AUTHOR AND EDITOR INFORMATION

Section 1 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Multimedia
• References

INTRODUCTION

Section 2 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Multimedia
• References

Background

Herpes zoster (HZ) is a viral infection that usually presents as a childhood infection of varicella (ie, chicken pox). The pathogen is human herpesvirus-3 (HHV-3), also known as the varicella zoster virus (VZV). Following the acute phase, the virus enters the sensory nervous system, where it is harbored in the geniculate, trigeminal, or dorsal root ganglia and remains dormant for many years. With advancing age or immunocompromised states, the virus reactivates and an eruption (ie, shingles) occurs. Even after the acute rash subsides, pain can persist or recur in shingles-affected areas. This condition is known as postherpetic neuralgia (PHN).

Pathophysiology

Some patients with postherpetic neuralgia (PHN) appear to have abnormal function of unmyelinated nociceptors and sensory loss (usually minimal). Pain and temperature detection systems are hypersensitive to light mechanical stimulation, leading to severe pain (allodynia). Allodynia may be related to formation of new connections involving central pain transmission neurons. Other patients with PHN may have severe, spontaneous pain without allodynia, possibly secondary to increased spontaneous activity in deafferented central neurons or reorganization of central connections. An imbalance involving loss of large inhibitory fibers and an intact or increased number of small excitatory fibers has been suggested. This input on an abnormal dorsal horn containing deafferented hypersensitive neurons supports the clinical observation that both central and peripheral areas are involved in the production of pain.

Frequency

United States

Frequency 1 month after onset of shingles is 9-14.3% and at 3 months is about 5%. At 1 year, 3% continue to have severe pain.

Family history as a risk factor for herpes zoster has been described. In a case-control study of 504 patients and 523 controls, Hicks et al found that the patients were more likely to report blood relatives with herpes zoster than the controls (39% vs 11%, p<.001). This risk was higher in patients with multiple blood relatives with herpes zoster compared with those with a single blood relative with herpes zoster.¹

International

A study from Iceland demonstrated variations in risk of PHN associated with different age groups. No patient younger than 50 years described severe pain at any time. Patients older than 60 years described severe pain: 6% at 1 month and 4% at 3 months from the onset of shingles.²

Mortality/Morbidity

• Postherpetic neuralgia is not fatal.
• Patients may experience significant pain for a prolonged period of time.
• Older age appears to be the most significant risk factor for developing PHN.

Sex

No predilection for developing PHN is known. Although 65% of patients in a study by Watson et al were women, this was believed to mirror the usual predominance of women in this age group.

Age

The association between greater age and PHN is strong. At age 60 years, approximately 60% of patients with shingles develop PHN, and at age 70 years, 75% develop PHN.

CLINICAL

Section 3 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Multimedia
• References

History

• A painful vesicular eruption in a dermatomal distribution is typical of herpes zoster (HZ).
• With resolution of the eruption, pain that continues for 3 months or more is defined as postherpetic neuralgia (PHN).
• Pain is intense and may be described as burning, stabbing, or gnawing.
• HZ can reactivate subclinically with pain in a dermatomal distribution without rash. This condition is known as zoster sine herpete and may be more complicated, affecting multiple levels of the nervous system and causing multiple cranial neuropathies, polyneuritis, myelitis, or aseptic meningitis.

Physical

• Area of previous HZ may show evidence of cutaneous scarring.
• Sensation may be altered over involved areas, in the form of either hypersensitivity or decreased sensation.
• Allodynia is pain produced by a non-noxious stimulus, such as a light touch by a brush, and may be present over the involved area.
• Changes in autonomic function such as increased sweating over the involved area may be seen.

