Abstract
Herpes zoster (HZ) is a reactivation of the varicella zoster virus (VZV), a human α-herpes virus. Most cases of acute HZ, defined as an infection occurring up to 30 days after rash onset with subacute HZ occurring 30–90 days after rash onset, are self-limited, although patients may continue to experience pain after resolution of the rash. This condition is known as postherpetic neuralgia (PHN). VZV reactivates to cause HZ, which primarily affects both the elderly and the immunosuppressed. The clinical diagnosis of HZ is based on the clinical presentation of prodrome, with pain and the subsequent papulovesicular rash, while the differential diagnosis of the zosteriform herpes simplex must be considered. Treatment options include antiviral therapy, topical treatments, and oral medications. Antiviral therapy is used as the first-line treatment, recommended for patients with increased risk of complications with HZ. Acyclovir, famciclovir, and valacyclovir are the most used antiviral medications. Topical treatments are considered for mild pain, whereas the US Food and Drug Administration has approved two topical medications, Lidocaine and Capsaicin, for PHN. Effective treatment of PHN often requires a multimodal approach. Medication to treat pain is the cornerstone of the treatment; some antidepressants or anticonvulsants are frequently used. For intense pain, epidural steroid injections or other procedures may be beneficial. PHN can have a profound impact on any affected individual. Patients may experience a reduced quality of life because of an inability to complete activities of daily living. Patients may socialize less, resulting in decreased physical functioning and psychological well-being.
Keywords
Herpes zoster, Neuropathic pain, Postherpetic neuralgia, Shingles, Varicella zoster virus
Introduction
Herpes zoster (HZ) is a reactivation of the varicella zoster virus (VZV). VZV is a human α-herpes virus. Primary infection causes varicella (chickenpox), after which VZV becomes latent in the dorsal root ganglia of sensory or cranial nerves. Most cases of acute HZ are self-limited, although a variable percentage of patients may continue to experience pain for months to years after the resolution of the rash, a condition known as postherpetic neuralgia (PHN). Acute HZ is defined as infection occurring up to 30 days after rash onset, with subacute HZ occurring 30–90 days after rash onset. PHN is often defined as pain that persists for >90 days after rash onset, although some sources define it as pain that persists >6 weeks after the onset of disease. PHN is the most frequent chronic complication of HZ (shingles).
Presentation: Historical and Physical Features
VZV reactivates to cause HZ, characterized by a maculopapular or vesicular rash along a dermatomal distribution. The rash is characterized by severe pain, unbearable itching, aching, burning, or electric shock–like pain. The pain may precede the HZ rash. PHN is relatively common, affecting 10%–20% of those with HZ. The most common distribution for HZ is the T3-L3 dermatomes (specifically T5 and T6) and the facial region innervated by the ophthalmic division of the trigeminal nerve. HZ preferentially afflicts the elderly and the immunosuppressed. Factors that decrease immune function such as human immunodeficiency virus (HIV) infection, chemotherapy, malignancies, and long-term steroid use may also increase the risk of developing HZ.
Demographics
The incidence of PHN is 4/1000 per year. The incidence of HZ and PHN increases after 50 years of age. The incidence increases to 12/1000 among individuals aged over 80 years. Two-thirds of HZ cases occur in those aged 50 years or older, and the lifetime risk is 30%. About 20% of patients with HZ develop PHN.
Advancing age and severity of acute HZ pain are the strongest risk factors for PHN. The disease usually occurs between 50 and 79 years of age, and approximately 60% of cases occur in women.
Course
HZ arrives when VZV multiplies in sensory ganglia and advances down the affected peripheral afferent sensory nerves in the affected dermatome. VZV is highly infectious, spread by respiratory droplets and direct contact with fluid from the vesicles. The disease course can be divided into four phases: prodrome, acute, subacute, and chronic. The prodrome often occurs 1–5 days before the onset of the HZ rash. The prodrome period consists of hyperesthesia, paresthesias, burning dysesthesias, or pruritus along the affected dermatomes. Constitutional symptoms generally occur during the prodrome phase, consisting of fever, headaches, and malaise. The acute phase of HZ is characterized by a maculopapular or vesicular rash along a dermatomal distribution in conjunction with acute pain.
