Rubella is usually a mild viral illness involving the skin, the lymph nodes, and, less commonly, the joints. The most important complication of rubella is congenital rubella syndrome (CRS).
Before the live rubella vaccine, epidemics of the disease were seen in young children (most common), adolescents, and young adults every 5-9 years in winter and early spring. Since the rubella vaccine, the number of rubella cases has decreased significantly.
Because of the morbidity of measles and rubella, the World Health Organization (WHO) maintains a worldwide Measles and Rubella Laboratory Network (LabNet) to monitor the behavior of the viruses.[1] Because of the unreliability of clinical diagnosis, laboratory surveillance is important in setting rubella elimination goals. Serum-based diagnostics remain the criterion standard; however, programs are being developed using dried blood samples and oral fluid for confirmation of infection in those areas where patients might resist venipuncture or where transportation and refrigeration of blood samples is difficult.
One major focus of infection in the recent past was unvaccinated adults.[2] Of concern was the high incidence of rubella in unvaccinated Hispanic immigrants and congenital rubella syndrome in their offspring.[3] Individuals from Columbia, the Dominican Republic, and Central America, where vaccination programs were just starting, were often susceptible to rubella. In one study, 44% of congenital rubella syndrome cases were in Hispanic infants.[4] This was a public health concern. In an outbreak in 1997-98 in New York State, the infections spread from the Hispanic community, along train and work lines, to involve 14 towns and 95 individuals.
Now fortunately, the Pan American Health Organization of the WHO announced that the endemic transmission of rubella has ended in the Americas and that the Americas are free of endemic rubella.[5] The last confirmed case was in Argentina in 2009. This end of endemic rubella was achieved by the high percentage of vaccination in the population. This does not mean that the threat of rubella is over, as the remainder of the world is not rubella–free, and, with the mobility of the world population, cases of rubella may still enter the United States.
The Centers for Disease Control and Prevention (CDC)[6] states that a nonimmune woman with a rubella infection in the first trimester stands a 90% chance of miscarriage, stillbirth, or transmittal of congenital rubella syndrome (CRS) to her baby. Five of 10 healthy babies do not receive the vaccine, even though it now costs about a dollar. The CDC maintains that 79 countries now are using the vaccine more, but the WHO[7] maintains that 45 member states have not yet introduced the vaccine and two regions (African and Eastern Mediterranean) have not yet set control targets. Therefore, it is possible for rubella to enter the United States, and so it is essential to maintain a high level of immunization in the population to ensure herd immunity. Constant vigilance remains crucial.
Race
Rubella has no racial predilection.
Sex
Both sexes are equally affected by rubella.
Age
Rubella primarily affects young children, but adolescents and young adults are also affected.
Now that endemic rubella is eliminated in the Americas, the threat of rubella epidemics and subsequent congenital rubella syndrome would be from cases of rubella that enter the United States from other areas of the world and infect the unvaccinated clusters in this country. Therefore, the Measles and Rubella Initiative calls for monitoring the disease using effective surveillance, developing and maintaining outbreak preparedness, communicating and engaging to build public confidence and demand for immunization, and continuing research to improve cost-effective vaccinations and diagnostic tools.[8]
For patient education materials, see the articles Immunization Schedule, Adults and Immunization Schedule, Children.
Studies on children at the New York Willowbrook State School in 1963, shortly after the isolation of the rubella virus, have shown that the disease is spread by nasal droplet infection and has an incubation period of 14-19 days, with onset of a rash usually on the 15th day.[9] The disease can be spread from a few days before to 5-7 days after the appearance of the exanthem. The virus can be detected in the pharynx from 7 days before until 7 days after the rash. A viremia was detected from 7 days before until the day of the rash, and the virus was present in the stool from 4 days before until 4 days after the rash. Isolating the virus from children with subclinical infections was also possible.
Patients are most contagious when the rash is erupting. Rarely, the virus may be shed from the pharynx up to 15 days after the appearance of the rash, in rapidly diminishing amounts, and it is very difficult to detect by culture after 5-7 days. Patients are not considered clinically contagious after 7 days.
Infection usually confers lifelong immunity, but reinfection is occasionally detected serologically after the natural disease or a vaccination upon reexposure to the virus and rarely results in clinical disease.
