Taisuke Eguchi

A Severe Form of Kawasaki Disease Presenting with Only Fever and Cervical Lymphadenopathy at Admission

OBJECTIVE To examine the characteristics of patients with Kawasaki disease (KD) presenting with only fever and cervical lymphadenopathy at admission. STUDY DESIGN The laboratory and clinical findings of patients with definite KD presenting with only fever and cervical lymphadenopathy at admission (KDiL) were compared with those of all other patients with KD. RESULTS Sixteen patients with KDiL (8.6%) and 171 patients without KDiL were examined. The patients with KDiL were significantly older (KDiL/non-KDiL: 4.9+/-2.5/2.2+/-1.9 years) and admitted earlier (3.0+/-1.2/3.9+/-1.3 days of illness) than the patients without KDiL. They also showed significantly elevated white blood cell counts and C-reactive protein levels. Patients with KDiL were treated with the same dose of intravenous immunoglobulin as the patients without KDiL but were treated slightly later and had significantly higher frequency of additional intravenous immunoglobulin treatment (38%/10%) and coronary artery abnormalities (25%/5%). After adjustment for age, white blood cell count, and day of illness at admission or first intravenous immunoglobulin administration, the presence of KDiL significantly increased the risk of being a nonresponder to IVIG treatment or development of a coronary artery abnormality. CONCLUSIONS KDiL indicates a severe form of KD associated with increased risks of additional intravenous immunoglobulin treatment and coronary artery abnormalities. Patients with KDiL may require heightened surveillance and more aggressive treatment.

Early diagnosis of Kawasaki disease in patients with cervical lymphadenopathy.

Background: Among typical patients with Kawasaki disease (KD), a few KD patients present with only fever and cervical lymphadenopathy at admission (KDL). These patients have a significant risk for misdiagnosis, delay in treatment for KD, and development of coronary artery abnormalities. Therefore, the development of an easy tool for early diagnosis in these patients is desirable.

An elevated value of high mobility group box 1 is a potential marker for poor response to high-dose of intravenous immunoglobulin treatment in patients with Kawasaki syndrome.

We examined the serum values of high mobility group box 1 (HMGB1) in 36 patients with Kawasaki syndrome (KS) (29 responders and 7 poor-responders to initial intravenous immunoglobulin treatment). A mean value of HMGB1 of poor-responders was significantly elevated compared with those of responders (P = 0.0042). Among the 6 factors showing significant differences between responders and poor-responders including HMGB1 (admission illness day, white blood cell counts, C-reactive protein, aspartate aminotransferase, lactate dehydrogenase), values of HMGB1 showed the widest area under the receiver operating characteristic curve. In conclusion, an elevated HMGB1 value could be a potential marker for poor-responders.

Establishment of a new Hodgkin's cell line (HD-70) of B-cell origin.

A new Hodgkins cell line, designated HD‐70, was established from the peripheral blood of a 69‐year‐old man with Hodgkins disease of nodular sclerosing type. The cell line grows in a single cell suspension and has a doubling time of 28 hours. The cells have a round or irregular nucleus or multiple nuclei in relatively abundant cytoplasm that is positive for acid phosphatase, alpha‐naphthyl butyrate esterase, and periodic acid‐Schiff stains. HD‐70 cells are positive for CD30 (Ki‐1 JBer‐H2), CD15 (Leu‐Ml), and CD71 (OKT9) antigens and contain cytoplasmic immunoglobulin (Ig) (A, kappa). Southern blot analysis showed that the cells have Ig heavy and kappa light chain gene rearrangement and lack T‐cell receptor gene rearrangement. Chromosome analysis disclosed that the cells have a human karyotype with complicated abnormalities, including a 14q+. Heterotrans‐plantation of the HD‐70 cell line into newborn hamsters treated with antilymphocyte serum produced massive tumors with remarkable fibrosis and collagen band formation. These tumors displayed histologic features similar to those of the nodular sclerosing type tumor of the patient. Such fibrosis production and collagen band formation in heterotransplanted tumors suggest that a certain cytokine that induces fibrosis might be produced by HD‐70 cells. This cell line may be useful for understanding the biology and pathogenesis of Hodgkins disease. Cancer 1992; 69:1034–1041.

EBV AND HODGKIN'S CELLS

haemopoietic recovery, due to the exacerbation of the chronic hepatitis which occurred 10 d after BMT. Successful treatment of aplastic anaemia with syngeneic BMT following preconditioning (Royal Marsden Hospital BMT team, 19 77) or immunosuppressive therapy (Appelbaum et al, 1985) indicates that some cases of post-hepatitic aplastic anaemia are immune-mediated. However, it is unlikely that an immune mechanism was involved in the bone marrow failure of this patient, because sustained marrow recovery was produced by the second BMT without preconditioning. A recent report showed that patients with fulminant non-A, non-B hepatitis who needed liver transplantation developed aplastic anaemia at a very high frequency (Tzakis et al, 1988). This finding indicates that severity of hepatitis correlates with the development of aplastic anaemia to some extent. This case seems to be worthy of note, because it differs from previous reports in terms of a successful second BMT without pretransplant immunosuppression following the unsuccessful first one. The clinical course of this case suggests that when failure of syngeneic BMT for aplastic anaemia is suspected of being associated with post-transplant hepatitis, simple marrow infusion from the same donor should be tried again after recovery or during the chronic phase of hepatitis.

