Epidemiology

There have been many epidemiological studies intended to define the incidence of BP, with most estimates between 18 and 40 cases per 100,000 persons annually ( Table 10.1 ).1–8 Epidemiological studies may be based on a specific population or on encounters by a specific provider. Each type of study has its own inherent strengths and weaknesses. Population-based studies define the population at risk and survey all providers to generate incidence figures; however, the diagnosis is not independently confirmed. Practice-based studies have the advantage of a consistent diagnosis, while making the assumption that all of the population at risk are examined at a specific site. Table 10.1 includes several large studies of each type, providing a consensus range for the annual incidence.

Several studies have examined annual incidence according to age, gender, ethnicity, climate, and season. There is some variability in the conclusions depending on the sample size and reliability of the correction of incidence figures to the control population. It is clear that BP is uncommon in children, with low incidence consistently reported in those under age 18. Incidence rates rapidly increase in the third decade to the overall population mean and then either reach a plateau or show a slight increase in the oldest age groups. The incidence of BP in women may be slightly greater. In reports that indicate a difference in incidence according to gender, women are universally cited as having the greater incidence. Likewise, there is some debate regarding seasonal variation of incidence figures. When seasonal variability is reported, the greater incidence is in the winter months. Campbell and Brundage show a modest increased risk in winter months with an odds ratio of 1.31 (95% confidence interval 1.13–1.51).3

Few studies examine ethnically heterogeneous populations. It is tempting to directly compare incidence figures between studies of geographically distinct populations, though it is not certain that the methodology is uniform. Slight differences in incidence among ethnic groups were encountered in a survey of U.S. military personnel, with the highest incidence in Hispanics.3 Comparisons between surveys of predominantly Mexican Americans in Laredo, Texas, and predominantly Caucasians in Olmsted County, Minnesota, tend to support the assertion of a greater incidence in Hispanics.2,6 However, these observations must be viewed within the context of HSV prevalence in the population.

Given the assumed role of HSV in the development of BP, it is useful to understand the epidemiology of HSV infection and basic virus physiology. HSV-1 is typically acquired via transmission of infected saliva. Introduction of the virus in the oral cavity allows retrograde uptake of the virus along sensory nerves, which can include branches of both the facial and trigeminal nerves. This results in establishment of a latent state of infection in sensory ganglia that is permanent. Viral replication is arrested by local and systemic immune responses primarily via CD8+ T cells, which also remain permanently in the ganglion.9,10 Presence of HSV in the geniculate ganglion is frequently documented in autopsy series, though the viral load is highly variable, indicating the significance of local cellular responses.11,12 The virus is capable of reactivation, during which it uses host cellular enzymes, including ribonucleic acid polymerase II, and transcription factors for viral replication. The complete virion may spread to adjacent cells or is transported ante-grade to peripheral tissues. The stimulus for reactivation of the virus is uncertain but may broadly involve intercellular signaling pathways including signal transduction and activators of transcription factors.13 Following the stimulus for reactivation, it takes ∼24 hours for viral synthesis to be completed. The process of viral replication results in lysis of many cell types, but this does not occur in neurons. The interaction between HSV, the host neuron, and the CD8+ T cell is incompletely understood, but predicts an ongoing process in which latency is maintained by successful arrest of intermittent viral synthesis and clinical reactivation is evident when the virus subverts CD8+ T cell–mediated suppression of viral synthesis.9

Prevalence of HSV infection increases with age, though the rate of acquisition varies substantially across different populations.14 In general, the age at time of infection is greater in developed countries, implying an increased rate of infection in association with lower socioeconomic status. Seropositivity of HSV in the United States has been examined over time by the National Health and Nutrition Examination Survey (NHANES), conducted during the years 1976–1980, 1989–1994, and 1999–2004. The most recent NHANES III finds a decreasing seroprevalence in the past 30 years, with an overall prevalence of HSV-1 of 60% by age 49.15

