Disseminated Kaposi's sarcoma in a human immunodeficiency virus-infected homosexual Indian man

Riti Bhatia, Shweta Shubhdarshini, Savita Yadav, M Ramam, Shipra Agarwal

 Department of Dermatology and Venereology, All Institute of Medical Sciences, New Delhi, India

Correspondence Address:
Savita Yadav
Department of Dermatology and Venereology, Teaching Block, All India Institute of Medical Sciences, New Delhi
India

Sir,

Kaposi's sarcoma has rarely been reported from India ^[1] though the burden of human immunodeficiency virus (HIV) infection in India is second only to that in sub-Saharan Africa, and human herpesvirus-8, the Kaposi sarcoma associated-virus is known to be prevalent here.

A 26-year-old HIV-positive male student from North India was referred to us for the evaluation of widespread violaceous plaques and nodules on the skin. The plaques had first been noticed on the dorsa of his hands 6 months back and then gradually spread to involve other parts of the body over the next few months. The patient complained of malaise and decreased appetite for the past 2 months. He had been detected to be seropositive for HIV-1 infection 3 years earlier in a voluntary screening camp but did not take antiretroviral treatment. Two months back, he was diagnosed with abdominal tuberculosis and was started on both anti-tubercular and antiretroviral treatment. There was a history of high-risk sexual behavior with multiple protected as well as unprotected homosexual exposures involving both insertive and receptive intercourse. There was no history of blood transfusion or of recreational intravenous drug use. On cutaneous examination, there were multiple (around fifty), well-defined, non-scaly, discrete, violaceous, non-tender plaques and nodules of various sizes (1–2.5 cm) scattered on the face, trunk and extremities [Figure - 1]a and [Figure - 1]b. Lesions were distributed in a 'Christmas tree-pattern' on the trunk. A similar plaque was present on the hard palate. Scalp, palms, soles and nails were normal. There was generalized lymphadenopathy: axillary, cervical and inguinal lymph nodes were enlarged (1.5–2.5 cm). They were firm, mobile, non-tender and non-matted. There was no organomegaly. Hemogram and serum biochemistry were unremarkable. Enzyme-linked immunosorbent assay (ELISA) for HIV-1 was positive and the CD4 count was 173 cells/mm ^[3]. Venereal disease research laboratory (VDRL), hepatitis B surface antigen and anti- hepatitis C virus antibody tests were negative. Biopsy of a plaque on the abdomen showed a spindle cell proliferation with slit-like congested capillaries dissecting between collagen bundles throughout the dermis, present individually as well as in groups with extravasation of erythrocytes. The “promontory sign” was noted [Figure - 2]a and [Figure - 2]b. The tumor cells stained positively with endothelial markers CD31 and CD34, confirming their vascular lineage. They also stained positively for human herpesvirus-8, confirming the diagnosis of Kaposi's sarcoma [Figure - 2]c. Fine needle aspiration of an inguinal lymph node showed reactive lymphoid hyperplasia. A computed tomography (CT) scan of the chest and abdomen showed flame-shaped opacities in the hilar regions bilaterally, suggesting pulmonary involvement [Figure - 3]. Endoscopy of the upper and lower gastrointestinal tracts did not show any abnormalities. With a final diagnosis of disseminated Kaposi's sarcoma (cutaneous and pulmonary involvement), the patient was treated with doxorubicin 20 mg/m ^[2] given as 3-weekly cycles, and antiretroviral treatment was continued. After six cycles of chemotherapy, there was significant flattening of all the skin plaques [Figure - 1]c There were no treatment-related adverse effects. Post-treatment, the CD4 count had increased to 201 cells/mm ^[3]. Three months after the completion of chemotherapy, there was further flattening of the plaques and nodules, along with complete resolution of the pulmonary opacities. However five months after completion of chemotherapy there was a relapse of cutaneous disease in the form of a single firm dusky erythematous nodule measuring 2 × 2 cm on the chin. Relapse was confirmed by a biopsy from the nodule which showed features of Kaposi's sarcoma. The patient is planned for 6 cycles of paclitaxel chemotherapy.

