Viral Diseases Affecting the Oral Cavity Flashcards
1
Q
Vaccine preventable diseases include:
A
- Diphtheria
- Haemophilus influenzae type b (Hib)
- Hepatitis A
- Hepatitis B
- Influenza
- Measles
- Meningococcal
- Mumps
- Pertussis (whooping cough)
- Pneucoccal disease
- Polio
- Rotavirus (severe diarrhea)
- Rubella (German measles)
- Tetanus (lockjaw)
- Varicella (chickenpox)
Note: MMRV = measles, mumps, rubella, varicella
2
Q
Neurotropic (affects nervous system preferentially) herpes viruses
A
- HSV-1
- HSV-2
- VZV
3
Q
Lymphotropic herpes viruses
A
- EBV
- CMV
- HHV-8
4
Q
Causes primary infection that are asymptomatic or symptomatic
A
Herpes viruses
5
Q
Remain latent in specific cell types for host’s life
A
Herpes viruses
6
Q
Can undergo reactivation after latent period to cause recurrent infections that are asymptomatic or non-symptomatic.
A
Herpes viruses
7
Q
How are herpes viruses spread?
A
Viruses shed in secretions –> spread to new hosts
8
Q
Initial contact of HSV-1 in lower s-eco groups early in life results in…
A
primary herpetic gingivostomatitis
9
Q
Initial contact of HSV-1 in wealthier individuals occur later. Disease that results is…
A
pharyngotonsillitis
10
Q
Most primary HSV-1 infections in previously seronegative individuals are from contact with infected person…
A
- Infected saliva
* Active lesions
11
Q
Three possible consequences of initial HSV-1 contact with oral tissues of seronegative individuals…
A
- Minority of children develop primary herpetic gingivostomatitis
- A few young adults develop pharyngotonsillitis
a. Repeated autoinoculation of eyes may –> blindness - Most individuals: effects are subclinical
12
Q
Where does HSV-1 migrate to remain latent or dormant?
A
Trigeminal nerve ganglion
13
Q
Cause of viral reactivation (HSV-1)
A
May be due to reduced local or systemic host resistance:
• Results in 2nd disease, which usually subsides without treatment and is often recurrent.
14
Q
Clinical features of primary herpetic gingivostomatitis
A
• Abrupt onset
• Malaise, fever, nausea
• Cervical lymphadenopathy
• Vesicles throughout mouth and vermilion; rupture rapidly
- Numerous pinhead vesicles –> ulcers (fibrin-covered)
• Lesions extend onto vermilion and perioral skin
• Severe edematous, enlarged, very erythematous painful gingivitis
- Punched out erosions along midfacial free gingival margins
15
Q
How long does primary herpetic gingivostomatitis last?
A
lasts 5-14 days
16
Q
How long is the incubation period of primary herpetic gingivostomatitis?
A
3 to 9 days
17
Q
Demography of primary herpetic gingivostomatitis
A
- Initial exposure in absence of antibodies (usually children)
- Most cases 6 months to 5 years of age
- Maternal antibodies before 6 months.
18
Q
What is herpetic pharyngotonsillitis?
A
- Primary infection in adults
- Sore throat, fever, malaise, headache
- Tonsils and posterior pharynx: vescles –> ulcers
19
Q
Viral cytopathy of HHV-1, HSV-1, and herpes simplex vius…
A
• Ballooning degeneration
- enlarged, vacuolated nucleus and cytoplasm
• Acantholysis –> Tzanck cells
- free-floating epithelial cells in intraepithelial vesicle
• Cowdry inclusions – uniform glassy appearance
- Surrounded by nuclear clear zone (halo)
• Chromatin condensed around nuclear margin
• Epithelial cells fuse –> multinucleated
20
Q
Distinct clinical presentation:
• Vesicles throughout mouth and vermilion; rupture rapidly
• Numerous pinhead vesicles –> ulcers (fibrin-covered)
• Lesions extend onto vermilion and perioral skin
A
primary herpetic gingivostomatitis
21
Q
How is the gingiva affected in primary herpetic gingivostomatitis?
A
- Severe edematous, erythematous gingivitis
- Gingiva enlarged, painful, and very erythematous
- Punched out erosion along midfacial free gingival margins
22
Q
What happens in recurrent (reactivation) / secondary HSV-1 infection?
A
- Latent virus in ganglia
- Reactivation follows exposure to: sunlight, cold, trauma, stress, immunosuppression, UV light
** Note: only UV light definitely induces lesions
23
Q
Where do symptomatic lesions in secondary (recurrent) HSV-1 infection occur?
A
Symptomatic lesions at site of primary inoculation or adjacent areas of epithelium supplied by involved ganglion
24
Q
What percentage of the population has antibdies to HSV? What percentage may develop 2nd herpes?
A
• Up to 90% of population has antibodies to HSV
- Up to 40% of this group may develop 2nd herpes
25
Shedding occurs in what percentage of secondary (recurrent) HSV-1 infection?
