Successful Treatment of Iatrogenic Cutaneous Siderosis with Pigment Lasers: A Retrospective Study in 15 Consecutive Patients.

Intravenous ferric carboxymaltose is increasingly used to treat iron deficiency. However, a common side-effect is paravenous extravasation of iron preparations, resulting in cutaneous siderosis. Quality-switched (QS) lasers and, recently, picosecond (PS) lasers have been used to treat these hyperpigmentations with variable success. The optimal treatment protocol remains unclear. The aims of this study were to assess the response of cutaneous siderosis to treatment with pigment lasers and to determine the optimal wavelength, number of treatment sessions and pulse duration. Fifteen patients with cutaneous siderosis on the arms were included. The effectiveness of laser treatment was evaluated using a 5-point standard Physician Global Assessment (PGA) grading system. Differences in continuous variables between distinct groups of patients were assessed with a Mann-Whitney U test. In all 15 patients clearance of at least 50% was obtained. In 12 patients, at least 75% of pigment was removed. In conclusion, pigment lasers are an effective and safe method to treat cutaneous siderosis.

Glutathione S-transferase gene polymorphism: Relation to cardiac iron overload in Egyptian patients with Beta Thalassemia Major.

OBJECTIVES: Estimating the prevalence of glutathione S-transferase gene polymorphism (GSTM1) null genotype among patients with beta thalassemia major (ß-TM) in relation to myocardial status assessed by tissue Doppler and cardiac siderosis assessed by cardiac magnetic resonance imaging (MRI) T2*. METHODS: Hundred patients with ß-TM and 100 healthy controls were enrolled. Complete blood count (CBC), mean serum ferritin and GSTM1 genotyping, echocardiography, tissue Doppler, and cardiac MRI T2* were done. RESULTS: Serum ferritin ranged from 1200 to 8000 ng/ml, and mean T2* value was 27.10 ± 11.20 ms. Of patients, 68 (68%) had no cardiac siderosis, while 24 (24%) with mild to moderate, and 8 (8%) with sever cardiac siderosis. T2* values were not correlated with serum ferritin (r = -0.09, P = 0.50). GSTM1 null genotype was prevalent in 46% of patients and 40% of controls (P = 0.69). Patients with null genotype had significantly shorter T2* (P = 0.001), higher left ventricular end-diastolic diameter (P = 0.002), and shorter ejection time (P = 0.005) with no significant relation to serum ferritin (P = 0.122). GSTM1 null genotype was the only predictor for cardiac iron overload (P = 0.002). DISCUSSION: Serum ferritin concentrations have been shown to correlate poorly with all stages of cardiac dysfunction. Low cardiac MRI T2* values occur in patients with ß-TM despite good chelation therapy, suggesting a possible role of genetic factors in cardiac siderosis. CONCLUSION: GSTM1 null genotype is significantly associated with cardiac iron overload independent of serum ferritin in Egyptian patients with ß-TM.

Follow-up report on the 2-year cardiac data from a deferasirox monotherapy trial.

The trial CICL670AUS04 was a single-arm, open-label study of the cardiac efficacy of 18 months of deferasirox monotherapy [1]. Cardiac response in this study was related to the degree of liver siderosis. Patients with mild to moderate liver siderosis improved their cardiac T2* while more severely siderotic patients did not, regardless of initial cardiac iron burden. In this letter, we report 2-year data in those patients who completed a 6-month extension phase (N 5 10). Cardiac and liver iron improved steadily during the 24-month period, with final cardiac T2* and LIC improving 37% and 27%, respectively, in this cohort. Serum ferritin and LVEF were not statistically different at anytime-point. When the extension phase (18-24 months) was considered in isolation, serum ferritin, liver iron concentration, and left ventricular ejection fraction were nearly identical to 18 month results. Despite this, cardiac T2* continued to trend higher, increasing 12.7% from 9.5 ms to 10.7 ms (P 5 0.06). Thus defersirox continued to demonstrate cardiac efficacy in patients with mild to moderate hepatic siderosis throughout 2 years of therapy.

Combined chelation therapy in thalassemia major for the treatment of severe myocardial siderosis with left ventricular dysfunction.

BACKGROUND: In thalassemia major (TM), severe cardiac siderosis can be treated by continuous parenteral deferoxamine, but poor compliance, complications and deaths occur. Combined chelation therapy with deferiprone and deferoxamine is effective for moderate myocardial siderosis, but has not been prospectively examined in severe myocardial siderosis. METHODS: T2* cardiovascular magnetic resonance (CMR) was performed in 167 TM patients receiving standard subcutaneous deferoxamine monotherapy, and 22 had severe myocardial siderosis (T2* < 8 ms) with impaired left ventricular (LV) function. Fifteen of these patients received combination therapy with subcutaneous deferoxamine and oral deferiprone with CMR follow-up. RESULTS: At baseline, deferoxamine was prescribed at 38 +/- 10.2 mg/kg for 5.3 days/week, and deferiprone at 73.9 +/- 4.0 mg/kg/day. All patients continued both deferiprone and deferoxamine for 12 months. There were no deaths or new cardiovascular complications. The myocardial T2* improved (5.7 +/- 0.98 ms to 7.9 +/- 2.47 ms; p = 0.010), with concomitant improvement in LV ejection fraction (51.2 +/- 10.9% to 65.6 +/- 6.7%; p < 0.001). Serum ferritin improved from 2057 (CV 7.6%) to 666 (CV 13.2%) microg/L (p < 0.001), and liver iron improved (liver T2*: 3.7 +/- 2.9 ms to 10.8 +/- 7.3 ms; p = 0.006). CONCLUSION: In patients with severe myocardial siderosis and impaired LV function, combined chelation therapy with subcutaneous deferoxamine and oral deferiprone reduces myocardial iron and improves cardiac function. This treatment is considerably less onerous for the patient than conventional high dose continuous subcutaneous or intravenous deferoxamine monotherapy, and may be considered as an alternative. Very prolonged tailored treatment with iron chelation is necessary to clear myocardial iron, and alterations in chelation must be guided by repeated myocardial T2* scans. TRIAL REGISTRATION: This trial is registered as NCT00103753.

