Eculizumab treatment in paediatric patients diagnosed with aHUS after haematopoietic stem cell transplantation: a HSCT-TMA case series from Japanese aHUS post-marketing surveillance.

Haematopoietic stem-cell transplantation (HSCT)-associated thrombotic microangiopathy (HSCT-TMA) is a serious complication with high mortality. Accumulating evidence suggests that complement dysregulation is potentially involved in the development of HSCT-TMA. We retrospectively analysed the clinical characteristics and outcomes of thirteen paediatric patients who were diagnosed with atypical haemolytic uremic syndrome and treated with eculizumab to manage HSCT-TMA during post-marketing surveillance in Japan. The median time from HSCT to TMA was 31 days (Interquartile range, IQR;21-58) and the median doses of eculizumab was three (IQR;2-5). Seven patients (54%) were alive at the last follow-up while six died due to complications related to HSCT. Six of seven survivors initiated eculizumab after insufficient response to plasma therapy. Following eculizumab treatment, median platelet counts and LDH levels in all survivors significantly improved and renal function improved in 4/7 patients. All survivors possessed potential risk factors of complement overactivation. During the follow-up period after eculizumab discontinuation (median;111.5 days, IQR;95-555), no TMA recurrence was observed. In this analysis, eculizumab showed benefit in over half of this paediatric patient population. Ongoing clinical studies are expected to optimize the treatment regimen of terminal complement pathway inhibitor, and it may become a therapeutic option for paediatric HSCT-TMA in the future.

The impact of vitamin D on the onset and progress of Kawasaki disease.

BACKGROUND: The seasonal epidemic of Kawasaki disease (KD) in winter in Japan suggests that low vitamin D status may affect KD through the immune system. We aimed to evaluate the effect of vitamin D on the onset and clinical course of KD. METHODS: We conducted a case-control study to compare 25-hydroxyvitamin D (25(OH)D) levels in KD patients admitted to our hospital between March 2018 and June 2021, with those in healthy controls from published Japanese data. In patients with KD, we evaluated the association of 25(OH)D levels with intravenous immunoglobulin resistance and coronary artery lesions. RESULTS: We compared 290 controls and 86 age-group-adjusted patients with KD. The 25(OH)D levels in KD patients were lower than those in the controls (median: 17 vs. 29 ng/mL, P < 0.001). In winter, 25(OH)D levels in KD patients were lower than those in summer (median: 13 vs. 19 ng/mL). The adjusted odds ratios for the onset of KD were 4.9 (95% CI: 2.5-9.6) for vitamin D insufficiency (25(OH)D: 12-20 ng/mL) and 29.4 (95% CI: 12.5-78.2) for vitamin D deficiency (25(OH)D < 12 ng/mL). Among 110 KD patients, 25(OH)D levels at diagnosis of KD were not associated with intravenous immunoglobulin resistance or coronary artery lesions. CONCLUSIONS: The 25(OH)D levels in patients with KD were lower than those in the controls, especially in winter. Lower 25(OH)D levels in winter were associated with an increased risk of KD onset. It remains to be elucidated whether the observed association has a causal relationship.

Evans syndrome after unrelated bone marrow transplantation for refractory cytopenia of childhood.

Post-transplant ES, which is often resistant to therapies, has seldom been described. This report describes a case of ES after UBMT for RCC. A five-yr-old boy developed RCC with no evidence of monosomy 7. Because no matching family donors were available for SCT and immunosuppressive therapy was ineffective, UBMT was performed when he was six yr old. The conditioning regimen included TAI (3 Gy) and administration of FLU, CY, and rabbit antithymocyte globulin. The recovery of blood cells was good. He displayed grade II acute GVHD involving only the skin. ES developed on day 66, with positive results for Epstein-Barr virus DNA and HHV 6. Cytopenia was resolved with treatment with RTX, GCV, an escalated dose of steroids, high-dose gammaglobulin, and romiplostim. No relapse has occurred since discontinuing steroids on day 177 and romiplostim on day 268. Post-SCT ES after UBMT is rare, and the risk factors and therapies are unclear. Prospective analysis and collection of cases from multiple centers are required for clarification.

Clinical features and outcome of acute exacerbation of interstitial pneumonia: collagen vascular diseases-related versus idiopathic.

