Monday, February 25, 2013

Deeper Knowledge Above the Exanthema Diseases: Measles

an acute communicable disease, is characterized by three stages: (1) an incubation stage of approximately 10–12 days with few, if any, signs or symptoms; (2) a prodromal stage with an enanthem (Koplik spots) on the buccal and pharyngeal mucosa, slight to moderate fever, mild conjunctivitis, coryza, and an increasingly severe cough; and (3) a final stage with a maculopapular rash erupting successively over the neck and face, body, arms, and legs and accompanied by high fever.

ETIOLOGY. Measles is an RNA virus of the family Paramyxoviridae, genus Morbillivirus. Only one antigenic type is known. During the prodromal period and for a short time after the rash appears, it is found in nasopharyngeal secretions, blood, and urine. It can remain active for at least 34 hr at room temperature.

Measles virus may be isolated in cultures of human embryonic or rhesus monkey kidney tissue. Cytopathic changes, visible in 5–10 days, consist of multinucleated giant cells with intranuclear inclusions. Circulating antibody is detectable when the rash appears.

INFECTIVITY. Maximal dissemination of virus is by droplet spray during the prodromal period (catarrhal stage). Transmission to susceptible contacts often occurs prior to diagnosis of the original case. An infected person becomes contagious by the 9th–10th day after exposure (beginning of prodromal phase), in some instances as early as the 7th day. Isolation precautions, especially in hospitals or other institutions, should be maintained from the 7th day after exposure until 5 days after the rash has appeared.

EPIDEMIOLOGY. Measles is endemic over most of the world. In the past, epidemics tended to occur irregularly, appearing in the spring in large cities at 2- to 4-yr intervals as new groups of susceptible children were exposed. Measles is very contagious; approximately 90% of susceptible family contacts acquire the disease. It is rarely subclinical. Prior to the use of measles vaccine, the age of peak incidence was 5–10 yr; most adults were immune. At present in the United States, measles occurs most often in unimmunized preschool-aged children and in teenagers and young adults who have been immunized. Epidemics have occurred in high schools and colleges where immunization levels were high. These epidemics are thought to be due primarily to vaccine failure. Despite a resurgence of measles in the United States from 1989–1991, reported numbers of measles cases dropped to an all-time low in 1993, probably a result of widespread vaccination. Those older than 30 years are virtually all immune. Because measles is still a common disease in many countries, infective persons entering this country may infect United States citizens, and Americans traveling abroad risk exposure there.

The many similarities among the biologic features of measles and smallpox suggest the possibility that measles may be eradicable. These features are (1) a distinctive rash, (2) no animal reservoir, (3) no vector, (4) seasonal occurrence with disease-free periods, (5) no transmissible latent virus, (6) one serotype, and (7) an effective vaccine. A prevalence of more than 90% immunization of infants has been shown to produce disease-free zones. In 1980, three fourths of all counties in the United States did not report a single case of measles, but by 1988 the number of measles cases was increasing and the disease was more widespread.

Infants transplacentally acquire immunity from mothers who have had measles or measles immunization. This immunity is usually complete for the first 4–6 mo of life and disappears at a variable rate. Although maternal antibody levels are generally undetectable in the infant by the usual tests performed after 9 mo of age, some protection persists, which may interfere with immunization administered prior to 15 mo. Most women of child-bearing age in the United States now have measles immunity by means of immunization rather than disease. Some studies now suggest that infants of mothers with measles vaccine–induced immunity lose passive antibody at a younger age than infants of mothers who had measles infection. Infants of mothers susceptible to measles have no measles immunity and may contract the disease with the mother before or after delivery.

PATHOLOGY. The essential lesion of measles is found in the skin; in the mucous membranes of the nasopharynx, bronchi, and intestinal tract; and in the conjunctivae. Serous exudate and proliferation of mononuclear cells and a few polymorphonuclear cells occur around the capillaries. There is usually hyperplasia of lymphoid tissue, particularly in the appendix, where multinucleated giant cells of up to 100 mmin diameter (Warthin-Finkeldey reticuloendothelial giant cells) may be found. In the skin, the reaction is particularly notable about the sebaceous glands and hair follicles. Koplik spots consist of serous exudate and proliferation of endothelial cells similar to those in the skin lesions. A general inflammatory reaction of the buccal and pharyngeal mucosa extends into the lymphoid tissue and the tracheobronchial mucous membrane. Interstitial pneumonitis resulting from measles virus takes the form of Hecht giant cell pneumonia. Bronchopneumonia may be due to secondary bacterial infection.