In children, a prodrome may not be present. The rash may be the first manifestation. In adults, fever, sore throat, and rhinitis may be present. The exanthem begins as discrete macules on the face that spread to the neck, the trunk, and the extremities. The macules may coalesce on the trunk. Appearance of the rash corresponds with the appearance of the rubella-specific antibody. The exanthem lasts 1-3 days, first leaving the face, and may be followed by desquamation. On occasion, a nonspecific enanthem (Forchheimer spots) of pinpoint red macules and petechiae can be seen over the soft palate and the uvula just before or with the exanthem. Note the images below.
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Young adult with macular rash.
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Child with generalized eruption.
The hallmark of rubella is the generalized, tender lymphadenopathy that involves all nodes, but which is most striking in the suboccipital, postauricular, and anterior and posterior cervical nodes. It is most prevalent at the time of appearance of the exanthem but may precede it by a week. The tenderness that accompanies this lymphadenopathy subsides rapidly; however, the enlargement may last days or weeks.
Although less common in children, in adults, polyarthralgia and even polyarthritis may occur and rarely may persist longer than 2 weeks. It may resemble rheumatic fever or rheumatoid arthritis, with small and large joints being involved bilaterally with or without swelling. The swelling can be very marked. Fifty percent of women may have arthralgias, and 10% have arthritis, 3 days post rash with the natural infection or within 2-6 weeks after a vaccination.
Rarely, recurrent episodes of inflammation of the fingers, the wrists, and the knees can continue for more than a year. Very rarely, a syndrome of low-grade fever, chronic fatigue, and myalgias can persist for months or years. The pathogenesis of the arthritis is not known. The virus can be isolated from joint effusions in acute and recurrent cases. Peripheral blood mononuclear cells may harbor the rubella virus in chronic arthritis. Test results for rheumatoid arthritis are negative.
Complications are rare with rubella in healthy infants and adults. Rarely, encephalitis or peripheral neuritis may occur; however, recovery is usually complete without sequelae. Thrombocytopenia usually resolves within a month, but it may result in purpura, epistaxis, and intestinal bleeding.
Congenital rubella syndrome (CRS)
This the most severe and important complication of rubella and occurs in the fetus of a pregnant woman without immunity to the virus. Of infants infected in the first trimester, 50% are affected, and the severity depends on how early the infection occurs. Note the following:
The most common abnormalities are ophthalmologic in nature (eg, cataracts, retinopathy).
Cardiac abnormalities (eg, patent ductus arteriosus, pulmonary stenosis) may be seen.
Auditory involvement may be present as sensorineural deafness.
Neurologic disorders (eg, meningoencephalitis, mental retardation with behavioral disorders) may occur.
If infection occurs after organ development, a variable picture may be seen, with hepatitis, splenomegaly, pneumonitis, myocarditis, and/or osteomyelitis.
If the bone marrow is affected, thrombocytopenia with purpura and petechiae occur. Bizarre purple macules and papules, which represent persistent dermal (extramedullary) hematopoiesis, are seen in the skin. This appearance is known as blueberry muffin baby. Note the image below.
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Blueberry muffin newborn with lesions on the forehead.
An infant who is affected may continue to shed the virus for up to 1 year. At least 85% of infants who are affected shed the virus at 1 month, and 1-3% do so at 1 year. Therefore, these individuals should be considered contagious for at least 1 year and should be considered an exposure threat to nonimmune pregnant women, unless nasopharyngeal or urine culture results are repeatedly negative.
Pregnancy
No adequate treatment is available for pregnant women exposed to rubella. Immunoglobulin is not recommended unless termination of the pregnancy is not an option because cases of congenital rubella syndrome have occurred in infants born to mothers who received immunoglobulin shortly after exposure.
In a healthy child or adolescent, the diagnosis of rubella is made on a clinical basis, and a laboratory workup is not necessary.
A WBC count, if performed, may be lower than normal, as in many viral infections, with increased percentages in the lymphocyte count. In those very rare cases in which encephalitis is present, lymphocytes are present in the cerebrospinal fluid (CSF). If necessary, rubella virus can be cultured from the nasopharynx, blood, urine, and CSF.[10]
If the diagnosis is in doubt, a rising titer of immunoglobulin M (IgM) antibody over a 2-week period indicates a recent infection. Two specific antibodies are associated with Rubella. The first to appear is IgM antibody, which rises and peaks 7-10 after infection and then tapers off after several weeks. One exception to this rule is in the infected newborn, in whom IgM may be detected for months to a year. The immunoglobulin G (IgG) antibody develops more slowly but remains positive for life. It confers immunity against repeat infection. Therefore, the presence of IgM antibody indicates a recent infection, whereas IgG antibody indicates an old infection and immunity. IgG antibody may also indicate immunity caused by the measles, mumps, rubella (MMR) vaccine.
