Deferasirox-induced urticarial vasculitis in a patient with myelodysplastic syndrome

Abstract Deferasirox is an iron chelator agent used in the treatment of diseases with iron overload, such as thalassemia and myelodysplastic syndrome. Although the majority of adverse reactions of deferasirox involve gastrointestinal symptoms and increase in serum creatinine and transaminases, skin rashes, such as maculopapular and urticarial eruptions, have also been reported. This study reports a case of myelodysplastic syndrome with urticarial vasculitis due to deferasirox therapy. Drug eruption was been confirmed by means of a challenge test, together with histopathological and clinical findings. To the best of our knowledge, we report the first case of deferasirox-induced urticarial vasculitis. Physicians should be aware of the possibility of urticarial vasculitis on deferasirox therapy and the fact that the discontinuation of the drug generally results in improvement.

Recent advances in treatment of aplastic anemia

Recent advances in the treatment of aplastic anemia (AA) made most of patients to expect to achieve a long-term survival. Allogeneic stem cell transplantation (SCT) from HLA-matched sibling donor (MSD-SCT) is a preferred first-line treatment option for younger patients with severe or very severe AA, whereas immunosuppressive treatment (IST) is an alternative option for others. Horse anti-thymocyte globuline (ATG) with cyclosporin A (CsA) had been a standard IST regimen with acceptable response rate. Recently, horse ATG had been not available and replaced with rabbit ATG in most countries. Subsequently, recent comparative studies showed that the outcomes of patients who received rabbit ATG/CsA were similar or inferior compared to those who received horse ATG/CsA. Therefore, further studies to improve the outcomes of IST, including additional eltrombopag, are necessary. On the other hand, the upper age limit of patients who are able to receive MSD-SCT as first-line treatment is a current issue because of favorable outcomes of MSD-SCT of older patients using fludarabine-based conditioning. In addition, further studies to improve the outcomes of patients who receive allogeneic SCT from alternative donors are needed. In this review, current issues and the newly emerging trends that may improve their outcomes in near futures will be discussed focusing the management of patients with AA.

Serum zinc level in children with beta-thalassemia major on iron chelator

Zinc as a second trace element of human body plays an important role in numerous functions Thalassemic patients are at risk of zinc deficiency due to various causes including the use of iron chelating agents oral or injectable. In this study we aim to measure the serum zinc level in beta-thalassemic patients on oral versus injectable iron chelator. A hospital based case control study conducted in the Center of Hereditary Blood Disorders in Al-Zahra Teaching Hospital for the period between 1st of December 2011 to 31th of Augest 2012. Seventy children with beta-thalassemia major were studied, patients were divided into two groups: 37 patients were treated by deferoxamine constituent of group A and 33 were those on deferasiroxe therapy constituent group B. Control group consisted of 35 healthy children. Serum zinc was measured by atomic absorption spectrophotometery. Patients aged between 5-11 years, boys were 34 and girls 36. The mean age of patients was 7.5 years. The mean serum zinc level in group A [patients on deferoxamine] 59.3784 +/- 28.44913 microg/dl was significantly lower than that of group B [patients on deferasiroxe] 105.5667 +/- 30.25488 microg/dl and control group 96.8974 +/- 24.98083 microg/dl respectively. Hypozincemia found in 70.7%, 20% and 17.9% in group A, B and control group respectively. There was a significant difference between patients of both groups and control [p<0.05], while high significant difference between patients of different iron chelators [p<0.001]. Hypozincemia is common in thalassemic patients. The low level of serum zinc mainly found in those with injectable iron chelator. Routine follow up of serum zinc level and other possible causes of hypozenicemia should be studied before giving zinc to these patients

Deferasirox induced liver injury in haemochromatosis

Drug-induced liver injury is a common side-effect of many medicines. It is particularly problem when the original condition under treatment is already causing liver damage. This report describes the hepatotoxicity induced by Deferasirox in a patient with haemochromatosis with a discussion of possible pathogenetic mechanisum

