What is herpes-zoster?

Varicella-zoster virus (VZV) causes two distinct clinical entities one is chickenpox (or varicella) and the other one is herpes zoster or shingles. Herpes zoster is clinically seen as a dermatomal (dermatome is an area of skin supplied by a particular nerve root) vesicular rash and generally associated with severe pain and commonly affects after the sixth decade of life, due to reactivation of latent VZV.

Varicella-zoster virus (VZV) belongs to a member of the family Herpesviridae, having a diameter of approximately180–200 nm (nanometer), with centrally located double-stranded DNA which is approximately125,000 bp in length.

How herpes zoster is transmitted?

Transmission of varicella-zoster virus occurs through respiratory route and subsequently localizes for replication at an undefined site (most probably the nasopharynx), which leads to seeding of the VZV in the reticuloendothelial system and ultimately development of viremia.

Patients with herpes zoster can transmit infection to seronegative individuals, which results in development of consequent chickenpox.

Primary infection by varicella-zoster virus (VZV) causes chickenpox and recurrent infection (reactivation of latent infection) causes herpes zoster. The exact mechanism of reactivation of VZV that results in herpes zoster is not known. It is postulated that the virus infects dorsal root ganglia (the dorsal root ganglia shows hemorrhage, edema, and lymphocytic infiltration) during chickenpox, where it remains latent until reactivation.

What is the pathogenesis of herpes zoster?

Replication of varicella-zoster virus in other organs (lung or the brain) can take place during either chickenpox or herpes zoster but is rare in the immunocompetent (normal immunity or body defence) host. Involvement of lung is characterized by interstitial pneumonitis, multinucleated giant cell formation, intranuclear inclusions, and lung hemorrhage. Central nervous system (CNS) infection leads to histopathologic changes similar to that seen in measles and other viral encephalitides. Focal hemorrhagic necrosis of the brain, characteristic of herpes simplex virus (HSV) encephalitis, is uncommon in VZV infection.

How common is herpes zoster?

Shingles or herpes zoster is a sporadic disease (occurs without any specific pattern). Most of the patients with herpes zoster do not give any history of recent exposure or contact with varicella-zoster virus infection. Herpes zoster is commonest in individuals of more than 60 years of age (the incidence of herpes zoster is as high as 5-10 cases per 1,000 population of above 60 years), but it can occur at any age. It is estimated that in United States alone there are more than a million cases of herpes zoster. Recurrent herpes zoster is extremely rare (but can occur in immunocompromised hosts like AIDS patients).

What are the signs and symptoms of herpes zoster?

The most common and important clinical feature of herpes zoster is a unilateral vesicular eruption within a dermatome (an area of skin supplied by a particular nerve root and most commonly T3 to L3 dermatomes are involved), commonly associated with severe pain. Symptoms may depend on the involvement of the nerve root, e.g. involvement of ophthalmic branch of the trigeminal nerve results in zoster ophthalmicus. If trigeminal nerve branches are involved, herpes zoster lesions may appear on the face, mouth, in the eye (zoster ophthalmicus), or on the tongue. Zoster ophthalmicus is a serious condition that can cause in blindness in the absence of antiviral therapy.

The onset of herpes zoster is with pain within the affected dermatome, which may precede skin lesions by 48–72 hours. The skin lesion is an erythematous (reddish color) maculopapular rash which appears and evolves rapidly into vesicular lesions. If the immune system of host is normal, the skin lesions (erythematous maculopapular rash) are only few in number and continue to form for only 3–5 days and the total duration of disease is generally 7–10 days, although it may take 2–4 weeks for the skin to return to normal. In some patients the typical pain of herpes (zoster-associated pain) to a dermatome with serologic evidence of herpes zoster may occur in absence of skin lesions. Ramsay Hunt syndrome may develop in herpes zoster in which there is pain and vesicles in the external auditory canal and patients lose their sense of taste in the anterior two-thirds of the tongue and also develop ipsilateral (on the same side) facial palsy.

In children, reactivation of varicella virus is usually benign, but in adults (especially in very old people), reactivation can be very serious.

What are the complications of herpes zoster?

The most serious complication of herpes zoster, in normal as well as in immunocompromised individuals is pain associated with acute neuritis and postherpetic neuralgia (uncommon in young individuals). Pain associated with acute neuritis and postherpetic neuralgia is seen in at least 50% of herpes zoster patients of more than 50 years of age in the involved dermatome even months after the resolution of cutaneous herpes.

