Top 5 Things You Should Know About Herpes Zoster, also known as Shingles: How to Prevent Post Herpetic Neuralgia: What to Know about Herpes Zoster

How to Prevent Post Herpetic Neuralgia

Herpes Zoster  also known as zoster and shingles or HZV, is very common.  It can happen in young patients over the age of 40, but is rare to see Zoster in patients under the age of 40. In patients that are younger than 40, most physicians will do further blood work to see if there are any issues with the patient’s immune system. 

There are 5 key things to remember when you suspect Herpes Zoster.

1. Treat Zoster as soon as possible: MDs now treat Zoster with strong antivirals when a patient only has pain along a  “Dermatome” (an area of skin that is mainly supplied by a single spinal nerve): before any sign of vesicles, bumps, or pimples break outs on the skin. There is really no reason to wait unless the patient is at high risk from the anti-viral medication which is very rare. 

If you suspect it is Zoster, get to MD asap or go to Healthtap, a Virtual MD pratice I use (see bottom of this blog post to learn more about how to make a virtual appointment with an MD for an antiviral Rx) & ask the MD to prescribe the drugs noted on this blog post.


To schedule an appointment with me: 
 https://drcremers.com/2015/01/hsv-and-acyclovir-treating-recurrent.html

2. Start Gabapentin or the other meds discussed below to prevent Postherpetic Neuralgia (PNH) which is a dreaded complication of Zoster as it can cause long term pain which can sometimes be worse than the original Zoster.  The good news, is that there are very effective medications which work well to prevent PHN. Of note, research below is not clear if oral steroids really help with PHN. Most MDs prefer Gabapentin to prevent PHN as the risks, as long as it is tapered slowly, are very low, especially compared with oral steroids. 

3. If you have any eye pain or if the Zoster affects the tip of the nose, you should see an eyeMD as soon as possible. The eyeMD will look under the microscope to be sure there is no inflammation in the eye.

4. Depression is commonly associated with Zoster for multiple reasons. Do not be embarrassed if you need an oral antidepressant or extra help from friends. This will go away but it can take some time. 


5. For the pain of the actual area: ask for the following meds:
a. Capsaicin 0.025% (Zostrix) ointment 3x/d after rash heals
b. Qutenza patch: apply for 1 hour every 3 months

The below articles are the best articles on Zoster and PHN.


I hope this helps those with new onset Herpes Zoster.


Sandra Lora Cremers, MD, FACS



References:

1.
Postherpetic Neuralgia:

https://en.wikipedia.org/wiki/Postherpetic_neuralgia
Herpes zoster, also known as zoster and shingles, is caused by the reactivation of the varicella-zoster virus (VZV), the same virus that causes varicella (chickenpox).
Primary infection with VZV causes varicella. Once the illness resolves, the virus remains dormant (latent) in the dorsal root ganglia. VZV can reactive later in a person’s life and cause a painful, maculopapular rash called herpes zoster.
Anyone who has had varicella or gotten varicella vaccine can develop herpes zoster. Most people typically have only one episode of herpes zoster in their lifetime. However, second and even third episodes are possible.

Clinical Features

People with herpes zoster most commonly have a rash in one or two adjacent dermatomes (localized zoster). The rash most commonly appears on the trunk along a thoracic dermatome. The rash does not usually cross the body’s midline. However, approximately 20% of people have rash that overlaps adjacent dermatomes. Less commonly, the rash can be more widespread and affect three or more dermatomes. This condition is called disseminated zoster. This generally occurs only in people with compromised or suppressed immune systems. Disseminated zoster can be difficult to distinguish from varicella.
The rash is usually painful, itchy or tingly. These symptoms may precede rash onset by days to weeks. Some people may also have headache, photophobia (sensitivity to bright light), and malaise in the prodromal phase.
The rash develops into clusters of clear vesicles. New vesicles continue to form over three to five days and progressively dry and crust over. They usually heal in two to four weeks. There may be permanent pigmentation changes and scarring on the skin.

Complications

Postherpetic neuralgia (PHN) is the most common complication of herpes zoster. It is a persistent pain in the area where the rash once was. PHN is diagnosed in people who have pain that persists after their rash has resolved. Some define PHN as any duration of pain after the rash resolves; others define it as duration of pain for more than 30 days, or for more than 90 days after rash onset. PHN can last for weeks or months and occasionally, for many years.
A person’s risk of having PHN after herpes zoster increases with age. Older adults are more likely to have PHN and to have longer lasting and more severe pain. Approximately 13% (and possibly more) of people 60 years of age and older with herpes zoster will get PHN. PHN is rare in people younger than 40 years old. Other predictors of PHN include the level of pain a person has when they have the rash and the size of their rash.
Other complications of herpes zoster include—
  • ophthalmic involvement with acute or chronic ocular sequelae (herpes zoster ophthalmicus);
  • bacterial superinfection of the lesions, usually due to Staphylococcus aureus and, less commonly, due to group A beta hemolytic streptococcus;
  • cranial and peripheral nerve palsies; and
  • visceral involvement, such as meningoencephalitis, pneumonitis, hepatitis, and acute retinal necrosis.
People with compromised or suppressed immune systems are more likely to have complications from herpes zoster. They are more likely to have severe rash that lasts longer. Also, they are at increased risk of developing disseminated herpes zoster.

