Unit 3 Flashcards
(133 cards)
1
Q
What is the genetic composition of the herpes viruses?
A
dsDNA
2
Q
What are the cells targeted for primary infection/latency by HSV1 and HSV2?
A
Sensory neural ganglia
3
Q
What are the cells targeted for primary infection/latency by varicella zoster virus?
A
Sensory neural ganglia
4
Q
What are the cells targeted for primary infection/latency by cytomegalovirus?
A
Monocytes, lymphocytes, and possibly others
5
Q
How is HSV transmitted?
A
Close contact with a person who is shedding active virus at a mucosal surface, or in genital/oral secretions
6
Q
What is the incubation period of HSV?
A
2-12 days (average is 4 days)
7
Q
What is the incubation period of VZV?
A
10-21 days after exposure
8
Q
What is the incubation period of cytomegalovirus?
A
2 weeks to 2 months
9
Q
Describe the virion structure of herpesviruses
A
Innermost: A dsDNA genome that is protected by an icosahedral capsid.
Next layer: tegument, composed of fully-formed and active proteins
Outermost: envelope derived from host membrane + glycoproteins important for binding
10
Q
Explain latency and reactivation
A
Latency: silent infection during which no virus particles are produced
Reactivation: (in sensory neuron infections) virus particles travel down the axon and reestablish an infection on skin or mucus membrane in area supplied by nerve
11
Q
What are some clinical manifestations of HSV infection?
A
Gingivostomatitis –> most common symptomatic infection)
Herpetic whitlow –> on fingers
Encephalitis –> HSV most common cause; predilection for temporal lobes
Herpes keratitis –> inflammation of the cornea; fluorescein staining reveals distinctive dendritic pattern
Genital herpes –> lesions last 10-14 days, very painful
12
Q
What are the 3 forms of neonatal HSV?
A
(1) Skin, eye, and mucous membrane disease (SEM)
Commonly seen at sites of trauma (forceps site). Eye lesions can lead to corneal ulcers & blindness
(2) CNS
Encephalitis, usually severe. Mortality with acyclovir 5%
(3) Disseminated
Pneumonitis, hepatitis, DIC +/- encephalitis, skin rash, eye involvement. Mortality with acyclovir 30%
13
Q
Are reactivated lesions in HSV infectious?
A
YES. People often continue to shed virus for a period of time after the lesions are healed!
Reactivation may be silent, but the person is still infectious & the virus can still be transmitted. Up to 70% of new genital HSV infections are transmitted via asymptomatic reactivation and shedding
14
Q
How do you diagnose HSV definitively?
A
- viral culture of lesions
- direct immunofluorescence of lesions
- PCR of lesions
15
Q
What is the treatment for HSV?
A
Acyclovir
C-section for pregnant women with active lesions at time of delivery
Severe infections: IV acyclovir
16
Q
How is VZV transmitted?
A
Primarily respiratory, via droplet or aerosole secretions (coughing, sneezing)
Or contact with lesions
17
Q
Describe the primary infection of varicella/chicken pox
A
Disease starts with fever, headache, malaise, +/- cough, and results in telltale rash
18
Q
Describe the rash of varicella
A
Generalized, itchy, vesicular rash. First on face/trunk, spreads to limbs. Appears in successive waves.
Lesions in multiple stages (blisters/pustules/scabs), vs. smallpox where the lesions are all at one stage
19
Q
What is the pathogenesis of varicella?
A
Entry via the respiratory tract and spread to regional lymphoid system
Viral replication in lymph nodes followed by a primary viremia
Virus replicates in the liver, spleen, and sensory ganglia
Secondary viremia to skin, causing the rash
20
Q
What are the complications of varicella?
A
Secondary infection of the lesions (Group A Strep), pneumonia, necrotizing fasciitis, encephalitis, hepatitis, congenital varicella
21
Q
What is the prophylaxis for varicella?
A
Live attenuated varicella vaccine:
2 dose series, given SQ (12-15 mos and 4-6 yrs)
May cause disease in pregnant and immunocompromised individuals
22
Q
What does reactivation of VZV result in?
A
SHINGLES :( aka herpes zoster
Lesions develop in a single dermatome that do not cross the midline
Very painful; heal in about 2 weeks
23
Q
What are some of the complications of herpes zoster?
