Measles (Rubeola, Morbill)

Are You Confident of the Diagnosis?

What you should be alert for in the history?

The prodromal phase of measles is highly symptomatic. A history of high fever (up to 105° F), pronounced catarrh (profusely running nose), harsh, dry cough (sometimes leading to croup) and an intense, nonpurulent conjunctivitis (often with photophobia), followed by appearance of skin rash in a child should, prompt the clinician to consider a diagnosis of measles. Enquire about a history of contact with a case of measles in school or in the family.

Characteristic findings on physical examination

During the prodromal phase, the conjunctival involvement starts as marked linear erythema along the eyelid margins, which is quite characteristic, and gradually becomes diffuse. It is accompanied or followed by the pathognomonic enanthem “Koplik’s spots”; these are transient , grayish, pin-point dots (simulating table salt crystals), surrounded by an erythematous halo, present in the buccal mucosa, opposite to the lower molar teeth (Figure 1).

Figure 1.

Koplik’s spots are rarely appreciable and fade away by 2 days, leaving behind a speckled, reddish discoloration of the buccal mucosa. The skin lesions of measles are nondescript, but its evolution is characteristic. A dusky-red, maculopapular rash appears along the ear, hairline, forehead, and upper lateral parts of the neck (Figure 2) and progresses cephalocaudally over the next 3-4 days to involve trunk and extremities (Figure 3). Initial lesions are discrete and thereafter become confluent and blanchable. It subsides in the same sequence of appearance leaving behind a brownish, branny desquamation. The fever continues till 2-4 days of the eruptive phase of the disease and ends abruptly. Epistaxis, posterior cervical lymphadenopathy, and splenomegaly may be present.

Figure 2.

Figure 3.

Expected results of diagnostic studies

In children, classical measles may be diagnosed clinically with a fair degree of accuracy. The diagnosis of measles in adults may be difficult because of lack of suspicion. Leucopenia with a relative lymphocytosis is observed. Thrombocytopenia is a feature of measles infection and may be quite severe. In absence of bacterial infections, erythrocite sedimentation rate (ESR) and C-reactive protein are normal.

If diagnostic confirmation is required, demonstration of anti-measles IgM antibodies is the simplest way to do this. It is detectable from 3 days after the onset of the rash and persists up to 1 month. The hemagglutination-inhibiting antibody assay technique done at the onset of the rash and again at 4 weeks when the titer is at its peak is the most sensitive method for detection of antibodies. Confirmation of diagnosis is done by demonstrating a fourfold (or more) rise in the IgM antibody titer in paired sera. The virus can be cultivated in tissue culture (human embryonic cell or Rhesus monkey kidney cells).

The specimens for viral culture include various body fluids like nasopharyngeal and conjunctival secretions, blood and urine, collected during late prodromal phase of the illness. Chances of virus isolation decreases following appearance of the skin rash. Histopathologic examination of the involved organs reveals pericapillary infiltration of mononuclear cells with or without pathognomonic, multinucleated, Warthin-Finkeldey giant cells. In skin, the inflammatory infiltrate is particularly located around the hair follicles and sebaceous glands.

Diagnosis confirmation

Other febrile illnesses with a maculopapular skin rash must be differentiated from measles. In rubella, a milder, pink-colored rash is observed with prominent suboccipital lymphadenopathy. In parvovirus B-19 infection, the skin rash appears when the fever subsides and the child appears apparently well. Infectious mononucleosis, human herpes virus-6 infection (roseola infantum), Coxsackie virus and Enteroviral infections may simulate measles but lack the intense catarrh and conjunctivitis seen during prodromal phase.

The morbilliform rash, fever and conjunctivitis of Kawasaki disease may be difficult to distinguish clinically from measles but cheilitis, strawberry tongue and the characteristic desquamation during subsidence of the rash in the former are the differentiating features. Maculopapular drug eruptions and the early stage of Stevens-Johnson syndrome may also simulate measles.

Who is at Risk for Developing this Disease?

Measles is a ubiquitous viral illness, with frequent outbreaks occurring in almost all countries. The usual season of occurrence is spring. Preschool children are the common sufferers but older children and adults may be affected. Measles is extremely rare before 3-4 months of age because of protective maternal immunity.

