Definition, prevalence and aetiology
Herpes zoster oticus is a viral infection of the inner, middle and external ear characterised by herpetic blisters (small vesicles) of the skin of the external canal, pinna and/or the oral mucosa and severe otalgia (ear pain). These symptoms can be accompanied by one or more of the following: vestibulocochlear dysfunction (e.g. vertigo, hearing loss, hyperacusis, tinnitus), taste impairment, dry mouth and eyes.

When herpes zoster oticus is associated with acute peripheral facial paralysis the condition is known as Ramsay Hunt syndrome type 2 (Ramsay Hunt 1907). Although the terms 'herpes zoster oticus' and 'Ramsay Hunt syndrome' are frequently used interchangeably in the literature, this review will focus only on Ramsay Hunt syndrome and will include trials with participants suffering from herpes zoster oticus with accompanying facial weakness.

The incidence of Ramsay Hunt syndrome is about five cases per 100,000 of the US population annually, with a significantly increased incidence in patients older than 60 years (Murakami 1997). The condition is considered to be both less frequent and less severe in children (Hato 2000; Sweeney 2001), but reports of children are limited in the literature and the clinical features and prognosis of paediatric Ramsay Hunt syndrome remain unclear. Vaccination against chickenpox (both in childhood and in later life) may prevent or reduce its occurrence (Guess 1985; Hato 2000; Oxman 1995).

Ramsay Hunt syndrome is caused by the reactivation of latent varicella‐zoster virus in the geniculate ganglion (the sensory ganglion of the facial nerve) which affects the seventh and eighth cranial nerves. This is due to the close proximity of the facial nerve (cranial nerve VII) and the vestibulocochlear nerve (cranial nerve VIII) (Sweeney 2001). The subsequent dysfunction of cranial nerves VII and VIII is thought to be caused primarily by varicella‐zoster virus neuritis and to a lesser extent by inflammatory oedema. Maximal facial paralysis is generally seen within one week. Although less common than Bell's palsy (i.e. idiopathic facial palsy), Ramsay Hunt syndrome generally causes more severe dysfunction and has a poorer prognosis for facial nerve recovery (Uri 2003).

History, examination and diagnosis
Early diagnosis of Ramsay Hunt syndrome is extremely important, as antiviral treatment within the first 72 hours of the onset of symptoms is generally considered to be crucial to the resolution of some (if not all) symptoms (Dworkin 2007).

Diagnosis is primarily clinical and is based on the presentation of a combination of severe ear pain, small vesicles on the pinna or oral mucosa and facial palsy. When patients present with acute facial weakness a high index of suspicion is required in order to recognise the condition, deliver prompt treatment and obtain the best possible outcome. Although the appearance of vesicles usually precedes or presents simultaneously with facial paralysis, it may be delayed until after facial weakness is clinically evident, thus making the condition initially indistinguishable from Bell's palsy. Symptoms and signs of vestibulocochlear dysfunction are not always present but can include hearing loss, tinnitus, vertigo, nystagmus, nausea and vomiting.

The clinical picture remains the cornerstone of diagnosis, as serum titres of varicella‐zoster virus antibodies are only useful when comparing the acute and convalescent stages of the condition (Dickins 1988). The use of a polymerase chain reaction (PCR) to detect varicella‐zoster virus from skin of the affected area of the ear may help to distinguish between patients with Bell's palsy and patients with Ramsay Hunt syndrome in the very early stages (Murakami 1998).

If diagnosis is made and antiviral treatment commenced within 72 hours of the onset of symptom(s), the facial palsy recovery rate has been reported in non‐randomised studies to be as high as 75% (Murakami 1997; Dickins 1988). However, even with early treatment, the absence of demonstrable lack of nerve excitability, complete paralysis and age over 50 years at presentation are said to be significant factors for increased risk of poor prognosis (Sweeney 2001). By contrast, the prognosis for associated sensorineural hearing loss associated with Ramsay Hunt syndrome is excellent, and only around 5% of patients will have residual hearing impairment (Kaberos 2002; Murakami 1997). Other potentially chronic sequelae are post‐herpetic neuralgia, tinnitus and vestibular dysfunction (Dworkin 2007).

Management options
The standard first‐line treatment for herpes zoster infections at sites in the body other than the ear is the anti‐viral agent acyclovir, which is given either intravenously for immunocompromised patients or orally in otherwise healthy patients. Other antiviral agents that may be prescribed include valacyclovir, famcyclovir or brivudin (Dworkin 2007).

Antiviral therapy is only effective against virus replication in herpes zoster ‐ that is, it can prevent further proliferation and spread of the varicella‐zoster virus ‐ and cannot eradicate herpes viruses. Oral antiviral treatment has been shown by two meta‐analyses (of four and five randomised controlled trials respectively) to lessen the severity of herpes zoster virus infection in immunocompetent adults by reducing the duration of viral shedding and new lesion formation, thereby accelerating rash healing and reducing the duration of pain (Wood 1996; Jackson 1997).

