Prevalence Of Kaposi's Sarcoma Research Articles

Incidence and outcome of Kaposi sarcoma after hematopoietic stem cell transplantation: a retrospective analysis and a review of the literature, on behalf of infectious diseases working party of EBMT.

The incidence, the clinical characteristics, and the outcome of Kaposi sarcoma (KS) in patients after hematopoietic stem cell transplantation (HSCT) were assessed. During the period 1987-2018, 13 cases of KS were diagnosed, 3 females and 10 males, median age of 50 years, median time from HSCT of 7 months. KS had an incidence of 0.17% in allogeneic and 0.05% in autologous HSCT. HHV-8 was documented in eight of nine tumor tissue samples assessed. The organ involvement was: skin in nine, lymph nodes in six, oral cavity in four, and visceral in three patients, respectively; seven patients had >1 organ involved. Five patients had immunosuppression withdrawn, whereas four and three patients received radiotherapy and chemotherapy, respectively. Eight patients are alive (median follow-up 48 months, range 5-128), whereas five patients died after a median time of 8 months from the diagnosis of KS. However, no death was caused by KS. We conclude that the incidence of KS after HSCT is very low. Although KS can be managed with the reduction of immunosuppression, visceral forms may require chemotherapy and/or radiotherapy. The low prevalence of KS indicates that screening for HHV-8 serology and surveillance for HHV-8 viremia are not indicated in HSCT patients.

HIV associated cancers.

e18254 Background: The incidence or the prevalence of AIDS-defining cancers has reduced drastically (70% or more in the United States) since the introduction of three-drug antiretroviral therapy (ART) in the mid-1990s. However, the data from the inpatient sample is lacking. Methods: This is a retrospective analysis using data from the 2014 National Inpatient Sample database. We identified patients with either primary or secondary diagnosis of human immunodeficiency virus (HIV). Then we identified patients with various cancers including AIDS-defining cancers. Afterward, we ran logistic regression to check the degree of association between the diagnosis of each cancer with the diagnosis of HIV during the identified hospitalizations. We also assessed the prevalence of each of the cancer among the identified HIV patients, as well as the mortality in this cohort. Results: A total of 115955 hospitalizations with a diagnosis of HIV were identified. Among them, there were 6985 hospitalizations with Non-Hodgkin lymphoma, 2230 with rectal and anal cancer, 1170 with Kaposi sarcoma, 870 with head and neck cancer, 865 with skin cancer, 840 with cervical cancer. Logistic regression showed odds ratio (OR) of 1632.857 (95% CI 1168 - 2284, p < 0.01) for Kaposi sarcoma, 9.13 (95% CI 5.7-14.5, p-value < 0.01) for other male cancer, 8.34 (95% CI 7.68-9.06; p-value < 0.01) for Non-Hodgkin's lymphoma, 6.65 (95% CI was 5.5-8, p-value < 0.01) for Hodgkin's lymphoma, 5.04 (95% CI 4.5-5.6 p < 0.01) for rectal and anal cancer, 2.33 (95% CI 1.9-2.8, p < 0.01) for cervical cancer. Mortality was statistically significant with liver cancer, lung cancer, brain cancer, Hodgkin lymphoma, and Kaposi sarcoma. Conclusions: The prevalence of Kaposi sarcoma, Non-Hodgkin lymphoma, and cervical cancer are found to be high among hospitalized patients with HIV most likely because of nonadherence to their HIV medications. Future studies to check their correlation of these cancers with disease control is required. It is interesting to note that the prevalence of rectal and anal cancer, head and neck cancer, and skin cancer is high in this cohort.

Kaposi Sarcoma in HIV-positive Solid-Organ Transplant Recipients: A French Multicentric National Study and Literature Review.

