Congenital TORCH infections: Pathology review

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Case Studies0:00–1:19

At the clinic, two mothers came in with their babies. The first baby is an 11 month old girl called Cecile, who is brought by her parents, who are immigrants, for a routine visit.
You immediately noticed that she doesn’t react when you call her name, as if she can’t hear you at all. Upon eye examination, you find that Cecile has bilateral clouding of the lens.
Then, upon cardiac auscultation, you hear a continuous rumbling murmur. Upon further questioning, Cecile’s mother tells you that, during the first trimester of pregnancy, she developed a rash that mainly involved her head and neck, as well as swollen lymph nodes behind the ears.
After Cecile, comes a 6 month old baby boy named Arthur with his mother, who is concerned because Arthur has developed multiple purple marks on his skin.
Upon physical examination, you noticed that Arthur has an unusually large head for his age. Then, on fundoscopy, his eyes show white and yellow scars that look like cotton.
You decide to order a CT scan of the brain, which reveals scattered calcifications. Upon further questioning, Arthur’s mother admits to handling her cat’s litter while she was pregnant, despite her doctor’s advice against it.
All right, now both Cecile and Arthur seem to have a congenital TORCH infection. TORCH is an acronym that stands for infections caused by Toxoplasma gondii; Other agents, such as syphilis, parvovirus B19, varicella zoster virus, and listeria; then there’s Rubella; Cytomegalovirus, and finally Herpes simplex virus-2 or HSV-2.

Pathology 1:19–2:33

All these infections are lumped together because they can be vertically transmitted, which means that a pregnant individual can transmit the infection to their child either before birth via the placenta, or during and after birth via blood, body fluids, or breast milk.
Now, keep in mind that TORCH infections may share some non-specific signs and symptoms, including delayed growth, and hepatosplenomegaly or enlarged liver and spleen, which can lead to jaundice or yellow skin, and thrombocytopenia or low platelet count.
So for your exams, it’s important that you’re able to distinguish the different TORCH infections based on additional characteristics.Okay, the first TORCH infection is toxoplasmosis, which is caused by the protozoan parasite Toxoplasma gondii.

Toxoplasmosis 2:33–4:18

For your exams, remember that pregnant individuals usually get infected from contact with cat feces, such as when handling cat litter, as well as consumption of undercooked meat, especially pork and lamb.
However, keep in mind that the pregnant individual typically remains asymptomatic, or may rarely develop lymphadenopathy or enlarged lymph nodes.
The bad news is that toxoplasma can be transmitted to the fetus via the placenta, and if that happens during the first six months of pregnancy, it can lead to congenital toxoplasmosis.
Now, the most high yield manifestations of congenital toxoplasmosis include the classic triad of chorioretinitis, hydrocephalus, and intracranial calcifications.
Chorioretinitis is an inflammation of the choroid and retina of the eye, which can be seen upon fundoscopy as white and yellow scars that look like cotton.
Then, hydrocephalus is when fluid builds up within the ventricles, which are cavities within the brain. As a result, there’s enlargement of the ventricles, so these babies develop macrocephaly or an enlarged head.
Finally, intracranial calcifications are basically calcifications that are typically randomly distributed within the brain tissue, and can be seen on brain CT scan.
An additional clue that you may find on a test question is that some babies with congenital toxoplasmosis may present with multiple purple-blue marks in the skin, which is often referred to as a “blueberry muffin” rash.The next TORCH infections are Other agents, which includes syphilis, parvovirus B19, varicella zoster virus, and listeria.