Causes

• Risk factors for development of PHN include the following:
• • Advancing age
  • Site of HZ involvement
    • Lower risk - Jaw, neck, sacral, and lumbar
    • Moderate risk - Thoracic
    • Highest risk - Trigeminal (especially ophthalmic division), brachial plexus
  • Severe prodromal pain (with HZ)
  • Severe rash

DIFFERENTIALS

Section 4 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Multimedia
• References

Other Problems to be Considered

Brachial plexitis
Diabetic mononeuritis

WORKUP

Section 5 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Multimedia
• References

Lab Studies

• No laboratory work is usually necessary in cases of postherpetic neuralgia (PHN).
• Results of cerebrospinal fluid (CSF) evaluation are abnormal in 61%.
• • Pleocytosis is observed in 46%, elevated protein in 26%, and varicella zoster virus (VZV) DNA in 22%.
  • These findings are not predictive of the PHN clinical course.
• Viral culture or immunofluorescent staining may be used to differentiate herpes simplex from herpes zoster in cases that are difficult to distinguish clinically.
• Antibodies to herpes zoster can be measured. A 4-fold increase has been used to support the diagnosis of subclinical herpes zoster (zoster sine herpete). However, a rising titer secondary to viral exposure rather than reactivation cannot be ruled out.

Imaging Studies

A study by Haanpaa et al revealed the following³:

• MRI lesions attributable to HZ were seen in the brain stem and cervical cord in 9  patients (56%).
• At 3 months after onset of HZ, 5 patients (56%) with an abnormal MRI had developed PHN.
• Of the 7 patients who had no HZ-related lesions on MRI, none had residual pain.

Histologic Findings

Although HZ symptoms may be confined to a few sensory dermatomes, pathological changes may be more widespread. Affected ganglia of the spinal or cranial nerve roots are swollen and inflamed with a primarily lymphocytic reaction. Some ganglion cells are swollen while others are degenerated.

Inflammation extends into the meninges and root entry zone and may be present in the ventral horn and perivascular space of the spinal cord. Pathological changes in the brain stem are similar to those in the spinal root and spinal cord. In the months following infection, fibrosis occurs in the ganglia, peripheral nerve, and nerve root. Degeneration occurs in the ipsilateral posterior column.

TREATMENT

Section 6 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Multimedia
• References

Medical Care

The financial implications for treatment of postherpetic neuralgia are becoming more important as the population ages. Dworkin et al examined annualized costs for persistent pain in patients with herpes zoster. Annualized costs were $4917 for commercially insured patients, $2696 for Medicare patients and $9310 for Medicaid patients.⁴

Surgical Care

• Dorsal root entry zone (DREZ) lesions have been used.
• • Efficacy - Improvement rate is 20% in long-term studies.
  • Complications - Gait disturbances are experienced by 12% of treated patients.
• Miscellaneous treatment
• • Epidural steroids
  • Nerve blocks

MEDICATION

Section 7 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Multimedia
• References

The goal of therapy for (postherpetic neuralgia) is to reduce morbidity through the use of tricyclic antidepressants, anticonvulsants, anesthetics, analgesics, corticosteroids, and antiviral agents. A recently approved vaccine is also effective for preventing herpes zoster (HZ) outbreaks and PHN.

Drug Category: Tricyclic antidepressants

Complex group of drugs that have central and peripheral anticholinergic effects as well as sedative effects. They have central effects on pain transmission. They block the active reuptake of norepinephrine and serotonin.

Drug Category: Analgesics

Pain control is essential to quality patient care; it ensures patient comfort and promotes pulmonary toilet. Most analgesics have sedating properties, which are beneficial for patients who experience pain.

Drug Category: Corticosteroids

These agents have anti-inflammatory properties. Glucocorticoids cause profound and varied metabolic effects. In addition, they modify the body's immune response to diverse stimuli.

Drug Category: Antiviral agents

The goal of antivirals is to shorten the clinical course, prevent complications, prevent the development of latency and/or subsequent recurrences, decrease transmission, and eliminate established latency.

Drug Category: Anesthetics

These agents stabilize the neuronal membrane so the neuron is less permeable to ions. This prevents the initiation and transmission of nerve impulses, thereby producing the local anesthetic action.

Drug Category: Anticonvulsants

These agents are used to manage severe muscle spasms and provide sedation in neuralgia. They have central effects on pain modulation.

Drug Category: Vaccines

Used for prevention of HZ outbreak.

FOLLOW-UP

Section 8 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Multimedia
• References

Deterrence/Prevention

See Medscape's CME activity Preventing Herpes Zoster and Postherpetic Neuralgia: Are Your Patients Adequately Protected?

Prognosis

• The natural history of postherpetic neuralgia (PHN) involves slow resolution of the pain syndrome.
• In those patients who develop PHN, most will respond to analgesic agents such as the tricyclic antidepressants.
• A subgroup of patients may develop severe, long-lasting pain that does not respond to medical therapy. Continued research for new agents is necessary.

