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Human herpesvirus-8 (HHV-8) has been associated with Kaposi's sarcoma, multicentric Castleman's disease and primary effusion lymphoma. Kaposi's sarcoma and multicentric Castleman's disease patients may develop body cavity effusions that, unlike primary effusion lymphoma, are poorly characterized. To better define these effusions, pleural and peritoneal fluids derived from 12 human immunodeficiency virus-seropositive and one seronegative patients affected by Kaposi's sarcoma or multicentric Castleman's disease were analyzed by a combination of morphologic, immunophenotypic, and DNA analyses, including polymerase chain reaction amplification of HHV-8, Epstein-Barr virus, and immunoglobulin heavy-chain (IgH) gene sequences. In addition, HHV-8 serologic status was assessed by using an immunofluorescence assay. All patients were adult men with high antibody titers to HHV-8; 11 of the 13 patients were homosexual/bisexual. Effusions revealed monocyte/macrophage-rich infiltration (10 patients) or large-cell lymphoma with CD45(+)/non-T/non-B phenotype (three of 13 patients); polymerase chain reaction analysis showed the presence of HHV-8 sequences (nine of 13 patients), germline IgH (seven of 12 patients) or clonal IgH rearrangements (four of 12 patients), and rarely Epstein-Barr virus sequences (two of 12 patients). In the setting of HHV-8 infection, two effusion types may occur. One fulfills the criteria for HHV-8-positive PEL (lymphoma-morphology, HHV-8-DNA(+), IgH rearrangement). The other seems more reminiscent of an HHV-8-associated nonneoplastic process (monocyte-macrophage morphology, HHV-8-DNA(+/-), germline IgH). Interestingly, a single case of the latter effusion type harbored a B-cell monoclonal proliferation, which suggests the hypothesis that a prelymphomatous effusion may precede overt body cavity lymphoma.

DUE to the growing populations of wild urban pigeons, the natural hosts of parasitic ticks such as Argas re exus (Arg r), there is an increased risk of allergic reactions to tick bites, presumably caused by the proteins secreted by the tick's salivary glands. Allergic reactions with symptoms ranging from local manifestations at the bite site (itching, edema, and erythema) to severe systemic reactions (urticariaangioedema and shock) have been reported in Europe (1±5). Here we report two patients who experienced severe systemic reactions after a bite by Arg r. A 37-year-old man, living in a small town in central Italy near an old building, experienced two severe systemic reactions: the ®rst one with urticaria-angioedema and the second one with cardiovascular failure and loss of consciousness. Both episodes occurred after nocturnal bites by a pigeon tick, identi®ed as Arg r. Clinical history, skin prick test, and speci®c IgE measurements (CAP System, Pharmacia & Upjohn, Sweden) did not indicate any sensitization to common inhalants or food allergens. Total IgE (UniCAP) was 32 kU/l. Interestingly, the patient had experienced local reactions to venom from Apis mellifera (honeybee). Speci®c IgE was detected to A. mellifera (2.34 kU/l, CAP class 2) and to Arg r (5.73 kU/l, CAP class 3). In contrast, no speci®c IgE could be detected to allergens of Dolichovespula maculata, Vespa crabo, Vespula spp., Polistes spp., Solenopsis invicta, Aedes comunis, Chironomus thummi, Tabanus spp., Blatella germanica, and Sitophilus granarius. The second patient was a 26-year-old man, also living in an ancient city of central Italy. He experienced several local reactions to bites of the pigeon tick, subsequently identi®ed as Arg r, before developing two episodes of systemic reactions, with anaphylactic shock, to the tick bite. History, skin prick test, and speci®c IgE to common inhalant and food allergens were negative. Total IgE was 77.1 kU/l; speci®c IgE to Arg r was 1.27 kU/l (CAP class 2). Severe, potentially life-threatening reactions in our patients con®rm former cases of anaphylactic manifestations after Arg r tick bite (2, 3, 5). The patients described were living close to old buildings. Attics or roofs might have served as pigeon breeding sites, and ticks such as Arg r could have migrated to apartments in the neighborhood. Repeated tick bites can induce IgE-mediated sensitization to allergens of the soft tick even in subjects without atopic predisposition. Severe immediate-type systemic reactions, as suggested by the clinical histories, were directly con®rmed by the presence of speci®c IgE to Arg r and indirectly by the absence of speci®c IgE (except for A. mellifera in one case) to other arthropods, including stinging insects, taxonomically different from Arg r. IgE-mediated cross-reactivity between proteins of the tick and other arthropods seems unlikely, in view of the speci®city of the test employed to assess speci®c IgE to Arg r. Future efforts should be made to identify and use recombinant single allergenic proteins of Arg r to demonstrate more accurately an IgE-mediated reaction to pigeon tick bite.

Evidence indicates that, at least in the early stage, Kaposi's sarcoma (KS) is a cytokine-mediated disease and that it is consistently associated with a novel herpesvirus termed human herpesvirus-8 (HHV-8). To gain insights into the mechanisms by which cytokines and HHV-8 may cooperate in disease pathogenesis, we examined the phenotype, the Th1 (γ-interferon [γIFN]) and Th2 (interleukin-4 [IL-4]) cytokine profile and the presence of HHV-8 in peripheral blood mononuclear cells (PBMC), tumor-infiltrating lymphocytes (TIL), and spindle cell cultures derived from skin lesions of patients affected by classical KS (C-KS) and acquired immunodeficiency syndrome (AIDS)-associated KS (AIDS-KS). TIL and spindle cell cultures were examined at day 0 or after culture in conditioned media from activated T cells (TCM) that contain the same cytokines increased in KS tissues. No differences were found in the immunophenotype of PBMC from C-KS patients versus controls, except for AIDS-KS patients who showed a T-CD8+ expansion. However, a preferential infiltration of T-CD8+ cells was found in all KS lesions examined, which was maintained after culture of TIL in TCM. γIFN production was found in both PBMC and cultures derived from all KS examined; some IL-4 positive supernatants were found only in three AIDS-KS cases. Uninvolved skin did not show appreciable lymphocyte infiltration or cytokine production. The culture conditions of the lesional skin allowed also the appearance of adherent, spindle-like cells bearing markers of tissue macrophages. Finally, most or all of the PBMC, lesions, and macrophagic cell cultures from the skin lesions were found to be positive for HHV-8 infection by nested polymerase chain reaction (PCR). These findings indicate that patients with KS express a Th1 phenotype with a prevalent γIFN production, likely accounted for by the local T-CD8+ infiltration. By analogy with other viral infections (ie, Epstein-Barr virus), this suggests that in loco recruitment of lymphoid cells and the subsequent γIFN production may be in response to or elicited by HHV-8 that was found in both PBMC and macrophagic cell cultures from the lesions of the same patients.