Prevalence rates (in NHANES III) also vary according to ethnicity with the highest rates in Mexican-Americans (81%), intermediate in African-Americans (68%), and lowest in Caucasians (50% at age 49).15 Similar trends are seen in a separate analysis of children under 13. In this group, Mexican-Americans born in Mexico have the highest prevalence rates, indicating earlier acquisition of HSV infection. Others born outside the United States had a greater prevalence than those born in the United States. The data also found correlation with socioeconomic status, as those children living in families with incomes below the poverty level had a greater prevalence of HSV-1 seropositivity (52% versus 24%; p < 0.001).16

The rate of acquisition of infection does vary by gender. Equal seroprevalence of HSV-1 is seen in children, emphasizing the role of intrafamilial spread of infection. Prevalence rates in women 14 to 29 years of age are significantly greater than men in each NHANES survey, though differences disappear with increasing age.15 The faster rate of acquisition in women implies infection through sexual contacts and is mirrored in acquisition of HSV-2 infections. The data also implies young women have a greater probability of an older partner.

The declining rate of infection over time is attributed to rising socioeconomic status, smaller family sizes, and improved hygiene, and is mirrored in other developed countries.17,18 This reasoning is confirmed by the higher prevalence in immigrant populations and greater decline in prevalence over time in individuals born in the United States. The strong trends linking HSV with socioeconomic status suggest that there may be little, if any, difference in susceptibility to HSV infection due to ethnicity. A difference in incidence of BP according to ethnicity was previously cited. Because none of the studies correct for seroprevalence of HSV, or socioeconomic status of the population of interest, differences in BP incidence are likely to be due to differences in HSV prevalence rather than a unique ethnic susceptibility to disease.

Natural History

The decision to prescribe treatment implies that there is benefit to the patient over nontreatment, creating a need for a thorough understanding of the natural history of the disease. Clinical observations and tests are used to classify patients according to severity with the intent to identify individuals with greater degrees of nerve degeneration. Several factors have a strong influence on the final outcome including degree of facial weakness, time to onset of recovery, degree of electrical degeneration, and age.

The largest series of untreated patients is described by Peitersen.1 In this extensive series, recovery to normal function occurs in 71% of all patients. Twelve percent had minor sequelae that could include mild contracture. Thirteen percent had moderate sequelae, such as moderate weakness, obvious contracture, and synkinesis. Only 4% had severe residual weakness, disfiguring contracture, and marked synkinesis. In this series, 70% of patients developed complete paralysis and attained recovery to normal in 61%. Of those with incomplete paralysis, 94% eventually recovered to normal. The sooner signs of recovery began, the greater the probability of full recovery. Individuals with initial signs of recovery beginning after the second week had a significantly poorer probability of recovery to normal. However, 85% of all patients showed some signs of recovery within the first 3 weeks. There was a significant effect of age on recovery, as only 36% of individuals over age 60 attained full recovery versus 90% of those under 15. The most common associated symptoms were pain in 52%, dysgeusia in 34%, and hyperacusis in 14%.

Adour et al8 reported a small series of 86 untreated patients seen within 5 days of onset. Of the entire group, 63% achieved return of normal function. Correction for degree of paralysis finds that complete recovery is seen in 72% of patients with incomplete paralysis, dropping to 40% if complete facial paralysis developed. Only 29% of their patients developed complete paralysis. Associated symptoms included pain in 62%, dysgeusia in 57%, and hyperacusis in 29%.

Devriese et al report an extensive series of 1,235 patients with BP, though treatment varied from none to medications or surgery.19 The untreated patients constituted almost half of the series. Factors dictating no intervention included incomplete paralysis, medical contraindication, delay in diagnosis, and unknown reason. The 371 patients who retained some degree of facial function showed recovery to normal in 80%. The 98 patients in whom steroids were deemed contraindicated had unspecified medical conditions but had a mean age significantly greater (62.7 years) than those with incomplete paralysis. Consequently, recovery to normal in this untreated group was only 30%.

