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Herpes Zoster Ophthalmicus

Ocular Herpes Zoster

Herpes zoster ophthalmicus is an infection resulting from the reactivation of the latent varicella-zoster virus in the ophthalmic branch of the trigeminal nerve. It manifests in a periorbital dermatomal rash and may lead to significant complications such as loss of vision


Presentation

The clinical picture of HZO is best described according to the phases of the disease.

Prodrome

Approximately 60% of patients experience the prodromal phase, in which they feel tingling and pain in the forehead. Additionally, this stage consists of flu-like symptoms such as fever, malaise, and myalgia, typically lasting for a week. 

Acute

The acute stage features a painful unilateral rash in a dermatomal pattern on the forehead representing the affected subdivision(s) of the ophthalmic nerve (supraorbital, lacrimal, and nasociliary). The rash is initially erythematous and macular in appearance. Over the next few days, the rash rapidly transforms into papules, vesicles, and pustules. Then they rupture, crust, scab and ultimately heal over several weeks [6]. Additionally, marked ocular pain and edema of the eyelid are commonly observed. These two can result in blepharitis, which subsequently causes ptosis. Further, most patients will have an accompanying rash on the eyelid, in which the vesicles heal and leave behind little scarring.

Further conditions may include photophobia, conjunctival hyperemia (circumcorneal or episcleral), corneal edema, keratitis, and uveitis. Moreover, conjunctivitis is frequently found in patients with HZO. Cornea diseases can impair vision and are observed in 65% of patients with HZO [5]. Anterior uveitis can occur individually or coexist with keratitis. These latter two conditions lead to scarring. In patients with HZO, Hutchinson’s sign is strongly associated with ocular presentation. However, even patients who do not exhibit this clinical sign can have ocular features [7].

Late sequelae

The later phase of HZO includes scarring and excessive blood vessel growth in the cornea. Additionally, eye diseases such as glaucoma, cataract, and chronic uveitis can occur. All of these may result in loss of vision. Another late complication, postherpetic neuralgia, may also develop especially if HZO is not treated early. In immunocompromised patients, the vesicular rash is followed by profound illness within one or two weeks. 

Soft Tissue Swelling
  • On orbit/brain imaging, abnormal enlargement of the extraocular muscles was present in 33%, and orbital soft tissue swelling was present in 17%. Enhancement of ocular motor cranial nerves was not reported.[ncbi.nlm.nih.gov]
Central Scotoma
  • It was characterized by decreased visual acuity, mid dilated pupil with sluggish reaction, normal optic disc and central scotoma in Humphrey visual field. Visual acuity improved with systemic Acyclovir and steroids.[ncbi.nlm.nih.gov]
Severe Unilateral Headaches
  • It thus highlights the need to consider this diagnosis among the differentials for severe unilateral headache in the elderly.[ncbi.nlm.nih.gov]
Neuralgia
  • The correlation of eruption severity and distribution with ocular complications, visual outcome and postherpetic neuralgia was statistically evaluated.[ncbi.nlm.nih.gov]
  • Corneal complication was seen in 38.2 % of cases, uveitis in 19.1 % and post-herpetic neuralgia (PHN) and secondary glaucoma each in 5.8 %.[ncbi.nlm.nih.gov]
  • Post-herpetic neuralgia, neurotrophic keratopathy, and secondary infectious keratitis were more frequent in the older patients (P 0.05).[ncbi.nlm.nih.gov]
  • Following acyclovir and prednisone treatment, all symptoms resolved, and neuralgia did not develop.[ncbi.nlm.nih.gov]
Hyperesthesia
  • HENT exam showed no obvious rashes or lesions; however, the patient had mild hyperesthesia over his right forehead. He had normal ear canals, tympanic membranes, nares, and oropharynx. The patient had no cervical or auricular lymphadenopathy.[ncbi.nlm.nih.gov]
  • It is the most frequent complication, observed in 9-45% of all cases. [4] Most people report a deep burning or aching pain, paresthesia, dysesthesia, hyperesthesia, or electric shock–like pains.[emedicine.com]
Hemichorea
  • After 4 weeks, he complained of hemichorea on his left side. Brain MRI showed a focal hemorrhage in the right subthalamic area. No evidence of aneurysmal lesion or cerebral angiitis was observed on cerebral angiography. Copyright 2012 Elsevier Ltd.[ncbi.nlm.nih.gov]

Workup

The diagnosis of HZO is determined through a detailed history and complete eye exam. The characteristic finding includes a unilateral dermatomal rash on the forehead and/or eyelid. If the patient presents after the rash has healed but has the suggestive history and signs such as hypopigmented scars, suspicion should be high for HZO.