From a public health standpoint, attempting to confirm a rubella infection in a pregnant woman or a newborn infant is important; a pregnant woman exposed to rubella should be tested immediately for a rubella-specific antibody. The presence of rubella-specific IgG is evidence that the patient is immune. If the test result is negative, repeat the test again in 3-4 weeks, and repeat the test on the first specimen. If an antibody is present in the second test and not in the first test, an infection has occurred. If the second test result is negative, repeat the test in 6 weeks, and, again, test it with the first specimen. A negative test result in both specimens means an infection has not occurred, whereas if the last specimen is positive and the first specimen is negative, then an infection has occurred.
An infant with congenital rubella syndrome shows the IgG antibody from the mother, which disappears in a few months, and an elevated IgM antibody level because of antibody production by the infant. The presence of the IgM antibody usually indicates recent infection because IgM does not cross the placenta from the mother as does IgG. After 1 year, confirming the diagnosis of congenital rubella syndrome in an infant with serology alone is very difficult.
The histopathologic features of the skin are those of the Togaviruses, namely, a light perivascular infiltrate of lymphocytes with mild endothelial swelling. If petechiae or purpura are present clinically, extravasation of erythrocytes may be observed.
No specific treatment is available for rubella. The disease is usually self-limited. Rest and oral fluids are appropriate. Individuals may remain contagious for 7 days after the onset of the rash, and they should be appropriately isolated from work, school, or other public settings.
While rubella usually has a mild clinical course, the sequel of congenital rubella syndrome can be devastating. The main defense against congenital rubella syndrome is a comprehensive vaccination plan nationally and internationally.
In 2003, an increase occurred in cases of rubella in England and Wales that was the direct result of a decrease in the vaccination rate, because of perceived adverse effects of the MMR vaccination, namely autism.[11] A population-based study in Denmark involving more than a half million children showed no significant increase in autism in children who had received the MMR vaccination compared with those who were not vaccinated.[12] These results have been confirmed by other studies.[13]
The idea that the MMR vaccine causes autism is a misconception that must be overcome. Because of the lack of valid evidence, the Federal "vaccine court" now rejects claims that the MMR vaccine causes autism.[14] Parents must be cautioned that by not vaccinating their children because of this misconception, they may be exposing them and others to the very real complication of congenital rubella syndrome. Physicians, who are usually the primary source of correct information for their patients, must work with these parents to understand and attempt to minimize these fears.[15]
The Measles and Rubella Initiative Strategic Plan 2010-2020,[8] which is indorsed by the WHO, the CDC and other global health organizations, models its plan to eliminate these viral diseases globally based on the experience in the Americas, where endemic rubella is now eliminated. The mainstay of this strategy is to achieve and maintain high levels of population immunity by providing high vaccination coverage with two doses of measles- and rubella-containing vaccines. One obstacle to achieving this goal is the increase in vaccine refusals for "personal belief" in the United States, resulting in geographic clusters of refusals and the possibility of outbreaks. This increases the risk of infection for those who refuse vaccination and for those who are not candidates for it because of age, immunosuppression, or some other contraindication.[15] Fortunately, some states are now passing legislation that removes personal belief as a reason not to be vaccinated.
The live rubella vaccine is an RA27/3 strain grown in human diploid cell cultures. The live rubella vaccine is usually given with the measles and mumps vaccine (ie, MMR vaccine) at age 12-15 months and again at school entry at age 4-6 years. The MMR vaccine can now be combined with the varicella vaccine (ie, MMRV vaccine) as one injection for ease of administration.[16]
The Centers for Disease Control and Prevention (CDC) have issued the following recommendations[17] :
One or more doses of MMR vaccine should be given to adults who were born during or after 1957 unless they have a medical contraindication, documentation of one or more doses, history of measles diagnosed by a healthcare provider, or laboratory evidence of immunity.
A second dose of MMR is recommended for adults recently exposed in an outbreak setting, previously vaccinated with a killed measles vaccine, or vaccinated with an unknown type of measles vaccine during 1963-1967.
Second doses should also be given to students in postsecondary educational institutions, who work in a healthcare facility, or who plan international travel.
Women of childbearing age, regardless of birth year, should be assessed for rubella immunity and counseled concerning congenital rubella syndrome. Women without immunity should receive the MMR vaccine upon completion or termination of pregnancy and before discharge from the healthcare facility.
