Neutrophil elastase in patients with homozygous beta-thalassemia and pseudoxanthoma elasticum-like syndrome.

In this study we investigated the possible role of neutrophil (PMN) elastase and its natural inhibitor, alpha1-proteinase inhibitor (alpha1-PI) in the pathogenesis of the pseudoxanthoma elasticum (PXE)-like syndrome which is found in patients with homozygous beta-thalassemia. We studied 30 beta-thalassemia homozygotes with the PXE-like syndrome [PXE(+) group], 20 beta-thalassemia homozygotes without this syndrome [PXE(-) group] and 15 healthy controls. Plasma PMN elastase concentration in the PXE(+) and in the PXE(-) group was 136.4 +/- 89 and 163.8 +/- 126 microg/L, respectively (P > 0.05). In the control group, the concentration was 42.9 +/- 16.8 microg/L (P < 0.01 for the comparison with both patients' groups). The plasma alpha1-PI concentration in the PXE(+) and in the PXE(-) group was 2.28 +/- 0.75 and 2.6 +/- 0.96 g/L, respectively (P > 0.05). Using logistic regression, we studied the prognostic value for PXE of the following independent variables: number of transfusions, chelation therapy, mean hemoglobin concentration, PMN elastase concentration, alpha1-PI concentration, chronic transaminase elevation, and positivity for anti-HCV. None of the above variables was found to have significant prognostic value for the PXE. Plasma PMN elastase concentration is elevated in all beta-thalassemia homozygotes; its role in the pathogenesis of the PXE-like syndrome in beta-thalassemia can not be established, but our findings suggest that neutrophils of beta-thalassemia patients are activated, since PMN elastase is a marker of neutrophil activation.

Arterial calcifications in beta-thalassemia.

The purpose of this study was to define the incidence of arterial calcifications in patients with beta-thalassemia. Beta-thalassemia patients have been shown to present a high prevalence of angioid streaks and skin lesions characteristic of pseudoxanthoma elasticum (PXE). Given the fact that vascular involvement in the form of arterial calcifications is also a common manifestation of PXE, the authors investigated radiographically the presence of arterial calcifications in beta-thalassemia patients. They studied 40 patients with beta-thalassemia over 30 years of age. Forty healthy, age- and sex-matched subjects were chosen as a control group. Radiographs of the tibias were performed in order to disclose arterial calcifications. The occurrence of PXE skin lesions and of angioid streaks (AS) was also investigated. Arterial calcifications were detected in the posterior tibial artery in 22 (55%) beta-thalassemia patients and in six (15%) controls (P < 0.01 for the comparison). PXE skin lesions and AS were found in eight (20%) and 21 (52%) patients respectively. A total of 34 patients (85%) had at least one of the three lesions, namely, arterial calcifications, angioid streaks, and/or PXE-like skin lesions. Stepwise logistic regression analysis did not reveal prognostic value in independent variables such as transfusions, chelation therapy, pseudoxanthoma elasticum skin lesions and/or angioid streaks, diabetes, hemoglobin, serum ferritin, and uric acid. It was concluded that arterial calcifications are common in older beta-thalassemia patients. This finding could be a manifestation of an acquired PXE syndrome associated with beta-thalassemia, and consequently, vascular events complicating PXE should be expected in these patients.

Angioid streaks in homozygous beta thalassemia.

One hundred patients with homozygous beta thalassemia (62 had beta thalassemia major and 38 had beta thalassemia intermedia) were examined by ophthalmoscopy for angioid streaks. Angioid streaks were found in 20 patients from both the beta thalassemia major and beta thalassemia intermedia groups (nine and 11 patients, respectively). A positive correlation was found between age and angioid streaks (P = .0017), as was a difference in the prevalence of angioid streaks between the two forms of the disease (P = .079). Additionally, a significant correlation was noted between chelating therapy and the prevalence of angioid streaks (P = .039). However, using multivariate analysis to correct for the effects of age, the correlation of angioid streaks with the form of disease disappeared, whereas the level of significance between chelation therapy and angioid streaks was reduced (P = .05). The high frequency of angioid streaks observed in patients with beta thalassemia and the severe complications observed in one patient render a thorough ophthalmoscopic examination and follow-up of such patients necessary for both early diagnosis and possible therapeutic intervention.