RESUMO
BACKGROUND: Classic Kaposi's sarcoma [KS] is a chronic, multifocal, vascular proliferation, which commonly presents purplish nodules on the distal extremities of elderly men. Excisional surgery is one of the traditional therapies, but is generally time consuming and costly. OBJECTIVE: To evaluate the safety and efficacy of curettage for the treatment of KS nodules. METHODS: A single arm, prospective study in patients with at least one KS nodule removed by curettage. Hemostasis was obtained using 130-volume hydrogen peroxide [H2O2] and the wound was left to heal by secondary intention. Follow-up was done after 15 days, 1, 3, 6 and 12 months. RESULTS: Ninety patients [88 male, 2 female] with mean age of 75.8 years were enrolled. Eighty-two of the curetted nodules were localized on the lower limbs, five on the face, and three on the upper limbs. No postoperative complications were encountered, and cosmetic outcome was rated excellent by 87 patients and good by the remaining 3 patients. After 3 months, we noticed only minimal hypo-/hyperpigmentation in 59 cases, while in the remaining 31 patients the scar appeared imperceptible. Recurrence after 12 months was null. CONCLUSION: Curettage followed by the application of H2O2 is a safe, effective and simple technique for the treatment of KS nodules in elderly patients.
Assuntos
Curetagem/métodos , Peróxido de Hidrogênio/administração & dosagem , Sarcoma de Kaposi/cirurgia , Neoplasias Cutâneas/cirurgia , Idoso , Idoso de 80 Anos ou mais , Cicatriz/etiologia , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia , Complicações Pós-Operatórias , Estudos ProspectivosRESUMO
Classic Kaposi's sarcoma (cKS) is a human herpesvirus-8 (HHV-8)-associated lympho-angioproliferative tumor typically occurring in the elderly. It is associated with HHV-8-driven perturbed balance of peripheral B-cell subsets, which may have an impact on immune responses to antigenic stimulation. We took advantage of the common practice of cKS patients to undergo seasonal influenza vaccination because of advanced age and analyzed the immunogenicity and safety of licensed trivalent influenza vaccine in 46 cKS patients and 44 matched controls. Licensure criteria for immunogenicity were fulfilled in both groups. Four weeks after vaccination, hemagglutination-inhibition antibody titers against each viral strain contained in the vaccine increased in patients and controls (all P<0.001). Protection against at least one strain was achieved by 96% of cKS and 91% of control subjects. Protection against all strains persisted after 12 weeks, demonstrating a long-lasting response to vaccination. The vaccine was equally well tolerated by patients and controls, as assessed by evaluating solicited local and systemic reactions to the vaccine, and appearance or increase of antinuclear autoantibodies. HHV-8 virological rebound was observed in four cKS patients, but was not accompanied by progression of KS lesions. We conclude that seasonal influenza vaccine given to cKS patients is immunogenic and safe.
Assuntos
Imunogenética , Vacinas contra Influenza/uso terapêutico , Influenza Humana/prevenção & controle , Sarcoma de Kaposi/imunologia , Estações do Ano , Neoplasias Cutâneas/imunologia , Idoso , Idoso de 80 Anos ou mais , Anticorpos Antinucleares/sangue , Anticorpos Antivirais/sangue , Estudos de Casos e Controles , Feminino , Humanos , Influenza Humana/imunologia , Masculino , Orthomyxoviridae/imunologia , Segurança do Paciente , Sarcoma de Kaposi/sangue , Neoplasias Cutâneas/sangue , Resultado do TratamentoRESUMO
BACKGROUND: Classic Kaposi's Sarcoma (cKS) is a rare vascular tumor associated with Human Herpesvirus 8 (KSHV) infection, nevertheless not all KSHV-infected individuals have cKS. OBJECTIVE: We investigated whether particular KIR/HLA receptor/ligand genotypes would be preferentially present in KSHV-infected and uninfected individuals who have or have not developed cKS. METHODS: KIR/HLA genotypes were analyzed by molecular genotyping in 50 KSHV-infected individuals who did or did not have cKS and in 33 age-and sex-matched KSHV seronegative individuals. RESULTS: There was no association of individual KIR, HLA or receptor ligand combinations with KSHV infection. However, activating KIR and KIR/HLA genotypes were significantly more frequent in cKS cases, specifically KIR3DS1, KIR2DS1, and KIR2DS1 with its HLA-C2 ligand. CONCLUSION: A nonspecific inflammatory response triggered by activation of NK cells upon KIR-HLA interaction could be associated with the pathogenesis of KS.