Vaccination

The Advisory Committee on Immunization Practices (ACIP) recommends zoster vaccine (Zostavax®) for people aged 60 years and older. Even people who have had herpes zoster should receive the vaccine to help prevent future occurrences of the disease.
Herpes zoster vaccine is approved by FDA for people aged 50 years and older. However, CDC does not recommend routine use of herpes zoster vaccine in people aged 50 through 59 years old. Health care providers considering the herpes zoster vaccine for certain persons aged 50 through 59 years should discuss the risks and benefits of vaccination with their patients. Although the vaccine has short-term efficacy, there have been no long-term studies of vaccine protection in this age group. In adults vaccinated at age 60 years or older, vaccine efficacy wanes within the first 5 years after vaccination, and protection beyond 5 years is uncertain; therefore, adults receiving the vaccine before age 60 years might not be protected when their risks for herpes zoster and its complications are highest.

Transmission

People with active lesions caused by herpes zoster can spread VZV to susceptible people. People who have not had varicella and never received chickenpox vaccine can get infected with VZV from someone with herpes zoster. If this happens, they are at risk of developing varicella not herpes zoster.
The virus spreads when a person has direct contact with the active herpes zoster lesions. The lesions are infectious until they dry and crust over. People with active herpes zoster lesions should avoid contact with susceptible people in their household and in occupational settings until their lesions dry and crusted.

Epidemiology

Risk Factors

Only people who had natural infection with wild-type VZV or had varicella vaccination can develop herpes zoster. Children who get the varicella vaccine appear to have a lower risk of herpes zoster compared with people who were infected with wild-type VZV. Many people do not remember having varicella; however, approximately 99.5% of people born in the United States who are 40 years of age and older have been infected with wild-type VZV. As a result, all older adults in the United States are at risk for herpes zoster.
The reasons why VZV reactivates and causes herpes zoster are not well understood. However, a person’s risk for herpes zoster may increase as their VZV-specific cell-mediated immunity declines. This decline in immunity can result from increasing age and/or medical conditions and medications that suppress the immune system.
A person’s risk for herpes zoster increases sharply after 50 years of age. Almost 1 out of 3 people in the United States will develop herpes zoster during their lifetime. A person’s risk of developing PHN also increases sharply with age. The risk of complications of herpes zoster, including PHN and hospitalization, also increases with age.
People with compromised or suppressed immune systems who have an increased risk for herpes zoster include those
  • with cancer, especially leukemia and lymphoma,
  • with human immunodeficiency virus,
  • who have undergone bone marrow or solid organ (renal, cardiac, liver, and lung) transplantation, or
  • who are taking immunosuppressive medications, including steroids, chemotherapy, or transplant-related immunosuppressive medications.
Other potential risk factors for herpes zoster have been identified but the findings are not consistent in all studies. For example-
  • Most, but not all, studies found that more women than men develop herpes zoster [1,2]; the reason for a possible difference between women and men is not known.
  • Some studies conducted in the United States and elsewhere found that herpes zoster is less common in blacks (by at least 50%) than in whites.[3]

Rates

  • Disease occurrence:
    • The incidence for herpes zoster is approximately 4 cases per 1,000 U.S. population annually, age-adjusted to the 2000 U.S. population
    • The incidence among people 60 years of age and older is about 10 cases per 1,000 U.S. population annually.
    • There are an estimated one million cases of herpes zoster in the United States annually.
  • Repeat episodes:
    • Although 2nd and even 3rd episodes of herpes zoster can occur, the annual incidence of recurrence is not known.
  • Hospitalizations:
    • Approximately 1 to 4% of people with herpes zoster get hospitalized for complications.
    • Older adults and people with compromised or suppressed immune systems are more likely to get hospitalized. About 30% of all people hospitalized with herpes zoster are those with compromised or suppressed immune systems.
  • Deaths:
    • A recent study estimated that there are 96 deaths each year in which herpes zoster was the actual underlying cause (0.28 to 0.69 per 1 million population). Almost all the deaths occurred in elderly people or those with compromised or suppressed immune systems. [4]

