skin 7: karposi sarcoma, measles, rubella, NPEs

Question 1

Kaposi sarcoma caused by ??

epidemiology

Answer 1

HHV-8
Low endemicity in US, but high endemicity in underdeveloped countries.
Secreted in saliva; unknown if shed chronically or only during primary infection. B
cells are one site of latency
HHV-8 is associated with all forms Karposi sarcoma (KS)

Question 2

Kaposi sarcoma risk factors:

Answer 2

older than 60yr males of Mediterranean and Middle Eastern

extraction; AIDS

Question 3

kaposi sarcoma Clinical Manifestation

Answer 3

bluish-red or purple bumps (tumors) on the skin (rich in blood vessels)
lesions may first appear on the feet or ankles, thighs, arms, hands, face, or any other part of the body. They also can appear on sites inside the body.

Question 4

kaposi sarcoma ddx

Answer 4

Bacillary angimatosis cause by Bartonella sp

Question 5

karposi sarcoma tx

Answer 5

localized nodular disease may respond well to surgical excision, radiotherapy, and
intralesional and outpatient low-dose vinblastine chemotherapy

Question 6

measles

Answer 6

(Rubeola or “hard” measles or “1st disease”)
acute highly contagious disease characterized by fever, a generalized maculopapular rash, and a high rate of complications and/or post-infection sequelae.
characterized by: cough, coryza, conjunctivitis, Koplik spots

Question 7

measles is a ??

Answer 7

Paramyxovirus virus -
measles: an enveloped ssRNA virus with one serotype (genus: Mobillivirus)

also includes mumps, parainfluenza and respiratory syncytial viruses (RSV), human metapneumovirus (hMNV), which all cause syncytia formation (HSV, HIV)

Question 8

measle: infectious?

host??

Answer 8

one of the most communicable diseases known -aerosolized!!
-Humans and other primates are the only known hosts; there is no carrier state.
-1 in 8 children and adolescents are at risk for measles (entire pop vulnerable)
-2% further reduction in immunity will result in levels below need for herd immunity: 1/1000 will dev. acute encephalitis/BD
1/2000 will die

Question 9

measles:
age ??
seasonality ??

Answer 9

• Major cause of death in younger than 5 years old (2-3 million primarily due to diarrhea and pneumonia) where there is malnutrition and poor medical care
• winter and spring peak incidence (crowding, like chickenpox, 5th disease, UNLIKE HHV6 (6th disease), which is yr round))

Question 10

measles POE is ??
pass how??

infectious period begins when??

Answer 10

URT and perhaps conjunctivae (like VZV, 5th, 6th disease), passed by direct contact with respiratory secretions through aerosols,
direct contact, or less commonly by fomites freshly soiled with respiratory secretions.

Period of communicability begins with prodrome until about 4 or 5 days after onset of rash.

Question 11

measles: high attack rate ??

what protects newborns??

Answer 11

Primary attack rate- 99%! (beats influenza virus, about 95%) and secondary attack rate is 90%. Herd immunity must be 90 to 95%. (need almost everyone vaccinated!)
can remain infectious in air up to 2 hrs
-Maternal antibodies prevent efficacious immunization until 12 months, vaccinate after 1 yr

Question 12

is measles eliminated in the US?

Answer 12

not completely, Sporadic epidemics and microepidemics in the nonimmunized and immigrant populations have thus far prevented it elimination in the U.S. Most outbreaks have been urban areas (Houston, L.A., etc.)

Question 13

measles incubation period

virus replicates ??

Answer 13

10-14 days

n the URT and draining lymph nodes

Question 14

what happens 2 to 3 days post-exposure to measles ??

Answer 14

primary viremia

due to the virus spreading to lymphoid tissue throughout body within monocytes.

Question 15

A ?? occurs from day 5 or 6 onward (post-measles exposure)- wide dissemination to ??.
Induces ??
The infection must be controlled by ??

