Parvovirus B19
Causes Fifth disease = “slapped cheek” facial erythema in Peds.
Once child has developed the red cheeks, he/she has immunologically cleared the illness (i.e., if they turn it into a behavioral science Q, tell parents to chill the fuck out / relax because the child has cleared the virus).
Can cause exanthem (body rash) +/- arthritis in adults, especially in daycare workers (USMLE is obsessed with this).
Can cause pure-RBC aplasia (i.e., only RBCs are low) or full-blown aplastic anemia (where all cell lines – RBCs, WBCs, and platelets – are down).
There is increased risk of pure-RBC aplasia and aplastic anemia if the infection occurs in utero and in sickle cell patients.
Next best step in diagnosis for Fifth disease or exanthem/arthritis is check serum IgM titers.
If any of the hematologic cell lines are down, do bone marrow biopsy to confirm diagnosis.
Human papillomavirus (HPV)
HPV 6+11 cause condylomata acuminata (geneital warts).
However, the warts caused by strains 6+11 are not limited to the genitalia and can cause laryngeal papillomatosis in neonates and infants (warts of the vocal cords), which is asked on NBME. Lesions will have papillary structures on biopsy. Acquired vertically via exposure from maternal vaginal canal.
HPV 16+18 cause squamous cell carcinoma of genitalia/anus; risk of overt SCC is increased in immunocompromised (i.e., HIV in MSM) and heavy smoking. Students will get maniacal about other SCC-causing strains beyond 16+18 but USMLE doesn’t give a fuck.
JC polyomavirus
Causes progressive multifocal leukoencephalopathy (PML).
Presents as neurodegeneration over weeks to months in immunocompromised patient – i.e., AIDS patient with CD4 count <100, patients undergoing chemoradiotherapy, or those on immunosuppressant drugs.
USMLE wants you to know this condition is due to “reactivation of latent infection,” which means the patient is infected at some point during life years ago, but the condition now manifests due to immunosuppression. “Acute infection in immunocompromised patient” is the wrong answer.
BK polyomavirus
Causes kidney infections in kidney transplant patients. Rare. You could just be aware it exists. I believe one Q ever in history exists on NBME somewhere.
Adenovirus
Hepatitis B
Mandatory stuff for USMLE is the serology (I discuss below).
Most common hepatitis infection in the worldwide. USMLE likes China for hepatitis B. Just a pattern I’ve noticed. Due to increased unvaccinated. In the USA, HepC is most common.
Parenteral; can be acute or chronic.
Transmitted vertically from mother to neonate, sex, IV drugs, or blood exposure.
Present in all body fluids, including breast milk.
Serology very HY (I discuss meaning of variables below the table):
HBsAg = HepB surface antigen.
HBsAb = HepB surface antibody; if positive, patient is immune; if negative, patient is not immune.
HBcAb = HepB core antibody; if positive, patient either currently has HepB or had it in the past (i.e., cleared it).
HBcAb IgM = has acute infection.
HBcAb IgG = has chronic HepB or has cleared it.
Window period = Once a susceptible patient is exposed to HepB and the immune system attempts to clear it, sometimes Surface antigen will decline to the point that it is no longer detectible. But at the same time, the Surface antibody might not be high enough / at detectable levels yet. This is called the “window period,” where both Surface antigen and antibody are negative, so it can appear as though the patient doesn’t have an infection. However, Core antibody IgM will be (+). So the key point is that 1) you know the double-negative Surface antibody/antigen combo is seen in the window period, and 2) that Core antibody IgM is most reliable during the window period.
Vaccination against HepB is at birth, 2 months, and 6 months (no longer at 4 months).
Only give HepB IVIG to neonate if mom is confirmed (+). A 2CK NBME Q gives mother’s status as unknown when child is born –> answer = “Give HepB vaccine now + only give IVIG if mother is positive.”
If patient has Hx of completed HepB vaccination but has titers that show susceptibility, the answer is just “give more vaccine.” Sometimes people’s immunity wanes.
USMLE really doesn’t give a fuck about HepB pharm (i.e., entecavir, tenofovir). Waste of time. You could be aware that interferon-alpha can be used for HepB.
Poxvirus
Largest DNA virus.
Causes molloscum cantagiosum, which presents as skin-colored or reddish papules with central umbilication. Very HY spot-diagnosis for Peds.
USMLE likes giving vignette where kid went to a recent pool party.
You can also be aware of another poxvirus called Vaccinia, which is similar to smallpox and was used in the development of the smallpox vaccine. “Vaccinia” shows up as an answer on a new NBME where they talk about smallpox eradication.
Herpes simplex (HSV) 1/2
Causes painful vesicular lesions of the lips and genitalia that recur at varying intervals (usually months).
Primary infection is most severe, often with fever, regional lymphadenopathy, burning/stinging/itching pain (herpetic neuralgia), and many vesicles. Recurrences are often less severe and preceded by herpetic neuralgia. USMLE wants you to know herpes goes latent in sensory nerves (makes sense, since recurrences cause neuralgia/pain).
