Herpes zoster and postherpetic Neuralgia

Herpes zoster and post herpetic Neuralgia

Dr.NEAZA.A,  PHYSICIAN

ESI H, PEROORKADA

drneaza@hotmail.com

A 63-year-old woman presented in our OPD with persistent pain and itching in the right T10 dermatome from just above the thoracolumbar junction to the umbilicus. She gives history of episode of herpes zoster in the same region one year earlier. She describes a severe, continuous, burning pain lasting a few seconds, and intense hypersensitivity to tactile stimulation.

On physical examination there are signs of cutaneous scarring throughout the right T10 dermatome, with areas of excoriation caused by scratching.

       Post herpetic neuralgia (PHN) is the most frequent chronic complication of herpes zoster.

Herpes zoster (HZ), commonly called shingles, is a distinctive syndrome caused by reactivation of varicella zoster virus (VZV) in the dorsal root ganglion of sensory nerves. This reactivation occurs when immunity to VZV declines because of aging or immunosuppression..

Historical Perspective:

VZV is estimated to have been around for more than 70 million years. It was initially named by Hippocrates; Herpein, meaning to creep; zoster  meaning girdle (Greek).  Shingles meaning belt, (Latin). Not until 1940 was the etiology of the virus established. VZV was finally isolated in 1952 by a Harvard Microbiologist. The genome was first sequenced in 1986.

Epidemiology:

Varicella zoster virus (VZV) has a high level of infectivity and has a worldwide prevalence.

Incidence:  5-10 cases per 1000 persons. It is highest among individuals in the sixth decade of life and beyond.

Following primary infection of the virus (Varicella -chicken pox), it lies dormant until reactivated in later life.

Varicella virus

Pathophysiology:

Reactivation can occur in the presence of stress, surgery, or injury. Following reactivation the virus travels at a possible rate of 1.7-10mm per hour. Cutaneous vesicles develop in 48-96 hours. Hemorrhagic inflammation is characterized at the cellular level. Fibrosis is noted at the dorsal root ganglion, nerve root and peripheral nerve upon resolution of the acute stage.

                                    

Postherpetic neuralgia is the 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.

Neuropathic pain is due to altered gene expression in sensory dorsal root ganglia neurons. Following nerve damage, NaCl channel accumulation causes hyperexcitability, and down regulation sensory neuron specific, SNS1 channel and upregulation of 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.

Clinical manifestations:

Prodromal symptoms may include chills, fever, malaise, G.I. disturbance and paraesthesia or neuralgia along the affected dermatome.

 Red papules usually appear along the affected dermatome within 3 days. The eruption of vesicles closely follows the maculopapular rash. Vesicles usually dry up in an average of 7 days and scarring occurs at the site.

                                                    

Distribution: 50-60% Thoracic, 10-20%Trigeminal, 10-20%Cervical, 5-10% Lumbar, and <5% Sacral. 99% of all cases are unilateral and do not cross the midline unless there is greater than one dermatome affected or dissemination has occurred.

Sensory disturbances face

    

Diagnosis and differential diagnosis:

If the rash has appeared, identifying this disease requires only a visual examination, since very few diseases produce unilateral vesicular lesion in a dermatomal pattern.

 Herpes simplex virus (HSV) can occasionally produce a rash in such a pattern (zosteriform herpes simplex). The Tzanck smear is helpful for diagnosing acute infection with a herpes virus, but does not distinguish between HSV and VZV.

Coxsackie virus infection also produce disseminated vesiculopapular lesion. Supportive diagnostic virology and fluorescent staining of skin scrapings with monoclonal antibodies ensure proper diagnosis.

Laboratory tests;

 The most popular test detects VZV-specific IgM antibody in blood; this appears only during chickenpox or shingles and not while the virus is dormant.   Lymph collected from a blister is tested by polymerase chain reaction for VZV DNA, or examined with an electron microscope for virus particles. Viral culture and quantitative PCR are done with samples of lesions on the skin, eyes, and lung.

To assess host response immunofluorescent detection of antibodies to VZV membrane antigens, fluorescent antibody to membrane antigen (FAMA) test and ELISA appears to be most sensitive.

Complication:

Secondary bacterial infection of the skin

Post herpetic neuralgia is a condition of chronic pain following shingles. The neuralgia typically begins when the herpes zoster vesicles have crusted over and begun to heal.

Nervous system involvement cause many cranial neuropathies, polyneuritis, myelitis, or aseptic meningitis, partial facial paralysis (usually temporary), ear damage, or encephalitis.