Kaposi sarcoma is a vascular tumor related to herpesvirus-8 and is promoted by immunosuppression. For the last 15 years, human immunodeficiency virus (HIV) patients have had access to organ transplantation. The dual immunosuppression of HIV and immunosuppressive treatments might increase the risk and severity of Kaposi sarcoma. We conducted a multicentric retrospective study by collecting cases from French databases and society members of transplanted patients, among which 7 HIV-infected patients who subsequently developed Kaposi sarcoma were included. In the CRISTAL database (114 511 patients) and the DIVAT (Données Informatisées et VAlidées en Transplantation) database (19 077 patients), the prevalence of Kaposi sarcoma was 0.18% and 0.46%, respectively, in transplanted patients; these values compare with 0.66% and 0.50%, respectively, in transplanted patients with HIV. The median time from HIV infection to Kaposi sarcoma was 20 years. Kaposi sarcoma occurred during the first year after transplantation in most cases, whereas HIV viral load was undetectable. Only 2 patients had visceral involvement. Five patients were treated with conversion of calcineurin inhibitor to mammalian target of rapamycin inhibitor, and 5 patients were managed by decreasing immunosuppressive therapies. At 1 year, 4 patients had a complete response, and 3 had a partial response. In our study, Kaposi sarcoma in transplanted patients with HIV did not show any aggressive features and was treated with the usual posttransplant Kaposi sarcoma management protocol.

Kaposi Sarcoma of the Gastrointestinal Tract in the Era of Combination Anti-Retro Viral Therapy

AIDS related Kaposi sarcoma (KS) is the most common tumor identified in HIV patients. Classically presents as cutaneous vascular endothelial tumors associated with HHV-8 infection. Visceral manifestation in the absence of cutaneous manifestation is uncommon. The annual incidence of Kaposi sarcoma in the United States has been steadily declining with the advent of highly potent combination anti-retroviral therapy (ART). We present an unfortunate case of a HIV positive male with extensive gastrointestinal Kaposi sarcoma. 50 year old male with prior diagnosis of HIV, non-compliant with ART presented with weight loss, abdominal pain, distention, vomiting and diarrhea for 3 months. Examination revealed a cachectic appearing male, moderate abdominal distention with mild diffuse tenderness throughout the abdomen. No cutaneous lesions identified on examination. Blood work significant for anemia, leukopenia, elevated HIV viral load >210,000 with a low CD4 count of 100. Stool studies for ova and parasites were negative. CT imaging revealed long segment mural thickening extending from the terminal ileum, descending colon to the rectum with multiple dilated fluid filled loops of small bowel with scattered large to small extensive mesenteric lymphadenopathy. EGD revealed multiple raised red to purplish nodular lesions in the oropharynx, esophagus, stomach and duodenum. Similar lesions were found on colonoscopy throughout the colon and terminal ileum associated with significant edema and narrowing in the region of the terminal ileum and sigmoid colon (Image 1). Biopsy from various sites revealed spindle cell proliferation with extravasation of red blood cells (Image2). Immunostain positive for HHV-8 consistent with the diagnosis of Kaposi's sarcoma (Image3). Patient improved on ART and was later discharged home with plans for outpatient chemotherapy. Significant advancements in the field of ART has led to a decrease in the prevalence of Kaposi sarcoma in the 21st century. Incidence of KS has shown a significant decline in United states from 47 cases per 1 million people in the 1990 to 6 cases per 1 million people because of highly effective treatments available for HIV/AIDS. Gastrointestinal manifestations commonly reported are abdominal pain, malabsorption, bleeding and rarely obstruction. GI manifestation can be easily missed in the absence of cutaneous manifestation, hence a high degree of suspicion can lead to early diagnosis and improved outcomes.2984_A Figure 1. Colonoscopy images showing multiple raised red to purple nodules throughout the colon2984_B Figure 2. H&E stain of the duodenal mucosa showing scattered bland spindle cell proliferation with extravasated red blood cells.2984_C Figure 3. Immunostain positive for HHV -8

A prospective ascertainment of cancer incidence in sub‐Saharan Africa: The case of Kaposi sarcoma

