S. Ferrucci

Treatment of classical Kaposi's sarcoma with gemcitabine

Background: Several drugs are active in aggressive classical Kaposi’s sarcoma (CKS); chemotherapeutic agents with fewer side-effects, more rapid response and able to overcome resistance to previous treatment are advisable when treating patients in a second line. Gemcitabine, an analogue of deoxycytidine with cytotoxic activity in the treatment of solid tumours, has been found to have no serious side-effects. Objective: To evaluate the usefulness of treating patients affected by aggressive CKS with gemcytabine. Methods: Twelve patients with a recurrent aggressive form of CKS previously treated with chemotherapy were treated with gemcitabine. The drug was administered intravenously at the dose of 1.2 g/week for 2 weeks, followed by a 1-week interval, until maximal response was reached. Objective responses and toxicity were evaluated according to WHO criteria. Results: Eleven evaluable patients achieved an objective response: CR in 1/11 and PR in 10/11. Toxicity was limited. Conclusion: This study shows the usefulness of treating patients affected with aggressive CKS with gemcitabine, in order to obtain control of the disease and to reduce the related symptoms as well as to overcome a possible resistance to previous treatments.

Human herpesvirus 8 DNA in the skin and blood of patients with Mediterranean Kaposi's sarcoma: clinical correlations

Background: Kaposi’s sarcoma is a multifocal lympho-angioproliferative disease that appears in elderly subjects of Mediterranean origin (classical form), young Africans and immunodepressed patients (as a result of organ transplantation or AIDS). In 1994, DNA sequences of a new human herpesvirus, called HHV-8, were detected in skin lesions and peripheral blood of patients with AIDS-related Kaposi’s sarcoma by confirmational display analysis and polymerase chain reaction. Objective: As HHV-8 in peripheral blood mononuclear cells is detected in about 50% of Mediterranean Kaposi’s sarcoma patients and its presence fluctuates in time in the same patient, maybe its detection correlates with the clinical behaviour of the disease. Methods: By using routine and nested polymerase chain reaction we evaluated the presence of HHV-8-specific DNA sequences in the skin lesions, perilesional healthy skin and peripheral blood mononuclear cells of a group of 40 HIV-negative patients with Mediterranean Kaposi’s sarcoma. Results: HHV-8 DNA sequences have been found in 40/40 (100%) lesional skin of Mediterranean Kaposi’s sarcoma, in 35/40 (85%) perilesional apparently normal skin and in 24/40 (60%) peripheral blood monuclear cell samples. The results of polymerase chain reaction on peripheral blood monuclear cells were positive in 41% of the patients with slowly evolving disease as opposed to 74% of those with rapidly evolving disease, and in 47.6% of the patients with stage I–II disease as opposed to 73.6% of those with stage III–IV. Conclusion: The detection of HHV-8 in peripheral blood monuclear cells seems to correlate with the more aggressive stages and the rapid evolution behaviour of Mediterranean Kaposi’s sarcoma.

Human immunodeficiency virus negative Kaposi sarcoma and lymphoproliferative disorders

The concomitant occurrence of more than one primary neoplasm in the same individual has led researchers to seek possible common etiopathogenetic factors. Kaposi sarcoma (KS) is a multicentric neoplasm of vascular origin and perhaps viral etiology. Four forms of KS are known: classic or Mediterranean, endemic or African, posttransplant, and epidemic or acquired immunodeficiency syndrome‐associated KS. In its classic form KS mainly affects elderly people and often has a long and indolent course that occasionally allows other malignancies to appear. Previous studies of the possible association between human immunodeficiency virus (HIV) negative KS and lymphoproliferative disorders (LDs) have produced discordant results.

Allergological and Toxicological Aspects in a Multiple Chemical Sensitivity Cohort

Background. Multiple chemical sensitivity (MCS) is a chronic condition characterized by an exaggerated response to toxicants. We ascertained the prevalence of allergy to metals and toxicological aspects in MCS patients. Methods. We conducted a retrospective review of medical records of 41 patients with MCS. We performed patch testing (n = 21) for dental series and did lymphocyte transformation test (n = 18) for metals. We measured mercury in samples of blood (n = 19), urine (n = 19), saliva (n = 20), and scalp hair (n = 17) to investigate the association between mercury levels and cases of MCS. Results. The prevalence of metal immune hypersensitivity in a subset of 26 patients was 92.3 percent. Elevations of mercury occurred in 81.2 percent (26 of 32). The mean (±SD) in blood concentrations of mercury was 7.6 ± 13.6 μg/L; mean in urine was 1.9 ± 2.5 μg/L; mean in scalp hair was 2.2 ± 2.5 μg/g; mean in saliva was 38.1 ± 52.1 μg/L. Subgroup analyses showed that elevation of mercury levels in biological matrices were associated with mercury amalgams in patients with MCS (22 patients), compared with controls (8 patients) (odds ratio 11 : 95 percent confidence interval 1.5 to 81.6; P = 0.023). Conclusions. Our data show an increased prevalence of metal allergy and elevation of mercury levels in bioindicators among patients with MCS.