Answer 15

secondary, prolonged viremia
wide dissemination to GI, RES, CNS, UT (virus can be detected in urine) – this viremia results in s/s
Induces multinucleated giant cell (syncytia) formation in all infected cells.
The infection must be controlled by CMI

Question 16

measles immune (CMI) response results in ??

Answer 16

-Rash - measles virus-specific T cells target viral antigens processed with HLA class I and class II molecules in the surface of cells in the capillary endothelium and in small blood vessels.
*UNLIKE 5th, 6th diseases: due to Ab-Ag deposition
-Full-body desquamation of all epithelial surfaces (exfoliation of epithelial cells).
-Anergy lasting weeks to months following measles infection. Anergy may also
occur immediately following immunization with MMR vaccine. (may have secondary pneumonia)

Question 17

measles clinical manifestations: prodromal phase

Answer 17

0-12 days post-infection and 3-4 days before the exanthem
roughly coincides with a persisting secondary viremia indicates onset of the adaptive immune response (note the 3 Cs below).
High fever, Fatigue/malaise
Coryza, Persistent, brassy, non-productive Cough (a measles bronchitis), Conjunctivitis with photophobia
Pharyngitis, Cervical lymphadenopathy
Koplik’s spots

Question 18

Koplik’s spots

Answer 18

Fleeting (last only 1-2 days) lesions that appear on buccal mucosa and can also be present on the conjunctiva and vagina
Early lesions are mm sized bluish-gray enanthem; Late lesions are white “grains of salt” on a red base.
virtually pathognomonic for measles in a patient with other prodromal s/s

Question 19

measles clinical manifestations: eruptive phase (rash)

Answer 19

appears at about 3 days following onset of prodromal stage
-A symmetrical, non-pruritic, bright (florid) red maculopapular rash (morbilliform) appears on the face (scalp line) and descends to lower extremities.
-Rash is confluent on the head and as the rash descends it thins and becomes discrete.
-Viral antigen can be demonstrated in lesions
(rash does not go away when fever defervesces)
viral Ag and T cells in lesion, but lesions not infections

*UNLIKE 5th, 6th diseases: due to Ab-Ag deposition

Question 20

measles clinical manifestations: resolution phase

Answer 20

1-2 days later (post-eruption), as antibody titers rise, disseminated viremia halts and symptoms abate - there is rapid defervescence and the rash clears by a fine briny desquamation, first on the face and then descends (fading in the same order as it appears).

Question 21

measles complications related to CMI suppression? Epithelial compromise? Both?

Answer 21

Not known.

Question 22

measles complications

Answer 22

-OM: most common complication, due to 2o bacterial infection of inner ear (1/10 lose hearing)
-Pneumonia occurs in 2-3 % of all measles cases – primary viral Giant cell pneumonia or a secondary bacterial infection or a bacterial superinfection as a
result of desquamation of RT epithelial surfaces.
-Diarrhea (can be protracted) as a result of desquamation of GI tract epithelial surfaces (particularly if Vitamin A or protein malnourished)

Question 23

measles CNS complications

Answer 23

Primary viral encephalitis and post-measles encephalomyelitis (immune- mediate) occurs in 1 in every 1,000 to 2,000 cases of measles. It is more likely to occur in children >10-y-o-age

Question 24

measles CNS complications: SSPE

Answer 24

Subacute sclerosing panencephalitis (SSPE) occurs in 1 of every 500 cases of measles encephalitis.
It is a fatal, slowly progressive, inflammatory, demyelinating disease of the CNS which occurs primarily in children & young adults caused by defective measles virus infection in the CNS.
SSPE is very rare in US-born children, more common in developing countries

Question 25

measles complications: congenital disease

Answer 25

Maternal primary infection during pregnancy may result in virus crossing placenta, infecting fetus, causing still birth, spontaneous abortion, fetal malformation.

Question 26

measles immunity is ??

Answer 26

lifelong and both antibody and cellular immunity are important.