In resource‐limited areas, such as sub‐Saharan Africa, problems in accurate cancer case ascertainment and enumeration of the at‐risk population make it difficult to estimate cancer incidence. We took advantage of a large well‐enumerated healthcare system to estimate the incidence of Kaposi sarcoma (KS), a cancer which has become prominent in the HIV era and whose incidence may be changing with the rollout of antiretroviral therapy (ART). To achieve this, we evaluated HIV‐infected adults receiving care between 2007 and 2012 at any of three medical centers in Kenya and Uganda that participate in the East Africa International Epidemiologic Databases to Evaluate AIDS (IeDEA) Consortium. Through IeDEA, clinicians received training in KS recognition and biopsy equipment. We found that the overall prevalence of KS among 102,945 HIV‐infected adults upon clinic enrollment was 1.4%; it declined over time at the largest site. Among 140,552 patients followed for 319,632 person‐years, the age‐standardized incidence rate was 334/100,000 person‐years (95% CI: 314–354/100,000 person‐years). Incidence decreased over time and was lower in women, persons on ART, and those with higher CD4 counts. The incidence rate among patients on ART with a CD4 count >350 cells/mm3 was 32/100,000 person‐years (95% CI: 14–70/100,000 person‐years). Despite reductions over time coincident with the expansion of ART, KS incidence among HIV‐infected adults in East Africa equals or exceeds the most common cancers in resource‐replete settings. In resource‐limited settings, strategic efforts to improve cancer diagnosis in combination with already well‐enumerated at‐risk denominators can make healthcare systems attractive platforms for estimating cancer incidence.

AIDS‐related Kaposi's sarcoma in Brazil: trends and geopolitical distribution

AIDS-related Kaposi's sarcoma (KS) is a unique model of the relationship between viral infection, immunity, environmental, and genetic factors in viral cancers. The goal was to determine the distribution of KS cases among Brazilian geopolitical regions, looking at the ecological relationship with median CD4 cell count. Ecological study using Brazilian National Diseases Reporting Databases: 1982-2009. Subjects ≥ 13 years of age who have KS cited in their AIDS reporting form were selected, and demographic and HIV exposure data were collected. We found 11,731 KS cases in the period, with a prevalence of 2.4% among AIDS cases; 88% were male, and 68% lived in the Southeast region, which accounted for 59% of AIDS cases. The regional and national prevalence trends were similar, although the highest proportion among women was found in the North region, which has the lowest number of both AIDS and KS cases. Heterosexual transmission accounted for 87% of HIV among women compared to 18% among men. Fifty-seven percent of all KS cases were diagnosed before antiretroviral therapy (ART). Injection drug use accounted for 11% of KS cases. Median survival was 472 days before the ART era and 1482 after it (P < 0.001). Median CD4 counts increased in all regions in the period as ART coverage expanded, and a resulting correlating decline in KS cases was observed. Prevalence of KS declined after the introduction of ART in all regions of Brazil, suggesting individual protection conveyed by ART.