Shedding in 2-10%
26
Describe how secondary (recurrent) HSV-1 infection can spread?
* Virus may spread to other sensory ganglia
| * Both asymptomatic shedding and symptomatic active lesions can spread to uninfected hosts
27
Locations involved in secondary (recurrent) HSV-1 infection
* Herpes labialis: "cold sores", "fever blisters"
| * Intraoral: keratinized mucosa
28
Relation of erythema multiforme and secondary (recurrent) HSV-1 infection
> 15% of erythema multiforme cases proceeded by 2nd HSV
29
Most common site for recurrent HSV-1 infection...
Vermilion and adjacent skin of lips (herpes labialis)
30
Percent of US population affected by herpes labialis?
15-45% of US population
31
Clinical features of herpes labialis
• Prodrome 6-24 hours before lesions
- Burning, tingling, itching, erythema
• Multiple small red papules
• Clustered fluid-filled vesicles
32
What presents as clustered fluid filled vesicles, which rupture & crust in 2 days?
Herpes labialis
33
Resolution of herpes labialis
* Clustered fluid-filled vesicles
* Rupture & crust in 2 days
* Healing 7 to 10 days
34
What is recurrent intraoral HSV infection?
Secondary HSV-1 infection within oral cavity; less common than herpes labialis
35
Location of recurrent intraoral HSV-1 infection
In otherwise healthy people, clustered vesicles on keratinized mucosa (mucoperiosteum)
• Hard palate and attached gingiva
36
What is herpetic whitlow (herpetic paronychia)?
• Primary or secondary HSV infection localized to hands or fingers
37
How is herpetic whitlow (herpetic paronychia) acquired?
Acquired by direct contact with active lesion:
• Dentists, etc.
• Self-inoculation in children with orofacial herpes
38
Clinical features of herpetic whitlow...
* Seronegative: Infection --> vesiculoulcerative eruption with signs and symptoms of primary systemic disease
* Pain (often throbbing) and redness
* Vesicles or pustules break to form ulcers
* High fever
* Regional lymphadenopathy
39
Can people who are seropositive (HSV history) contract herpetic whitlow?
Seropositive (HSV history): whitlow less likely
40
Resolution of herpetic paronychia (whitlow)
* Lasts 4-6 weeks
| * May --> paresthesia and permanent scarring
41
Where can herpetic paronychia (whitlow) recur?
May recur on fingers
42
Clinical presentation of herpes simplex virus infection in IMMUNOCOMPROMISED hosts
* Oral lesions at any site usually with herpes labialis
| * Enlarging lesion has central necrosis with raised yellow border (zone of active viral destruction)
43
Diagnosis of oral herpes simplex virus infection
* Often made clinically
| * Lab tests
44
What lab tests are done to diagnose oral herpes simplex virus infection?
* Cytologic smear or tissue biopsy of active lesion
* Serology in primary HSV
* Culture
45
Results of culture lab test in the diagnosis of oral herpes simplex virus infection
* Requires intact vesicle, rare intraorally
| * Up to 2 weeks for definitive result
46
Results of serology lab test in the diagnosis of oral simplex virus infection
Serology in primary HSV:
| • Igs positive in 4-8 days
47
Results of cytologic smear in the diagnosis of oral simplex virus infection
Cytologic smear or tissue biopsy of active lesion:
• Viral cytopathy
• Fluorescent monoclonal antibody to rule out HZV
48
How do you rule out HZV in lab tests done to diagnose oral herpes simplex infection?
In cytologic smear or tissue biopsy of active lesion, do fluorescent monoclonal antibody to rule out HZV.
49
Treatment for healthy patients with oral herpes simplex virus infection
• Mild cases don't require treatment
• Symptomatic treatment:
- NSAIDs
- Topical dyclonine hydrochloride spray
- SPF 15 sunscreen for herpes labialis
• Early antiviral agents
50
Treatment for immunocompromised patients with oral herpes simplex virus infection
Oral and IV antiviral agents
51
Primary ____ infection in children is varicella
HHV-3
52
HSV-1 causes...
* Primary herpes gingivostomatitis
| * Secondary herpes infections
53
HSV-2 causes...
Genital herpes
54
Varicella-zoster causes...
* Varicella (chickenpox)
| * Zoster (shingles_
55
Epstein-Barr causes...
* Mononucleosis
* Burkitt's lymphoma
* Nasopharngeal carcinoma
* Hairy leukoplakia
56
Cytomegalovirus causes...
Salivary gland inclusion disease
57
HHV-6 causes...
Roseola infantum
58
HHV-8 causes...
Kaposi's sarcoma
59
Papillomaviruses causes...
* Oral papillomas/warts
* Condyloma acuminatum
* Focal epithelial hyperplasia
* Some carcinomas
60
Coxsackieviruses causes...
