AUTHOR AND EDITOR INFORMATION

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INTRODUCTION

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Background

Rubella is usually a mild viral illness involving the skin, the lymph nodes, and, less commonly, the joints. Its most important complication is congenital rubella syndrome (CRS).

Pathophysiology

Rubella is an RNA virus classified as a Rubivirus in the Togaviridae family.

Frequency

United States

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 vaccine, the number of cases has decreased by approximately 99%.

One major focus of infection is now unvaccinated adults (eg, college students). As many as 10% of young adults may still be susceptible to infection. Of increasing concern is the high incidence of rubella in unvaccinated Hispanic immigrants and CRS in their offspring. Individuals from Columbia, the Dominican Republic, and Central America, where vaccination programs are just starting, are most susceptible to rubella. In a recent study, 44% of CRS cases were in Hispanic infants. This is a public health concern. In a recent outbreak in New York State, the infections spread from the Hispanic community, along train and work lines, to involve 14 towns and 95 individuals.

Mortality/Morbidity

Rubella is usually mild. Rarely, encephalitis, thrombocytopenia, or neuritis may occur. Such manifestations are usually self-limited.

Race

The disease has no racial predilection.

Sex

Both sexes are equally affected.

Age

Rubella is a disease primarily affecting young children, but adolescents and young adults are also affected.

CLINICAL

Section 3 of 11  

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History

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. 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.

Physical

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.

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. It may be related to the presence of circulating immune complexes, which are seen more frequently in persons who have had vaccinations with joint complaints than those who have had vaccinations but are without joint complaints. 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.

Causes

Rubella is an RNA virus classified as a Rubivirus in the Togaviridae family.

DIFFERENTIALS

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Other Problems to be Considered

Juvenile rheumatoid arthritis

WORKUP

Section 5 of 11  

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Lab Studies

• In a healthy child or adolescent, the diagnosis is made on a clinical basis, and a laboratory workup is not necessary.
• If the diagnosis is in doubt, a rising titer of immunoglobulin M (IgM) antibody over a 2-week period indicates a recent infection.
• 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 where encephalitis is present, lymphocytes are present in the cerebrospinal fluid (CSF).
• Rubella virus can be isolated from the nasopharynx, the blood, the urine, and CSF.
• In rubella, complement-fixing, hemagglutination-inhibiting, and neutralizing antibodies are seen. The latter 2 persist for life. The hemagglutination-inhibiting antibodies are tested for easily, and a 4-fold increase in the convalescent period is indicative of new infection. Now, newer tests with a higher specificity (eg, latex agglutination, fluorescence immunoassay, passive hemagglutination, hemolysis in gel, enzyme immunoassay tests) are available. From a public health standpoint, attempting to confirm a rubella infection in a pregnant woman or a newborn or an infant is important.
• A pregnant woman exposed to rubella should be tested immediately for a rubella-specific antibody. The presence of rubella-specific immunoglobulin G (IgG) is evidence that the patient is immune.
• • If the test result is negative, repeat the test again in 3-4 weeks, and also 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 CRS will show 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 CRS in an infant with serology alone is very difficult.

Histologic Findings

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 clinically present, extravasation of erythrocytes may be observed.

TREATMENT

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Medical Care

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.

MEDICATION

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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 where fever and polyarthralgia are more common, acetaminophen, aspirin, or other nonsteroidal anti-inflammatory drugs (NSAIDs) are useful.

Drug Category: Salicylates

These agents can reduce inflammation and fever.

Drug Category: Nonsteroidal anti-inflammatory agents

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.

FOLLOW-UP

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Deterrence/Prevention

• While rubella usually has a mild clinical course, the sequel of CRS can be devastating. The main defense against this condition is a comprehensive vaccination plan nationally and internationally.
  • In 2004, the US Centers for Disease Control and Prevention announced that since 2001, fewer than 25 cases of rubella have been reported annually in the United States, with a 95% vaccination rate among school-aged children and an estimated 91% rate of population immunity. The national objective is to completely eliminate rubella and CRS in the United States by 2010.
  • In contrast, 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.
  • A population-based study in Denmark involving over 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. These results have been confirmed by other studies. The theory that the MMR vaccine causes autism is a misconception that must be overcome. Parents must be cautioned that by not vaccinating their children because of this misconception, they may be exposing them and society to the very real complications of CRS.
• The live rubella vaccine is a RA27/3 strain grown in human diploid cell cultures. It is usually given with the measles and mumps vaccine (MMR) at age 12-15 months and again at school entry at 4-6 years. The MMR vaccine can now be combined with varicella vaccine (MMRV) as one injection for ease of administration.
• Postpubertal males and females should be vaccinated, especially college students, military recruits, postpartum women, health workers, and immigrant men and women who have no evidence of immunity or history of at least 1 vaccination. Clinical evidence of infection should not be relied upon because it is too unreliable.
• • A few contraindications to vaccination exist.
  • Pregnant women should not be vaccinated; however, vaccination of her household contacts is not contraindicated because no evidence exists that the virus would spread to her even though the vaccinee may shed the virus for 1-4 weeks.
  • Patients receiving immunoglobulin should avoid vaccination 2 weeks before and 3 months after immunoglobulin administration. If immunoglobulin 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 no 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.
• 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.