Kaposiʼs Sarcoma

A 56 y/o HIV-infected African American male presented with non-bloody diarrhea for 3 days. He also complained of diffuse abdominal pain, worse in the epigastric area, for the past 4 months and associated with nausea and intermittent non-bloody, non-bilious vomiting, especially after eating solid food. He admits to 33 pounds weight loss over 6 months. He denies any fever or chills, any rash or skin lesions. His HIV risk factor was intravenous drug use. His CD4 count was 46 cells/mm3 and HIV RNA was 123,664/ml. He was non-compliant with HAART. Co-morbid conditions included polysubstance abuse and HCV infection. There was moderate epigastric tenderness on physical examination. Laboratory studies showed anemia, stool studies were negative for enteric pathogens, but stool occult blood was positive. A CT scan of abdomen with contrast showed prominent lymph nodes in the paraesophageal and retroperitoneal areas. An EGD showed a large, fungating, circumferential mass with no bleeding in the gastric antrum. Biopsies were performed and the pathologic diagnosis was Kaposi's sarcoma (KS). Immunohistochemical stains for HHV-8 were positive.Figure: [648]Conclusion: In the pre-HAART era, the prevalence of KS was over 20,000 times higher in patients with AIDS than in the general population. The use of HAART has led to a decline in the prevalence of AIDS-related KS, but the benefit is limited to patients who adhere to therapy. Skin involvement is characteristic but extracutaneous spread is common, particularly to the oral cavity, GI tract, and respiratory tract. Before the HAART era, GI tract involvement was 40% and occurred without cutaneous disease in many cases. Patient may be asymptomatic or can have weight loss, nausea, vomiting, abdominal pain, malabsorption, GI hemorrhage, intestinal obstruction, or diarrhea. The visual lesions are characteristic and the diagnosis can be confirmed on histopathology. The staging system, developed by AIDS Clinical Trials Group (ACTG) of the National Institute of Health, which consists of 3 parameters: extent of tumor, Immune status and severity of systemic illness, divides patients into good and poor risk categories. Treatment depends on the presence or absence of clinical symptoms as well as on CD4 count, HIV viral load and presence of HHV-8. For symptomatic patients, the treatment is chemotherapy with liposomal anthracyclines as well as antiretroviral therapy to optimize cellular immune function.

Detection of human herpesvirus 8 by quantitative polymerase chain reaction: development and standardisation of methods

BackgroundHuman herpesvirus 8 (HHV-8), the aetiological agent of Kaposi’s sarcoma (KS), multicentric Castleman’s disease (MCD), and primary effusion lymphoma (PEL) is rare in Australia, but endemic in Sub-Saharan Africa, parts of South-east Asia and Oceania. While the treatment of external KS lesions can be monitored by clinical observation, the internal lesions of KS, MCD and PEL require extensive and expensive internal imaging, or autopsy. In patients with MCD and PEL, if HHV-8 viraemia is not reduced quickly, ~50% die within 24 months. HHV-8 qPCR is a valuable tool for monitoring HHV-8 viraemia, but is not available in many parts of the world, including those with high prevalence of KS and HHV-8.MethodsA new molecular facility with stringent three-phase workflow was established, adhering to NPAAC and CLSI guidelines. Three fully validated quantitative assays were developed: two for detection and quantification of HHV-8; one for GAPDH, necessary for normalisation of viral loads in tissue and peripheral blood.ResultsThe HHV-8 ORF73 and ORF26 qPCR assays were 100% specific. All qPCR assays, displayed a broad dynamic range (102 to 1010 copies/μL TE Buffer) with a limit of detection of 4.85x103, 5.61x102, and 2.59x102 copies/μL TE Buffer and a limit of quantification of 4.85x103, 3.01x102, and 1.38x102 copies/μL TE Buffer for HHV-8 ORF73, HHV-8 ORF26, and GAPDH respectively.The assays were tested on a panel of 35 KS biopsies from Queensland. All were HHV-8 qPCR positive with average viral load of 2.96x105 HHV-8 copies/μL DNA extract (range: 4.37x103 to 1.47x106 copies/μL DNA extract): When normalised these equate to an average viral load of 2.44x104 HHV-8 copies/103 cells (range: 2.20x102 to 7.38x105 HHV-8 copies/103 cells).ConclusionsThese are the first fully optimised, validated and MIQE compliant HHV-8 qPCR assays established in Australia. They worked well for qualitative detection of HHV-8 in archival tissue, and are well-suited for quantitative detection in whole blood. They are now available for research, for clinical diagnosis of HHV-8 infection, and for monitoring treatment efficacy.

