David Kouba, M.D. and Christopher Hoffmann, MD, MPH
- Infection with KSHV/HHV-8 common in Zambia (44% seroprevalence amongst healthy adults)
- KS is most common at CD4 <200
- Incidence among HIV-infected in Africa 1/1000 - 10/1000 per year
- Similar prevalence in men & women in Zambia (women may be more symptomatic)
- Most individuals with KS have cutaneous findings, particularly on face, hard pallet, or lower extremities, often with significant edema/nodularity
- Visceral involvement of lungs or GI tract may occur without cutaneous disease. Sx of pulmonary KS include dyspnea on exertion, dry cough, and wheezing with or without fever. GI KS can be asymptomatic or present with mild GI bleeding or GI obstruction
- KS can first present during immune reconstitution on ART. Continue ART and consider chemotherapy.
- Dx with direct visualization (consider other cutaneous diseases on differential - see below)
- Pulmonary KS: often bilateral nodular infiltrates with or without pleural effusions; however radiographic findings highly variable and can also appear as focal consolidation
- Treat with ART (possibly with PI) regardless of CD4 count (also place on cotrimoxazole prophylaxis)
- For extensive disease: ART + chemotherapy (vincristine 1.2mg/m2 + bleomycin 10mg/m2 twice weekly for 6-8 cycles)
Zambia Information Author: Christopher Hoffmann, MD, MPH
HHV-8, a gamma herpes virus, also known as Kaposi sarcoma-associated herpesvirus (KSHV) is etiologic agent of all clinical variants of KS.
- KS was once the AIDS-defining illness in ~10-20% of cases in U.S.; it has become rare in era of HAART
- In U.S. and Europe, AIDS-related KS occurs overwhelmingly in MSM; evidence suggests sexual transmission of HHV-8 in that population. Incidence in HIV+ children low (4%) vs. 50% of HIV+ MSM (prior to HAART), with higher prevalence with more lifetime sexual partners and history of anal sex. Prevalence of HHV-8 much higher in in general population of many African countries (>50%) and may be transmitted vertically.
- AIDS-related KS is most aggressive form of KS (others are classic/sporadic; endemic/African; iatrogenic/post-transplant).
- Clinical features variable, from single lesions to disseminated disease. Skin lesions commonly painless, oval, red-purplish or rust-colored macules, papules or plaques to deep violaceous or purple-black nodules. May appear as subcutaneous nodules less commonly. With extensive disease may develop B symptoms (fevers, night sweats, malaise, weight loss)
- Coalescing plaques may obstruct lymphatic flow, causing significant lymphedema.
- Any skin surface may be affected, although commonly on trunk and face or oral mucosa.
- Visceral disease includes GI involvement, lymphatic and pulmonary disease. Poor prognosis with pulmonary KS, with median survival of 3-10 mos prior to the use of HAART. Visceral disease may occur without identifiable skill lesions.
- Pts with history of KS are at higher risk for other HHV-8-associated malignancies (primary effusion body lymphoma and Castleman's syndrome).
- Definitive Dx by Bx for H&E. Immunostains for vascular differentiation (CD31 & CD34) will aid Dx, if pathology equivocal.
- Histopathology shows dermal infiltrate of atypical spindle cells, which splay apart collagen bundles while attempting to form rudimentary vascular slits. Diffuse erythrocyte extravasation and hemosiderin deposition into the dermis is characteristic. Plasma cell infiltrate frequently observed.
- DDx includes bacillary angiomatosis, pyogenic granuloma, cutaneous metastases of lymphoma, angiosarcoma.
- PCR can be used to detect KSHV viral DNA or serologic assays for KSHV antibodies. Several commercially available ELISA tests for various KSHV antigens exist. There is no "gold standard" test for identifying infected pts.
HHV-8 DNA strongly predictive for the development of KS when detected in serum of HIV+ males.
- ART sometimes results in resolution of cutaneous or systemic disease, though cases of KS exacerbation due to immune reconstitutionhave also been reported.
- Treatment required for: (1) systemic visceral involvement; (2) rapid progression; (3) interference with a vital function; (4) negative affect on quality of life.
- Limited disease: can monitor lesions after starting ART, small lesions will resolve.
- Intralesional injection of vinblastine. Good option for solitary/few lesions when cosmesis is important, since cosmetic results can be excellent.
- Aggressive cryotherapy: multiple lesions in areas not cosmetically important, as healing times and cosmesis are inferior to excision or vinblastin injection.
- Surgical excision: solitary or few lesions in cosmetically sensitive locations.
- Laser ablation: poor healing, similar to cryotherapy therefore should be used for debulking in cosmetically unimportant areas.
- Radiation therapy: larger and/or multiple lesions in one specific site not amenable to destructive modalities or excision. May cause or exacerbate lymphatic obstruction and lymphedema, especially in lower extremities.
- Aliretinoin gel: apply to KS lesions twice-daily initially, then titrate to 3-4x/d as tolerated. Response rate 35% at 12 wks in alitretinoin-treated pts vs.18% in placebo-treated pts.
- For generalized cutaneous disease: systemic chemotherapy (see below) or radiation therapy, either to an extended field or as total body electron-beam therapy.
- For visceral disease: systemic chemotherapy with liposomal anthracyclines such as doxorubicin to reduce side effects, or combinations of vincristine, doxorubicin and bleomycin. Paclitaxel is effective chemotherapeutic option; however, usually recommended as 2nd line agent due to toxicity.
- Systemic treatment includes: interferon-alpha and chemotherapy with a single agent such as pegylated-liposomal anthracyclines (pegylated liposomal doxorubicin20mg/m2 q 2-3 wks), paclitaxel (120-125 mg/m2 q 2-3 wks), or etoposide (50-60 mg daily x 7days every 2 - 3 wks).
- Investigational treatment options: angiogenesis inhibitors, IL-12, and HIV-tat inhibitors.
- Steroids may help prevent inflammatory response from severe visceral disease causing airway impingement or bowel obstruction
| doxorubicine liposomal ||Generalized cutaneous and/or systemic disease, lymphedema secondary to lymphatic obstruction by KS.
| paclitaxel ||Refractory systemic disease. Second line agent due to toxicity.
|vinblastin ||Generalized cutaneous and/or systemic disease.
|aliretinoin gel ||May be useful for cosmetic treatment of cutaneous KS
- While limited cutaneous disease is primarily cosmetic issue, regular (3-6 mos) follow-up required to monitor for disseminated disease.
- Disseminated cutaneous disease requires regular follow-up, as lymphatic obstruction is common complication.
- Visceral disease requires regular follow-up with oncology and/or radiation oncology, depending on regimen selected.