Periorbital Herpes Zoster

Etiology

• Latent varicella-zoster virus from cranial nerve or dorsal root ganglion becomes reactivated.
  • Path of infection is retrograde from sensory ganglion along sensory nerve to the dermatome.
• Primary infection clinically manifests as chicken pox
  • Primary infection occurs in childhood
  • Diffuse rash.
  • Seeding of sensory ganglia.
  • Lifelong latency established.
• When primary infection occurs in utero or early infancy then reactivation can occur in childhood.

Epidemiology

• More than one million cases of Herpes Zoster (HZ) annually in the US.
  • Rate is 3-4 cases per 1000 persons.
• In a retrospective study of 90 patients mean age at onset was 68±13.8 years (range 27-95 years) (Tran, 2016).
  • Miami Veterans Administration study.
  • 80% were immunocompetent.
  • 25% had recurrence within five years.
•  Study of 217,061 people in Hawaii, 134 cases of HZ ophthalmicus identified over ten years (Borkar, 2013).
  • Dermatitis was most common, followed by keratitis and conjunctivitis
• Without varicella-zoster vaccine, by age 85, 50% risk of developing clinical HZ reactivation.
• Age at presentation may be declining
  • In a survey of 913 HZ ophthalmicus cases at Massachusetts Eye and Ear Infirmary mean age was 61.2 years in 2007 and 55.8 years in 2013 (Davies, 2016).
• Incidence highest in immunocompromised hosts
  • Organ transplant recipients.
  • Hematopoietic stem cell transplant recipients.
  • Leukemia/lymphoma.
  • Human immunodeficiency virus infection.
• Post-herpetic neuralgia occurs in 10-50% of cases
  • Risk is higher with onset after age 50 years
  • Correlates with severity of rash
    • More severe pain at onset of rash.
    • Larger number of lesions.
    • Broader distribution of lesions.

History

• Rash in V1 dermatome (periocular)
• Paraesthesia may precede eruption
  • May be continuous or episodic
  • Tingling
  • Itching
  • Typically 2-3 days before the eruption
• Pain described as aching, onset with eruption
  • Dysesthesia = painful sensitivity to touch
  • Allodynia = pain associated with nonpainful stimulus
  • Hyperesthesia = exaggerated response to pain

Clinical features

• Pustules and vesicles in V1 dermatome
  • Does not cross the midline
  • Few scattered lesions can extend beyond the dermatome
  • Begins as macules and papules
  • Evolve into vesicles and pustules
  • New lesions evolve over 3-5 days
  • Fills dermatome
  • Evolution of rash typically continues despite antiviral treatment
  • Rash resolves in 7-10 days
• Zoster sine herpete = dermatomal pain without rash
• Involvement of the tip of the nose = Hutchinson’s sign
• In immunocompromised host lesions may develop and evolve for up to two weeks.
• Blurred vision
• Epithelial keratopathy – pseudodendrites
• Stromal haze
• Corneal hypesthesia
• Palpebral subconjuctival hemorrhages (Najjar, 2008)
• Myositis that responds to antiviral therapy and corticosteroids (Badilla, 2007)
  • Myositis may precede the vesicular eruption (Kawasaki, 2003)

Establishing the diagnosis

• Mostly based on clinical appearance
• Unusual cases require direct immunofluorescence assay for antigen or polymerase chain reaction for DNA.
  • Sample cells from the base of the lesion  

• Increasing age.
• T-cell immunity to HZ virus diminishes with age
• Antibody levels may seem adequate – correlation is significantly with T-cell immunity levels.
• Women more than men.
• Whites have higher incidence.
• Family history of HZ eruption.

• Herpes simplex eruption
• Erysipelas

Natural history

• In a study of 71 patients observed in England without treatment mean duration of rash was 22 days (range 6-35 days) (Harding, 1987).
• HZ is less contagious than varicella but can transmit to susceptible host
  • Risk is varicella developing
  • Lesions should be covered
  • Avoid contact with persons who have not had varicella or are not immunized

