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Education, proper management can keep herpes zoster from progressing to postherpetic neuralgia

One out of three individuals in this country will eventually get shingles.

by Richard B. Mangan, OD, FAAO

Special to Primary Care Optometry News

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Postherpetic neuralgia is a painful and often debilitating complication of herpes zoster, or shingles. This article will review the natural course of herpes zoster with an emphasis on the eye care practitioner’s role in education, prevention and management of postherpetic neuralgia.

According to a recent population-based epidemiology study by Yawn and colleagues on the incidence and complication rates of herpes zoster, one out of three individuals living in the United States can expect to be diagnosed with shingles in their lifetime. This would equate to about 1 million cases of shingles each year.

Eye care professionals are more likely to be involved in the care of the shingles patient when the ophthalmic division of the trigeminal nerve has become involved. This is known as herpes zoster ophthalmicus (HZO). Of the estimated 1 million shingles infections each year, about 10% to 20% will present as HZO, according to Liesegang, and in 8% to 12% of cases, one of the more feared sequelae, postherpetic neuralgia (PHN), will develop according to Galil and colleagues and Oxman and colleagues.

In herpes zoster ophthalmicus, cutaneous lesions may form on the scalp, forehead, lids and periorbital region. Note this midline rash involving V1.
Blepharodermatitis secondary to HZO.
In herpes zoster ophthalmicus, cutaneous lesions may form on the scalp, forehead, lids and periorbital region. Note this midline rash involving V1.
Images: Swartz TS
 Blepharodermatitis secondary to HZO.



Incidence rates for shingles and PHN increase progressively with age. While shingles can occur at any age, it is most common in those older than 50 years, according to Schmader. As the general age of our adult population increases, we can expect to see an increase in not only the incidence of herpes zoster, but also the severity.

Ninety percent at risk for shingles

Exposure and infection by the primary form of varicella-zoster virus (VZV, or chicken pox) usually occurs in early childhood. During the virulent phase, the virus migrates along sensory nerve fibers and enters the dorsal root ganglia where it may lay dormant indefinitely or until reactivated. Choo and colleagues estimate that 90% of U.S. adults would serologically test positive for VZV and be considered at risk for shingles.

The biggest risk factor for developing herpes zoster is increasing age. As we age, our cell-mediated immune system naturally wanes. It is especially at times of physiological stress that the latent VZV is most opportunistic. In the majority of cases, the virus may reactivate and result first in prodromal pain involving a specific dermatome where subsequent lesions will develop.

Pain levels, symptoms

The following are the pain characteristics of the herpes zoster prodromal phase:

The prodromal phase of herpes zoster has been misdiagnosed as influenza, myocardial infarction, colic, pleurisy, dental pain, glaucoma, duodenal ulcer and appendicitis, according to Sampathkumar and colleagues. However, the acute phase of active shingles leaves little room for misdiagnosis.

According to Gnann, what starts as a unilateral painful eruption of red macules and papules along a specific dermatome (adjacent dermatomes may become active in 20% of cases) over a 7 to 10 day period later evolves into vesicles, then pustules and finally scabs. Complete resolution of the active phase may take up to 4 weeks. It is important to note, however, that there are rare occasions when cutaneous lesions never form after herpes zoster prodromal nerve pain. This is known as zoster sine herpete, reported Sampathkumar and colleagues.

Herpes zoster pseudodendritic lesions of the cornea.
Raised, largely peripheral pseudodendritic satellite lesions from HZO.
Herpes zoster pseudodendritic lesions of the cornea.

Image: Swartz TS
 Raised, largely peripheral pseudodendritic satellite lesions from HZO.

Image: Epstein A

In HZO, these cutaneous lesions may form on the scalp, forehead, lids and periorbital region. When the nasociliary branch of the ophthalmic division of the trigeminal nerve is affected, as indicated by a vesicular lesion on the side, root or tip of the nose (Hutchinson sign), the patient has a 66% to 75% chance of incurring some form of globe involvement. According to Harding and colleagues, the risk of globe involvement decreases to 33% for those with no Hutchinson sign.

Ocular or globe involvement from HZO can be varied, both in presentation and timing. Presentation of ocular signs and symptoms may be acute – within a few days of the development of cutaneous lesions – or delayed for years. Ocular involvement includes and is not limited to blepharodermatitis, conjunctivitis, dendriform keratitis, anterior stromal (nummular) keratitis, deep stromal keratitis, neurotrophic keratitis, scleritis, anterior uveitis, choroiditis, iridocyclitis, optic neuritis, retrobulbar optic neuritis, oculomotor palsies, pupillary abnormalities, acute or secondary glaucoma, acute retinal necrosis and Bell’s palsy.

