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 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%; at 3 months, about 5%; at 1 year, 3% continue to have severe pain.

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.

Mortality/Morbidity

• The condition 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 HZ.
• With resolution of the eruption, pain that continues for 3 months or more is defined as PHN.
• Pain is intense and may be described as burning, stabbing, or gnawing.
• Herpes zoster 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.

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.
• Results of cerebrospinal fluid (CSF) evaluation are abnormal in 61%.
• • Pleocytosis is observed in 46%, elevated protein in 26%, and 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 following:
• • MRI lesions attributable to HZ were seen in the brain stem and cervical cord in 56% (9/16) of patients.
  • At 3 months after onset of HZ, 56% (5/9) of patients 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

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 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 HZ outbreaks and postherpetic neuralgia.

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 Name	Nortriptyline (Pamelor, Aventyl HCl)
Description	Has demonstrated effectiveness in treatment of chronic pain; by inhibiting reuptake of serotonin and/or norepinephrine by presynaptic neuronal membrane, may increase synaptic concentration in CNS; pharmacodynamic effects such as desensitization of adenyl cyclase and down-regulation of beta-adrenergic receptors and serotonin receptors also appear to play role in its mechanisms of action.
Adult Dose	25 mg PO tid/qid; not to exceed 150 mg/d
Pediatric Dose	<25 kg: Not established 25-35 kg: 10-20 mg/d PO 35-54 kg: 25-35 mg/d PO >25 kg: Administer as in adults
Contraindications	Documented hypersensitivity, narrow-angle glaucoma, MAOIs in past 14 d
Interactions	Cimetidine may increase levels; may increase PT in patients stabilized with warfarin
Pregnancy	D - Unsafe in pregnancy
Precautions	Use caution in renal or hepatic impairment, cardiac conduction disturbances, or history of hyperthyroidism

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 Name	Prednisone (Deltasone, Orasone, Sterapred)
Description	Decreases inflammation by suppressing migration of polymorphonuclear leukocytes and by reversing increased capillary permeability.
Adult Dose	5-60 mg/d PO qd or divided bid/qid; taper over 2 wk as symptoms resolve
Pediatric Dose	4-5 mg/m2/d PO; alternative: 1-2 mg/kg/d PO; taper over 2 wk as symptoms resolve
Contraindications	Documented hypersensitivity; viral, fungal, or tubercular skin lesions
Interactions	Concurrent estrogens may decrease clearance; when used concurrently with digoxin, may increase digitalis toxicity secondary to hypokalemia; phenobarbital, phenytoin, and rifampin may increase metabolism (may require dose increase); patients taking diuretics must be monitored for hypokalemia
Pregnancy	B - Usually safe but benefits must outweigh the risks.
Precautions	Caution in hyperthyroidism, cirrhosis, nonspecific ulcerative colitis, osteoporosis, peptic ulcer, diabetes, or myasthenia gravis; adrenal crisis may occur if withdrawn abruptly; increased risk for possible complications, including infections, hyperglycemia, edema, osteonecrosis, peptic ulcer disease, hypokalemia, osteoporosis, euphoria, psychosis, growth suppression, myopathy

Drug Name	Methylprednisolone (Solu-Medrol, Adlone, Duralone)
Description	Decreases inflammation by suppression of migration of polymorphonuclear leukocytes and reversal of increased capillary permeability.
Adult Dose	Loading dose: 125-250 mg IV Maintenance dose: 0.5-1 mg/kg/dose IV q6h for up to 5 d
Pediatric Dose	Loading dose: 2 mg/kg IV Maintenance dose: 0.5-1 mg/kg/dose IV q6h for up to 5 d
Contraindications	Documented hypersensitivity; viral, fungal, or tubercular skin lesions
Interactions	Concurrent estrogens may decrease clearance; when used concomitantly with digoxin, may increase digitalis toxicity secondary to hypokalemia
Pregnancy	C - Safety for use during pregnancy has not been established.
Precautions	Caution in patients with hyperthyroidism, cirrhosis, nonspecific ulcerative colitis, osteoporosis, peptic ulcer, diabetes, or myasthenia gravis

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 Name	Gabapentin (Neurontin)
Description	This medication has been approved by the FDA for the treatment of PHN. Has properties common to other anticonvulsants and antineuralgic effects. Exact mechanism of action is not known. Structurally, gabapentin is related to GABA, but it does not interact with GABA receptors. Believed to have a binding site at the alpha 2-delta protein, an auxiliary subunit of voltage-gaited calcium channels. In the rat brain, binding is localized on neuronal dendritic areas. Relevance of these observations to treatment of PHN is not known.
Adult Dose	100 mg PO tid; titrate dose prn; recommended dose is 900-1800 mg PO qd; not to exceed 900 mg PO qid
Pediatric Dose	<12 years: Not established >12 years: Administer as in adults
Contraindications	Documented hypersensitivity
Interactions	Antacids may significantly reduce bioavailability, should be administered > 2 h following antacid; cimetidine may reduce clearance, but this may not be of clinical significance; may significantly increase norethindrone levels
Pregnancy	C - Safety for use during pregnancy has not been established.
Precautions	Caution in severe renal disease

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

Prognosis

• The natural history of 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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• Bowsher D. The management of postherpetic neuralgia. Postgrad Med J. Oct 1997;73(864):623-9. [Medline].
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• Nurmikko T. Clinical features and pathophysiologic mechanisms of postherpetic neuralgia. Neurology. Dec 1995;45(12 Suppl 8):S54-5. [Medline].
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• 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].
• 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].
• Rowbotham MC, Davies PS, Fields HL. Topical lidocaine gel relieves postherpetic neuralgia. Ann Neurol. Feb 1995;37(2):246-53. [Medline].
• 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].
• Watson CP. Postherpetic neuralgia. Neurol Clin. May 1989;7(2):231-48. [Medline].
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• Watson CPN, Gershon AA. Herpes Zoster and Post Herpetic Neuralgia. Vol 11. 2001:90-93, 108-109.
• Whitley RJ, Shukla S, Crooks RJ. The identification of risk factors associated with persistent pain following herpes zoster. J Infect Dis. Nov 1998;178 Suppl 1:S71-5. [Medline].

Article Last Updated: Oct 2, 2006