* Herpangina
| * Hand-foot-mouth disease
61
Path of virus during varicella active disease...
* The virus follows along sensory nerve to sensory ganglia
| * Resides there in latent form
62
Recurrent HZV infection is called...
Zoster/Shingles
63
How is varicella spread?
Spread by air droplets or direct contact with active lesions
64
Demography of varicella
Most cases ages 5 to 9
65
Incubation period of varicella
Incubation 10-21 days
66
Clinical features of of varicella
```
• Start: malaise, pharyngitis, rhinitis
• Then rash:
- Intensely pruritic exanthem
- Starts on face and trunk
- Then extremities
```
67
Describe the rash in Varicella
* Pruritic rash: red macules --> vesicles --> pustules --> crusting
* Successive crops (so see all stages at any one time)
68
Duration of varicella
* New lesions appear for 4-7 days
* Lasts several weeks
* Self-limiting
69
"Dewdrop on rose petal" is classic in this...
Varicella
70
Occurrence of oral lesions in varicella?
* Oral and perioral lesions may precede skin
* Vermilion, hard palate, etc.
* Usually few oral lesions (2 or 3 ulcers) that heal in 3 days
* Many lesions in severe cases
71
What do oral lesions in varicella resemble?
• Occasionally gingival lesions resemble primary HSV, but less pain
72
Diagnosis of varicella involves: history of exposure within past __ weeks
history of exposure within past 3 weeks
73
Viral cytopathy for varicella reveals...
Viral cytopathy in Tzanck cells (same as HSV)
74
Rapid diagnosis of varicella involves...
Rapid diagnosis by fluorescent-conjugated monoclonal antibodies on smear or biopsy (separates HZV from HSV)
75
Serum samples in acute stage of varicella shows....
Should show 4x increase in antibody titers to VZV
76
Tissue culture diagnosis of varicella...
Viral isolation in tissue culture
77
Management of varicella...
HZV vaccination (Varivax):
• Most children in USA are vaccinated
• But efficacy diminishes over time
78
Management of varicella in immunosuppressed children
• Peroral antiviral meds in immunosuppression
- Acyclovir, valacyclovir, famciclovir
- Reduce duration and severity
• Purified V-Z immune globulin
79
Varicella complications in childhood...
* 2nd skin infections
* Encephalitis
* Reye's syndrome
80
Varicella complications in adults...
* Varicella pneumonitis
* Encephalitis
* Potentially fatal
81
Varicella complications in immune-compromised...
* Extensive cutaneous involvement
* High fever
* Hepatitis
* Pneumonitis
* ~ 7% mortality before there was effective antiviral treatment
82
10-20% of pregnant women who get VZV get...
pneumonia
83
Women who get varicella in early pregnancy...
* Small chance (0.4-2.0%) baby could be born with "congenital varicella syndrome"
* Low birthweight, scarring of skin, and problems with arms, legs, brain, and eyes
84
Women with varicella rash from 5 days before to 2 days after delivery...
* Babies at risk for chickenpox shortly after birth
| * Chance of death <30%
85
Herpes zoster is...
reactivated HHV-3
86
How many episodes occur in herpes zoster (reactivated HHV-3)?
• Recurrent HZV but usually only ONE episode
87
In what percentage of people does reactivated HHV-3 occur?
10-20% of people
88
Predisposing factors for herpes zoster (reactivated HHV-3)
* Immunosuppression
* Maliganancies
* Dental treatment
89
Herpes zoster goes through stages. What is it called, and what are the stages?
"Immunosenescence"
• Prodrome
• Acute phase
• Chronic phase
90
What is zoster sine herpete?
Zoster without rash
91
What happens in the prodrome phase of herpes zoster?
* Initial viral replication in sensory trigeminal ganglion
| * Ganglionitis --> neuronal necrosis & severe neuralgia
92
Path of pain in herpes zoster (prodrome phase)?
Pain in area of epithelium innervated by the affected sensory nerve
93
Timing of onset of pain in herpes zoster (prodrome)...
Pain 1-4 days before mucosal or skin lesions
94
Clinical symptoms of herpes zoster in prodrome phase
* Sensitive teeth, etc.
| * Fever, malaise, headache
95
UNILATERAL lesions in epithelium innervated by affected sensory nerve occurs in...
Herpes zoster - acute phase
96
Occurrence of rash in herpes zoster acute phase...
* Erythematous macular-papular rash --> clusters of vesicles
* Vesicles --> pustular and ulcerate in 3-4 days --> crusting in 7-10 days
* On keratinized or non-keratinized mucosa or skin
97
Oral lesions occur in herpes zoster acute phase with...
