HHV 8, Structure, Epidemiology, risk factors, clinical manifestation, associated malignancy, diagnosis, Transmission/ Preventing Exposure, treatment and prevention images

1. HHV 8
Dr. Rasika Deshmukh

2. Structure

3. Epidemiology
• The seroprevalence of human herpesvirus-8 (HHV-8)—a/k/a Kaposi
sarcoma-associated herpesvirus (KSHV
• 1% to 5% in the general U.S. population
• 10% to 20% in certain Mediterranean countries and
• 30% to 80% in parts of sub-Saharan Africa.

4. Risk population
• men who have sex with men (MSM)
• persons with HIV infection
• MSW without HIV sero prevalence ranges from 13% to 20%
• MSW with HIV sero prevalence ranges from 30% to 35%
• Injection drug
• CD4 T lymphocyte [CD4] cell counts <200 cells/mm3

5. HHV 8 a/w
• Kaposi sarcoma (KS) including classic, endemic, transplant-related,
and AIDS-related,
• primary effusion lymphoma [PEL] and solid organ variants
• multicentric Castleman’s disease (MCD)

6. Clinical Manifestations
Immunocompetent children and organ transplant recipients
• fever, rash, lymphadenopathy, bone marrow failure, and occasional rapid
progression to KS
Kaposi sarcoma
• vary widely
• most common: nontender, hyperpigmented, macular or nodular skin lesions.
• Oral lesions : predictors of pulmonary involvement and less favorable treatment
outcomes.
• Lymphatic involvement >>debilitating lower extremity edema.
• Patients with visceral : asymptomatic, shortness of breath, painless rectal
bleeding or melena, and other non-specific pulmonary and gastrointestinal
symptoms

7. Clinical Manifestations
PEL
• effusions isolated within the pleural, pericardial, or abdominal cavities, but
mass lesions and “extracavitary” disease within skin, hematopoietic
organs, and the gastrointestinal tract have been described
MCD
• fever and night sweats, generalized adenopathy, fever and
hepatosplenomegaly
• mimic other inflammatory conditions including sepsis, with hypotension,
clinical evidence of a systemic inflammatory response, and progression to
multi-organ failure.

8. Clinical Manifestations
KSHV inflammatory cytokine syndrome (KICS)
• frequently critically ill and
• demonstrate marked elevations in IL-6 and IL-10, as well as high
plasma HHV-8 viral loads

9. Diagnosis
• cytologic and immunologic cell markers, as well as histology
• tissue examination is needed to confirm the diagnosis
• immunohistochemical staining of tumors with antibodies recognizing
the HHV-8-encoded latency-associated nuclear antigen (LANA)
• polymerase chain reaction (PCR) to identify HHV-8 DNA
• serologic testing for HHV-8 antibodies is currently not indicated
• due to lack of standardization and poor sensitivity and specificity of
these assays.

10. lymphoma cells are large and pleomorphic with variable
nuclear shapes
LANA 1 POSITIVE IMMUNOFLUROSCENT STAINING

11. Transmission/ Preventing Exposure
Transmission
• mode(s) of transmission remains unclear
• epidemiologic and virologic data suggest that saliva and genital
secretions is a source>>viral shedding saliva and occasional shedding in
genital secretions
Preventing Exposure
• Recommendations do not yet exist
Preventing Disease
• supporting a role >>the toxicity of current anti-HHV-8 treatments
outweighs the potential use for prophylaxis
• early initiation of ART is likely to be the most effective measure

12. Treating Disease
KS:
• Chemotherapy, in combination with ART, should be administered to
patients with visceral involvement
• Liposomal doxorubicin preferred as first-line therapy> exhibits less high-
grade toxicity relative to paclitaxel
• Paclitaxel effective with relapse following treatment failure with liposomal
doxorubicin
• avoid concurrent use of corticosteroids
• ganciclovir, foscarnet, and cidofovir exhibit in vitro activity
PEL:
• Chemotherapy, in combination with ART,
• combination of cyclophosphamide, doxorubicin, vincristine, and
prednisolone (CHOP)
• combination of infusional etoposide, (EPOCH) demonstrated superior
survival
• valganciclovir or zidovudine, may be used as adjunctive therapies

13. Treating Disease
• MCD:
• no standardized treatments
• IV ganciclovir or oral valganciclovir are options
• Rituximab :as an important adjunctive treatment
• Therapeutic monoclonal antibodies targeting either interleukin-6 (IL-
6) or the IL-6 receptor

14. Preventing Recurrence
• Effective suppression of HIV replication with ART