02-17 Viruses & Exanthems

Question 1

Definition of “exanthem”

Answer 1

An exanthem is “a skin eruption that bursts forth or blooms.”

• characterized by wide-spread, symmetric, erythematous, discrete, or confluent macules and papules that initially do not form scale.
  
  • Widespread red eruptions (e.g. guttate psoriasis or pityriasis) have a similar beginning/ symmetry, but have scale and are therefore “papulosquamous eruptions”
• one of the few dzs where using “maculopapular” is appropriate
• may be caused by bacteria, viruses, or drugs

Question 2

What are the 3 basic ways that viruses can affect the skin?

Answer 2

1. Epidermal degeneration (cytolysis)
   
   • usually DNA viruses. Herpes = prototypes.
2. Epidermal proliferation (cytoproliferation)
   
   • usually DNA viruses. Warts = prototype.
3. Dermal inflammation: usually RNA viruses.
   
   • Exanthematic viral infx = prototypes.

Question 3

• What is this?
• Physical Findings
  
  • By subtype
• Causative agent?
• Pathophysiology?
• How do you dx it?
• How do you tx it?

Answer 3

• This is a WART
• Findings vary by site:
  
  1. Common (verrucae vulgaris): single or multiple, flesh-colored to whitish-gray papules with a rough, hyperkeratotic surface.
     
     • Black surface dots = thrombosed capillaries.
     • Capillary bleeding may follow shaving of the hyperkeratotic surface
     • On hands, fingers, other sites prone to trauma (knees, elbows)
     • Scratching can spread warts in line.
     • Finger nail biting may cause warts to appear about the finger nails.
       
       • JOSEPH!
  2. Plantar: often appear initially as a callus or corn-like lesion w/ painful hyperkeratotic area flush w/ surrounding skin.
     
     • nl surface skin lines are interrupted by wart
     • Punctate microhemorrhages are typical.
     • may become extensive and confluent, giving so-called “mosaic warts”.
     • Painless lesions can go untreated. Painful warts must be controlled.
  3. Filiform/digitate: hyperkeratotic, elongated, projecting papule
     
     • Often on face/neck
  4. Plane/flat: smoother, slightly elevated, keratotic papules, flesh to reddish-brown in color. Usually multiple, affecting face, dorsum of hands, elbows, knees, shins. These are difficult to eradicate.
     Genital (condylomata acuminata): moist, soft papillary projections, sometimes producing confluent cauliflower-like growths on the genital mucosa and surrounding skin
• Causative agent = HPV Strains
  
  • Common & plantar = 1, 2, 4
  • Genital = 6, 11
  • Cancer = 16, 18
• Pathophysiology
  
  • Person-to-person touch spreads virus
  • Virus replicates in nucleus, fills cytoplasm w/ virions
  • Wart is “hyperplastic response of epithelium to infx w/ virus.”
  • Immuno response of the host important:
    
    • many warts regress spontaneously
    • immunocomp’d pts develop numerous, recalcitrant warts
  • HPV can lead to carcinoma
    
    • most commonly of “cervical, vaginal, vulvar, and penile sites”
• Diagnosing Warts
  
  • Usually clinical dx
  • Biopsy would show:
    
    • marked hyperkeratosis and thick epidermis
    • Vacuolated cells in upper epiderm often show basophilic inclusion bodies.
  • Pap
  • Digene HPV Test: screens for 13 types of high–risk HPV most assoc’d w/ cervical cancer
• Treating Warts
  
  • Treatment of warts can be very difficult and frustrating as recurrences are common.
  • “Suggestion” therapy may be quite useful, especially in children.
  • Common therapeutic modalities for common and genital warts:
    
    • Liquid N2 cryotherapy
    • Electrodesiccation (may scar)
    • Chemocauterants (salicylic acid, podophyllin, trichloroacetic acid): time-consuming, requires multiple tx
    • Surgical excision
  • Podofilox 0.5% gel for genital warts
  • Imiquimod cream for genital warts.

Question 4

What do you call this pattern?

Answer 4

Mosaic pattern as seen in warts.

Question 5

Answer 5

Seborrheic keratosis

• Common benign skin growth
• Vary in shape and color
  
  • Starts flat
  • generates scale
  • scales, dry, darken, thicken, CRACK
    
    • not of uniform size as in warts
• Look like melanomas or moles
• Commonly mistaken for wart
• Not viral
• Often in geriatrics

Question 6

Dx?

