INTRODUCTION

Measles virus (rubeola) is a member of the family Paramyxoviridae, genus Morbillivirus. Measles virus infection can cause a variety of clinical syndromes, including [1]:

• Classic measles infection in immunocompetent patients
• Modified measles in patients with preexisting, but incompletely protective, anti-measles antibody
• Atypical measles in patients immunized with the killed virus vaccine
• Neurologic syndromes following measles infection, including acute disseminated encephalomyelitis (ADEM) and subacute sclerosing panencephalitis (SSPE)
• Severe measles
• Complications of measles including secondary infection, giant cell pneumonia, and measles inclusion body encephalitis

Despite high community vaccination coverage, measles outbreaks can occur among undervaccinated children [2,3]. The clinical manifestations and diagnosis of classic measles, variant presentations, and unusual neurologic complications will be reviewed here. The epidemiology, transmission, treatment, and prevention of measles are discussed separately. (See "Epidemiology and transmission of measles" and "Prevention and treatment of measles".)

CLINICAL MANIFESTATIONS

Stages of infection — Classic measles infection can be subdivided into the following clinical stages: incubation, prodrome, exanthem, and recovery [4].

• Incubation period — The incubation period begins after measles virus entry via the respiratory mucosa or conjunctivae. The virus replicates locally, spreads to regional lymphatic tissues, and is then thought to disseminate to other reticuloendothelial sites via the bloodstream. The incubation period of measles is usually 10 days with a range generally of 8 to 10 days [5]. Infected individuals are characteristically asymptomatic during the incubation period, although some have been reported to experience transient respiratory symptoms, fever, or morbilliform rash [6,7].
  
  The dissemination of measles virus due to viremia, with associated infection of endothelial, epithelial, monocyte, and macrophage cells, may explain the variety of clinical manifestations and complications that can occur with measles infection. A second viremia occurs several days after the first, coinciding with the appearance of symptoms signaling the beginning of the prodromal phase.
• Prodrome — The prodrome phase is defined by the appearance of symptoms which typically include fever, malaise, and anorexia, followed by conjunctivitis, coryza, and cough. The severity of conjunctivitis is variable and may also be accompanied by lacrimation or photophobia [6]. The respiratory symptoms are due to mucosal inflammation from viral infection of epithelial cells. Fever is typically present; the pattern may be variable. Various fever patterns have been described; fever as high as 40ºC can occur. The prodrome usually lasts for two to three days but may persist for as long as eight days [5].
  
  Patients may develop an enanthem known as Koplik's spots; these are 1 to 3 mm whitish, grayish, or bluish elevations with an erythematous base, typically seen on the buccal mucosa opposite the molar teeth, though they can spread to cover the buccal and labial mucosa (picture 1) as well as the hard and soft palate [8]. They have been described as "grains of salt on a red background" [7]. Koplik's spots subsequently may coalesce and generally last 12 to 72 hours [4].
  
  It is important to search carefully for Koplik's spots in patients with suspected measles, since they are considered pathognomonic for measles infection and occur approximately 48 hours before the characteristic exanthem. However, this enanthem does not appear in all patients with measles.
  
  Uncommonly, patients with severe measles develop generalized lymphadenopathy and splenomegaly [7].
• Exanthem — The exanthem of measles is a maculopapular, blanching rash beginning on the face and spreading cephalocaudally and centrifugally to involve the neck, upper trunk, lower trunk, and extremities (picture 2A-B). The lesions may become confluent, especially in areas such as the face, where the rash develops first (picture 2B). The rash may also have some petechiae; in severe cases it may appear hemorrhagic [9-11]. In general, the extent and degree of confluence of the rash correlates with the severity of the illness in children. The palms and soles are rarely involved. The cranial to caudal progression of the rash is characteristic of measles but is not pathognomonic [6].
  
  Other characteristic findings during the exanthematous phase include lymphadenopathy, high fever (peaking two to three days after appearance of rash), pronounced respiratory signs including pharyngitis, and nonpurulent conjunctivitis. Koplik's spots often begin to slough when the exanthem appears.
  
  Clinical improvement typically ensues within 48 hours of the appearance of the rash. After three to four days the rash darkens to a brownish color and begins to fade, followed by fine desquamation. The rash usually lasts six to seven days.
• Recovery and immunity — Cough may persist for one to two weeks after measles infection. The occurrence of fever beyond the third to fourth day of rash suggests a measles-associated complication (see 'Complications' below).
  
  Immunity after measles infection is thought to be lifelong, although there are rare reports of measles reinfection [12,13]. A measles surveillance program conducted in mid 1960s, for example, identified measles in a 16-year old female with a prior history of measles at age 8. A rise in anti-measles IgG but not IgM was noted, suggesting an anamnestic response [12]. (See 'Modified measles' below.)
  
  Measles infection can cause transient immunosuppression due to suppression of T-cell responses [8]. Anergy may be present before the appearance of the exanthem and for several weeks after measles infection [8,14]. This is exemplified by reports of tuberculosis reactivation in the setting of recent measles infection [8,15].