Assessment of iron stores in children with transfusion siderosis by biomagnetic liver susceptometry.

To investigate the applicability of noninvasive Superconducting Quantum Interference Device (SQUID) biomagnetic liver susceptometry and its limitations in thalassemic children, 23 patients with beta-thalassemia major and other iron loading anemias (age: 4-16 years) and 16 age-related normal children were studied. Liver iron concentrations ranged from 600 to 11,000 microg/g(liver) for thalassemic patients and from 60 to 340 microg/g(liver) for normal patients. Measuring the respective organ volumes by sonography, liver and spleen iron stores, accounting for 80% of total body iron stores, were estimated. Nonliver contributions from the lung or intestine to the measured SQUID signals in the small-sized patients were not observed. Moreover, livers in thalassemia were found to be enlarged by 18% per 1,000 microg/g (r = 0.75, P < 10(-3)). Serum ferritin values correlate significantly with iron stores (r = 0.64, P < 10(-3)), but predict iron stores only within large error intervals of 4,000 microg/g(liver). Analyzing the experimental data from biomagnetometry and from related transfusion and chelation treatment data within the framework of a two-compartment model, we were able to derive additional information on total body iron elimination and chelation therapy efficacy. The exponential decline of iron stores allows forecast of steady-state conditions of the final iron load for a particular transfusion and chelation therapy regimen.

Prevention of heart disease by subcutaneous desferrioxamine in patients with thalassaemia major.

BACKGROUND: Cardiac siderosis from transfused iron remains the major cause of death in thalassaemia major, despite iron chelation therapy with desferrioxamine. AIMS: Our aim was to determine the nature and extent of cardiac involvement and its relationship to desferrioxamine use in a group with thalassaemia major. METHODS: We reviewed 76 patients with thalassaemia major and performed multiple logistic regression to analyse factors affecting cardiac involvement. Factors studied included: patient sex, age, haemoglobin, serum ferritin, total transfusions, liver iron, duration of desferrioxamine use, electrocardiograms, echocardiograms and compliance to desferrioxamine treatment. RESULTS: Thirty-seven patients developed heart disease. They were older (p < 0.001), began desferrioxamine later (p < 0.001), had more liver iron (p = 0.014), higher serum ferritin levels (p = 0.023) and received more blood (p = 0.018). Compared to those with optimal compliance the odds of developing heart disease were increased 10.7 times in fair compliers (p < 0.001) and 5.1 times in poor compliers (p = 0.016). However, there was no significant difference between those with fair and poor compliance. After multivariate analysis only compliance (p = 0.02) and age at desferrioxamine onset (p = 0.004) remained significant. Compliance was inversely related to liver iron (p < 0.001), serum ferritin (p < 0.001) and age at desferrioxamine commencement (p < 0.001). CONCLUSIONS: We conclude that late commencement of desferrioxamine and noncompliance are associated with greater iron loading and an increased risk of heart disease.

Electroretinographic and visual-evoked potential abnormalities in patients with beta-thalassemia major.

Various ocular abnormalities have been reported in patients with thalassemia, and have been, for the most part, attributed to the toxic effects of high-dose desferrioxamine (DFO). We have performed an electroretinographic and visual-evoked potential (VEP) study in 31 thalassemic patients who had never received high doses of DFO. The abnormalities found were very similar to those reported in early siderosis bulbi and included a b1-wave of significantly higher amplitude at 1 min and at the alpha point. VEPs showed a N1-P1 amplitude significantly greater than in controls. These findings, which were more marked in older patients, point to an important causative role of iron in their genesis.

Serum ferritin in children with thalassaemia regularly transfused.

A controlled trial of continuous chelation therapy in regularly transfused children with homozygous beta-thalassaemia has been in progress at the Hospital for Sick Children since April 1966. In the sixth and seventh years of the trial the effect of this treatment on iron overload has been assessed by estimating serum ferritin levels and liver iron concentrations in both chelator-treated and control groups. When compared with non-chelated controls, results of both these estimations were invariably lower in the chelated group. However, all the results in both groups were very high, and fell within the ranges observed in untreated idiopathic haemochromatosis. A close correlation was found between serum ferritin levels and liver iron concentrations in these children, indicating that serum ferritin is a valuable alternative to liver iron concentration in the assessment of visceral iron overload, even when massive tissue siderosis is present.