Patient Education

For excellent patient education resources, visit eMedicine's Bacterial and Viral Infections Center. Also, see eMedicine's patient education articles Shingles and Chickenpox.

MULTIMEDIA

Section 9 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Multimedia
• References

Media file 1:  Hypopigmented rash in thoracic dermatome of postherpetic lesion.
	View Full Size Image
Media type:  Photo

REFERENCES

Section 10 of 10

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Multimedia
• References

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2. Helgason S, Petursson G, Gudmundsson S, Sigurdsson JA. Prevalence of postherpetic neuralgia after a first episode of herpes zoster: prospective study with long term follow up. BMJ. Sep 30 2000;321(7264):794-6. [Medline].
3. Haanpaa M, Dastidar P, Weinberg A, et al. CSF and MRI findings in patients with acute herpes zoster. Neurology. Nov 1998;51(5):1405-11. [Medline].
4. Dworkin RH, White R, O'Connor AB, Hawkins K. Health care expenditure burden of persisting herpes zoster pain. Pain Med. Apr 2008;9(3):348-53. [Medline].
5. Baron R, Saguer M. Mechanical allodynia in postherpetic neuralgia: evidence for central mechanisms depending on nociceptive C-fiber degeneration. Neurology. Dec 1995;45(12 Suppl 8):S63-5. [Medline].
6. Bowsher D. The management of postherpetic neuralgia. Postgrad Med J. Oct 1997;73(864):623-9. [Medline].
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8. Freynhagen R, Strojek K, Griesing T, et al. Efficacy of pregabalin in neuropathic pain evaluated in a 12-week, randomised, double-blind, multicentre, placebo-controlled trial of flexible- and fixed-dose regimens. Pain. Jun 2005;115(3):254-63. [Medline].
9. Johnson RW. Herpes zoster and postherpetic neuralgia. Optimal treatment. Drugs Aging. Feb 1997;10(2):80-94. [Medline].
10. Kotani N, Kushikata T, Hashimoto H, et al. Intrathecal methylprednisolone for intractable postherpetic neuralgia. N Engl J Med. Nov 23 2000;343(21):1514-9. [Medline].
11. Merritt HH. A Textbook of Neurology. 1979;90. [Medline].
12. Nurmikko T. Clinical features and pathophysiologic mechanisms of postherpetic neuralgia. Neurology. Dec 1995;45(12 Suppl 8):S54-5. [Medline].
13. Oxman MN, Levin MJ, Johnson GR, et al. A vaccine to prevent herpes zoster and postherpetic neuralgia in older adults. N Engl J Med. Jun 2 2005;352(22):2271-84. [Medline].
14. Rath SA, Braun V, Soliman N, et al. Results of DREZ coagulations for pain related to plexus lesions, spinal cord injuries and postherpetic neuralgia. Acta Neurochir (Wien). 1996;138(4):364-9. [Medline].
15. Rowbotham M, Harden N, Stacey B, et al. Gabapentin for the treatment of postherpetic neuralgia: a randomized controlled trial. JAMA. Dec 2 1998;280(21):1837-42. [Medline].
16. Rowbotham MC, Davies PS, Fields HL. Topical lidocaine gel relieves postherpetic neuralgia. Ann Neurol. Feb 1995;37(2):246-53. [Medline].
17. Tyring S, Barbarash RA, Nahlik JE, et al. Famciclovir for the treatment of acute herpes zoster: effects on acute disease and postherpetic neuralgia. A randomized, double-blind, placebo-controlled trial. Collaborative Famciclovir Herpes Zoster Study Group. Ann Intern Med. Jul 15 1995;123(2):89-96. [Medline].
18. Watson CP. Postherpetic neuralgia. Neurol Clin. May 1989;7(2):231-48. [Medline].
19. Watson CP, Vernich L, Chipman M, Reed K. Nortriptyline versus amitriptyline in postherpetic neuralgia: a randomized trial. Neurology. Oct 1998;51(4):1166-71. [Medline].
20. Watson CPN, Gershon AA. Herpes Zoster and Post Herpetic Neuralgia. Vol 11. 2001:90-93, 108-109.
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Article Last Updated: Sep 18, 2008