Herpes Flashcards
What is herpes?
dsDNA virus with eight virus; 3 subfamilies: alpha, beta, gamma
What is the alpha herpes family?
HSV-1, HSV-2 and VZV
What is the beta herpes family?
CMV, roseola
What is the gamma herpes family?
EBV and Kaposi’s sarcoma
What are the layers of herpes?
episomal DNA genome, capsid, tegument, envelope
What is the capsid?
surrounds the center of the virus, encases dsDNA genome, connection between viral capsid and host envelope allows herpes virus to enter host’s cytoplasm
Where does viral replication take place?
in the host cell’s inner nuclear membrane of the nucleus
What is the tegument?
dense protein layer surrounding the capsid, creates link between capsid and the host cell’s lipid bilayer envelope
What enzyme is used in herpes replication?
virus uses host’s DNA polymerase (the DNA populating mechanism) and reverse transcriptase to transcribe and produce viral proteins
What is the leading cause of infectious corneal blindness in developed countries?
HSV-1; 1.5 million cases a year globally (40,000 cause severe monocular VA loss)
How is herpes simplex categorized?
by viral strand (1 or 2) and infection (primary or recurrent)
What is HSV-2?
genital herpes, mostly associated with sexual transmission or neonatal infection; can involve any mucosal membrane
How is primary HSV-1 transmitted?
mucosal membranes, saliva, tears; highly contagious
What is the incidence of primary HSV-1?
60% of population by age 5 and 100% by age 60
Where are most primary HSV-1 signs located?
oropharynx>ocular
Who gets primary HSV-1?
school-aged children>neonates and a severe presentation in neonates and immunocompromised
What symptoms are there for primary HSV-1?
symptoms are rare; 94% asymptomatic; flu like malaise, low-grade fever, concurrent upper respiratory infection
What are clinical signs of primary HSV-1?
pre-auricular node swelling unilaterally, vesicular rash (eyelids and adnexa), follicular conjunctivitis, corneal punctate lesions rare but can coalesce into epithelial dendrite, labial vesicular eruptions aka cold sores, gingivostomatitis
Where is the herpes virus present in the oropharynx?
stratified squamous epithelium of oral mucosa
T/F dendritic ulceration for primary HSV-1 is limited to the epithelium and cannot involve the stroma
true
What is the transmission of primary HSV-1?
primary HSV 1 transmission to active infection to latency in trigeminal and dorsal root ganglion to reactivation and recurrent HSV-1
What is latency?
via retrograde transport, infected epithelial cells –> trigeminal and dorsal root ganglia, inactive
What is reactivation?
via anterograde transport, trigeminal and dorsal root ganglion –> epidermis, reactivated
Can recurrent HSV-1 become latent?
yes, establishes latency after active infection and can become reactivated
What are triggers for HSV recurrence (old theory)?
stress, UV light, menstruation, illness, surgery/iatrogenic, toxic
How is recurrent HSV-1 transmitted?
mucosal membranes, saliva, tears
What is the predilection for recurrent HSV-1?
male, no correlation to race or age
Who has the most severe recurrent HSV-1 presentation?
children and immunocompromised
Is recurrent HSV-1 unilateral or bilateral?
unilateral»_space;> bilateral
What are symptoms of recurrent HSV-1 (HSK)?
pain/ocular discomfort, photophobia, watering, itching, FBS, decreased vision/blurry vision, corneal desensitization
What are signs of recurrent HSV-1 (HSK)?
pre-auricular node swelling, vesicular rash, follicular conjunctivitis, dense coalesced punctate keratitis, dendritic keratitis (72% occurrence), adnexal vesicles
T/F any insult to the cornea can cause lid edema?
true
What are types of HSK?
epithelial, stromal, necrotizing
What is epithelial HSK?
dendritic, geographic, neurotrophic, marginal
What is stromal HSK?
disciform, immune
What is necrotizing HSK?
aka interstitial endotheliitis
Describe neurotrophic keratitis
rapid progression, creates false sense of improvement/asymptomatic, round/oval shaped, smooth borders, stain completely with fluorescein
What is marginal/limbal epithelial HSK?
immune response to viral cells, (+) limbal neo, (-) stain
What is disciform keratitis?
