A 66-year-old black male presented with a chief complaint of unilateral ocular itching in his right eye. He claimed that the itch involved his lower eyelid and cheek, radiating back to his right ear, and that the condition had persisted for at least a year. His ocular history was positive for a “lazy” right eye since childhood which had never received any treatment. Six years earlier, he had been diagnosed with and treated for herpes zoster involving the right side of his face. The patient’s medical history was positive for hypertension and generalized seizure disorder. Medications included amlodipine, phenobarbital and Dilantin (phenytoin, Pfizer).

Diagnosis
An evaluation revealed his best-corrected acuity as 20/50 OD and 20/20 OS. A constant, right exotropia of 40 prism diopters was noted, consistent with the patient’s amblyopic history. Pupils were equal and reactive in both eyes without afferent defect. Motilities and confrontation visual fields were grossly full, in both eyes. Physical examination revealed no focal lesions, edema or discoloration of the “itchy” areas. Both eyes were white and quiet, with clear media and unremarkable fundus examination. Based upon the history and presentation, he was diagnosed with post-herpetic itch (PHI), a less-common and underreported form of post-herpetic neuralgia (PHN).

Shingles Background
Herpes zoster, or “shingles,” results from reactivation of dormant varicella zoster virus (VZV) in the regional nerve ganglia. This viral infection first manifests clinically as chickenpox, a relatively common infection of childhood. Researchers believe that 99% of adults in the United States are seropositive for VZV.¹ Immune stress, often seen with advancing age or illness, allows the virus to emerge from dormancy and begin replication.² This secondary infection is not disseminated like chickenpox, but rather limited to a single neural dermatome in most cases. The term herpes zoster ophthalmicus (HZO) is used when the first branch of the trigeminal nerve (i.e. ophthalmic nerve, V1) is involved. 

Ocular involvement may also be seen when the second branch (i.e., maxillary nerve, V2) is implicated, although this is much less common and, in such cases, the severity of ocular sequelae tends to be far less substantial. In the acute stage, herpes zoster presents with painful vesicular eruptions of the skin, corresponding to the terminal points of sensory innervation along the involved dermatome. While the lesions of herpes zoster are transient and will typically resolve within several weeks, the associated neuropathic irritation may continue well beyond the resolution of the dermatitis. We refer to this persistent discomfort as PHN.

Post-Herpetic Neuralgia
PHN is believed to affect roughly 20% of those with herpes zoster, although older age at onset, a more intense prodrome, greater severity of presentation and a history of chronic illness (e.g., respiratory disease, diabetes) are associated with an increased likelihood of PHN.^2-5

By convention, this phenomenon exists when clinically significant pain or painful abnormal sensation endures for more than 90 days beyond the first appearance of the vesicular rash.^2,6 PHI, sometimes called post-herpetic pruritis, represents a smaller subcategory of PHN. It was first described in 1974 and has since been reported sporadically.^4,7-14 In one retrospective study, PHI was found to occur in only six of 178 (3.4%) patients with herpes zoster in a three-year period.¹⁰ Another study found eight of 113 (7.1%) patients with recent herpes zoster to have experienced PHI.¹¹ The phenomenon appears more commonly in those who suffer from shingles of the head, face and neck as compared with those who manifest the disease on their torso or elsewhere.¹⁵

	Active herpes zoster ophthalmicus (as seen in another patient). Prompt intervention is required to prevent post-herpetic neuralgia.

