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Shingles and Postherpetic Neuralgia

Shingles is a common, unpleasant condition characterized by localized rash and pain caused by the same virus that causes chickenpox. Shingles occurs in roughly 20% of the general population regardless of race, gender, or time of year. It is more common with age: 50% of cases occur in people over 50 (Beydoun 1999), and up to 50% of those who live to be 80 will experience shingles. Its most feared consequence is postherpetic neuralgia (PHN)--chronic pain that persists after the outbreak of the rash has been put into remission.

This protocol will give suggestions to help stop a shingles outbreak in its tracks and minimize the risk of PHN, as well as explain other complications, the cause of shingles and its symptoms, conventional medical treatments, and helpful nutritional supplements.

CauSE

Shingles is caused by a reactivation of the varicella zoster virus (VZV), also known as human herpes virus-3 (HHV-3). This virus is related to herpes simplex viruses types 1 and 2. It is a relatively fragile virus susceptible to disinfectants such as alcohol and hypochlorite. Initial infection with VZV results in chickenpox (varicella). Despite recovery from this illness, the virus lies dormant in the sensory nerve roots of the spinal cord for years or decades until it becomes active again and is then classified as herpes zoster. The condition is then diagnosed as shingles. It is not known why the virus becomes active again, but age-associated immune dysfunction or any other compromise of immune function is highly suspect.

Thus, all people who have ever had chickenpox (nine of 10 adults) are at risk for developing shingles. Shingles arises from viruses that are already within the body and is not caught from someone else. Someone who has never had chickenpox has a low risk of contracting that illness from close contact with the shingles rash (vesicles containing virus). VZV infection typically occurs through inhalation of virus particles. Chickenpox is highly contagious because in that disease virus is shed from the throat into the air that others breathe. Because this does not occur in shingles, it is not very contagious and normal hand-washing minimizes the risk. A second attack of shingles is very unusual and may signal an underlying immune disorder. Herpes simplex infection, which does recur, can also be misdiagnosed as shingles.

SymptoMS

Shingles has two primary symptoms: rash and pain. More generalized symptoms include enlarged, tender lymph nodes draining the affected area and occasional mild malaise (fatigue).

Rash
The affected area is red with small vesicles or blisters. Unlike the "dew drop on a rose petal" appearance of chickenpox, several blisters per area are common in shingles. New lesions may occur for up to 1 week, after which the rash shows signs of healing. In severe cases, lesions may grow together, yielding a carpet of scabs and sometimes permanent scars. Overall, the rash usually lasts 2-5 weeks.

Pain
Pain in the area in which the rash will appear may precede the rash, known as prodromal pain, sometimes by a few days. The area often becomes flushed and unusually, sometimes unbearably, sensitive to pain. This is known as allodynia. The appearance of the rash often heralds a decrease in pain.

Shingles symptoms usually correspond to the skin area or dermatome supplied by the affected sensory nerve roots. The dermatome most commonly involved is the thoracic (trunk, palms, inner arms, legs, and feet), followed by the trigeminal (face). Cervical (back of head, neck, shoulders, outer arms, and backs of hands), lumbar (waist, front of legs, and tops of feet), and sacral (buttocks, backs of legs, and soles of feet) dermatomes may also be affected. About 16% of shingles sufferers have more widespread rash.

ComplicatioNS

Postherpetic Neuralgia (PHN)
Pain that persists more than 30 days after the appearance of the rash is the most feared consequence of herpes zoster. The burning or stabbing pain of PHN is attributed to virus-induced damage to the nerve roots. General risk factors include anything that compromises the immune system such as age, illness, immune system disorders, certain cancers (especially those that affect the lymph or immune system), and medications that affect the immune system. More specifically, PHN has been linked to the following four factors:

  • Age, which increases the likelihood and severity of PHN; people over 50 have about a 50% chance of having PHN.
  • Prodromal (prerash) pain.
  • Severe acute (with rash) pain.
  • Failure to obtain adequate antiviral treatment within 3 days of the appearance of the rash.

Secondary Infection
Shingles lesions usually dry quickly and heal well. However, secondary infection can occur, resulting in redness and swelling and often leading to scarring. Staphylococcus aureus is a common cause and may require consultation with a microbiologist because of problems with resistance.