12% of HSK pts will develop stromal involvement, epithelium is intact, arises from endothelial involvement (immune response to endo compromise); not necrotizing
What is stromal keratitis?
immune response (delayed hypersensitivity) to herpetic virus antigens, epi intact
What is interstitial keratitis?
from herpes or other conditions, if not managed properly can thin permanently leading to corneal perforation
Describe necrotizing endotheliitis
endothelial edema in response to virus itself, usually in absence of epithelial disease, endotheliitis can induce endothelial cell damage or loss, permanent swelling, scarring, opacification, and irregular stigmatism, commonly requires corneal transplant
What leads to hypoesthesia
recurrent HSK and stromal involvement typically with neurotrophic ulcer
How can you check hypoesthesia?
cotton swab test on normal eye first
Describe the assessment of corneal nerve regeneration of HSK-stromal vs normal
HSK eyes had significantly lower mean corneal sensation, central total nerve density, and overall total nerve density; true at initial visit and 3 year f/u
What is true of regenerated corneal nerves?
structurally disorganized, not fully functional, not responsive to stimuli
When does herpetic uveitis occur?
with SK, IK, or endotheliitis in stomal and endothelial disease
What is herpetic uveitis?
can be anterior, intermediate, posterior or pan; A/C reaction, granulomatous > non KPs, elevated IOP, iris atrophy, PS, hypopyon, secondary angle closure due to trabeculitis
How many HSK patients develop iris/uveal complications?
9%
What is herpetic scleritis?
more likely seen with active corneal disease; won’t see a quiet cornea with scleritis in the absence of herpes
What is acute retinal necrosis?
rare! severe, bilateral, rapid progression of herpetic retinitis in neonates, immunocompromised, or concurrent HIV/AIDs infection
What is treatment of ARN?
order blood work, systemic antivirals and immediate referral to retina
What is optic neuritis?
ONH edema secondary to viral infection; indistinct ONH borders, hyperemic, may have surrounding hemes, typically presents with retinal necrosis
What is the pathway of VZV?
primary infection –> latency in trigeminal ganglion –> reactivation along branches of trigeminal nerve –> dermatome pattern of outbreak
What is the dermatome pattern of outbreak for VZV?
trigeminal to ophthalmic to nasociliary, frontal and lacrimal
What are the 3 stages of reactivated VZV?
prodrome (pre-eruptive), active virus outbreak (acute eruptive), and post-herpetic neuralgia (chronic)
What are s/s of VZV prodrome?
HA, fever, malaise, pain, blurred vision, moodiness, depression, insomnia
What are s/s of reactivated VZV outbreak aka shingles?
vesicular rash following trigeminal dermatome (respects midline), erythematous rash, pain, hutchinson’s sign, ocular complications
What is hutchinson’s sign?
vesicular eruptions on tip of nose which signals nasociliary nerve involvement and higher risk of ocular involvement
What is herpes zoster ophthalmicus?
10-20% of all shingles patients, reactivation of VZV along the ophthalmic branch of the trigeminal nerve
What is HZO linked to?
weakening T cell immunity of elderly and immunocompromised patients
What is more likely to have severe ocular complications: HSK dendritic keratitis or herpes zoster ophthalmicus?
HZO
What is corneal involvement of HZO?
corneal pseudodendrite; elevated mucosal plaque with painted on tapered lines, not a true epi ulcer (less vibrant with fluorescein), no terminal endbulbs
What are other HZO corneal complications?
SPK, disciform stomal keratitis, immune stromal keratitis, IK, neurotrophic ulcer
What is true of HZO retinitis/choroiditis?
slightly increased predilection to involve the choroid than HSV
T/F HZO causes papillitis from spread of ARN or progressive RN
true
What are ischemic complications of VZV?
increased risk of CVA after recurrent VAV; potential visual awareness issues, mobility decline, personality fluctuations, mental/functional degradation
What is orbital apex syndrome?
paralysis of CN 2, 3, 4, 6, and ophthalmic branch of 5; optic nerve atrophy, permanent visual loss even with restoration of EOM movement and reduction of orbital inflammation with systemic steroids
What is Ramsey-Hunt sydrome?
