Exam #8: Viral infections of the skin, soft tissue, bone, muscle, & joints I & II Flashcards
How viruses get into the skin?
1) Direct infection via disrupted skin or mucosa
2) Other tissues e.g. spread from the lung
Once the virus is in the skin, what are the two possible outcomes?
1) Replication in the skin & infective skin lesions
2) Immune response to virus–>lesion without infectivity
Define papilloma.
Benign growth on the surface of the skin or mucous membrane
Define macule.
Small discolored patch of skin that forms an area distinct from the normal surrounding surface
Define papule.
A small, circumscribed, raised portion of the skin
Define vesicle.
Small pouch on the surface of the skin filled with clear liquid; blister
Define pustule.
Small circumscribed, raised portion of the skin filled with purulent material
What are the shared features of warts?
- Hyperkeratotic
- Painless
- Koilocytes
- Lump, papilloma, nodule
- Caused by HPV
What is the same of the common wart? Where is it most commonly found?
Verruca valgaris
- Hands
What is the technical name for warts on the soles of the feet?
Verruca plantaris
What are flat warts called?
Verruca plana
*Note that these most commonly occur on the face, hands, and neck of children
What are the black dots in warts?
Punctate hemorrhages
List the characteristics of HPV.
Papoviridae
Small
Nonenveloped
dsDNA genome
How is the replication of HPV closely tied to the differentiation status of the tissue it infects?
- The layers of the skin are listed below from superficial to deep:
1) Suprabasal
2) Basal
3) Basement membrane
4) Dermis - Infection occurs in the basal layer
- E6 & E7 promote proliferation by inactivating p53 & Rb
- The infected epithelial cell differentiates and moves toward the surface of the skin, where late genes are expressed & virions are assembled
*Thus, production of NEW PHV virions occurs in the most superficial layer, the suprabasal layer
Review the roles of HPV E7 & E6.
HPV E7= Inhibits Rb
HPV E6= Inhibits p53
How are the 100 different serotypes of HPV classified? Specifically, how are the cutaneous warts classified?
Common= HPV 2, 3, 10 Plantar= HPV 1 & 4
How is HPV transmitted?
Direct contact with wart or contaminated surface (non-slip shower/pool)
How long is the incubation period for warts?
4 months
How are warts diagnosed?
1) Clinical appearance
2) Hyperkeratosis
3) Koilodal cells
*Note that PCR can be used to distinguish between high and low-risk HPV
Describe the apperance of a Koilodal cell.
Large nucleus
How are common and plantar warts treated?
1) Cryotherapy
2) Cytotoxic chemicals
3) Surgical removal
*Note that common and plantar warts usually spontaneously regress after a few months- 2 years
How are warts prevented?
Flip-flops for plantar warts
Will the HPV vaccine help with common and plantar warts?
NO–different serotypes
What is Molluscum Contagiosum? What are the manifestations?
- Painless lesion
- “Pearly umbilicated nodules in the epidermis”
- Purulent material can sometimes be expressed from the lesions
Young children= anywhere
Adult= genital
List the characteristics of the virus that causes Molluscum Contagiosum.
Poxviridae family
Large dsDNA genome
Replicates in cytoplasm
What are molluscum bodies?
Large eosinophilic cytoplasmic inclusions
*Note that these are present in the purulent material that is expressed from these lesions
How is What is Molluscum Contagiosum transmitted?
Direct contact with lesions
Fomites
How is What is Molluscum Contagiosum treated?
- Surgery
- Cryotherapy
*Will spontaneously resolve in 2-12 months
What is Herpes Labialis?
Cold Sores
What causes Herpes labialis?
Reactivation of HSV infection
How do primary HSV infections compare to Herpes labialis?
Primary= worse= primary herpetic gingivostomatitis
Aside from Herpes labialis, what else can HSV cause?
1) Herpes Simplex Keratitis (leading cause of infectious blindness in the US)
2) Herpes Simplex Encephalitis (most common cause of infectious encephalitis in the US)
3) Herpetic Whitlow
4) Neonate HSV infection
List the characteristics of HSV.
Herpesviridae family
Enveloped
dsDNA genome
Latent & lytic cycles
What are the two different serotypes of HSV?
HSV-1 & HSV-2
Which serotype of HSV typically causes oral lesions?