Trends

Herpes zoster rates are increasing among adults in the United States. The increase has been gradual over a long period of time. We do not know the reason for this increase.[5,6,7]
Some experts suggest that exposure to varicella boosts a person’s immunity to VZV and reduces the risk for VZV reactivation. Thus, they are concerned that routine childhood varicella vaccination, recommended in the United States in 1996, could lead to an increase in herpes zoster in adults due to reduced opportunities for being exposed to varicella. However, two CDC studies have found that herpes zoster rates:
  • started increasing before varicella vaccine was introduced in the United States, and
  • did not accelerate after the routine varicella vaccination program started.[5,8]
Other countries, that do not have routine varicella vaccination programs, have also observed similar increases in herpes zoster rates.[9]

Herpes Zoster in People Who Received Varicella Vaccine

Although uncommon among children, the rate of herpes zoster in U.S. children has been declining since the routine varicella vaccination program started. Varicella vaccine contains live attenuated VZV, which causes latent infection. The attenuated vaccine virus can reactivate and cause herpes zoster; however, children vaccinated against varicella appear to have a lower risk of herpes zoster than people who were infected with wild-type VZV.[10] The reason for this is that vaccinated children are less likely to become infected with wild-type VZV, and the risk of reactivation of vaccine-strain VZV is lower compared with reactivation of wild-type VZV.
  • In a study of children with leukemia, those who got varicella vaccine had a 67% lower risk of herpes zoster compared with children who had natural infection with wild-type VZV.[11]
  • Data on healthy children show a similar pattern of reduced risk of herpes zoster in those vaccinated against varicella.
  • The number of older adults who have gotten varicella vaccine since it was licensed in 1995 is quite small. There is very little information on the risk of herpes zoster in people who got varicella vaccine as adults.
CDC continues to study the epidemiology of herpes zoster among adults and children and to monitor the effects of the U.S. varicella and zoster vaccination programs.

References

  1. CDC. Prevention of herpes zoster: recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR Recomm Rep. 2008;57(05):1-30.
  2. Thomas SL, Hall AJ. What does epidemiology tell us about risk factors for herpes zoster? Lancet Infect Dis. 2004;4(1):26-33.
  3. Tseng HF, Smith N, Harpaz R, Bialek SR, Sy LS, Jacobsen SJ. Herpes zoster vaccine in older adults and the risk of subsequent herpes zoster disease.JAMA. 2011 Jan 12;305(2):160-6.
  4. Mahamud A, Marin M, Nickell SP, Shoemaker T, Zhang JX, Bialek SR. Herpes zoster-related deaths in the United States: validity of death certificates and mortality rates, 1979-2007. Clin Infect Dis.2012 Oct;55(7):960-6.
  5. Leung J, Harpaz R, Molinari NA, Jumaan A, Zhou F. Herpes zoster incidence among insured persons in the United States, 1993-2006: evaluation of impact of varicella vaccination. Clinical Infectious Diseases. 2011;52(3):332-340.
  6. Yih W, Brooks D, Lett S, Jumaan A, Zhang Z, Clements K, Seward J. The Incidence of varicella and herpes zoster in Massachusetts as measured by the Behavioral Risk Factor Surveillance System (BRFSS) during a period of increasing varicella vaccine coverage. BMC Public Health. 2005;5(68).
  7. Jumaan AO, Yu O, Jackson LA, Bohlke K, Galil K, Seward JF. Incidence of herpes zoster, before and after varicella vaccination-associated decreases in the incidence of varicella. Journal of Infectious Diseases. 2005;191:2002-7.
  8. Hales CM, Harpaz R, Joesoef MR, Bialek SR (2013). Examination of links between herpes zoster incidence and childhood varicella vaccination. Annals of Internal Medicine. 159(11):739-45
  9. Russell ML, Dover DC, Simmonds KA, Svenson LW. Shingles in Alberta: before and after publicly funded varicella vaccination. Vaccine. DOI 10.1016/j.vaccine.2013.09.018.
  10. Weinmann S, Chun C, Schmid DS, Roberts M, Vandermeer M, Riedlinger K, et al. Incidence and clinical characteristics of herpes zoster among children in the varicella vaccine era, 2005–2009. Journal of Infection Diseases. 2013;208(11):1859-68.
  11. Hardy I, Gershon AA, Steinberg SP, LaRussa P. The incidence of zoster after immunization with live attenuated varicella vaccine. A study in children with leukemia. Varicella Vaccine Collaborative Study Group. N Engl J Med. 1991;325(22):1545-50.


