Herpes Zoster Oticus

Varicella-zoster virus infection initially starts as varicella, commonly known as chickenpox. After infectivity with chickenpox, VZV lies dormant within the nerve roots of cranial nerves and sensory ganglia. Reactivation of latent VZV can result in localized vesicular rash, known as herpes zoster or shingles. Reactivation of VZV along the distribution of the sensory nerves innervating the ear, which usually includes the geniculate ganglion, is responsible for HZ oticus. ^{[3, 4]} Associated symptoms, such as hearing loss and vertigo, are thought to occur as a result of transmission of the virus via direct proximity of cranial nerve (CN) VIII to CN VII at the cerebellopontine angle or via vasa vasorum that travel from CN VII to other nearby cranial nerves. Another theory regarding the pathophysiology of cranial nerve polyneuropathy is that VZV may spread to other CNs via brainstem reflex pathways through intersynaptic transmission in an anterograde direction resulting in polycranial neuritis. ^[8]  

Patient history

Typically, patients present with severe otalgia. ^{[3, 4]} Complaints include the following:

• Painful, burning blisters in and around the ear, on the face, in the mouth, and/or on the tongue 

  Herpes zoster oticus. Image courtesy of Manolette Roque, MD, Ophthalmic Consultants Philippines Co, EYE REPUBLIC Ophthalmology Clinic.

• Vertigo, nausea, vomiting

• Hearing loss, hyperacusis, tinnitus

• Eye pain, lacrimation

Onset of pain may precede the rash by several hours or days. Also, in patients with Ramsay Hunt syndrome, vesicles may appear before, during, or after facial palsy (zoster sine herpete). ^{[3, 4]} When asked, patients may recall a distant history, perhaps in childhood, of chickenpox (varicella). A minority of patients (< 10%) give a history of previous herpes zoster viral infection.

Physical examination

Physical examination shows a vesicular exanthem, usually of the external auditory canal, concha, and pinna. The rash also may appear on postauricular skin, lateral nasal wall, soft palate, and anterolateral tongue.

Vertigo and sensorineural hearing loss may be noted, and paralysis of the facial nerve, mimicking Bell palsy, may be present. Complete loss of the ability to wrinkle the ipsilateral brow distinguishes a peripheral lesion of cranial nerve VII from a central lesion of the same nerve, which spares the forehead.

Associated findings include the following:

• Dysgeusia (alteration in taste)

• Inability to fully close the ipsilateral eye, which may lead to the occasional presentation of drying and irritation of the cornea.

House-Brackmann facial nerve grading system

The following House-Brackmann facial nerve grading scale provides a standardized way to quantify facial nerve function and objectively track recovery ^{[9, 10]} :

Grade I - Normal

Normal facial function in all areas

Grade II - Slight Dysfunction

Gross: slight weakness noticeable on close inspection; may have very slight synkinesis

At rest: normal symmetry and tone

Motion: forehead - moderate to good function; eye - complete closure with minimum effort; mouth - slight asymmetry.

Grade III - Moderate Dysfunction

Gross: obvious but not disfiguring difference between two sides; noticeable but not severe synkinesis, contracture, and/or hemi-facial spasm.

At rest: normal symmetry and tone

Motion: forehead - slight to moderate movement; eye - complete closure with effort; mouth - slightly weak with maximum effort.

Grade IV - Moderate Severe Dysfunction

Gross: obvious weakness and/or disfiguring asymmetry

At rest: normal symmetry and tone

Motion: forehead - none; eye - incomplete closure; mouth - asymmetric with maximum effort.

Grade V - Severe Dysfunction

Gross: only barely perceptible motion

At rest: asymmetry

Motion: forehead - none; eye - incomplete closure; mouth - slight movement

Grade VI - Total Paralysis

No movement

Complications

Complications of HZ oticus may include the following ^{[11, 12, 13]} :

• Postherpetic neuralgia

• Residual paralysis

• Rarely, herpes zoster encephalitis ^[12]

Herpes zoster oticus is caused by the reactivation of latent VZV that has remained dormant within sensory ganglia (commonly the geniculate ganglion) of the facial nerve. ^{[3, 4]} Individuals with decreased T cell-mediated immunity resulting from carcinoma, radiation therapy, chemotherapy, or HIV infection; transplant recipients; or those on immunomodulatory therapy are at greater risk for reactivation of latent VZV and more prone to complication. Physical stress and emotional stress often are cited as precipitating factors.