Oral lesions occur with trigeminal nerve involvement
98
Ocular (V1) involvement in herpes zoster acute phase results in....
blindness
99
Describe osteonecrosis in the acute phase of herpes zoster
Osteonecrosis with loss of devitalized teeth:
• Inflammation in nerves extends to adjacent vessels that supply alveolar ridges and teeth
• Vessel damage --> necrosis
100
Describe the chronic phase of herpes zoster
* Postherpetic neuralgia: pain+++ for one to mainy months after rash
* Burning sensation with episodic "stabbing" pain
* "Tactile allodynia": even light touch causes pain
* Due to chronic VZV ganglionitis
101
Management of herpes zoster
* Live attenuated HZV vaccine for all people over 60 years olf
* Early use of antiviral meds
* PHN
102
Discuss the vaccine for herpes zoster..
* Live attenuated HZV vaccine for all > 60 years
| * 14x more powerful than childhood vaccine
103
Discuss the early use of antiviral meds for the management of herpes zoster.
* Accelerate healing of skin lesions
| * Acyclovir, valacyclovir, famciclovir
104
Discuss PHN in the management of herpes zoster
• Many methods (topical and systemic)
• Topical capsaicin (red pepper origin)
- takes 2 weeks
- too irritating for oral mucosa or open lesions
105
What is Ramsay Hunt Syndrome?
HZV cutaneous lesions of external auditory canal or face
106
What nerves are involved in Ramsay Hunt Syndrome?
Involvement of ipsilateral VII and VIII nerves, as well as V
107
Ramsay Hunt Syndrome causes...
* Facial paralysis
* Hearing deficits
* Vertigo
108
Research has not yet produced a vaccine for....
EBV (HHV-4)
109
What does EBV bind to and infect?
EBV binds to and infects nasopharyngeal epithelial cells --> B cells
110
EBV is "linked" to:
* Infectious mononucleosis
* Oral hair leukoplakia
* Nasopharyngeal carcinoma
* Burkitt's lymphoma
* Hodgkin disease
111
Herpes virus (HHV-4/EBV) is tropic for ...
Herpes virus is tropic for human B lymphocytes
| • Target cell receptors on their surface
112
What percent of the population harbors EBV?
~ 90% of the population
113
How is EBV transmitted?
* EBV shed from epithelial cells and transmitted via saliva
| * Because it is shed into saliva, contacts are frequent
114
Describe infection of EBV in childhood...
Initial infection in childhood is mild, often subclinical
115
Describe the infection of EBV in adults...
Adults have higher risk for disease (infectious mononucleosis) than children
116
Infectious mononucleosis is synonymous with...
"Kissing Disease"
117
EBV infection in young adults results in...
EBV --> infectious mononucleosis if initial infection occurs in young adults
118
Percentage of people entering college that are EBV negative...
* In US, 50% entering college are EBV negative
| * 10-15%/year then become positive
119
In adults afflicted with infectious mononucleosis prodrome occurs...
Prodrome up to 2 weeks before fever:
| • fatigue, malaise
120
Clinical feature pf infectious mononucleosis (in adults)
```
• Fever 90% of cases
• Tonsils enlarged in > 80% of cases
- Exudate +/- abscess
- Enlarged lingual tonsils
• Pharyngitis, tonsillitis
- Rare respiratory obstruction
```
121
Symptoms less common in infectious mononucleosis includes....
* Hepatosplenomegaly
* Rash
* Thrombocytopenia
* Palatal petechiae for 2 days
* NUG
122
Diagnosis of infectious mononucleosis
* Rising titer of antibodies specific for EBV antigens
* Positive heterophil reaction (Monospot test)
* Lymphocytosis with mononucleosis cells (atypical lymphocytes) in peripheral blood
123
What does a positive heterophile reaction entail (infectious mononucleosis)?
Positive heterophile reaction (Monospot test):
• Heterophile antibody is a byproduct of rapid increase in B lymphocytes
• IgM binds to and agglutinates Paul-Bunnell antigen of sheep and bovine red blood cells
124
Prognosis for infectious mononucleosis
• Most resolve in 4-6 weeks
| - but some symptoms for 6 months
125
Complications of infectious mononucleosis includes...
* Splenic rupture
* Chronic fatigue syndrome
* Bell's palsy
126
Complications of infectious mononucleosis in immunocompromised...
Potentially fatal polyclonal B-lymphocyte proliferation
127
Cytomegalovirus is also...
HHV-5
128
What percent of the US population has been exposed to cytomegalovirus?
At least 60% of U.S. population has been exposed to CMV
129
How is CMV spread?
* Person to person contact in saliva, urine, etc
* Sexual transmission
* Transplacenal and perinatal transmission
130
What percentage of CMV infections are asymptomatic?
* ~90% CMV infections are asymptomatic
| * Infection is nearly always asymptomatic in healthy people
131
Cytomegalovirus inclusion disease from primary CMV infection _____ occurs.
```
CID from primary infection rarely occurs. CID includes:
• Congenital & perinatal CMV infection
• CMV mononucleosis
• CMV in Immunosuppressed individuals:
- Transplants
- HIV infection
```
132
Latency and CMV
Infection followed by latency:
| • In glands, endothelium, macrophages, lymphocytes
133
Reactivation of CMV linked to...