Human herpesvirus-8 in northwestern China: epidemiology and characterization among blood donors

BackgroundHuman herpes virus 8 (HHV-8) is the etiologic agent associated with development of classical, AIDS-related, iatrogenic, and endemic Kaposi's sarcoma (KS). Several studies provide strong evidence that HHV-8 can be transmitted by blood transfusion. We evaluated the seroprevalence and potential risk factors of HHV-8 infection in blood donors in one region. We surveyed HHV-8 infection among 4461 blood donors in Xinjiang, China, a unique endemic area for HHV-8 and KS.ResultsThe HHV-8 seroprevalence was higher in local minority groups which comprise most KS cases in China, than in Han people. HHV-8 prevalence was 18.6% in the Han ethnic group, 25.9% in Uygur subjects, 29.2% in Kazak subjects, 36.8% in Mongolian subjects, and 21.9% in other ethnic groups. In several subgroups, the time of donation of whole blood seemed to be a risk factor. In HHV-8-seropositive subjects, a larger fraction of local minorities (23.9%) had high HHV-8 titers than that of Han subjects (9.2%). HHV-8 infection was associated with ethnicity and residence.ConclusionHHV-8 seroprevalence was significantly high among blood donors in Xinjiang, where the prevalence of KS correlates with HHV-8 prevalence and titers in Uygur and Kazak ethnic groups. Blood exposure represented by the frequency of blood donation indicated a possible blood-borne transmission route of HHV-8 in Xinjiang. Detecting anti-HHV-8 antibodies before donation in this region is therefore important.

Impact of HIV Infection and Kaposi Sarcoma on Human Herpesvirus-8 Mucosal Replication and Dissemination in Uganda

IntroductionKaposi sarcoma (KS) is the leading cause of cancer in Uganda and occurs in people with and without HIV. Human herpesvirus-8 (HHV-8) replication is important both in transmission of HHV-8 and progression to KS. We characterized the sites and frequency of HHV-8 detection in Ugandans with and without HIV and KS.MethodsParticipants were enrolled into one of four groups on the basis of HIV and KS status (HIV negative/KS negative, HIV positive/KS negative, HIV negative/KS positive, and HIV positive/KS positive). Participants collected oral swabs daily and clinicians collected oral swabs, anogenital swabs, and plasma samples weekly over 4 weeks. HHV-8 DNA at each site was quantified by polymerase chain reaction (PCR).Results78 participants collected a total of 2063 orals swabs and 358 plasma samples. Of these, 428 (21%) oral swabs and 96 (27%) plasma samples had detectable HHV-8 DNA. HHV-8 was detected more frequently in both the oropharynx of persons with KS (24 (57%) of 42 persons with KS vs. 8 (22%) of 36 persons without, p = 0.002) and the peripheral blood (30 (71%) of 42 persons with KS vs. 8 (22%) of 36 persons without, p<0.001). In a multivariate model, HHV-8 viremia was more frequent among men (IRR = 3.3, 95% CI = 1.7–6.2, p<0.001), persons with KS (IRR = 3.9, 95% CI = 1.7–9.0, p = 0.001) and persons with HIV infection (IRR = 1.7, 95% CI = 1.0–2.7, p = 0.03). Importantly, oral HHV-8 detection predicted the subsequent HHV-8 viremia. HHV-8 viremia was significantly more common when HHV-8 DNA was detected from the oropharynx during the week prior than when oral HHV-8 was not detected (RR = 3.3, 95% CI = 1.8–5.9 p<0.001). Genital HHV-8 detection was rare (9 (3%) of 272 swabs).ConclusionsHHV-8 detection is frequent in the oropharynx and peripheral blood of Ugandans with endemic and epidemic KS. Replication at these sites is highly correlated, and viremia is increased in men and those with HIV. The high incidence of HHV-8 replication at multiple anatomic sites may be an important factor leading to and sustaining the high prevalence of KS in Uganda.

Kaposi sarcoma in calabar, southern Nigeria.

There has been an increase in the prevalence of Kaposi sarcoma (KS) with the emergence of Human Immunodeficiency Virus (HIV). Patients with histologic diagnosis of KS seen in the University of Calabar Teaching Hospital, Calabar between January 2007 and December 2008 were studied. Diagnosis of HIV was based on enzyme linked immunosorbent assay (ELISA). In total, 15 patients (10 males, 5 females, M: F=2:1) presented with KS and accounted for 33.0% of total skin malignancy and ranked second after squamous cell carcinoma, 42.0%. Their ages ranged from 5 and 60 years (mean 37.5 years). Twelve patients (M=8, F=4), 80%, were HIV seropositive, while 3 (M=2, F=1) were HIV seronegative. The lower limb was the commonest affected site, 57.9%. The most common clinical type was HIV related KS. Ignorance, sociocultural beliefs, poverty, late presentation were underlying issues.