A
Post-herpetic neuralgia!
Nerve palsies, encephalitis, secondary skin infections
24
Q
What is the vaccine for shingles? Whom is it given to?
A
Zostavax, for use in persons 50+ years of age to prevent shingles
Live attenuated vaccine (contraindicated in those with immune deficiencies & pregnant)
Reduces risk for developing shingles by 50%; reduces risk of PHN
25
What happens if a woman gets varicella during pregnancy?
Very bad. Can lead to varicella pneumonia and death.
Can also get congenital varicella syndrome. Occurs when a pregnant woman gets VZV in first 8-20 weeks of pregnancy. Fetus can exhibit multiple tissue and organ abnormalities, such as microcephaly, mental retardation, hypoplasia of extremities, microphthalmia, and hypopigmentation.
26
Describe the primary infection of cytomegalovirus
For most healthy people, no symptoms and no long-term consequences.
In immunocompromised patients, serious --> can infect most organs. CMV retinitis and colitis in HIV patients
27
How is CMV transmitted?
Infected body fluids - saliva, breast milk sexual contact, blood, tears, contact with urine, blood transfusions, organ transplantations, in utero
28
What is the pathogenesis of CMV?
Affects the epithelial cells of the salivary gland or the genital tract, resulting in persistent infection and intermittent viral shedding
29
What happens if a mother has a primary CMV infection during pregnancy?
3-5% chance the child with be born with congenital CMV infection
Leads to low birth weight, microcephaly, hearing loss, mental impairment, skin rash ("blueberry muffin spots"), jaundice, etc.
30
How is serology useful for testing for CMV?
Negative IgM, negative IgG = patient has never been infected with CMV
Positive IgM, negative IgG = acute CMV disease
Negative IgM, positive IgG = patient has previously been infected with CMV
at some time in their life
Positive IgM, positive IgG = recent CMV REACTIVATION
31
What does CMV look like on histology?
Cells with CMV have characteristic "owl's eye" appearance, with dark spot --> intranuclear inclusion
32
How is CMV treated?
In normal people, no need (asymptomatic)
In immunocompromised people, Ganciclovir (anti-viral). CMV-IG, an immunoglobulin preparation with high titer of CMV antibodies, together with Ganciclovir are sometimes used to treat CMV pneumonia.
33
What is Ehlers-Danlos Syndrome?
Genetic mutation leading to erroneous COLLAGEN production. Leads to hyperextensible skin, joints, fragile blood vessels, & poor wound healing.
34
Absence of what is strongly associated with Ehlers-Danlos Syndrome?
Inferior labial (100% sensitivity, 99.4% specificity) and lingual (71.4% sens, 100% spec) frenulum
35
What is a method of identifying the age of a person on a slide under the microscope?
Solar elastosis - sun damages elastin fibers in the skin over time. Has bluish-gray appearance.
36
What is a congenital problem of elastin fiber production?
Pseudoxanthoma elastin (PXE)
37
What happens in PXE?
Calcium deposits on the elastin fibers, causing them to become brittle.
Dx associated with "plucked chicken" skin, systemic HTN, and arterial ruptures in the eyes.
38
What are the components of ground substance?
(1) hyaluronic acid
(2) dermatan sulphate
"Glued" together with (3) fibronectin
39
What are two important types of nerve fibers in the skin?
Type A - myelinated, fast conductance
Carry sensations of proprioception, touch, pain, & muscle sensations.
Type C - unmyelinated, slow conductance
Carry sensations of itch, dull, non-localizing, temperature
40
What are two specialized skin receptors?
Meissner's corpuscles: "pine cone like"; located near DEJ; involved in fine touch, in greatest amounts on fingers
Pacinian's corpuscles: "onion like"; in dermis, involved in vibration and pressure, in greatest amount in genitals
41
What are the different glandular structures in the dermis?
Apocrine glands: sweat gland in armpits/groin; empties into hair follicles. Secrete thicker fluid; create BO smell :). Also in eyelids, ears, and breasts.