BACKGROUND: Relatively little is known about acute exacerbation (AE) of interstitial pneumonia associated with collagen vascular diseases (CVD-IPs). OBJECTIVES: This study was aimed at clarifying clinical characteristics and outcome in AE of CVD-IPs, compared with those of idiopathic interstitial pneumonias (IIPs). METHODS: We retrospectively reviewed 112 admission cases with suspected AE of CVD-IPs or IIPs during 2003-2009. IIPs were diagnosed with idiopathic pulmonary fibrosis (IPF) or non-IPF, mostly based on radiologic findings. Of these, 15 AEs of CVD-IPs (6 rheumatoid arthritis, 6 dermatomyositis and 3 systemic sclerosis) and 47 AEs of IIPs (13 IPF and 34 non-IPF) were included. RESULTS: The clinical characteristics in AE of CVD-IPs were similar to those of IIPs, except for younger age (63.3 ± 6.8 vs. 73.8 ± 9.1 years; p = 0.0001) and higher PaO(2)/FiO(2) at the onset of AE (205 ± 81.2 vs. 145 ± 53.8 mm Hg; p = 0.002) in the former. Dermatomyositis-related interstitial pneumonia (IP) showed a relatively indolent onset and was often associated with worsening control of the underlying disease, whereas AE of other CVD-IPs resembled that of IIPs. 90-day mortality of 33% in AE of CVD-IPs was similar to that of IIPs (44%; p = 0.44) or non-IPF (34%; p = 0.94), but was significantly better than that of IPF (69%; p = 0.04). CONCLUSION: Clinical features and outcome in AE of CVD-IPs were similar, if not identical, to those of IIPs, having a significant impact on the clinical course. AE of advanced IPF with typical radiologic features seems to have higher mortality compared with other forms of IP.

[Two cases of successfully treated intravascular lymphoma presenting with fever and dyspnea].

We report two patients with intravascular large B-cell lymphoma who presented with fever and dyspnea. Serum level of lactate dehydrogenase (LDH) and soluble interleukin-2 receptor (sIL-2R) levels were extremely high in both cases. Chest CT revealed tumor mass and ground glass opacity in one patient, and no abnormality in another patient who had severe hypoxemia. Their perfusion ventilation lung scintigraphy demonstrated multiple defects, and gallium scintigraphy showed abnormal accumulation in both lungs, and the spleen. Both patients were successfully treated with rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP). Initial chemotherapy was followed by high dose systemic chemotherapy with peripheral blood stem cell support. Intravascular large B-cell lymphoma should always be considered in the differential diagnosis of fever and hypoxemia with elevated serum LDH and sIL-2R, regardless of the chest CT findings.

The use of non-invasive ventilation for life-threatening asthma attacks: Changes in the need for intubation.

BACKGROUND AND OBJECTIVE: Although non-invasive ventilation (NIV) has been shown to be effective in a wide variety of respiratory diseases, its role in severe asthma attacks remains uncertain. The aim of this study was to clarify the effectiveness of NIV in patients experiencing severe attacks of asthma. METHODS: A retrospective cohort study was performed, comparing the periods November 1999-October 2003 (pre-introduction of NIV) and November 2004-October 2008 (post-introduction of NIV). The data and clinical outcomes for patients who experienced severe attacks of asthma, and who fulfilled the inclusion criteria, were retrieved and compared. RESULTS: Fifty events (48 patients) from the pre-NIV period and 57 events (54 patients) from the post-NIV period, which required hospitalization, were included in the analysis. Nine of the 50 pre-NIV events (mean PaO(2)/fraction of inspired O(2) (FiO(2)) 241 +/- 161; PaCO(2) 79 +/- 40) were treated primarily by endotracheal intubation (ETI), while 17 of the 57 post-NIV events (PaO(2)/FiO(2) 197 +/- 132, P = 0.39; PaCO(2) 77 +/- 30, P = 0.95) were treated primarily by NIV. The rate of ETI decreased in the post-NIV period (2/57 (3.5%) vs 9/50 (18%), P = 0.01). NIV was started earlier than mechanical ventilation (MV) with ETI (mean time interval between arrival and start of MV 171.7 +/- 217.9 min vs 38.5 +/- 113.8 min for NIV, P < 0.05). In the post-NIV cohort, there was a trend towards a reduction in the duration of MV with ETI or NIV (36.9 +/- 38.4 h vs 20.3 +/- 35.8 h, P = 0.09), and hospital stay was shortened (12.6 +/- 4.2 vs 8.4 +/- 2.8 days, P < 0.01). No deaths occurred during this period as a consequence of asthma attacks. CONCLUSIONS: The need for ETI in patients with severe attacks of asthma was decreased after introduction of NIV. The ready availability of NIV enabled the rapid commencement of MV and may decrease the need for ETI. NIV is an acceptable and useful method of stabilizing patients experiencing severe attacks of asthma.