HSV-1 = oral HSV-2= genital
*Remember 1 mouth, 2 testicles
How are HSV oral lesions transmitted?
1) Direct contact with lesions
2) Saliva
Describe the mechanism of action of Acyclovir.
Acyclovir= nucleotide analog that must be phosphorylated by VIRAL ENZYMES to be activated
1) Activated by viral thymidine kinase enzyme
2) Acyclovir monophosphate–>Acyclovir triphosphate
3) Acyclovir triphosphate= active form that inhibits viral DNA polymerase & can incorporate into viral DNA to cause chain termination
*Note that Foscarnet is the second line treatment for HSV. it does NOT require the action of thymidine kinase & is associated with higher toxicity.
What is the technical name for chickenpox?
Varicella
What virus causes Varicella?
Varicella Zoster Virus (VZV)
What are the symptoms of Varicella?
- Mixture of evolutionary lesions that are most prevalent on trunk, face, and scalp
- Fever lasts ~5 days & preceeds lesions by ~2 days
Describe the evolution of lesions in chicken pox.
Vesicles–>pustules–>scabs
*Lesions are often found in multiple evolutionary stages in a single area of the body, called “crops of lesions”
Where do lesions in chicken pox most often appear? Where do they NOT appear?
Prevalent on: trunk, face, scalp
*NOT observed on the palms or soles
What are the complications of varicella?
1) Bacterial infection of lesions
2) Pneumonia
3) Neonatal complications
4) Shingles (Herpes Zoster)
What causes the neonatal complications of VZV?
Maternal infection during the first 20 weeks of gestation
What are the neonatal complications of VZV?
Low birth weight Skin scarring Encephalitis Chorioretinits Microcephaly
In what patient population is Shingles most commonly seen?
Elderly
Immunosuppressed
What are the symptoms of shingles?
- Paresthesia prodrome
- Vesicular lesions on trunk (dermatomal pattern)
- Fever & malaise
- Postherpetic neuralgia
What pattern does Shingles follow?
Dermatomal pattern
List the characteristics of VZV.
Herpesviridae
Enveloped
dsDNA
How is VZV transmitted?
Respiratory secretions
Saliva
Contact with lesions
How is VZV diagnosed?
- Chickenpox and Shingles are diagnosed clinically
- Tzanck smear
- Serological testing: ELISA & Latex Agglutination
How is VZV prevented?
Varicella Vaccine, which has been approved for use in the US in persons 12 & older
What is the VZV vaccine?
- Live attenuated VZV virus that is given with mumps, measles, and rubella vaccines
- MMRV
What is the Zoster Vaccine?
Same live attenuated strain as varicella vaccine
- Higher varicella titer
*Recommended for all adults that are 60 & older
What is given to individuals at risk for VZV complications?
Passive immunization with VZV antibodies
What is used to treat VZV?
Acyclovir
*Note that this is not as effective as with HSV
What are the symptoms of smallpox?
- Abrupt onset fever
- Malaise
- Headache
- Muscle pain
- Nausea
- Lesions
Describe the lesions associated with smallpox.
- Mouth (enanthem)
- Skin (exanthem)
Usually on the face & extremities (centrifugal distribution)
Common on palms of hands and soles of feet
Synchronous evolution
What virus causes smallpox? List the characteristics of the virus.
Variola virus:
Poxviridae
dsDNA
Replicates in cytoplasm
Strictly human
How is smallpox transmitted?
- Contact with virus in lesions
- Fomite transmission
- Air in enclosed spaces
How long are individuals considered contagious with smallpox?
Until all scabs have separated from lesions (21-28 days)
What complications are associated with smallpox?
- Bacterial infection of skin lesions
- Arthritis
- Respiratory tract infections
- Encephalitis
*Note that there is a higher mortality rate with hemorrhagic & flat forms of smallpox
What is the vaccine for smallpox?
- Live strain of vaccinia virus, which is another virus in the poxvirus family but NOT variola virus
- Cross-protection mechanism
What is eczema vaccinatum?
Complication of smallpox vaccination
Compare and contrast smallpox and chickenpox.
Smallpox=
- centrifugal (face & extremities)
- palms & soles
- synchronous lesion evolution
Chickenpox=
- centripetal (trunk & face)
- rarely on palms and soles
- asynchronous lesion evolution
What is the postexposure protocol for smallpox?