Other Agents: Syphilis 4:18–7:52

Now, syphilis is caused by the spirochete bacterium treponema pallidum, which is transmitted through sexual contact, including vaginal, anal, and oral sex.
Now, syphilis has three stages. The first stage as soon as the person gets infected is called primary syphilis or early localized stage, and it’s characterized by the presence of chancres or painless skin ulcers, which usually appear on the labia, anal region or cervix.
About 2 to 10 weeks later begins the second stage, which is called secondary syphilis, or the dissemination stage, where treponema pallidum enters the bloodstream.
As a result, individuals develop generalized lymphadenopathy. In addition, individuals may present with a maculopapular rash, which are small bumps that start on the trunk and spread out to the arms and legs and eventually to the palms, soles, genitalia, and other mucous membranes.
And some individuals may also develop condyloma lata, which are smooth, white, painless, wart-like lesions on the genitals and around the anal region.
The third stage is called latent syphilis, and it’s when the disease enters a dormant or asymptomatic phase. Individuals who don’t get any treatment eventually progress into the final stage of syphilis, which is called tertiary syphilis.Here, the immune cells start to huddle around and form characteristic granulomatous lesions called gummas.
In addition, various organs get damaged, especially the heart and blood vessels leading to cardiovascular syphilis, as well as the brain and spinal cord leading to neurosyphilis.
What’s really important to remember is that the first and second stages are the most infectious, so that’s when the fetus is most likely to get infected, either via the placenta or during childbirth.
Now, congenital syphilis often results in hydrops fetalis, which is when the fetus has an abnormal accumulation of fluid in soft tissues.
This poses a great risk for still-birth, which is when the fetus dies within the womb. Babies who survive the pregnancy typically develop some characteristic features that can be divided into early signs, which appear during the first two years of life; and late signs, which appear after the child is two years old.
Early signs can include a maculopapular rash involving palms and soles of the feet, as well as snuffles or increased nasal secretions, which are laden with treponema.
On the other hand, late signs include frontal bossing where the forehead is really prominent, as well as a saddle nose with a depressed nasal bridge, and a short maxilla.
Another very characteristic finding is Hutchinson teeth, which are small, notched, and widely spaced permanent teeth. These children may also develop saber shins, which refers to bending of the shinbone or tibia.
Finally, congenital syphilis may lead to progessive damage to the vestibulocochlear nerve or cranial nerve VIII, which normally transmits sound.
As a result, congenital syphilis may cause deafness or hearing loss.Next up is parvovirus B19 infection, which is primarily transmitted via respiratory droplets when someone coughs or sneezes.

Parvovirus B19 infection7:52–9:28

In a pregnant individual, parvovirus B19 infection causes arthritis or joint inflammation with pain and stiffness. This usually affects the small joints of the hands, wrists, knees, and feet, and is often symmetrical, meaning that the same joints on both sides of the body will be affected.
Now, this presentation is very similar to that of rheumatoid arthritis, so to set these two apart, remember that parvovirus B19 also leads to a decreased red blood cell production in the bone marrow, which can result in pure red blood cell aplasia.
This is a type of anemia characterized by the absence of reticulocytes, which are red blood cell precursors in the bone marrow.
Now, parvovirus B19 can also be transmitted by a pregnant individual to the fetus via the placenta. As a result, the fetus will also develop anemia.
Because there are fewer red blood cells to carry oxygen, the heart will pump a larger volume of blood to give the growing fetus all the oxygen it needs.
This raises the pressure inside the fetal blood vessels, and fluid may start to leak out. This can ultimately result in hydrops fetalis, which poses a great risk for spontaneous abortion or still-birth, especially if the infection occurs in the first half of the pregnancy.
The good news is that fetuses who survive the infection don’t develop any permanent defects or malformations.Okay, moving onto the next one.

Varicella zoster virus9:28–10:56

Varicella or chickenpox is caused by the varicella zoster virus, or VZV for short. VZV can be transmitted by respiratory droplets when someone coughs or sneezes, as well as via contact with the oral or skin lesions of an infected person.
What can be concerning is when the VZV infection is transmitted to a pregnant individual who is unvaccinated or has no history of previous infection.
Maternal varicella zoster usually causes a fever, headache, and overall weakness. After a couple days, the pregnant individual will develop an intensely pruritic, vesicular rash, which starts on the trunk and then spreads outward, eventually covering the entire body.
And most importantly, the pregnant person can transmit the infection to the fetus via the placenta. The main issue is when this occurs in the first or second trimester, when the fetus is still undergoing major development and is most vulnerable.
This can lead to congenital varicella syndrome, where babies are born underdeveloped, and the most high yield findings include low birth weight, limb atrophy, and microcephaly or an abnormally small head.
In addition, these babies may develop eye defects, such as cataracts, which refers to clouding or opacification of the lens, as well as neurological defects like cortical atrophy or brain degeneration, and intellectual disability.Next up is listeria infection, caused by the bacteria listeria monocytogenes.