Reactivation linked to reduced host resistance:
| • Immunosuppression including AIDS
134
Histologic appearance of CMV
• Very large cells
- Epithelium of glands
- Neurons
- Alveolar macrophages, epithelium and endothelium
- Kidney tubular epithelium and glomerular endothelium
• Single dark basophilic nuclear inclusion with peripheral halo
• Multiple indistinct cytoplasmic basophilic inclusions
135
What is CMV (heterophil-negative) mononucleosis?
* Mononucleosis-like infection in healthy individuals
| * Clinically like infectious mononucleosis but heterophil antibody negative
136
Symptoms of CMV mononucleosis
* Fever
* Lymphadenopathy
* Atypical lymphocytosis
* Hepatomegaly
* Rarely acute salivary sialadenitis w/ xerostomia
137
Prognosis of CMV mononucleosis
Most recover without sequelae, but excretion of virus via body fluids may occur for months or years
138
Congenital CMV infection?
* 95% in utero CMV infections asymptomatic
* CID when mother has primary infection
* Some surviving infants: permanent mental retardation, hearing loss, etc.
* Most with mild CID recover but may have later delayed-onset mental retardation with hearing deficits
139
Consequences of congenital CMV infection when mother has primary infection...
* Intrauterine growth retardation
* Profound illness
* Jaundice
* Hepatosplenomegaly, anemia, thrombocytopenia --> bleeding
* Encephalitis
* Enamel hypoplasia
140
CMV in AIDS occurs as a result of...
* Reactivation of latent infection
| * Also infection by sex partners
141
Most common opportunistic viral pathogen in AIDS
CMV
142
Oral manifestation of CMV in AIDS
Oral: chronic ulcers
143
CMV in AIDS causes serious life-threatening disseminated infections including...
* Pneumonitis can --> ARDS
* Colitis: debilitating diarrhea due to intestine necrosis and ulceration
* Retinitis: most common form of opportunistic CMV disease. May --> blindness
144
Most common form of opportunistic CMV disease...
Retinitis (may cause blindness)
145
Diagnosis of CMV infections involves...
```
• Biopsy: morphology of viral cytopathy
- Electronmicroscopy
• Viral culture
• Rising Ig titer
- ELISA (serology)
```
146
How are CMV antigens detected?
* IHC
* In situ hybridization
* PCR
147
Treatment for CMV infections, particularly infectious mononucleosis-like cases
Most infectious mononucleosis-like cases resolve spontaneously
148
Treatment for CMV infections in immunocompetent
Immunocompetency:
• NSAIDS
• Corticosteroids
• IV gammaglobulins
149
Treatment for CMV infections in immunosuppressed
Immunosuppression:
• Antivirals
• Improve immune status
150
Demographic of coxsackievirus infections
Infections occur mostly in infants or young children
151
Coxsackie viruses have 3 clinical patterns closely related and not separate infections...
* Herpangina
* HFM
* Acute lymphonodular pharyngitis
152
Coxsackie viruses involved in herpangina...
A1 to A6, A8, A10, A22 and others
153
Coxsackie viruses involved in HFM
A16 and others
154
Coxsackie viruses involved in acute lymphonodular pharyngitis
A10 in some cases
155
Incubation period for Coxsackie viruses
4 to 7 days
156
Most coxsackievirus infections occur during this time...
Most in summer or early fall
157
How does coxsackievirus infections spread?
* Crowding and poor hygiene aid spread
| * Fecal-oral route or saliva or respiratory droplets
158
Describe the severity in the 3 patterns of coxsackievirus infections...
In all 3 patterns, severity varies:
• Most strains cause self-limiting disease
• Occasional epidemics, even mortalities
159
Diagnosis of coxsackievirus infections involves...
* Usually by clinical criteria
* Culture or PCR
* Serology: rising antibody titers
160
What is herpangina?
Coxsackie childhood infection. Usually subclinical or mild.
161
Clinical presentation of herpangina...
• Lesions occur on soft palate and oropharynx
• Red macules --> fragile vesicles --> soon ulcerate
- 2 to 6 vesiculo-ulcers
• Acute flulike onset: sore throat, dysphagia, fever
162
Prognosis of herpangina
* Self-limited
| * Heal 7-10 days
163
Acute flulike onset, such as sore throat, dysphagia, and fever, are associated with this...
Herpangina
164
This disease presents with oral lesions like herpangina...
Hand, foot, & mouth disease
165
Oral lesions in hand, foot, and mouth disease...
* Precede skin lesions
| * More extensive than herpangina
166
Appearance of oral lesions in HFM disease
* Vesicles --> ulcers
* Most ulcers small, but may > 1 cm
* Resolve in one week
167
Skin rash associated with flulike symptoms are associated with this disease...
