USMLE® Step 1 style questions USMLE
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A 34-year-old woman, gravida 2, para 1 at 28 weeks' gestation presents to the clinic for routine antepartum surveillance. She explains that recently, she has not felt her baby move as much as she has in the past. She complains of fatigue and joint pain. Ultrasound shows accumulation of fluid in the subcutaneous tissue and abdomen. Fetal Doppler assessment shows severe anemia. Amniocentesis shows fetal infection with parvovirus B19. Which of the following is the most likely diagnosis?
Content Reviewers:Rishi Desai, MD, MPH
Parvovirus B19 is the smallest known DNA animal virus, coming in at an itty bitty 18 to 28 nanometers in diameter.
In comparison, the average size of a single human red blood cell is a whopping 7200 nanometers!
While it’s mostly known for causing fifth disease, or “slapped cheek syndrome,” in children, parvovirus B19 can also affect adults and it can cause serious illness in individuals with pre-existing conditions like sickle-cell anemia and HIV.
Parvovirus B19 is part of the parvoviridae family.
It’s a single-stranded DNA virus surrounded by an icosahedral capsid, which is a spherical protein shell made up of 20 equilateral triangular faces.
And it’s “naked” because the capsid isn’t covered by a lipid membrane.
Parvovirus B19 is primarily transmitted by respiratory droplets when someone coughs or sneezes.
You can also catch it via an infected blood transfusion and a pregnant female can also transmit it through the placenta to her unborn child.
Now, although the virus first enters cells of the respiratory tract by binding to receptors on host cells, it doesn’t replicate in them.
Instead it keeps travelling through cells and into the circulatory system until it reaches bone marrow, where red blood cells are made, a process called erythropoiesis.
Once there, parvovirus B19 uses receptor-mediated endocytosis to enter erythroid progenitor cells, also called proerythroblasts, the early cells that eventually become red blood cells.
It then uses these cells’ DNA replication machinery in the nucleus to replicate its DNA and assemble new copies of the virus.
Why not simply replicate in cells of the respiratory system?
Well it turns out that Parvovirus B19 needs two things: it prefers to bind to a specific receptor, the P antigen, which is found in large numbers on proerythroblasts’ cell membrane and it needs cells that pass through the S phase of the cell cycle, which is the phase where cell DNA is replicated.
Since the body is constantly producing new red blood cells, there are always proerythroblasts going through the S phase at any given time.
As the virus replicates and matures, it produces a protein called non-structural protein 1 or NS1, which is toxic to human cells and causes apoptosis, or cell death.
This means that erythropoiesis breaks down, and fewer new red blood cells go into circulation as a result of parvovirus B19 infection.
But thankfully this is only temporary.
When the cell dies, it bursts open, releasing copies of the virus into the blood, also called viremia.
Our immune system detects the virus and starts producing specific immunoglobulin M and immunoglobulin G antibodies to fight the infection by forming immune complexes with the parvovirus B19 antigen.
For individuals with a functioning immune system, this typically happens between 10 and 14 days after first becoming infected with the virus.
Parvovirus B19 is most common in young children and those who live or work with them, like parents, siblings, and daycare workers.
Fetuses are at risk of parvovirus B19 if their pregnant mother has never had the virus in the past.
Immunocompromised individuals are also particularly at risk of chronic parvovirus B19 infection, since their immune system cannot mount an appropriate response to the virus.
The incubation period for parvovirus B19 - basically the period before viremia starts - is between 4 and 14 days, after which symptoms develop.
Flu-like symptoms - like a mild fever, headache, and aching muscles - are most common during viremia.
Once the immune response begins and the viremia ends, these symptoms go away and some individuals will then develop a rash and/or joint pain.
The rash appears as uniform redness of the cheeks, but not the area around the mouth, giving the classic fifth disease “slapped cheek” appearance.
A lace-like rash might also appear on the trunk and the limbs.
Joint pain and inflammation, or arthralgia and arthritis, linked to parvovirus B19 infection usually affects the small joints of the hands, wrists, feet, and knees, and are often symmetrical, meaning that the same joints on both sides of the body will be affected.
Children tend to get the rash whereas adults are more likely to develop joint pain, but it’s not exclusive to either group.
There are a few complications caused by parvovirus B19 infection.