CHILDHOOD EXANTHEMS: Measles Rubeola

 

Exanthems are a common cause of generalized rashes in children. They pose a diagnostic challenge to even the most experienced physician because of the diversity of their clinical presentations. The morphology distribution, and associated signs and symptoms are sometimes specific enough for a definitive diagnosis, but, nonspecific clinical findings often make this impossible. Advances in laboratory techniques (particularly in viral diseases), new antiviral drugs and vaccines, epidemics of old exanthems, and the recognition of new clinical syndromes have stimulated renewed interest in exanthems. Historically, exanthems were numbered in the order in which they were first differentiated from other exanthems. Thus, "first" disease was measles (rubeola), "second" disease was scarlet fever, and "third" disease was rubella (German measles). The specific disease described as "fourth" disease, so-called Pilatov-Dukes disease, is no longer accepted as a distinct clinical entity, with some authors speculating that it represented staphylococcal scalded skin syndrome, and others speculating that it was concurrent infection with both scarlet fever and rubella. Fifth disease is erythema infectiosum, and sixth disease is roseola infantum. Only in the last decade, with the identification of parvovirus B19 as the cause of erythema infectiosum and human herpesvirus 6 as the cause of roseola infantum, have the causative agents of the classic exanthems been identified.

Measles

Measles is caused by paramyxovirus RNA virus. The spherical virus particles are approximately 100-200 nm in diameter. Measles virus is highly labile which results in a very short survival time when it is not associated with a host. Measles usually occurs in the winter and spring, although sporadic cases can occur year 'round. Its clinical manifestations are sufficiently distinctive so that a specific clinical diagnosis can be made in most cases. The incubation period of measles is approximately 1 week. Three forms of measles are recognized clinically, typical, modified, and atypical.

Symptoms

Measles usually begins like a common cold after a seven to fourteen day incubation period, with sinus congestion, a runny nose, a cough, and red, irritated eyes. Two days later, although often unnoticed, Koplik's spots (small red spots with bluish-white specks in the center) form inside the mouth opposite the molars. After four days of these worsening symptoms, a telltale rash appears first on the face and neck, then on the trunk, arms and legs. Patients may have some degree of sensitivity to light. After two to four days of listlessness, the rash, cough, stuffiness, and red eyes (conjunctivitis) abruptly improve. If no complications have set in, measles has run its course by the tenth day. Measles patients can have lowered resistance to infections such as bronchitis, ear infections, or other bacterial infections. Possible direct complications may include pneumonia and inner ear infections such as otitis media and mastoiditis which can possibly lead to deafness. Encephalitis, which occurs in up to one out of 1,000 measles cases, can result in mental retardation. In some extreme cases, corneal ulceration may occur. Measles virus may also be associated with Subacute Sclerosing Panencephalitis (SSPE), a slow virus infection. (Slow viruses may stay dormant in humans for extended periods of time, then for reasons yet unknown, may become reactivated.) SSPE is a chronic brain disease of children and adolescents that can occur months to years (usually years) after an attack of measles. SSPE can cause intellectual deterioration, convulsive seizures, coma and motor abnormalities. Three forms of measles are recognized clinically, typical, modified, and atypical.

Typical measles  is the most common form, occurring in individuals without immunization. A characteristic prodome of 2 to 4 days of high fever, coryza, cough, and conjunctivitis virtually always precedes the onset of the exanthem. Koplik spots, the pathognomonic enanthem of measles appear during the prodrome and fade within 2 to 3 days after the onset of rash. These spots, are tiny, white or blue-gray specks superimposed on an erythematous base, located on the buccal mucosa, most prominently adjacent to the molars.

        The rash measles begins behind the ears and at the scalp margin, rapidly spreading downward to involve the entire body. Lesions begin as discrete erythematous papules that gradually become confluent. The rash is usually not pruritic. It lasts 4 to 7 days before fading, often with branny desquamation.

        Fever usually begins to decline on the second or third day of the rash unless complications of infection occur. Pneumonia, diarrhea, and otitis media are the most common complications. Other complications include laryngo-tracheobronchiolitis, myocarditis, and encephalitis.

        Modified measles occurs in partially immune hosts, either young infants with partial protection through maternal antibody or immunized individuals with partial vaccine failure. In these cases the prodrome may be shorter and the rash less severe. Koplik spots help greatly in diagnosis, if present, but without them, the rash may be difficult to differentiate from other viral exanthems.