RESUMO
The link between Kaposi's sarcoma-associated herpesvirus (KSHV or human herpesvirus 8) and Kaposi's sarcoma has been proven, but the transmission routes, especially in the heterosexual population, are not yet completely understood. To assess the intrafamilial patterns of transmission among first-degree relatives of Italian classic Kaposi's sarcoma (cKS) patients, KSHV seroprevalence and the presence of viral DNA in blood and saliva were evaluated in 18 families (32 cKS patients and 35 family members), comparing the results with those obtained in 200 elderly healthy controls without known exposure to KSHV. The KSHV genotype of variable region VR1 of the hypervariable ORF K1 gene was subsequently analysed in all KSHV-positive samples. The results showed that KSHV infection was significantly higher in relatives of cKS patients (11/35 cases) than in healthy controls (17/200 cases; P=0.001). The 11 infected relatives included spouses (n=3), siblings (n=2) and offspring (n=6) of the cKS patients; the same KSHV genotype was shared within the same family in the majority of cases (85%), indicating the presence of person-to-person transmission within families. Viral DNA was mostly observed in the saliva of infected relatives (45.4%); detection of DNA in blood was less frequent (27.3%). Notably, KSHV DNA was present in saliva and/or blood of three KSHV-infected relatives with indeterminate or negative serostatus. Thus, the risk of KSHV infection is greatly enhanced within families of cKS patients, where close contacts (horizontal and/or sexual) can contribute to the spread of KSHV.
Assuntos
Transmissão de Doença Infecciosa , Saúde da Família , Herpesvirus Humano 8/isolamento & purificação , Sarcoma de Kaposi/epidemiologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Sangue/virologia , Análise por Conglomerados , DNA Viral/sangue , DNA Viral/química , DNA Viral/genética , Família , Feminino , Genótipo , Humanos , Itália , Masculino , Pessoa de Meia-Idade , Dados de Sequência Molecular , Filogenia , Saliva/virologia , Sarcoma de Kaposi/virologia , Análise de Sequência de DNA , Estudos Soroepidemiológicos , Proteínas Virais/genéticaRESUMO
BACKGROUND: Human herpesvirus-8 (HHV-8) is the etiological agent of Kaposi's sarcoma (KS) and of some lymphoproliferative disorders of B cells. Most malignancies develop after long-lasting viral dormancy, and a preventing role for both humoral and cellular immune control is suggested by the high frequency of these pathologies in immunosuppressed patients. B cells, macrophages and dendritic cells of peripheral lymphoid organs and blood represent the major reservoir of HHV-8. Due to the dual role of B cells in HHV-8 infection, both as virus reservoir and as agents of humoral immune control, we analyzed the subset distribution and the functional state of peripheral blood B cells in HHV-8-infected individuals with and without cKS. METHODOLOGY/PRINCIPAL FINDINGS: Circulating B cells and their subsets were analyzed by 6-color flow cytometry in the following groups: 1- patients HHV-8 positive with classic KS (cKS) (nâ=â47); 2- subjects HHV-8 positive and cKS negative (HSP) (nâ=â10); 3- healthy controls, HHV-8 negative and cKS negative (HC) (nâ=â43). The number of B cells belonging to the preimmune/natural effector compartment, including transitional, pre-naïve, naïve and MZ-like subsets, was significantly higher among HHV-8 positive subjects, with or without cKS, while was comparable to healthy controls in the antigen-experienced T-cell dependent compartment. The increased number of preimmune/natural effector B cells was associated with increased resistance to spontaneous apoptosis, while it did not correlate with HHV-8 viral load. CONCLUSIONS/SIGNIFICANCE: Our results indicate that long-lasting HHV-8 infection promotes an imbalance in peripheral B cell subsets, perturbing the equilibrium between earlier and later steps of maturation and activation processes. This observation may broaden our understanding of the complex interplay between viral and immune factors leading HHV-8-infected individuals to develop HHV-8-associated malignancies.
Assuntos
Linfócitos B/imunologia , Infecções por Herpesviridae/imunologia , Herpesvirus Humano 8/imunologia , Sarcoma de Kaposi/imunologia , Idoso , Idoso de 80 Anos ou mais , Apoptose/imunologia , Subpopulações de Linfócitos B/imunologia , Subpopulações de Linfócitos B/metabolismo , Linfócitos B/metabolismo , Feminino , Citometria de Fluxo , Infecções por Herpesviridae/sangue , Infecções por Herpesviridae/virologia , Herpesvirus Humano 8/fisiologia , Interações Hospedeiro-Patógeno , Humanos , Imunofenotipagem , Masculino , Pessoa de Meia-Idade , Sarcoma de Kaposi/sangue , Sarcoma de Kaposi/virologia , Carga Viral/imunologiaRESUMO
Kaposi's sarcoma (KS) is a virally driven vascular tumor that usually has a multifocal origin, with multiple vascular nodules in the skin and other organs, particularly the gastrointestinal tract. Four variants of KS have been described: HIV-related, African, iatrogenic and classic. Primary classic KS of the head and neck is rare in any case, but KS arising in intraparotid lymph nodes, especially with no cutaneous involvement, is exceptionally rare. We report the case of an immunocompetent 71-year-old man who presented with a three-month history of a slowly progressive swelling in the right parotid region. After parotidectomy and histopathological diagnosis of lymph node localization of KS, a thorough dermatological examination did not reveal any skin lesions, and chest and abdominal computed tomography scans, esophagogastroduodenoscopy, and fecal occult blood test were all negative for visceral and other lymph node localizations. We here discuss the peculiarity of the presentation, the differential diagnosis, and the management strategy of such a rare disease.
