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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.

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.

A patient with Wiskott‐Aldrich syndrome who developed Epstein‐Barr virus‐associated haemophagocytic lymphohistiocytosis (EBV‐HLH) is described in this study. At 4 mo of age the patient developed fever associated with bicytopenia and splenomegaly. Analysis of a bone marrow specimen revealed extensive haemophagocytosis, and in situ hybridization for EBV of the bone marrow specimen using an EBV‐encoded RNA probe was positive. Diagnosis of EBV‐HLH was established and immunotherapy with HLH‐94 protocol was started. HLH has been described in patients with other well‐defined primary immunodeficiencies such as X‐linked lymphoproliferative syndrome, Chediak‐Higashi syndrome and Griscelli disease. Also, HLH was reported recently in severe combined immunodeficiency and DiGeorge syndrome. Conclusion: The possibility of an underlying primary immunodeficiency should be considered in paediatric patients who present with HLH during infancy.

Hemoglobin (Hb) Sabine is a rare, unstable Hb variant resulting from the point mutation in codon 91 (CTG --> CCG) of beta-globin gene. We report a case of Hb Sabine patient with mild hemolytic anemia, unusually high Hb F level and severe central nervous system thrombotic disturbances. We have tried to elucidate possible genetic background of this unusual Hb Sabine phenotype. Extremely high level of Hb F and rather mild anemia in our patient could be partially explained by the presence of G gamma Xmn I polymorphism. This case of Hb Sabine, unlike all other reported to date, shows extremely severe thromboembolic complications. It is our opinion that the hypercoagulable state described in thalassemia is not the only factor responsible for this specific clinical state. The presence of MTHFR C677T mutation in heterozygous state found in our patient and unstable Hb Sabine molecules could contribute to development of thromboembolic phenomena. However, it remains unclear whether other factors participate in pathogenesis of the disease. In this paper we emphasize different genetic background of father and son both affected with Hb Sabine, but with markedly different severity of the disease.

Several reports have documented various forms of glomerular diseases in adults with myelodysplastic syndromes (MDS), but similar reports in children are lacking. We describe two children with MDS-associated steroid-responsive nephrotic syndrome (NS). Patient 1, who had MDS with myelofibrosis, presented with hepatosplenomegaly, pancytopenia, chronic hepatitis, moderate proteinuria, hypocomplementemia and elevated ANA titer. During initial prednisone treatment proteinuria markedly diminished and partial but transient hematological improvement occurred. Relapse subsequently occurred that manifested by overt NS and pancytopenia. High doses of prednisolone led to remission of the renal disease, but hematological remission did not occur. Persisting pancytopenia and repeated infections terminated in sepsis, 2 years after the onset of the MDS. Patient 2, who had refractory anemia with clonal monosomy 19, presented with bowel disease, hepatosplenomegaly, anemia and non-organ-specific autoantibodies. Prednisone led to both clinical and hematological remission. The hematologic disease relapsed 12 months later, when nephrotic-range proteinuria, hematuria and mild azotemia were also found. Corticosteroid treatment led to long-lasting renal and hematologic remission, maintained by a small dosage of prednisone. In both patients, renal biopsy findings were consistent with those seen in idiopathic NS. A Medline search disclosed 16 cases of glomerulopathy in the course of MDS in adult patients. Clinical features included NS, usually accompanied by renal insufficiency with acute, chronic, or rapidly progressive glomerulonephritis. On biopsy, membranous nephropathy, crescentic or mesangial proliferative glomerulonephritis, and AL amyloidosis were found. We conclude: (1) that glomerular disease may be present and should be searched for in patients with MDS and (2) that MDS can be added to the list of rare conditions associated with corticosteroid-responsive NS in children.