Complications

• 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.
• CRS is 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% will be affected, and the severity depends on how early the infection occurs.
• • The most common abnormalities are ophthalmologic (eg, cataracts, retinopathy).
  • Cardiac abnormalities (eg, patent ductus arteriosus, pulmonary stenosis) may be seen.
  • Auditory involvement may be present with sensineural 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.
  • 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.
• 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 CRS have occurred in infants born to mothers who received immunoglobulin shortly after exposure.

Prognosis

• The prognosis is usually excellent with the exception of CRS.

Patient Education

• The major source of CRS and epidemics of rubella in the United States is among nonimmune immigrant adults, especially those from Central America and the Caribbean. Public health measures are needed to educate this group on the need for vaccination to protect themselves, their unborn children, and the community.
• For excellent patient education materials, see eMedicine's articles Immunization Schedule, Adults and Immunization Schedule, Children.

MISCELLANEOUS

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Medical/Legal Pitfalls

• Ruling out rubella in every pregnant woman with an erythematous rash is extremely important. To do so, one must have laboratory proof that the pregnant woman is immune. Clinical history should not be relied upon. If in doubt, proper testing is mandatory as outlined in the discussion of CRS (see Lab Studies). Not doing so could result in the birth of a child with CRS, which would most certainly result in legal action.

MULTIMEDIA

Section 10 of 11  

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Media file 1:  Young adult with macular rash.
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Media file 2:  Child with generalized eruption.
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Media file 3:  Blueberry muffin newborn with lesions on the forehead.
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REFERENCES

Section 11 of 11

• Authors and Editors
• Introduction
• Clinical
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• Centers for Disease Control and Prevention. Rubella and congenital rubella syndrome--United States, 1994-1997. MMWR Morb Mortal Wkly Rep. Apr 25 1997;46(16):350-4. [Medline].
• Centers for Disease Control and Prevention. Achievements in public health: elimination of rubella and congenital rubella syndrome-US, 1969-2004. Ann Pharmacother. Jun 2005;39(6):1151-2. [Medline].
• DeStefano F, Bhasin TK, Thompson WW, et al. Age at first measles-mumps-rubella vaccination in children with autism and school-matched control subjects: a population-based study in metropolitan atlanta. Pediatrics. Feb 2004;113(2):259-66. [Medline].
• Fauci AS, Braunwald E, Isselbacher KJ, eds. Harrison's Principles of Internal Medicine. 14th ed. New York, NY: McGraw-Hill; 1998:. 1226.
• Gellis SE. Rubella (German measles). In: Fitzpatrick's Dermatology in General Medicine. Vol 2. New York, NY: McGraw-Hill; 1999:. 2395-8.
• Georges P, ed. Rubella. In: 1997 Redbook: Report of the Committee on Infectious Diseases, American Academy of Pediatrics. 24th ed. 1997:456-62.
• Giles JP, Balsamo MR, Green RH, et al. Rubella: Studies on the Natural History and Prevention of the Disease. J Pediatr. 1963;63:816-7.
• Jensen V. Measles on the rise as vaccinations fall, study reports. What's New, Royal Holloway, University of London. News Release 8 August 2003.
• Lennette EH, Schmidt NJ. Diagnostic Procedures for Viral and Rickettsial Infections. 7th ed. American Public Health Association; 1979:. 725-66.
• Madsen KM, Hviid A, Vestergaard M, et al. A population-based study of measles, mumps, and rubella vaccination and autism. N Engl J Med. Nov 7 2002;347(19):1477-82. [Medline].
• Mandell GL, Bennett JE, Dolan R. Principles and Practice of Infectious Diseases. 5th ed. Philadelphia, Pa: WB Saunders; 2000:. 1708-14.
• Plotkin SA, Katz M, Cordero JF. The eradication of rubella. JAMA. Feb 10 1999;281(6):561-2. [Medline].
• Schluter WW, Reef SE, Redd SC, Dykewicz CA. Changing epidemiology of congenital rubella syndrome in the United States. J Infect Dis. Sep 1998;178(3):636-41. [Medline].
• Shinefield H, Black S, Digilio L, et al. Evaluation of a quadrivalent measles, mumps, rubella and varicella vaccine in healthy children. Pediatr Infect Dis J. Aug 2005;24(8):665-9. [Medline].
• Weedon D, Strutton G. Skin Pathology. Edinburgh, Scotland: Churchill Livingston; 1997:. 597.

Article Last Updated: Mar 7, 2007