A few contraindications to vaccination should be noted, as follows:
Pregnant women should not be vaccinated; however, vaccination of her household contacts is not contraindicated because no evidence indicates that the virus would spread to her even though the vaccinee may shed the virus for 1-4 weeks.
Patients receiving hyperimmune globulin should avoid vaccination 2 weeks before and 3 months after its administration. If hyperimmune globulin is given, the patient should be tested for immunity at least 8 weeks following vaccination.
Patients who are seriously ill should not be vaccinated; however, fever in itself is not a contraindication.
Patients with severe altered immunity should not be vaccinated. Patients on immunosuppressive therapy should not be vaccinated for 3 months. Patients with HIV disease may be vaccinated if they are not severely immunocompromised.
Also see the Recommended Immunization Schedule for Adults Aged 19 Years or Older, United States, 2017 from the CDC.[18]
Adverse reactions to vaccination include rash, fever, and/or lymphadenopathy developing 5-12 days later in 5-15% of children. Joint pain is rare but is more prevalent in women and is usually less severe than that seen in the naturally occurring disease. Rarely, transient peripheral neuritis symptoms have been reported.
The combined MMRV vaccine (ProQuad) has been shown to be associated with an increased risk of febrile seizures occurring 5-12 days following vaccination, at a rate of 1 in 2300-2600 in children aged 12-23 months compared with a separate MMR vaccine and a varicella vaccine administered simultaneously.[19, 20] As a result, the CDC Advisory Committee on Immunization Practices (ACIP) recommends that separate MMR and varicella vaccines be used for the first dose, although providers or parents may opt to use the combined MMRV for the first dose after counseling regarding this risk.[21] MMRV is preferred for the second dose (at any age) or the first dose if given at age 48 months or older.
Data from postlicensure studies do not suggest that children aged 4-6 years who received the second dose of MMRV vaccine had an increased risk for febrile seizures after vaccination compared with children of the same age who received the MMR vaccine and varicella vaccine administered as separate injections at the same visit.[21]
No specific medication is available for rubella, except that given for symptomatic relief. High fever and polyarthralgia are rare in children; however, if present, acetaminophen may be used. In adults, in whom fever and polyarthralgia are more common, acetaminophen, aspirin, or other nonsteroidal anti-inflammatory drugs (NSAIDs) are useful.
Clinical Context:
Aspirin treats mild to moderate pain and headache. It inhibits prostaglandin synthesis, which prevents the formation of platelet-aggregating thromboxane A2. Aspirin acts on the heat-regulating center of the hypothalamus and vasodilates peripheral vessels to reduce fever.
Clinical Context:
Ibuprofen is the drug of choice for mild to moderate pain. It inhibits inflammatory reactions and pain by decreasing prostaglandin synthesis. It is one of the few NSAIDs indicated for reduction of fever.
These agents have analgesic and antipyretic activities. Their mechanism of action is not known, but they may inhibit cyclo-oxygenase activity and prostaglandin synthesis. Other mechanisms (eg, inhibition of leukotriene synthesis, lysosomal enzyme release, lipoxygenase activity, neutrophil aggregation, various cell membrane functions) may also exist. Although its effects in the treatment of pain tend to be patient-specific, ibuprofen is usually DOC for initial therapy.
Peter C Lombardo, MD, Associate Clinical Professor, Department of Dermatology, Columbia University College of Physicians and Surgeons; Private Practice, Sutton Place Dermatology, PC
Disclosure: Nothing to disclose.
Specialty Editors
Richard P Vinson, MD, Assistant Clinical Professor, Department of Dermatology, Texas Tech University Health Sciences Center, Paul L Foster School of Medicine; Consulting Staff, Mountain View Dermatology, PA
Disclosure: Nothing to disclose.
Van Perry, MD, Assistant Professor, Department of Medicine, Division of Dermatology, University of Texas School of Medicine at San Antonio
Disclosure: Nothing to disclose.
Chief Editor
Dirk M Elston, MD, Professor and Chairman, Department of Dermatology and Dermatologic Surgery, Medical University of South Carolina College of Medicine
Disclosure: Nothing to disclose.
Additional Contributors
Gregory J Raugi, MD, PhD, Professor, Department of Internal Medicine, Division of Dermatology, University of Washington at Seattle School of Medicine; Chief, Dermatology Section, Primary and Specialty Care Service, Veterans Administration Medical Center of Seattle
Disclosure: Nothing to disclose.
Acknowledgements
The authors and editors of Medscape Reference gratefully acknowledge the contributions of previous Chief Editor, William D. James, MD, to the development and writing of this article.
References
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