Prevention and Treatments
Since the management of PHN and PHI is often challenging, maximal effort should be exercised to prevent it from occurring in the first place. The current recommendation requires initiation of systemic antiviral medications within 72 hours of herpetic rash onset. Although early antiviral therapy does not ensure PHN prevention, numerous studies have demonstrated reduced rates or duration, or both, of subsequent neuralgia, and expert consensus still greatly favors this clinical practice.^16-20 

Currently accepted drug regimens for immunocompetent adults include: 

• Oral acyclovir, 800mg five times daily for seven to 10 days; 
• Oral famciclovir, 500mg three times daily for seven days; 
• Oral valacyclovir, 1000mg three times daily for seven days.¹⁹ 

Unfortunately, systemic antiviral therapy has not been shown to be of value in ameliorating the discomfort of PHN after the critical 72-hour period.^21,22 Similarly, vaccination with live, attenuated varicella-zoster virus (Zostavax, Merck) in patients 60 years and older has been shown to diminish the subsequent incidence of PHN by more than 50%.²³ However, Zostavax is not effective in PHN treatment.

Numerous other pharmaceuticals have been investigated for the relief of PHN, all with varying degrees of success. Oral NSAIDs are generally ineffective for neuropathic pain.² Topical Lidoderm (5% lidocaine, Endo Pharmaceuticals) and 0.075% capsaicin cream both represent treatment options for those with mild discomfort from PHN.² 

Unfortunately, neither of these is ideal for ocular or adnexal tissues. For those with more pronounced or persistent neuropathic pain, the use of oral tricyclic antidepressants—such as amitriptyline or nortriptyline—as well as the anticonvulsant medications Neurontin (gabapentin, Pfizer) and Lyrica (pregabalin Pfizer), have demonstrated fairly good efficacy in controlled clinical trials.^2,24-26 A once-daily formulation, Gralise, (gabapentin 1800mg, Depomed), is now specifically approved for PHN. 

Antidepressants and anticonvulsants may also be combined to yield a greater analgesic effect (e.g., amitriptyline and pregabalin).²⁷ The use of opioids such as hydrocodone or oxycodone is generally discouraged due to the potential for abuse and limited evidence of benefit; these drugs have been relegated to third tier in the treatment of PHN and should only be used under the supervision of a pain management specialist.^2,28 

Persistent Discomfort
Post-herpetic itch is a more complex disorder than typical post-herpetic neuralgia, and prone to greater complications. One of the primary concerns is the risk of self-injury. Because the affected neurons have diminished ability to sense pain, the stimulus to cease scratching of the area may be lost. Bizarre and gruesome cases have been reported, including one woman whose persistent scratching resulted in a wound that completely penetrated her scalp and part of her skull.⁹ PHI is often more resistant to the above mentioned treatments than PHN as well.⁴ Antihistamines, used widely for conditions with symptomatic itching, appear to be comparatively ineffective for PHI.^4,12 Likewise, topical steroids provide seemingly little relief.¹² Topical anesthetic patches and capsaicin may be helpful, but suffer the same limitations as in PHN. 

Clinical improvement has been documented with the use of both amitriptyline and gabapentin in several case reports, although there have yet to be any prospective clinical trials involving their use specifically for post-herpetic itch.^13,14 A published report showed resolution of PHI in a 22-year-old patient using hydroxyzine (an antihistamine that is also indicated for the treatment of anxiety) in combination with carbamazepine (an anti-convulsant, though in a different class than gabapentin and pregabalin).⁴ 

Other systemic agents—including oxycarbazepine, diphenylhydantoin, mexiletine and mirtazapine—have also been proposed as alternatives for PHI.^4,12 Failing oral therapy, doctors may turn to serial ganglionic block injections with bupivacaine and even surgical amputation of the involved nerve.^4,34

PHN is arguably the worst potential complication of herpes zoster, resulting in persistent discomfort that is difficult to mitigate. Despite numerous treatment modalities and ongoing research, no single therapy has emerged as universally effective. The optometrist’s role involves early detection and treatment of herpes zoster, education regarding the nature and prevention of PHN, and appropriate intervention for the unfortunate few who develop persistent neuralgias. 

Knowledge of the various therapeutic options can help to minimize suffering and subsequent complications for the victims of PHN and PHI.

Drs. Kabat and Sowka have no financial interest in any products mentioned in this article.

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