The diagnosis of Ramsay Hunt syndrome is complex due to the asynchronous presentation of its characteristic symptoms, which include earache, facial paralysis, and a distinctive rash. ^[1] Diagnostic confirmation is achieved through a meticulous clinical evaluation, an extensive patient history, and the identification of specific symptoms such as unilateral facial palsy and/or a vesicular rash around the ear. Laboratory confirmation can be obtained by analyzing samples from the vesicular lesions, which differentiates Ramsay Hunt syndrome from differential diagnoses such as Bell’s palsy, acoustic neuroma, or trigeminal neuralgia.

While viral assays can detect the varicella-zoster virus in biological fluids like saliva, tears, and blood, these tests are not requisite for establishing a diagnosis of Ramsay Hunt syndrome.

Before initiating treatment with acyclovir, consider a baseline set of the following laboratory studies:

• Blood urea nitrogen (BUN)

• Creatinine

• Blood cell counts

• Electrolytes

Consider screening for anti-VZV antibodies (IgM and IgA) in at-risk immunocompromised patients. ^[14]

PCR testing is the most sensitive laboratory test to diagnose herpes zoster (>95%), and is more rapid to obtain when compared with culture techniques. 

If diagnosis of Ramsay Hunt syndrome is not established by physical examination alone, consider a head CT scan to investigate other etiologies of facial paralysis.

Magnetic resonance imaging (MRI)

Herpes zoster oticus may involve vestibular nucleitis, as opposed to being solely a neuritis, contrasting with traditional views that liken it to a cranial nerve equivalent of shingles. In a retrospective comparison of brain MRIs between patients diagnosed with HZ oticus and those with vestibular neuritis (VN), notable differences were observed in the radiologic changes within the brainstem. ^[4] Specifically, signal abnormalities were detected in the vestibular nuclei of five out of ten HZ oticus patients, areas which span multiple vascular territories. In contrast, such abnormalities were absent in patients suffering from VN. This suggests that the pathology of HZ oticus might extend beyond the vestibular nerve to include the brainstem, potentially altering the approach to its diagnosis and treatment.

Audio-vestibular deficits are well-correlated with increased signal intensity of the inner ear endorgans in 4 h post-contrast 3D-FLAIR MRI. This advancement in imaging technology, specifically the 3D-fluid-attenuated inversion recovery sequence (3D-FLAIR), has significantly enhanced the ability to assess inner ear structures and pathology. ^[3]   Lee et al conducted a study focused on 18 patients with HZ oticus; a significant 77% exhibited high-signal intensity in the inner ear structures on 4-hour post-contrast 3D-FLAIR images. The findings were particularly pronounced in the lateral semicircular canal and cochlea, correlating strongly with clinical symptoms of canal paresis and hearing loss, respectively. However, the vestibulo-cochlear nerve showed less frequent enhancement in post-contrast T1-weighted images, suggesting a more complex interaction between clinical symptoms and MRI findings. These results underscore the importance of 3D-FLAIR MRI in diagnosing and understanding the extent of inner ear involvement in HZ oticus, potentially guiding more targeted therapies.

The management of Ramsay Hunt syndrome typically involves a combination of antiviral agents such as acyclovir or famciclovir and corticosteroids like prednisone to enhance treatment efficacy against varicella zoster virus. ^[1] Whereas steroids may alleviate pain by reducing nerve inflammation, the definitive effectiveness of antiviral medications remains unconfirmed. Despite treatment, some patients may experience persistent facial paralysis and hearing loss.