May et al reported a series of untreated patients (compared with transmastoid decompression) and supplemented this report with additional data supporting the wide difference in outcome depending on degree of weakness.20 In the personal series of 405 untreated patients, 56% developed complete paralysis. Normal recovery was seen in 59% of these individuals compared with 97% in the patients with incomplete paralysis. Most of these patients had electroneuronography studies over a period of 14 days from the onset. The minimal electromyography amplitude was expressed as a percentage of the amplitude of the normal side. Individuals with < 10% function recovered to normal in only 13% of cases, while those with > 25% function attained a normal outcome 90% of the time.21

These reports are generally in agreement that those individuals with incomplete paralysis have a more favorable prognosis. The probability of normal recovery varies as does the incidence of complete paralysis in each series. Adour et al noted the lowest percentage of complete paralysis and the lowest probability of normal function in the incomplete group.8 There are likely to be differences in how each group rates the degree of function, with Adour et al possibly being the most critical of small differences in facial function. Nonetheless, as recovery with incomplete paralysis is substantially better without treatment, these individuals must be accounted for in studies discussing efficacy of any proposed treatment. Differences in practice referral patterns or treatment philosophy over time and possibly intrarater variability may also influence reported results.

Insight into the natural history of HSV reactivation is gained by considering herpes labialis, a manifestation of reactivation from the trigeminal ganglion. Clinical features include characteristic vesicular lesions (from which HSV can be cultured) in a dermatomal pattern involving the perioral region or nasal cavity. A prodrome consisting of pain at the affected site, headache, and mild general malaise may begin 1 to 2 days prior to the development of cutaneous lesions. The vesicles are painful at onset and accompanied by local tissue edema that resolves as the lesions become crusted. The lesions typically heal completely in 7 to 10 days. Recurrences are triggered by stress, sun exposure, illness, and trauma.22 Approximately 30% of the population has experienced recurrent herpes labialis, with no differences according to gender or seasonality.22,23 Those who experience recurrences report a frequency of once per year or less in 48% of cases, and four times per year or greater in only 16%.23 The frequency and severity of recurrences tends to diminish with time.24 Those with frequent recurrences display considerable variability in interval between recurrences, severity of lesions, and site (or side of face) involved.25 The appearance of clinical lesions does not reflect the true frequency of viral reactivation. Sensitive methods of detection coupled with daily surveillance finds that > 90% of HSV-1 reactivation in the oral cavity is subclinical with 54% of episodes lasting < 24 hours.26 These observations indicate that episodes of reactivation are not uniform at the molecular level and likely illustrate differing levels of viral synthesis prior to immune system intervention.

Obviously, there is a significant difference in the observed frequency of clinical reactivation of HSV from the geniculate and trigeminal ganglia. There are multiple potential explanations based on differences in local neuronal populations and their susceptibility to viral reactivation. In addition, it is likely that many instances of disturbed function limited to sensory branches of the facial nerve are unrecognized clinically. Finally, development of motor division paralysis (which is not observed in trigeminal nerve reactivation) is likely due to the unique anatomic relationship of the facial nerve to the meatal foramen, where it occupies ∼98% of the available lumen.27 The impact of developing intraneural edema will be manifest at the site where it is least tolerated.

Management

The list of therapies proposed for treatment of BP is as variable as it is long. Early therapies were presumably applied based on an assumed ischemic injury to the nerve. Thus, vasodilators such as histamine and nicotinic acid were promoted. Evolution to minimally invasive techniques included cervical sympathetic and stellate ganglion blocks, and steroid injections given intratympanically or to the stylomastoid foramen. Other more obscure therapies included radiation therapy, electrical stimulation, hyperbaric oxygen, and acupuncture. Support for any of these therapies is weak, including lack of controlled trials to address efficacy and an uncertain physiological mechanism to mitigate the disease development or progression.

The most commonly accepted clinical treatments include oral corticosteroids, antivirals, and topical eye care. Of these, eye care is the least controversial, and it is very important to prevent ocular complications such as corneal abrasion. Eye care usually consists of preservative-free artificial tears, a thicker ointment to be placed while sleeping, and possibly taping, patching, or use of a moisture chamber.

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