Forgotten but not gone: Update on measles infection for hospitalists

The presenting symptoms of primary measles infection are nonspecific, particularly if Koplik spots are not identified. The differential diagnosis for a patient who presents with high fever and rash include Kawasaki disease, dengue, parvovirus B19, serum sickness, syphilis, systemic lupus erythematous, toxic shock syndrome, enterovirus infection, human herpes virus 6 (roseola), viral hemorrhagic fever, drug eruption, infectious mononucleosis, Rocky Mountain spotted fever, rubella, scarlet fever, chikungunya, and Zika virus infection.

Measles complications can affect nearly every organ system (Table). Rates of complications from measles infection depend on age and underlying condition. Coexisting vitamin A deficiency increases complication rates.²⁰

Bacterial infections in the setting of measles infection are more common in adults than in children, and are more severe among people who are malnourished or have an immunodeficiency disorder. The most common infectious complications, which involve the respiratory tract, include pneumonia, laryngotracheitis (“measles croup”), bronchitis, otitis media (most common complication among children in the United States), and sinusitis.^7,13,21

Indications for hospitalizing children include respiratory distress, laryngeal obstruction, dehydration that requires intravenous fluids, diarrhea with more than 10 stools a day or bloody stool, severe anemia, altered mental status, convulsion, severe rash with developing hemorrhagic areas, extensive mouth ulcers, corneal clouding or ulcers, visual disturbance, and mastoiditis.²²

Pneumonia is a common indication for hospitalizing adults.^23,24 Measles-associated interstitial giant cell (Hecht) pneumonia is most often recognized among immunocompromised and malnourished patients.¹³ Primary pneumonia is caused by the measles virus, but bacterial superinfection can occur. The most common bacterial pathogens include Streptococcus, Pneumococcus, and Staphylococcus,^13,24 and less commonly isolated organisms include gram-negative bacteria, such as Haemophilus influenzae, Pseudomonas aeruginosa, Neisseria meningitides, and Enterobacter cloacae.²³

Uncommon complications of measles are myocarditis, glomerulonephritis, acute renal failure, and thrombocytopenic purpura.^25,26

Neurologic complications in measles are an important concern. Measles-associated central nervous system complications are considered a result of an immune-mediated reaction to myelin protein and not from direct viral insult.^26-28 Immunocompromised patients are at risk for developing fatal encephalitis, and those who survive often experience cognitive decline or seizures.

Measles is associated with four different encephalitic diseases: primary measles encephalitis, acute post-measles encephalomyelitis, measles inclusion body encephalitis, and subacute sclerosing panencephalitis.

Primary measles encephalitis is characterized by fever, headache, stiff neck, and meningeal signs. Onset occurs between 1 and 15 days after rash onset, and the disease affects 1/1000 patients. Seizure, altered mental status, and coma can also develop. Viral RNA detection in the cerebrospinal fluid (CSF) confirms the diagnosis.²⁹Acute post-measles encephalomyelitis is more common in adults than in children.¹² It typically develops after the rash fades and the other symptoms subside. Patients suddenly experience a recurrence of fevers or seizures. Deafness, intellectual decline, epilepsy, postencephalitic hyperkinesia, hemiplegia, and/or paraplegia also can develop.^27-29

Measles inclusion body encephalitis is described only in immunocompromised patients, and onset occurs within 1 year of infection. Seizures are an initial and common symptom, and some patients also experience hemiplegia, stupor, hypertonia, and dysarthria.²⁹ Diagnostic findings include seroconversion during the disease course, improvement after withholding of the immunosuppressive regimen, and normal CSF. Brain biopsy confirms the diagnosis.

Subacute sclerosing panencephalitis (SSPE) is a slowly progressing and untreatable degenerative neurologic disorder characterized by demyelination of multiple brain areas. SSPE develops 7 to 10 years after natural measles infection, and usually affects children or adolescents. Clinical presentation includes intellectual decline, frequent rhythmic myoclonic jerks, seizure, and dementia. As the disease progresses, coma, quadriplegia, vegetative state, and autonomic instability develop. Death usually occurs within 2 years of onset.^30,31 In children, the risk for SSPE after measles infection is estimated to be 4 to 11 per 100,000 infections. After the 1989-1991 resurgence of measles in the United States, however, the risk for SSPE was estimated to be 22 per 100,000 infections.^30-32 The pathogenesis of SSPE is not fully understood but is thought to result from persistent aberrant measles virus infection.³²

The SSPE diagnosis is based on clinical presentation, presence of anti-measles antibodies in CSF, typical electroencephalography pattern (periodic paroxysmal bursts) with accompanying myoclonus, tissue analysis, and magnetic resonance imaging.³⁰

Suspicion for measles should prompt immediate consultation with local or state public health officials. Laboratory testing can be carefully considered after consultation, and care is needed in interpreting serologic studies.

The mainstays of measles infection diagnosis are detection of viral RNA by reverse transcriptase–polymerase chain reaction, or isolation of the virus in the clinical specimen, and detection of measles-specific IgM (immunoglobulin M) antibodies. A detailed protocol for collecting specimens for viral isolation appears on the Centers for Disease Control and Prevention website (https://www.cdc.gov/measles/lab-tools/rt-pcr.html).

IgM antibodies are detectable over the 15 weeks after rash onset, but the recommendation is to collect serum between 72 hours and 4 weeks after rash onset.³³ Clinicians should be aware that false-positive IgM results may occur with rheumatologic diseases, parvovirus B19 infection, rubella, and infectious mononucleosis.

IgG (immunoglobulin G) antibodies are usually detectable a week after rash onset. The laboratory can confirm measles by detecting more than a 4-fold increase in IgG titers between the acute phase and the convalescent phase. After measles infection, most adults develop lifelong immunity with positive IgG serology.³⁴

Additional tests, such as IgG avidity and plaque reduction neutralization assay, can be used to confirm suspected cases in previously vaccinated individuals.³⁴