Paralysis of the Affected Area
Some degree of motor paralysis is not uncommon, but is not very evident on the trunk as opposed to the face or limbs. It occurs from extension of the disease to the motor regions of the spinal cord or brainstem. Weakness follows the rash by a few days or weeks. About 55% of those affected make a complete recovery; 30% of those remaining show significant improvement.

Ramsay-Hunt Syndrome
This syndrome has a well-known association with shingles. Its symptoms are pain in the middle ear; blistering of the external ear canal, pinna, and throat; and loss of taste (reflecting the involvement of the nerve supply to the tongue). Complete recovery is usual, although it may take months; in some cases a residual deficit may remain.

Meningoencephalitis
This very rare inflammation of the brain, despite the severity of symptoms such as coma, normally resolves completely.

Recurrent or Disseminated Herpes Zoster
Shingles is 9 times more likely to develop in those infected with HIV. In the early stages of HIV infection, shingles symptoms are fairly typical (Wilkerson et al. 1987). In more advanced infection, herpes zoster may take the form of repeated episodes of severe, prolonged, and sometimes atypical (VZV retinitis) disease. Shingles is also more common in immunocompromised children and adults (including organ recipients and chemotherapy patients). In these patients it may be recurrent and may disseminate or spread cutaneously (on the skin) or viscerally (among the organs), with life-threatening consequences necessitating intravenous antiviral drugs.

Standard Shingles TreatmeNT

The standard treatment of shingles uses two types of drugs, analgesics (pain relievers), and antiviral agents, which reflect its two goals.

Resolve Pain Rapidly
Severe pain can predispose patients to PHN by permanently sensitizing nerves to even the mildest stimulation. Therefore, aggressive pain relief with paracetamol (codeine plus acetaminophen) is advised; some patients require opioids such as morphine. The goal is to reduce pain to a level compatible with daily activities and to have the patient confirm that the level of relief is satisfactory.

Stop Virus Replication
Antiviral drugs stop the virus from reproducing itself, thereby minimizing the damage it does to nerve cells. Three antiviral drugs are currently in use. Acyclovir is the standard and has proven effective in accelerating pain resolution. Valacivclovir has been shown to be about a third faster in resolving pain than acyclovir. Famciclovir does not appear to offer a significant advantage over acyclovir.

Older studies with a limited number of patients have indicated that oral corticosteroids (prednisone, triamcinolone) might decrease the likelihood of PHN. An article in the New England Journal of Medicine reported a slight benefit of these drugs in decreasing the severity of acute herpes zoster, but no long-term effects (Wood et al. 1994). A 1996 article by Whitley et al. in the Annals of Internal Medicine agreed, but found that oral corticosteroids may benefit quality of life. In general, the side effects of steroid therapy are felt to outweigh the benefits, although it may be considered in patients over 50 who have no contraindications.

The rash may be treated with bland protective creams like zinc oxide. Calamine lotion may provide cooling comfort.

Cimetidine
Herpes simplex outbreaks have been shown to go into remission in response to the proper dose of cimetidine. In cases of herpes zoster (shingles), which targets the older population, cimetidine has been successfully used to lessen the debilitating pain and intensity of the skin rash and eruptions. Published studies indicate that viruses like herpes simplex and herpes zoster can be put into quick remission, or the breakouts prevented altogether, when T-lymphocyte suppressor cell function is inhibited. The best way of accomplishing this is to take 200 mg of cimetidine (Tagamet), 3 times a day, and then 400 mg at bedtime. Tagamet is available in pharmacies over-the-counter. Suggested use is to initiate Tagamet as soon as symptoms of a herpes-related virus infection appear. Continue to take it for 1-2 weeks after all symptoms of the outbreak have abated.