In fatal cases of encephalomyelitis, perivascular demyelinization occurs in areas of the brain and spinal cord. In Dawson subacute sclerosing panencephalitis (SSPE), there may be degeneration of the cortex and white matter with intranuclear and intracytoplasmic inclusion bodies.


The incubation period is approximately 10–12 days if the first prodromal symptoms are selected as the time of onset, or approximately 14 days if the appearance of the rash is selected; rarely it may be as short as 6–10 days. A slight rise in temperature may occur 9–10 days from the date of infection and then subside for 24 hr or so.

The prodromal phase, which follows, usually lasts 3–5 days and is characterized by low-grade to moderate fever, a hacking cough, coryza, and conjunctivitis. These nearly always precede Koplik spots, the pathognomonic sign of measles, by 2–3 days. An enanthem or red mottling is usually present on the hard and soft palates. Koplik spots are grayish white dots, usually as small as grains of sand, with slight, reddish areolae; occasionally they are hemorrhagic. They tend to occur opposite the lower molars but may spread irregularly over the rest of the buccal mucosa. Rarely they are found within the midportion of the lower lip, on the palate, and on the lacrimal caruncle. They appear and disappear rapidly, usually within 12–18 hr. As they fade, red, spotty discolorations of the mucosa may remain. The conjunctival inflammation and photophobia may suggest measles before Koplik spots appear. In particular, a transverse line of conjunctival inflammation, sharply demarcated along the eyelid margin, may be of diagnostic assistance in the prodromal stage. As the entire conjunctiva becomes involved, the line disappears.

Conjunctivitis in measles

Koplik spots


Occasionally, the prodromal phase may be severe, being ushered in by sudden high fever, at times with convulsions and even pneumonia. Usually the coryza, fever, and cough are increasingly severe up to the time the rash has covered the body.

The temperature rises abruptly as the rash appears and often reaches 40–40.5º C (104–105º F). In uncomplicated cases, when the rash appears on the legs and feet, within about 2 days, the symptoms subside rapidly; the subsidence includes a usually abrupt temperature drop. Patients up to this point may appear desperately ill, but within 24 hr after the temperature drop, they appear essentially well.

The rash usually starts as faint macules on the upper lateral parts of the neck, behind the ears, along the hairline, and on the posterior parts of the cheek. The individual lesions become increasingly maculopapular as the rash spreads rapidly over the entire face, neck, upper arms, and upper part of the chest within approximately the first 24 hr

Fig. Maculopapular rash of measles, the first day of the eruption

Fig. Maculopapular rash of measles, the second day of the eruption

Fig. Maculopapular rash of measles, the third day of the eruption

Fig. Hemorrhagic rash of measles

The rash pigmentation

During the succeeding 24 hr it spreads over the back, abdomen, entire arms, and thighs. As it finally reaches the feet on the 2nd–3rd day, it begins to fade on the face. The fading of the rash proceeds downward in the same sequence in which it appeared. The severity of the disease is directly related to the extent and confluence of the rash. In mild measles the rash tends not to be confluent, and in very mild cases there are few, if any, lesions on the legs. In severe measles the rash is confluent, the skin being completely covered, including the palms and soles, and the face is swollen and disfigured.

The rash is often slightly hemorrhagic; in severe cases with a confluent rash, petechiae may be present in large numbers, and there may be extensive ecchymoses. Itching is generally slight. As the rash fades, branny desquamation and brownish discoloration occur and then disappear within 7–10 days.

The rash may vary markedly. Infrequently a slight urticarial, faint macular, or scarlatiniform rash may appear during the early prodromal stage and disappear in advance of the typical rash. Complete absence of rash is rare except in patients who have received human antibodies during the incubation period, in some patients with human immunodeficiency syndrome (HIV) infection, and possibly in infants younger than 8 mo who have appreciable levels of maternal antibody. In the hemorrhagic type of measles (black measles), bleeding may occur from the mouth, nose, or bowel. In mild cases the rash may be less macular and more nearly pinpoint, somewhat resembling that of scarlet fever or rubella.