Medical therapy

• Live attenuated virus is available for persons 60 years of age and older (Kimberlin, 2007).
• Immunocompetent patient criteria for treatment includes involvement of eye and face, therefore all periocular warrants treatment
  • Criteria also include age 50 years or older, moderate or severe pain, severe rash
• Antiviral therapy is recommended for immunocompromised patient
• Start medical treatment as early as possible, ideally within 72 hours of onset of rash
• Medical treatment does not reduce incidence of post-herpetic neuralgia
• Medical antiviral treatment hastens resolution of lesions
  • Reduces formation of new lesions
  • Reduces viral shedding
  • Decreases severity of acute pain
• If medical therapy is started within 48 hours of onset formation of new lesions reduced by 0.5-1 day, reduction of shedding and pain by 2 days.
• Acyclovir (Zovirax)
  • 800 mg five times daily for 7-10 days
  • For immunocompromised host, 10 mg/kg intravenously every 8 hours for 7-10 days
• Valacyclovir (Valtrex)
  • Better bioavailability than acyclovir
  • 1 gram three times daily for 7 days
• Famciclovir (Famvir)
  • Better bioavailability than acyclovir
  • 500 mg three times daily for 7 days
• Foscarnet (Foscavir)
  • For immunocompromised host with acyclovir resistance
  • 40 mg/kg intravenously 8 hours until lesions have healed
• Corticosteroids – in addition to antiviral therapy
  • Does not improve incidence of post-herpetic neuralgia
  • May reduce pain and promote healing

Radiation therapy options

• None

Surgery options

• For secondary lid malformation, notably cicatricial ectropion

• Oral acyclovir can produce malaise.
• Intravenous acyclovir can produce renal insufficiency.
• Famciclovir and valacyclovir can produce headache and nausea.

• Ophthalmic complications
• Keratopathy.
• Uveitis.
• Acute retinal necrosis.
• Post-herpetic neuralgia – defined as pain persisting for 90 days or more after onset of the rash.
• Pain may persist for months or years.
• May interfere with sleep.
• May trigger depression, social withdrawal, limitation of daily activities.
• Bell’s palsy – acute onset facial paralysis.
• Ramsey-Hunt syndrome – acute peripheral facial neuropathy associated with erythematous vesicular rash of skin on ear canal, and/or external ear, and/or mucous membrane of oropharynx.
• Origin is geniculate ganglion of facial nerve.
• Transverse myelitis.
• Severe infection in immunocompromised host
• Disseminated skin eruption
• Acyclovir resistant infection
• Chonic skin infection
• Pneumonitis
• Hepatitis
• Cerebritis
• Pancreatitis

• Stern suggested in 1937 that the virus travels from the ganglion along the sensory nerve to the skin (Stern, 1937).
• Pituitary solutions were used in the early 1900’s to treat HZ eruption (Walker, 1938). 

• Badilla J, Dolman PJ: Orbital myositis involving the oblique muscles associated with herpes zoster ophthalmicus. Ophthal Pl Reconstr Surg 2007; 23:411-3.
• Borkar DS, Tham VM, Esterberg E, et al: Incidence of herpes zoster ophthalmicus: Results from the Pacific Ocular Inflammation Study. Ophthalmology 2013; 120:451-6.
• Cohen JI: Herpes Zoster. N Engl J Med 2013; 369:255-63.
• Davies EC, Pavan-Langston D, Chodosh J: Herpes zoster ophthalmicus: declining age at presentation. Br J Ophthalmol 2016; 100:312-4.
• Gelb LD: Preventing herpes zoster through vaccination. Ophthalmology 2008; 115:S35-8.
• Harding SP, Lipton JR, Wells JCD: Natural history of herpes zoster ophthalmicus: predictors of postherpetic neuralgia and ocular involvement. Br J Ophthalmol 1987; 71:353-8.
• Kawasaki A, Borruat F: An unusual presentation of herpes zoster ophthalmicus: Orbital myositis preceding vesicular eruption. Am J Ophthalmol 2003; 136:574-5.
• Kimberlin DW, Whitley RJ: Varicella-zoster vaccine for the prevention of herpes zoster. N Engl J Med 2007; 356:1338-43.
• Najjar DM, Youssef OH, Flanagan JC: Palpebral subconjunctival hemorrhages in herpes zoster ophthalmicus. Ophthal Pl Reconstr Surg 2008; 24:162-4.
• Pavan-Langston D: Herpes Zoster: Antivirals and pain medication. Ophthalmology 2008; 115:S13-20.
• Stern ES: The mechanism of herpes zoster and its relation to chicken pox. Br J Dermatol 1937; 49:263.
• Tran KD, Falcone MM, Choi DS, et al: Epidemiology of herpes zoster ophthalmicus: Recurrence and chronicity. Ophthalmology 2016; 123:1469.
• Walker JR, Walker BF: A specific treatment for herpes zoster. Arch Ophthalmol 1938; 20:304-6.