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EBAC - Infectious Disease > Human Herpesvirus-8 Disease > Flashcards

Human Herpesvirus-8 Disease Flashcards

1
Q

What is the estimated seroprevalence of human herpesvirus-8 (HHV-8) in the general U.S. population?

A

1% to 5%

This compares to 10% to 20% in certain Mediterranean countries and 30% to 80% in parts of sub-Saharan Africa.

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2
Q

Which groups are at increased risk for HHV-8 infection in the United States?

A

Men who have sex with men (MSM) and persons with HIV infection

Among MSM without HIV, seroprevalence ranges from 13% to 20%, increasing to 30% to 35% among MSM with HIV.

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3
Q

What diseases are etiologically associated with HHV-8?

A

Kaposi sarcoma (KS), primary effusion lymphoma (PEL), multicentric Castleman’s disease (MCD)

KS includes classic, endemic, transplant-related, and AIDS-related forms.

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4
Q

What is the increased risk of developing Kaposi sarcoma for patients with HHV-8 viremia?

A

Approximately nine-fold

This is relative to those without HHV-8 viremia.

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5
Q

What is the overall prevalence of Kaposi sarcoma in the U.S. among patients with AIDS before effective antiretroviral therapy (ART)?

A

As high as 30%

The incidence rose steeply between 1981 and 1987, then gradually declined.

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6
Q

What factors contributed to the reduction in Kaposi sarcoma incidence prior to widespread ART availability?

A
  • Deaths of patients with advanced AIDS
  • Increasing use of antiviral drugs

Antiviral drugs included zidovudine, ganciclovir, foscarnet, and cidofovir.

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7
Q

True or False: Kaposi sarcoma is one of the most common cancers among the AIDS population in the U.S.

A

True

HIV infection increases the risk of KS several thousand fold even in the ART era.

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8
Q

What are the common clinical manifestations of Kaposi sarcoma?

A
  • Nontender, hyperpigmented skin lesions
  • Oral lesions
  • Lymphatic involvement
  • Visceral involvement

Oral lesions occur in approximately one-third of patients and may predict pulmonary involvement.

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9
Q

What is the characteristic presentation of primary effusion lymphoma (PEL)?

A

Effusions isolated within pleural, pericardial, or abdominal cavities

Mass lesions and ‘extracavitary’ disease may also occur.

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10
Q

What are the systemic symptoms associated with multicentric Castleman’s disease (MCD)?

A
  • Fever
  • Night sweats
  • Generalized adenopathy
  • Hepatosplenomegaly

MCD may mimic other inflammatory conditions.

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11
Q

What is the role of serologic testing for HHV-8 antibodies in diagnostics?

A

Currently not indicated for diagnostic testing or routine screening

This is due to lack of standardization and poor sensitivity and specificity.

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12
Q

What is the suspected primary mode of transmission for HHV-8?

A

Saliva

Asymptomatic HHV-8 infection is often associated with shedding in saliva.

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13
Q

Fill in the blank: Early initiation of _______ is likely to be the most effective measure for the prevention of Kaposi sarcoma.

A

ART

This is particularly important for HIV-positive individuals.

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14
Q

What chemotherapy agents are preferred for treating Kaposi sarcoma with visceral involvement?

A
  • Liposomal doxorubicin
  • Paclitaxel

Liposomal doxorubicin is preferred due to lower toxicity.

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15
Q

What is a significant concern when using corticosteroids in patients with Kaposi sarcoma?

A

Potential exacerbation of life-threatening disease

Corticosteroids are associated with the development of KS.

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16
Q

What are the recommended treatments for primary effusion lymphoma?

A
  • Chemotherapy
  • ART

Limited data exists due to the rarity of PEL.

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17
Q

What treatment options are available for multicentric Castleman’s disease?

A
  • IV ganciclovir
  • Oral valganciclovir
  • Rituximab

Combination therapies have shown some benefit.

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18
Q

What is Immune Reconstitution Inflammatory Syndrome (IRIS)?

A

A condition that may occur among HHV-8-infected patients initiating ART

KS-IRIS can present as unmasking or worsening of KS.

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19
Q

What are the risk factors for developing KS-IRIS?

A
  • Advanced KS tumor stage (T1)
  • Pre-treatment HIV viral load >5 log10 copies/mL
  • Detectable pre-treatment plasma HHV-8
  • Initiation of ART alone without concurrent chemotherapy

KS-IRIS is associated with significant morbidity and mortality.

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20
Q

What are the risk factors for developing KS-IRIS?

A

Advanced KS tumor stage (T1), pre-treatment HIV viral load >5 log10 copies/mL, detectable pre-treatment plasma HHV-8, initiation of ART alone without concurrent chemotherapy.

KS-IRIS refers to Kaposi’s Sarcoma-Immune Reconstitution Inflammatory Syndrome.

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21
Q

What is the recommended treatment for KS-IRIS?

A

Systemic chemotherapy and supportive measures. Steroids are strongly discouraged.

Corticosteroid therapy has been associated with exacerbation of pre-existing KS in persons with HIV.

22
Q

Is there data on how initiation of ART affects primary effusion lymphoma (PEL)?

A

No data exist on the frequency with which initiation of ART complicates the course of primary effusion lymphoma.