Assuntos
Imunocompetência , Linfonodos/patologia , Neoplasias Parotídeas/diagnóstico , Sarcoma de Kaposi/diagnóstico , Idoso , Diagnóstico Diferencial , Humanos , Imuno-Histoquímica , Masculino , Procedimentos Cirúrgicos Bucais , Neoplasias Parotídeas/diagnóstico por imagem , Neoplasias Parotídeas/patologia , Neoplasias Parotídeas/cirurgia , Sarcoma de Kaposi/diagnóstico por imagem , Sarcoma de Kaposi/patologia , Sarcoma de Kaposi/cirurgia , UltrassonografiaRESUMO
The link between human herpesvirus 8 (KSHV) and Kaposi's sarcoma (KS) has been proven, but many important aspects including risk factors, genetic predisposition to tumor development, transmission of KSHV, and the pathogenic potential of different genotypes remain to be elucidated. Possible associations between clinical parameters and antibody levels, viral load fluctuations, and viral genotype were analyzed by quantitative real-time PCR, an in-house developed IFA assay, and sequence analysis of ORF K1-VR1 in blood, serum and saliva of 38 subjects with classic KS (cKS). KSHV lytic antibodies were significantly increased in stage IV compared to stage I and II patients (p = 0.006 and p = 0.041, respectively). KSHV blood, serum, and saliva viral load was comparable in all stages. The highest viral loads were detected in saliva, and they decreased in stages III-IV compared to stages I-II patients. Higher concentrations of lytic antibodies and higher viral loads were observed in fast progressing cKS patients, in whom KSHV detection from blood was also more frequent. Type A KSHV strain was almost exclusively present in rapid progressors (12/17 cases), while C type was mainly present in slow progressing patients (6/7 cases). Finally, detection of type A KSHV strain associated with higher blood viral loads. KSHV lytic antibody levels and viral load can be used to monitor clinical evolution of cKS. Infection supported by KSHV A subtype is associated with more rapid progressive disease. Careful monitoring and aggressive therapeutic protocols should be considered in patients with KSHV A-supported infection.
Assuntos
Herpesvirus Humano 8/classificação , Herpesvirus Humano 8/patogenicidade , Sarcoma de Kaposi/virologia , Anticorpos Antivirais/sangue , Sangue/virologia , Análise por Conglomerados , Progressão da Doença , Genótipo , Humanos , Filogenia , Reação em Cadeia da Polimerase/métodos , Saliva/virologia , Análise de Sequência de DNA , Soro/virologia , Estatística como Assunto , Fatores de Tempo , Carga Viral , Proteínas Virais/genéticaAssuntos
Endotélio Vascular/imunologia , Endotélio Vascular/patologia , Células-Tronco Mesenquimais/imunologia , Células-Tronco Mesenquimais/patologia , Sarcoma de Kaposi/sangue , Neoplasias Cutâneas/sangue , Antígeno AC133 , Idoso , Antígenos CD/metabolismo , Antígenos CD34/metabolismo , Biomarcadores/sangue , Estudos de Casos e Controles , Contagem de Células , Feminino , Glicoproteínas/metabolismo , Humanos , Masculino , Peptídeos/metabolismo , Sarcoma de Kaposi/diagnóstico , Sarcoma de Kaposi/imunologia , Neoplasias Cutâneas/diagnóstico , Neoplasias Cutâneas/imunologia , Receptor 2 de Fatores de Crescimento do Endotélio Vascular/metabolismoRESUMO
BACKGROUND: The cellular reservoirs of Kaposi's sarcoma-associated herpesvirus (KSHV) and the exact nature of the putative KSHV-infected circulating precursor of spindle cells of Kaposi's sarcoma (KS) still remain poorly defined. Because KS spindle cells are thought to be of endothelial origin, and because mature endothelial cells do not sustain persistent KSHV-infection, our attention was focalized on circulating hematopoietic precursors able to differentiate into endothelial lineage. METHODS AND FINDINGS: Late endothelial progenitor cells (late-EPCs) were cultured from the peripheral blood mononuclear cells of 16 patients with classic KS. The presence and load of KSHV genomes were analyzed by real-time polymerase chain reaction in DNA extracted from cells and supernatants of late-EPC cultures obtained from 7 patients. Endothelial colonies cultured from the peripheral blood of KS patients were found to satisfy all requisites to be defined late-EPCs: they appeared from the CD14-negative fraction of adherent cells after 11-26 days of culture, could be serially expanded in vitro, expressed high levels of endothelial antigens but lacked leukocyte markers. Late-EPC cultures were found to harbor KSHV-DNA at variable levels and to retain the virus after multiple passages in cells as well as in supernatants, suggesting that a quote of KSHV lytic infection may spontaneously occur. Lytic phase induction or hypoxia could amplify virus release in supernatants. CONCLUSION: Our results suggest that circulating endothelial progenitors from KS patients are KSHV-infected and support viral productive replication and may therefore represent potential virus reservoirs and putative precursors of KS spindle cells.