Trigeminal nerve involvement in herpes ophthalmicus should be treated early and aggressively as it may lead to blindness. Involvement of the tip of the nose in the zoster rash is a strong predictor of herpes ophthalmicus.

Herpes of the geniculate ganglion presents with facial nerve palsy causing Ramsay- Hunt syndrome

 During pregnancy, first infections with VZV, causing chickenpox, may lead to infection of the fetus and complications in the newborn, but chronic infection or reactivation in shingles are not associated with fetal infection.

There is a slightly increased risk of developing cancer after a shingles infection.

Treatment:

The aims of treatment are to limit the severity and duration of pain,

 shorten the duration of a shingles episode, and reduce complications. Symptomatic treatment is often needed for the complication of post herpetic neuralgia.

Antivirals:

Antiviral drugs may reduce the severity and duration of shingles; however, they do not prevent postherpetic neuralgia.

 Of these drugs, acyclovir has been the standard treatment, but drugs  valaciclovir  and famciclovir demonstrate similar or superior efficacy and good safety and tolerability.

 The drugs are used both for prevention and as therapy during the acute phase. Complications in immunocompromised individuals with shingles may be reduced with intravenous acyclovir. In people who are at a high risk for repeated attacks of shingles, five daily oral doses of acyclovir are usually effective. 

Analgesics:

People with mild to moderate pain can be treated with analgesics.

Locally applied topical agents

Aspirin mixed into an appropriate solvent such as diethyl ether may reduce pain.

 Lidocaine skin patches

Once the lesions have crusted over, capsaicin cream (Zostrix) can be used.

 Calamine lotions can be used on the rash or blisters.

Paracetamol or the non-steroidal anti-inflammatory drugs and opioids  including higher dosages of codeine, tramadol, morphine  or fentanyl  are beneficial for pain relief.

Pain modification therapy:

Antidepressants:

 Low dosages of tricyclic antidepressants, including amitriptyline, are used for the deep aching pain. They do not eliminate the pain, but they may make it easier to tolerate.

Other antidepressants- venlafaxine, bupropion and selective serotonin reuptake inhibitors also used in postherpetic neuralgia .

Anticonvulsants:

 These agents are used to manage severe muscle spasms and provide sedation in neuralgia.  Phenytoin and carbamazepine can lessen the pain associated with postherpetic neuralgia. The medications stabilize abnormal electrical activity in the nervous system caused by injured nerves

Gabapentin  and lamotrigine, are generally tolerated better and can help control burning and pain in PHN.

Steroids:

Corticosteroids have been recommended to help with acute pain but do not appear to decrease the risk of long term pain.

Non-pharmacological treatments for post herpetic neuralgia:

Acupuncture.

Moxibustion:  A traditional Chinese medicine therapy using moxa.

Relaxation techniques. These can include breathing exercises, visualization and distraction.

Heat therapy.

Cold therapy   Cold packs can be used.

Transcutaneous Electrical Nerve Stimulation. This involves the stimulation of peripheral nerve endings by the delivery of electrical energy through the surface of the skin.

Spinal cord stimulator. The electrical stimulation of the posterior spinal cord works by activating supraspinal and spinal inhibitory pain mechanisms.

Prevention:

A  live attenuated varicella vaccine (Oka) is recommended for all children >1 year of age (up to 12 years of age) who have not had chickenpox and for adults known to be seronegative for VZV.

A second approach is to administer varicella-zoster immune globulin (VZIG) to individuals who are susceptible, are at high risk for developing complications of varicella, and have had a significant exposure

Lastly, antiviral therapy can be given as prophylaxis to individuals at high risk who are ineligible for vaccine or who are beyond the 96-h window after direct contact.

Prognosis:

The rash and pain usually subside within three to five weeks.

One in five people develop post herpetic neuralgia, which is often difficult to manage.

In some people, shingles can reactivate presenting as zoster sine herpete: pain radiating along the path of a single spinal nerve, but without an accompanying rash.

Bibliography

1.    Longo, Fauci, Kasper et al ; Harrison’s  principles of internal medicine 18^th edition 180:1462,2012.

2.    Kantaria SM.Bilateral  asymmetrical herpes zoster, Indian Dermatology online j2015;6:236.

3.    Am Fam Physician. 2000 Apr 15;61(8):2437-2444

 (copy of article published in JIMOA vol111 issue 1 sep 2015)