Various studies support the use of cimetidine in suppressing herpes infections. The first case observation occurred in August 1977, when a patient developed shingles just before commencing a course of cimetidine for a chronic stomach ulcer. The patient experienced dramatic relief of the shingles pain and rapid disappearance of the eruption. On the basis of this observation, cimetidine was prescribed to 21 patients with herpes zoster (shingles). The results were encouraging in 18 of these 21 patients. The trial was then extended to other herpes virus infections. In six of seven patients with herpes labialis (lip), the blisters were aborted, and in one patient with herpes keratitis (cornea), the result was also encouraging, with the attacks being markedly shortened in duration and reduced in frequency. The results of these preliminary trials showed the potential role of cimetidine in the treatment of herpes virus infection ( Van der Spuy et al. 1980 ).

In 1996, a clinical trial was conducted on 221 patients with herpes zoster who were treated daily with cimetidine at 200 mg, 3 times during the day and 400 mg at night. The results showed that cimetidine shortened the period of disease duration. The authors suggested using cimetidine in the treatment of shingles during the earliest stages of the disease ( Kapinska-Mrowiecka et al. 1996 ).

A case reported in Canada resulted in the statement that cimetidine therapy appeared to reduce the expected length of the active phase of herpes zoster from 35 days or more to just 10 days (Hayne et al. 1983). At the Golda Medical Center in Israel, in 1994, a double-blind, placebo-control study of cimetidine treatment versus placebo was conducted for 1 week in 22 patients with herpes zoster. Those who were treated with cimetidine were found to recover much more quickly from skin rash and pain than those who were given the placebo ( Komlos et al. 1994 ).

At the Department of Neurology at Lady Davis Carmel Hospital in Israel, a randomized study evaluated the effect of cimetidine in the treatment of herpes zoster virus. The conclusion was that cimetidine treatment "shortened the median interval until the first decrease in pain, shortened the median interval until the complete resolution of pain, and promoted faster complete healing of skin lesions" ( Miller et al. 1989 ).

A paper presented by a researcher at Michigan State University in the Department of Pediatrics and Human Development (Kumar 1990) stated:

  • Suppressor T lymphocytes possess histamine 2 (H2) receptors and contribute significantly to the function of the immune system. Cimetidine has been shown to enhance a variety of immunologic functions both in vivo and in vitro because of its inhibitory effects on suppressor-cell function. Successful tumor immunotherapy has been reported in experimental animals. Patients who received cimetidine were shown to exhibit enhanced cell-mediated immunity as evaluated by increased response to skin-test antigens, restoration of sensitivity following development of acquired tolerance, and increased responses of lymphocytes to mitogen stimulation. Patients also demonstrated that patients with herpes zoster and herpes simplex who were given cimetidine may have benefitted therapeutically from the drug.

The consensus from these studies is that when cimetidine is administered to those with herpes simplex or shingles, the result is a dramatic relief of the herpetic pain as well as rapid disappearance of the blisters.

Neuralgia TreatmeNT

Tricyclics
The first line of PHN (postherpetic neuralgia) treatment is tricyclic antidepressants. In PHN, these drugs act as analgesics, not antidepressants. Therapy begins at doses lower than required for antidepressant activity, with stepwise increases. Their mechanism of action is unclear. They block reuptake of monoamine neurotransmitters (norepinephrine and/or serotonin) and may act on descending systems from the brainstem. Amitriptyline (Elavil), which affects both transmitters, is most effective, but nortriptyline, which works only on norepinephrine, has fewer side effects (dry mouth, constipation, drowsiness). Tricyclics are effective in 60-70% of patients. They decrease the intensity of pain but do not relieve it. Therapy should not end until 3-6 months after pain reduction, and then should be decreased gradually. Some shingles patients, however, may choose to end tricyclic drug therapy early because of unpleasant side effects.

Anticonvulsants and Phenothiazines
Although these drugs have been used for certain types of PHN pain, there has been little research evidence to support their effectiveness. Gabapentin (Neurontin), a structural gamma-aminobutyric acid (GABA) analogue, which is approved as an anticonvulsant, but is chemically unrelated to any other mood-regulating or anticonvulsant medication, has been shown to be efficacious and safe at reducing pain levels in patients with PHN and other disorders (Beydoun 1999; Block 2001; Alper et al. 2002). In a multicenter double-blind, randomized, placebo-controlled 7-week study, gabapentin was shown to reduce pain scores, and a number of patients reported significant reduction of over 50% in a variety of pain scores. Gabapentin was used in divided doses of 1800 and 2400 mg a day in this study (Rice et al. 2001).

