• Summary
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• Background
• Clinical Diagnosis
• Treatment

Criteria for use of guidelines

• All adult patients with evidence of oropharyngeal herpes.

Investigations required

• Nil
• PCR of vesicle fluid can be done in difficult to diagnose cases
• Serology can determine previous infection
• Type specific and IgM assays are available but rarely needed in the diagnosis of oropharyngeal herpes.

Non-Antimicrobial Management  

• Rehydration
• Lubricant- petroleum jelly

Antimicrobial treatment

• Topical Aciclovir 5% cream if given promptly.
• Oral antivirals not recommended routinely.
• If exceptionally severe Aciclovir 200mg - 400mg 5 times a day for 5 days should be used.
• In immunocompromised patients valaciclovir 500mg bd for at least 5 days may be used. Longer may be required. Please seek advice if failure to respond after 10 days treatment.

Antimicrobial allergy

• contact microbiology or Infectious Diseases for advice

Prophylaxis

• seek expert advice.

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Herpes Simplex Virus (HSV) is a member of the herpes viridae family which frequently causes infection ranging from mild to fatal illness. HSV 1 is normally associated with orofacial infections. Following primary infection both viruses cause latent infection and can cause disease upon reactivation. Many individuals will be asymptomatic despite being seropositive. Individuals who are HSV seronegative will develop a ‘primary’ infection after their first exposure. “Initial” infection will occur when an individual has antibodies to either HSV 1 or 2 and is exposed to the other virus. Seropositivity increases with age and may be over 90% by the fifth decade. Rates of seropositivity vary according to socioeconomic group and ethnic factors.

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This is often clinical in the case of uncomplicated HSV infection.
Symptomatic oropharyngeal disease is characterised by lesions of the buccal and gingival mucosa. Intraoral lesions indicate a primary infection whilst lip lesions suggest reactivation. Primary infection is also normally more severe in nature. Recurrent lesions are preceded by pain, burning or tingling – vesicles may then appear a few hours later. It is this prodromal time that affords a window of opportunity for treatment. The vesicles then become pustules and finally crust over. The lesions are normally healed within 10 days.
In an immunocompromised host the disease process can be much more severe and even life threatening in some cases.

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The treatment of herpes simplex infection is largely based on the use of various nucleoside derivatives that interfere with the synthesis of viral DNA.

Treatment of uncomplicated oropharyngeal disease

Non-microbial:
Rehydration if necessary. If severe lesions and unable to drink. Evidence level C

• No evidence for topical pain relief. Prodigy recommends topical choline salicylate gel or lidocaine ointment, based on evidence from studies on ulcers. Evidence level D
• Lubricant- petroleum jelly to prevent cracked lips.

Microbial:
Topical:
 Aciclovir cream 5% five times a day for 5 days, only if started at prodromal stage no benefit once crust formed.

Studies with Aciclovir 5% cream demonstrated small but statistically significant reduction in pain and lesion duration when administered within 1 hr of onset and then five times a day for 4 days compared with placebo. Duration of lesion episode < 1 day.¹
One study also found topical Aciclovir had an impact on aborting lesions-prevention of development of vescicular lesion and subsequent hard crust formation. ² Evidence level A

Penciclovir 1% administered up to six times a day for first day and then every 2hr for 4 days small, significant improvement in lesion healing.³ Compared with Aciclovir non-significant - similar efficacy, clinical cure rates, but penciclovir shorter time to resolution ⁴.

•  Aciclovir 5% cream may be used if given promptly.

Oral:
Primary infection
There is limited evidence for antivirals in primary infection and most studies seem to be aimed at severe reactivation of disease. There is one grade A trial in children which shows a benefit.¹¹
As primary infections tend to be more severe many clinicians advocate the use of oral antivirals.
Secondary infection
Treatment with oral antivirals decreases the duration of recurrent lesion episodes and pain by approximately one day; however, the antivirals do not abort lesions from developing. Clinical implications of these results appear relatively modest. ⁵
Greater biovailability of valaciclovir may translate into an improved clinical benefit in that some lesions can be aborted by patients administered valaciclovir during prodromal phase. ⁶

There have been no trials directly comparing the newer antivirals with Aciclovir . There have, however, been a few placebo controlled studies. Significantly more work has been done in the area of genital herpetic infection. Valaciclovir is superior to placebo in reactivation of HSV if given in the prodromal phase of the illness. Famciclovir is also superior to placebo. Both can be given in very short courses.

There has been a large randomised, double blind, placebo – controlled trial of valaciclovir in North America which led to the licensing of valaciclovir in the treatment of oropharyngeal herpes in the USA. They showed that short course valaciclovir when given early in the course of disease, during the prodrome and prior to any clinical signs significantly reduces the duration of the episode and the time to cessation of pain/discomfort was also significantly reduced. They showed no difference between using 2g 12 hourly for 2 doses and 2g bd for 24 hours followed by 1g bd. ⁷ A second study, also by Spruance showed Famciclovir (single dose of 1500mg) to reduce the healing time of lesions when compared with placebo. ⁸ Evidence level D

There have been no trials looking at either of these agents in primary infection.

• Oral antivirals not recommended routinely.
• In primary infection and exceptionally severe episodes of reactivation Aciclovir 200mg - 400mg 5 times a day may be used.

Treatment in the immunocompromised host
All trials refer to the treatment of reactivation of HSV rather than primary infection.
HSV reactivation remains a problem in immunosuppressed individuals. There have been a few studies comparing valaciclovir and Aciclovir in this setting. Eisen et al looked at the use of valaciclovir and Aciclovir for the prevention of HSV reactivation following bone marrow transplant or stem cell rescue therapy. This was a descriptive study using a historical Aciclovir control group. Their data did show that fewer patients in the valaciclovir group required IV Aciclovir treatment. ⁹

A further placebo controlled trial (not randomised) shows a significant difference between Famciclovir and placebo in reduction of HSV shedding and symptomatology in HIV infected patients. This was seen in both anogenital infection and oropharyngeal infection. ¹⁰ Evidence level D

In view of the possible increased pill burden in immunocompromised patients and the perceived concept that adherence may be poorer, and the consequences of such non adherence will be more significant, it may be sensible to use valaciclovir in this situation. However, there is no evidence to suggest that this is more effective than Aciclovir .

• In immunocompromised patients oral valaciclovir 500mg bd for 5 days may be used.

Prophylaxis

The role of prophylaxis of recurrent herpes simplex infection is beyond the scope of this guideline. Seek expert opinion in such cases.

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