Prospective evaluation of high-cost management of severe chronic ITP in children and adolescents<16 years.

Chronic ITP rarely presents with severe bleeding episodes (SBE). Number and duration of SBE were evaluated in relation to the cost of management. Out of 157 chronic ITP patients attending our institution from 1994 to 2003, 37 patients, <16 years with persistent thrombocytopenia (>6 months), suffering from SBE or platelet count<10x10(9)/L were prospectively randomized to receive either intravenous immunoglobulins (IVIG), anti-D immunoglobulin (anti-D) or high-dose methyl prednisolone (HDMP). Sixty-one patient-years were followed, during which 351 SBE were documented. The high-cost management (IVIG and anti-D) showed insignificantly better platelet recovery, less frequent SBE with shorter duration per patient, higher rate of CR, and less splenectomy in contrast to the steroid groups. The effectiveness of high-cost management compared with methyl prednisolone could not be documented in this study.

Frequency of inhibitor development in severe haemophilia A children treated with cryoprecipitate and low-dose immune tolerance induction.

The frequency of factor VIII inhibitor development was evaluated in a hundred severe haemophilia A patients < 18 years of age (mean 10.4 +/- 5.1 years); 25 were previously untreated patients (PUPs), with a mean age of 11.2 +/- 2.9 months. All were followed up for 3 years from December 1996. Immune tolerance (IT) was induced with low-dose factor VIII (FVIII); 25-50 IU kg(-1) every other day for the 10 haemophiliacs who developed persistent inhibitors. The incidence of inhibitors for PUPs was 3/25 (12%; 95% confidence interval [CI], 0. 7-24.7%) and were detected after 4, 15 and 20 exposure days (mean 13 +/- 8.2 days; 95% CI, 3.7-22.2%). Children with maximum inhibitor levels of > 40 Bethesda units (BU) per mL (n=4) received IT therapy as 25 U kg(-1) FVIII in the form of cryoprecipitate every other day for 1-4 months (mean 2.4 +/- 1.6 months; 95% CI, 0.8-3.9%), which was successful in all of them. FVIII (50 U kg(-1)) was given every other day for six patients with maximum inhibitor level > 40 BU mL(-1) for 3-9 months (mean 5.4 +/- 3.2 months; 95% CI, 2.9 -7.9%) with success in 4/6 (66.6%; 95% CI, 28.8-104.3%). Patients who showed a good IT response had an inhibitor level < or = 30 BU mL(-1), were < or = 9 years of age at inhibitor development with few exposure days to FVIII and had an early immune tolerance. In conclusion, inhibitor development in severe haemophilia A children exclusively treated with cryoprecipitate is low. Early low-dose IT induction for high responders may be achieved successfully if inhibitor level is < or = 50 BU mL(-1).

Serum levels of tumour necrosis factor alpha (TNF-alpha) versus immunoglobulins (IgG., IgM., and IgE.) in Egyptian scabietic children.

The tumour necrosis factor-alpha (TNF-alpha or Cachectin) is a protein produced mainly by macrophages, with a wide range of biological activities and in inflammatory process. On the other hand, scabies is a skin disease caused by Sarcoptes scabiei which is typified by severe itching (particularly at night), red papules and often secondary infection. The female mite tunnels in the skin to lay her eggs and the newly hatched mites pass easily from person to person by contact. Commonly the infested areas are the groin, penis, nipples and the skin between the fingers. In this paper, the serum levels of TNF-alpha versus IgG., IgM., and IgE. were estimated in parasitologically proven scabietic male children (8-13 years) with no secondary infection or other parasitic infection. The results showed high significant elevation of serum TNF-alpha in 94.1% (P = 7.763E-04) and IgE in 100% (P = 1.530E-07) in the scabietic patients than in the control group, and non significant increase in IgG in 47% (P = 0.0605) and in IgM in 5.9% (P = 0.9404). It was concluded that TNF-alpha plays a role in the pathogenesis of human scabies. Extensive study is ongoing to clarify the outcome of TNF-alpha in human scabies.

Therapeutic splenic ultrasound for immune thrombocytopenia in children.