Buzz words?

Answer 6

1. Hyperkeratotic surface 2. Papillomatosis 3. Mosaic surface pattern 4. Punctate micro hemorrhages

Question 7

Dx?

Buzz words?

Answer 7

Plantar Warts

1. Appear as a callus or corn

• Shaving callous w/ 15 blade reveals tips of blood vessels
• (as in this image, NOT seen w/ corn)

2. Normal surface lines interrupted
3. Punctate micro hemorrhages
4. Painful lesions must be treated
5. Patients call any wart a plantar wart

Question 8

Corn v. Plantar Wart? How can you tell?

Answer 8

Can’t be sure

Shave it, and corn comes out (As seen here)

It’s a corn!

Question 9

Dx? Where do these usually occur?

Answer 9

Digitate warts

• Look like digits (fingers)
• Occur on thin skin surfaces

Question 10

Dx?

Answer 10

Plane/Flat Warts

• Tricky to tx

Question 11

Dx?

Answer 11

Pearly Penile Papules

• NOT genital warts
• Benign/normal variant
• angiofibroma
• Do not treat

Question 12

Dx?

Answer 12

Genital warts

• They spread extensively over moist skin services
• Wart occur on the penis, anus, vulva, vaginal tract and cervix

Question 13

Dx here?

1. Natural History?
2. Pathophysiology?
3. Physical findings?
4. Lab findings?
5. DDx?
6. Tx?

Answer 13

Molluscum contagiosum

1. Natural history: a common viral infection of the skin, primarily affecting children, spread by close physical contact. In adolescents and adults, it is frequently transmitted venereally. Patients with atopic dermatitis or who are at particular risk of more extensive infection. HIV patients may have a florid infection.
2. Pathophysiology: caused by molluscum contagiosum virus, a pox virus. This is a DNA virus which replicates within the cytoplasm of the infected epidermal cell. Infected cells continue to divide, and the typical epidermal response to infection is one of hyperplasia.
3. Physical findings
   
   • Discrete pink to flesh-colored, dome-shaped papules with a central whitish umbilicated area. Usually about 2-5 mm, but can be quite large.
   • White, cheesy material can sometimes be expressed from the center of the lesions.
   • Lesions are typically multiple.
4. Lab findings:hyperplastic epidermis, with infected cells showing intracytoplasmic dense inclusion bodies displacing the nucleus to one side.
5. DDx
   
   • Warts
   • Pyogenic granuloma
6. Treatment
   
   1. Liquid nitrogen
   2. Curettage
   3. Imiquimod
   4. No tx just wait for spont. resolution

• Image here: Molluscum contagiosum w/ spont onset of inflam
  
  • Looks like recurrent herpes simplex
• Lesions may be obscured by pubic hair
• Genital lesions in kids: r/o sexual abuse =(

Question 14

Approach to pt w/ suspected viral exanthem?

Answer 14

1. Do the clinical features suggest a specific disorder?
2. What is prevalent in the community?
3. Can a drug reaction be excluded as a cause?

Question 15

Dx here?

1. Natural History?
2. Pathophysiology?
3. Physical findings?
4. Lab findings?
5. DDx?
6. Tx?

Answer 15

“Fifth disease” - Erythema Infectiosum

1. Epidemics in 5-14 year olds
   
   • Fetal infection can be deadly
2. Caused by Parvovirus B19
3. Physical Findings
   
   • Polyarthropathy syndrome
   • Women - itching, arthralgias, arthritis
   • Mimics rheumatoid arthritis in acute state
   • Lasts weeks or months
     4.

Question 16

Dx here?

1. Natural History?
2. Pathophysiology?
3. Physical findings?
4. DDx

Answer 16

Hand, Foot and Mouth Disease

1. Natural Hx
   
   • The disease occurs in sporadically and in epidemics.
2. Pathophys
   
   • A distinctive exanthem caused by several strains of the Coxsackie virus group.
     
     • Coxsackievirus A16 and enterovirus 71
3. Physical findings
   
   • Fever and cough
   • Vesicle in mouth and on palms and soles.
   • Cutaneous lesions
     
     • Dorsal aspect of hands, sides of fingers, palmar surfaces, feet, buttocks
   • Elliptical lesion begins as a 2-10 mm erythematous macule on which a central, gray, oval vesicle develops.
   • Oral lesions -2-3 mm, painful, ulcers on a red base
4. DDX
   
   • Pemphigoid
   • apthous stomatosis
   • 1° Herpes simplex

Question 17

Which herpeviridae species causes Kaposi’s sarcoma?