Figure 1a: Multiple violaceous and dusky erythematous plaques and nodules on the anterior trunk. The shape of many plaques is linear along the skin creases

Figure 1b: Close-up view of the plaques and nodules on the chest

Figure 1c: Marked flattening of plaques and nodules after completion of chemotherapy leaving behind hyperpigmentation

Figure 2a: Dense aggregates of spindle cell proliferation in the superficial, mid- and deep dermis with congested capillaries (H and E, ×100)

Figure 2b: “Promontory sign” showing proliferation of irregular, jagged vascular channels surrounding preexisting blood vessels (H and E, ×400)

Figure 2c: Positive staining of spindle cells for human herpesvirus-8 (immunohistochemical staining for latencyassociated nuclear antigen of human herpesvirus-8, ×400)

Figure 3: Flame-shaped opacities in both lungs

There are four clinical variants of Kaposi's sarcoma described: classical, African-endemic, immunosuppressive therapy-associated and acquired immune deficiency syndrome (AIDS)-associated.^[2] A necessary factor implicated in the causation of Kaposi's sarcoma is human herpesvirus-8, also known as Kaposi's sarcoma-associated herpesvirus. Seroprevalence of human herpesvirus-8 varies from 50% in the general population in sub-Saharan Africa to around 6% in the United States. In India, seroprevalence was found to range from 4.7% in 379 patients (309 HIV infected and 70 healthy individuals) in South India to 26% in 165 HIV-positive, antiretroviral therapy-naïve patients in North India.^[3],[4], A wide variation in human herpesvirus-8 seroprevalence has previously been observed in East Asian countries namely, Japan (11.7%), China (12.7–43.2%) and Thailand (1–28.1%).^[5],[6],[7] Some studies suggest that regions high in silicaceous volcanic soil and blood-sucking insects are hot spots of human herpesvirus-8, but the exact cause for this remains unknown. It has been seen that the burden of Kaposi's sarcoma is higher in areas which are endemic for human herpesvirus-8. However, our patient had not traveled abroad to areas endemic for human herpesvirus-8 infection.

Apart from human herpesvirus-8, other factors implicated in the causation of Kaposi's sarcoma are interlekuin-6 polymorphisms and genetic variations in the human leukocyte antigen (HLA) loci, which may explain the low prevalence of Kaposi's sarcoma in India. However, we found no published genetic studies of the presence of such variations.

An online search was done on the PubMed database using the key words “Kaposi's sarcoma,” “cutaneous” and “India.” Relevant articles as well as those they cited were studied. Since the description of the first case of Kaposi's sarcoma in India in 1993, 23 more cases have been reported [Table - 1].^{[8],[9],[10],[11],[12],[13],[14],[15],[16],[17],[18],[19],[20],[21],[22],[23],[24],[25],[26],[27],[28],[29],[30]} All but one were seropositive for HIV. Three cases were documented to be positive for human herpesvirus-8 infection. Elsewhere, Kaposi's sarcoma has been reported to be more common in men having sex with men (5.7 and 0.7/100 person years in men having sex with men and heterosexual men, respectively).^[31] However, all the previous reports from India were of heterosexual men and women, though our patient was homosexual.

Treatment includes local modalities such as cryotherapy, intralesional vincristine and radiation therapy. Indications for systemic therapy include visceral involvement, extensive Kaposi's sarcoma associated with lymphedema, extensive and rapidly progressing Kaposi's sarcoma and failure to respond to local therapy. We administered liposomal doxorubicin, the current first-line chemotherapeutic agent for Kaposi's sarcoma because of pulmonary involvement. The risk of relapse following chemotherapy has been found to be 13.5%/year, usually occurring in the first year after treatment. In a study involving 140 patients with advanced stage Kaposi's sarcoma-AIDS treated with a combination of highly active antiretroviral therapy and liposomal anthracycline, the 5-year overall survival was found to be 85%.^[32] Pulmonary Kaposi's sarcoma has a poor prognosis with a median survival of 1.6 years.^[33] The 5-year survival in patients with pulmonary Kaposi's sarcoma was found to be lower than in those with classic Kaposi's sarcoma in a cohort of 305 HIV-positive patients.^[34]

Acknowledgment

We are grateful to Dr. Beth Ruben, Professor of Clinical Dermatology and Pathology, University of California, San Francisco, for her help with human herpesvirus-8 immunohistochemical staining.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

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