Opioids
Opioids can be used to manage PHN pain, although there is debate over whether PHN pain responds to opioids. Several studies indicate relief from pain for patients using opioids. A study done with controlled-release oxycodone showed it to be an effective analgesic for the type of pain that characterizes postherpetic neuralgia (Watson et al. 1998). Another study with several modalities of treatment, including opioids, showed that the success of the treatment was dependent upon the history of pain being less than 1 month. The majority of those patients showed good to excellent results, whereas only a third of the patients with a history longer than 6 months had adequate relief. The authors concluded that early and appropriate treatment is desirable for patients who have zoster neuralgias (Wulf et al. 1991). Another study indicated opioids given intravenously can be beneficial for pain (but likely very inconvenient for the patient) (Rowbotham et al. 1991).

Topical Therapies
Topical skin creams offer the benefit of massage as well as direct pain relief. Silvadene, Aspercreme, and capsaicin creams may supply some pain relief, although capsaicin must be used 3 to 4 times a day for several weeks to achieve relief. A benefit of using capsaicin is the lack of drug interactions. Capsaicin has been shown to reduce the pain in PHN patients by as much as 80% in studies from 1987 to present (Bernstein 1987; Bernstein et al. 1987, 1989; Watson et al. 1988; Carmichael 1991; Peikert et al. 1991). In one study of 17 patients, 11 reported more pain and allodynia after use (Petersen et al. 2000). Wearing light cotton fabric or using plastic "artificial skin" sprays can minimize tactile allodynia caused by clothing. Cold packs applied over a cotton towel may also be helpful.

Psychological Interventions
These therapies that can be useful in any chronic pain syndrome include counseling, cognitive behavior modification, relaxation training, biofeedback, and hypnosis.

Physical Therapies
Physical therapies such as ultrasound, laser therapy, and transcutaneous electrical nerve stimulation (TENS) can be helpful (Robertson et al. 1990). Acupuncture reportedly has proven disappointing. A handheld vibromassager may be just as effective and easier to manage than TENS, especially for elderly patients.

Surgery
A specialist may blockade peripheral nerves or use subcutaneous intravenous injection of a local anesthetic such as lidocaine to control PHN pain.

Nutrient Supplements
Nutrient supplements and plant extracts helpful for shingles and PHN fall into four categories. The first two categories, those with antiviral and/or anti-inflammatory properties and those that enhance the immune system, have the same goal as conventional antiviral drugs: to stop the virus from replicating. Unlike antiviral drugs, however, many supplements have a number of health-optimizing actions and therefore also support recovery; these represent the third category of nutrient supplements helpful for shingles and PHN. Topical pain relievers comprise the fourth category.

Antiviral and/or Anti-Inflammatory Supplements
A variety of plants are known for their virus-killing action, including garlic (Weber et al. 1992; Guo et al. 1993), elderberry (Zakay-Rones et al. 1995), and rosemary (Paris et al. 1993; Aruoma et al. 1996), which is also an antioxidant and anti-inflammatory. Olive leaves have an active ingredient called Oleuropein, which has been shown in studies to be antiviral (Ma et al. 2001). It is also believed to have anti-inflammatory effects and has been used since ancient times to clean wounds. Flaxseed oil and fish oil contain omega-3 fatty acids with anti-inflammatory properties (Raederstorff et al. 1996; James et al. 2000; Thies et al. 2001). Particularly helpful supplements include the following:

Monolaurin
Monolaurin is a fatty acid with antiviral properties that is found in coconut oil. It disrupts the lipid membranes of envelope viruses such as herpes and rhinovirus, and has been proven effective against HSV-1 (herpes symplex virus Type 1) (Kristmundsdottir et al. 1999; Clarke et al. 2000).

Grapefruit Seed Extract
Grapefruit seed extract contains unstable polyphenolic compounds that are chemically converted into more stable substances that belong to a diverse class called quaternary ammonium compounds. These compounds exhibit broad-spectrum antimicrobial activity--the ability to kill a wide variety of bacteria and viruses--without the toxic side effects of the chemically derived quaternary ammonium compounds such as benzethonium chloride and benzalkonium chloride, which are used industrially as antimicrobials. In laboratory tests conducted at the Southern Research Institute, William M. Shannon, Ph.D. (head of the Microbiology/Virology Division), reported that grapefruit seed extract ". . .was effective in inactivating HSV-1 after a 10-minute exposure at a 1:256 dilutions."