PEL is a type of lymphoma associated with HHV-8.

23
Q

What has been observed in a small number of patients with HIV-associated MCD upon initiation of ART?

A

Clinical decompensation.

MCD stands for Multicentric Castleman Disease.

24
Q

What are the key components of therapy for HHV-8-associated IRIS?

A

Suppression of HIV replication and immune reconstitution.

Initiation of ART should not be delayed.

25
Q

What is the recommendation for ART in patients with active KS?

A

ART is indicated for all patients with active KS.

KS is an AIDS-defining cancer.

26
Q

What is recommended to prevent KS recurrence in patients with HIV?

A

Effective suppression of HIV replication with ART.

This is also recommended for patients with MCD and malignant lymphoproliferative disorders.

27
Q

What is the seroprevalence of HHV-8 infection among pregnant women with HIV in New York City?

A

Ranges from 1.7% among U.S.-born to 3.6% among Haitian-born women, and up to 11.6% among pregnant women from 4 other U.S. cities.

Seroprevalence varies by geographic area.

28
Q

Does pregnancy affect the prevalence of antibodies to HHV-8?

A

No, pregnancy does not appear to affect the prevalence or antibody levels.

However, levels of HHV-8 DNA in peripheral blood may increase late in pregnancy.

29
Q

Is routine screening for HHV-8 by PCR or serology indicated for pregnant women with HIV?

A

No, routine screening is not indicated.

Antiviral therapy for HHV-8 infection in pregnancy is also not recommended.

30
Q

What should be done when KS, PEL, or MCD occur during pregnancy?

A

Managed with consultations between the obstetrician, infectious disease specialist, and oncologist; treatment may be deferred until after delivery.

This is due to the rarity of these conditions in pregnancy.

31
Q

What does in vitro models suggest about beta-human chorionic gonadotropin?

A

It induces regression of KS tumors.

Clinical reports on KS incidence and natural history in pregnancy are conflicting.

32
Q

Is perinatal transmission of HHV-8 common?

A

Occurs infrequently.

Evidence includes cases of KS in infants shortly after birth.

33
Q

What increases the risk of HHV-8 transmission from mother to infant?

A

Higher maternal antibody titer and levels of HHV-8.

Detection of similar strains of HHV-8 DNA in specimens drawn at birth also supports this.

34
Q

What is the mortality rate among infants with HIV born to HHV-8-seropositive mothers compared to seronegative mothers?

A

Increased mortality through age 24 months.

Studies could not completely account for other confounding factors affecting infants with HIV.

35
Q

How does the rate of HHV-8 seropositivity compare between children born to HHV-8 antibody-positive versus antibody-negative women?

A

Substantially higher rate among children born to antibody-positive women.

Multiple studies document this finding.

36
Q

What are strong risk factors for the development of Kaposi Sarcoma (KS)?

A

Low CD4 cell count and uncontrolled HIV viremia

Early initiation of ART is likely the most effective measure for prevention of KS.

37
Q

What is the recommended treatment for mild-to-moderate KS?

A

Initiation or optimization of ART

This is categorized as AII in treatment recommendations.

38
Q

What is the preferred first-line chemotherapy for advanced KS?

A

Liposomal doxorubicin

This is categorized as AI in treatment recommendations.

39
Q

What should be avoided in patients with KS, including those with KS-IRIS?

A

Corticosteroids

Their use can exacerbate life-threatening disease.

40
Q

Are antiviral agents with activity against HHV-8 recommended for KS treatment?

A

No

This is categorized as AIII in treatment recommendations.

41
Q

What is the treatment approach for Primary Effusion Lymphoma (PEL)?

A

Chemotherapy + ART

Consultation with a specialist is recommended.

42
Q

What adjunctive therapies can be used for PEL?

A

Oral valganciclovir or IV ganciclovir

This is categorized as CIII in treatment recommendations.

43
Q

What therapy options should all patients with Multicentric Castleman’s Disease (MCD) receive?

A

ART

This is categorized as AIII in treatment recommendations.

44
Q

What are some therapy options for MCD depending on patient status?

A
  • IV ganciclovir (or oral valganciclovir) +/- high dose zidovudine
  • Rituximab +/- prednisone
  • Rituximab + liposomal doxorubicin for concurrent KS
  • Monoclonal antibody targeting IL-6 or IL-6 receptor

Consultation with a specialist is necessary.

45
Q

What caution should be taken regarding corticosteroids in MCD treatment?

A

They should be used with caution or avoided

Especially in patients with concurrent KS.

46
Q

What potential issue may patients experience after receiving rituximab or corticosteroids for MCD?

A

Subsequent exacerbation or emergence of KS

This is an important consideration in treatment planning.

47
Q

What does ART stand for?

A

Antiretroviral therapy

48
Q

What does PEL stand for?

A

Primary effusion lymphoma

49
Q

What does MCD stand for?

A

Multicentric Castleman’s disease

50
Q

What classification is used to categorize KS patients into ‘Good Risk’ and ‘Poor Risk’?

A

AIDS Clinical Trials Group (ACTG) KS Staging Classification

It uses T (Tumor), I (Immune), and S (Systemic illness) criteria.

EBAC - Infectious Disease (36 decks)

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