Infection with human herpesvirus type 8 and Kaposi's sarcoma in Sardinia.

BACKGROUND: A cross-sectional study was conducted in the provinces of Sassari (northern Sardinia, covered by a population-based cancer registry), and of Cagliari (southern Sardinia) to estimate the prevalence of infection with human herpesvirus type 8 (HHV8) and the incidence of classic Kaposi's sarcoma (KS) among HHV8-infected individuals. PATIENTS AND METHODS: Sera from 297 hospitalized persons potentially at risk of developing classic KS (i. e., those aged 50 years or older) were tested for antibodies against HHV8. HHV8 seroprevalence rates (with 95% confidence intervals-CI) and yearly incidence rates (IR/100,000) of KS were calculated according to age and sex. RESULTS: Of tested individuals, 32.0% had antibodies against HHV8 in Sassari and 30.0% in Cagliari. Estimated IR of KS among HHV8-positive persons and KS:HHV8 ratio were two times higher in Sassari (1:3,891) than in Cagliari (1:8,114), and higher in men (1:2,846 in Sassari; 1:5,483 in Cagliari) as compared to women (1:6,827 in Sassari; 1:12,489 in Cagliari). CONCLUSIONS: Although the overall prevalence of HHV8 seemed similar in Sassari and in Cagliari, the risk of KS was higher in Sassari, suggesting that different cofactor(s), or different distribution of the same cofactor(s) between the two provinces of Sardinia, might have played a role in KS development.

A psoriasis vulgaris protective gene maps close to the HLA-C locus on the EH18.2-extended haplotype.

We determined the molecular haplotypes of the HLA-A, HLA-C and HLA-B loci and the MHC class I-B-related (MIB) microsatellite in 179 unrelated psoriatic patients (72 familial cases) and in 120 controls. The HLA-A*3002-Cw*0501-B*1801-MIB1 haplotype showed a strong negative association with psoriasis vulgaris (PV) and in particular with familial PV, revealing the presence of a PV-protective gene. Analysis of association and linkage disequilibrium of the single alleles and the various two-three-four-locus segments of this haplotype indicated the presence of a protective gene telomeric to the HLA-C locus. This finding was confirmed in 13 informative multiplex PV families, in which at least one parent carried the EH18.2 haplotype. In two families, an affected sibling presented HLA-A/C recombination on the EH18.2 haplotype. A study of 12 polymorphic microsatellites in all members of the informative families, 145 PV patients, 120 controls and 32 EH18.2 homozygous healthy individuals demonstrated that the protection conferred by the EH18.2 haplotype lies within a 170 kb interval between the C143 and C244 loci, most probably in a 60 kb segment between the C132 and C244 loci.

Usefulness of 99mTc-tetrofosmin scintigraphy in different variants of Kaposi's sarcoma.

We investigated (99m)Tc-tetrofosmin scintigraphy in 27 patients with Kaposi's sarcoma: 20 had classic (CK), 5 AIDS-associated (AK) and 2 transplantation-associated (TK) variants. Twenty-three patients had clinically evident cutaneous and/or mucosal lesions, 9 of them with associated sarcomatous lymphadenopathy; 2 TK patients had only lymph nodes or other extracutaneous Kaposi sites. Both planar and SPECT (99m)Tc-tetrofosmin scintigraphies were performed in all cases and neck pinhole (P)-SPECT in selected patients. (99m)Tc-tetrofosmin uptake was observed in 88% of patients with clinically evident cutaneous and/or extracutaneous Kaposi lesions. Scintigraphy gave additional information on cutaneous lesion extent, particularly SPECT regarding deep invasion and subclinical sites in some cases. However, scintigraphy was less sensitive in the detection of small, isolated and scattered lesions. SPECT/P-SPECT were positive in 8/8 patients with sarcomatous lymph nodes, planar imaging in 5/8, ultrasonography in 7/8, while all procedures were negative in 6 other patients with reactive or HIV infection lymph nodes. SPECT demonstrated lymphadenopathy remission in 1 TK patient after immunosuppressive therapy modification and, like planar imaging, ascertained an associated lymphoma with (67)Ga-citrate combined. (99m)Tc-tetrofosmin scintigraphy, especially SPECT, can be useful both in the detection and staging of Kaposi sarcoma lesions as a complementary tool to clinical and other conventional diagnostic methods.

Psoriasis is associated with a SNP haplotype of the corneodesmosin gene (CDSN).

