155 Varicella Zoster

Varicella (chickenpox) is an acute infection of short duration caused by Varicella-Zoster virus (VZV), which is spread in the early stages of disease by droplets of secretions from the nasopharynx.

Epidemiology and Incidence

Chickenpox is endemic worldwide, is highly commu­nicable, and commonly appears as epidemics among children who are usually attacked between 2 and 8 years of age. (Infants are protected by transplacental maternal antibodies.) Few escape infection until adult life, and these usually live in isolated rural communities. Probably most of those who have seemed to escape the disease had Subclinical infec­tions. (The annual Report OfMorbidity and Mortality in the United States shows, for 1984, 221,983 cases of varicella reported from 33 states, an incidence of 138 cases per 100,000 population. The age was known in 28 percent; 56 percent of these cases appeared in the 5- to 9-year age group, less than 6 percent were 15 years of age or older.)

The sporadic reactivation of the virus as shingles is unrelated to exposure to exogenous infection and, in general, is uncommon even in populations in which practically all have had chickenpox. Its peak incidence is after age 50. Of those who develop shin­gles, only 1 percent have two attacks. Patients with impaired cellular immunity are at risk, and herpes zoster is not uncommon in those suffering from ma­lignant disease.

Immunology

A viremia develops promptly after infection with VZV of which there is only one serotype. Circulating antibody is demonstrable within 1 to 4 days after the appearance of the rash. Although immunity is life­long, it has been suggested that a waning of immu­nity in older age explains shingles, and viremia would seem to account for a varicella-like rash in some instances.

Clinical Manifestations and Pathology

Presumably the virus enters and replicates briefly in the cells of the respiratory mucosa followed by an intermittent viremia. The histopathology is identical with that described for herpes simplex infection. The virus is present in the vesicles. During viremia the virus travels from cutaneous sensory nerve endings to the posterior ganglia where it remains latent to be reactivated in some patients as herpes zoster. Then the dorsal ganglia show intense inflammation even with hemorrhagic necrosis, leptomeningitis, and my­elitis of the posterior spinal columns. Although N7N has been isolated from ganglia during active disease, it has not been found during quiescent periods.

After an incubation period of 10 to 20 days and some 24 hours before the rash of varicella appears, the prodromes of mild headache, malaise, and moder­ate fever appear. Because these are commonly unrec­ognized in young children, the rash seemingly is the initial evidence of disease. It appears as a cutaneous blush, with the development of successive crops of macules, papules, and superficial vesicles sur­rounded by a red areola, which go on to crusting within 24 hours. The acute phase lasts about a week.

Although the rash may be generalized, it usually involves the trunk and face, with fewer lesions on the extremities. Vesicles may appear in the mouth, and laryngeal involvement may cause dyspnea. Chicken­pox is a benign disease in children unless they suffer from leukemia or are taking corticosteroids. Other than acute encephalitis, an occasional circumstance late in the disease, complications have been reported very rarely in almost all the body systems. In adults varicella tends to be less benign, and commonly the X-ray reveals pulmonary infiltrates.

An attack of herpes zoster may be ushered in with 1 or 2 days of fever, chills, malaise, and gastrointesti­nal symptoms before symptoms of local disease ap­pear. Either with or without prodromal symptoms the patient becomes aware of some pain, at times with itching, in the area of the affected segmental nerves. After several days, crops of vesicles on an erythematous base appear in the distribution of the nerves of one or several posterior root ganglia, usu­ally accompanied by hyperesthesia and pain. The vesicles dry and become crusted in about a week, although the course may be slower in aged persons. Hyperesthesia or pain may last for weeks and months especially in those patients with malignant disease. In an occasional aged patient, these residua never disappear. Herpes of the ophthalmic branch of the trigeminal nerve is not uncommon and may be accompanied by keratoconjunctivitis, which may be followed by serious corneal scarring and glaucoma. Zoster of the geniculate ganglion produces Ramsey Hunt’s syndrome. The characteristic pain syndrome of zoster may run its course without skin eruption, contrary to the clinician’s initial prediction.

