbreak and starting therapy at the onset of prodromal symptoms. Topical antiviral products (i.e., acyclovir, penciclovir) have been shown to shorten the lesion healing process if started during the prodromal stage.2 In one study of skiers with recurrent HSL, acyclovir cream (applied 12 hours before sun exposure) demonstrated a significant effect on lesion development, but other trials of UV light exposure showed more conflicting results.4

A new topical preparation containing 5% acyclovir and 1% hydrocortisone in a proprietary formulation (ME-609) for patients with recurrent oral lesions targets both local viral replication and the associated inflammatory cascade. In a Phase 3 study of adults with a history of three or more HSL episodes within the past year, this combination topical agent was more effective than acyclovir alone or placebo in reducing lesion size and increasing the number of nonulcerated (aborted) lesions.5 This is the first approved treatment (topical or oral) for recurrent HSL to demonstrate a reduction in ulcerated lesions (prevents development of vesicles or more advanced stages of a cold sore). The treatment was similar to acyclovir in reducing lesion healing time and is currently approved for early treatment of recurrent HSL.5

Oral antiviral agents (i.e., acyclovir, famciclovir, valacyclovir) are reserved for patients with frequent/persistent outbreaks of HSL, disfiguring lesions, or considerable anxiety.1 For acute (episodic) treatment of recurrent HSL in adults, acyclovir has been shown to have significant antiviral effects and to hasten lesion resolution (if started during prodromal or erythematous stages); however, acyclovir does not appear to significantly affect abortion of lesion development.2 Pre-emptive antiviral therapy in patients with known triggers has been shown to prevent (or suppress) HSL outbreaks. Several trials have shown various acyclovir regimens (200 mg five times daily or 400 mg b.i.d., started seven days to 12 hours before or immediately after UV light exposure, given for five to 14 days) to effectively suppress lesion development (within two to seven days post UV-light exposure) in patients with a history of sun-induced recurrences.3 The recommended approach is to start acyclovir (400 mg b.i.d.) 12 to 24 hours prior to sun exposure and continue throughout the period of intense exposure. Other antiviral agents (famciclovir 250 mg twice daily, valacyclovir 500 mg daily) may also suppress sun-induced HSL outbreaks.

Given our patient’s predictable pattern of HSL recurrences in response to UV light and frequent recurrences within the past months, he was given acyclovir 400 mg b.i.d. to be started 12 to 24 hours before known sun exposure and continued throughout exposure. He was also informed that diligent sunscreen application may help reduce development of HSL lesions.3 To avoid transmission, the patient was advised to avoid kissing and sharing kitchen/bathroom utensils during outbreaks. However, treatment did not prevent the development of classical lesions, so our patient was given combination 5% acyclovir and 1% hydrocortisone cream with instructions to start at the earliest signs of HSL recurrence and use five times daily for five days. He was educated about recognizing prodromal symptoms and instructed to apply the cream with a cotton swab and wash his hands after application. He has reported milder HSL episodes with more rapid resolution of lesions. There has been an overall reduction in recurrences, with one reported episode in the past six months.

Dr. Hull is assistant professor of dermatology at the University of Utah Health Care in Salt Lake City. He has no relationships to disclose relating to the contents of this article.

This activity was supported by an educational grant from Meda Pharmaceuticals.

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  1. Fatahzadeh M, Schwartz RA. Human herpes simplex virus infections: epidemiology, pathogenesis, symptomatology, diagnosis, and management. J Am Acad Dermatol. 2007;57:737-763.
  2. Esmann J. The many challenges of facial herpes simplex virus infection. J Antimicrob Chemother. 2001;47:17-27.
  3. Hull C, Spruance S. Situational antiviral drug prophylaxis for HSV type 1 recurrences. Herpes. 2007;14:37-40.
  4. Raborn GW, Martel AY, Grace MG, McGaw WT. Herpes labialis in skiers: randomized clinical trial of acyclovir cream versus placebo. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 1997;84:641-645.
  5. Hull C, Harmenberg J, Arlander E, et al. Episodic treatment with topical ACV/hydrocortisone prevents cold sore: A randomized, double-blind, patient-initiated clinical trial. J Am Acad Dermatol. In press, 2010.