2. CDC:
http://www.cdc.gov/shingles/hcp/clinical-overview.html
Postherpetic neuralgia is a nerve pain due to damage caused by the varicella zoster virus. Typically, the neuralgia is confined to a dermatomic area of the skin, and follows an outbreak of herpes zoster (commonly known as shingles) in that same dermatomic area. The neuralgia typically begins when the herpes zoster vesicles have crusted over and begun to heal, but can begin in the absence of herpes zoster—a condition calledzoster sine herpete (see Herpes zoster).
Treatment options for postherpetic neuralgia include antidepressants, anticonvulsants (such as gabapentin, pregabalin, or topiramate), gabapentin enacarbil (a prodrug of gabapentin) and topical agents such as lidocaine patches or capsaicin lotion. Opioid analgesics may also be appropriate in many situations. There are some sporadically successful experimental treatments, such as rhizotomy (severing or damaging the affected nerve to relieve pain) and TENS (a type of electrical pulse therapy).
Contents
  • Symptoms:
  • With resolution of the herpes zoster eruption, pain that continues for three months or more is defined as postherpetic neuralgia.
  • Pain is variable, from discomfort to very severe, and may be described as burning, stabbing, or gnawing.

Signs:

  • Area of previous herpes zoster may show evidence of cutaneous scarring.
  • Sensation may be altered over the areas involved, in the form of either hypersensitivity or decreased sensation.
  • In rare cases, the patient might also experience muscle weakness, tremor, or paralysis if the nerves involved also control muscle movement.

Pathophysiology


Postherpetic neuralgia is thought to be nerve damage caused by herpes zoster. The damage causes nerves in the affected dermatomic area of the skin to send abnormal electrical signals to the brain. These signals may convey excruciating pain, and may persist or recur for months, years, or for life.[1]A key factor in the neural plasticity underlying neuropathic pain is altered gene expression in sensory dorsal root ganglia neurons. Injury to sensory nerves induces neurochemical, physiological and anatomical modifications to afferent and central neurons, such as afferent terminal sprouting and inhibitory interneuron loss.[1] Following nerve damage, NaCl channel accumulation causes hyperexcitability, and downregulation of the TTX-resistant Nav1.8 (sensory neuron specific, SNS1) channel and upregulation of TTX-sensitive Nav1.3 (brain type III) and TRPV1 channels. These changes contribute to increased NMDA glutamate receptor-dependent excitability of spinal dorsal horn neurons and are restricted to the ipsilateral (injured) side. A combination of these factors could contribute to the neuropathic pain state of postherpetic neuralgia.
Frequency[edit]In the United States each year approximately 1,000,000 individuals develop herpes zoster.[2] Of those individuals approximately 10-18% develop postherpetic neuralgia.[3]Less than 10 percent of people younger than 60 develop postherpetic neuralgia after a bout of herpes zoster, while about 40 percent of people older than 60 do.
Predisposing factors[edit]
  • Race: It may influence susceptibility to herpes zoster. African Americans are one fourth as likely as Caucasians to develop this condition.
  • Often an older, debilitated or immune compromised population.

Diagnosis[edit]Lab Studies:

  • No laboratory work is usually necessary.
  • Pleocytosis is observed in 46%, elevated protein in 26%, and VZV DNA in 22%.
  • These findings are not predictive of the clinical course of postherpetic neuralgia.
  • Viral culture or immunofluorescence 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:

  • Magnetic resonance imaging lesions attributable to herpes zoster were seen in the brain stem and cervical cord in 56% (9/16) of patients.
  • At three months after onset of herpes zoster, 56% (5/9) of patients with an abnormal magnetic resonance image had developed postherpetic neuralgia.
  • Of the seven patients who had no herpes-zoster-related lesions on the magnetic resonance image, none had residual pain.

Treatment[edit]Treatment for postherpetic neuralgia depends on the type and characteristics of pain experienced by the patient. Pain control is essential to quality patient care; it ensures patient comfort. Possible options include:

  • Antiviral agents, such as famciclovir, are given at the onset of attacks of herpes zoster to shorten the clinical course and to help prevent complications such as postherpetic neuralgia. However, they have no role to play following the acute attack once postherpetic neuralgia has become established.
  • Aspirin mixed into an appropriate solvent such as diethyl ether may reduce pain.[4]
  • Lidocaine skin patches. These are small, bandage-like patches that contain the topical, pain-relieving medication lidocaine. The patches, available by prescription, must be applied directly to painful skin and deliver relief for four to 12 hours. Patches containing lidocaine can also be used on the face, taking care to avoid mucus membranes e.g., the eyes, nose and mouth.
  • Systemically delivered
  • Opioids provide more potent pain control and the weaker members such as codeine may be available over the counter in combination with paracetamol (co-codamol). Other opioids are prescription-only and include higher dosages of codeine, tramadol, morphine or fentanyl. Most opioids have sedating properties, which are beneficial for patients who experience pain.
  • Pain modification therapy
  • Anticonvulsants. These agents are used to manage severe muscle spasms and provide sedation in neuralgia. They have central effects on pain modulation. Medications such asphenytoin (Dilantin, Phenytek), used to treat seizures, also can lessen the pain associated with postherpetic neuralgia. The medications stabilize abnormal electrical activity in the nervous system caused by injured nerves. Doctors often prescribe another anticonvulsant called carbamazepine (Carbatrol, Tegretol) for sharp, jabbing pain. Newer anticonvulsants, such as gabapentin (Neurontin) and lamotrigine (Lamictal), are generally tolerated better and can help control burning and pain.
  • gabapentin enacarbil (HORIZANT), an alpha-2-delta-1 ligand and a prodrug of gabapentin, was approved by the FDA in 2012 for the management of postherpetic neuralgia.
  • Other non-pharmacological treatments for postherpetic neuralgia include the following:
  • Cold therapy. Cold packs can be used.
  • Spinal cord stimulator. The electrical stimulation of the posterior spinal cord works by activating supraspinal and spinal inhibitory pain mechanisms.[7]

