Phòng khám chuyên khoa da li�u - Thạc s� bác s� Hu�nh Văn Quang

Rubella (German Measles)

DEFINITION

Rubella is an acute viral infection of children and adults that characteristically includes rash, fever, and lymphadenopathy and has a broad spectrum of other possible manifestations. However, a high percentage of rubella infections in both children and adults are subclinical. In addition, the illness can resemble a mild attack of measles (rubeola) and can cause arthritis, especially in adults. Rubella was formerly known as German measles because it was first described clinically as distinct from rubeola in Germany, where it generated much medical interest in the mid-eighteenth and early nineteenth centuries. Rubella during pregnancy can lead to fetal infection, with the production of a significant constellation of malformations (congenital rubella syndrome) in a high proportion of infected fetuses. Rubella virus was first isolated in cell culture just before the last pandemic of the disease began in 1962. Since the licensing of rubella vaccine in the United States in 1969, there have been no further epidemics in this country.

ETIOLOGIC AGENT

Rubella virus, a togavirus, is the only member of the Rubivirus genus and is closely related to the alphaviruses. Unlike these agents, however, it does not require a vector for transmission. Moreover, there is no RNA sequence homology between rubella virus and the alphaviruses.The rubella virion is composed of an inner icosahedral capsid of RNA and protein that is surrounded by a lipid-containing envelope with glycoprotein spikes and a diameter of about 60 nm. The structural proteins associated with rubella virus are E1 and E2 (transmembrane envelope glycoproteins) and C (the capsid protein that surrounds the viral RNA). Only one serotype has been identified.

EPIDEMIOLOGY

In the United States during the prevaccine era, rubella was most common in the spring and most often affected school-age children; only 80 to 90% of adults were immune; and major epidemics occurred every 6 to 9 years. The most recent epidemic in the United States occurred in 1964 to 1965, when more than 12 million cases of postnatal rubella and more than 20,000 cases of the congenital rubella syndrome were reported. Although there have been no epidemics since the introduction of live attenuated rubella vaccine in 1969, limited outbreaks have been reported in settings where susceptible individuals come into close contact with one another (e.g., schools and workplaces). In 2001, only 23 cases of postnatally acquired rubella most of them in young adults and 3 confirmed cases of congenital rubella syndrome were reported to the Centers for Disease Control and Prevention (CDC).Whether symptomatic or subclinical, rubella is contagious, albeit less so than measles. Its incubation period is 18 days on average, with a range of 12 to 23 days. The virus, which is spread in droplets shed in respiratory secretions, infects the respiratory tract and then the bloodstream. In postnatally acquired infections, rubella virus is shed during the prodromal phase of the illness, and shedding from the pharynx can continue for about a week after onset. Despite high titers of specific neutralizing antibodies, infants with congenital rubella may excrete rubella virus from the respiratory tract and in the urine until the age of 2 years. This excretion raises important issues related to infection control in hospital and day-care settings. Persons recently immunized with live attenuated rubella vaccine do not transmit the vaccine virus to others, although low titers of rubella virus may be detected transiently in the pharynx.After an attack of rubella, specific antibodies and cell-mediated immunity develop and probably play a significant role in protection against future disease. Asymptomatic reinfection at the level of the respiratory tract is common upon re-exposure to the virus but is rarely, if ever, associated with viremia.Rubella virus has been cultured from respiratory secretions during reinfection. Fetal infection may occur during maternal reinfection but is acknowledged to be extremely rare because of the absence of maternal viremia under these circumstances. Viremia following reinfection of individuals immunized against rubella is also rare. Thus the current level of congenital rubella in the United States is exceedingly low. Recently, however, it has been observed that young immigrants to the United States from countries in Latin America and the Caribbean, where rubella vaccine is not routinely given to children, are at increased risk for rubella susceptibility. Because infants with the congenital rubella syndrome have been born to immigrant Hispanic women, increasing efforts are being made to identify and vaccinate such women before they become pregnant.

PATHOGENESIS AND PATHOLOGY

Little is known about the microscopic pathology of postnatally acquired rubella because the disease is invariably self-limited. Like that of measles, the rash of rubella is immunologically mediated; its onset coincides with the development of specific antibodies. Viremia can be demonstrated for about a week before and ends within a few days after the onset of rash.The cause of the damage to cells and organs in congenital rubella is not well understood. Proposed mechanisms of fetal damage include mitotic arrest of cells, tissue necrosis without inflammation, and chromosomal damage. The growth of the fetus may be retarded. Other findings may include decreased numbers of megakaryocytes in the bone marrow, extramedullary hematopoiesis, and interstitial pneumonia.