reactivation of VZV in geniculate ganglion, triad of ipsilateral facial paralysis, ear pain, and vesicles in the auditory canal and auricle + loss of taste sensation over anterior 2/3 tongue
What is post-herpetic neuralgia?
develops if recurrent VZV is unmanaged in 72 hours; severely painful, can last months to years post active infection, #1 cause of suicide in patient with chronic pain >70 years
How is VZV transmitted?
direct contact with rash, blister fluids; contagious until vesicles crust over
How is VZV prevented?
varicella vaccine (chicken pox est 1995) and Shingrix (est 2017) with 90% effectivity for 50-70 year olds– 2 doses separated by 2-6 months
What is cytomegalovirus?
common virus from herpes 5, dormant in healthy people and no symptoms but ocular signs in immunocompromised
When do people get ocular signs of CMV?
high viral load and CD4 less than 50 or following organ transplant, lymphoma, etc)
What are signs of CMV?
bilateral ARN with more hemorrhages and less vitritis, ON edema, RD
What is treatment of CMV?
IV antivirals, intravitreal antiviral injection, ganciclovir retinal implant, systemic treatment for etiology
What is roseola?
Herpes 6 or 7, contagious; very common in children 6 months to 2 years old
What are signs of roseola?
fever ~103, painless rash, eyelid edema
What is the treatment of roseola?
fever reduction, fluids, no vaccine
What is Epstein-barr virus?
Herpes 4, very common and highly contagious, infection can cause monocucleosis in teenagers and young adults
What are symptoms of EBV?
symptoms 2-4 weeks, fatigue for months, swollen lymph nodes, fever, enlarged spleen, swollen liver rash, or asymptomatic
What is treatment of EBV?
fluids, rest, fever reduction
What are signs of EBV?
oculoglandular syndrome, conjunctivitis, dry eye, keratitis, SEIs, uveitis, choroiditis, retinitis, papillitis, ophthalmoplegia
What is treatment of ocular signs of EBV?
oral acyclovir, IV antiviral, intravitral injections or surgery
What is Kaposi sarcoma?
painless tumors/masses in skin, lymph nodes and other internal organs from Herpes 8, often in immunocompromised patients
What can symbolize high risk of mortality due to an underlying systemic condition?
Kaposi sarcoma
How is Kaposi sarcoma diagnosed?
biopsy
What is treatment of Kaposi sarcoma?
surgical excision, cryotherapy, radiation, chemo and systemic care ex: antiretrovirals for AIDs
When might you use amniotic membrane therapy AMT?
with stromal involvement, necrotizing, or neurotrohpic disease and in tandem with topical corticosteroid and oral antiviral treatment
What is the new push for AMT?
use prior to concluding patient is surgical candidate because AMT is easy, safe, effective compared to PKP, stromal healing occurs after 2 weeks of AMT, and no recurrence per studies
What is penetrating keratoplasy?
full thickness transplant; remove entirety of host’s cornea and replace with health graft cornea, indicated for severe stomal scarring/limited visual prognosis/corneal perforation
T/F patient must continue prophylactic oral antiviral for at least 1 year and topical corticosteroid for graft acceptance
true, steroid slowly tapered over 6-12 months then continued as limited but lifetime
Topical treatments of herpes
trifluridine 9x day for 10 days or ganciclovir gel 5x day for 10 days
What are oral herpes treatments?
famciclovir (250 or 500 3x), acyclovir (400 or 800 5x), or valacyclovir (500 or 1000 3x)
What is the herpes treatment for facial lesions?
erythromycin ung or bacitracin ung PRN
What was HEDS I?
no benefit to simultaneous dosing of topical and oral antiviral; topical prednisone is beneficial for SK
What was HEDS II?
confirmed no benefit to simultaneous dosing topical and oral, oral antiviral will not prevent progression of HSK epithelial to SK, prophylactic oral antiviral (acyclovir 400 mg bid) dosed months to 1 year is beneficial in preventing recurrence of all herpetic infection subtypes, supports longer taper >10 weeks of topical prednisone in treating SK
