CNR2 functional variant (Q63R) influences childhood immune thrombocytopenic purpura.

Immune thrombocytopenic purpura is an acquired autoimmune disorder that is the most common cause of thrombocytopenia in children. The endocannabinoid system is involved in immune regulation. We evaluated a common missense variant (CAA/CGG; Q63R) of the gene encoding the cannabinoid receptor type 2 (GeneID 1269) in 190 children with immune thrombocytopenic purpura and 600 healthy controls. The allelic frequencies and genotype distribution of the polymorphism in the patients were significant compared to control samples (P=0.006 and P=0.0001, respectively). Interestingly, when acute and chronic immune thrombocytopenic purpura patients were analyzed separately with respect to controls, a significant overrepresentation of the RR genotype and of the R allele was observed only for the chronic form (P=0.00021 and P=0.011, respectively). The relative odds ratio suggested the risk of developing chronic form was more than double in immune thrombocytopenic purpura children homozygous for the variant (odds ratio=2.349, 95% CI: 1.544-3.573; P<0.001).

Effect of eradication of Helicobacter pylori in children with chronic immune thrombocytopenia: a prospective, controlled, multicenter study.

BACKGROUND: The eradication of Helicobacter pylori has been associated with remission of immune thrombocytopenia (ITP) in approximately half of eradicated patients. Data on children are limited to small case series. PROCEDURE: Children from 16 centers in Italy, who were less than 18 years of age and diagnosed with chronic ITP (cITP), were screened for H. pylori infection. Positive patients underwent standard triple therapy with amoxicillin, clarithromycin, and omeprazole. The eradication response was defined as follows: complete response, platelet (PLT) count ≥ 150 × 10(9) /L; partial response, PLT count of at least 50 × 10(9) /L; no response, PLT count <50 × 10(9) /L. RESULTS: Of 244 screened patients, 50 (20%) had H. pylori infection, 37 of which received eradication therapy and completed follow-up. Eradication was successful in 33/37 patients (89%). PLT recovery was demonstrated in 13/33 patients after eradication (39%), whereas spontaneous remission was observed in 17/166 (10%) H. pylori-negative patients (P < 0.005). Responders more often required second line eradication (9/13), whereas a second cycle was required in 3/20 non-responders (P < 0.005). CONCLUSIONS: Among the large cohort of patients, those who underwent successful H. pylori eradication showed a significantly higher PLT response. Therefore, it may be appropriate to look for H. pylori and eventually eradicate it in children with cITP.

Amoxicillin-induced hemolytic anemia in a child with glucose 6-phosphate isomerase deficiency.

OBJECTIVE: To describe the first case of amoxicillin-induced nonimmune hemolytic anemia in a child with glucose-6-phosphate isomerase (GPI) deficiency. CASE SUMMARY: A 3-year-old boy with GPI deficiency was admitted for upper respiratory tract infection and fever. The patient was treated with a standard dose of amoxicillin (50 mg/kg/day). On hospital admission, the child had a chronic moderately low hemoglobin level (8.6 g/dL), but within 24 hours of the first amoxicillin dose, the hemoglobin level markedly decreased (5.8 g/dL), the reticulocyte level increased (58%), and the urine darkened. Results of the direct and indirect Coomb's tests were negative and the acute hemolytic phase ended spontaneously 8 days after amoxicillin withdrawal (hemoglobin 9.5 g/dL, reticulocytes 22%). DISCUSSION: All previous cases of amoxicillin-induced hemolytic anemia have been attributed to an immune mechanism. Given the absence of anti-reticulocyte antibodies (Coomb's test), we suggest that the amoxicillin-induced hemolytic anemia in our patient occurred via a nonimmune mechanism favored by the child's GPI deficiency. Based on a MEDLINE search, we believe this to be the first report of amoxicillin-induced nonimmune hemolytic anemia in a child with GPI deficiency. GPI deficiency has been associated with well-compensated chronic hemolytic anemia that can become clinically relevant consequent to the administration of drugs. GPI deficiency can lead to impairment of the system that removes free radicals generated by amoxicillin, thereby resulting in oxidation of hemoglobin and destabilization of red cell membranes, with acute hemolysis and severe hemoglobinuria. The Naranjo probability score was consistent with a probable relationship between the hemolytic anemia and amoxicillin therapy. CONCLUSIONS: This report reinforces the hypothesis that a drug-sensitivity reaction is closely related to a genetically transmitted enzyme deficiency.

Long-term follow-up analysis after rituximab therapy in children with refractory symptomatic ITP: identification of factors predictive of a sustained response.

We report the long-term follow-up (median 39.5 months) of 49 paediatric patients (33 females and 16 males) with refractory symptomatic immune thrombocytopenic purpura (ITP) treated with rituximab. The overall response rate was 69% (34/49 patients). Twenty-one responders had a platelet count >50 x 10(9)/l at a median 20.2 months from treatment. Kaplan-Meier analysis showed a probability of relapse-free survival (RFS) of 60% at 36 months from the first rituximab infusion. The number of infusions and a previous splenectomy did not influence overall response rate. Patients who achieved complete response were significantly older at diagnosis and first rituximab infusion than partial responders (P = 0.027). Older children displayed a significantly greater probability of sustained response (RFS) at 36 months than younger children (88.9% vs. 56.7%, P = 0.037). Earlier responses (within 20 d from treatment) were significantly associated with both complete (P = 0.004) and sustained response (P = 0.002). Only mild and transient side-effects were observed in 9/49 children; no major infections nor delayed toxicities were recorded during the follow-up.