Measles (Rubeola)

Measles (Rubeola) is a highly infectious disease that is caused by the measles virus. There are two phases of disease: a catarrhal (prodromal) stage and an exanthem stage. The catarrhal stage is characterized by a fever with conjunctivitis, coryza, cough, and pathognomonic Koplik spots on the buccal mucosa. The sudden development of a high fever, malaise, and exanthem represents the next phase. The exanthem stage is typically characterized by an erythematous maculopapular rash that originates behind the ears and spreads to the rest of the body towards the feet. Infection is usually self-limiting and followed by lifelong immunity. Disease management includes vitamin A supplementation, symptomatic treatment, and possible post-exposure prophylaxis (PEP). Measles causes transient immunosuppression and may lead to serious complications such as encephalitis, otitis, or pneumonia. A rare but lethal late complication of measles is subacute sclerosing panencephalitis (SSPE), which may also affect immunocompetent individuals. Active immunization against measles is available in form of a combination vaccine against mumps and rubella (MMR). The first dose is recommended between the ages of 12 and 15 months and the second dose between 4 and 6 years of age or at least 28 days after the first dose. The prognosis is good in uncomplicated cases. However, newborns and immunocompromised patients are more likely to suffer from severe complications.

• Distribution: Measles typically occurs in regions with low vaccination rates and in resource-limited countries. ^[1]
• Peak incidence: < 12 months of age ^[1]
• Infectivity ^[1]
  • ∼ 90%
  • Highly contagious 4 days before and up to 4 days after the onset of exanthem.

Epidemiological data refers to the US, unless otherwise specified.

• Pathogen: measles virus (MV), an RNA virus of the Morbillivirus genus belonging to the Paramyxoviridae family
• Route of transmission: direct contact with or inhalation of virus-containing droplets ^[1]

Incubation period

• Duration: ∼ 2 weeks after infection

Prodromal stage (catarrhal stage) ^[2]

• Duration: ∼ 4–7 days
• Presentation
  • Coryza, cough, and conjunctivitis
  • Fever
  • Koplik spots
    • Pathognomonic enanthem of the buccal mucosa
    • Tiny white or bluish-gray spots on an irregular erythematous background that resemble grains of sand

Exanthem stage ^[2]

• Duration: ∼ 7 days (develops 1–2 days after enanthem)
• Presentation
  • High fever, malaise
  • Generalized lymphadenopathy
  • Erythematous maculopapular, blanching, partially confluent exanthem
    • Begins behind the ears along the hairline
    • Disseminates to the rest of the body towards the feet (palm and sole involvement is rare)
    • Fades after ∼ 5 days of onset, leaving a brown discoloration and desquamation in severely affected areas

Recovery stage

The cough may persist for another week and may be the last remaining symptom.

The most important findings of measles are the 3 Cs and 1 K: Coryza, Cough, Conjunctivitis, and Koplik spots.

Measles should be suspected in a patient with typical clinical findings. Laboratory tests are always necessary to confirm the diagnosis. ^[3]

• CBC: ↓ leukocytes, ↓ platelets
• Serology
  • Gold standard: detection of Measles-specific IgM antibodies
  • IgG antibodies
• Identification of pathogen: direct virus detection via reverse-transcriptase polymerase chain reaction (RT-PCR) possible
• Biopsy: affected lymph nodes show paracortical hyperplasia and Warthin-Finkeldey cells (multinucleated giant cells formed by lymphocytic fusion).