D-Dimer Plasma Levels Parallel the Clinical Response to Omalizumab in Patients with Severe Chronic Spontaneous Urticaria

Omalizumab is very effective in the majority of patients with severe chronic spontaneous urticaria (CSU), but its mechanism of action is still unclear. In CSU the coagulation cascade is activated with an intensity that parallels the disease severity, and elevated plasma D-dimer levels are associated with a poor response to both antihistamines and cyclosporin. We measured D-dimer plasma levels before and after the first administration of omalizumab in 32 patients with severe CSU. A number of clinical and laboratory parameters were recorded, including the urticaria activity score, presence of angioedema, disease duration, C-reactive protein, anti-nuclear, and anti-thyroid antibodies. Baseline D-dimer levels were elevated in 19 (59%) cases. Omalizumab induced a complete response in 25 patients (78%), in most cases already after the first administration. At baseline, 14/25 responders had increased D-dimer plasma levels versus 5/7 non-responders. All responders showed a dramatic decrease of D-dimer plasma levels after the first administration of the drug (from 1,024 ± 248 [mean ± SE] to 251 ± 30 ng/mL; p = 0.003). In contrast, non-responders did not show any reduction in D-dimer levels after omalizumab administration (from 787 ± 206 to 1,230 ± 429 ng/mL; p = ns). In conclusion, plasma levels of D-dimer are frequently elevated in patients with severe CSU before omalizumab administration and decrease according to the clinical response of the disease to the drug, suggesting a possible effect of omalizumab on coagulation activation and fibrin degradation in a subset of CSU patients.

Vinorelbine therapy for Kaposi's sarcoma in a kidney transplant patient

We report the case of a patient with Kaposis sarcoma after kidney transplantation. Despite the discontinuation of azathioprine and a reduction in the cyclosporin dosage, the disease continued to evolve, and antineoplastic treatment became necessary. After 14 cycles of vinorelbine chemotherapy, there was a 75% regression of the initial lesions, despite the continuation of cyclosporin A.

Serum heavy metals and childhood skin diseases

Editor, We were very interested in the views of Hon et al. (1) about the relationship between serum heavy metals’ concentrations in children with cutaneous manifestations and their conditions. We also agree with their opinion that there is no evidence to suggest that chelation therapy can ameliorate the clinical course of eczema in children with suspected (not proved) exposure to heavy metals. However, we would like to clarify that the serum levels of heavy metals do not accurately reflect the chronic environmental exposure to toxic heavy metals (2). From the data in Table 1 of their article, it appears that two heavy metals – lead (Pb) and mercury (Hg) – were measured in the serum of children instead of whole blood (1). It is well known that the pattern of distribution of lead is elective in red blood cells (more than 90%) (3–5). Studies on mercury disposition have also shown that distributions of mercury levels (both inorganic and organic mercury) between red blood cell (RBC) and plasma are different. In humans, the RBC/plasma ratio are about 1:1 (or 2:1) for inorganic mercury upon exposure to elemental mercury as well as for inorganic mercury compounds, whereas methyl mercury RBC/plasma ratio is 10:1 (6–8). The reasons for this discrepancy are that mercury in RBC is bound to glutathione as well as to hemoglobin (9). Thus, it would have been important, as well as clinically relevant, if the authors had measured both lead and mercury in fresh whole blood collected from 151 children with skin manifestations (1). In addition, it has been reported that the most important biomarker of exposure to cadmium in humans is elevated cadmium excretion in urine, a useful marker in monitoring environmental exposures to this toxicant (2). So, an association between serum level of cadmium and long-term low-level exposure to daily cadmium is questionable. The cross-sectional study by Hon et al. (1) with regard to a possible association between heavy metal exposures and skin disorders among children by measurements of metals is both interesting and timely. Further research is needed to develop the most favorable screening programs for heavy metal pollutants associated with skin disorders.