In some cases, treatment of postherpetic neuralgia brings complete pain relief. But most people still experience some pain, and a few do not receive any relief. Although some people must live with postherpetic neuralgia the rest of their lives, most people can expect the condition to gradually disappear on its own within five years.
Prognosis[edit]The natural history of postherpetic neuralgia involves slow resolution of the pain syndrome. Most people who develop postherpetic neuralgia respond to agents such as tricyclic antidepressants. A subgroup of affected individuals may develop severe, long-lasting pain that does not respond to medical therapy.
Prevention[edit]Primary prevention[edit]In 1995, the Food and Drug Administration (FDA) approved the Varicella vaccine to prevent chickenpox. Its effect on postherpetic neuralgia is still unknown. The vaccine—made from a weakened form of the varicella-zoster virus—may keep chickenpox from occurring in nonimmune children and adults, or at least lessen the risk of the chickenpox virus lying dormant in the body and reactivating later as shingles. If shingles could be prevented, postherpetic neuralgia could be completely avoided.
In May 2006 the Advisory Committee on Immunization Practices approved a new vaccine by Merck (Zostavax) against shingles. This vaccine is a more potent version of the chickenpox vaccine, and evidence shows that it reduces the incidence of postherpetic neuralgia.[8] The CDC recommends use of this vaccine in all persons over 60 years old.[9]Secondary prevention[edit]An April 2013 Cochrane Collaboration meta-analysis of 6 randomized controlled trials (RCTs) investigating oral antiviral medications given within 72 hours after the onset of herpes zoster rash in immunocompetent people for preventing postherpetic neuralgia (PHN) found no significant difference between placebo and acyclovir. Combining four RCTs, 44.1% of the acyclovir treatment group developed herpetic neuralgia whereas 53.3% of the placebo group developed herpetic neuralgia. Heterogeneity between the four RCTs was moderate: Chi2 =3.36, df = 2 (P=0.19); I2 = 40%. Additionally, there was no significant difference in preventing the incidence of PHN found in the one RCT included in the meta-analysis that compared placebo to PO famciclovir treatment within 72 hours of HZ rash onset. Studies using valaciclovir treatment were not included in the meta-analysis. PHN was defined as pain at the site of the dermatomic rash at 120 days after the onset of rash, and incidence was evaluated at 1, 4, and 6 months after rash onset. There was a slight reduction in the incidence of pain at 4 weeks after the onset of rash in the aciclovir group (153 study participants with pain out of 347 study participants in the aciclovir group) versus the placebo group (184 study participants with pain out of 345 study participants in the placebo group). Patients who are prescribed PO antiviral agents after the onset of rash should be informed that their chances of developing PHN are no different than those not taking PO antiviral agents.[10]A randomized controlled trial found that amitriptyline 25 mg per night for 90 days starting within two days of onset of rash can reduce the incidence of postherpetic neuralgia from 35% to 16% (number needed to treat is 6).[11]Research directions[edit]

References[edit]

