Recurrent bacterial meningitis by three different pathogens in an isolated asplenic child.

Isolated congenital asplenia (ICA) is a rare condition at risk for overwhelming infection. When complicated by invasive infection, the mortality remains high, at greater than 60%. We describe a girl with ICA who developed recurrent meningitis by three different pathogens. The first, meningitis by Escherichia coli, occurred 4 days after premature birth. The other two pathogens were serotype 6B Streptococcus pneumoniae and Haemophilus influenzae type b (Hib), at 18 and 25 months of age, respectively. The patient was successfully treated with prompt antimicrobial therapy in all episodes. Serum anti-polyribosylribitol phosphate (PRP) and anti-6B-type pneumococcal antibodies were below the levels for protective activity after natural infections. Although anti-PRP antibody was significantly increased after Hib vaccination, two (6B and 19F) of seven serotype-specific pneumococcal antibodies were not elevated to protective levels after the second 7-valent pneumococcal conjugate vaccine (PCV7). We, therefore, added a third PCV7. To our knowledge, this is the first neonatal ICA patient with invasive infection and the first case of bacterial meningitis occurring three times. Our findings indicate that monitoring of immune responses after natural infections and vaccinations, and reevaluations of vaccine schedule, are important for ICA patients to prevent subsequent invasive infections.

Spinal cord compression by epidural involvement over 21 vertebral levels in acute lymphoblastic leukemia.

Spinal cord compression is a rare complication of acute lymphoblastic leukemia (ALL). We report a 13-year-old boy with B-precursor ALL, presenting with restriction of breathing and back pain. Cerebrospinal fluid examination showed extremely high protein levels. Radiologic examination indicated that leukemia extended from the thoracic to sacral epidural spaces over 21 vertebral lengths in a band-shaped form, threatening to induce compressive spinal cord neuropathy. Prompt initiation of systemic chemotherapy relieved the obstruction of cerebrospinal fluid flow without local irradiation or surgical intervention. To our knowledge, this patient has shown the most extensive epidural involvement among ALL patients previously reported.

Parvovirus B19-associated hemophagocytic lymphohistiocytosis in a child with precursor B-cell acute lymphoblastic leukemia under maintenance chemotherapy.

Development of hemophagocytic lymphohistiocytosis (HLH) is quite rare among acute lymphoblastic leukemia (ALL) patients. We present a 3-year-old boy with precursor B-cell ALL, who was complicated by HLH because of parvovirus B19 infection during maintenance chemotherapy. Remarkable erythroid hypoplasia, giant normoblasts, and hemophagocytosed macrophages in bone marrow were important clues for the diagnosis. The patient was successfully treated with high-dose steroids and intravenous immunoglobulins. To our knowledge, this is the first report describing parvovirus B19-associated HLH in ALL. Our case highlights that parvovirus B19 can cause HLH, a potentially fatal disorder, and prolonged unexpected cytopenia in childhood ALL.

Reversible splenial lesion in influenza virus encephalopathy.

We describe a rare case of clinically mild, influenza-associated encephalopathy with a reversible splenial lesion. A 12-year-old Japanese girl presented with fever and headache, followed by muscle weakness and somnolence. Magnetic resonance imaging on day 4 of her illness showed a solitary lesion of the splenium of the corpus callosum that was most prominently visualized on diffusion-weighted images. The patient was diagnosed with influenza B-associated encephalopathy. Her neurologic signs had completely recovered by day 6, and the splenial abnormalities disappeared on day 11. A review of the literature identified four additional pediatric cases of this type of influenza-associated encephalopathy: three and one were caused by influenza A and B viruses, respectively. Common features include prompt and complete recovery from clinical and radiologic abnormalities, a relatively older age (> or = 5 years), and a higher incidence among the Japanese. To better understand the pathophysiology of this encephalopathy, we examined interleukin-6, tumor necrosis factor-alpha, and soluble tumor necrosis factor receptor 1 levels in serum and cerebrospinal fluid from this patient. The results did not reveal any elevations of these cytokines in the sera or cerebrospinal fluid, suggesting that this condition is not mediated by augmented cytokine responses.

[Combination therapy with low-dose cyclosporin A, azathiopurine, and prednisolone for a child with refractory chronic idiopathic thrombocytopenic purpura].

