Measles (Rubeola)

Measles (Rubeola) is a highly infectious disease that is caused by a paramyxovirus. 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. Vaccination against measles (active immunization) is administered in association with the mumps and rubella (MMR) vaccine; the first dose is recommended between the ages of 12–15 months and the second dose between 4–6 years of age or at least 28 days after the first dose. The prognosis is good in uncomplicated cases; newborns and immunocompromised patients are more likely to suffer from severe complications.

• Distribution: Measles typically occurs in regions with low vaccination rates and in developing countries.
• Peak incidence: < 12 months of age
• Infectivity: ∼ 90%; highly contagious 5 days before and up to 4 days after the onset of exanthem.

References:^[1][2]

Epidemiological data refers to the US, unless otherwise specified.

• Pathogen: Morbillivirus = RNA virus of the Paramyxoviridae family
• Route of transmission: direct contact with or inhalation of virus-containing droplets

References:^[1]

Incubation period

• Duration: ∼ 2 weeks after infection

Prodromal stage (catarrhal stage)

• Duration: lasts ∼ 4–7 days
• Presentation
  • Coryza, Cough, and Conjunctivitis (the “3 Cs”)
  • Fever
  • Koplik spots
    • Pathognomonic enanthem of the buccal mucosa
    • Tiny white or bluish-gray spots, resembling "grains of sand", on an irregular erythematous background
  • Photophobia

Exanthem stage

• Duration: appears 1–2 days after enanthem and lasts ∼ 7 days
• Presentation
  • High fever, malaise
  • Generalized lymphadenopathy
  • Erythematous maculopapular, blanching, partially confluent exanthem
    • Usually begin in the face, frequently behind the ears along the hairline
    • Disseminates to the rest of the body towards the feet (palm and sole involvement is rare)
    • Mild pruritus is possible

Recovery phase

• The rash begins to fade after ∼ 5 days of onset; leaving a brown discoloration and desquamation in severely affected areas
• The cough; may persist for another week and it may be the last remaining symptom.

References:^[3][4][5][6]

Differential diagnoses of pediatric rashes

Differential diagnoses of pediatric rashes	Measles	Scarlet fever	Rubella	Fifth disease (erythema infectiosum)	Roseola infantum (exanthem subitum)	Chickenpox (Varicella)	Hand, foot, and mouth disease
Exanthem	Erythematous maculopapular, blanching, partially confluent exanthem Usually begins on the face, frequently behind the ears → disseminates to the rest of the body (palms and soles typically spared) Exanthem begins to fade after ∼5 days, with a brown discoloration and desquamation	Fine erythematous, maculopapular, blanching exanthem Usually begins in the neck region; disseminates to the head, trunk, and extremities Distinct appearance in the groin and bends of the joints Pastia's lines Brown discoloration and desquamation of the skin during the second to fourth week of infection Early symptoms: sudden onset with high fever	Pink maculopapular, non-confluent exanthem Begins at the head, primarily behind the ears → extends to the trunk and extremities Transient; symptoms usually disappear within 3 days	Maculopapular, initially confluent exanthem → adopts a lace-like and reticular appearance over time Initially typical red flushed appearance of the cheeks with perioral pallor; “slapped cheek” appearance; spreads to extremities and trunk Mild pruritus in 50% of cases Becomes more pronounced after exposure to sunlight or heat Exanthem fades after ∼5–8 days; may be recurrent for several months following the initial infection	Rose-pink maculopapular, patchy, blanching exanthem Originates on the trunk; may spread to face and extremities Develops as the fever subsides Frequently observed from only several hours to a maximum of 3 days	Vesicular rash on an erythematous background; simultaneous occurrence of various stages of rash (“starry sky” appearance): papules, vesicles, crusted papules and hypopigmented healed lesions Rash begins on the trunk, scalp, face and proximal limbs Involve hands, feet and mucous membranes Severe pruritus Exanthem fades after ∼1 week	Tender macules and vesicular rash, especially affecting the feet and hands, and sometimes the buttocks and groin areas Rarely generalized Exanthem fades after ∼4 days
Other features	Prodromal stage Coryza, cough and conjunctivitis (the “3 Cs”) Enanthem of the buccal cavity with Koplik spots after 3 days Exanthem stage: high fever, malaise, generalized lymphadenopathy	Exanthem stage (within 48 hours following disease onset) Typical red flushed appearance of the cheeks with perioral pallor Red tongue with papillary hyperplasia → "strawberry tongue" Tonsillopharyngitis	General health primarily unaffected; mild disease Suboccipital and post-auricular lymphadenopathy Forchheimer sign: pin-point enanthem of the soft palate	General health primarily unaffected (mild disease) Arthritis	Initial sudden high fever for 3–5 days (three-day fever); otherwise good general condition Nagayama spots: A papular enanthem may be occasionally observed on the uvula and soft palate Followed by a sudden decrease in temperature with the development of a rapidly spreading exanthem (exanthem subitum)	Prodrome possible but not typical (1–2 days prior to the onset of exanthem) Fever Headache and muscle or joint pain Associated oropharyngeal and urogenital ulcers	Poor general condition Highly contagious In most cases, begins with stomatitis and enanthem: involve the tongue, buccal mucosa and hard palate; the vesicles erode leaving behind an erythematous base Fever Almost always self‑limiting

As with all rashes, always consider drug reactions!

References:^[8][9][10]

The differential diagnoses listed here are not exhaustive.

• Symptomatic treatment
• Vitamin A supplementation
• PEP in patients without prior vaccination (→ see “Prevention” below)
  • In immunosuppressed patients and severe cases of measles: administration of immunoglobulin and if necessary, ribavirin treatment

References:^[5][11][12]

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

• Bacterial superinfection: otitis media, pneumonia, laryngotracheitis
• Gastroenteritis
• (Viral) giant-cell pneumonia
• Acute encephalitis, often with permanent neurological deficits
  • Frequency: ∼ 1:1000
  • Develops within days of infection
  • Acute disseminated encephalomyelitis may develop within weeks
• Subacute sclerosing panencephalitis (SSPE): a lethal, generalized, demyelinating inflammation of the brain caused by persistent measles virus infection
  • Epidemiology: very rare
    • Primarily affects males between 8 and 11 years old
    • Usually develops at least 7 years after measles
  • Three clinical stages
    • Dementia
    • Epilepsy and myoclonus
    • Decerebration (increased tone, vegetative state, coma)
  • Diagnosis
    • Electroencephalography: paroxysmal delta waves (very slow, 1–3/s), periodic sharp and slow wave complexes
    • Cerebrospinal fluid: elevated anti-measles antibody titer (IgG)

References:^{[13][1][4][5][14][15][16]}

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

Immunization

• Vaccine: : live, attenuated virus; in combination with the mumps and rubella (MMR) vaccine and possibly varicella (MMRV) vaccine
• Primary immunization
  • Two vaccinations during childhood → see immunization schedule
  • In adults born after 1957 with unknown immunization or incomplete status
• PEP
  • Indication: In negative or indeterminate serology
  • Active immunization ;:
    • Immunocompetent patients after direct exposure
  • Passive immunization
    • Vulnerable, chronically ill, and immunocompromised patients
• Further measures for individuals with contact
  • Persons with close contact to infected individuals should avoid communal facilities.
  • Not required for: immunization, postexposure prophylaxis, or following prior infection

Reporting regulations

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

References:^[1][7]