Listeria10:56–11:56

In a test question, look for an individual that gets infected after ingestion of contaminated foods like unpasteurized dairy products and deli meats.
Now, in pregnant individuals, listeria infection may cause fever, fatigue, and gastroenteritis with diarrhea, vomiting, and abdominal cramps.
Another high yield presentation is amnionitis or infection of the amniotic fluid. And the most severe cases may even develop sepsis, which is when listeria spreads to the bloodstream.
Now, the main route of transmission to the fetus is via the placenta, which may result in spontaneous abortion or still-birth.
If the fetus survives to term, it may develop sepsis and meningitis, which is an inflammation of the meninges that cover and protect the brain and spinal cord, and is fatal if untreated.The next letter in TORCH is R, which stands for rubella infection, previously known as German measles.

Rubella11:56–13:30

This is caused by rubella virus, which can be transmitted to a pregnant person via respiratory droplets. A very important fact you must remember is that most children from 12 to 15 months of age get the MMR vaccine against measles, mumps, and rubella.
So in a test question, you should be suspicious of rubella infection in an individual that may not be vaccinated, such as an immigrant.
Now, the maternal infection manifests with a maculopapular rash that starts from the head and neck and spreads downward; as well as postauricular lymphadenopathy, which is an enlargement of the lymph nodes behind the ears.
Another high yield manifestation of maternal rubella infection is polyarthritis, so arthritis that involves at least five joints.
And if the infection occurs during the first trimester of pregnancy, the fetus may develop congenital rubella syndrome. For your exams, you have to know the characteristic triad of congenital rubella syndrome, which includes deafness, cataracts, and congenital heart defects, like patent ductus arteriosus.
Now, an important clue for patent ductus arteriosus may be heard upon cardiac auscultation as a continuous rumbling murmur, which is often referred to as a “machinery” murmur.
In addition, keep in mind that some newborns may also present with a “blueberry muffin” rash.Next up in TORCH, we have cytomegalovirus or CMV infection, which is mainly transmitted through sexual contact, but can also be transmitted via organ transplantation.

Cytomegalovirus 13:30–14:41

Now, pregnant people who get infected by CMV are usually asymptomatic, but some can develop mononucleosis-like symptoms.
These typically include fever, lymphadenopathy, and a sore throat. Now, CMV infection can be passed to the fetus via the placenta.
Babies born with congenital CMV infection can present with petechiae, which are tiny purple, red, or brown spots on the skin, as well as a “blueberry muffin” rash.
Other hallmark features of congenital CMV include progressive and permanent deafness, as well as eye abnormalities, such as chorioretinitis or an inflammation of the choroid and retina.
Now, congenital CMV can also affect the brain, causing seizures and intellectual disability, which are often associated with microcephaly.
And a high yield finding that can be seen on brain CT scan are periventricular calcifications, which are calcifications around the ventricles of the brain.Finally, there’s herpes simplex virus-2 or HSV-2 infection, which is transmitted through direct contact with infected areas of the skin or mucous membranes.