  1. ^ 
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  1. a b Gharibo, Christopher; Kim, Carolyn (December 2011). “Neuropathic Pain of Postherpetic Neuralgia” (PDF). Pain Medicine News. McMahon Publishing. Retrieved 6 October 2014.
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  1. ^ Brian J. Hall, John C. Hall. “Infectious diseases in the skin”. Sauer’s Manual of Skin Diseases. Lippincott Williams & Wilkins, 2010. p. 232.
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  1. ^ Weaver, B A (2009). “Herpes zoster overview: natural history and incidence.” (PDF). J Am Osteopath Assoc 109 (6 (Suppl 2)): S2–6. PMID  Retrieved 6 October 2014.
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  1. ^ De Benedittis G, Besana F, Lorenzetti A (1992). “A new topical treatment for acute herpetic neuralgia and post-herpetic neuralgia: the aspirin/diethyl ether mixture. An open-label study plus a double-blind controlled clinical trial”. Pain 48 (3): 383–90. doi:
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  1. ^ Chen N, Yang M, He L, Zhang D, Zhou M, Zhu C (2010). He, Li, ed. “Corticosteroids for preventing postherpetic neuralgia”. Cochrane Database Syst Rev (12): CD005582.doi:.
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  1. ^ Doble S (2008). “Spinal Management of patients with post-herpetic neuralgia”. Nursing Standard22 (39): 49–56.
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  1. ^ Harke H, Gretenkort P, Ladleif HU, Koester P, Rahman S (2002). “Spinal cord stimulation in postherpetic neuralgia and in acute herpes zoster pain”. Anesthesia & Analgesia 94 (3): 694–700.doi:
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  1. ^ Chen N, Li Q, Zhang Y, Zhou M, Zhou D, He L (2011). He, Li, ed. “Vaccination for preventing postherpetic neuralgia”. Cochrane Database Syst Rev (3): CD007795
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  1. ^ Chen N, Li Q, Yang J et al. (2014). He, Li, ed. “Antiviral treatment for preventing postherpetic neuralgia”. Cochrane Database Syst Rev 2 (2): CD006866.doi:
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  1. ^ Bowsher D (1997). “The effects of pre-emptive treatment of postherpetic neuralgia with amitriptyline: a randomized, double-blind, placebo-controlled trial”. Journal of pain and symptom management 13 (6): 327–31. 
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  1. ^ Bernstein, L.R. (2013). “Gallium, therapeutic effects” (PDF). In Kretsinger, R.H.; Uversky, V.N.; Permyakov, E.A. Encyclopedia of Metalloproteins. New York: Springer. pp. 823–835. ISBN 978-1-4614-1532-9.



3. Cochrane Database Syst Rev. 
2014 Feb 6;2:

Antiviral treatment for preventing postherpetic neuralgia.

Chen N1, Li Q, Yang J, Zhou M, Zhou D, He L

Abstract

BACKGROUND:

Postherpetic neuralgia (PHN) is a painful and refractory complication of herpes zoster. Treatments are either partially or totally ineffective for many people with PHN. Antiviral agents, used at the time of the rash, have been proposed as an intervention to prevent the development of PHN. This is the first update since the first publication of the review in 2009.

OBJECTIVES:

To assess the effectiveness of antiviral agents in preventing PHN.

SEARCH METHODS:

On 26 April 2013, we updated the searches in the Cochrane Neuromuscular Disease Group Specialized Register, CENTRAL, MEDLINE, EMBASE, LILACS, and the Chinese Biomedical Retrieval System. We checked the references of published studies to identify additional trials, and contacted authors to obtain additional data. We searched other databases in The Cochrane Library for information for the Discussion and two clinical trials registries for ongoing trials.

SELECTION CRITERIA:

We considered all randomised controlled trials (RCTs) of antiviral treatment given within 72 hours after the onset of herpes zoster for preventing PHN. There were no language restrictions.

DATA COLLECTION AND ANALYSIS:

Two authors independently selected trials, evaluated the risk of bias in included trials, and extracted and analysed data.

MAIN RESULTS:

Six RCTs with a total of 1211 participants were eligible; five trials evaluated oral aciclovir, and one, with 419 participants, evaluated oral famciclovir. We were able to conduct meta-analyses as there were sufficient similarities in the included studies, such as the reporting of the presence of PHN, duration of rash before treatment initiation and treatment regimen. For our primary outcome, based on three trials (609 participants) we found no significant difference between the aciclovir and control groups in the incidence of PHN four months after the onset of the acute herpetic rash (risk ratio (RR) 0.75, 95% confidence interval (CI) 0.51 to 1.11), nor was there a significant difference at six months (RR 1.05, 95% CI 0.87 to 1.27, two trials, 476 participants). In four of the trials (692 participants), there was some evidence for a reduction in the incidence of pain four weeks after the onset of rash. In the trial of famciclovir versus placebo, neither 500 mg nor 750 mg doses of famciclovir reduced the incidence of herpetic neuralgia significantly. The most commonly reported adverse events were nausea, vomiting, diarrhoea and headache for aciclovir, and headache and nausea for famciclovir. For neither treatment was the incidence of adverse events significantly different from placebo. None of the studies were at high risk of bias, although the risk of bias was unclear in at least one domain for all but one study. We found no new RCTs when we updated the searches in April 2013.

AUTHORS’ CONCLUSIONS:

There is high quality evidence that oral aciclovir does not reduce the incidence of PHN significantly. In addition, there is insufficient evidence to determine the effect of other antiviral treatments; therefore, further well-designed RCTs are needed to investigate famciclovir or other new antiviral agents in preventing PHN. Future trials should pay more attention to the severity of pain and quality of life of participants, and should be conducted among different subgroups of people, such as people who are immunocompromised.

