POTD: Measles (Part 2)

Part two in our two part series about measles! 

Again, TL;DR at the bottom and here's another plug for Dr. Anna Pickens' EM in 5: http://www.emdocs.net/em-in-5-measles/

This section goes over the diagnosis, management, and complications of measles. 

Transmission
Measles virus is a single-stranded, enveloped, RNA virus of the genus Morbillivirus within the family Paramyxoviridae. It is spread via respiratory droplets that may remain in the air for up to two hours

Clinical Presentation
Incubation
 period: 6-21 days (median 13 days)

Prodrome (days 2-4): fever, malaise, and anorexia followed by “the 3C’s” (conjunctivitis, coryza, and cough). This phase of infection can last up to 8 days. 

Koplik spots typically present 48 hours prior to the onset of the exanthem. They are white/gray/bluish elevations, described as “grains of salt” on an erythematous base. These are typically seen on the buccal mucosa, but may spread to the soft and hard palates. These generally last for 12-72 hours. 

koplik+spots.jpg

Exanthem: starts 2-4 days after onset of fever. Classically is a blanching, maculopapular rash that starts on the hairline and progresses downward and outwards to the extremities. It tends to coalesce and become non-blanching with time. 

Patients will become clinically better within 48 hours of the appearance of rash, the rash will darken in color, and eventually desquamate. 

Measles may vary in severity and there are several clinical variants including: modified measles (milder symptoms) in those with pre-existing measles immunity, those who have received IVIG, and in babies with passive immunity from placental migration of immunoglobulins; atypical measles in those who have received the killed virus vaccine (not seen frequently now), which is characterized by higher and more prolonged fevers, pneumonitis, and transaminitis. Patients that are immunocompromised will also not present classically. 

Complications
Immunocompromised patients and pregnant patients are more likely to develop complications. 

Superimposed infection is common because T-cells and dendritic cells are directly infected, which leads to immune suppression that can persist for up to three years. Infections include:

  • Otitis media

  • Gastrointestinal (most common) - diarrhea, gingivostomatitis, appendicitis

  • Pulmonary (most common cause of death) - bronchopneumonia, croup, bronchiolitis

  • Neurologic

    • Encephalitis: occurs several days after rash. Patients have neurodevelopmental sequelae in 25% of cases, fatal in 15% of cases

    • Acute Disseminated Encephalomyelitis (ADEM): occurs several weeks after rash. Demyelinating disease likely due to immune response to the virus. Fatal in 10-20% of cases and survivors commonly have residual neurologic abnormalities. 

    • Subacute Sclerosing Panencephalitis (SSPE): occurs 7-10 years after infection. More likely the younger the time of infection

      • Stage I (weeks-years): insidious neurological symptoms (trouble concentrating, lethargy, personality changes, strange behavior)

      • Stage II (3-12 months): dementia, myoclonus

      • Stage III (variable): myoclonus resolves, neurologic function deteriorates leading to flaccidity/decorticate rigidity, autonomic dysfunction

      • Stage IV: death

Diagnosis:
First off, isolate your patient if you suspect measles!! Place the patient in a negative pressure room. Despite the high efficacy of MMR, there is still a 1% chance that you are not immune. As such, everybody entering the room should wear an N95 mask and the patient should wear a mask during transport. 

Test used depends on the prevalence of disease and the local governing body for infection control. In general, IgM and IgG are tested in the serum and a nasopharyngeal swab should be obtained for serological testing. False positive PCR does not rule out infection

Treatment:
Mainly supportive and treating any superimposed bacterial infections. In children, they tend to have low vitamin A levels, which can contribute to delayed recovery and more complications. Low vitamin A levels also causes blindness in children in the developing world. As such, children benefit from vitamin A supplementation. Ribavirin can also be considered especially for higher risk individuals (< 12 months, requiring ventilatory support, and severe immunosuppression). 


TL;DR:

  • Measles is transmitted airborne, stays in the air for 2 hours

  • Characterized by a prodrome of fever, malaise, coryza, conjunctivitis, and cough for 2-4 days followed by a maculopapular rash that progresses downward

  • Measles can be complicated by bacterial infections. Most common cause of death is from pneumonia

  • Long-term effects include severe neurological sequelae: encephalitis, acute disseminated encephalomeningitis, and subacute sclerosing panencephalitis

  • Diagnose via IgM, IgG, nasopharyngal swab

  • Treatment primarily supportive

  • Consider vitamin A and ribavirin

Sources:
https://www.uptodate.com/contents/measles-clinical-manifestations-diagnosis-treatment-and-prevention
http://www.emdocs.net/em-in-5-measles/
http://epmonthly.com/article/ready-for-the-measles-comeback/


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POTD: Measles (Vaccination and Post-Exposure Prophylaxis)

Ok guys, time for a big topic very relevant in current events - Measles! This is going to cover mostly immunization and post-exposure prophylaxis recommendations and not the clinical symptoms.