        Atypical measles characteristically occurs in individuals who became infected after having received the killed measles virus vaccine which was given only until 1967, but a few less severe cases have been reported in children receiving live attenuated vaccine. The abrupt onset of high fever, myalgias, and cough is followed 2 to 5 days later by a rash beginning on the extremities, which gradually spreads centrally. The morphology is usually papular or papulovesicular, and lesions are often hemorrhagic. Koplik spots are usually absent. A lobule or segmental pneumonia is virtually always present, and pleural effusions are common. Other findings include hepatosplenomegaly, hyperesthesias or dysesthesia, and weakness. The exanthem of atypical measles differs from that of typical measles. It is often variable but can generally be categorized into one of three types. The exanthem usually begins as erythematous macules and papules on the distal extremities around the palms, wrists, soles, and ankles. This centripetal pattern also occurs in Rocky Mountain spotted fever and meningococcal sepsis. It then spreads to involve the trunk and face. The lesions may continue in this pattern or progress to vesicles or petechial lesions with purpura. The vesicles appear singly or in crops with erythematous bases, mainly over the trunk, and resemble the rash of varicella (chicken pox).

LABORATORY and PATHOLOGIC FINDINGS

Recovery of the measles virus is difficult. Verification of infection is best performed by blood testing. A fourfold or greater increase in either neutralizing, hemagglutinin-inhibition (HI) or complement-fixing (CF) antibodies between acute and convalescent serum samples is diagnostic of measles. Antibodies first appear 1 to 2 days after the rash, and peak titters are reached 2 to 4 weeks later. Uncomplicated measles infection is usually associated with a leukopenia (low white blood cell count). The leukopenia persists until recovery, after which a mild to moderate leukopenia is observed. Cause: Measles is caused by a paramyxovirus. The virus infiltrates the nose and mouth (nasopharynx), and is highly contagious. Affected Population Measles affects males and females equally, and can occur worldwide. Supposedly on the verge of extinction in the United States in 1983 when only 1,497 cases were reported, measles (rubeola) rebounded to a total of 2,813 in 1985. As of May 1986, a total of 1,976 Americans (more than in all of 1983) had been afflicted. The licensing of the first widely used measles vaccines in 1963, followed shortly by an improved version, reduced the number of reported cases from a pre-vaccine total of 525,000 annually to the record low in 1983, which reflects a ninety-nine percent decline. It is believed that measles virus initially gains access to the respiratory tract. By the onset of the prodrome of measles, the virus is widely distributed in the body. During this time multinucleated giant cells (characteristic of measles infection) can be recovered from urinary sediment, sputum, nasal secretions, and various lymphoid tissues.

Similar Disorders

Similar Disorders Include:  Rubella, or three-day measles, is marked by mild constitutional symptoms that may result in abortion, stillbirth, or congenital defects in infants born to mothers infected during the early months of pregnancy. Other symptoms may include a two to three week incubation period with no recognizable symptoms, mild course of short duration, low fever, rash (less extensive than other types of measles), a reddish flush simulating that of scarlet fever which may be noticed on the face, enlargement of Iymph nodes, and a normal blood count. Symptoms are usually mild in children with Rubella. Adults characteristically experience fever, discomfort, headache, weakness or exhaustion, stiff joints, and mild nasal membrane inflammation (rhinitis). Encephalitis is a rare complication that has occurred during extensive outbreaks of rubella among young adults in the armed services. Transient testicular pain is also a frequent complaint in affected adult males. Scarlet Fever is an infection caused by a bacteria that usually affects the mouth and throat area (pharynx), but may also affect the skin or birth canal. Patients may experience headache, abdominal pain, nausea, and a skin rash. Rarely, complications are Iymphocytic meningitis and hepatitis. A reddish flush may be apparent on the face, chest and extremities, with tiny red spots in some cases. The disease is much milder now than in the past, and complications are rare when properly treated. Roseola Infantum (Exanthem Subitum or Pseudorubella) is an acute disease of infants or very young children characterized by high fever, absence of localizing symptoms or signs, and appearance of red spots (a rubelliform eruption) simultaneously with, or following, lowering of the fever (defervescence). The cause and mode of transmission are not known, but the disease is probably communicable and caused by a neurodermotropic virus. It occurs most often in the spring and fall. Minor local epidemics have been reported. Atypical Measles Syndrome (AMS) is most common in adolescents and young adults and usually associated with prior immunization using the original killed measles vaccines, which are no longer in use. However, live measles vaccine administration has also been known to precede development of AMS, perhaps as a result of inadvertent inactivation due to improper storage. Presumably, inactivated measles virus vaccines do not prevent wild virus infection and can sensitize patients so that disease expression is altered significantly. AMS may begin abruptly, with high fever, toxicity, headache, abdominal pain, and cough. The rash may appear one to two days later, often beginning on the extremities. Swelling (edema) of the hands and feet may occur, pneumonia is not uncommon, and nodular densities in the lungs may persist for three months or longer. 