Platelet vascular endothelial growth factor is a useful predictor for prognosis in Kawasaki syndrome

Kawasaki syndrome (KS) is an acute febrile vasculitis of childhood. Coronary artery abnormalities (CAA) are a significant problem in KS patients. High dose intravenous immunoglobulin (IVIG) is effective for reducing the occurrence of CAA. Clinical and histopathological findings suggest that vascular endothelial growth factor (VEGF) is involved in CAA. In circulating blood, newly activated platelets are the major source of VEGF, which is released in large amounts in vascular inflammation. The present study analysed 80 KS patients (69 IVIG responders and 11 IVIG non‐responders) and evaluated the role of platelet VEGF in KS vasculitis. Serum VEGF and platelet VEGF levels were significantly higher in KS patients than controls (P < 0·001). Platelet VEGF reflected the reactivity of IVIG treatment and was decreased in responders (P < 0·001), but remained increased in non‐responders (P = 0·01). Platelet VEGF levels, but not serum VEGF levels, before IVIG were significantly correlated with the maximum CAA z‐score (r = 0·524, P = 0·02). Our findings demonstrate that platelet VEGF may reflect the severity of vasculitis related to the pathological development of CAA in KS. Platelet VEGF may be an important feature of KS pathophysiology.

Large intracardiac thrombus in a child with refractory nephrotic syndrome

Patients in a hypercoagulative state with nephrotic syndrome have a risk of various complications, such as salt water retention, thromboembolism, hyperlipidemia, metabolic bone diseases and infections. The hypercoagulative state in nephrotic syndrome is induced by elevated platelets counts, high levels of cholesterol and low levels of albumin and protein C, high plasma levels of fibrinogen and low plasma levels of anti-thrombin III. We describe here the case of an 11-year-old boy with refractory nephrotic syndrome, complicated by a large isolated thrombus in the right ventricle. The patient urgently underwent thoracotomy with resection. In order to detect asymptomatic intracardiac thrombus, it is important to be aware of the possibility of this complication in patients with refractory nephrotic syndrome.

Potential risk factors for dexmedetomidine withdrawal seizures in infants after surgery for congenital heart disease

PURPOSE Few studies are available on withdrawal seizures about dexmedetomidine (DEX). Thus, we retrospectively evaluated the incidence of withdrawal seizures after discontinuation of DEX and examined potential risk factors in infants after cardiovascular surgery. METHODS The medical records of 142 infants who had undergone cardiovascular surgery between April 2010 and November 2013 were examined. Clinical characteristics and usage of DEX were analyzed. DEX withdrawal seizures were evaluated using Withdrawal Assessment Tool - version 1 (WAT-1). All the patients and controls were categorized according to DEX discontinuation strategy, which was either gradual or abrupt. RESULTS Nine patients (6.3%) developed generalized clonic or generalized tonic-clonic seizures accompanied by preceding fever of >38°C approximately four to eight hours following the discontinuation of DEX, and were clinically diagnosed as DEX withdrawal seizures with a median WAT-1 score of 3. Clinical characteristics and operative data were similar, but median cumulative dose and maximum temperature after discontinuation of DEX were significantly higher in infants with withdrawal seizures than in those without (P=0.007 and P<0.001, respectively). Eight of the 9 patients with withdrawal seizures (88.9%) and 20 of the 133 patients (15.0%) with no withdrawal seizures had discontinued DEX abruptly (P<0.001). Cumulative dose and abrupt discontinuation of DEX were significantly associated with DEX withdrawal seizures in infants after cardiovascular surgery (R=0.619, P=0.004). CONCLUSIONS Physicians should be aware that infants who received DEX after cardiovascular surgery had potential to cause withdrawal seizures accompanied by preceding pyrexia after discontinuation of DEX. Higher cumulative dose and abrupt discontinuation of DEX appears to increase the risk for these withdrawal seizures.

Immunoglobulin G values before treatment are correlated with the responsiveness to initial intravenous immunoglobulin therapy for Kawasaki disease.

Background: Low levels of serum immunoglobulin G (IgG) before intravenous immunoglobulin (IVIG) therapy for Kawasaki disease (KD) have been reported as one of the risk factors for coronary artery abnormalities (CAAs). This risk factor needs to be re-evaluated because the dosage of IVIG has changed from 0.2-0.4 g/kg/day for 5 days to a single high dose of 2 g/kg. Methods: We reviewed the clinical records of KD patients admitted to our hospital from January 2001 to August 2011. Patients who were given a single high dose of IVIG within 7 days of illness, and who had blood collected for serum immunoglobulin values before treatment, were selected. The serum immunoglobulin levels and coronary artery diameters measured by echocardiogram were transformed to z-scores. Results: The subjects were 197 KD patients, including 22 IVIG nonresponders and 16 patients with CAAs. Of these, 150 (76%) had a z-score for IgG (IgGz) of ≤0. There were no differences in IgGz values between patients with CAAs and those without CAAs. However, nonresponders had higher IgGz values than responders (median, 25th percentile and 75th percentile: −0.26, −0.83 and 0.34 vs. −0.79, −1.40 and −0.03; p = 0.020). Logistic regression analysis showed that the IgGz value was an independent risk factor for resistance to IVIG (OR 1.36, 95% CI 1.002-1.849; p = 0.048). Conclusions: Low IgGz values were not a risk factor for CAAs in this study. However, KD patients with relatively high IgGz values before treatment may have an increased risk of resistance to initial IVIG therapy.

Development of Kawasaki syndrome in autoimmune neutropenia after treatment with granulocyte colony-stimulating factor

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