Hand, Foot, and Mouth disease
168
Skin rash associated with flulike symptoms in HFM disease occurs on...
Palms, soles, fingers and toes, etc...
169
Appearance and quantity of skin rashes in HFM disease...
* Few to dozens of lesions
| * Red macules --> vesicles --> ulcers
170
Histology of HFM disease and herpangina...
• Epithelium
- Intracellular and intercellular edema
- Spongiosis
- Intraepithelial vesicle
- Vesicles enlarges & ruptures through basal layer
• So subepithelial vesicle is formed
• Epithelial necrosis --> ulceration
171
Hyperplastic lymphoid aggregates occurs in...
Acute lymphonodular pharyngitis
172
Clinical features of acute lymphonodular pharyngitis
* Sore throat, fever, headache lasts 4-14 days
* 1-5 yellow to pink nodules on soft palate or tonsils
* No clinical vesicles or ulcers
* Hyperplastic lymphoid aggregates
173
Resolution of acute lymphonodular pharyngitis...
Resolves in 10 days
174
Rubeola is synonymous with...
* Measles
| * "Nine day measles"
175
Worldwide statistics for Rubeola (Measles)
Worldwide: ~20 million cases and 164 thousand deaths each year
• Encephalitis in 1 in 1,000
• Subacute sclerosing panencephalitis in 1 in 100,000 as late as 11 years later
176
Severe disease in immunosuppression (e.g. HIV)
Rubeola (measles)
177
Vaccine for this disease was introduced in the US in 1963
Rubeola (measles):
| • Vaccine led to dramatic decreased incidence
178
Rubeola (measles) is in this family and genus of viruses...
* Family: paramyxovirus
| * Genus: Morbillivirus
179
Rubeola is transmitted via...
* Highly contagious
| * Virus spreads via respiratory droplets
180
Incubation period of rubeola
7 to 12 days
181
How rubeola spreads...
* First multiples within upper respiratory tract epithelial cells
* Spreads to lymphoid tissues (where it replicates in mononuclear cells)
* Then spreads via blood throughout body
182
Oral manifestations of Rubeola include..
* Koplik's spots
* Candidiasis
* NUG
* Can affect odontogenesis -- enamel hypoplasia in primary teeth
183
Describe the first stage of rubeola
* 3 Cs: coryza (runny nose), cough, conjunctivitis
* Fever
* Koplik's spots on oral mucosa
* Lymphoid organ hyperplasia
184
What are the 3 Cs observed in the first stage of rubeola?
* Coryza (runny nose)
* Cough
* Conjunctivitis
185
Describe the second stage of rubeola
* Rash: vasculitis of small vessels in skin
* T lymphocytes act on virally infected vascular endothelium
* Erythematous macular-papular rash spreads from face to runk and extremities
186
Describe the third stage of rubeola
Rash fades with desquamation
187
When are Koplik's spots observed?
First stage of Rubeola
188
What are Koplik's spots?
* Areas of erythema on buccal and labial mucosa, etc.
* Small blue-white macules within these areas
* Due to foci of epithelial necrosis
* As spot ages, neutrophil exocytosis into epithelium leads to microabscess formation, necrosis, ulceration
189
Effect of rubeola/measles on lymphoid organs
* Marked follicular hyperplasia with large germinal centers
* Virus --> fusion of infected lymphocytes
* Warthin-Finkeldey cells (multinucleated lymphocytes)
190
What are Warthin-Finkeldey cells (multinucleated lymphocytes)...
Multinucleated lymphocytes observed in measles/rubeola:
• Up to 100 nuclei
• Intranuclear & intracytoplasmic eosinophilic inclusions
191
Rubella is also known as...
* German measles
| * "Three day measles"
192
Virus responsible for rubella...
* Togavirus
| * Genus: Rubivirus
193
Prognosis of rubella...
Mild disease, but can cause congenital rubella syndrome
| • If primary infection in early pregnancy
194
Vaccination for rubella...
Vaccine (MMRV) needs boosters:
• Rubella - 2 dose vaccine
• 2004: no longer endemic in U.S.
195
Clinical presentation of rubella...
Symptoms often mild (< 50% infections subclinical):
• Rash: discrete pink macules --> papules --> fade
• Lymphadenopathy
• low-grade fever
• Malaise
196
Oral manifestations of rubella include...
* Forchheimer's sign in 20% of cases
| * Confused with palatal petechiae
197
Infected (rubella) adults often have...
Transient arthralgia or arthritis
198
What is Forchheimer's sign?
* Small discrete dark red papules on soft palate and may extend to hard palate.
* Arises simultaneous with rash and lasts only 14 hours
Note: observed in rubella
199
How is HIV transmitted?