Herpes simplex virus-214:41–15:39

Now, HSV-2 infection in a pregnant individual is usually asymptomatic, but it can develop genital herpes, which is characterized by vesicular skin lesions that form on the vaginal mucosa, mons pubis, cervix, and labia.
Now, HSV-2 infection can also be passed from a mother to a baby, but this mainly happens during childbirth, when the baby passes through infected vaginal secretions.
Neonatal HSV-2 infection also presents with the characteristic vesicular skin lesions, which mainly involve the scalp, the eyelid margins, and the oral mucosa.
But what’s really high yield is that HSV-2 infection in neonates can lead to meningoencephalitis, or inflammation of the meninges and the brain.
This can present with lethargy, irritability, and even seizures.All right, as a quick recap… Congenital TORCH infections are vertically transmitted infections caused by Toxoplasma gondii; Other agents, such as syphilis, parvovirus B19, varicella zoster virus, listeria; Rubella; Cytomegalovirus; and Herpes simplex virus-2.

Review15:39–18:55

Toxoplasma is transmitted via contact with cat feces or consumption of undercooked meat, and a pregnant individual can then transmit it to the fetus via the placenta.
If that happens during the first six months of pregnancy, it can lead to congenital toxoplasmosis with the triad of chorioretinitis, hydrocephalus, and intracranial calcifications.
Syphilis is usually transmitted to the pregnant person via sexual contact, while the fetus can get infected either through the placenta or during childbirth.
Congenital syphilis often results in hydrops fetalis, and poses a great risk for still-birth. Babies who survive typically present with frontal bossing, a saddle nose, short maxilla, Hutchinson teeth, saber shins, and may develop deafness.
Parvovirus B19 infection is primarily transmitted via respiratory droplets when someone coughs or sneezes. It can present in the pregnant individual with arthritis and pure red blood cell aplasia, while the fetus can develop anemia and hydrops fetalis, which poses a great risk for spontaneous abortion or still-birth.
Varicella zoster virus infection can occur in unvaccinated people without a history of previous infection. A pregnant person can then transmit it to the fetus via the placenta.
Now, if the infection occurs in the first or second trimester of pregnancy, the fetus can develop congenital varicella syndrome, which is characterized by low birth weight, limb atrophy, and microcephaly, as well as eye and neurological defects.
Listeria infection occurs after consumption of unpasteurized dairy products and deli meats, and is mainly transmitted to the fetus via the placenta, which can result in spontaneous abortion or still-birth.
If the fetus survives to term, it may develop sepsis and meningitis. Rubella infection can be transmitted via respiratory droplets to a pregnant person who did not get the MMR vaccine, and it can pass onto the fetus especially during the first trimester, causing the triad of deafness, cataracts, and congenital heart defects.
Cytomegalovirus can be transmitted via sexual contact or organ transplantation to the pregnant person, who can in turn pass it to the fetus via the placenta.
Congenital cytomegalovirus is characterized by petechiae, deafness, and chorioretinitis, as well as periventricular calcifications and seizures.
Finally, herpes simplex virus-2 infection is transmitted through direct contact with infected areas of the skin or mucous membranes, so it can be transmitted during childbirth to the baby.
These babies can develop vesicular skin lesions, and meningoencephalitis.All right, finally going back to our cases, Cecile is the 11 month old baby girl that presents with deafness and cataracts.

Summary18:55–20:19

These two symptoms alone are present in various congenital TORCH infections, but combined should already make you think of rubella.
Upon cardiac auscultation, Cecile has a “machinery” murmur, which indicates that she has a congenital heart defect. This completes the characteristic triad of congenital rubella syndrome.
An additional clue is that Cecile’s mother developed, when pregnant, a rash that mainly involved her head and neck, combined with postauricular lymphadenopathy, which are typical of maternal rubella infection.
And because Cecile’s parents are immigrants, her mother might not have gotten the MMR vaccine. On the other hand, Arthur is the 6 month old baby boy who developed a blueberry muffin rash.
Now, a very suggestive clue here is the fact that Arthur’s mother handled her cat’s litter while she was pregnant, which should immediately make you think of toxoplasmosis.
The key here is that Arthur has a unique combination of chorioretinitis and intracranial calcifications, which are two out of three manifestations of the classic triad of congenital toxoplasmosis.
And remember that the third manifestation is hydrocephalus, which is probably what caused Arthur’s macrocephaly.