Causative Agent Of Arthritis

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Epidemiology

Prevention and treatment

22.4 Skin Diseases Caused by Viruses 547

Stage l: Enlarging, red rash at the site of the bite; fever, malaise, headache, general achiness, enlargement of lymph nodes near bite, joint pains. Stage 2: Acute involvement of heart and nervous system. Stage 3: Chronic arthritis and impairment of the nervous system.

Approximately 1 week

Borrelia burgdorferi, a spirochete

Spirochetes injected into the skin by an infected tick multiply and spread radially; the spirochetes enter the bloodstream and are carried throughout the body; the immune reaction to bacterial antigen causes tissue damage.

Spread by the bite of ticks, Ixodes sp., usually found in association with animals such as white-footed mice and white-tailed deer living in wooded areas.

Protective clothing; tick repellents. Early treatment with doxycycline and others; prolonged antibiotic therapy in chronic cases.

Symptoms

Most cases of chickenpox are mild, sometimes unnoticed, and recovery is usually uncomplicated. The typical case has a rash that is diagnostic. It begins as small, red spots called macules, little bumps called papules, and small blisters called vesicles, surrounded by a narrow zone of redness. The lesions can erupt anywhere on the body, although usually they first appear on the back of the head, then the face, mouth, main body, and arms and legs, ranging from only a few lesions to many hundreds. The lesions appear at different times, and within a day or so they go through a characteristic evolution from macule to papule to vesicle to pustule, a pus-filled blister. After the pustules break, leaking virusladen fluid, a crust forms, and then healing takes place. At any time during the rash, lesions are at various stages of evolution (figure 22.17). The lesions are pruritic, meaning itchy, and scratching may lead to serious, even fatal, secondary infection by Streptococcus pyogenes or Staphylococcus aureus.

Symptoms of varicella tend to be more severe in older children and adults. In about 20% of adults, pneumonia develops, causing rapid breathing, cough, shortness ofbreath, and a dusky skin color. The pneumonia subsides with the rash, but respiratory symptoms often persist for weeks. Varicella is also a major threat to newborn babies if the mother develops the disease within 5 days before delivery to 2 days afterward. Mortality in these babies has been as high as 30%. Also, congenital varicella syndrome develops in a fraction of a percent of babies

Congenital Scar Face Neonate

Figure 22.17 A Child with Chickenpox (Varicella) Characteristically, lesions in various stages of evolution—macules, papules, vesicles, and pustules—are present.

Figure 22.18 Shingles (Herpes Zoster) The rash mimics that of chickenpox, except that it is limited to a sensory nerve distribution on one side of the body.

Figure 22.17 A Child with Chickenpox (Varicella) Characteristically, lesions in various stages of evolution—macules, papules, vesicles, and pustules—are present.

Figure 22.18 Shingles (Herpes Zoster) The rash mimics that of chickenpox, except that it is limited to a sensory nerve distribution on one side of the body.

whose mothers contract varicella earlier in pregnancy. These babies are born with such defects as underdeveloped head and limbs, and cataracts. In addition, the disease is a threat to immunocompromised patients of any age. The virus can damage the lungs, heart, liver, kidneys, and brain, resulting in death in about 20% of the cases.

Reactivation of chickenpox is called shingles, or herpes zoster. It can occur at any age but becomes increasingly common with advancing age. It begins with pain in the area supplied by a nerve of sensation, often on the chest or abdomen but sometimes on the face or an arm or leg. After a few days to 2 weeks, a rash characteristic of chickenpox appears, but unlike chickenpox the rash is usually restricted to an area supplied by the branches of the involved sensory nerve (figure 22.18). The rash generally subsides within a week, but pain may persist for weeks, months, or longer. In people with AIDS or other serious immunodeficiency, instead of being confined to one area the rash often spreads to involve the entire body, as in a severe case of chickenpox.

A curious affliction known as Reye's syndrome occasionally occurs in association with chickenpox, usually within 2 to 12 days of the onset of the infection. The patients begin vomiting and slip into a coma. The syndrome occurs predominantly in children between 5 and 15 years old and is characterized by liver and brain damage. It occurs uncommonly, with a general trend to declining incidence, but the death rate has been around 30%. Reye's syndrome is also seen in association with a number of other viral infections including influenza A and B. Epidemiologic evidence suggesting that aspirin therapy increases the risk of Reye's syndrome has led physicians to use this drug sparingly in children with fever.