• HIV in most bodily fluids
- but transmission by oral fluids is rare
• Sexual contact/venereal
- male to male
- heterosexual contact with high risk group
• Parenteral exposure to contaminated blood
- Tranfusion
- IV drug use
• Organ transplant
• Mother-to-fetus
• Breast-feeding
200
Rubella infection in pregnant women, especially during the first trimester can result in...
* Miscarriages
| * Stillbirths
201
Congenital Rubella Syndrome birth defects often includes:
* Cataracts
* Hearing loss
* Mental retardation
* Congenital heart defects
202
Discuss viral integration of HIV
• Virus enters host cell
• Viral RNA uses reverse transcriptase to synthesize proviral DNA using viral RNA as template
- Viral RNA reversed to proviral DNA
• Proviral DNA splices into host genome using viral enzyme, integrase
• Integrated proviral DNA transcribes to RNA which directs host cell to synthesize more HIV virions
203
How does HIV enter the body...
HIV enters body through mucosa --> blood
204
___ molecule is a high-affinity receptor for HIV
CD4 molecule
205
What cells does HIV first infect?
HIV first infects cells with CD4 receptor:
• CD4+ helpter T lymphocyte
• Monocytes/macrophages
• Dendritic cells
206
Where does HIV infection establish itself?
* Infection establishes in lymphoid tissues
| * Virus may be latent for long periods
207
How are T-cells depleted in HIV?
• Major mechanism of loss of CD4+ T cells is lytic HIV infection of the cell, and cell death during viral replication and production of virions
• Other mechanisms include:
- apoptosis of uninfected cells
- killing of infected cells by cytotoxic T lymphocytes
208
Ratio of CD4+/CD8+ in peripheral blood
* Normal ratio is ~ 2 to 1
| * Ratio gradually falls to 0.5 as CD4+ T cells are destroyed
209
CD4+ T cell count
• Normal is 500-1000/milli-micro-liter but falls below 200 in AIDS
210
HIV stages
• Acute: acute viral syndrome
• Chronic
- Clinically asymptomatic (latent): 8 to 10 years
- Persistent generalized lymphadenopathy
- Minor opportunistic infections
• CRISIS (progression to AIDS)
211
In the acute stage of HIV, HIV infection may be _________ initially
Asymptomatic
212
In the acute stage of HIV, ____-_______ illness develops in 50-70% of affected persons _ to _ weeks after infection
* Self-limited
| * 3 to 6 weeks
213
Non-specific symptoms or symptoms resembling severe influenza in the acute phase of HIV include...
* Generalized lymphadenopathy
* Sore throat
* Myalgia
* Fever
* Rash
* Fatigue
* Diarrhea
* Photophobia
* Peripheral neuropathy
* Weight loss
* (sometimes) aseptic meningitis
214
Resolution of acute viral syndrome (acute phase of HIV)
Acute viral syndrome clears spontaneously in a few weeks
215
Oral manifestations in acute phase of HIV
Oral mucosa erythema and focal ulcers
216
Virus production in the acute phase of HIV ...
* Seroconversion 3 to 17 weeks after exposure with development of virus specific CD8+ CTLs (cytotoxic lymphocytes)
* High level of virus production, viremia, and widespread seeding of lymphoid tissues with modest reduction in CD4+ T cells
217
Chronic phase of HIV entails...
• Most newly infected individuals enter latent period with slow immune system decline
• Average of ~10 years before serious immune compromise develop
- Viral replication continues but is restrained by immune reaction
• Viral replication almost always begins to increase with decrease in CD4+ T cells
- Minor opportunistic infections
- Thrombocytopenia (in some cases)
- Persistent generalized lymphadenopathy
• Concurrent fever, rash, and fatigue
• Signals immune breakdown and abrupt increased viral replication
218
What does the Crisis phase of HIV entail?
```
• Progression to AIDS
• Increasing viremia
• Breakdown of host defenses
• Clinical disease
- Long-lasting fever, fatigue, weight loss, diarrhea
```
219
AIDS indicator diseases include
```
• Opportunistic infections
- ~ 80% of deaths
• Opportunistic neoplasms
- Kaposi sarcoma
- Non Hodgkin lymphoma
- Neurologic dysfunction
```
220
HIV testing can be done using...
* Antibody tests
* Antigen tests
* PCR test
* Viral load test
* CD4 cell count
* Home testing kits
* HIV-1/2 Ag/Ab Combo test
221
Antibody tests are the most common HIV tests to look for HIV antibodies, and they include...
* ELISA or EIA (enzyme-linked immunosorbent assay or enzyme immunoassay) tests detect HIV antibodies in blood, oral fluid, or urine as early as 3 weeks after exposure. Results for these tests can take up to two weeks.
* Rapid HIV antibody tests also use blood, oral fluid, or urine to detect HIV antibodies. Results for these test can take 10-20 minutes.
* A positive result from either of these tests requires a Western blood to confirm that result. It can take up to two weeks to confirm a positive result.
222
Antigen tests in HIV testing are...
