Herpes and Varicella Zoster

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INTRODUCTION Herpes zoster (shingles) and varicella zoster (chickenpox) are both systemic infections with manifestations caused by herpes virus varicellae. The virus is an obligate human parasite requiring person-to-person transmission for its survival. Varicella most commonly occurs in children and is almost always a mild, self-limited disease; however, when the disease occurs in adults it is often a much more severe process. Zoster, meaning belt or girdle in Greek, is felt to be a reactivation of a previous varicella infection within a single dermatome. Herpes zoster is most prevalent in middle to late adulthood; however, it can occur in children and rarely even in infants, in whom it is usually a mild disease. Eyelid symptoms result from involvement of the first or ophthalmic division of the trigeminal (5th cranial) nerve and are seen in up to 10% of cases of zoster infections. Adults with herpes zoster are contagious during the early stages and often transmit the virus to susceptible youngsters who then develop chickenpox. The incidence of post herpetic neuralgia increases with age; it is seldom seen under age 50 years but occurs in up to 50% of victims over 70 years old. Most cases subside after several months, but those that persist can be sever enough to lead to incapacitation and may even result in suicide.

CLINICAL PRESENTATION Following an incubation period of approximately two weeks and a prodrome of fever and malaise, the cutaneous lesions begin as a mild maculo-papular eruption. The papules evolve into clear vesicles that show an umbilicated center. Characteristic vesicles overlie a larger patch of erythema and develop in several successive crops. The vesicles become cloudy, rupture, and form crusts. Healing occurs over the ensuing few weeks with little or no scarring unless they become infected. In contrast to varicella, the lesions in herpes zoster are limited to a single dermatome; however, hematologic dissemination of the virus can result in a few distant skin lesions as well. Pain in the region supplied by the involved nerve is not common but can precede the skin changes by several days. Preauricular adenopathy is often seen. The nasociliary branch of the ophthalmic nerve supplies sensation to the eye, with terminal branches going to the tip of the nose. Lesions on the tip of the nose, therefore, are usually accompanied by ocular manifestations (Hutchinson's sign). Associated ocular involvement may include a follicular conjunctivitis, nummular keratitis, dendritic keratitis, disciform keratitis, acute anterior uveitis, or rarely a necrotizing retinitis. Less often, optic nerve involvement or selective palsies of the oculomotor, trochlear, or abducens nerves may be seen. Late ocular sequelae may include glaucoma, neuro-paralytic keratopathy, and Addie's tonic pupil due to ciliary ganglion damage may occur.

Oculomotor Paralysis

HISTOPATHOLOGY The characteristic lesion of herpes zoster infection is an intraepidermal vesicle (blister) with swollen and multinucleated epidermal cells. Swollen epidermal cells lose their attachment to adjacent cells and separate from them; a subepidermal vesicle may result if this process involves the basal epidermal cells. Eosinophilic nuclear inclusions are found in some of the multinucleated keratinocytes. Neutrophils are present within vesicles and within the subjacent dermis. The lesions of herpes zoster resemble those of herpes simplex, but they can be distinguished using immunohistochemical stains.

Dermis Multinucleated Cells Neutrophils

DIFFERENTIAL DIAGNOSIS The differential diagnosis includes Herpes simplex, impetigo, and Coxsackie virus infections.

TREATMENT A vaccine against varicella is now available and may limit its occurrence in future generations.

For active disease oral antihistamines may be useful in decreasing pruritis and scratching which may lead to scarring. Systemic antivirals including acyclovir and valcyclovir may limit the duration of the disease in adults. Systemic steroids should be avoided owing to the risk of inducing encephalitis. Herpes zoster also runs a limited course, however the incidence of post herpetic neuralgia is much higher. Antiviral agents such as valcyclovir and famcyclovir may limit the course, and in the case of famcyclovir may actually reduce the instance of post herpetic neuralgia. High-dose systemic steroids during the acute disease, in the range of 60 mg of prednisone daily, also appear to reduce the incidence and severity of post herpetic neuralgia. In debilitated or immunosuppressed individuals systemic steroids carry a considerable risk of inducing disseminated zoster. In patients with immunologic defects, varicella can be devastating and even fatal, therefore, when known exposure has occurred or is suspected, gamma globulin or zoster immune globulin can abort or reduce the severity of the disease.

REFERENCES

Eaglestein WH, Katz R, Brown JA. The effects of early corticosteroid therapy on the skin eruption and pain of herpes zoster. JAMA 1970; 211:1681-1683.

Grimson BS, Glaser JS. Isolated trochlear nerve palsies in herpes zoster ophthalmicus. Arch Ophthalmol 1978; 96:1233-1235.

Liesegang TJ. Corneal complications from herpes zoster ophthalmicus. Ophthalmology 1985; 92:316-324.

Marsh RJ. Current management of ophthalmic zoster. Aust N Z J Ophthalmol 1990; 18:273-279.

Mok CH. Zoster-like disease in infants and young children. N Engl J Med 1971; 285:294.

Naumann G, Gass JD, Font RL. Histopathology of herpes zoster ophthalmicus. Am J Ophthalmol 1968; 65:533-541.

Pavan-Langston D, McCully JP. Herpes zoster dendritic keratitis. Arch Ophthalmol 1973; 89:25-29.

Pavan-Langston D. Varicella-zoster ophthalmicus. Int Ophthal Clin 1975; 15:171-185.

Piebenga LW, Laibson PR. Dendritic lesions in herpes zoster ophthalmicus. Arch Ophthalmol 1973; 90:268-270.

Severson EA, Baratz KH, Hodge DO, Burke JP. Herpes zoster ophthalmicus in Olmsted County, Minnesota: have systemic anitvirals made a difference? Arch Ophthalmol 2003; 121:386-390.

Yoshida M, Hayasaka S, Yamada T, et al. Ocular findings in Japanese patients with varicella-zoster virus infection. Ophthalmologica 2005; 219:272-275.

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