AIDS-associated Kaposi's sarcoma in Sokoto, Nigeria.

Since the advent of the HIV/AIDS pandemic, Kaposi's sarcoma (KS) is now seen in places not previously considered endemic for this disease. In Nigeria, the African-endemic KS had been known to be prevalent in the southern parts of the country, particularly the southeast. Until now, reports on the disease from northern Nigeria are few. To describe the prevalence ofKaposi's sarcoma in Sokoto, northwestern Nigeria. A retrospective review of 27 cases of histologically confirmed KS seen over an 11-year period (Jan.1994-Dec.2004) at the Usmanu Danfodiyo University Teaching Hospital (UDUTH), Sokoto, Northwestern Nigeria. The average hospital incidence of KS in this review was 2.5 cases per annum (27 cases in 11 years). The modal age was the 4th decade of life (range 18-70 years). Fifteen percent were females; M: F = 5.8: 1. There was no case of childhood involvement identified. More cases of the disease were HIV-positive (59.3%). The commonest symptom was cutaneous nodules in 96.3% of cases. The body region with the highest affectation of the lesions was the lower limb (70.4%). Kaposi's sarcoma is still uncommon in the northwestern region of Nigeria. The epidemic variant of the disease predominates among the few cases diagnosed. The finding of nodular lesions and/or indurated leg swelling in any adult male in our environment must be considered to be KS until histologically investigated.

Prevalence And Characteristics Of Human Immunodeficiency Virus Associated Kaposi Sarcoma

Skin manifestations are frequently associated with the Human Immunodeficiency Virus (HIV) infection. Kaposi's Sarcoma (KS) is one of the most common cancers seen in people with HIV, and is an AIDS defining illness. The incidence of HIV associated Kaposi's Sarcoma has decreased since the advent of antiretroviral drugs in developed countries. This is not the case with Cameroon people present with generalized and aggressive KS. This study reviews the characteristics and prevalence of KS and the impact of antiretroviral drugs in a treatment center in YaoundE, Cameroon. The prevalence of KS among HIV infected patients was found to be 10.0%. Both sexes were equally affected unlike in endemic KS which is more common in males. Most patients had generalized disease, and death occurred within six months of diagnosis. These cases were associated with low CD4 cell count, anemia and low platelet counts. Patients with less extensive lesions, had tumor regression ranging from partial to total when Highly Active Antiretroviral Therapy was administered. Early diagnosis and antiretroviral therapy will decrease morbidity, mortality and severe Immune Reconstitution Inflammatory syndrome (IRIS) common in patients with aggressive HIV associated KS.

US1 HIV – changing patterns in HAART era, patients’ quality of life and occupational risks

Oral manifestations are early and important indicators of HIV‐infection. Several lesions with strong association to HIV infection have been described: oral candidiasis (OC), oral hairy leukoplakia (OHL), Kaposi's sarcoma (KS), Non‐Hodgkin‐Lymphoma (NHL), necrotising ulcerative gingivitis and periodontitis. These lesions may be present in up to 50% of patients with HIV‐infection and up to 80% of those with AIDS. Changing patterns in HAART era: With the advent of highly active antiretroviral therapy (HAART) the prevalence of OC, OHL and HIV – associated periodontal disease has decreased in adults. The prevalence of KS has not changed. However, there has been an increase in HPV‐associated oral lesions (papillomas, condylomas and focal epithelial hyperplasia) and HIV‐related salivary gland disease. In children receiving HAART no change in the prevalence of HIV‐related oral lesions has been found. Quality of life: The presence of oral lesions has a marked impact on health related quality of life. HIV‐associated orofacial lesions may lead to facial disfigurement (KS, NHL) or may impair speech and swallowing. Consequently, weight loss and pain may be result. Studies have shown that patients with OC, angular cheilitis and OHL have a high score of decayed teeth (DMFT). Xerostomia and taste disturbances may also be factors with impact on quality of life. Occupational risks: Occupational exposure to HIV has resulted in 57 documented cases of HIV sero‐conversion among healthcare workers in the US (December 2001). Exposure to HBV and HCV carries a much higher risk of occupational infection than that for HIV‐exposure.