Additional therapeutic measures target specific symptoms unique to each patient. These include pain relievers, carbamazepine for neuralgic pain and vertigo, and vertigo suppressants such as antihistamines and anticholinergics. Diazepam (Valium) may be used to manage pain and vertigo. For neuropathic pain and difficulties in eyelid closure, Botulinum toxin type A (Botox) has shown benefits. In cases where facial weakness persists, physical therapy can be crucial in rehabilitating facial muscles.

Capsaicin, approved by the US Food and Drug Administration (FDA), is utilized for managing neuropathic pain associated with postherpetic neuralgia. Initiating treatment within 3 days of symptom onset is critical for optimal outcomes.

Patients with Ramsay Hunt syndrome are at increased risk for corneal injury due to difficulties in closing one eye, necessitating measures to prevent excessive drying and foreign body exposure. Protective strategies include the use of artificial tears, lubricating ointments, and potentially an eye patch.

Preventative measures against the varicella-zoster virus include the chickenpox vaccine for children and the shingles vaccine for individuals aged 50 and older. These vaccines significantly lower the risk of infection with the varicella zoster virus and subsequently reduce the likelihood of developing Ramsay Hunt syndrome.

Antiviral agents

Antiviral agents clearly play a role in limiting the severity and duration of symptoms if given early in the course of the illness. ^[15] Early administration (< 72 h) of acyclovir showed an increased rate of facial nerve function recovery and prevented further nerve degeneration. Furthermore, use of antivirals has been shown to decrease the incidence and severity of postherpetic neuralgia. ^{[11, 16, 17, 18]}

Varicella-zoster virus (VZV) may be misdiagnosed as Bell palsy because of a lack of cutaneous findings (zoster sine herpete). Accordingly, the clinician should entertain more liberal use of antivirals such as acyclovir, valacyclovir, and famciclovir. ^{[6, 7]} Studies have shown no difference between oral and IV acyclovir in immunocompetent patients with facial nerve paralysis. ^[19]

Valacyclovir and famciclovir have been shown to be more effective than acyclovir in reducing risk for pain, with comparable lesion healing and safety profile. Patient compliance is likely to be higher with valacyclovir and famciclovir because each has an easier dosing regimen (3 times per day) compared with acyclovir (5 times per day). ^{[20, 21]} When controlled for compliance and House-Brackmann score, the overall complete recovery rate was significantly higher in patients treated with famciclovir than those treated with acyclovir. This may be due to several reasons, including the excellent oral bioavailability of famciclovir, as well as the fact that it is not affected by food. Acyclovir, conversely, has low oral bioavailability, which is further reduced when it is taken with food. Lastly, the active metabolite of famciclovir has a much longer intracellular half-life in VZV-infected cells than acyclovir and is highly selective against herpes virus–infected cells. ^[22]

Corticosteroids

Multiple studies have shown a significant effect on long term complications with the use of antiviral therapy and steroids used in combination. Systemic corticosteroids are used to relieve acute pain, decrease vertigo, and limit the occurrence of postherpetic neuralgia. Different regimens of corticosteriods have been studied in Ramsay Hunt syndrome with inconclusive results. A meta-analysis of the literature shows a trend towards acyclovir plus prednisone improving the liklihood of restoring facial nerve function in affected patients and prevention of nerve degeneration compared to monotherapy. ^[16]  Along with prednisone, methylprednisolone and hydrocortisone are shown to improve the likelihood of restoring facial nerve function when given with acyclovir. ^[23]  Patients treated with combination therapy had favorable clinical outcomes, including decreased healing time of rash, cessation of acute neuritis, decreased analgesic use, and resumption of usual activity. ^[24]  

However, no evidence indicates that use of corticosteroids prevents the development of postherpetic neuralgia. ^{[17, 18]}

Treatment in patients with HIV

For treatment of herpes zoster in patients with HIV, inpatient parenteral regimens should be reserved for those with severe immunosuppression, trigeminal nerve involvement, ocular lesions, or involvement of multiple dermatomes. Treatment of VZV is the same for both HIV-seronegative and seropositive patients. For acyclovir-resistant VZV, IV foscarnet is an appropriate alternative therapy (famciclovir and valacyclovir are not effective against acyclovir-resistant VZV). For outpatient regimens, famciclovir or valacyclovir for 7-10 days is recommended (both have the advantage of easier dosing regimens). Routine use of steroids is discouraged secondary to its immunosuppressive effects. ^[25]

Treatment in other situations

Treatment of pregnant individuals with VZV is the same as that of nonpregnant persons.