Lymph nodes at the angle of the jaw and in the posterior cervical region are usually enlarged, and slight splenomegaly may be noted. Mesenteric lymphadenopathy may cause abdominal pain. Characteristic pathologic changes of measles in the mucosa of the appendix may cause obliteration of the lumen and symptoms of appendicitis. Changes of this type tend to subside with the disappearance of Koplik spots. Otitis media, bronchopneumonia, and gastrointestinal symptoms, such as diarrhea and vomiting, are more common in infants and small children (especially malnourished ones) than in older children.

The diagnosis of measles is frequently delayed in adults because practitioners providing health care for adults are not used to encountering the disease and rarely include it in the differential diagnosis. The clinical picture is similar to that seen in children. Liver involvement, with abdominal pain, mild to moderate elevation of aspartate aminotransferase (AST) levels, and occasionally jaundice, is common in adults. In developing countries and in recent outbreaks in the United States, measles frequently occurs in infants younger than 1 yr; possibly because malnutrition is concomitant there, the disease is very severe and has a high mortality.


This is usually made from the typical clinical picture; laboratory confirmation is rarely needed. During the prodromal stage multinucleated giant cells can be demonstrated in smears of the nasal mucosa. Virus can be isolated in tissue culture, and diagnostic rises in antibody titer can be detected between acute and convalescent sera. The white blood cell count tends to be low with a relative lymphocytosis. Lumbar puncture in patients with measles encephalitis usually shows an increase in protein and a small increase in lymphocytes. The glucose level is normal.


The rash of rubeola must be differentiated from exanthem subitum, rubella, infections resulting from echovirus, coxsackie virus, and adenovirus, infectious mononucleosis, toxoplasmosis, meningococcemia, scarlet fever, rickettsial diseases, serum sickness, Kawasaki disease, and drug rashes.
Koplik spots are pathognomonic for rubeola, and the diagnosis of unmodified measles should not be made in the absence of cough.

Roseola infantum (exanthem subitum) is distinguished from measles in that the rash of the former appears as the fever disappears. The rashes of rubella and of enteroviral infections tend to be less striking than that of measles, as do the degree of fever and severity of illness. Although cough is present in many rickettsial infections, the rash usually spares the face, which is characteristically involved in measles. The absence of cough or the history of injection of serum or administration of a drug usually serves to identify serum sickness or drug rashes. Meningococcemia may be accompanied by a rash that is somewhat similar to that of measles, but cough and conjunctivitis are usually absent. In acute meningococcemia the rash is characteristically petechial purpuric. The diffuse, finely papular rash of scarlet fever with a "goose flesh" texture on an erythematous base is relatively easy to differentiate.

The milder rash and clinical picture of measles modified by gamma globulin or by partial immunity induced by measles vaccine, or in infants by maternal antibody, may be difficult to differentiate.


The chief complications of measles are otitis media, pneumonia, and encephalitis. Noma of the cheeks may occur in rare instances. Gangrene elsewhere appears to be secondary to purpura fulminans or disseminated intravascular coagulation following measles.

Pneumonia (see Chapter 170) may be caused by the measles virus itself; the lesion is interstitial. Measles pneumonia in patients with HIV infection is often fatal and not always accompanied by rash. Bronchopneumonia is more frequent, however; it is due to secondarily invading bacteria, particularly the pneumococcus, streptococcus, staphylococcus, and Haemophilus influenzae. Laryngitis, tracheitis, and bronchitis are common and may be due to the virus alone.

One of the potential dangers of measles is exacerbation of an existing tuberculous process. There may also be a temporary loss of hypersensitivity to tuberculin.

Myocarditis is an infrequent serious complication; transient electrocardiographic changes are said to be relatively common.

Neurologic complications are more common in measles than in any of the other exanthems. The incidence of encephalomyelitis is estimated to be 1-2/1,000 reported cases of measles. There is no correlation between the severity of the measles and that of the neurologic involvement or between the severity of the initial encephalitic process and the prognosis. Rarely, encephalitis has been reported in association with measles modified by gamma globulin or by live attenuated measles virus vaccine. Infrequently, encephalitic involvement is manifest in the pre-eruptive period, but more often the onset occurs 2–5 days after the appearance of the rash. The cause of measles encephalitis remains controversial. It is suggested that when encephalitis occurs early in the course of the disease, viral invasion plays a large role, although measles virus has rarely been isolated from brain tissue; encephalitis that occurs later is predominantly demyelinating and may reflect an immunologic reaction. In this demyelinating type the symptoms and course do not differ from those of other parainfectious encephalitides. Fatal encephalitis has occurred in children receiving immunosuppressive treatment for malignancies. Other central nervous system complications, such as Guillain-Barré{acute-e} syndrome, hemiplegia, cerebral thrombophlebitis, and retrobulbar neuritis, are rare.