Don’t confuse HSV1/2 with chancroid caused by the bacterium Haemophilus ducreyi. HSV1/2 will be usually be clusters of painful lesions that demonstrate recurrence, whereas chancroid will be a singular lesion that is not recurrent. There is one Q out there where they give you a singular painful lesion with recurrence, and the answer is HSV, not H. ducreyi. In this case, the recurrence is what tells you it’s HSV1/2. Perhaps in some cases, herpetic infections can start as a single vesicle before erupting into the typical cluster-appearance. H. ducreyi is also typically acquired overseas, e.g., in backpackers traveling in the third-world.
HSV1/2 can cause herpes encephalitis (confusion + blood in CSF due to temporal lobe hemorrhage).
I would say 4/5 herpes encephalitis Qs mention blood in the CSF. There’s one 2CK neuro form Q where the blood is negative, but the CSF findings are otherwise viral (normal glucose and protein; high lymphocytes).
You also need to know that CT of the head can be negative. I mention this because even though it can cause temporal lobe hemorrhage, the Q can say CT shows no abnormalities. They might mention spikes over the temporal region (implying there’s still abnormality/hemorrhage there). So they can say something like: 24-year-old male with confusion and fever + viral CSF findings + blood in CSF + CT of head shows no abnormalities + EEG shows spikes over temporal region. Answer = intravenous acyclovir.
Can cause herpetic whitlow, which presents as vesicles on the finger in a child who’s touched a mother’s cold sore while breastfeeding, or in dental workers/hygienists.
Can cause eczema herpeticum, which is HSV1/2 infection superimposed on eczema. Can present with stinging/burning pain (herpetic neuralgia). Treat with acyclovir.
Can cause herpes keratitis (inflammation of the cornea). Presents as dendritic (tree-like) pattern on fluorescein instillation of the eye. It may or may not present with periorbital vesicles.
Herpes esophagitis presents as punched-out ulcers and odynophagia (pain with swallowing). This is in contrast to CMV esophagitis, which causes linear/confluent ulcers.
Viral culture can be negative in stem (not 100% sensitive).
Treat with acyclovir (or valacyclovir), which is a DNA polymerase inhibitor. HSV1/2 resistance to acyclovir occurs via altered viral thymidine kinase.
Varicella zoster virus (VZV; human herpes virus-3; HHV-3)
Causes chickenpox; can be described as clusters of vesicles at different stages of healing on an unvaccinated child or adult. Chickenpox Qs are exceedingly rare for USMLE. What they actually care about is shingles.
Shingles is aka herpes zoster. Herpes zoster is not the name of a virus. This is just another name for shingles. So we can say, shingles, aka herpes zoster, is caused by varicella zoster virus.
Shingles presents as vesicles erupting in a dermatomal distribution (i.e., usually on the flank or back of neck) idiopathically in middle-age individuals or older. Can be brought on by stress or transient negative flux in immunity.
Once the vesicles rupture, they can sometimes look black. So just know it’s weird but possible. What’s most telling for herpetic infections (whether it be HSV1/2, or VZV causing shingles) is that they form characteristic clusters of small vesicles. It’s this characteristic clustering that can be buzzy/easy for herpetic infection.
Shingles can occur in immunocompromised kids (e.g., those undergoing chemotherapy). This is called pediatric shingles. Just know “it’s a thing.” Because most students think it only occurs in middle age or older.
Can cause herpes zoster ophthalmicus (periorbital vesicles), which means shingles of the eye. This may or may not co-present with keratitis (and the dendritic pattern) that looks identical to that caused by HSV1/2.
Can cause herpes zoster oticus (vesicles in the ear), which means shingles of the ear. This may or may not present with concurrent Bell’s palsy due to CN VII involvement. Bell’s palsy due to shingles is called Ramsay-Hunt syndrome type II.
Vaccination against VZV occurs with two doses: the first at 12-15 months; the second at 4-6 years.
Shingles vaccine is given at age 50 (on new Family Med form).
These vaccines are live-attenuated.
Treat shingles with acyclovir (or valacyclovir).
Varicella can cause pneumonia in immunocompromised and pregnant women. Slightly unusual, but just know it’s possible.
VZV immunoglobulin is given to a neonate if an unvaccinated pregnant woman develops a chickenpox rash within 5 days prior to 2 days post-parturition.
If pregnant woman contracts chickenpox, the fetus may develop congenital varicella syndrome, which can present as microcephaly and skin vesicles demonstrating a “zig-zag” pattern.
Ebstein-Barr virus (EBV; human herpes virus-4; HHV-4)
Causes mononucleosis, nasopharyngeal carcinoma, oral hairy leukoplakia, and both Hodgkin and non-Hodgkin (notably Burkitt) lymphomas.
Mononucleosis is usually caused by EBV, but can also be CMV.
The virus invades B cells, which then stimulates the immune system to produce CD8+ T cells attacking the viral-infected B cells. In mono, these CD8+ T cells are called “atypical lymphocytes.” The USMLE wants you to know these are reactive CD8+ T cells. They are “reactive” because they are responding to the viral-infected B cells.