Role of environmental factors in the pathogenesis of classic and African-endemic Kaposi sarcoma

Kaposi sarcoma (KS) is a mesenchymal tumour associated with human herpesvirus-8 (HHV-8) infection. However, the incidence of HHV-8 infection is far higher than the prevalence of KS, suggesting that viral infection per se is not sufficient for the development of aggressive phenotype and that one or more additional cofactors are required. The great geographical variation in African-endemic and classic KS incidence points to a role for environmental factors in the etiology of Kaposi sarcoma. However, there are few unequivocably established environmental factors involved in KS pathogenesis. This review focuses on the environmental factors thought to be associated with KS, more particularly iron exposure and facilitation of transmission of HHV-8 infection by contact with blood-sucking arthropods.

Biology of Kaposi's sarcoma-associated herpesvirus

Kaposi's sarcoma-associated herpesvirus (KSHV) or human herpesvirus-8 (HHV-8) is a newly identified herpesvirus. KSHV is an important pathogen capable of causing disease that affects all age groups worldwide. KSHV is etiologically associated with all forms of Kaposi's sarcoma (KS), body cavity lymphomas, and multicentric Castleman disease (MCD). The use of highly active antiretroviral therapy (HAART) since 1996 has markedly reduced the prevalence of KS in western countries, but because 99% of the 40 million patients with AIDS in the world cannot afford HAART, KSHV pathogenesis is still a very common problem. In this chapter, we delineate some of the latest findings about KSHV infection and pathogenesis.

Iron: a target for the management of Kaposi's sarcoma?

BackgroundKaposi's sarcoma (KS) is a mesenchymal tumour associated with human herpesvirus-8 infection. However, the incidence of human herpesvirus-8 infection is far higher than the prevalence of KS, suggesting that viral infection per se is not sufficient for the development of malignancy and that one or more additional cofactors are required.DiscussionEpidemiological data suggest that iron may be one of the cofactors involved in the pathogenesis of KS. Iron is a well-known carcinogen and may favour KS growth through several pathways. Based on the apoptotic and antiproliferative effect of iron chelation on KS cells, it is suggested that iron withdrawal strategies could be developed for the management of KS. Studies using potent iron chelators in suitable KS animal models are critical to evaluate whether iron deprivation may be a useful anti-KS strategy.SummaryIt is suggested that iron may be one of non-viral co-factors involved of KS pathogenesis and that iron withdrawal strategies might interfere with tumour growth in patients with KS.

Kaposi sarcoma in kidney transplanted patients.