Answer 17

Herpes Virus 8

Question 18

Herpes Infection

• Viral Life Cycle
• Natural History
  
  • Primary Infection
  • Reoccurence
• Evolution of lesions during 1° infx and recurrence
• HSV 1 vs HSV 2
• Dx
• DDx
  
  • 1°?
  • 2°?
• Tx

Answer 18

• Viral life cycle
  
  • Enters via skin/mucosa
  • Settles in sensory nerve roots
  • HSV then can travel back along the nerves to cause
    
    • asymptomatic shedding
    • recurrence
• Natural History
  
  • Prior HSV-1 infx ameliorates symptoms of later HSV-2 infx.
  • In developed countries, rates of childhood HSV-1 are declining → more severe 1° HSV-2 infx in adults.
  • Most transmission occurs duringasymptomatic shedding.
  • 80-90% of pts w/ symptomatic 1st HSV-2 genital infection will recur within 1 yr an avg of 4 times/yr
    
    • vs. 50-60% w/ HSV-1 who recur 1x/yr
• Evolution of Lesions (same for 1° or 2°)
• NOTE: Majority of pt’s have _asymptomatic_ 1° infection
  
  1. Vesicles →
  2. Umbilicated pustules →
  3. Crusts →
  4. Black crusts
• HSV 1 vs HSV 2
  
  • HSV 1 causes mostly orolabial (cold sores, fever blisters)
    
    • AND 40% of 1° genital herpes (mouth-to-genital spread)
  • HSV 2 causes most genital herpes
    
    • >95% of recurrent genital herpes
    • oral infection rare
• Dx
  
  • PCR for HSV 1 and 2
    
    • More accurate if done w/in first few days of eruption
  • Biopsy: rarely needed
    
    • shows multiloculated vesicles in epidermis, w/ acantholysis, multinucleated giant cells.
• DDx
  
  • a. Primary infection
    
    • (1) Hand, foot, and mouth disease (Coxsackie A16 virus)
    • (2) Aphthous stomatitis
    • (3) Erythema multiform
  • b. Recurrent infection
    
    • (1) Impetigo
    • (2) Herpes zoster
• Tx: We can’t eliminate the virus from neurons
  
  • a. Uncomplicated recurrent disease in a normal host: Keep lesion clean, dry; OTC salves/lip balm.
    
    • Penciclovir (Denavir) cream for recurrent orolabial herpes.
  • b. Severe 1° disease, dz in immunocompromised: Consider PO (or IV) acyclovir, famciclovir or valacyclovir.
  • c. Disseminated disease: intravenous acyclovir or foscarnet for acyclovir resistant infections.
  • d. Neonatal infection: intravenous acyclovir
  • e. Eye infections: Trifluridine
  • f. Suppression of frequent recurrent disease: oral acyclovir, famciclovir or valacyclovir for up
    to a 6-month course. Longer courses are frequently prescribed and are safe.
  • g. No therapy currently available has been shown to prevent establishment of latent infection.

Question 19

What are some things that trigger HSV recurrence?

Answer 19

Several factors trigger reactivation of HSV, such as:

• sunlight
• skin trauma
• cold or heat
• stress
• concurrent infection
• and menstruation.

Question 20

“Herpetic whitlow”?

Answer 20

Herpes involving the peri-nail (or “paronychial”) area

Question 21

Neonatal herpes?

Answer 21

• occurs when delivered through infected birth canal.
• Untreated → disseminated or CNS infx in >70%, w/ 65% mortality
• In most cases of neonatal HSV infx, mother has no hx of genital dz.
• Women w/ h/o recurrent lesions transmit dz to their newborns at a much lower rate than those with 1°, asx infx acquired at term.
• Severe neonatal HSV infection is most likely to occur when the mother acquires primary infection at term.

