Life-threatening exacerbation of Kaposi's sarcoma after prednisone treatment for immune reconstitution inflammatory syndrome

Abstract

The recovery of immune functions after the initiation of HAART has been associated with clinical deterioration despite control of immunological and virological parameters, a condition that is now termed ‘immune reconstitution inflammatory syndrome’ (IRIS) [1]. The most common IRIS-associated diseases are mycobacterial, cytomegalovirus, and herpes-associated conditions, including Kaposi's sarcoma (KS) [1–3]. IRIS conditions associated with mycobacterial infections [4], retinal cytomegalovirus [5], cryptoccocal meningitis [6], and herpes zoster [7], have been treated with primary anti-infective therapy, the continuation of HAART and anti-inflammatory therapy, usually steroids, with varying degrees of success. It is recognized that long-term corticosteroid immunosuppressive therapy can induce KS in non-HIV and HIV-infected patients [8–11]. Such reports state that removing the drug usually results in total or partial remission of KS. A 19-year-old man was diagnosed with HIV 3 months earlier, with a self-reported history of purple skin lesions that appeared 2 years before and spontaneously remitted. At diagnosis he had extensive nodal and mucocutaneos KS, with a CD4 cell count of 182 cells/μl (13%) and a viral load of 21 000 copies/ml. He started antiretroviral therapy with lamivudine, stavudine, indinavir and ritonavir. The time course of treatments and events are shown in Fig. 1.Fig. 1: Time course of treatment and clinical manifestations of the patient. Chemotherapy for Kaposi's sarcoma (KS) included bleomycin and vincristine. Photographs: Day 0, KS at the beginning of HAART treatment. Day 37, magnetic resonance image and photograph of the lesion, with total pharyngeal obstruction. Day 45, lesion after chemotherapy, right panel is at start and left panel after 3 days. Day 112, follow-up visit after remission.He experienced an initial flattening of the KS lesions after 52 days, and was hospitalized with fever, vomiting and diarrhoea. Based on the time between the initiation of HAART and an increase in CD4 cell numbers at the onset of the symptoms (an increase of CD4 cell count from 182 to 322 cells/μl in 18 days, last viral load 1840 copies/ml), IRIS was diagnosed by his original attending physician, who prescribed prednisone 20 mg twice a day and the patient was discharged. After 2 weeks of prednisone, he experienced an explosive growth of mucocutaneous lesions, facial oedema and haemorrhagic lesions in both eyes. He reported that he perceived the oral lesions growing in a matter of hours, and was referred to our institution. An emergency tracheotomy was performed, steroids were withdrawn and a first cycle of 2 mg vincristine and 15 mg bleomycin was administered. He developed Streptococcus pneumoniae purulent otitis media and thrombocytopenia. He was discharged with a silver cannulae, oral amoxycillin and unchanged HAART. Three weeks later he was hospitalized with epistaxis and profuse bleeding of the exophytic lesion in the oral cavity. Antiretroviral therapy was stopped, platelet aphaeresis was transfused and 5 days later a second course of bleomycin and vincristine was administered. He was discharged with a marked remission of all KS lesions as well as of the lymphoedema. He resumed HAART 2 weeks later. Three months after the tracheotomy, the silver cannulae was removed, and at this point the lesions had almost disappeared. He did not return until one year later, remained regularly on HAART with complete remission of KS and a CD4 cell count of 328 cells/μl and a viral load of less than 50 copies/ml. KS is an infectious proliferative disease, cytokine mediated, in which the presence of human herpes virus 8 is essential for the process, and immunosuppression a necessary fact [12]. The disease is insidious, with an unpredictable course; remission of KS with HAART is not infrequent, although a small percentage of patients still require chemotherapy in the HAART era. Oncostatine is an autocrine cytokine for KS cells [13]. Guo and Antakly [14] have shown that steroids have a synergistic effect with oncostatine, and both stimulated or unstimulated KS cells have unusually high levels of glucocorticoid receptor protein. We speculate that the explosive exacerbation of KS in this case was caused by the additive effect of the use of glucocorticoids over KS cells in a milieu rich in other cytokines involved in KS cell proliferation, such as IL-6, as increases in the level of IL-6 and its receptor have been observed in patients with IRIS [15] and in KS lesions [16]. In the present case, a life-threatening exacerbation of KS shortly after steroids were used to treat IRIS was seen. In other corticoid-related KS manifestations in the literature, the onset was not explosive nor life threatening, and all remitted by simply removing steroids. The potential additive effects of IRIS with steroid use in KS, contraindicates its use as an anti-inflammatory therapy in this condition, other therapeutic measures such as non-myelosuppressive chemotherapy, as was seen in this case, has shown clinical benefit. Conflicts of interest: None.