When secondary impetigo is present, a suitable antistaphylococcal antibiotic should be prescribed.

Cyclic antidepressants, anticonvulsants, opioids, and topical analgesics are sometimes used in the treatment of postherpetic neuralgia. ^[11] These agents are more appropriately started by a pain management specialist in an outpatient setting.

Prevention of herpes zoster by vaccination is recommended for all persons older than 60 years, even if they have had chickenpox or zoster in the past. This age group suffers significant morbidity from zoster and may, therefore, benefit from the vaccine. Contraindications to vaccine administration include age younger than 60 years, current use of antivirals, pregnancy, and certain immunosuppressive conditions. ^[26]

Ensure that the patient has adequate and timely outpatient follow-up for management of HZ oticus.

Physical therapy may reduce non-recovery rates and improve the composite score of the Sunnybrook facial grading system in patients with peripheral facial palsy, although its effectiveness in reducing sequelae remains uncertain. ^[2] Researchers synthesized results from seven randomized controlled trials, focusing on outcomes like non-recovery and facial grading scores. Despite promising findings, the evidence quality was low, highlighting the need for more rigorous trials to confirm these effects.

Emergency department care

Adequate analgesia is important for individuals with significant pain from herpes zoster. Nausea and vomiting may require ED treatment. Complications, such as corneal irritation or secondary bacterial infection of the vesicles, should be managed with routine therapies. Involvement of more than 1 dermatome is atypical and should prompt the search for possible immunosuppression.

Consider hospital admission for any of the following situations:

• Severe symptoms

• Involvement of multiple (>2) dermatomes

• Immunocompromise

Consultations

Consider an ophthalmology consultation if corneal involvement with vesicles is noted, and consider a neurology consultation if the etiology of the facial paralysis is unclear. Consultation with an ear, nose, and throat (ENT) specialist may be appropriate. These patients can also be referred to ENT on an outpatient basis.

Prolonged or permanent facial paralysis is possible. Most patients with partial paralysis fully recover; many with severe symptoms are left with partial deficits.

Patients with HZ oticus have poorer prognoses than do those with Bell palsy. HZ oticus may result in permanent unilateral facial nerve paralysis, but also present as a polycranial neuropathy. Common disabilities may include hearing loss, vertigo, incomplete eye closure with dry eye, and speech disturbances. ^{[27, 28]}

Although diplopia and swallowing abnormalities are rare symptoms, their presence suggests a trend toward a worse outcome. These findings are suggestive of a more widespread herpetic polyneuropathy with possible brainstem involvement by the zoster virus. More common cochleovestibular symptoms such as sensorineural hearing loss and vestibular disturbance are not significantly related to prognosis overall. However, recovery of vestibulo-ocular reflex may be significantly faster in patients with vestibular neuritis than in those with Ramsay Hunt syndrome. ^[29]

Other factors, including initial House-Brackmann grades V or higher, time to commencement of treatment, age older than 50 years, and the presence of comorbid disease, influence recovery. Patients with House-Brackmann grade I or II had recovery rates of 84.6%. Furthermore, patients without vertigo, diabetes mellitus, or hypertension have a higher likelihood of complete recovery. ^[30] Patients with diabetes mellitus have poor outcomes overall, which may be further compounded by the presence of diabetic neuropathy. Microcirculatory failure of the vasa nervosum in patients with hypertension and diabetes may attenuate the effects of antiviral agents in patients with these comorbidities. ^[22]

Instruct patients how to tape eyes shut or to use protective eye coverings if lid paralysis is present. Artificial tears may help avoid eye trauma such as corneal abrasions and/or ulcerations by improving lubrication. 

Outpatient follow-up with a primary care provider is crucial to monitor progression of disease and to continue to assist with supportive measures.