It is generally held that the use of oral antivirals is limited to a period of seven to ten days and needs to be started within 72 hours of the onset of a rash. They are generally very well tolerated if administered at standard doses (acyclovir: 800 mg five times/day for 7 to 10 days; famcyclovir: 500 mg three times/day for seven days; valacyclovir: 1000 mg three times/day for seven days) and providing patients are kept well hydrated (Goodman 2006; Lampee 1986; Kinishi 2001; Dworkin 2007). The most common side effects are nausea (and occasionally vomiting) and headache, which occur in 10% to 20% of cases. Other possible side effects include renal impairment, diarrhoea, dizziness, fatigue, skin rash, anorexia, leg pain, medication taste, sore throat and hair loss from prolonged use (Bean 1982; Dickins 1988). Any allergic reaction to antiviral medications is a contraindication to their use (Peterslund 1981).

Oral brivudin appears to have a higher potency against varicella‐zoster virus than the oral regimes of acyclovir, valacyclovir and famcyclovir. It also has a simpler regime (once a day) and no nephrotoxic effects (Dworkin 2007; Gross 2003). However, antivirals cannot prevent either the acute or chronic pain experienced by about 20% of patients over 50 years of age with herpes zoster and therefore supplementary therapies, most frequently adjuvant corticosteroids, are often prescribed for herpes zoster infections, including Ramsay Hunt syndrome. The rationale for their use is to reduce nerve inflammation and associated pain.

Corticosteroids
Corticosteroids are used therapeutically in a wide variety of conditions. In herpes zoster infections, synthetic glucocorticoids such as prednisone and prednisolone are frequently prescribed for their anti‐inflammatory properties. A recent comprehensive overview of treatments for all types of herpes zoster infections states that although, "Two well‐designed clinical trials [have] demonstrated that the addition of a 3‐week tapering dosage of a corticosteroid did not contribute significantly, beyond the benefits achieved by acyclovir alone, in reducing prolonged pain . . . the addition of the corticosteroid [to antiviral therapy] did have beneficial effects on acute pain and some cutaneous end points in both of these trials; in one of the trials, the times to uninterrupted sleep, return to normal daily activity, and cessation of analgesic therapy were all significantly accelerated in patients who received combination therapy. Individuals with contraindications to the use of corticosteroids, including hypertension, diabetes, and peptic ulcer disease, were excluded from these studies. Nevertheless, adverse effects of corticosteroids were reported, including gastrointestinal symptoms, edema, and granulocytosis." (Dworkin 2007: p. S13. Trials: Whitley 1996; Wood 1994).

In the case of Ramsay Hunt syndrome, Dworkin goes on to state that "Corticosteroids can be considered as soon as possible after diagnosis for patients with at least moderately severe pain and no contraindications. In addition, corticosteroids should be considered for patients with VZV‐induced [varicella‐zoster virus‐induced] facial paralysis and cranial polyneuritis to improve motor outcomes, peripheral nerve damage from foraminal compression, or evidence of CNS [central nervous system] involvement, although the benefit of such treatment has not been systematically studied. Contraindications (e.g. hypertension, diabetes, gastritis, osteoporosis and psychosis) and risks associated with the use of corticosteroids must be carefully evaluated. Treatment with corticosteroids should be initiated only in combination with antiviral therapy. There is no evidence base for the use of topical corticosteroids for treatment of patients with HZ [herpes zoster], and such treatment is not recommended." (Dworkin 2007: S17)

Corticosteroids ‐ side effects
Prolonged use or overdose of corticosteroids may exaggerate their physiological action, leading to a broad range of unwanted side effects including adrenal gland suppression and atrophy, fluid and electrolyte impairment, endocrine disturbances, gastrointestinal disorders, dermatologic and musculoskeletal dysfunctions, neurological disorders (e.g. convulsions, increased intracranial pressure with papilloedema, vertigo, headache), and psychiatric disorders (e.g. euphoria, depression, mania). Most side effects from steroid use are dose‐ and length of treatment‐dependent (Goodman 2006; Lampee 1986), and it is generally accepted that corticosteroid use should be limited to a duration of 7 to 10 days. There is very little information in the medical literature on side effects during treatment with short courses.

Notwithstanding the potential (but unquantified) risk of adverse effects associated with short courses of steroids, some patients in the UK and elsewhere with Ramsay Hunt syndrome are currently being prescribed corticosteroids in combination with antiviral therapy ‐ for example, the German Dermatology Society (DDG) guidelines for the treatment of herpes zoster oticus with or without facial palsy recommend "high dose antiviral therapy (intravenously preferred) [within 72 hours of onset] in combination with glucocorticoids" (Gross 2003: p. 285). However, the evidence base for corticosteroids as adjuvant to antiviral therapy for Ramsay Hunt syndrome remains unclear. We found no systematic review of corticosteroids as adjuvant therapy.

This systematic review aims to evaluate whether the use of steroids as an adjuvant to antiviral therapy improves outcomes in patients with Ramsay Hunt syndrome.