Human herpesvirus-8 (HHV-8), associated with Kaposi sarcoma (KS), has varying seroprevalence rates based on geography and risk groups, particularly among men who have sex with men and individuals with HIV. Clinical manifestations of HHV-8 infections can include KS, primary effusion lymphoma, and multicentric Castleman’s disease, with diverse symptoms affecting different patients. Diagnosis requires tissue examination, while treatment typically involves chemotherapy combined with antiretroviral therapy, with strategies differing depending on the specific manifestations and disease progression.

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