The spleen acts as a major site of clearance of antibody-coated platelets from circulation in immune thrombocytopenia (ITP). Splenectomy carries a high cure rate. The biological effect of a single therapeutic dose of ultrasound directed transthoracically to the spleen at 1 MHz and 1 W/cm2 with a mean treatment time of 5 min as generated by Sonopuls 463 (Enraf Nonius) was studied in 30 children with ITP (20 chronic, 10 acute) aged 8-14 years (median 10) and 10 control children. The chronic ITP cases had platelet counts (PC) of 20-50 x 10(9)/l (mean 36 x 10(9)/l), showed peak responses at 4 h after exposure 5-18 x 10(9)/l (mean 10 x 10(9)/l) in 70% of cases, while the remaining 6 patients showed either no change in PC (n = 3) or a decline in PC (n = 3) 5-7 x 10(9)/l. Children with acute ITP had pretreatment PC of 30-50 x 10(9)/l (mean 40 x 10(9)/l). All had increments of PC after ultrasonic exposure (10-30 x 10(9)/l; mean 18 x 10(9)/l) peaking at 4 h. Six patients with acute ITP maintained the rise in PC while in an other 4, PC returned to baseline in 24 h. The control group showed no change in PC. This therapy was well tolerated and was not associated with significant change in serum lactate dehydrogenase (LDH) levels except in 2 cases with chronic ITP, in whom the LDH levels doubled. All above results were reproduced when therapy was repeated 2 weeks later. In conclusion, this therapy would seem to be safe and well tolerated at such a dose. The effectiveness, rapidity and low cost of this therapy compared with conventional approaches may suggest its use as an alternative therapy in ITP.

Idiopathic thrombocytopenic purpura in Egyptian children.

350 patients with idiopathic thrombocytopenic purpura (ITP) aged 2/12-15 years (mean 6.3 +/- 2.7) were followed up during the period January 1st, 1975 to March 31, 1992. They constituted 40% of cases with hemorrhagic diathesis attending the Hematology/Oncology Clinic, Children's Hospital, Ain Shams University (relative frequency of 37.4/100.000 of the general Out-Patient Clinic in the same hospital). These patients presented with acute (71.4%), chronic (22.9%) and recurrent (5.7%) forms. The age of presentation was younger in acute ITP. In the recurrent form there was significant female predominance. Most cases of acute ITP (66%) presented in winter and spring, with a positive history of preceding viral illness in 50% in contrast to 10% in chronic form. Four chronic ITP cases developed lupus erythematosus; all were females > 9 years. As regards therapy, acute ITP cases with initial platelet count (PC) < 10 x 10(9)/l were randomized to receive either high-dose methyl prednisolone (HDMP) 10 mg/kg/day for 5 days i.v. (n = 10) or intravenous immunoglobulin (IVIG) 0.4 g/kg/day for 5 days (n = 10) or conventional-dose prednisone (CDP) 2 mg/kg/day 4 weeks p.o. (n = 10). A dramatic response was noticed in the first two groups. In chronic ITP, (n = 80) CDP induced complete response (CR) in 30% and partial response (PR) in 20%; 50% were nonresponders. Twenty-four refractory ITP with persistent PC < or = 20 x 10(9)/l received second-line therapy: vincristine 1.5 mg/m2/week i.v. 4 doses (n = 4) with no clinical or hematological improvement. IVIG 0.4 g/kg/day for 5 days (n = 8) with sustained CR only in 2 patients (25%) and PR in 2 patients (25%). Splenectomy was performed (n = 12) with CR in 50%; out of them, 2 patients had shown no improvement on prior IVIG therapy. In conclusion, ITP is a benign condition with no fatality reported, but it could run a chronic refractory course.

Effect of desferrioxamine B on hemolysis in glucose-6-phosphate dehydrogenase deficiency.

Twenty-four infants and children suffering from glucose-6-phosphate dehydrogenase (G6PD) deficiency during hemolytic crisis were included in this study. Their ages ranged between 3 and 36 months with a median of 10 months. 22 were males and 2 were females. Fourteen out of them received a single bolus dose of desferrioxamine B 500 mg intravenously followed by packed red cell transfusion, while the remaining 10 cases were only transfused. Sequential estimation of hemoglobin level, reticulocytic count and hemoglobinuria was done before treatment, 3, 24, 48 and 72 h thereafter. The hemoglobin level was higher in the desferrioxamine B group. The degree of increase was statistically significant at 48 and 72 h (p less than 0.01). Hemoglobinuria stopped in 78.5% in the first group and only in 30% of the second group at 72 h. It was concluded that desferrioxamine B is helpful in shortening the course of hemolytic crisis in G6PD-deficient patients. It could be used as an adjuvant to packed red cell transfusion.