Immunocompromised and malnourished children are at special risk of developing prolonged and severe clinical features of the disease. Measles is highly contagious with a secondary attack rate of about 90%. The source of infection is a case of measles. Transmission is through respiratory droplets. The period of infectivity spans from the prodromal phase to the early phase of appearance of the rash (approximately 4 days before and 5 days after the appearance of the rash). The portal of entry is mostly the respiratory mucosa and probably intact conjunctiva. The incubation period of measles is around 10-12 days.

One attack of measles confers life-long immunity and second attacks are rare except in severely immunocompromised children. Newborns acquire immunity to measles transplacentally from the mothers who were immunized or had natural infection. This immunity provides complete protection up to 4-6 months during infancy and thereafter gradually wanes off by 1 year. Natural infection confers better immunity than acquired infection by vaccination; infants born of vaccinated mothers experience early waning of maternal antibodies.

In resource-limited countries, measles-associated mortality rate may be as high as 25%.

What is the Cause of the Disease?

Etiology

Measles is caused by a single-stranded RNA virus, genus Morbillivirus, family Paramyxoviridae.

Pathophysiology

Initial localization of the virus is in the epithelia of nasopharynx and conjunctiva, from where it is spread to the regional lymph nodes. After 2-3 days, viremia ensues and the virus is carried to other reticuloendothelial organs. There is hyperplasia of the lymphoreticular tissue, particularly involving spleen, appendix, and posterior cervical and mesenteric lymph nodes. A secondary intense viremia occurs after 5-7 days, followed by onset of prodromal phase. Secondary viremia leads to involvement of other organs, most importantly skin, respiratory tract and conjunctiva. Viral replication continues in these organs, with a peak tissue viral load by 14th day ; thereafter the level falls rapidly by next 2-3 days, along with appearance of antimeasles antibody – this coincides with the appearance of skin rash.

During the viremic stage, there is marked depression of the cell-mediated immunity, as evidenced by low CD4+ T cell count and low level of interleukin-12. This persists up to 1 month in the postmeasles period, with gradual recovery thereafter and explains the propensity to infectious episodes during this time. Activation of CD8+ T cells facilitates viral clearance from the system and activation of type 2 CD4+ T cells facilitates antimeasles antibody production.

Systemic Implications and Complications

Multiorgan complications are common in measles. Frequent serious complications are myocarditis and pneumonia. Secondary bacterial pneumonia is more common than the interstitial pneumonia (Hecht’s giant cell pneumonia) caused by the measles virus itself. Hecht’s pneumonia is more common in immunocompromised patients. Respiratory tract involvement like laryngitis, tracheitis, bronchitis, and otitis media may be caused by measles virus or superimposed bacterial infection. Persistent fever beyond 1-2 days of the onset of skin rash is likely to be an indicator of secondary bacterial infection. Acute abdominal pain may result from appendicitis (obstruction of appendicular lumen due to lymphoid hyperplasia) or mesenteric lymphadenitis.

In developed countries, the most common complication associated with measles is otitis media, followed by pneumonia and diarrhea. In developing countries, measles associated complications are severe, leading to a high mortality rate. Pneumonia and diarrhea are the most common complications in these children, which are enhanced in the background of a preexisting malnourished state. Staphylococcal pneumonia is life threatening. Pneumonia is the most common cause of death in children with measles. Preexisting low vitamin A reserve in the body makes these children prone to developing blindness.

Rare complications are purpura fulminans with or without digital gangrene, encephalitis, Guillain-Barre syndrome, cerebral thrombophlebitis, hemiplegia, and retrobulbar neuritis.

Subacute sclerosing panencephalitis (SSPE) is a very rare complication of measles infection (1/100,000 cases). It results from persistent infection by defective measles virus. It is common among children who had measles before 1 year of age. Clinical manifestations start at around 9 years of age, approximately 7-13 years after the childhood measles infection. There is progressive mental and motor deterioration, personality changes and myoclonic seizures. Coma and death is the ultimate end of the children suffering from SSPE.

There is a persistent high titer of antimeasles antibody over several years in children with SSPE. A higher cerebrospinal fluid antimeasles antibody titer compared to seum may be helpful in diagnosis. If facilities with immunofluorescence and electron microscopy are available, a brain biopsy and histopathologic examination is diagnostic.

Treatment Options

Treatment options for measles are summarized in Table I.

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