PDF(Pubmed)
Abstract：
Mucormycosis (MCR) is an emerging and frequently lethal fungal infection caused by the Mucorales family, with Rhizopus, Mucor, and Lichtheimia, accounting for > 90% of all cases. MCR is seen in patients with severe immunosuppression such as those with hematologic malignancy or transplantation, Diabetes Mellitus (DM) and diabetic ketoacidosis (DKA) and immunocompetent patients with severe wounds. The recent SARS COV2 epidemy in India has resulted in a tremendous increase in MCR cases, typically seen in the setting of uncontrolled DM and corticosteroid use. In addition to the diversity of affected hosts, MCR has pleiotropic clinical presentations, with rhino-orbital/rhino-cerebral, sino-pulmonary and necrotizing cutaneous forms being the predominant manifestations. Major insights in MCR pathogenesis have brought into focus the host receptors (GRP78) and signaling pathways (EGFR activation cascade) as well as the adhesins used by Mucorales for invasion. Furthermore, studies have expanded on the importance of iron availability and the complex regulation of iron homeostasis, as well as the pivotal role of mycotoxins as key factors for tissue invasion. The molecular toolbox to study Mucorales pathogenesis remains underdeveloped, but promise is brought by RNAi and CRISPR/Cas9 approaches. Important recent advancements have been made in early, culture-independent molecular diagnosis of MCR. However, development of new potent antifungals against Mucorales remains an unmet need. Therapy of MCR is multidisciplinary and requires a high index of suspicion for initiation of early Mucorales-active antifungals. Reversal of underlying immunosuppression, if feasible, rapid DKA correction and in selected patients, surgical debulking are crucial for improved outcomes.
摘要：
毛霉菌病（MCR）是由毛霉菌家族引起的一种新兴且经常致命的真菌感染，与根霉，Mucor,还有Lichtheimia,占所有病例的90%以上。MCR见于严重免疫抑制患者，如血液系统恶性肿瘤或移植患者，糖尿病（DM）和糖尿病酮症酸中毒（DKA）和具有严重伤口的免疫功能的患者。印度最近的SARSCOV2流行导致MCR病例大量增加,通常见于不受控制的DM和皮质类固醇的使用。除了受影响宿主的多样性之外，MCR具有多效性临床表现，犀牛眶/犀牛脑，肺和坏死性皮肤形式是主要表现。MCR发病机理中的主要见解已引起了宿主受体（GRP78）和信号通路（EGFR激活级联）以及Mucorales用于侵袭的粘附素的关注。此外，研究已经扩大了铁的可用性和铁稳态的复杂调节的重要性，以及霉菌毒素作为组织侵袭的关键因素的关键作用。研究Mucorales发病机理的分子工具箱仍然不发达，但是RNAi和CRISPR/Cas9方法带来了希望。早期已经取得了重要的进展，MCR的培养非依赖性分子诊断。然而,开发针对Mucorales的新型有效抗真菌药仍未满足。MCR的治疗是多学科的，需要高度怀疑早期具有Mucorales活性的抗真菌药的启动。潜在免疫抑制逆转，如果可行，快速DKA矫正和选定的患者，手术切除对改善预后至关重要.