A thorough evaluation warrants an ophthalmology consultation. The ophthalmologic exam consists of numerous components such as external inspection of the eye, testing of extraocular movement and pupillary reflex, and assessing visual fields and acuity. Very importantly, a slit lamp exam, fundoscopy, and corneal exam with and without staining are all performed. Measurement of intraocular pressure is also obtained. These key components will determine associated eye pathology and complications.

Since diagnosis is usually achieved through a history and eye exam, diagnostic testing is rarely performed unless the presentation is atypical. Serologic testing, viral culture, PCR, and immunofluorescence assay are options. Tzanck smear or Wright stain can be utilized but they identify presence of herpes virus in general.

Hyponatremia
  • Further investigation revealed hyponatremia 112 mEq/L, low serum osmolality, high urine osmolality, normal renal function, normal adrenal and thyroid hormones, and high plasma vasopressin 40 pg/mL.[ncbi.nlm.nih.gov]
  • We describe two diabetic men with herpes zoster ophthalmicus (HZO) who developed hyponatremia (114 and 116 mmol/L) during acute illness.[ncbi.nlm.nih.gov]
Central Scotoma
  • It was characterized by decreased visual acuity, mid dilated pupil with sluggish reaction, normal optic disc and central scotoma in Humphrey visual field. Visual acuity improved with systemic Acyclovir and steroids.[ncbi.nlm.nih.gov]
Viral Inclusion Body
  • A single autopsy report described granulomatous angiitis of the meninges and large vessels in the anterior cerebral circulation, as well as periaxial infarction in the optic nerve, pons, and medulla but without viral inclusion bodies or antigen.[ncbi.nlm.nih.gov]

Treatment

HZO is commonly seen in the emergency department. The components of urgent management include wound care, pain control, antiviral therapy, and management of complications. Certain cases may warrant antibiotic therapy as well. Outpatient treatment is optimal for stable patients without significant eye involvement. Ill patients require inpatient intravenous antivirals and other indicated therapies depending on the presentation.

In early disease, there are three antiviral options 1) acyclovir 800mg orally five times daily for seven days 2) famciclovir 500mg orally three times a day for seven days, or 3) valacyclovir 1g orally three times a day for seven days. If taken early, these antivirals are associated with a profound reduction in adverse outcomes. Additionally, acyclovir has been observed to reduce the occurrence of postherpetic neuralgia if taken within the first three days of initial symptoms [8] [9] [10]. Valacyclovir has demonstrated effectiveness in prevention of conjunctivitis, keratitis and pain [11]. While all options are equally effective, famciclovir and valacyclovir offer less frequent dosing which is more convenient for patient compliance.

Corticosteroids are used in ocular complications. Topical prednisolone is necessary for treatment of uveitis or keratitis. Additionally, corticosteroids may provide pain relief and shorten the length interval of skin healing. However, the use of oral corticosteroids for prevention of postherpetic neuralgia in the elderly is debatable. Pain control is achieved with opioid medications and/or nonsteroidal anti-inflammatory drugs (NSAIDs).

Prognosis

The prognosis of HZO depends on the severity of the disease. Complications may cause visual impairment or blindness, whether short-term or permanent. Corneal damage can result in a significant visual loss. Other long-term manifestations include ocular inflammation and devastating pain. Also, relapses are known to occur even a decade after initial onset.

It is thought that all patients with a nasociliary nerve (sub-branch of the ophthalmic nerve) infection will exhibit pathology in the eye [4]. Since the nasociliary nerve innervates the globe of the eye, the effects of its involvement are more severe. Furthermore, if the tip of the nose is affected, this is indicative of eye manifestations. This is called Hutchinson’s sign. Immunocompromised patients frequently become very ill and exhibit marked visual problems [5].

