Rituximab for treatment of autoimmune hemolytic anemia

We report the successful use of rituximab as single treatment modality in a five-month-old boy with fulminant warm autoantibody autoimmune hemolytic anemia, resistant to standard treatment. On admission, laboratory tests showed a profound anemia with a hemoglobin of 2.6 g/dL. Indirect and direct antiglobulin tests were strongly positive, and nonspecific IgG autoantibodies were detected. Two days of intravenous corticosteroids (methylprednisolone 4mg/kg) and immunoglobulins (1g/kg) did not halt the hemolysis and the infant was severely transfusion-dependent. Rituximab 375mg/sq m weekly was given for 4 weeks, the hepatosplenomegaly gradually regressed, the lymphocytes normalized and he is free from hemolysis two years after treatment.     

Distinctive and common features of moderate aplastic anaemia

The therapy algorithm for severe aplastic anaemia (sAA) is established but moderate AA (mAA), which likely reflects a more diverse pathogenic mechanism, often represents a treatment/management conundrum. A cohort of AA patients (n = 325) was queried for those with non-severe disease using stringent criteria including bone marrow hypocellularity and chronic persistence of moderately depressed blood counts. As a result, we have identified and analyzed pathological and clinical features in 85 mAA patients. Progression to sAA and direct clonal evolution (paroxysmal nocturnal haemoglobinuria/acute myeloid leukaemia; PNH/AML) occurred in 16%, 11% and 1% of mAA cases respectively. Of the mAA patients who received immunosuppressive therapy, 67% responded irrespective of time of initiation of therapy while conservatively managed patients showed no spontaneous remissions. Genomic analysis of mAA identified evidence of clonal haematopoiesis with both persisting and remitting patterns at low allelic frequencies; with more pronounced mutational burden in sAA. Most of the mAA patients have autoimmune pathogenesis similar to those with sAA, but mAA contains a mix of patients with diverse aetiologies. Although progression rates differed between mAA and sAA (P = 0·003), cumulative incidences of mortalities were only marginally different (P = 0·095). Our results provide guidance for diagnosis/management of mAA, a condition for which no current standard of care is established.     

Asymptomatic pharyngeal carriage of beta-haemolytic streptococci and streptococcal pharyngitis among patients at an urban hospital in Croatia

In a one-year study at the University Hospital of Infectious Diseases in Zagreb, Croatia the rate of asymptomatic throat carriage of beta-haemolytic streptococci was investigated. Throat carriage was investigated in 1796 patients, none of whom had a sore throat nor signs and/or symptoms of a respiratory tract infection. The carrier rate of beta-haemolytic streptococci was 8.3%, for group A streptococci 6%, group B 1.3%, group C 0.3% and group F 0.1%. The highest rate was observed in the 6 to 14 year age group: 13.8% for all streptococcal groups, 11.7% for group A alone. The proportion of non-A streptococci was higher in older age groups. Tonsillectomised individuals were less frequently carriers. No sex or season-dependent variations were observed. In a four-month study of 629 patients with pharyngitis the throat cultures yielded: group A streptococci in 44.7%, group B in 1.7%, group C in 0.8%, and group G in 0.6% of the patients. Group A streptococcal rates in carriers compared to rates in patients with pharyngitis suggest that approximately one fourth of the schoolchildren with culture-positive pharyngitis actually are not truly infected, but only carriers currently having a sore throat of non-streptococcal etiology.Antibiotics were administrated to 605 (96.2%) patients with pharyngitis; in 571 (94.4%) of the cases before culture results became available. After culture-negative results were obtained the therapy was discontinued in only 28.5% of the cases. The throat culture is the standard for laboratory testing of group A streptococcal infection and should have more influence on the management of patients with pharyngitis at our hospital.     

Treatment results of childhood acute myeloid leukemia in Serbia

We present the results of a retrospective study of acute myeloid leukemia (AML) treatment in Serbia in the period 2000–2012. Treatment was performed in four centers, two of which were located in Belgrade, one in Nis, and one in Novi Sad. Children affected by non-acute promyelocytic leukemia (non-APL) subtypes received treatment regimens derived from protocols of Berlin Frankfurt Munster AML study group, whereas children with APL were treated according to the AIEOP/GIMEMA ATRA plus Idarubicin “AIDA” protocol. Total number of patients was 106, out of whom 48 were girls (45.3 %) and 58 boys (54.7 %); median age at diagnosis was 9.0 years (range 1 month–17.9 years). In total, 82.1 % of patients achieved complete remission after induction treatment. Twelve patients (11.3 %) died during induction, before achieving complete remission; there were nine deaths during remission (10.5 %) and 20 patients relapsed (23.2 %). Median time of follow-up was 54 months. Two patients (1.9 %) were lost to follow-up. Event-free survival was 50.3 % and overall survival was 58.9 %.     

Fever of unknown origin in 185 paediatric patients: a single-centre experience

Aim: We conducted a prospective study to evaluate the causes and outcome in children with fever of unknown origin (FUO). Methods: From 1990 to 1999, 185 children with FUO were evaluated. Initial evaluation included routine haematological analysis, Epstein-Barr virus (EBV) serology, urine, stool or blood cultures, chest X-ray and tuberculin probe. Results: In 131 (70%) patients diagnosis was established, and 70 (37.8%) had infectious disease. EBV infection was the most common infection followed by visceral leishmaniasis (VL), urinary tract infection (UTI) and tuberculosis. Autoimmune disorders were diagnosed in 24 (12.9%), Kawasaki disease in 12 (6.4%), malignant diseases in 12 (6.4%) and miscellaneous conditions in 15 (8.1%) patients. In the remaining 54 (30%) patients, diagnosis was not established and most of them had self-limited disease. During the investigation, 26 (14%) patients developed serious organ dysfunction and five patients (two with virus-associated haemophagocytic syndrome, one with VL and two unknown) died.

Conclusion: The most important infectious causes of FUO in our study were EBV infection and VL. Kawasaki disease represented a significant cause of FUO at the beginning of our study because it was not recognized by primary-care physicians. We report myelodysplastic syndrome as another emerging cause of paediatric FUO. Repeated clinical examination and careful use of specific laboratory examinations, invasive diagnostic procedures or imaging are crucial in approaching paediatric FUO.