Question 27

measles dx

Answer 27

Clinical appearance of rash 3-4 days after typical prodromal symptoms.
Laboratory diagnosis via serology or FAT and giant cell formation in affected tissues. (syncytial cell formation)
reportable disease
consider in pts with febrile rash illness esp. with recent exposure or travel hx

Question 28

measles tx

Answer 28

• Supportive therapy is recommended. Vitamin A supplementation may speed recovery due to increased epithelial cell regeneration. (esp malnourished populations)
• IgG for immunocompromised or unvaccinated individuals w/in 6 days of exposure.
• Disease resolution confers life-long immunity?? up for debate, may need re-vaccination?

Question 29

measles ppx

Answer 29

trivalent measles, mumps, rubella live attenuated vaccine (MMR). Attenuated vaccine. (2 doses better than 1)
-First dose is recommended at 15-18 months
-second dose at 4-6 years (school-entry age) or age 11-13 years but can be administered at any time after the first dose so long as at least 4 weeks have elapsed
(US currently at less than 85% herd immunity)

Question 30

measles vaccine risks ??

given to adults??

Answer 30

Risk of vaccine-associated febrile seizures – are not associated with any long-term adverse outcomes (e.g. autism or rheumatic diseases).

In adults, one dose is recommended if not previously immunized. Two doses in the occupationally or geographically exposed.

Question 31

contraindications for MMR vaccine

Answer 31

should not be administered to the immunocompromised, pregnant, or those who may wish to become pregnant within 3 months of administration.
(like other live attenuated vaccines)

Question 32

Rubella

Answer 32

(German measles, “soft” measles, 3 day measles)

mild benign exanthematous disease characterized by minimal or absent prodromal stage, a 3 day rash (mobilliform), generalized lymph node enlargement
(Virus originally isolated by a German doc., hence name)

Question 33

rubella etiology

Answer 33

Togavirus (an enveloped ssRNA) unlike other Togaviridae, is NOT arthropod-borne. There is only one serotype

Question 34

rubella host

Answer 34

Humans are the sole hosts; there is no carrier state. (like measles)

Question 35

rubella POE

Answer 35

is URT and perhaps

conjunctivae, passed by direct contact with respiratory secretions

Question 36

rubella: age??

seasonality??

Answer 36

higher incidence in older children, adolescents and young adults.

peak incidence is in the winter and spring (like other viruses exp. HHV6)

Question 37

rubella communicability

Answer 37

Patient is communicable from 5 days before to 5 days after appearance of rash.
Not as communicable as measles or chicken pox - about 20% of pre-vaccine era persons reached adulthood without exposure.

Question 38

rubella in the US: common or rare??

Answer 38

Due to vaccination the incidence of rubella and congenital disease is now rare in US. (seropositivity due to vaccination)
Populations at risk include immigrants from developing countries and continental Europe.
on the rise due to anti-vaccine movement (MMR)

Question 39

rubella incubation period is ??

prolonged viral replication in the ??

Answer 39

14-21 days
pharynx (for up to 2 weeks) Then a viremia occurs
which results in s/s

Question 40

rubella clinical manifestations: prodrome??

Answer 40

Prodromal symptoms are minimal or absent (relatively asymptomatic) but virus replicates in the pharynx for up to 2 weeks

Question 41

rubella clinical manifestations: symptoms (if present)

Answer 41

Low-grade fever, Fatigue/malaise
Conjunctivitis, Coryza, Pharyngitis
Pronounced lymph node enlargement/lymphadenitis(postauricular, suboccipital, cervical)
Discrete pink-red (not brick red like measles) maculopapular rash lasting 3-5 days. Appears initially on face then spreads downward to involve the trunk and extremities.
Arthralgia (like Parvovirus B19)
thrombocytopenia purpura and encephalitis (more common in adults)

Question 42

rubella arthralgia

Answer 42

arthropathy, increasing incidence with age, more common in women – very similar to parvovirus B19 in this regard. Adults may manifest with only mild fever and joint involvement. Some think many “viral syndromes with fever and arthralgia” may be secondary rubella or breakthrough rubella in adults.

Question 43

rubella complications: Congenital Rubella Syndrome (CRS):

Answer 43

No risk to mother.