Eccrine glands: sweat glands over most of body
Apoeccrine glands: hybrid, located mostly in axilla. Secrete nearly 10x as much sweat as eccrine glands. Lots of fluid (like eccrine) but thicker (like apocrine). Lovely.
42
What type of hair is on the ears?
Vellus hair (thin, fine, apigmented)
43
What are the stages of hair growth?
Hairs randomly engaged in 1 of 3 stages:
(1) Anagen (growth): 85%
(2) Telogen (rest): 10-15%
(3) Catagen (involution): 1-5%
```
Anagen = 3 years
Telogen = 3 months
Catagen = 3 weeks (or less)
```
44
What is another name for male pattern baldness? What causes it?
Androgenic hair loss
Conversion of testosterone to DHT
45
What do holocrine glands secrete?
The whole cell
46
What neurotransmitter causes the causes of sweat from eccrine glands?
Acetylcholine
47
What is miliaria?
Skin disease marked by small and itchy rashes.
"Heat rash". Caused by blocked sweat ducts.
48
What is a genetic cause of abnormal eccrine glands?
Anhidrotic Ectodermal Dysplasia
Genetically abnormal eccrine glands - can't sweat. Also have funky teeth, sparse hair, & (obvi) poor temperature regulation.
49
When does a majority of atopic dermatitis start?
Before age 5
50
What is atopic diathesis?
Atopic dermatitis, asthma, and allergic rhinitis
| Genetic predisposition to develop 1+ of the above
51
What are the diagnostic criteria for atopic dermatitis?
Itchy skin AND 3+ of the following:
(1) Involvement of skin creases
(2) Asthma or hay fever
(3) Dry skin in the last year
(4) Visible flexural eczema
(5) Onset under 2 years of age
52
What is the mutation associated with atopic dermatitis?
Filaggrin
53
What is the bacteria associated with atopic dermatitis?
Staph. aureus (acts as a superantigen)
54
What is lichenification?
Areas of thickened areas of skin w/ greater creases; sign of chronic dx
55
Where is atopic dermatitis located?
Areas of flexural skin
Antecubital fossa, popliteal fossa, neck, wrists, ankles
56
What is keratosis pilaris?
Bumpy skin around the hair follicles
57
Is contact dermatitis immunologically mediated?
NO.
Non-immunologically mediated; caused by direct cytotoxic effect from contact with irritant.
58
What is intertrigo?
Irritant contact dermatitis in the folds of the skin, where they rub against one another
59
What is allergic contact dermatitis?
IMMUNE MEDIATED
Type IV hypersensitivity
60
What is the typical time span of a drug rash?
Usually occurs 7-14 days after starting a new medication
Starts sooner in cases of receiving an "old" medication
Eruption will resolve spontaneously in 1-2 weeks. However, it can take up to 3 months to resolve completely.
61
In what contexts does stasis dermatitis occur?
In cases of venous insufficiency
Varicose veins, chronic LE edema, venous stasis ulcers
Can be BILATERAL
62
Lichen simplex chronicus
Thickened plaques ("lichenification") that result from chronic itching
Topic steroids are 1st line therapy. Antihistamines can be used for itching.
63
Venous stasis ulcers. Where do they occur? After what? What do they look like?
Occur primarily just above ankle on medial leg. Occur after leg swelling, varicose veins, or in patients with a history of blood clots. Appear erythematous, with a yellow base. Irregular borders. Can be purulent if infected.
64
Nummular dermatitis. Also called what? Where does it appear? What does it look like? In whom does it appear?
Also called discoid eczema. Appears mostly on legs, but also on arms/trunk. Looks like round pink circles with irregular borders. More common in men 50+
65
What is cradle cap sebbhoreic dermatitis?
Flaky, white/yellow oily scales on scalp. Can become confluent & a thick scale on the scalp. Begins 1 week after birth and may persist for several months.
66
What is sebbhoreic dermatitis characterized by? Where does it usually occur?
Flaky, greasy scales.
Occurs symmetrically on the face. Occurs in areas rich in sebaceous glands.
67
What is the pathogenesis of seborrheic dermatitis?
Caused by a combination of overproduction in sebaceous glands and the yeast organism Malassezia furfur
68
What is sebbhoreic dermatitis linked to?