Green Tea Extract
Green tea exhibits antiviral, anti-inflammatory, and antioxidant powers (Das et al. 2002; Fassina et al. 2002). Research has demonstrated that green tea catechins can inhibit the viral enzymes of reverse transcriptase and polymerases used in replication (Tao 1992). They have been shown to be effective against herpes simplex 1 experimentally. In addition, various polymeric oxidation products of polyphenols contained in green tea have been found to inhibit the herpes simplex virus.

Immune-Enhancing Supplements
The healing properties of echinacea have long been known among American Indians. Studies have shown that it begins stimulating the immune tissue in the mouth as soon as it is taken. Echinacea enhances the body's ability to dispose of infected and damaged cells; it has interferon-like activity against viruses; and it stimulates the white blood cells that fight infection (Burger et al. 1997; Thompson 1998). Another supplement that enhances the immune system is HSOs (homeostatic soil organisms), beneficial bacteria that will survive and grow in the intestine for a variety of health benefits, including stimulating the immune system. Scientific research has demonstrated that HSOs stimulate the body's production of alpha-interferon, used by the body to protect cells from invaders such as viruses (see the Immune Enhancement protocol for more information).

Supplements That Support Recovery
Almost all damage to the body occurs via molecules called free radicals, which oxidize molecules within cells. The remarkable health benefits of antioxidants, including vitamins C and E and beta-carotene, are supported by volumes of scientific research. Taking antioxidants in the course of shingles or PHN will support the body's recovery from the disease. A multinutrient formula like Life Extension Mix contains the key antioxidants in addition to a variety of other nutrients such as the B vitamins important for healing.

Topical Pain Relievers
A review of the actions of Chinese motherwort, Leonurus sibericus, in the American Journal of Chinese Medicine (1976) reported that a bath prepared from the leafy shoot relieves the discomfort and itching of shingles. An article by Hijikata et al. (1998) in the same journal reported the findings of an experiment in which administration of hot water-soluble extracts of Ganoderma lucidum (36-72 grams dry weight a day) in a bath dramatically decreased pain in two patients with PHN unresponsive to standard treatment and two others with severe shingles pain. Also known as Ling Zhi, or "mushroom of immortality," this plant is a general tonic that stimulates the immune system with sedative and analgesic properties and is known especially for its benefits to the skin (ganoderma means "smooth skin"). Its active ingredients include polysaccharides, triterpenoids, adenosine and other amino acids, minerals, and organic germanium. Inflacin is the trademark name of a topical pain relief cream that functions by suppressing excess production of arachidonic acid, an proinflammatory precusor.

Ribavirin
A double-blind, placebo-controlled study using topically applied 5% ribavirin in ointment base against herpes zoster in cancer patients indicated definite efficacy as reported in the Annals of the New York Academy of Sciences (Zertuche et al. 1977). Ribavirin is approved in the United States only as a secondary therapy against the hepatitis C virus and as a primary therapy against respiratory syncytial virus (RSV) in infants. This drug has been politically suppressed by the FDA, and no further studies to substantiate the role of ribavirin in treating shingles can be found. Offshore pharmacies might offer topical ribavirin ointment.

ConclusiON

Because almost all adults have been infected with the varicella zoster virus that causes chickenpox, almost everyone is at risk of developing shingles, an unpleasant condition characterized by rash and pain. Symptoms are usually localized in a particular area of the body supplied by the sensory nerve root in which the virus has lain dormant. It is not known why the virus becomes active again, although age and any compromise of the immune system are factors. Normally, with prompt antiviral and pain-relieving therapy, shingles resolves within about 1 month, never to return. However, herpes zoster infection can have serious complications, including secondary infection leading to scarring, paralysis of the affected area, and pain that persists beyond 30 days after rash onset, known as postherpetic neuralgia (PHN).

