Johns Hopkins ABX Guide
HHV 8
MICROBIOLOGY
- Human herpesvirus-8 (HHV8): human gammaherpesvirus, also known as Kaposi’s sarcoma herpesvirus (KSHV).
- 20-30% of men who have sex with men (MSM) are HHV8 seropositive vs 1% of HIV-1 negative blood donors.
- Associated with receptive anal intercourse and the number of partners.
- An unknown cofactor may be involved in transmission.
- HHV-8 gene products promote spindle cell proliferation and angiogenesis and may therefore eventually lead to tumor transformation.
CLINICAL
- Virus is either likely cause or has been associated with the following:
- HIV-associated Kaposi sarcoma (KS): typically characterized by violaceous vascular lesions on skin [Fig 1], mucous membranes [Fig 2] and/or viscera (e.g., GI tract and lungs).
- HIV-associated KS is seen mostly in MSM. HHV-8 found in saliva and semen.
- Pulmonary KS typically presents with dyspnea, cough, chest pain or hemoptysis.
- Gastrointestinal KS can cause abdominal pain, intestinal obstruction or hemorrhage.
- Classic KS (non-HIV-associated): variant is usually limited to the skin [Fig 3] and typically affects elderly Mediterranean and East European men.
- Endemic African KS: presentation varies from skin lesions only to aggressive systemic disease.
- Multicentric Castleman’s disease: lymphoproliferative disorder mostly seen in HIV+ patients, characterized by B type symptoms, lymphadenopathy, hypergammaglobulinemia.
- Primary effusion lymphoma: a non-Hodgkin’s Disease B cell lymphoma mostly seen in HIV+ patients. Presents with body cavity-based effusions in the absence of a solid tumor.
- HIV-associated Kaposi sarcoma (KS): typically characterized by violaceous vascular lesions on skin [Fig 1], mucous membranes [Fig 2] and/or viscera (e.g., GI tract and lungs).
- The virus has been associated with KS as well as a febrile illness in the setting of bone marrow failure in transplant populations.
SITES OF INFECTION
- Mucocutaneous: skin, oropharynx.
- Endothelial and spindle cells contain HHV-8 DNA.
- Visceral organs
- Lung
- Gastrointestinal tract
- HHV-8 DNA found in saliva, semen, blood (viremia in HIV and transplant pts), B cells of primary effusion lymphoma and lymphoid tissue of multicentric Castleman’s disease.
TREATMENT
Kaposi Sarcoma (local disease < 25 lesions)
Options include cryotherapy, radiation therapy or surgery.
- Topical alitretinoin has been shown to have an approximately 35% partial response: apply 0.1% gel to affected site 2-4x/day.
- Intralesional vinblastine injection: 0.2-0.3 mg/ml: 0.1ml/0.5 cm2 lesion; result in 60-90% clinical response rate.
Kaposi Sarcoma (Systemic Disease)
- The first line of therapy should probably be antiretroviral therapy (ART) in HIV infected patients or reduction of immunosuppressive therapy in transplant patients.
- Combination chemotherapy often suggested.
- Paclitaxel 100 mg/m2 every 2 weeks was associated with a 59% response rate.
- Pegylated liposomal doxorubicin 40 mg/m2 q2wk has been shown to be more effective than chemotherapy with 58% response rate.
- A regimen of bleomycin, doxorubicin and vincristine given in combination with HAART had a better response rate than HAART alone.
Multicentric Castleman’s Disease
- Combination chemotherapy usual, consult oncology.
- Rituximab (375 mg/m2, once weekly for 4 weeks) has been shown to be very effective
- Rituximab in combination with liposomal doxorubicin has been effective in patients with severe disease
- Etoposide 100-200mg/m2, once weekly for 4 weeks, can be given with rituximab to help prevent relapses
- Anti-IL6 antibody has been useful in alleviating symptoms due to IL-6 overproduction (one of the HHV-8 genes encodes a viral variant of this cytokine).
- A case series showed that the initiation of ART did not prevent relapse of disease, but may prolong survival.
Primary febrile illness with BM failure
- A reduction in immunosuppressive therapy in conjunction with foscarnet 80 mg/kg twice-daily x 2 weeks was successful on a case report basis in a transplant patient.
OTHER INFORMATION
- HHV-8 mostly causes disease mainly in immunocompromised individuals
- Interferon-alpha probably is effective in KS because it has both antiviral and immunomodulatory effects.
- Pulmonary KS can be life-threatening and should be treated immediately.
Basis for recommendation
Comment: A comprehensive review of KS.
References
Comment: Reviews 8 trials of rituximab in Castleman disease. Most patients achieved remission
Comment: Review that describes current concepts and using immunomodulators as knowledge of oncologic pathogenesis expands.
Comment: This combination regimen was effective and well tolerated and 3 year survival rate was 81%
Rating: Important
Comment: Patients treated with HAART and chemotherapy had higher KS response rate, but there was no difference in survival at 12 months
Rating: Important
Comment: The authors advocate rituximab, and for aggressive disease adds chemotherapy.
Comment: Retrospective analysis showed that chemotherapy and HAART were the two factors associated with positive outcomes in 114 patients with KS. There was no difference in outcome seen in PI-based vs NNRTI based HAART.
Rating: Important
Comment: Study showing 95% 2-year survival in 21 previously untreated patients with HIV-associated Castleman’s disease treated with rituximab.
Comment: Study showing that rituximab infusions after chemotherapy lead to prolonged sustained remission in HIV-infected patients with Castleman's disease.
Comment: Study showing 2.8% excess risk of HHV-8 seroconversion following blood transfusion in Uganda.
Rating: Important
Comment: Editorial on the risk of transmission of HHV-8 via blood transfusions.
Comment: Study defining positive and negative prognostic factors in AIDS-associated KS.
Comment: Large retrospective study showing a dramatic decrease in the incidence of KS related to HAART. No difference in incidence was seen in pts on PI vs NNRTI based regimens.
Comment: Five patients with HIV-KS and 2 pts with non-HIV KS were treated with cidofovir at 5mg/kg q wk x 2 weeks then every other week. All 7 pts had a progression of the disease with no decrease in HHV-8 viral load.
Rating: Important
Comment: Case series of 7 HIV infected patients with Castleman's disease who were treated with HAART. While relapse of disease occurred, mean survival (48 months) was longer than expected.
Rating: Important
Comment: A case report of a kidney transplant patient who developed a febrile illness and BM failure in the setting of HHV-8 viremia. Treatment with foscarnet leads to the restoration of blood counts.
Comment: Description of febrile illness and BM failure in the setting of primary or reactivation HHV-8 disease in 3 solid organ transplant patients
Comment: Six patients with HIV associated KS were treated with foscarnet at 180 mg/Kg once-daily for a mean of 19.5 days. By 3 months after the end of treatment, the disease had progressed in all patients.
Comment: First identification of HHV-8 sequences in Kaposi Sarcoma lesions.
Media
Kapso sarcoma
Typical cutaneous lesion that ranges in presentation from flatter to nodular, pigmented to violaceous/vascular.
Source: CDC/Dr. Steve Kraus
KS mucosal lesion
Intraoral KS in patient with AIDS. About 10% of patients with advanced AIDS will have mucosal lesions of KS. Lesions may be small to larger, nodular growths.
Source: CDC, S. Silverman DDS San Francisco
Cutaneous KS
WIth endemic or classic KS, lesions often seen on ankle or foot region with flat, violaceous lesions.
Source: CDC/
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