CLINICAL MANIFESTATIONS

Postnatally Acquired RubellaInfection acquired after birth usually results in an extremely mild or subclinical illness. A prodromal phase is uncommon in children; adults may have more severe disease, with a brief prodrome of malaise, fever, and anorexia. The foremost symptoms of postnatally acquired rubella include posterior auricular, cervical, and suboccipital lymphadenopathy; fever; and rash. The rash often begins on the face and spreads down the body. It is maculopapular but not confluent, is sometimes accompanied by mild coryza and conjunctivitis, and generally lasts for 3 to 5 days. A petechial enanthem on the soft palate, designated Forschheimer spots, may occur but is not specific for rubella. Fever may be absent entirely or may be present for only several days in the early phase of the illness.Complications of postnatally acquired rubella are uncommon; bacterial superinfection is rare. One particularly troublesome complication is seen almost exclusively in women: arthritis, most frequently involving the fingers, wrists, and/or knees. Arthritis develops as the rash is appearing and may take several weeks to resolve. Chronic arthritis resulting from rubella is extremely rare. Rubella virus has been isolated from joint fluid during acute rubella arthritis and from peripheral blood in chronic rubella arthritis.Another complication of postnatally acquired rubella is hemorrhage due to both thrombocytopenia and vascular damage; this complication occurs in 1 of every 3000 patients. Thrombocytopenia may last for weeks or months; it can have long-term consequences if there is bleeding into organs such as the eye or the brain.Both children and adults may develop encephalitis after rubella; the incidence is about five times lower than that of encephalitis following measles. Adults are more likely than children to develop encephalitis; the mortality rate from this complication is 20 to 50%. Mild hepatitis is an unusual complication. Immunosuppressed patients are not at increased risk for rubella as they are for measles.Congenital RubellaMaternal infection in early pregnancy can lead to fetal infection, with resultant congenital rubella. The classic signs of congenital rubella are cataract, heart disease, deafness, and myriad other defects(Table 1). The most important factor in the pathogenicity of rubella virus for the fetus is gestational age at the time of infection. Maternal infection during the first trimester leads to fetal infection in about 50% of cases; maternal infection early in the second trimester leads to fetal infection in about one-third of cases. Fetal malformations not only are more common after maternal infection in the first trimester but also tend to be more severe and to involve more organ systems. Whereas a fetus infected in the fourth week of gestation may develop many problems, one infected later (e.g., in the twentieth week) may have isolated deafness as the only symptom.

DIAGNOSIS

Because postnatally acquired rubella is often a mild disease and because many cases are subclinical, diagnosis on clinical grounds can be difficult. Other diseases that may mimic rubella include toxoplasmosis, scarlet fever, modified measles, roseola, fifth disease (erythema infectiosum due to parvovirus B19), and enteroviral infection. Routine laboratory tests usually reveal leukopenia and atypical lymphocytes.The isolation of rubella virus in cell cultures of throat samples, urine, or other secretions is difficult and expensive but is sometimes undertaken. This technique is most useful when congenital rubella is suspected. A laboratory diagnosis is more often made serologically. The most commonly used test is an enzyme-linked immunosorbent assay (ELISA) for IgG and IgM antibodies. Acute rubella is diagnosed by the documentation of a fourfold or greater rise in the titer of IgG antibodies in paired acute- and convalescent-phase serum specimens or by the detection of rubella-specific IgM antibodies in one serum specimen. However, false-negative and false-positive IgM reactions are sometimes obtained. Moreover, true-positive IgM reactions can occur in both primary infection and reinfection. Congenital rubella is diagnosed by the isolation of rubella virus, the detection of IgM antibodies in a single serum sample, and/or the documentation of either the persistence of rubella antibodies in serum beyond 1 year of age or a rising antibody titer anytime during infancy in an unvaccinated child. Biopsied tissues and/or blood and cerebrospinal fluid have also been used for the demonstration of rubella antigens with monoclonal antibodies and for the detection of rubella RNA by in situ hybridization and polymerase chain reaction.

PREVENTION

Live attenuated rubella vaccine was licensed in 1969, 7 years after the virus was first isolated in culture. This vaccine was developed as a strategy to prevent congenital rubella by ensuring that very few pregnant women would be susceptible and that there would be little circulating wild-type virus. Rubella vaccine induces seroconversion in more than 95% of recipients. Since its licensure, there have been no major epidemics in the United States, and the number of cases has declined by 98%. The vaccine currently licensed in the United States, RA 27/3, is propagated in human diploid cells and is more immunogenic (particularly with regard to the stimulation of secretory immunity) than previously licensed vaccines. The present vaccination strategy, developed in part when measles was not being adequately controlled, is to immunize all infants at 12 to 15 months of age with measles-mumps-rubella (MMR) vaccine and to administer a second dose in early childhood. Rubella vaccine may also be administered to anyone who is thought to be susceptible to the infection and is not pregnant; it is particularly important that hospital workers of either sex be immune to rubella so that nosocomial transmission is avoided. Although there has been little change in the prevalence of immunity to rubella among women of childbearing age (about 80%), the incidence of congenital rubella is extremely low fewer than 10 cases annually. It is likely that, although antibody may be undetectable years after immunization, protection against infection possibly due to cell-mediated immunity is the rule. At present, there is little if any evidence of significant waning of clinically important immunity to rubella with time.On occasion, rubella vaccine may cause arthralgia or arthritis, especially in young women. Very rarely, rubella vaccination results in chronic arthritis; however, even cases of frank arthritis in vaccinees are self-limited, lasting only about 1 week.After investigation of a series of more than 400 women who were inadvertently immunized during pregnancy and who carried their infants to term, the CDC has concluded that vaccine-type rubella virus either does not cause the congenital rubella syndrome at all or does so at an incidence too low to be detected. Nonetheless, rubella vaccine is contraindicated for use in pregnant women, and it is recommended that pregnancy be avoided for at least 3 months after rubella vaccination. It is acceptable for rubella-susceptible children whose mothers are also susceptible to be immunized, as vaccinated individuals do not shed rubella virus or transmit it to susceptible individuals. Although it is recommended that rubella vaccine not be given to immunosuppressed persons, the vaccine is given to children infected with HIV. No adverse effects of rubella vaccine have been reported in immunocompromised patients.

TREATMENT

There is no specific therapy for rubella. At one time, immune globulin was used in an effort to prevent congenital rubella when pregnant women became infected. However, because administration of immune globulin did not prevent maternal viremia, this approach was discarded. Symptom-based treatment is given for manifestations such as fever, arthralgia, and arthritis.

• < Trước
• Tiếp tục >