Clinical course of disseminated Kaposi sarcoma in a HIV and hepatitis B co-infected heterosexual male.

AIDS associated Kaposi sarcoma (AIDS-KS) was first reported from India in 1993. Since then only 16 cases have been reported. Three of them had proven Human Herpesvirus 8 (HHV-8) infection. We report a case of disseminated KS in a heterosexual male from India with HIV, hepatitis B and HHV-8 infection. He was given six cycles of chemotherapy with liposomal doxorubicin over three months to which he showed a good response. The case highlights the clinical course and management of a HHV-8 positive disseminated KS in a patient co-infected with Hepatitis B and HIV.

INTRODUCTION

Kaposi sarcoma (KS) is a lymphoangioproliferative disease caused by human herpes virus 8 (HHV-8). Early KS seems to be a reactive process of polyclonal nature, which may remain so or progress to become a true sarcoma.[1] Acquired immune deficiency syndrome (AIDS)-KS may have an unpredictable clinical course varying from an incidental finding to a rapidly progressing cancer that can severely affect the quality of life. Treatment is with existing chemotherapy regimens, with dose depending on the extent and severity of the condition. It involves a substantial burden of toxicity. There have been only few reports of HHV-8 associated KS from India.[234] This has been attributed to the low prevalence of HHV-8 infection.[5] Here, we report the clinical profile and management of a case of KS associated with HIV-HBV co-infection from Manipur, India.

CASE REPORT

A 38-year-old known HIV positive male from Manipur presented with complaints of purple colored skin lesions over the trunk and extremities since three years. The initial skin lesion appeared over the inner aspect of the thigh. Gradually, new lesions appeared. Spontaneous resolution was not seen, and there was no trauma-induced bleeding. He had a history of multiple unprotected heterosexual exposures; however, homosexuality was denied. He also gave a history of recurrent herpes genitalis. There was no history of blood transfusion or intravenous drug abuse.

The patient was first diagnosed with HIV infection in 2008 when he presented with fever, weight loss, and diarrhea. The CD4 count was 231 cells/ml with a viral load of 86 copies/ml. He was started on a combination of stavudine and lamivudine along with nevirapine. A year later, he tested positive for hepatitis B surface antigen (HBsAg) after which telbivudine was added to the existing regimen. A suspicion of KS was considered for which he received two cycles of paclitaxel in 2011. Six months later, he was referred to our center for further therapy as there was no improvement. General examination showed the patient to be cushingoid with cervical lymphadenopathy. Cutaneous examination revealed multiple discrete, nonulcerated, nontender violaceous nodules of size 2 cm × 2 cm, and plaques over the trunk and extremities [Figure 1]. Laboratory investigations revealed hemoglobin 13.8 g%; total white blood cell count 13,200/cu mm. Antibodies to HIV-1 were positive with CD4 cell count of 540 cells/ml (normal range: 559–1710). HBsAg was positive, and the viral load as detected by quantitative PCR was <10 IU/ml. The patient tested negative for HBeAg. PCR for HHV-8 from the peripheral blood sample was positive. Hepatitis C virus IgG antibodies were absent and VDRL test was nonreactive. Chest radiograph and computed tomography scan showed scattered postinflammatory changes in both lungs with no significant adenopathy. Sputum was negative for acid-fast bacilli. Ultrasonography revealed grade I to II fatty liver, whereas contrast-enhanced computed tomography scan of the abdomen did not reveal any abnormality.

Figure 1

Discrete, non ulcerated, non tender violaceous nodules and plaques over the trunk and feet

Biopsy done from the skin lesion on left ankle was consistent with a diagnosis of KS [Figure 2]. Biopsy done from left supraclavicular lymph node and ulcerated nodules seen on gastroscopy also showed features of KS, thus confirming the metastasis. The patient also had esophageal candidiasis. Based on the above findings, he was staged as T1I0S1 as per the AIDS Clinical Trial Group staging system for KS[6] [Table 1]. After two years, the highly active antiretroviral therapy (HAART) was changed to lamivudine, tenofovir, and efavirenz when he presented to our centre. He was given six cycles of chemotherapy with liposomal doxorubicin over three months. He also received topical imiquimod for genital warts. At last follow-up six months later, he showed good response to therapy with regressing skin lesions and absence of new lesions. Repeat CT thorax, abdomen, and pelvis were normal.

Figure 2

Skin with the dermis containing clusters of proliferated spindle shaped cells (a) lining slit like spaces (c) with numerous extravasated erythrocytes (b)

Table 1

Revised ACTG staging classification for KS

DISCUSSION

Acquired immune deficiency syndrome associated KS is infrequently reported from India. Only 16 cases have been reported till date, the first in 1993[78] [Table 2]. Documented HHV-8 infection of the skin has been previously reported in three cases from India.[234] This may be attributed to low prevalence of HHV-8. In a recent study, prevalence of HHV-8 infection in South India was estimated to be 4.7%.[9] PCR for HHV-8 from the peripheral blood sample was positive in our patient. Co-infection of HHV-8 and HIV-1 increases the probability of developing KS by 60%/year post-HIV infection.[10]

Table 2

AIDS-KS reported in Indian literature from 1993 to June 2013

Kaposi sarcoma has been described more commonly in homosexual men. KS however has not been reported extensively in India, which may be attributed to both the social stigma associated with homosexuality, as well as underreporting of cases. Our patient denied any homosexuality. Interestingly, half of the cases reported in Indian literature are from Mumbai and three from Manipur. Metastasis has been described in three previous cases from India, out of which one patient died and in the other two treatment outcomes are not known. Our patient had gastrointestinal involvement which is described in 40% of patients with AIDS-KS at presentation and suggests a poorer prognosis.[11] Further, HIV-HBV co-infection is associated with more severe liver disease and greater hepatotoxicity due to antiretroviral drugs. However, liver disease was not seen in our patient.

Acquired immune deficiency syndrome-KS is an aggressive disease often affecting the mouth, lungs, gastrointestinal tract or genitalia. HAART forms the mainstay of treatment in HIV-associated KS. Chemotherapy with pegylated liposomal doxorubicin being the recommended standard of care was administered for advanced KS in our patient. It is a superior formulation of conventional doxorubicin, with minimal toxicity and an enhanced pharmacokinetic profile. This case highlights the clinical course and response to treatment with anthracyclines and HAART of an HHV-8 positive disseminated KS in a HIV positive patient with HBV co-infection.