Hospital Medicine

Post-herpetic neuralgia

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Post-Herpetic Neuralgia

I. What every physician needs to know.

Post-herpetic neuralgia (PHN) refers to the development of pain in a dermatomal distribution after a varicella zoster infection. Zoster infection reflects latent virus harbored in nerve cells, which reactivates due to a decrease in immunity, most commonly as patients age. Varicella zoster frequently causes pain, but only a subset of patients develop post herpetic neuralgia, or pain that persists beyond the initial zoster rash. PHN occurs in fewer than 10% of patients overall, but at higher rates in patients over 60, with rates ranging from 15-40%. Mortality is rare, but increases with age.

The definition of PHN is debated. Commonly, it is described as post herpetic pain that persists after 3 months. Prior to developing PHN, patients usually have acute herpetic pain (up to 1 month) and subacute pain (up to 3 months).

The nature of the pain can vary. Most commonly the discomfort follows essentially the same dermatomal distribution as the recent zoster rash, although there may be some extension. It can cause burning, as well as allodynia, or hypersensitivity to non-painful stimuli. The pain can also be associated with sensory deficits and local areas of anesthesia.

The pain is hypothesized to result from hemorrhage of the nerves that harbored the virus initially and were the site of the zoster outbreak, and subsequent fibrosis of the same nerve fibers. Biopsies of patients with PHN showed greater destruction of the central and peripheral nervous system, relative to other patients with zoster who did not develop PHN.

The most important issue related to PHN is prevention of zoster infection, as treatment of PHN is of marginal efficacy, with significant side effects and long term implications for quality of life and independence of elderly patients in particular. However, current data suggests that vaccination of patients between 50 and 59 is unlikely to be cost effective and should be reserved for older patients.

II. Diagnostic Confirmation: Are you sure your patient has Post-Herpetic Neuralgia?

The diagnosis of PHN is clinical. Confirmatory tests can be performed at the time of an initial zoster infection, including DFA for the herpes virus. However, after the initial infection, diagnosis is based on the symptoms and recent history of herpes zoster.

A. History Part I: Pattern Recognition:

A typical patient with PHN is an older patient, either male or female, with history of recent zoster infection, with a neuropathic pain syndrome in a dermatomal distribution, possibly with evidence of scarring from a recent rash. See Figure 1 and Figure 2 for a map of anterior and posterior dermatomes.

Figure 1.

Map of Anterior Dermatomes and Cutaneous Nerves

Figure 2.

Map of Posterior Dermatomes and Cutaneous Nerves

Key symptoms:

Neuropathic pain syndrome, including burning, anesthesia, and hypersensitivity/allodynia in distribution of prior herpes zoster infection, usually dermatomal.

Evidence of prior zoster, such as rash.

Dermatomal distribution, usually upper thoracic, cervical or trigeminal.

B. History Part 2: Prevalence:

Patients at higher risk for development of PHN are older, with more severe pain or rash associated with the initial infection. PHN occurs in fewer than 10% of patients overall, but at higher rates in patients over 60, with rates ranging from 15-40%.

Risk factors:

Age >50

Prodromal pain

More severe initial rash

More severe initial pain

Ophthalmic involvement

Cancer, especially lymphoproliferative*

Immunocompromise (HIV, high dose steroid use)*

*These two groups are more likely to get herpes zoster, but not more likely to get PHN once they get zoster.

C. History Part 3: Competing diagnoses that can mimic Post-Herpetic Neuralgia.

Radiculopathy - more radicular, more classic neuropathic pain syndrome.

Peripheral neuropathy, due to diabetes, B12 deficiency, hypothyroidism - more often peripheral neuropathy, less often on face or trunk.

D. Physical Examination Findings.

Skin exam:

Scarred dermatomal rash

Neurologic exam:

Cranial nerves:

Decreased visual acuity for V1 distribution zoster

Sensory:

Allodynia in dermatomal area

Anesthesia to cold, light touch, vibration in dermatomal area, and at times beyond

Distribution usually thoracic, cervical or trigeminal

E. What diagnostic tests should be performed?

None. Diagnosis is made clinically.

1. What laboratory studies (if any) should be ordered to help establish the diagnosis? How should the results be interpreted?

None. Diagnosis is made clinically.

2. What imaging studies (if any) should be ordered to help establish the diagnosis? How should the results be interpreted?

No radiologic imaging is necessary.

F. Over-utilized or “wasted” diagnostic tests associated with this diagnosis.

No need to check any virus antibodies or PCR.

III. Default Management.

Symptomatic treatment of PHN, with neuropathic pain medications as well as opioids.

A. Immediate management.

Pain control:

Multiple agents have some efficacy in pain management, but pain control is difficult. Overall, fewer than half of PHN patients will have a 50% reduction in pain with treatment. A combination approach can be beneficial, however, the side effects can also be additive, particularly in the elderly population. Classes of medication include TCAs (amitriptyline, nortriptyline), anti-epileptics (gabapentin), opiates, both short and long acting, and topical agents. There is no role for antiviral medication after PHN has already developed.

The best evidence supports TCAs (amitriptyline, nortriptyline) and antiepileptic agents (gabapentin, pregabalin), in conjunction with topical lidocaine or capsaicin. There is only anecdotal data behind topical agents, such as lidocaine and capsaicin. The evidence for opiates is unconvincing.

Recent trials of invasive interventions, such as nerve blocks, have not been shown to be effective.

See Table I for treatment options for PHN.

Table I.