Causative Agent

Chickenpox is caused by the varicella-zoster virus, a member of the herpesvirus family. It is an enveloped, medium-sized

(150-200 nm), double-stranded DNA virus, indistinguishable from other herpesviruses in appearance (figure 22.19).

Pathogenesis

The virus enters the body by the respiratory route, establishes an infection, replicates, and disseminates to the skin via the bloodstream. After the living layers of skin cells are infected, the virus spreads directly to adjacent cells, and the characteristic skin lesions appear. Stained preparations of infected cells show intranuclear inclusion bodies, visible as pink staining bodies at the place in the nucleus where the virus reproduces. Some infected cells fuse together, forming multinucleated giant cells. The infected cells swell and ultimately lyse. The virus enters the sensory nerves, presumably when an area of skin infection advances to involve a sen-

100 nm

Figure 22.19 Electron Micrograph of Varicella-Zoster Virus, Cause of Chickenpox and Shingles

100 nm

Figure 22.19 Electron Micrograph of Varicella-Zoster Virus, Cause of Chickenpox and Shingles sory nerve ending. Conditions inside the nerve cell do not permit full expression of the viral genome; however, viral DNA is present in the ganglia (singular: ganglion) of the nerves and is fully capable of coding for mature infectious virus. Ganglia are small bulges in sensory nerves located near the spine; they contain the nuclei and cell bodies of the nerves. The mechanism of suppression of viral replication within the nerve cell is not known but is probably under the control of immune cells.

The occurrence of shingles correlates with a decline in cellmediated immunity. With the decline, infectious varicella-zoster virus is presumably produced in the nucleus of the nerve cells and is carried to the skin by the normal circulation of cytoplasm within the nerve cell. With the appearance of the skin lesions, a prompt, intense anamnestic boost of both cellular and humoral immunity ensues. A marked inflammatory reaction occurs in the ganglion with an accumulation of immune cells, and shingles quickly disappears, although sometimes leaving scars and chronic pain. ■ secondary response, p. 405

Epidemiology

The annual incidence of chickenpox in the United States has been estimated at 3.7 million but is probably lower now that immunization is widespread. Reporting the disease is not required, so that most cases go unreported, and many are so mild that they go unnoticed. Both respiratory secretions and skin lesions are infectious; as with many diseases transmitted by the respiratory route, most cases occur in the winter and spring months. Humans are the only reservoir, and because the disease is highly contagious, about 90% of people are infected by the age of 15. The incubation period of the disease averages about 2 weeks, with a range of 10 to 21 days. Cases are infective from 1 to 2 days before the rash appears until all the lesions have crusted (usually 4 days after the onset).

The mechanism by which the varicella-zoster virus persists in the body allows it to survive indefinitely in small isolated populations. By contrast, when a virus such as measles is introduced into an isolated community, it spreads quickly and infects most of the susceptible individuals, who either become immune or die. If susceptible victims are unavailable, the measles virus will disappear from the community. On the other hand, varicella-zoster virus will reappear from cases of shingles whenever sufficient numbers of susceptible children have been born. Shingles occurs in about 1% of elderly people.

Prevention and Treatment

In 1995, an attenuated chickenpox vaccine was licensed in the United States. It has proven safe with use in millions people in various countries, since about 1984. The vaccine is recommended for all healthy persons age 12 months or older who do not have a history of chickenpox or who lack laboratory evidence of immunity to the disease. Immunization should be done sometime before one's 13th birthday because of the increased likelihood ofserious complications from chickenpox in older children and adults. It is not given during pregnancy, and pregnancy should be avoided for 3 months after vaccination because of fear the vaccine might rarely result in congenital varicella syndrome. In general, the vaccine should not be administered to people with malignant or immunodeficiency diseases. Healthy, non-immune contacts of such people, however, should be vaccinated. By pre-

22.4 Skin Diseases Caused by Viruses 549

venting chickenpox, the vaccine markedly decreases the chance of developing shingles. ■ attenuated vaccines, p. 422

Increasing numbers of individuals with impaired immunity are at risk of severe disseminated varicella-zoster virus infections. These include persons with cancer, AIDS, and organ transplants and newborn babies whose mothers contracted chickenpox near the time of delivery. They can be partially protected from severe disease if they are passively immunized by injecting them with zoster immune globulin (ZIG) derived from the blood of recovered herpes zoster patients. The antiviral medications acyclovir and famciclovir, among others, are helpful in preventing and treating varicella-zoster infections. ■ passive immunity, p. 420

The main features of chickenpox are summarized in table

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