A psoriasis susceptibility locus has been mapped to the HLA region in the proximity of the HLA-C locus. This critical region also contains the CDSN gene coding for the corneodesmosin protein. In a case-control association study of psoriasis in the Sardinian population, we analyzed the allele distribution of eight intragenic SNPs (positions 619, 767, 1215, 1118, 1236, 1243, 1331, 1593) of the CDSN gene and the six haplotypes that are coded by these SNPs. Our study showed that these CDSN haplotypes are very stable and well-conserved in the Sardinian population. The CDSN2 haplotype was found to be associated with susceptibility to psoriasis. The association did not depend upon any one of the intragenic SNPs taken separately. At the HLA-C locus, the Cw6 and Cw7 alleles were dragged along by linkage disequilibrium with the CDSN2 haplotype and only revealed a trend towards association with the disease. Therefore, the intragenic SNPs of the CDSN gene and the HLA-Cw6 and Cw7 alleles are not directly involved in susceptibility to psoriasis. However, the strong association of the CDSN2 haplotype suggests a possible role for the CDSN gene and its chromosome region in susceptibility to psoriasis.

Direct correlation between human herpesvirus-8 seroprevalence and classic Kaposi's sarcoma incidence in Northern Sardinia.

The human herpesvirus-8 (HHV-8) has been associated with the development of Kaposi's sarcoma. A high incidence of classic Kaposi's sarcoma has been described in Sardinia, an island West of Italy's mainland. Different seroepidemiological analyses have reported that prevalence of HHV-8 infection varies worldwide: a high HHV-8 seroprevalence has been shown in Italy. The present survey was carried out to evaluate the correlation between HHV-8 infection and classic Kaposi's sarcoma incidence in northern Sardinia. Blood samples were collected from 226 healthy donors born and resident in five different areas of North Sardinia. Seroprevalence to HHV-8 was determined searching antibodies to viral lytic proteins by immunofluorescence in sera diluted at 1:10. Classic Kaposi's sarcoma incidence data spanning a period of 23 years were examined in the areas studied. The present screening revealed that seroprevalence was 35%, within a range of 15.3-46.3% in the five areas, although it should be considered that the seroprevalence to HHV-8 can be established more accurately by the combined use of different assays. Age emerged as an important risk factor. Indeed, subjects aged > 50 years showed a higher seroprevalence to HHV-8 as compared with younger individuals. A strong direct correlation between HHV-8 prevalence and classic Kaposi's sarcoma incidence has been also observed. The wide diffusion of HHV-8 in Sardinia appears to represent an important factor in the high incidence of classic Kaposi's sarcoma reported in the island. However, additional co-factors, such as age, sex, genetic traits, or viral strain pathogenicity, are likely to play a role in the development of the disease.

Acantholytic dyskeratotic epidermal naevus localized unilaterally in the cutaneous and genital areas.

A 38-year-old woman presented with unilateral lesions on the left side of the body and in the genital area. Clinically, the lesions showed a polymorphic pattern: brownish papules in the axilla, keratotic comedo-like papules on the hand and foot, and whitish papular plaques on the labia majora and anal canal. There was no family history of skin diseases. Histologically, cutaneous and mucosal specimens were characterized by acantholytic and dyskeratotic cells, corps ronds and grains in the parakeratotic zone, and by hyperkeratosis and parakeratosis. A diagnosis of epidermal naevus with acantholytic dyskeratosis was made.

High prevalence of antibodies to human herpesvirus 8 in relatives of patients with classic Kaposi's sarcoma from Sardinia.

A survey for antibodies to a recombinant small viral capsid antigen (sVCA) of human herpesvirus type 8 (HHV-8) was conducted in Sardinia, one of the world's highest incidence areas for classic Kaposi's sarcoma (KS). Prevalence of antibodies to HHV-8 sVCA was greatest in patients with KS (95%), followed by family members (39%) and a Sardinian control population age- and sex-matched to the relatives (11%). Within families, prevalence of antibodies was about equal among spouses, children, and siblings of KS patients, a finding that raises the possibilities of intrafamilial person-to-person or vertical transmission. Antibodies were detected 2-3 times more frequently in males than in females. The data show that prevalence of antibodies to HHV-8 sVCA correlates with the distribution of classic KS in a high- incidence area. Clustering of seroprevalence within some families suggests the presence of familial risk factors for active HHV-8 infection.

The role of occupation and a past history of malaria in the etiology of classic Kaposi's sarcoma: a case-control study in north-east Sardinia.

A case-control study was performed to determine the role of rural factors including occupation and previous malaria exposure in the development of classic Kaposi's sarcoma (CKS) in a high incidence area of Europe. The occurrence of CKS association with other malignancies was also examined. The results showed that the risk of having CKS was significantly increased in subjects farming cereals, while a previous history of malaria did not influence the risk of developing CKS. A near-significant increase in associated tumours was found.

Familial Kaposi's sarcoma: case reports and review of the literature.

We report 4 new families with Kaposi's sarcoma, occurring in 2 members of the same family (2 pairs of brothers, uncle and nephew and father and son) in a series of 160 patients with Kaposi's sarcoma. In addition, HLA typing was also carried out for 6 of the 8 patients. A detailed review of the literature is also presented. The total number of familial cases of Kaposi's sarcoma is low (only 30 cases are described); the great majority of these cases consist of siblings and Italians.