Etiology

Herpes zoster ophthalmicus is caused by the varicella zoster virus, also known as herpes virus 3, which is responsible for chickenpox. This virus is a member of the herpes viridae family which also includes herpes simplex virus, Epstein-Barr virus and cytomegalovirus.

Herpes zoster is frequently diagnosed in the emergency room setting. It results from the reactivation of latent virus in the ophthalmic branch of the trigeminal nerve. Specifically this reactivated virus causes inflammation of the sensory nerves that innervate the eye [1].

Epidemiology

HZO accounts for 10% to 25% of herpes zoster infections [2]. Almost 50% of HZO patients develop complications and the risk of serious sequelae is not related to gender, age or severity of the rash. Note that the risk of developing HZO is greater in immunocompromised patients such as individuals with HIV [3].

Sex distribution
Age distribution

Pathophysiology

To understand the pathogenesis of HZO, it is important to describe the infection that precedes it. The primary varicella zoster virus (VZV) infection causes chickenpox. After this infection resolves, the virus resides in the dorsal root ganglia and remains dormant for many years. Reactivation of this latent virus in the ophthalmic branch of the trigeminal nerve causes the secondary infection, HZO. Other branches of the fifth cranial nerve may be involved. 

Prevention

The live varicella zoster virus vaccine (Varivax), available since 1995, is as high as 99% effective in the prevention of infection. A higher potency vaccine (Zostavax) was introduced in 2005. A three-year follow-up study of Zostavax observed a 51% reduction in the incidence of herpes zoster [12]. Herpes zoster and associated complications are common in the elderly, which is attributed to diminished cell-mediated immunity. Therefore, prevention of herpes zoster in this population is crucial. Furthermore, older individuals do well with Zostavax [13].

Zoster vaccination in older individuals is cost effective and beneficial in the prevention of herpes zoster and limitation of its severity [14] [15]. Additionally, post exposure prophylaxis with VZIG is warranted in special populations. Nontherapeutic preventative measures should always be practiced. For example, affected patients should be under respiratory and contact isolation precautions until the lesions fully crust.

Summary

Herpes zoster ophthalmicus (HZO) occurs when the latent varicella zoster virus is reactivated in the ophthalmic nerve (V1), which is a branch of the trigeminal nerve (cranial nerve 5). The dosorder is a common emergency room diagnosis, and can account for up to 25% of all herpes zoster infections.

The disease, which occurs in three phases, is most notable for the acute dermatomal rash on the forehead. This rash is associated with painful inflammation of ocular tissues and progresses in a characteristic pattern. Following the acute phase, late sequelae can result in significant eye disease.

Diagnosis is established through a detailed history and physical exam. The presence of a rash in a dermatomal distribution on forehead or eyes or a reported history of this hallmark rash will confirm HZO. A very thorough and prompt ophthalmologic exam consisting of external and internal testing is paramount. Furthermore, evaluation of the eye structures is crucial in determining the presence of any damage. 

Treatment includes antiviral therapy, pain control, and management of any present complications. If treatment with acyclovir, valacyclovir, or famciclovir is initiated within 72 hours of initial symptoms, there is a significant reduction in eye involvement. Varicella zoster vaccines are available. They are very effective and recommended for all adults 60 years old or above. 

Patient Information

Herpes zoster ophthalmicus (HZO) occurs when a previous varicella zoster infection becomes active again. To understand better, it is important to explain the background. When a person has chickenpox, the virus responsible for it can remain in the body and go to sleep. Many years or even decades later, this virus can wake up and start a new infection. In HZO, the new infection occurs in of one the nerves that control the eye. Therefore, the region of the eye develops a painful red rash that follows a certain a pattern. A few days later, the rash blisters and crusts over. Eventually, the blisters become scans and heal over time.

Most people will have swelling and crusting of eyelids. Also, individuals with this disease can develop eye infections such as conjunctivitis as well as damage to important structures in the eye such as the cornea. This can result in visual impairment. Since there serious complications can occur, it is crucial to seek urgent care if one experiences these symptoms. In fact, treatment within 72 hours of the first symptoms can produce better results.