- Prophylaxis with vaccine within 3 days of exposure
* Note that a vaccine within 4-7 days of exposure will provide partial protection or lessening degree of disease
List the classic childhood exanthems.
1) Measles (Rubeola)
2) Scarlet fever
3) German Measles
4) Atypical Scarlet Fever
5) Erythema Infectiosum
6) Roseola
What are the symptoms of the measles?
- Prodrome for 2-4 days, then
- Maculopapular rash that begins in the hairline and spreads downward for 5-6 days
What are the 3 C’s of the measles prodrome?
Cough
Coryza
Conjunctivitis
*Coryza= catarrhal inflammation of the mucous membrane in the nose, caused especially by a cold or by hay fever.
What causes Measles?
“Measles Virus”
Paramyxovirus
ssRNA
Enveloped
What are the important parts of the Measles virus envelope?
- F gene that is important for fusion
- HA protein that is important for attachment
How is Measles transmitted?
- Respiratory
- Highly contagious–90% secondary attack rate
*Note that an infected individual is contagious from prodrome to 3-4 days following onset of rash
Why is the Measles so infective?
Infectious for up to 2x hours in the air
What are Koplik spots?
- Small white spots with red border opposite of the molars
- Pathognomonic for Measles
How is measles diagnosed?
- Clinical diagnosis
- Confirmed w/ lab
What are the complications of Measles?
Complications occur in ~30% of cases:
- Diarrhea
- Otitis Media
- Pneumonia (due directly to Measles in adults & bacterial superinfection in children)
- Encephalitis
- Seizures
- Death
How is Measles prevented?
*Vaccination
- Infected patients should limit contact with susceptible individuals
- Passive immunoprophylaxis for exposed contacts
*Note that Measles is a reportable disease
Who is resistant to Measles?
1) Documented receipt of 2x doses of Measles vaccine
2) Lab evidence of immunity (titer)
3) Documentation of physician diagnosed Measles
4) Birth before 1957
Describe the Measles vaccine.
- Live attenuated virus
- Prepped in chicken embryo fibroblasts
- MMR or MMRV
What are the vaccination recommendations for Measles?
Children:
- 1st dose @ 12-15 months & 2nd @ 4-6 years
Adults
- One dose for those born after 1957
- 2nd dose for international travelers, post high-school students, & healthcare workers
How is a Measles outbreak defined?
Three or more cases linked in time or place
What are the symptoms of German Measles? How is this different from Measles?
- Maculopapular rash that appears on the face and spreads downward
- Fainter than measles
- Less severe prodrome
- Arthralgia and arthritis
What causes German Measles?
Rubella virus
What is Congenital Rubella Syndrome?
Mother gets Rubella during 1st trimester
- Deafness
- Cataracts
- Congenital glaucoma
- Pigmentary retinopathy
- Congenital heart disease
List the characteristics of Rubella virus.
Togaviridae
Eveloped
+ssRNA
How is Rubella transmitted?
Respiratory route
How is Rubella diagnosed?
- Direct culture of virus from patient samples
- RTPCR
- Serology
Describe the Rubella vaccine.
Live attenuated vaccine
MMRV
- Vaccinating one generation to prevent disease in another
What is 5th Disease/ Erythema Infectiosum ?
“Slap Cheek”
- Fever
- Rash beginning on cheeks & spreads to the rest of the body
What causes 5th disease?
B19 virus
- Parvoviridae
- ssDNA
- grows exclusively in mitotically active cells i.e. hematopoietic cells in bone marrow
Aside from 5th disease, what are the disease manifestations caused by B19 virus?
- Aplastic crisis
- Arthralgia & Arthritis
- Pregnancy complications
What is Roseola Infantum?
- High fever that lasts 4 day
- Maculopapular rash follows fever resolution
- Rash lasts 24-48 hours & then resolves spontaneously
What causes Roseola?
HHV-6 & HHV-7
- Herpesviridae
- dsDNA
- Enveloped
- Replicates in T, B, or oral pharyneal cells
- Latent infection in T-cells
How does HHV-7 differ from HHV-6?
Present more predominantly in CD4+ T cells; later infection