History and Geography

Both J. E. Schmidt (1959) and F. H. Garrison (1960) credit Giovanni Filippo Ingrassia, an Italian physi­cian, with differentiating chickenpox from scarlet fe­ver in 1553, and state that the English physician William Heberden (1785) gave the earliest clear de­scription of varicella and distinguished it from small­pox in 1768. Jean Alibert (1832) included varicella in his group II category of exanthematous dermatoses - acute febrile contagous diseases. E. E. Tyzzer (1905), an American pathologist, described cellular inclu­sion bodies, and T. M. Rivers and W. S. Tillett (1924) reported isolation of the virus.

P. A. Rayer, in his 1845 treatise on diseases of the skin, described the microscopic contents of zoster vesicles and of the underlying skin. F. von Baren- sprung (1861-3) concluded that zoster was due to disease of the posterior roots.

R. H. Kampmeier

Bibliography

Alibert, J. L. 1832. Monographie des dermatoses. Paris.

Barensprung, F. von. 1861-3. Ueber die Gurtel Krank- heit. Annalen Charite Krankenhaus 9: 40-128, 10: 27-53, 11: 96-116.

Bokay, Janos. 1892. Das Auftreten von Varizellen unter eigentumlichen Verhaltnissen. Magyar orvosi Ar­chivum. Nov 3.

Campbell, A. W, and Henry Head. 1900. Hemorrhagic inflammation of posterior nerve roots and homologous spinal ganglia. Brain 23: 353-523.

Crissey, John T., and Lawrence C. Parish. 1981. The derma­tology and Syphilology of the nineteenth century. New York.

Garrison, Fielding Hudson. 1960. History of medicine, 4th edition. Reprint. Philadelphia.

Heberden, William. 1785. On the chickenpox. Medical Transactions of the Royal College OfPhysicians of Lon­don i: 427—36.

Kibrick, Sidney. 1982. Varicella and herpes zoster. In Cecil’s textbook of medicine, 16th edition, ed. James B. Wyngaarden and Lloyd H. Smith, Chapter 300. Philadelphia.

Kundratitz, Karl. 1925. Experimentelle Uebertragung von Herpes Zoster auf den Menschen and Bezie- hungen von Herpes Zoster zu Varizellen. Monatschrift fur Kinderheilkunde 29: 516—23.

Marcy, S. Michael, and Sidney Kibrick. 1983. Varicella and herpes zoster. In Infectious diseases, 3d edition, ed. Paul D. Hoeprich, Chapter 93. Philadelphia.

NIH Conference. 1978. Herpes zoster varicella infections in immunosuppressed patients.

Rivers, T. M., and W. S. Tillett. 1924. The lesions in rabbits experimentally infected by a virus encountered in the attempted transmission of varicella. Journal of Experi­mental Medicine 40: 281—7.

Schmidt, J. E. 1959. Medical discoveries: Who and when. Springfield, Ill.

Tyzzer, E. E. 1905. The histology of the skin lesions of varicella. Journal OfMedicalResearch 14: 361—89.

Weller, T. H., and A. H. Coons. 1954. Fluorescent antibody studies with agents of varicella and herpes zoster propagated in vitro. Proceedings of the Society for Ex­perimental Biology and Medicine 86: 789—94.

Weller, T. H., H. M. Witton, and E. J. Bell. 1958. The etiology agents of varicella and herpes zoster: Isola­tion, propagation, and cultural characteristics in vi­tro. Journal OfExperimental Medicine 108: 843—86.

Wyss, 0.1872. Beitrag zur Kenntnis des Zoster. Archiv fiir Dermatologie und Syphilis 4: 449-50.

Zulia, J. A. 1981. Clinical spectrum of varicella zoster virus infection. In The human herpesviruses — An in­terdisciplinary perspective, ed. Andre J. Nahmias, Wal­ter Dowdle, and Raymond F. Schinzi. New York.