Differential Diagnosis
The clinical diagnosis of HZ is made if there is pain and the typical rash in a dermatomal distribution. The main consideration in the differential diagnosis is zosteriform herpes simplex ( Table 12.1 ). Herpes simplex virus (HSV-1) causes oral herpes, also known as cold sores. Herpes simplex virus 2 (HSV-2) causes genital herpes, which usually involves the genitals, buttocks, mouth, lips, and fingers. HSV-2 most commonly affects younger adults and is not associated with chronic pain.
| HHV1 | Herpes simplex virus (HSV-1) | Oral herpes (cold sores) |
| HHV2 | Herpes simplex virus (HSV-2) | Genital herpes |
| HHV3 | Varicella zoster virus | Chickenpox (infected first time) Shingles (with recurrence) |
| HHV4 | Epstein Barr virus | Mononucleosis |
| HHV5 | Cytomegalovirus | Symptoms similar to rubella |
| HHV6 | Roseolovirus | Roseola infantum |
| HHV7 | Similar to HHV6 | |
| HHV8 | Kaposi sarcoma associated herpes virus | Form of cancer commonly seen in AIDS |
During the prodromal stage of HZ, the cause is not readily apparent (as the rash has not yet erupted), leading to difficulty in diagnosis. The intensity of the pain associated with HZ and PHN may lead to misdiagnosis such as renal colic, appendicitis, myocardial infarction, pleurisy, trigeminal neuralgia, acute musculoskeletal pain, or gastrointestinal or gynecologic disorders, depending on the location of symptoms. One clue may be hyperesthetic skin in the affected dermatome. The characteristic rash of HZ erupts an average of 3–5 days after the prodrome, at which point diagnosis becomes apparent.
Diagnostic Testing
The diagnosis of HZ is usually based on clinical presentation of prodrome and rash. Laboratory confirmation is not usually necessary to diagnosis HZ but may be useful to differentiate HZ from herpes simplex for atypical presentations ( Table 12.2 ). A patient may have prodromal symptoms without developing the characteristic rash (zoster sine herpete), making diagnosis difficult and requiring laboratory confirmation of VZV.
| Test | Sensitivity | Specificity | Turnaround |
|---|---|---|---|
| Immunofluorescence | Very high (82%) | High (76%) | Hours |
| Culture | Low (20%) | High (99%) | Days |
| Polymerase chain reaction (DNA) | Very high (95%) | High (99%) | Hours |
| Serology | Moderate | Moderate | Weeks |
If a rash is present, fluid obtained from vesicles may be evaluated with polymerase chain reaction (PCR) testing, viral culture, or direct immunofluorescent antigen staining. Vesicle scrapings evaluated using immunofluorescence is the preferred method because it is rapid, specific, and very sensitive. Standard culture is slow with a turnaround time of days and has low sensitivity. VZV DNA detection using PCR has very high sensitivity and specificity, with fast turnaround time of hours. PCR, however, is not readily available and is used only in select research laboratories. Tzanck smears of lesions are inexpensive and can be performed at bedside. This technique is nonspecific and cannot differentiate VZV from herpes simplex virus infections.
If a rash is not present, serologic (antibody) methods may be used for laboratory diagnosis of HZ. Two classes of VZV antibodies may be found in the blood: IgM and IgG. There are challenges to interpreting the results.
Treatment
Medication Options
Treatment of PHN includes treatment of the acute viral infection, treatment of the acute pain associated with HZ, and prevention/treatment of PHN.
Antiviral Therapy
Antiviral therapy is the first-line treatment. Three guanosine analogues, acyclovir (Zovirax), famciclovir (Famvir), and valacyclovir (Valtrex), are approved by the US Food and Drug Administration (FDA) for the treatment of acute HZ ( Table 12.3 ). It is recommended that treatment be initiated within 72 h after the onset of the rash. Antivirals have been shown to decease the duration of the HZ rash, reduce the formation of new lesions, reduce viral shedding, and decrease the severity of acute pain, if received within 72 h after the onset of rash and before the crusting of lesions. Studies are variable regarding the effectiveness of antivirals in preventing PHN. Treatment with antivirals is recommended for patients with an increased risk for complications with HZ, which include age >50 years of age, moderate to severe pain, severe rash, involvement of the face or eye, or immunocompromised state.
| Medication | Dosage |
|---|---|
| Acyclovir (Zovirax) | 800 mg orally five times daily for 7–10 days; or 10 mg per kg intravenously every 8 h for 7–10 days |
| Famciclovir (Famvir) | 500 mg orally three times daily for 7 days |
| Valacyclovir (Valtrex) | 1000 mg orally three times daily for 7 days |
Related posts:
Stay updated, free articles. Join our Telegram channel
Full access? Get Clinical Tree