How is the diagnosis made?

The doctor will ask relevant questions and then perform an exam. Usually, an ophthalmologist (special eye doctor) will inspect the eye and perform key tests to check for damage to the function and structures of the eye. S/he uses instruments that shine light into the eye, and also a microscope device for close evaluation. The ophthalmologist will then determine if there are any complications.

How is it treated?

If the disease is mild and there are no eye complications, the doctor will prescribe antiviral and pain medications with close follow-up. Acyclovir, valacyclovir, and famciclovir are the options for antivirals. If taken within the first 72 hours, they can prevent eye involvement. If the patient is ill or has significant eye damage, then hospital admission and aggressive therapy are needed.

Can this be prevented?

There are vaccines available that can prevent herpes zoster infections. They are recommended for people who are 60 years old or more. 

References

Article

  1. Naumann G, Gass JD, Font RL. Histopathology of herpes zoster ophthalmicus. American Journal pf Ophthalmology. 1968;65(4):533–41.
  2. Ragozzino MW, Melton LJ 3rd, Kurland LT, Chu CP, Perry HO. Population-based study of herpes zoster and its sequelae. Medicine (Baltimore). 1982;61(5):310-6.
  3. Sandor EV, Millman A, Croxson TS, Mildvan D. Herpes zoster ophthalmicus in patients at risk for the acquired immune deficiency syndrome (AIDS). American Journal of Ophthalmology. 1986;101(2):153–5.
  4. Zaal MJ, Völker-Dieben HJ, D'Amaro J. Prognostic value of Hutchinson's sign in
    acute herpes zoster ophthalmicus. Graefes Archive for Clinical and Experimental Ophthalmology. 2003;241(3):187-91. Epub 2003 Feb 11.
  5. Baratz KH, Goins K, Cobo M. Varicella-zoster viral infections. In: Kaufman HE, ed. The cornea. New York: Churchill Livingstone, 1988.
  6. Burgoon CF, Burgoon JS, Baldridge GD. The natural history of herpes zoster. Journal of American Medical Association. 1957; 174(3):265.
  7. Harding SP, Lipton JR, Wells JC. Natural history of herpes zoster ophthalmicus: predictors of postherpetic neuralgia and ocular involvement. British Journal of Ophthalmologgy. 1987; 71(5):353–8.
  8. Peterslund NA. Management of varicella zoster infections in immunocompetent hosts. American Journal of Medicine. 1988; 85(2A): 74–8.
  9. Morton P, Thomson AN. Oral acyclovir in the treatment of herpes zoster in general practice. New Zealand Medical Journal. 1989; 102(863): 93–5.
  10. Huff JC, Bean B, Balfour HH Jr, Laskin OL, Connor JD, Corey L, et al. Therapy of herpes zoster with oral acyclovir. American Journal of Medicine. 1988; 85(2A):84–9.
  11. Colin J, Prisant O, Cochener B, Lescale O, Rolland B, Hoang-Xuan T. Comparison of the efficacy and safety of valaciclovir and acyclovir for the treatment of herpes zoster ophthalmicus. Ophthalmology. 2000; 107(8): 1507–11.
  12. Ongkosuwito JV, Feron EJ, van Doornik CE, Van der Lelij A, Hoyng CB, La Heij EC, et al. Analysis of immunoregulatory cytokines in ocular fluid samples from patients with uveitis. Investigative Ophthalmology & Visual Science. 1998; 39(13):2659-65.
  13. Sanford M, Keating GM. Zoster vaccine (Zostavax): a review of its use in preventing herpes zoster and postherpetic neuralgia in older adults. Drugs Aging. 2010; 27(2):159-76.
  14. Caple J. Varicella-zoster virus vaccine: a review of its use in the prevention of herpes zoster in older adults. Drugs Today (Barc). 2006; 42(4):249-54.
  15. van Hoek AJ, Gay N, Melegaro A, Opstelten W, Edmunds WJ. Estimating the cost-effectiveness of vaccination against herpes zoster in England and Wales. Vaccine. 2009; 27(9):1454-67.

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Last updated: 2018-06-21 21:13