Serum zinc level in thalassemia major

To compare serum zinc level between Thalassemia Major [TM] patients and normal population at Shafa Hospital in South West of Iran. A total of 25 male and 36 female of TM patients were enrolled in this study. Out of 61 patients thirty were treated by deferroxamine [DFO] and 31 were on the combination of DFO and deferiprone [DEF] protocol therapy. Sixty normal subjects of the matching age and gender were recruited as controls. From each patient and control group 2 ml of blood was taken in fasting condition. Cell blood count and serum zinc were carried out for both thalassemia patients and normal subjects. The mean age of patients and control group was 15 +/- 5years. Mean serum zinc level was 68.97 +/- 21.12microg/dl, 78.10 +/- 28.50 microg/dl, and 80.16 +/- 26.54 microg/dl in the TM with DFO, TM with DFO + DEF combination protocol and control group respectively. There was no significant correlation between patients and control group. However 50 percent of TM with DFO, 38.7 percent of TM with DFO + DEF and 32.8 percent of control group had hypozincemia. Nearly 40 to 50 percent of TM patients and one third of normal subjects are suffering from hypozincemia. This study shows that low level of serum zinc is a health problem in both thalassemia patients and normal population in South West of Iran

Agranulocyosis in beta thalassemia major patients treated with oral iron chelating agent [deferiprone]

Deferiprone is an oral chelating agent that has been recently shown to reduce cardiac siderosis, but is also known to be associated with serious side effects like agranulocytosis which can be fatal. This report is a single centre experience of 5 cases with severe agranulocytosis in amongst 144 patients [3.47%] of thalassemia major on combined chelation therapy with subcutaneous desferrioxamine and oral deferiprone which is much higher than the previous reports

evaluation of sensory neural hearing loss in thalassaemic patients treated with desferrioxamine and its risk factors

In major thalassaemia patients who need blood transfusion, iron overload is a major therapeutic disadvantage that leads to heart failure which is the major cause of death in such patients. Desferrioxamine [DFO] is the most efficient factor for iron chelation, but it carries adverse effects such sensory-neural hearing loss. The study began in March 2002 and continued untill March 2003, on 160 cases of thalassaemia to determine the incidence of sensory - neural hearing loss and its risk factors in patients who received Desferrioxamine [DFO]. All cases underwent audiometric tests. Retrospectively, other needed information were either obtained through interview or extracted from the medical files. Results were analyzed with ANOVA, t-test and Chi-square tests. Seventy-six patients of the total 156 patients showed impairment in PTA [48.7%] with 24 of them suffering significant involvement [15.4%]. These abnormalities generally affected high frequencies including, 4000 and 8000 Hz. Male gender, increased serum billirubin level and fasting blood sugar were statistically correlated with hearing loss [p.v = 0.038, p.v = 0.38, p.v = 0.002 respectively]. There was no significant correlation between hearing loss and other factors. Mean DFO administration in patients, was 29.69 mg/kg/day and mean therapeutic index of DFO was 0.01 mg/kg/day/mg/lit. Both of them were below the critical level [<40mg/kg/day and <0.025mg/kg/day/mg/lit respectively],however hearing loss had developed. Controlling DFO dosage per se does not seem to be enough for decreasing ototoxicity rate. Periodic audiometric tests are highly recommended to detect hearing loss as soon as possible. There are some other factors such as male gender, increased billirubin and FBS, which contribute to DFO ototoxicity. Looking for these risk factors and controlling them, would help identifying susceptible patients and preventing this complication

Copper and zinc concentrations in patients with beta - thalassemia major receiving iron chelator therapy

Fifteen patients with B-thalassemia major [10 males and 5 females] receiving desferoxanine [DFX] as iron chelating drug were included in this study. The patients were compared with 10 normal control subjects [7 males and 3 females]. Serum ferritin, cupper and zinc, as well as, 24 hour urinary excretion of cupper and zinc were estimated before receiving DFX and 13 months after. Serum ferritin was decreased significantly after treatment [p < 0.001]. No significant change were detected in 24 h urinary excretion of cupper as well as in serum cupper. On the other hand, there was a significant increase in 24 h urinary zinc excretion [p<0.02] and a significant decrease in serum - zinc [p < 0.05] after administration of DFX. However, symptoms attributed to zinc deficiency appeared only in two patients. So, in thalassmic patients with iron overload need chelation, a balanced dietary intake is being normally sufficient to prevent development of zinc deficiency and measurement of serum zinc is recommended