Question 22

Herpes Zosters

1. Natural Hx
2. Pathophysiology
3. Physical Findings
   
   • Chicken Pox
   • Shingles
4. Lab Findings
5. DDx
6. Tx

Answer 22

1. Natural history
   
   • a. Varicella (chicken pox) is the highly contagious primary infection with an 85% incidence by age 9-10 years.
   • b. Herpes zoster increases in incidence with age.
2. Pathophysiology
   
   • a. Only one type of virus identified.
   • b. 1° exposure → chicken pox.
   • Transmission = airborne from upper resp secretions or from dried crust → entry → viremia ensues → widespread cutaneous infx
   • c. Virions migrate w/in axons of involved cutaneous sensory nerves to their ganglia, where latency is established similar to herpes simplex virus.
   • d. Subsequent ganglionic reactivation results in a necrotizing ganglionitis and cutaneous re- infection, usually limited to a single dermatome. Changes in cell-mediated immunity appear to be important in clinical reactivation, although decreasing levels of anti-varicella-zoster virus antibodies occur with advancing age. Reactivation is common in immunosuppressed patients such as transplant recipients and AIDS victims.
3. Physical findings
   
   • a. Chicken pox
     
     • (1) 10-20 days incubation w/ prodrome → eruption
       
       • first as pink macules and papules → vesicular
       • 3-4 mm vesicle with an erythematous halo. Vesicles become turbid, then dry into crusts. Crusts separate in 5-20 days.
       • Lesions occur in successive crops.
       • occur on all cutaneous surfaces and mucosae, including conjunctiva, larynx, and urinary bladder. Lesions in different stages in same area.
     • (2) Disease is usually relatively benign, and complications are rare, especially in children. Adults have more severe disease which may be complicated by a pneumonitis.
   • b. Zoster (shingles)
     
     • (1) Cutaneous often preceded by 1-7 days of pain +/- hyperesthesia.
     • (2) Then: grouped umbilicated vesicles on erythematous base in aunilateral dermatomal pattern
       
       • may become hemorrhagic and subsequently pustular
       • Crusting and healing typically occur in 2-3 weeks.
     • (3) A persistent neuralgia, which may be incapacitating, occurs in some, esp those >50 y/o.
     • (4) disseminated zoster may occur, esp in immunocomp pts
4. Laboratory findings
   
   • Viral culture Biopsy is similar to herpes simplex.
5. Differential diagnosis
   
   • a. Herpes simplex
   • b. Impetigo
6. Treatment
   
   • a. Chicken pox requires symptomatic (calamine, oatmeal baths, PO antihistamines).
     
     • Keep lesions clean/dry to avoid 2° infx
   • b. Immunodef pts exposed to varicella should be treated w/ zoster Ig
     
     • Acyclovir (oral or intravenous) may also be used in severe infections especially in postpubertal agents.
   • c. Zoster, lesions should be kept clean and dry.
     
     • Compresses may help dry oozing lesions. Systemic steroids may help severe neuralgia and may abort post-herpetic neuralgia in the elderly.
     • Acyclovir (PO or IV), valacyclovir, or famciclovir if begun w/in 24hrs decr severity
       
       • can also treat localized, ophthalmic or disseminated zoster.
   • d. Varicella vaccine: all children at 12-18 months of age
     
     • h/o chickenpox is considered adequate evidence of immunity.
     • blood test is available to test immunity in persons who are uncertain of their hx or who have not had chickenpox.
   • e. Zostavax. vaccine to reduce the risk of shingles in people > 50 y/o age
     
     • reduces the occurrence of shingles ~50-65%

Question 23

Dx?

Answer 23

1° HSV-1 Infx

Question 24

Dx?

Answer 24

2° HSV-1 Infx

this one may be secondarily infected w/ bacteria

Question 25

Dx?

Answer 25

HSV infection

• tricky to dx when not on genitals/peri-oral area
• This shot is HSV 2° to wrestlers transmiting HSV via saliva
  
  • hot.

Question 26

Dx?

Answer 26

Herpes Simplex + Atopic Dermatitis = Eczema herpeticum

Question 27

DDx of genital ulcer?

Answer 27

• Herpes simplex (painful)
• Syphilis (painless)
• Chancroid (painful, rare here)
• Scabies
• Candidiasis
• Trauma

Question 28

Dx? (painful)

Answer 28

1° HSV-2 infx

• here in this image: so deep it will likely scar

Question 29

Dx? (painful, on vulva)

Answer 29

1° HSV-2 Infection

Question 30

Dx?

Answer 30

Herpes zoster (shingles)

• Tricky in this image: seen in multiple dermatomes