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Complete regression of AIDS-related Kaposi‚s sarcoma in a child treated with highly active antiretroviral therapy

Niehues, Tima; Horneff, Gerdc; Megahed, Mosaadb; Schroten, Horsta; Wahn, Volkera


aChildren‚s Hospital and bDepartment of Dermatology, Heinrich Heine University, Düsseldorf, Germany, and cChildren‚s Hospital, Martin Luther University Halle, Wittenberg, Germany.

Received: 24 February 1999; accepted: 2 March 1999.

Children with HIV infection are at a lower risk of malignancies in comparison with adults. Kaposi‚s sarcoma (KS) is a rarity and represents 5% of all tumours found in children with AIDS [1]. KS is caused by human herpes virus type 8 (HHV-8), which can be transmitted horizontally before puberty [2,3]. In adults, HHV-8 is mostly transmitted via the sexual route and KS is the most frequent malignant manifestation of AIDS. In this paper we report on a child with KS and her successful therapy with highly active antiretroviral therapy (HAART).

The 5-year-old girl was born in Germany to an HIV-infected mother from Zaire. Although HIV infection of the child had been diagnosed elsewhere at the age of 3 years, no therapy was carried out. At presentation she was in a reduced condition with tachydyspnoea, frequent coughing and haemoptysis. Marked hepatosplenomegaly (liver 5cm and spleen 6cm below the costal margin) and a generalized lymphadenopathy were present. Over the sternum, 5cm above the xiphoid, there was a single purple brown nodule approximately 2cm in diameter. At the medial side of the left thigh a similar nodule could be detected.

Laboratory investigations confirmed HIV infection by the presence of HIV antibodies in the serum (enzyme immunoassay and Western blot) and an HIV RNA viral load of 81670 copies/ml upon initial presentation (Quantiplex HIV-RNA 2.0; Chiron, Fernwald, Germany). IgG antibodies to HHV-8, herpes simplex virus, Epstein-Barr virus and cytomegalovirus were positive, whereas IgM antibodies to these viruses were undetectable. The CD4 cell count was 155/μl (CD4 cells 5% of lymphocytes, CD4:CD8 cell ratio 0.06).

A skin biopsy of the nodule on the thigh was performed and revealed an increased vascularization with slitlike lumen. Spindle-shaped and thickened collagen fibres were seen surrounding the blood vessels. The histological picture was consistent with the diagnosis of KS.

A chest radiograph and a thoracic computed tomography showed bilateral interstitial infiltration. A bronchoalveolar lavage was performed and was negative for all common opportunistic infections. In-situ hybridization for HHV-8 was attempted but did not lead to conclusive results.

Therapy with zidovudine (100mg/m2 three times a day), lamivudine (4mg/kg twice a day) and nelfinavir (25mg/kg three times a day) was started soon after the laboratory results had been obtained. Regression of the skin nodules, a decrease in liver (2cm), spleen (1cm below costal margin) and lymph node size, as well as the disappearance of the haemoptysis occurred over a period of 6 months. The HIV RNA viral load dropped to undetectable levels (detection limit 500 copies/ml) within 2 months. CD4 cell counts increased to 232/μl after 3 months and 286 cells/μl after 6 months.

The clinical presentation of KS in this case was diagnosed by the characteristic skin lesions. Tachydyspnoea and haemoptysis were also probably attributable to KS, although our attempts to demonstrate HHV-8 in the bronchoalveolar fluid were not successful. KS affecting the lungs is frequently found in adult patients and is often associated with haemoptysis. In this case, lymphoid interstitial pneumonitis (LIP) was first thought to be present. Whereas the chest X-ray and computed tomography were compatible with LIP, haemoptysis did not fit into the clinical picture of LIP. Pulmonary involvement of KS was thus suspected but could not be proved.

Before the availability of HAART, treatment of paediatric KS consisted of experimental approaches, including combination chemotherapy with bleomycin, doxyrubicin and vincristine [4], etoposide [5] and IFN-agr; [6].

Recent reports in adults provide evidence that HHV-8 DNA can be cleared from peripheral blood by HAART [7]. Under HAART, regression of both KS [8] and HHV-8-associated lymphoma [9] has been documented. This prompted us to administer HAART to our patient in order to avoid cytotoxic drugs. Therapy in this case was well tolerated and in addition to a virological and immunological response resulted in the disappearance of KS and haemoptysis.

The suppression of HHV-8 is likely to be mediated by effector cells of the immune system, which regain their function after the initiation of HAART. To our knowledge there is no evidence of a direct anti-HHV-8 effect of the three antiretroviral drugs used.

In conclusion, this case suggests that HAART can induce the remission of KS in HIV-infected children without additional therapy. HAART may offer a chance to avoid the use of cytotoxic drugs in HHV-8-related malignant complications.

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© 1999 Lippincott Williams & Wilkins, Inc.