Subacute sclerosing panencephalitis  is due to measles virus.


Case fatality rates in the United States have decreased in recent years to low levels for all age groups, largely because of improved socioeconomic conditions but also because of effective antibacterial therapy for the treatment of secondary infections.

When measles is introduced into a highly susceptible population, the results may be disastrous. Such an occurrence in the Faroe Islands in 1846 resulted in the deaths of about one fourth, nearly 2,000, of the total population regardless of age. At Ungava BayCanada, where 99% of 900 persons had measles, the mortality rate was 7%.


Quarantine is of little value because of the contagiousness during its prodromal stage, when measles may not be suspected.

The initial measles immunization may be given at 12 to 15 mo but may be given earlier in areas where disease is occurring. Because the seroconversion rate following immunization is not 100% and there may be some waning of immunity with time, a second immunization against measles, usually given as measles-mumps-rubella (MMR), is indicated. This dose can be given when the child enters school or later on entry to middle school. Adolescents entering college should also have received a second measles immunization.

The response to live measles vaccine is unpredictable if immune globulin has been administered in the 3 mo preceding immunization. Anergy to tuberculin may develop and persist for 1 mo or longer after administration of live, attenuated measles vaccine. A child with active tuberculous infection should be receiving antituberculosis treatment when live measles vaccine is administered. A tuberculin test prior to or concurrent with active immunization against measles is desirable.

Use of live measles vaccine is not recommended for pregnant women or for children with untreated tuberculosis. Live vaccine is contraindicated in children with leukemia and in those receiving immunosuppressive drugs because of the risk of persistent, progressive infection such as giant cell pneumonia. After exposure of these susceptible children to measles, measles immune globulin (human) should be given intramuscularly in a dose of 0.25 mL/kg as soon as possible. A larger dose may be advisable in children with acute leukemia, even those in remission. Children with HIV infection should receive measles vaccine because mortality from measles is high in this group and they tolerate the vaccine well. Despite a history of having received measles immunization, these children should receive gamma globulin after exposure to measles in a dose of 0.5 mL/kg (maximum 15 mL). This is twice the usual recommended dose. Measles vaccine can be given following exposure to the disease. Reactions are not increased, and measles may be prevented.

The use of inactivated (killed) virus vaccine is not recommended.

Passive Immunization.

Passive immunization with pooled adult serum, pooled convalescent serum, placental globulin, or gamma globulin of pooled plasma is effective for prevention and attenuation of measles. Measles can be prevented by using immune serum globulin (gamma globulin) in a dose of 0.25 mL/kg given intramuscularly within 5 days after exposure but preferably as soon as possible. Complete protection is indicated for infants, for children with chronic illness, and for contacts in hospital wards and children's institutions. Attenuation may be accomplished by the use of gamma globulin in a dosage of 0.05 mL/kg. Gamma globulin is approximately 25 times as potent in antibody titer as pooled adult serum, and it avoids the risk of hepatitis. Attenuation is variable, and the modified clinical patterns may vary from those with few or no symptoms to those with little or no modification. Encephalitis may follow measles modified by gamma globulin.

After the 7th–8th day of incubation the amounts of antibody administered must be increased greatly for any degree of protection. If the injection is delayed until the 9th, 10th, or 11th day, slight fever may already have started and only slight modification of the disease may be expected.


Sedatives, antipyretics for high fever, bed rest, and an adequate fluid intake may be indicated. Humidification of the room may be necessary for laryngitis or an excessively irritating cough, and it is best to keep the room comfortably warm rather than cool. The patient should be protected from being exposed to strong light during the period of photophobia. The complications of otitis media and pneumonia require appropriate antimicrobial therapy.

With complications such as encephalitis, subacute sclerosing panencephalitis, giant cell pneumonia, and disseminated intravascular coagulation, each case must be assessed individually. Good supportive care is essential. Gamma globulin, hyperimmune gamma globulin, and steroids are of limited value. Currently available antiviral compounds are not effective. Treatment with oral vitamin A (400,000 IU) reduces morbidity and mortality in children with severe measles in the developing world.

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