Neurological disorders, like Parkinson's, head injury, and stroke
Annnd HIV :(
69
Guttate psoriasis is associated with what?
Strep throat
70
What other diseases is psoriasis associated with?
Arthritis!
(5-20% of pts)
Metabolic syndrome, CVD, and MI
71
```
What are the locations of the following skin diseases?
Stasis dermatitis
Sebbhoreic dermatitis
Psoriasis
Atopic dermatitis
```
Stasis dermatitis - lower legs
Sebbhoreic dermatitis - scalp
Psoriasis - extensor surfaces (knees, elbows)
Atopic dermatitis - flexor surfaces (popliteal fossa, antecubital fossa)
72
```
What are the etiologies of the following diseases?
Stasis dermatitis
Sebbhoreic dermatitis
Atopic dermatitis
Irritant derm
Contact derm
```
```
Stasis derm - lower extremity edema
Sebbhoreic dermatitis - Malassezia furfur
Atopic derm - Filaggrin
Irritant derm - common irritants
Allergic contact derm - common allergens
```
73
What are the genetic transformations in BCC?
The majority of BCCs have a loss of function of PTCH1
PTCH1 normally blocks SMO (smoothened). Both are transmembrane proteins. If SMO is unchecked --> signals tumor growth --> cancer!
74
What is the chemotherapy for BCC?
Vismodegib (inhibitor of SMO)
75
What is actinic keratosis?
Pre-cancer
| Most common type of pre-cancer. Approx 65% of SCCs and 36% of BCCs started as AKs.
76
What is SCC in situ?
SCC only in the epidermis
77
What is a keratoacanthoma?
A subtype of SCC.
| Rapid growth over 6-8 weeks. 1-3 cm papule/nodule. Has crater in the middle like a volcano!
78
When is metastasis of SCC more common?
When it's on the lip
79
What are the risk factors for skin cancer?
Age, skin type, UV radiation
Genetic factors
HPV
Level of immunosuppression: CD4 count, meds, transplant (heart > kidney > liver)
80
What type of skin cancer are transplant pts more likely to get? Non-transplant?
```
Transplant = SCC:BCC 4:1
Non-transplant = BCC:SCC 4:1
```
Transplant = you're SCrewed
81
ABCDE for melanoma?
```
Asymmetry
Border irregularity
Color changes
Diameter >6mm
Evolution
```
82
What is the Breslow Depth for skin cancer?
Tumor invasion in mm
83
What are Clarks Levels for skin cancer?
```
I. Epidermis
II. Papillary dermis
III. Mid dermis
IV. Reticular dermis
V. Subcutaneous fat
```
84
What is the most frequent mutation in melanoma?
BRAF
BRAF acts on MEK --> --> --> acts on genes affecting growth & proliferation
85
What is the chemotherapy used to treat melanoma?
Vermurafenib
86
What is Kaposi's sarcoma?
Endothelial malignancy triggered by HHV-8. Slowly progressive.
87
What are the types of Kaposi's sarcoma?
Classic - occurs primarily in elder men of Eastern European descent
Lymphadenopathic - aggressive form primarily in equatorial Africa. Affects young men and is rapidly fatal.
AIDS-associated - incidence is declining with better ARTs
88
What do infantile hemangiomas stain with?
Glut-1, a placental antigen
89
What is one complication of a port wine stain?
Sturge Weber Syndrome
10-15% of port wine stains in V1 distribution are associated with ocular and neurologic abnormalities, including glaucoma, seizures, and developmental delay
90
What is nevus sebaceus?
A hamartoma that most commonly presents as a papillomatous yellow-orange linear plaque on the face or scalp
On the scalp, associated with alopecia
Somatic mutations in HRAS and KRAS
Epithelial neoplasms occur in 10-30%
91
What is the term for nuclear shrinking?
Pyknosis
92
What is the term for cell fusion?
Syncytia
93
Influenza - basic structure?
Genome is 8 pieces of ssRNA
94
Influenza - important proteins?
The hemagglutinin (H) and neuraminidase (N) glycoproteins. Both are surface proteins. Names of viruses are based on the numbers of each on the viral coat.
95
Influenza - what does it look like in neonates/children/adults?
