Miceli Marisa H, Maertens Johan, Buvé Kristel, Grazziutti Monica, Woods Gail, Rahman Mazhar, Barlogie Bart, Anaissie Elias J
Myeloma Institute for Research and Therapy, University of Arkansas for Medical Sciences, Little Rock, Arkansas 72205, USA.
Cancer. 2007 Jul 1;110(1):112-20. doi: 10.1002/cncr.22738.
Assessing the outcome of patients with invasive pulmonary aspergillosis by using conventional criteria is difficult, particularly when clinical and radiologic worsening coincides with neutrophil recovery. Usually, it is assumed that this deterioration is related to progressive aspergillosis, prompting changes in patient management. However, its temporal relation with neutrophil recovery suggests that it may be caused by an immune reconstitution syndrome (IRIS). Galactomannan is an Aspergillus-specific polysaccharide that is released during aspergillosis and is detected by the serum galactomannan test, which has been approved by the United States Food and Drug Administration for the diagnosis of invasive aspergillosis. In this study, the authors used sequential galactomannan testing to distinguish IRIS responses from progressive aspergillosis.
From April 2001 to December 2006, patients with hematologic malignancies underwent galactomannan screening during periods when they were at risk. The clinical and laboratory findings from patients who had >or=2 consecutive positive galactomannan assays (optical density, >or=0.5) were reviewed.
Nineteen neutropenic patients with aspergillosis developed clinical and radiologic pulmonary deterioration during neutrophil recovery. Deterioration coincided with microbiologic response, as documented by rapid normalization of serum galactomannan, and, in 16 patients, was followed by complete clinical response and survival at 3 months, although there were no changes in antifungal therapy. The 3 patients who died during the first month had no evidence of aspergillosis at autopsy examination.
The authors propose that IRIS was responsible for the current findings and provide a definition for the syndrome. They also recommend serial galactomannan testing to guide aspergillosis management. Declining galactomannan values imply IRIS with an aspergillus response and obviate the need for invasive procedures and alternative antifungal therapies, whereas persistent galactomannan elevation indicates progressive aspergillosis and requires prompt treatment modification.
采用传统标准评估侵袭性肺曲霉病患者的预后很困难，尤其是当临床和影像学恶化与中性粒细胞恢复同时出现时。通常认为这种恶化与曲霉病进展有关，从而促使调整患者的治疗方案。然而，其与中性粒细胞恢复的时间关系提示，这可能是由免疫重建综合征（IRIS）所致。半乳甘露聚糖是曲霉属特异性多糖，在曲霉病发病时释放，可通过血清半乳甘露聚糖检测来检测，该检测已获美国食品药品监督管理局批准用于诊断侵袭性曲霉病。在本研究中，作者采用连续半乳甘露聚糖检测来区分IRIS反应与曲霉病进展。
2001年4月至2006年12月，血液系统恶性肿瘤患者在处于发病风险期间接受半乳甘露聚糖筛查。对连续≥2次半乳甘露聚糖检测呈阳性（光密度≥0.5）患者的临床和实验室检查结果进行回顾。
19例患有曲霉病的中性粒细胞减少患者在中性粒细胞恢复期间出现临床和影像学肺部恶化。恶化与微生物学反应同时出现，血清半乳甘露聚糖迅速恢复正常即可证明，并且在16例患者中，随后出现完全临床反应且3个月时存活，尽管抗真菌治疗并无变化。在第一个月内死亡的3例患者尸检时未发现曲霉病证据。
作者提出IRIS是当前这些发现的原因，并为该综合征给出定义。他们还建议进行连续半乳甘露聚糖检测以指导曲霉病的治疗。半乳甘露聚糖值下降意味着伴有曲霉反应的IRIS，无需进行侵入性操作和更换抗真菌治疗，而持续的半乳甘露聚糖升高表明曲霉病进展，需要迅速调整治疗。