Our former clerkship director Dr. Anna Pickens has a great video summarizing all things measles available on emdocs.net:
http://www.emdocs.net/em-in-5-measles/

Scroll to the bottom for the TL;DR version. 

Vaccine_Measles_Vials-1296x728-Header.jpg

Measles

A little bit of background first. One of the most infectious pathogens, measles was targeted for eradication in the 1960s because of its highly infectious nature and it's human-only infectivity, which led to a dramatic decrease in the number of cases in developed countries. Before this, about 90% of children acquired the virus before age 15. In the United States, the immunization program has resulted in a staggering 99% percent decrease in the number of cases. Since then, largely due to under-vaccination or unvaccinated populations, cases have been on the rise since 2008. Most of these cases are imported from abroad. Of the cases in the US, 85% of cases were unvaccinated despite being eligible for vaccination. 

Measles is highly contagious and carries a 90% infectious rate when a susceptible person is exposed. Population immunity of > 95% is needed to stop ongoing transmission. 


Vaccination

In the US, two doses of vaccination MMR is recommended, the first at 12-15 months (conferring 95% immunity) and a second dose at 4-6 years of age (conferring 99% immunity) or at least 28 days after the first dose. 

Fun fact: vaccination is recommended no earlier than 12 months because maternal antibodies seem to interfere with seroconversion (87% seroconversion if administered at 9 months, 95% at 12 months, and 98% at 15 months). 

A third dose is not routinely recommended as it is not associated with any more protection than two doses. 

For those who received two doses of MMR based on the CDC recommended schedule, the CDC, NYCOH, and NYCOHMH all discourage serologic testing if the vaccine history is available. 

What this means: if your patient has had two doses of MMR, they do not need titers and if they have titers, it doesn't matter!!

For those born before 1957, they are presumed to have immunity to measles and mumps. This is not the case for rubella (not covered here). 

Pregnant women are at higher risk than the general public of measles related morbidity and mortality and should therefore be counseled by their ob/gyn regarding vaccination status. As with all adults, pregnant women that have evidence of two doses of MMR are considered immune and should not have titers performed. If documentation is not available, pregnant women should not receive MMR due to a theoretical risk of vertical transmission of rubella to the fetus. MMR vaccine should then be administered after delivery. That being said, studies on neonates that are born to women that have inadvertently received MMR shows no risk of of MMR vaccine to the fetus. 

Healthcare workers are also considered a special population due to our frequent exposure to communicable disease. The recommendations for vaccination and testing are the same as the general public regardless of date of birth (ie. two doses or serological evidence is always required). Additionally, during outbreaks, healthcare workers without evidence of immunity should receive 2 doses MMR. 


Post-Exposure

First things first: who qualifies as "being exposed to measles"? You qualify if you have shared the same air as someone while they were infectious. The infectious period lasts from 4 days before until 4 days after the onset of rash. 

Un-vaccinated individuals should receive MMR vaccination within 72 hours of exposure if there are no contraindication (ie. pregnancy, immunocompromise, anaphylactic reaction to any of the vaccine components, infants < 12 months of age). Between 72 hours and 6 days of vaccination, they should receive IMIG (0.5mL/kg IM, max 15 mL). 

Infants < 12 months of age exposed to measles should receive IMIG 0.5mL/kg IM, max 15 mL within 6 days of exposure. 

Because of the increased risk of complications and death in pregnancy, pregnant women exposed to measles should receive IVIG 400mg/kg within 6 days of exposure. Additionally, peri-partum, pediatrics should be made aware of the potential risk of congenital measles if born to a mother with measles. 

Immunocompromised individuals should also receive IVIG 400mg/kg within 6 days after exposure regardless of vaccination status.

Infants exposed to measles (< 12 months of age) should receive IMIG 0.5mL/kg (max 15 mL)

Healthcare workers who do not show evidence of immunity either by records or serological testing should receive MMR and be removed from work for 21 days following exposure. Those who do not receive MMR should be removed from work for 21 days following exposure even if they have received IMIG. If there is only one dose documented, they may remain at work and should receive a second dose. 