HZO: A case study

A 71-year-old white male, PZ, came in on referral from his primary care physician (PCP) after being diagnosed with herpes zoster ophthalmicus. The patient went to his PCP the same day after reporting the onset of a rash on the right side of his scalp and forehead.

When asked about the onset of his condition, PZ indicated that he developed pain and tenderness to his scalp and forehead about 4 days prior, but the rash started yesterday. His PCP started him on 1,000 mg of Valtrex (valacyclovir, GlaxoSmithKline) three times daily and referred him to our clinic, as his right upper lid was edematous and swollen shut.

External examination was positive for a unilateral maculopapular rash that respected the midline of the scalp and forehead, with extension to the right upper lid with edema. There was a positive Hutchinson sign.

Standard dosing of oral antivirals for treating herpes zoster

Despite the significant lid edema, the view of the globe was straightforward. PZ had 2+ ciliary injection of the conjunctiva and mild chemosis. There were multiple raised pseudodendrites located at the peripheral cornea and a low grade anterior chamber response, all in the right eye. Spectacle corrected visual acuity in the right eye was 20/100, pinholing to 20/40. Dilated examination was unremarkable, and there was no apparent cranial nerve involvement.

We diagnosed him with HZO with dendriform keratitis and secondary iritis. Our treatment plan included topical Pred Forte 1% (prednisolone acetate, Allergan) in the right eye every 3 hours while awake; refrigerated, preservative-free Refresh Plus (Allergan) four times daily to as needed in both eyes; bacitracin ointment at bedtime in the right eye; continue Valtrex as prescribed; cool, moist compresses to the scalp and forehead.

PZ’s acute HZO was managed successfully with this treatment plan. Ocular findings were resolved within 6 weeks of rash onset, with minimal effect on best-corrected visual acuity. However, PZ later developed PHN. It was later determined through a retrospective chart analysis that 4 years later PZ was still experiencing intermittent pain along the dermatomal distribution of V1, requiring the use of gabapentin 600 mg twice daily and Zoloft (sertraline, Pfizer) 100 mg once daily. During that 4-year period, other treatments were ordered in varying doses, at different times, by a pain specialist and include tramadol, methadone, amitriptyline, topical capsaicin, 4% lidocaine cream, epidural methylprednisolone and stellate ganglion block.

During the first year following the resolution of his cutaneous lesions, his pain symptoms were most severe. For a 3-month period of time, PZ reported having about eight attacks per day of intermittent “excruciating” pain lasting 5 minutes each. At one visit, the comment, “I am not sure how much longer I can stand this,” was documented.

Managing postherpetic neuralgia

PHN is one of the most feared sequelae of herpes zoster. Often described as excruciating, throbbing, burning or lancinating, Oxman and colleagues define PHN as an intermittently chronic pain lasting more than 90 days after cutaneous lesion development from HZ. While not fully understood, the principal cause of pain is suspected neuronal destruction and inflammation from continuous replication of the varicella zoster virus (VZV), according to Acosta and Balfour. While PHN symptoms usually occur intermittently with no correlation to external stimuli, some patients may exhibit allodynia, where even the lightest touch to sensitive areas of the skin may be terribly painful.

Schmader reported that it is not uncommon for patients to experience physical changes (i.e., insomnia, chronic fatigue, anorexia, weight loss), emotional changes (mood swings, anger and depression) and functional challenges (lack of concentration, ability to perform simple chores or tasks) related to PHN.

Anterior uveitis secondary to HZO.
Anterior uveitis secondary to HZO.
Image: Karpecki P

Managing PHN can be challenging. While there is mention of a wide array of proposed treatments for PHN in the medical literature, the American Academy of Neurology (www.aan.com) recommends the following evidence-based treatment protocol either in isolation or in combination for the treatment of PHN:

Topical anesthetics offer the advantage of providing localized pain relief without systemic side effects. Even though topical lidocaine comes in a patch, it is not to be confused with other patches that offer cutaneous administration for a systemic effect (i.e, estrogen or scopolamine). Potential localized side effects include blistering, burning, bruising, depigmentation, erythema, edema and pruritus. Up to three patches may be used at one application per day and they are not to be used for more than 12 hours at a time.