Most risk factors for PHN--age, pain before rash, and severe pain with rash--cannot be controlled. However, rapid and sufficient therapies that stop virus replication, which damages the nerve root and leads to PHN, and pain, which sensitizes the nerve root, can minimize the risk. For this reason, complementing conventional drugs with nutrient supplements and plant extracts is recommended by the Life Extension Foundation. These supplements do not have the side effects of conventional treatments, and they offer a variety of actions that optimize health and support recovery from the infection (refer to the Foundation's Immune Enhancement protocol for more specific information on what can be done to boost immune function, which appears to be an important adjuvant therapy in the prevention and treatment of shingles).

SUMMARY

Acute Herpes Zoster

  1. Within 3 days after the onset of the shingles rash, see a physician to begin a program of antiviral drugs and aggressive pain relief therapy. If you are over 50 and have no contraindications, steroid therapy may hold benefits for quality of life.
  2. Cimetidine (Tagamet) may put a shingles outbreak into remission. Begin administration as soon as symptoms appear: 200 mg 3 times daily, followed by 400 mg at bedtime.
  3. At the same time, begin a regimen of nutrient supplements with antiviral and anti-inflammatory actions. These supplements will help minimize the replication of the virus and therefore complications like PHN.
    • Garlic extract (Pure-Gar), up to eight 900-mg capsules daily.
    • Oregano, 30 drops of liquid extract daily, or rosemary oil, 20-40 drops of tincture daily.
    • Olive leaf extract, one to two 500-mg capsules daily.
    • Fish oil: Take a high-concentrated supplement providing at least 1000 mg of DHA, 400 mg of EPA, and 900 mg of GLA (gamma-linolenic acid) daily.
    • Monolaurin, one to two 300-mg capsules.
    • Grapefruit seed extract, one to three 125-mg capsules daily, or green tea extract, five to seven capsules daily.
    • Echinacea, one to two 250-mg capsules daily.
  4. Support recovery by taking an antioxidant formula that will neutralize free-radical damage. Life Extension Mix contains vitamins C, E, beta-carotene, and B vitamins that will promote healing, 9 tablets daily.
  5. Extracts of Chinese motherwort and Ling Zhi can be used in a bath to relieve the itching and discomfort of the shingles rash.
  6. Use zinc oxide or calamine lotion on the rash, and watch for signs of secondary infection such as redness or swelling. If these signs are present, consult a physician immediately to help prevent scarring.

Postherpetic Neuralgia

  1. If pain persists for 30 days after the onset of rash, consult a physician for tricyclic therapy and pain relievers.
  2. Try topical therapies as well to reduce pain. Ling Zhi extract can be used in a bath. Creams such as Silvadene, Aspercreme, or capsaicin may provide relief. Cold packs applied over cotton may be helpful. Wear light cotton clothing or use an "artificial skin" spray to minimize allodynia. Topical application of Inflacin may alleviate inflammatory-related pain.
  3. Nutrient supplements with anti-inflammatory actions (such as fish oil) may provide some benefit by soothing inflammation of the irritated nerve roots.
  4. Consider physical therapies such as ultrasound, laser therapy, transcutaneous electrical stimulation, and acupuncture. Use a handheld vibromassager.
  5. Consider psychological interventions such as counseling, cognitive behavior modification, relaxation training, biofeedback, and hypnosis to aid in coping with chronic pain.
  6. If pain is unresponsive to these therapies, consult a specialist regarding surgical treatments such as peripheral nerve blockade or subcutaneous injection of local anesthetic.
  7. Take 3 tablets of Life Extension Mix 3 times a day to provide the antioxidants and other nutrients necessary to support recovery.

For more informatiON

Contact the American Academy of Dermatology, (708) 330-0230.

Product availabiliTY

Green tea extract, Life Extension Mix, olive leaf extract, oregano liquid extract, monolaurin, Pure Gar, Super GLA/DHA (fish-borage oil), Mega EPA (fish oil), grapefruit seed extract, Inflacin and echinacea can be ordered by telephoning (800) 544-4440 or by ordering online. Cimetidine can be obtained in pharmacies over-the-counter without a prescription. Antiviral drugs like acyclovir and other drugs such as ribavirin and tricyclics require a physician's prescription.