Neonates - lethary, decreased eating, mottling, apnea
Children - GI symptoms, fever, anorexia, respiratory symptoms
Adults - we know
96
Describe the antigenic drift of influenza that is a result of reassortment of genome segments
Because influenza has a segmented genome, gene segments can be “swapped” between strains.
Pigs can be infected by pig, bird, & human strains of influenza - simultaneous infection might allow for reassortment of genes.
Pigs = "mixing vessel"
97
What is the fomite contamination of influenza?
Steel & plastic - 24-48 hours
Cloth, paper, & tissue - 8-12 hours
Hands - 5 min
98
What are the two types of influenza vaccine?
(1) Inactivated influenza vaccine - injectable, killed virus. All people 6 mos+. Trivalent or quadrivalent.
(2) Live attenuated influenza vaccine - intranasal. For people 2 yrs - 49 years. Quadrivalent.
99
What is H5N1?
A highly virulent strain circulating in bird populations in Asia, with mortality up to 40%. Currently cannot infect humans effectively; however could mutate the hemagglutinin alpha 2,3 linkage into an alpha 2,6 linkage, leading to human susceptibility.
100
RSV - basic structure?
ssRNA, non-segmented
2 subtypes, A & B
A causes more severe disease
101
RSV - important proteins?
F protein: causes fusion of viral envelope to host cell. Fusion of membranes of infected cells to each other to cause “syncytia”
G protein: Initial binding of virus to the host cell
102
RSV - pathophys?
Invades conjunctiva & nasopharynx; 3-5 day incubation period.
Results in collection of fluid in alveoli & bronchioles. Causes constriction of SM in bronchioles --> respiratory symptoms (hypoxia, hyperexpansion by mucus plugging, wheeze, etc.)
103
RSV - whom does it affect?
90% of children have had it by 2 years of age
| can be asymptomatic to severe
104
Is there a vaccine for RSV?
Nope. They tried in the 1960s and made the infections considerably worse. Serum antibody without local respiratory antibody may worsen the disease.
105
What is Respigam?
Human pooled Ab with high RSV titer --> decrease in dx severity & hospitalization
Once-monthly IM injection for high risk groups. Expensive :(
106
Ebola - basic structure?
Filo virus
7 structural proteins and 2 non-structural proteins
(-) sense RNA
107
Ebola - important proteins?
Glycoprotein spikes on envelope - key for pathogenicity
Matrix proteins VP40 and VP24 - virus structure, assembly, budding, etc.
Nucleocapsid & nucleoproteins
Polymerase complex: VP35 & L. Function is replication.
108
Ebola - pathophys?
Enters body through mucosal surfaces or cuts; travels to lymph nodes.
End result: CYTOKINE STORM. T cell depletion, hemorrhage/fluid imbalance, hepatic dysfunction (preventing shutting off of cytokine storm), DIC.
Die from hypovolemia +/- end-organ failure.
109
What enables ebola virus to evade the immune system?
Glycoprotein on the surface
Masks sites on virus that our Ab bind to
Can mutate to evade
Shields/blocks proteins on the surface of host cells from recognized as infected by immune cells
Secreted GP (sGP) acts as a "decoy" and tricks our immune system - Ab secreted against it are non-neutralizing for virus
110
What are the drugs that are inhibitors of viral neuraminidase (for the influenza virus)?
Oseltamivir (Tamiflu), Zanamivir (Relenza), and Peramivir (Rapivab)
111
What is the mechanism of action of oseltamivir, zanamivir, and peramivir?
Block the activity of the viral enzyme neuraminidase. The enzyme cleaves sialic acid from the cell's plasma membrane, allowing for interaction between viral hemagglutinin and cell sialic acid. Without the enzyme activity, viral particles cannot translocate within & bud out of the cell.
112
What are the pharmacokinetics of oseltamivir, zanamivir, and peramivir?
Oseltamivir: ORALLY as prodrug. Renal elim.
Zanamivir: INHALED bid x 5 days. Renal.
Peramivir: Single IV dose
113
When are influenza drugs used during the course of influenza?
If started within 48 hours, can reduce duration of symptoms by 1-2 days.
Can be used prophylactically in contacts of sick person.