Tricyclic antidepressants are considered the mainstay treatment in otherwise healthy individuals with PHN. There are advantages and disadvantages to using these agents. Advantages are: they have been proven to reduce neurogenic pain; they help improve depressive symptoms that accompany chronic pain; and amitriptyline in generic form is relatively inexpensive. Disadvantages are largely attributed to the cholinergic side effects, such as sedation, constipation, blurred vision, orthostatic hypertension, urinary retention and cardiac arrhythmia. These should be used with caution in the elderly. Selective serotonin re-uptake inhibitors such as Prozac (fluoxetine, Eli Lilly), Zoloft and Paxil (paroxetine, GlaxoSmithKline) are less effective at reducing pain, but also offer less severe side effects.

Antiepileptic drugs, including the newer generation medication, gabapentin, have been well studied for PHN by Rowbotham and colleagues and Serpell. While the exact mechanism of action is unknown, gabapentin is believed to decrease the calcium-mediated synthesis of excitatory neurotransmitters, reported Fink and colleagues.

The chemical analogue to gabapentin, Lyrica (pregabalin, Pfizer), has been shown to be equally effective, according to Dworkin and colleagues, while offering a more convenient twice daily dosing regimen. Lyrica is prescribed initially at 50 mg to 75 mg twice a day, with planned increases up to 300 mg/day within 7 days until adequate response or a maximum dose of 600 mg/day is reached. Side effects are generally mild but may include dizziness, diarrhea, diplopia, conjunctivitis, somnolence and hyperglycemia, dry mouth and weight gain.

While the above treatments have shown mild to moderate success in reducing neurological pain related to PHN, there is no evidence to suggest they are curative or reduce the overall morbidity of the condition. Because PHN can have such an adverse effect on quality of life, the most important aspect of the optometrist’s role in PHN management is patient and staff education regarding prevention.

Preventing PHN with Zostavax

One possible way of preventing PHN is by decreasing the incidence of herpes zoster by vaccination.

The zoster vaccine contains the same live attenuated strain of VZV as in Varivax (varicella vaccine virus live, Merck), which is used to prevent chickenpox in children. However, Zostavax (zoster vaccine live, Merck) is 14 times more potent.

In a double-masked, randomized, placebo-controlled trial known as the Shingles Prevention Study, the vaccine was found by Oxman and colleagues to reduce the incidence of herpes zoster by 51.3% and the risk of PHN by 66.5% in patients 60 years or older. The vaccine was most effective for patients in their seventh decade of life, with efficacy persisting for at least 4 years.

Side effects associated with this vaccine are generally mild. Some patients will experience some erythema, swelling and pruritis at the injection site, resulting in mild pain or discomfort. Systemic side effects (notably headache and fever) are also mild with proper patient selection. Because the vaccine has a relatively strong safety profile, the Advisory Committee on Immunization Practices, an advisory committee to the U.S. Centers for Disease Control and Prevention, recommends routine vaccination of all people 60 years or older with one dose of the zoster vaccine.

As health care practitioners, we can play a pivotal role in the dissemination of information about the herpes zoster vaccine. Information should be practical and specific and include guidance about access to the vaccine. Eligible patients can be encouraged to speak to their primary care physicians about the vaccine at a future appointment.

Considerations for prescribing Zostavax

The vaccination costs about $160, with administration fees pushing the overall cost up to $200 to $225. Insurance coverage for Zostavax varies from plan to plan. For patients 65 years of age or older who are enrolled in a qualified Medicare Part D prescription drug plan, the vaccine is usually covered, but administration fees typically are not, and co-pay amounts will vary. Medicare Part B does not cover the vaccination.

Because the vaccine is supplied frozen and must be reconstituted and administered immediately (within 30 minutes), not all pharmacists are able to provide it. The PCP should perform a thorough review of systems before the patient is scheduled for vaccine acquisition, preparation and injection. Doctors in your area who are providing these vaccinations will already have an arrangement with a local pharmacy to obtain the vaccine.

The zoster vaccine is administered as a single 0.65-mL dose subcutaneously in the upper arm. It may be given concurrently with other vaccinations.

Patients anticipating immunosuppression (i.e., high dose oral steroid use) may still have the vaccine as long as it is delivered at least 2 weeks prior to the anticipated start of therapy that may lead to immunosuppression.

Patients who are currently receiving antiviral therapy for other herpes infections may receive the vaccine as long as the antiviral therapy is discontinued for 24 hours prior to vaccination and delayed for 2 to 4 weeks post-injection.

While less common, patients with a history of recurrent shingles may have the vaccine as long as it is not in the active phase.

The vaccine is contraindicated in patients who are currently immunocompromised, those with a known allergy to any component of the vaccine, women who are or might be pregnant (unlikely in this recommended age group), those who have received the varicella vaccine and patients with active herpes zoster or PHN.