Table I. Treatment Options for PHN
Treatment Options for PHN
Medication Initial/maximum dose
Amitriptyline 25 mg qhs/100 mg qhs
Gabapentin 300 mg TID, up to 1200 mg TID
Pregabilin 50 mg three times daily, up to 300 mg per day in 1 week/600 mg per day for non-responders
Oxycodone 5-10 mg q 6 hours
Lidoderm 1 patch as needed daily
Capsaicin 1 application TID

B. Physical Examination Tips to Guide Management.

None

C. Laboratory Tests to Monitor Response To, and Adjustments in, Management.

None

D. Long-term management.

Long term pain control is often necessary.

For patients who do not respond to conventional treatments, intrathecal glucocorticoids have shown benefit, and bupivacaine nerve blocks are also supported by minimal trials.

E. Common Pitfalls and Side-Effects of Management.

Adverse medication side effects are the most common pitfall, and development of chronic pain syndrome.

The adverse effects are usually related to sedation, ataxia, orthostasis, and constipation, with particular side effects associated with particular classes of drugs.

IV. Management with Co-Morbidities.

N/A

A. Renal Insufficiency.

Doses of gabapentin and pregabalin need to be adjusted by creatinine clearance.

B. Liver Insufficiency.

No change in standard management.

C. Systolic and Diastolic Heart Failure.

No change in standard management.

D. Coronary Artery Disease or Peripheral Vascular Disease.

No change in standard management.

E. Diabetes or other Endocrine issues.

No change in standard management.

F. Malignancy.

No change in standard management.

G. Immunosuppression (HIV, chronic steroids, etc.).

No change in standard management.

H. Primary Lung Disease (COPD, Asthma, ILD).

No change in standard management.

I. Gastrointestinal or Nutrition Issues.

No change in standard management.

J. Hematologic or Coagulation Issues.

No change in standard management.

K. Dementia or Psychiatric Illness/Treatment.

Caution needs to be used due to medication side effects, such as sedation and constipation from neurontin, opiates, and pregabalin.

V. Transitions of Care.

A. Sign-out considerations While Hospitalized.

Continue to adjust pain control, with discharge only after pain well controlled, given high risk of readmission with poor pain control.

B. Anticipated Length of Stay.

Dependent on severity of pain. Often not hospitalized except in cases of debilitating pain.

C. When is the Patient Ready for Discharge.

With adequate pain control.

D. Arranging for Clinic Follow-up.

Within 1 week of discharge for symptom check.

1. When should clinic follow up be arranged and with whom.

PCP follow up within 1 week. If necessary, referral to pain specialist might be helpful for complex pain syndromes.

2. What tests should be conducted prior to discharge to enable best clinic first visit.

None

3. What tests should be ordered as an outpatient prior to, or on the day of, the clinic visit.

None

E. Placement Considerations.

None

F. Prognosis and Patient Counseling.

Most PHN resolves after 6 months, but the range is reported as from 3 months to over 10 years. Symptom management with medications is often inadequate, and many patients can have significant decrease in their quality of life and independence as a result of the chronic pain.

VI. Patient Safety and Quality Measures.

A. Core Indicator Standards and Documentation.

None

B. Appropriate Prophylaxis and Other Measures to Prevent Readmission.

Zoster vaccination should be considered in patients with shingles or PHN to avoid recurrent episodes. The timing of the vaccination is not clear. Pain control and close monitoring of side effects of medications are the cornerstones of management and reductions in readmissions.

VII. What's the evidence?

Fashner, J, Bell, AL. "Herpes zoster and postherpetic neuralgia: prevention and management". American family physician,. vol. 83. 2011. pp. 1432-1437.

Gnann, JW, Whitley, RJ. "Clinical practice. Herpes zoster". N Engl J Med. vol. 347. 2002. pp. 340-346.

Johnson, RW, Bouhassira, D, Kassianos, G, Leplege. "The impact of herpes zoster and post-herpetic neuralgia on quality-of-life". BMC medicine. vol. 8. 2010. pp. 37.

Levin, MJ, Gershon, AA, Dworkin, RH, Brisson. "Prevention strategies for herpes zoster and post-herpetic neuralgia". Journal of clinical virology : the official publication of the Pan American Society for Clinical Virology. vol. 48. 2010. pp. S14-19.

Li, Q, Chen, N, Yang, J, Zhou, M. "Antiviral treatment for preventing post-herpetic neuralgia". Cochrane Database Syst Rev. 2009. pp. CD006866.

Watson, CP. "Herpes zoster and post-herpetic neuralgia". CMAJ : Canadian Medical Association journal = journal de l'Association medicale canadienne,. vol. 182. 2010. pp. 1713-1714.

Whitley, RJ. "A 70-year-old woman with shingles: review of herpes zoster". JAMA: the journal of the American Medical Association,. vol. 302. 2009. pp. 73-80.

Forbes, HJ. "A systematic review and meta-analysis of risk factors for postherpetic neuralgia". Pain. vol. 157. 2016 Jan. pp. 30-54.

(Updated risk factors.)

Bricout. "Herpes zoster-associated mortality in Europe: a systematic review". BMC Public Health. vol. 15. 2015 May. pp. 466.

(Provided information on mortality.)

McNicol, ED, Midbari, A, Eisenberg, E. "Opioids for neuropathic pain". Cochrane Database Syst Review. 2013. pp. CD006146.

(Updated treatment recommendations.)

Johnson, RW, Rice, AS. "Post Herpetic Neuralgia". N Engl J Med. vol. 371. 2014. pp. 1526-33.

(Overall review.)
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