4.  
2013 Mar 28;3:


Corticosteroids for preventing postherpetic neuralgia.

Han Y1, Zhang J, Chen N, He L, Zhou M, Zhu C.


Abstract


BACKGROUND:

Postherpetic neuralgia is a common, serious painful complication of herpes zoster. Corticosteroids are anti-inflammatory and might be beneficial. This is an update of a review first published in 2008 and previously updated in 2010.


OBJECTIVES:

To examine the efficacy of corticosteroids in preventing postherpetic neuralgia.


SEARCH METHODS:

We updated the searches for randomised controlled trials (RCTs) of corticosteroids for preventing postherpetic neuralgia in the Cochrane Neuromuscular Disease Group Specialized Register (16 April 2012), CENTRAL (2012, Issue 3), MEDLINE (January 1966 to April 2012), EMBASE (January 1980 to April 2012), LILACS (January 1982 to April 2012), and the Chinese Biomedical Retrieval System (1978 to 2012). We also reviewed the bibliographies of identified trials, contacted authors and approached pharmaceutical companies to identify additional published or unpublished data.


SELECTION CRITERIA:

We included all RCTs involving corticosteroids given by oral, intramuscular, or intravenous routes for people of all ages with herpes zoster of all degrees of severity within seven days after onset, compared with no treatment or placebo but not with other treatments. We did not include quasi-RCTs (trials in which a systematic method of randomisation such as alternation or hospital number was used).


DATA COLLECTION AND ANALYSIS:

Two authors identified potential articles, extracted data, and independently assessed the risk of bias of each trial. Disagreement was resolved by discussion among the co-authors.


MAIN RESULTS:

Five trials were included with 787 participants in total. All were randomised, double-blind, placebo-controlled parallel-group studies. We conducted a meta-analysis of two trials (114 participants) and the results gave moderate quality evidence that oral corticosteroids did not prevent postherpetic neuralgia six months after the onset of herpes (RR 0.95, 95% CI 0.45 to 1.99). One of these trials was at high risk of bias because of incomplete outcome data, the other was at low risk of bias overall. The three other trials that fulfilled our inclusion criteria were not included in the meta-analysis because the outcomes were reported at less than one month or not in sufficient detail to add to the meta-analysis. These three trials were generally at low risk of bias. Adverse events during or within two weeks after stopping treatment were reported in all five included trials. There were no significant differences in serious or non-serious adverse events between the corticosteroid and placebo groups. There was also no significant difference between the treatment groups and placebo groups in other secondary outcome analyses and subgroup analyses. The review was first published in 2008 and no new RCTs were identified for inclusion in subsequent updates in 2010 and 2012.


AUTHORS’ CONCLUSIONS:

There is moderate quality evidence that corticosteroids given acutely during zoster infection are ineffective in preventing postherpetic neuralgia. In people with acute herpes zoster the risks of administration of corticosteroids do not appear to be greater than with placebo, based on moderate quality evidence. Corticosteroids have been recommended to relieve the zoster-associated pain in the acute phase of disease. If further research is designed to evaluate the efficacy of corticosteroids for herpes zoster, long-term follow-up should be included to observe their effect on the transition from acute pain to postherpetic neuralgia. Future trials should include measurements of function and quality of life.