Preventing PHN by treating acute herpes zoster or HZO

Another possible way of decreasing the likelihood or severity of PHN is the timely initiation of oral antiviral therapy during the acute phase of shingles. At this time, oral antivirals such as acyclovir, valacyclovir and famciclovir hasten resolution of signs and symptoms by decreasing viral shedding and the formation of new skin lesions.

In 1997, Jackson and colleagues offered a meta-analysis on the effect of acyclovir on PHN prevention. They found that acyclovir used within 72 hours of rash onset significantly reduced the incidence of PHN by 46% at 6 months. Since that time, head-to-head studies with acyclovir by Beutner and colleagues and Shafran and colleagues have shown that valacyclovir and famciclovir offer a more rapid resolution of acute neuritis and shorten the duration of PHN. Another advantage of prescribing the latter two products is a more convenient dosing regimen.

Oral antiviral therapy should be initiated in uncomplicated zoster cases if the patient comes in within 48 to 72 hours. The efficacy of therapy started outside this 72-hour window has not been clearly established. In theory, these antiviral medications should decrease viral replication as long as the acute rash persists. As these medications offer a favorable safety profile, many clinicians will still recommend treatment at any time during the acute phase of shingles.

As shown in the accompanying table, generic acyclovir is the least expensive therapy, followed by generic famciclovir. It is natural for physicians to be sensitive to the cost discrepancy of these medications and immediately choose acyclovir. However, it is imperative to discuss in a cooperative doctor-patient relationship the advantages and disadvantages of these medications. In doing so, the patient can make an educated decision based on his or her own situation or concerns.

The use of oral corticosteroids has been considered and studied by Whitley and colleagues and Wood and colleagues as an adjunctive treatment for managing acute HZ. While steroids in combination with oral antiviral therapy may modestly reduce the severity and duration of acute symptoms, they appear to have no effect on PHN incidence, severity or duration. In general, steroids should be reserved for severe presentations and carefully monitored, as they may increase systemic dissemination of the infection. McFarlane and colleagues propose the following treatment schedule for oral prednisone: 30 mg twice daily for days 1 to 7, 15 mg twice daily for days 8 to 14 and 7.5 mg twice daily for days 15 to 21.

Preventing PHN with education

Education is also important regarding the mildly contagious nature of VZV during the acute phase. While VZV is less contagious than primary varicella in susceptible people, the zoster lesions do contain high concentrations of VZV that can be spread by contact and, to a lesser degree, air. Patients should be notified that they pose a risk to those who have never had the primary infection of chickenpox and should take appropriate measures to decrease the risk of infecting others, especially those who are immunosuppressed. Lesions are no longer contagious when crusting occurs, according to Seward and colleagues. Until that time, keeping the lesions covered reduces the risk of transmission.

As the skin of patients with herpes zoster is inflamed, tender and sensitive to touch, local application of compounds such as Burow’s solution, calamine lotion, or Aspercreme (10% trolamine salicylate, Chattem) covered by a moist or wet dressing can be soothing and decrease pain associated with the rubbing of loose clothing. This also keeps contamination of clothing, bed sheets or pillowcases to a minimum. Keep in mind that these crèmes or lotions should not be used on or near the periorbital region. If there is concern about secondary infection, a topical antibiotic ointment such as bacitracin or erythromycin may be applied instead.

Unfortunately, not all patients present in a timely fashion to their primary care or eye care physicians when zoster signs and symptoms first arise. Should this occur, the risk of debilitating pain and vision loss increases. With that said, even if timely therapy is initiated, this is no guarantee that permanent vision loss or PHN will be avoided or abated, as evidenced by our patient, PZ.

As health care providers, we have the opportunity and responsibility to begin educating patients in their early 50s about the natural course and warning signs of shingles. Take the time to explore which physicians in your area are offering the VZV vaccine and contact them regarding their vaccination protocol. They will often be able to provide you with some referral cards and handouts that describe the process, costs and insurance-related questions. You will then be ready to spend a few available minutes during the course of a routine office visit to discuss the risk factors and warning signs of shingles, the success rate associated with the VZV vaccine and the importance of timely treatment with oral antiviral therapy. Additionally, a brochure or direction to informational Web sites (i.e, shingles.com, aftershingles.com and cdc.gov/vaccines) will help solidify the information given during the office visit.

Finally, education is not just for the patient, but also our staffs. Take the time to provide an in-service for your entire staff, including telephone operators and schedulers, so they are more likely to triage a patient’s symptoms appropriately. A few days may mean the difference between a more rapid recovery of a self-limiting condition (shingles) and a year or more of severe lancinating pain (PHN) that has pushed some patients to the brink of suicide.

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