• Maternal viremia may result in placental infection leading to fetal viremia. first trimester is the most critical time:
• Organogenesis is disrupted by viral infection of fetal cells (50-60% risk that maternal viremia will result in fetal infection and teratogenic effects).
• Chronic and persistent infection of the infant/child is likely.
• Isolation is required for infected neonate because of prolonged (months) shedding of virus in urine and respiratory secretions.

Question 44

clinical manifestations associated with Congenital Rubella Syndrome (CRS)
prognosis?

Answer 44

Cardiac defects: *pulmonary artery stenosis, patent ductus arteriosis*
Eye defects: cataracts, glaucoma.
Hearing loss or deficit.
CNS involvement (learning and/or speech deficits).
-purpuric lesions: destruction of vasculature

15% mortality: The lower the birth weight, the greater likelihood of severe complications.

Question 45

rubella dx

Answer 45

• lab dx for newborn: (Syphilis, Toxoplasmosis, Rubella, Cytomegalovirus, Herpes virus ([S]TORCH or TORCH[S]) by measuring agent-specific IgM Ab titers in cord blood.
• Tests for immune status via latex agglutination tests in prenatal exam, not TORCH.

Question 46

clinical diagnosis of rubella is difficult because ??

Answer 46

many ECHO viruses and can mimic manifestations of rubella and are more common than rubella. (summer/fall)

Question 47

rubella tx: IgG??

Answer 47

Treatment with immunoglobulin (IgG) is NOT recommended under most conditions
Most treatments are supportive
Based on risks above, some physicians provide counsel that includes therapeutic abortion if
CRS is likely.

Question 48

rubella ppx

Answer 48

MMR vaccine (see above)
Immune globulin: Post-exposure prophylaxis does not prevent rubella infection or viremia.

Question 49

If a susceptible pregnant woman is exposed to rubella and wishes not to consider termination of the pregnancy under any circumstance, then ?? within ?? might reduce (not eliminate) the risk of CRS.

Answer 49

20 ml IgG IM
72 hours (3 days) of exposure

Question 50

Preventive measures for CRS: Vaccinate non-pregnant women; how to deal with preggos??

Answer 50

pregnant women should avoid exposure and immunization. Screen pregnant women and those who plan to become pregnant for rubella antibody. Non-pregnant women wishing to become pregnant and are seronegative or have no history of immunization should be immunized.

Question 51

Since the advent of the MMR vaccine, ?? has become the leading cause of infection and morbidity in the neonate.

Answer 51

CMV!

It is estimated that 40,000 CMV-infected neonates are born each year in the USA and 8,000 (20%) of these will have serious neurological sequelae due to congenital disease.

Question 52

NPEs: importance?
causes ??
seasonality ??

Answer 52

ne of the most common and important viral pathogens in humans, causing 5 to 15 million cases of
nonspecific febrile illness with or without rash/year in the US
with peak incidence in summer and fall months.

Question 53

NPEs are responsible for ??

Answer 53

more than 1⁄2 of all febrile illness in infants and young children during the summer and early fall months.
Major reason why blood culture and/or spinal taps are
done on infants and young children in the U.S

Question 54

NPE etiologic agents

Answer 54

ECHOvirus (enteric cytopathic human orphan virus – many [31] serotypes)
Coxsackie viruses (A and B - many [30] serotypes).
Enteroviruses 68-71

(very little cross-protection between serogroups occurs and there are many (>70) serotypes)

Question 55

NPE manifestations

Answer 55

(In children and adults)
Abrupt onset of undifferentiated febrile illness (nonspecific, constitutional s/s):
Sore throat, Vomiting and diarrhea, Malaise

Question 56

sometimes NPE febrile illness develops into the ??

Answer 56

classic common syndromes:

Fever + rash (mostly maculopapular, can be petechial, vesicular)
Pharyngitis
Conjunctivitis
Hand, foot and mouth disease (HFMD)
Herpangina
Epidemic pleurodynia.