TL;DR

  • Measles very contagious, MMR has been successful in greatly decreasing cases

  • Most outbreaks have been due to under-vaccination or unvaccinated populations

  • Recommended schedule: 1st dose at 12-15 months, 2nd dose at 4-6 years or 28 days after the first dose

  • Titers are not necessary if there is evidence of two appropriately administered vaccinations for everyone

  • If record/evidence of vaccination is not available, serological testing should be performed

  • Post exposure:

    • Unvaccinated individuals should receive MMR within 72 hours of exposure or IMIG 72 hours-6 days after exposure

    • Infants < 12 months should receive IMIG within 6 days

    • Pregnant women and immunocompromised should received IVIG within 6 days

  • Exposed healthcare workers who do not have evidence of immunity should not return to work for 21 days following exposure regardless of whether they received MMR or IMIG. 

Sources:
https://www.uptodate.com/contents/measles-mumps-and-rubella-immunization-in-adults
https://www.uptodate.com/contents/measles-mumps-and-rubella-immunization-in-infants-children-and-adolescents
https://www.health.ny.gov/prevention/immunization/toolkits/docs/health_advisory.pdf
https://www.cdc.gov/mmwr/preview/mmwrhtml/rr6007a1.htm
http://www.emdocs.net/em-in-5-measles/
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4552307/

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POTD: Lithium Toxicity (Toxicology Thursday)

Lithium has been used to treat patients with bipolar disorder since the 1870s and is still widely used today, but has a very narrow therapeutic index! Toxicity can due to acute deliberate ingestions (18%) or, more commonly, chronic ingestions.

There are three categories of toxicity:

Acute: due to ingestion in a lithium naive patient, generally, an ingestion of > 7.5mg/kg of elemental lithium or 40 mg/kg of lithium carbonate. Prognosis tends to be better in acute poisoning because there is not sufficient time for distribution, which decreases the risk of neurotoxicity.

Acute-on-Chronic: an acute ingestion in a patient chronically on lithium

Chronic poisoning: occurs when chronic ingestion exceeds elimination. Highest risk of neurotoxicity because there is sufficient time to accumulate. Also the half life of lithium in chronic toxicity is prolonged due to underlying renal impairment.

Etiology 

Toxicity from chronic ingestions occur from impaired excretion due to:

  • Reduced GFR (NSAIDs, ACE inhibitors)

  • Increased renal tubular reabsorption (thiazides, spironolactone)

  • Calcium channel blockers (unknown mechanism)

 Renal processing is similar to that of sodium – meaning if the kidneys find any reason to retain sodium, it will also retain lithium! A major example is dehydration.

Serum lithium levels may be high, but the patient may be asymptomatic because effects only occur when moved intracellularly.

 

Manifestations:

Neurological:

  • Coarse tremor

  • Hyperreflexia

  • Nystagmus

  • Ataxia

  • Altered mental status

  • Seizures/non-convulsive status epilepticus

Renal:

  • Nephrogenic diabetes insipidus

  • Sodium losing nephritis

  • Nephrotic syndrome

Cardiovascular (usually mild)

  • Wandering atrial pacemaker

  • Sinus bradycardia

  • ST-segment elevation

  • Prolonged QT syndrome

  • T-wave flattening

Gastrointestinal

  • Nausea/vomiting

  • Diarrhea

  • Ileus

**this can worsen toxicity due to increased renal reabsorption of sodium and lithium

Endocrine

  • Hypothyroidism (inhibition of hormone synthesis)

    • Also worsens lithium toxicity

Evaluation:

Labs including TFTs, renal function, calcium, serum lithium level, EKG, cardiac monitoring. Make sure the tube was not treated with lithiated heparin. Remember, the serum level does not reflect the intracellular level, so a patient may be asymptomatic with high levels and normal levels do not exclude toxicity!!

However, generally:

  • Mild intoxication (1.5-2.5 mEq/L): nausea/vomiting, lethargy, tremor

  • Moderate intoxication (2.5-3.5 mEq/L): confusion, agitation, delirium, tachycardia, hypertonia

  • Severe intoxication (> 3.5 mEq/L): coma, seizures, hyperthermia, hypotension 

Treatment

Symptomatic treatment (e.g. benzos for seizures, magnesium for torsades).

IVF – the goal is to preserve GFR so that lithium does not get reabsorbed!

Activated charcoal does not work, but you may consider gastric lavage or whole-bowel irrigation for acute ingestions.

Hemodialysis for severe toxicity or renal failure

Patient should be admitted to a monitored setting. Admit to ICU for severe symptoms!! If patients are asymptomatic with a lithium level < 1.5 mEq/L, they may be discharged.

References:
https://emcrit.org/wp-content/uploads/2016/09/Lithium-Toxicity.pdf
https://www.ncbi.nlm.nih.gov/books/NBK499992/
https://www.uptodate.com/contents/lithium-poisoning