Newly developed malignancies in kidney transplanted patients are one of the complications attributed to immunosuppression. Kaposi sarcoma is an unusual malignancy in general population, but may develop in kidney transplanted patients with highly varying prevalence. Our aim is to evaluate the prevalence, clinical manifestations, and outcome of Kaposi sarcoma in kidney transplanted patients. Five hundred and eighty cases (330 male, 250 female) with a mean age of 38.2 were followed for 36 months (range 9 months to 10 years), visiting every two months. History taking and physical examination with emphasis on skin and mucosa were taken. Biopsy of suspicious sin, mucosal, and visceral lesions assigned by other paraclinical methods was performed. Except 7 cases which were HLA identical to donors, all patients were managed with cyclosporine, Azathioprine and Prednisolone. Fourteen patients (2.2%) developed Kaposi sarcoma (biopsy documented which constituted 60% of all post-transplantation malignancies. They were 11 males and 3 females with a mean age of 41 years. Sarcoma developed 8 to 31 months after transplantation with an average of 18 months. Of these patients, 13 had skin involvement that one of them had pulmonary involvement too. Another patient had only abdominal involvement. Azathioprine was discontinued all patients, and cyclosporine was reduced in skin affected patients. In patients with visceral involvement cyclosporine was discontinued and then chemotherapy was initiated. All 3 patients with visceral involvement didn't respond to chemotherapy and expired after 6 months. Of 11 patients with skin involvement, one had complete and 2 had incomplete remission of whom, one expired due to acute rejection. Renal function in 8 patients was acceptable, but 2 had impaired renal function, yet didn't need dialysis. Prevalence of Kaposi sarcoma in our patients is more than western countries. Visceral involvement is uncommon. But has poor prognosis. Reducing immunosuppression with discontinuation of azathioprine and significant reducing cyclosporine dosage can cease skin evolvement, with preserving renal function in most of the patients.

Kaposi's sarcoma in renal transplant patients: experience at the Cruces Hospital in Bilbao.

Kaposi's sarcoma (KS) in renal transplant recipients (RTRs) probably arises from a complex interplay of multiple factors. In order to analyze the prevalence of KS in patients transplanted at the Cruces Hospital in Bilbao, together with their clinical features, treatment, and etiologic factors, we performed a study using the registry of RTRs in our center. The records of 1,230 kidney transplant patients at the Cruces Hospital between 1979 and 1998 were reviewed. Immunosuppressive therapy was reduced once a diagnosis of KS was made. A nested polymerase chain reaction was used to detect human herpesvirus 8 (HHV-8) DNA in the biopsy tissue. The DNA was extracted from fresh tissue (n = 2) or from formalin-fixed, paraffin-embedded specimens (n = 5). Six cases of KS were diagnosed. All patients with cutaneous KS improved with a reduction in immunosuppressive drugs. HHV-8 was detected in 100% (2/2) of the frozen biopsies and 20% (1/5) of the formalin-fixed samples investigated. Our experience indicates that a continuous state of immunodeficiency is important for the development of KS in RTRs. The association, previously described between HHV-8 and transplant-associated KS, also exists in the studied population.

Kaposi's sarcoma and other manifestations of human herpesvirus 8

Kaposi's sarcoma (KS) was described by Moritz Kaposi in 1872 and was known for an entire century as a rare disorder of older men usually of Eastern European, Mediterranean, and/or Jewish origin. In the early 1980s, the prevalence of KS began to increase dramatically and soon became the most common malignancy in patients with AIDS, especially those who were male homosexuals. In 1994, a new human herpesvirus (HHV) was found to be present in almost 100% of KS lesions. This virus was found to be a gammaherpesvirus, closely related to Epstein-Barr virus, and was designated HHV-8. Subsequently, HHV-8 DNA was found in almost all specimens of classic KS, endemic KS, and iatrogenic KS, as well as epidemic KS (ie, AIDS KS). It is now believed that HHV-8 is necessary, but not sufficient, to cause KS and that other factors such as immunosuppression play a major role. The use of highly active antiretroviral therapy (HAART) since 1996 has markedly reduced the prevalence of AIDS KS in western countries, but because 99% of the 40 million patients with AIDS in the world cannot afford HAART, KS is still a very common problem. Primary effusion lymphoma and multicentric Castleman's disease are also thought to be due to HHV-8. Although HHV-8 DNA has been described in a number of other cutaneous disorders, there is little evidence that HHV-8 is of etiologic significance in these diseases. The mechanism by which HHV-8 causes KS, primary effusion lymphoma, and multicentric Castleman's disease is not well understood but is thought to involve a number of molecular events, the study of which should further our understanding of viral oncology. (J Am Acad Dermatol 2002;47:641-55.)Learning objective: At the completion of this learning activity, participants should be familiar with Kaposi's sarcoma and other manifestations of human herpesvirus 8.