5. http://www.medscape.com/viewarticle/736969


Acute Administration of Gabapentin Can Prevent Postherpetic Neuralgia

Fran Lowry

February 07, 2011

February 7, 2011 (New Orleans, Louisiana) — Acute administration of gabapentin reduces the incidence of postherpetic neuralgia (PHN), and might even prevent it from developing if administered when the first herpes zoster vesicle appears, according to research presented during a late-breaking abstract session here at the American Academy of Dermatology 69th Annual Meeting.
The US Food and Drug Administration approved gabapentin for the treatment of PHN last week.
“Postherpetic neuralgia is very, very difficult to treat once it’s in place. In some cases, it can last for the patient’s entire life,” Whitney Lapolla, MD, from the Center for Clinical Studies in Houston, Texas, toldMedscape Medical News. “We wanted to study something that would be more of a preventive measure than a treatment for PHN, because once it develops, nothing really works very well.”
Current available treatments include tricyclic antidepressants, anticonvulsants, and a variety of systemic and topical analgesics, but the result is very poor symptom control, she added.
Several animal studies have suggested that gabapentin is more effective when given acutely than after PHN develops, Dr. Lapolla noted.
“We think that gabapentin prevents neuronal sensitization from occurring, although the mechanism is not completely clear,” she said.
In this open-label prospective study, she and her coinvestigators added gabapentin to valacyclovir in 133 patients presenting to their clinic within 72 hours of the appearance of the first herpes zoster vesicle. Patients were followed to see how many complained of PHN at 3, 4, and 6 months.
The patients were 50 years or older (mean age, 64.6 years) and had a self-rated pain level of at least 4 on a 10-point Likert scale, where 0 equals no pain and 10 equals the worst pain imaginable. Of these, 38% presented with moderate pain (4 to 6 on the Likert scale), and 62% presented with severe pain (7 to 10 on the Likert scale).
All patients received valacyclovir 1000 mg 3 times a day plus gabapentin at a starting dose of 300 mg daily.
The dose of gabapentin was titrated up weekly to a maximum of 1200 mg 3 times a day, as tolerable.
“Dizziness can be a problem, so it is important to titrate the dose carefully. The dizziness usually goes away, but . . . [patients who are] dizzy definitely will not want to use it. We prefer to go slow and to titrate up to the maximum tolerated dose,” Dr. Lapolla noted.
Patients were seen weekly and then at 3, 4, and 6 months. At each visit, they were assessed for rash healing and pain, and were given several quality of life surveys, including the Short Form 36, a survey of sleep disturbance, and a survey about their use of supplementary analgesics.
At the 4-week mark, if patients reported a pain score of 4 or more, they were continued on gabapentin for another 4 weeks. If their pain was less than 4, they were titrated down. “No patient received gabapentin beyond 8 weeks because we wanted to see what the long-term effects on pain would be,” Dr. Lapolla said.
The researchers found that the proportion of patients reporting pain decreased steadily. At 3 months, 20% of patients had pain; at 4 months, 18% had pain; and at 6 months, 9.8% had pain.
These results are superior to those reported in a meta-analysis on the management of PHN, Dr. Lapolla said.
“Our proportion of patients who still had pain at 6 months with this regimen was lower than every single study we found,” she said.
“All physicians who have patients with acute shingles should begin gabapentin immediately in addition to the antiviral, because, as we have shown, it is beneficial,” she concluded.
Commenting on this study for Medscape Medical News, Richard L. Gallo, MD, PhD, professor and chief of dermatology at the University of California at San Diego, said that the data from this study are encouraging.
“Managing postherpetic neuralgia is a very big problem for clinicians and dermatologists. Her data were, I think, supportive of other studies that suggest that this simultaneous use of gabapentin and an antiviral within the first 72 hours of onset of lesions can be helpful,” said Dr. Gallo, who moderated the session. He was not part of the study.
Valacyclovir was provided by GlaxoSmithKline. Dr. Lapolla reports that she has financial relationships with NeurogesX and Inhibitex. Dr. Gallo reports financial relationships with Allergan, Ceregenex, Galderma, Inimex, Intendis, Johnson and Johnson, Novartis, and Skin Epibiotics.
American Academy of Dermatology (AAD) 69th Annual Meeting. Presented February 5, 2011.




6. August 2011, Vol 147, No. 8 >


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Practice Gaps | Aug 2011

Prevent Rather Than Treat Postherpetic Neuralgia by Prescribing Gabapentin Earlier in Patients With Herpes ZosterComment on “Incidence of Postherpetic Neuralgia After Combination Treatment With Gabapentin and Valacyclovir in Patients With Acute Herpes Zoster ”

Clayton B. Green, MD, PhD; Erik J. Stratman, MD
Arch Dermatol. 2011;147(8):908. doi:10.1001/archdermatol.2011.199.
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The article by Lapolla et al1 demonstrates important practice gaps in the management of acute herpes zoster and the prevention of postherpetic neuralgia (PHN). Dermatologists vary in the approach to treating acute herpes zoster, including the selection of antiviral agents, the decision to use concurrent prednisone, and the timing and role of gabapentin therapy. Antiviral agents, including acyclovir, valacyclovir, and famciclovir, are the mainstay of treatment for acute herpes zoster in the United States. There is good evidence to support the use of each of these antiviral agents alone or in combination with prednisone to reduce the pain of acute herpes zoster.2 There is conflicting evidence for the utility of antiviral agents in preventing PHN, and recent meta-analyses did not support the use of prednisone or acyclovir in preventing PHN.3,4 There were insufficient data to conclude whether the use of famciclovir or valacyclovir reduced the incidence of PHN.4 The study by Lapolla and colleagues presents data regarding gabapentin therapy and PHN in patients with acute herpes zoster and provides convincing evidence that the use of gabapentin combined with valacyclovir during an episode of acute herpes zoster reduces the rates of PHN. The authors’ careful selection of the study patients, as well as strict disease and end point definitions, makes this study practically applicable to routine clinical practice. Based on the study results, we recommend that dermatologists begin prescribing gabapentin in addition to antiviral agents in healthy patients with acute herpes zoster who are older than 50 years and have pain scores higher than 4 out of 10.









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