114
What are some of the adverse reactions of oseltamivir, zanamivir, and peramivir?
Oseltamivir: minor, occasional nausea and vomiting (reduced by taking with food)
Zanamivir: bronchospasm reported uncommonly in patients with asthma or COPD
Peramivir: diarrhea and GI effects; neutropenia has occurred; rarely serious skin reactions
115
What is the mechanism of amantadine (Symmetrel) and rimantadine (Flumadine)?
They block the virally-encoded H+ ion channel (M2 protein) that's necessary for membrane fusion & viral content release when it's in the endosome (uncoating)
116
What are the pharmacokinetics of amantadine and rimantadine?
Effective orally - accumulate in the lungs
Amantadine - excreted in urine
Rimantadine - hepatic elimination
117
What are the clinical uses of amantadine and rimantadine?
Prophylaxis and treatment of influenza A infections
118
What are some of the adverse reactions of amantadine and rimantadine?
Amantadine - may cause dizziness, lightheadedness, difficulty concentrating
Rimantadine - better tolerated because of poorer CNS penetration
119
What are the mechanisms of antiherpes drugs (acyclovir, valacyclovir, penciclovir, famciclovir)?
Broadly: they inhibit the viral DNA polymerase.
When they enter the nucleus, get initially phosphorylated by a VIRAL enzyme (usually thymidine kinase). Then, cell enzymes convert the monophosphate to a triphosphate form.
Drug-TP competes with cell dGTP for the viral DNA polymerase & gets incorporated into the replicated DNA strand --> terminates further replication and elongation, AND binds & inactivates viral DNA polymerase.
120
What are the pharmacokinetics of the antiherpes drugs?
Acyclovir: poor oral absorption; available as topical & IV
Valacyclovir: prodrug of acyclovir --> oral availability good
Penciclovir: topical only
Famciclovir: prodrug of penciclovir --> oral availability good
Neonatal acyclovir clearance is only 1/3 of adults.
121
What does Docosanol (Abreva) do?
Prevents fusion between cellular & viral envelope --> blocks viral entry into cell
Topical treatment 5x daily to lips begun within 12 hours reduces healing time about one day in HSV.
122
What is the most common form of resistance to antiherpes drugs?
Reduction or loss of expression of viral thymidine kinase
123
What is the drug for RSV?
Ribavirin
Oral: Copegus®, Rebetol®
Aerosolized: Virazole
124
What is the mechanism of action of ribavirin?
Ribavirin-TP inhibits GTP-dependent 5' capping of viral mRNA
125
What are the pharmacokinetics of ribavirin?
Oral absorption is good; increases with fatty foods
Elimination is via hepatic metabolism and renal excretion of unchanged drug
126
What are the adverse reactions of ribavirin?
Inhalation: generally well tolerated
Oral-systemic: high incidence of hemolytic anemia!!
TERATOGENIC. Should not be administered during pregnancy. Pregnant health care workers should not care for pts using aerosolized ribavirin.
127
What is Palivizumab?
Humanized mAb to RSV F glycoprotein that is indicated for RSV immunoprophylaxis in infants and young children with congenital heart disaese
128
What is the mechanism of action of gancyclovir and valgancyclovir?
Cell uptake, initial phosphorylation by viral enzyme (main mechanism of selectivity). Gancyclovir-TP gets incorporated by viral DNA polymerase --> stops elongation.
129
What are the clinical uses of gancyclovir?
Treatment & chronic suppression of CMV retinitis in immunocompromised patients. Also good at controlling CMV in transplant patients.
130
What is the major adverse reaction with gancyclovir?
Myelosuppression with neutropenia and thrombocytopenia
131
What is the mechanism of action of foscarnet?
DOES NOT REQUIRE CELL ACTIVATION
Binds to pyrophosphate binding site of DNA/RNA polymerases --> blocks viral replication.
132
What are the clinical uses of foscarnet?
Effective against CMV retinitis, particularly in immunocompromised patients
Also effective against ganciclovir-resistant CMV infections and acyclovir-resistant HSV and VZV
infections
133
What are the adverse reactions of foscarnet?
Major side effect is nephrotoxicity and hypocalcemia, can be quite severe or even fatal
CNS abnormalities also have been reported