Differential diagnoses of infectious pediatric conditions
	Appearance of exanthem	Course of exanthem	Other clinical features
Measles	Erythematous, maculopapular Blanching Partially confluent	Begins on the face, frequently behind the ears Disseminates to the rest of the body Fades after ∼ 5 days with brown discoloration and desquamation	Prodromal stage Coryza, cough and conjunctivitis Koplik spots Exanthem stage High fever, malaise Generalized lymphadenopathy
Scarlet fever	Fine, erythematous, maculopapular Blanching Pastia's lines Distinct appearance in the groin and bends of the joints	Begins in the neck region Disseminates to the head, trunk, and extremities Brown discoloration and desquamation of the skin during the second to fourth week of infection	High fever with sudden onset "Strawberry tongue" Tonsillopharyngitis
Rubella	Pink, maculopapular Non-confluent	Begins behind the ears Extends to the trunk and extremities Symptoms usually disappear within 3 days	Good general condition Suboccipital and post-auricular lymphadenopathy Forchheimer sign
Fifth disease (erythema infectiosum)	Maculopapular Initially confluent Lace-like and reticular appearance over time Becomes more pronounced after exposure to sunlight or heat	“Slapped cheek” appearance: flushed cheeks with perioral pallor Spreads to extremities and trunk in 50% of cases Fades after ∼ 5–8 days May be recurrent for several months following the initial infection	Good general condition Arthritis
Roseola infantum (exanthem subitum)	Rose-pink, maculopapular Patchy, blanching	Develops as the fever subsides Originates on the trunk and may spread to face and extremities Frequently observed from only several hours to a maximum of 3 days	Good general condition Initial sudden high fever for 3–5 days (three-day fever) Nagayama spots
Chickenpox (Varicella)	Vesicular rash on erythematous background “Starry sky”: simultaneous occurrence of different stages (e.g., vesicles, crusted papules)	Begins on trunk, scalp, face and proximal limbs Involves hands, feet and mucous membranes Severe pruritus Fades after ∼ 1 week	Prodrome possible (1–2 days prior to exanthem onset) Oropharyngeal and urogenital ulcers
Hand, foot, and mouth disease	Tender macules Vesicular rash	Affects feet and hands Rarely generalizes Fades after ∼ 4 days	Poor general condition Highly contagious Stomatitis and enanthem Fever

Drug reactions should always be considered as potential cause for a rash.

The differential diagnoses listed here are not exhaustive.

• Symptomatic treatment ^[4]
• Vitamin A supplementation reduces morbidity and mortality (especially in malnurished children). ^[5]
• PEP in patients without prior vaccination (see “Prevention” below)

Subacute sclerosing panencephalitis (SSPE) ^[6][1][7]

• Definition: a lethal, generalized, demyelinating inflammation of the brain caused by persistent measles virus infection ^[8][9]
• Epidemiology
  • Primarily affects males between 8 and 11 years of age
  • Usually develops ≥ 7 years after measles infection
• Clinical presentation: characterized by four clinical stages
  • Stage I: dementia, personality changes
  • Stage II: epilepsy, myoclonus, autonomic dysfunction
  • Stage III: decerebration, spasticity, extrapyramidal symptoms
  • Stage IV: vegetative state, autonomic failure
• Diagnosis
  • Electroencephalography
    • Paroxysmal delta waves (very slow, 1–3/sec)
    • Periodic sharp and slow wave complexes
  • Cerebrospinal fluid: ↑ anti-measles IgG
• Prognosis: SSPE leads to death within 1–3 years of diagnosis) ^[10]

Other complications ^[6][1]

• Bacterial superinfection
  • Otitis media
  • Pneumonia (most common cause of death)
  • Laryngotracheitis
• Gastroenteritis
• Acute encephalitis
  • Frequency: ∼ 1:1000 ^[11]
  • Develops within days of infection
  • Acute disseminated encephalomyelitis may develop within weeks.
• Giant cell pneumonia (viral, most commonly seen in immunosuppressed individuals)

Complications are likely to occur when the fever does not subside after a few days after onset of the exanthem.

We list the most important complications. The selection is not exhaustive.

Immunization ^[1][3]

Primary immunization

• Indications
  • Every infant
  • Adults born after 1957 with unknown immunization or incomplete status
• Method
  • Live vaccination with attenuated virus in combination with mumps and rubella (MMR) vaccine and possibly varicella (MMRV) vaccine
  • Infants: two vaccinations during childhood
  • See “Immunization schedule.”

Postexposure prophylaxis (PEP)

• Indication: negative or indeterminate serology
• Methods
  • Active immunization; for immunocompetent individuals after direct exposure
  • Passive immunization; for chronically ill and immunocompromised individuals
• Further measures for contact persons: avoidance of communal facilities

Reporting regulations ^[1][3]

• Measles is a notifiable disease.
• Cases should be reported within 24 hours to the CDC or National Center for Immunization and Respiratory Diseases (NCIRD).