Primary infection presents usually in teenager or young adult with fever >38 C, lymphadenopathy, tonsillar exudates, and lack of cough, making the presentation appear bacterial (in the HY Pulmonary PDF, I talk about CENTOR criteria for differentiating bacterial from viral URTIs). As a result, it is often misdiagnosed as Strep pharyngitis.
If amoxicillin or penicillin is given to treat EBV, this can cause a rash. This is not to be confused with a rash caused by allergy to beta-lactams. If pre-adolescent receives beta-lactam and gets a rash, that is likely beta-lactam allergy. If a patient adolescent or older gets a rash, we do a heterophile antibody (Monospot) test as next best step in diagnosis, as EBV mono is more likely.
The heterophile antibody test is how we diagnose EBV, where for some magical reason, the antibodies we produce against EBV cross-react with horse and sheep RBCs, hence the antibodies like (-phile) different (hetero-) antigens.
Following the primary infection, mono can present as recurrent episodes of extreme fatigue that arise at interval of months to years.
Nasopharyngeal carcinoma is a type of squamous cell carcinoma.
Oral hairy leukoplakia presents as white lesions on the tongue that cannot be scraped off. They are not pre-cancerous (no dysplasia on biopsy). This is in contrast to “regular” leukoplakia caused by tobacco, which is a precursor to SCC.
The increased risk of Hodgkin and non-Hodgkin lymphomas is because EBV invades B cells.
Cytomegalovirus (CMV; human herpes virus-5; HHV-5)
Most common organism transmitted via blood transfusions and organ transplants.
Causes infections of many different organ systems (e.g., lung, kidney, GI tract, retina), as well as CMV mono. There is an NBME Q where they give CMV pneumonia in patient following renal transplant, where they show the buzzy owl-eye appearance of cells.
USMLE likes “intranuclear inclusions” or “intranuclear inclusion bodies” for CMV. This refers to the “owl eyes” that can be seen on histo.
CMV esophagitis presents as linear/confluent ulcers and odynophagia. This is in contrast to HSV1/2, which cause punched-out ulcers.
CMV colitis presents as linear/confluent ulcers in AIDS patients with CD4 counts under 50-100.
Blurry vision in HIV patient = CMV retinitis until proven otherwise.
CMV mono is differentiated from EBV mono in that the former has a negative heterophile antibody (Monospot) test. Additionally, CMV can cause cold autoimmune hemolytic anemia due to the production of IgM antibodies against RBCs, with a positive Coombs test (means we have antibodies against RBCs). So if patient with mono has low hemoglobin and high LDH, for instance, that could point toward CMV over EBV. High LDH on USMLE almost always means hemolysis, since RBCs are packed with LDH.
CMV is treated with ganciclovir, which is a DNA polymerase inhibitor. CMV resistance to ganciclovir occurs via altered viral thymidine kinase. The MOA and resistance mechanisms are the same as HSV1/2 and VZV with respect to acyclovir.
The stem might mention a patient who had a kidney transplant 6 months ago who now has deteriorating renal function + intra-nuclear inclusions seen on biopsy. The answer is just “ganciclovir therapy.”
Human herpes virus-6 (HHV-6)
Causes roseola infantum, aka Sixth disease, or exanthema subitum.
Very easy/buzzy descriptor for USMLE: causes a “spiking fever followed by a rash” in a kid.
USMLE will literally say something to the effect of a kid having a maculopapular body rash that was preceded by a worrisome fever of 39C for the 3 days prior. Once the rash has formed, the child has cleared the infection (similar to slapped cheek appearance with Fifth disease due to Parvo).
Virus is self-limiting / no treatment necessary.
Human herpes virus-7 (HHV-7)
Causes pityriasis rosea, which is a rash that starts as Herald patch (larger pink ellipse), usually on the back or trunk, then spreads upward onto the shoulder blades (“Christmas tree distribution”); USMLE will show you image and expect you can make spot-diagnosis.
Can occur in teenagers, although more common in the 20s. May or may not be itchy.
Virus is self-limiting / no treatment necessary.
Kaposi sarcoma-associated herpesvirus (KSAH; human herpes virus-8; HHV-8)
Kaposi sarcoma is violaceous, tumorous lesions of vascular-lymphatic origin.
Usually seen in immunocompromised patients (i.e., AIDS, chemotherapy).
Q can show you image such as above and then the answer is just “anti-neoplastic” for the Tx (whereas answers like anti-fungal, anti-bacterial, etc., are wrong).
Bacillary angiomatosis caused by Bartonella henselae (normally causes cat-scratch disease) can present as Kaposi sarcoma-like lesions. What USMLE will do is give you a vignette that sounds just like Kaposi sarcoma (i.e., AIDS patient with violaceous skin lesions), followed by asking you for the organism that causes it. You’ll notice that HHV-8 (as well has HepC for lichen planus) isn’t listed, where all the answers are bacteria, and you just select Bartonella henselae.