* Not as common as antibody tests, but they can be used to diagnose HIV infection earlier (from 103 weeks after intial infection with HIV).
* Antigen tests require a blood sample.
223
In HIV testing, PCR (polymerase chain reaction test) detects...
* Detects the genetic material of HIV itself
| * Can identify HIV in the blood within 2-3 weeks of infection
224
Viral load test for HIV testing determines....
The amount of HIV-1 in blood plays a role in determining when to start anti-HIV treatment or to change treatment.
225
In HIV testing CD4 cell count is a useful indicator...
* It is a useful indicator for when to start antiretroviral treatment.
* It can also help predict the risk of complications such as infections.
226
In HIV testing, home testing kits entails...
* HIV antibody tests is not a true HIV testing kit, but a sample-collection kit.
* A blood sample obtained by sticking a finger with a sterile lancet is put the blood on a special collection card in the kit, and send it back to laboratory for testing.
227
In HIV testing, HIV-1/1 Ag/Ab Combo tests involves...
* Recently approved
* Detects HIV-1 p24 antigen that can appear just 12-26 days after infection and HIV-1/2 antibodies 20-45 days after infection
* Results are generated in 20 minutes
* The antigen test is not definitive
228
What is Truvada?
a multidrug antiretroviral medication used in the treatment of HIV
229
Different classes of drugs target distinct steps in the HIV lifecycle, so they are prescribed to be taken in combination...
* Protease inhibitors
* Entry inhibitors
* Nucleoside/nucleotide reverse transcriptase inhibitors
* Non-nucleoside reverse transcriptase inhibitors
230
Effects of treatment in HIV
```
• Therapies reduce symptoms
• CD4+ count increases
• Reduced viral load
• Reduced oral lesions
• But lymphomas not reduced
• Some reports increased:
- HPV lesions
- HIV related salivary gland disease
```
231
What are the different types of Kaposi Sarcoma?
* Classic
* Endemic (African)
* Iatrogenic immunosuppression-associated
* AIDS-related
232
Etiology of Kaposi Sarcoma
* All caused by HHV8 (KS-associated herpes virus)
| * Endothelium is cell of origin
233
Clinical features of Kaposi Sarcoma
* Most common tumor in HIV infection
* Highest frequency in men who have sex with men (in U.S.)
* Often appear first in mouth
* Usually multiple lesions
* Palate and gingivae are most common sites
234
Stages of Kaposi Sarcoma
* Patch (macular). Early stages flat & slightly discolored
* Plaque
* Papules and nodules
* Enlarge, darken, hemorrhagic, and painful
235
Histology of the patch stage of Kaposi Sarcoma...
* Resembles granulation tissue or capillary hemangioma
| * Bizarre-shaped vessels
236
Histology of plaque stage of Kaposi Sarcoma...
* Proliferation of vessels
* Spindle cell component
* Bland cytology
237
Histology of nodular stage of Kaposi Sarcoma...
* Fascicles of malignant spindle cells compress extravasated erythrocytes with release of hemosiderin
* Positive for CD34 antigen immunoreactivity
238
Management of Kaposi Sarcoma includes...
```
• HIV therapy
• Chemotherapy
- Deoxyrubicin
- Paclitaxel
• Surgery
• Cryotherapy
• Intralesional
- Chemotherapy
- Sclerosing agent
```
239
Oral hair leukoplakia occurs in vast majority in immunosuppression including...
* HIV infection
* Transplant patients
* Rarely in immunocompetent people
240
Characteristics of oral hairy leukoplakia...
* White adherent lesions
* Most on lateral borders of tongue (often bilateral)
* Occasionally other sites
* Surface typically corrugated
241
Definitive diagnosis of oral hairy leukoplakia must...
Definitive diagnosis must show EBV within lesion by in situ hybridization, PCR, or EM
242
Histology of oral hairy leukoplakia...
* Thickened parakeratin surface projections
* Epithelium is acanthotic with bandlike zone of lightly stained cells with abundant cytoplasm ("balloon cells") in upper spinous layer
* Nuclear beading
* No dysplasia
* Heavy candida without normal inflammatory reaction
243
What is nuclear beading, and when is it examined?
* Nuclear beading: scattered cells with nuclear clearing and peripheral margination of chromatin
* Oral hairy leukoplakia
244
Management of oral hairy leukoplakia...
* Treatment is not needed (unless there is discomfort or esthetic problem)
* Systemic antiherpesviral drugs produce rapid resolution but recurs when treatment stops
* Surgery
* Cryotherapy
* HAART reduces OHL
245
What is hyperpigmentation in HIV?
Macules in skin and mucosa
246
Why does hyperpigmentation in HIV occur?
Due to:
• AIDS meds
• Infectious destruction of adrenal cortex
• Idiopathic
247
Histology of hyperpigmentation in HIV...
* Histology: focal melanosis
| * Increased melanin in basal cell layer