We report on a boy with refractory chronic idiopathic thrombocytopenic purpura (ITP) successfully treated with combination therapy composed of low-dose cyclosporin A (CsA), azathiopurine, and prednisolone. The patient was diagnosed as having ITP at 5 years of age, and received high-dose intravenous immunoglobulin (IVIG), followed by oral prednisolone, intravenous pulsed dexamethasone, oral cepharantin, and intermittent IVIG therapies. Because there were no or only transient responses to these medical therapies over 2 years, he was splenectomized. However, 3 months after the splenectomy, his platelet counts fell to below 10 x 10(3)/microl accompanied by wet purpura. We resumed low-dose intermittent IVIG treatment for 1 year without sustained efficacy. We then started combination therapy with CsA (2.5 mg/kg/day), azathiopurine (1.7 mg/kg/day), and prednisolone (0.8 mg/kg/day). Complete remission was achieved within 2 weeks and the platelet counts remained > 50 x 10(3)/microl even after tapering off the prednisolone and azathiopurine at 6 and 12 months, respectively and have moreover remained normal for more than 10 months after completion of 2 years of CsA treatment. There were no adverse events during the therapeutic course. This is the first pediatric case of ITP treated with CsA in Japan. Such combination therapy may be promising and tolerable for childhood ITP with splenectomy failure.

[A case of group B streptococcal occult bacteremia].

We reported an infant with occult bacteremia caused by group B Streptococcus (GBS). An 8-week-old girl, who was uneventfully born to an 18-year-old mother, was hospitalized because of a 4-hour history of fever. On admission, she appeared nontoxic, and the temperature was 39.0 degrees C, and the pulse and respiratory rates were 162/min and 42/min, respectively. Laboratory findings showed a total white blood count of 5,200/microliter with 44% neutrophils and C-reactive protein of 0.7 mg/dl. Cerebrospinal fluid and urine examinations did not disclosed any abnormalities. After a complete evaluation of sepsis including cultures from blood, cerebrospinal fluid, urine, stool, and throat swab, intravenous cefotaxime was administered at 100 mg/kg/day in three fractions. Nine hours after the start of the culture, GBS was isolated from blood, and thereafter from the throat, but not from other culture sites obtained on admission. However, at that time she fed well and her temperature was subsiding. Forty-eight hours after admission, she became afebrile and cefotaxime administration was continued for 7 days. Based on the examinations of minimal inhibitory concentrations of various antibiotics, serotype analysis, and restriction-digestion patterns of genomic DNA, the 3 GBS strains isolated from the patient's blood and throat and the maternal anus were identical, suggesting that the infant was infected by her mother. This is the first report in Japan describing the clinical course of GBS occult bacteremia. According to a case series published in the English literature and our case, there are few clinical and laboratory markers predictive for GBS occult bacteremia, but this condition may develop focal invasive infections. A high index of suspicion is required for correct diagnosis. Further accumulation of such patients is warranted to establish the appropriate treatment.

[Salmonella enteritidis osteomyelitis of the tibia--a case report and review of literature on Salmonella osteomyelitis of Japanese patients].

We described a rare case of Salmonella enteritidis osteomyelitis of the tibia combined with arthritis of the ankle joint. A 4-year-old, otherwise healthy girl was hospitalized with 9-day history of fever, left leg pain, and diarrhea. On admission, her left lower leg and ankle were markedly reddened and swollen. Laboratory examinations disclosed a WBC of 16,300/microliter and a C-reactive protein of 15.6 mg/dl. A T2-weighed magnetic resonance image of the leg depicted a high intensity area around the left distal tibia and an extremely high intensity fluid in her left ankle joint, leading to our diagnosis of purulent osteomyelitis of the tibia and arthritis of the ankle joint. Salmonella enteritidis was isolated from ankle joint fluid and later aspirated bone marrow of the tibia, but not from blood or stool. Because of poor response to intravenous treatment with panipenem/betamipron for 2 days, she underwent drainage and washing of the joint fluid, and intramedullary administration of cefotaxime and ampicillin. She completely recovered without sequelae following treatment with sensitive antibiotics for 4 weeks in total. There has not been any relapse for more than 1.5 years. The authors also bibliographically surveyed the literature published from 1966 to 2002 and found 35 Japanese patients with Salmonella osteomyelitis. The present patient was the second case caused by Salmonella enteritidis in Japan. Septic arthritis is a rare complication, accounting for only 8% of the patients. Since Salmonella enteritidis has been a leading serotype among human isolates of Salmonella species during the past decade, it would be warranted to determine whether osteomyelitis due to this organism is likely to increase.