Cutaneous herpes zoster may involve CNS (central nervous system). If CNS is involved, meningoencephalitis may develop with headache, vomiting, fever, photophobia and meningitis. Other rare neurological (CNS) involvement of herpes zoster includes transverse myelitis (with or without motor paralysis), granulomatous angiitis with contralateral (opposite side to the skin lesion) hemiplegia (can be diagnosed by cerebral arteriography) etc.

Herpes zoster is more severe with higher incidences of complications in immunocompromised individuals than normal individuals. In immunocompromised persons the skin lesions continue to for more than a week and complete scabbing may take as long as 3 weeks. In patients with Hodgkin's disease and non-Hodgkin's lymphoma there is great risk for progressive herpes zoster with cutaneous dissemination of approximately 40%. If there is cutaneous dissemination the risk of pneumonitis, meningoencephalitis, hepatitis, and other serious complications are much higher. But the good news is even in immunocompromised individuals with complications, herpes zoster is rarely fatal.

Varicella-zoster virus (VZV) is common among hematopoietic stem cell transplants recipients and approximately one third of these occur within 1 year (50% of these occur within 9 months) after transplantation. Cutaneous or visceral dissemination is common among these patients and as is postherpetic neuralgia, scarring, and bacterial superinfection. The mortality rate is more than 10% among these patients of herpes zoster with complications.

How to diagnose herpes zoster?

Clinical manifestations and history of herpes zoster are characteristic and it is easy to diagnose herpes zoster clinically, although unequivocal confirmation of the diagnosis is possible only by isolating VZV in tissue-culture cell lines, by demonstration of either seroconversion or a fourfold or greater rise in antibody titer between convalescent- and acute-phase serum specimens, or by detection of VZV DNA by PCR (polymerase chain reaction). But PCR technique for the detection of viral DNA in vesicular fluid is available only in few centers. The most frequently employed serologic tools are FAMA (fluorescent antibody to membrane antigen) test, immune adherence hemagglutination, and ELISA (enzyme-linked immunosorbent assay). These tests are used for assessing host response and detect antibodies by immunofluorescent. The FAMA test and the ELISA are most sensitive.

A rapid impression can be obtained by a Tzanck smear, with scraping of the base of the lesions, which can demonstrate multinucleated giant cells, but the sensitivity of this method is only 60% and not very useful.

What is the differential diagnosis of herpes zoster?

Although herpes zoster is not difficult to diagnose due to the characteristic clinical findings another disease can cause similar clinical manifestations which is coxsackievirus infections which also cause similar dermatomal vesicular lesions. Herpes zoster can also occur without a rash, although rarely and diagnosis may pose serious problem.

How herpes zoster is treated?

Patients with herpes zoster should be treated with antiviral drugs like acyclovir (now off patent and affordable and cheap), valacyclovir, or famciclovir. Administration of antiviral drugs can accelerate healing of skin lesions and resolution of zoster-associated pain. Currently most commonly used antiviral drug in herpes zoster is acyclovir which is administered at a dose of 800 mg five times daily for 7–10 days. Famciclovir (at the dose of 500 mg three times a day orally for 7 days) is the prodrug of penciclovir, is as effective as acyclovir (many experts claim it to be more effective). Valacyclovir (at the dose of 1,000 mg orally three times a day for 5-7 days), the prodrug of acyclovir, is also equally or more effective and accelerates healing and resolution of zoster-associated pain more promptly than acyclovir. Famciclovir and valacyclovir has at least one advantage over acyclovir, which is less frequent administration (thrice a day instead of 5 times a day for acyclovir). Aluminum acetate soaks are soothing and cleansing in management of herpes zoster.

In severely immunocompromised individuals like transplant recipients, patients with lymphoproliferative malignancies, AIDS etc. herpes zoster should be treated, at the beginning of disease with intravenous acyclovir, to reduce visceral complications, although it has no effect on healing of skin lesions or pain. The dose of acyclovir is 10–12.5 mg/kg every 8 hourly for 7 days. If risk is low, oral valacyclovir or famciclovir is sufficient in immunocompromised hosts. Along with the administration of intravenous acyclovir immunosuppressive treatment should be gradually stopped or reduced, for desired result.