THERAPY, COURSE, AND PROGNOSIS

Standard Therapies:  Treatment of measles is symptomatic. Antimicrobial therapy is recommended when bacterial superinfection has been documented. Complete resolution of the illness usually occurs within 14 days. The prognosis for uncomplicated measles is excellent. Serious illness and death can result from secondary bronchopneumonia and encephalitis. In general, once a person is infected, there is little to do other than let measles run its course, and make the patient as comfortable as possible. The use of aspirin to treat viral diseases in children and young adults should be avoided because of the risk of Reye Syndrome, a rare but life-threatening condition. Bed rest and a light diet seem to be of benefit. Vaccination for measles is the most effective method found to prevent outbreaks of measles. Vaccine failure occurs in just ten percent of cases. The vaccine approved in 1963 is no longer in use. Anyone who received one of these vaccines between 1962 and 1969 should be reimmunized with the current vaccine. This new live vaccine is strong enough to produce immunity to measles, but not so strong as to produce severe reactions. The age for vaccination has also changed. Currently, measles vaccination is now recommended at fifteen months - after antibodies passed on by the mother have disappeared. Some authorities advocate lowering the age to twelve or even six months, with revaccination at fifteen months, when measles is usually epidemic. Children should be vaccinated before exposure to measles, or within seventy-two hours of exposure, if the protection is to be effective. The American Academy of Pediatrics recommends that an initial immunization of measles, mumps, and rubella (MMR) be given at fifteen months of age and a second (MMR) immunization be given (MMR) at the beginning of middle school or junior high school. The new recommendation for measles immunization consists of two doses of vaccine - one at 15 months of age and the second one at four to six years of age. Students entering college and medical personnel with direct patient contact should also have a second vaccination. Pregnant women exposed to measles should have their immunity tested to avoid possible risk to their unborn babies. Rubella, more than any other type of measles, can pose a great risk to fetuses. Investigational Therapies:  The number of anti-viral agents which may be useful in treating measles is still limited. Immunoglobulins and interferons, as well as a variety of immune stimulators or immune modulators, are possible therapies that are still undergoing further investigational evaluation at this time.

PREVENTION

Measles is a highly contagious disease occurring primarily in children. This disease is characterized by fever, cough, acute nasal mucous membrane discharge (coryza), inflammation of the lining of the eyelids (conjunctivitis), a spreading rash, and eruption of small, irregular, bright red spots (Koplik's spots) on the inner cheeks in the mouth with a minute bluish or white speck in the center of each. Because measles can be contracted from someone whose symptoms have not yet appeared, it is often difficult to avoid exposure. Measles ceases to be contagious four days after appearance of the rash. Although concerted efforts have been made to eliminate measles in the United States, increasing numbers of cases have been reported recently in some areas. This may be due in part to a drastic rise in the cost of vaccine, shortage of supplies due to liability insurance problems, or fear by the public of possible side effects of vaccines. This is in spite of strict observance of immunization / attendance requirements by school officials. However, parents may underestimate the need for this immunization. Usually measles and the danger of its complications can be avoided by timely immunization. Protection against measles should be accomplished by immunization with the live-attenuated measles vaccine. It is available as a monovalent vaccine (measles only) or in combination with the mumps and rubella vaccine (MMR). The Pediatric Red Book currently recommends that the vaccine be given at 15 months of age. Children vaccinated before 12 months of age should be vaccinated again. Other indications are those persons who previously received killed-virus measles vaccine, received an unknown form of measles vaccine between 1963 and 1967, or are unvaccinated with no history of natural measles. The vaccine is contraindicated in pregnancy. Approximately 50% of prior recipients of killed-virus measles vaccine will have reactions after re-vaccination with the live-attenuated vaccine. The reactions usually consists of mild local swelling and erythema. Other reported reactions include low-grade fever, headache, and malaise.