[FISH detected 11q23 microdeletion and translocation at the long arm of chromosome 11 in a child with normal karyotypic acute lymphoblastic leukemia].

We report on a 6-year-old girl with acute lymphoblastic leukemia (ALL) with 11q23 microdeletion and translocation at the long arm of chromosome 11, which were detected by fluorescence in situ hybridization (FISH) but not by conventional cytogenetics. She was hospitalized because of fever and generalized bone pain. Results of peripheral blood examination included a WBC of 5,400/microliter with 12% lymphoblasts. Bone marrow studies showed 75% of early pre-B lineage lymphoblasts with L1 morphology. G-banding chromosome analysis demonstrated a normal karyotype. However, FISH using mixed lineage leukemia (MLL) and 11q subtelomere probes demonstrated 11q23 microdeletion and translocation at the long arm of chromosome 11 to an undefined chromosome. MLL rearrangement was not detected by Southern blotting analysis. The patient achieved complete remission 15 days after receiving high-risk group chemotherapy of the Kyoto University Pediatric Hematology/Oncology Study Group and has remained in complete remission for more than 30 months. Since MLL/11q23 abnormalities confer a poor prognosis in childhood ALL, the accurate detection of such abnormalities is of paramount significance in assigning individual cases to risk categories. The findings from the present case and recent literature indicate that the FISH-based approach is complementary to conventional cytogenetics, and should be systematically used in childhood ALL at diagnosis.

Methylprednisolone pulse therapy for refractory Mycoplasma pneumoniae pneumonia in children.

OBJECTIVES: To determine the efficacy of methylprednisolone pulse therapy for children with Mycoplasma pneumoniae pneumonia (MP) that is refractory to antibiotic treatment. METHODS: Refractory patients were defined as cases showing clinical and radiological deterioration despite appropriate antibiotic therapy for 7 days or more. We identified 6 such children (male/female: 3/3) aged 3-9 years who were treated between 1998 and 2006. During the same period, 190 children with MP were admitted to our institution. RESULTS: Common laboratory findings of the patients included cytopenia, elevated serum lactate dehydrogenase and ferritin levels, and elevated urine beta(2)-microglobulin levels, suggesting complication of hypercytokinemic condition. We initiated intravenous methylprednisolone at a dose of 30 mg/kg on 10.2+/-2.8 clinical days and administered it once daily for 3 consecutive days. Fever subsided 4-14 h after initiation of steroid pulse therapy in all patients. This dramatic effect was accompanied by rapid improvement of radiological abnormalities including infiltrates and pleural effusion, followed by improvement of laboratory abnormalities. There were no adverse events of steroid therapy. CONCLUSIONS: This is the first case-series study showing an effect of 3-day methylprednisolone pulse therapy on refractory MP in children. This therapy is apparently an efficacious and well-tolerated treatment for refractory MP.

Acute lymphoblastic leukemia with coexpression of CD56 and CD57: case report.

The authors present the clinical profile of a 6-year-old girl with an unusual immunophenotype of acute lymphoblastic leukemia (ALL). At the initial presentation, massive hepatosplenomegaly developed. The leukemic cells were myeloperoxidase-negative and morphologically lymphoblastic. These cells were positive for B-precursor-cell (CD10, CD19) antigens and natural killer cells (CD56, CD57). Rearrangements of both immunoglobulin heavy chain alleles and monoallelic rearrangement of T-cell receptors (TCRs)-beta and -delta genes, but not that of TCR-gamma gene, were detected, suggesting that these cells being of B-precursor origin. The patient received chemotherapy for extremely high-risk ALL with a good response. To the authors' knowledge, this is the first pediatric case describing coexpression of CD56 and CD57 on B-lineage ALL.