Krithinaki Maria I, Kokkinakis Ioannis, Markatzinou Styliani, Masaoutis Christos, Solomou Elena, Papakitsou Ioanna, Xirouchaki Nektaria, Liapis Ioannis, Papadaki Helen A, Pontikoglou Charalampos G
Department of Hematology, School of Medicine, University of Crete, University General Hospital of Heraklion, 71500 Heraklion, Greece.
Department of Pathology, School of Medicine, University of Crete, 71500 Heraklion, Greece.
Hematol Rep. 2025 May 6;17(3):25. doi: 10.3390/hematolrep17030025.
Severe aplastic anemia (SAA) is an uncommon life-threatening disorder characterized by hypocellular bone marrow and pancytopenia. It is typically associated with immune-mediated mechanisms, requiring immunosuppressive therapy (IST) or hematopoietic stem cell transplantation (HSCT). Infections, especially invasive fungal infections such as mucormycosis and aspergillosis, constitute principal causes of morbidity and mortality in patients with SAA. Genetic predispositions, including perforin (PRF1) polymorphisms, may further complicate disease outcomes by impairing immune function.
We describe a case of a 36-year-old female patient diagnosed with SAA, for whom IST was considered, due to the unavailability of a matched sibling donor for HSCT. The patient presented with a feverish condition and deep neck space abscesses were revealed by imaging, caused by invasive aspergillosis. To prioritize infection control, IST was postponed and antifungal therapy with abscess drainage was initiated. However, aspergillosis progressed, despite aggressive and prompt treatment, and ultimately resulted in sepsis, multiorgan failure, and death. In addition, mucormycosis was confirmed post-mortem. Two heterozygous polymorphisms (c.272C>T and c.900C>T), were identified by genetic testing, which may have contributed to immune dysregulation and fungal dissemination.
The complex interplay between managing SAA and addressing invasive fungal infections, which remain a leading cause of mortality in immunocompromised patients, is highlighted in this case. The latter emphasizes the importance of prompt diagnosis and targeted treatment to alleviate infection-related complications while maintaining care continuity for the hematologic disorder. The detection of polymorphisms raises questions about their implication in immune regulation and disease trajectory, emphasizing the need for further research in this field.
重型再生障碍性贫血（SAA）是一种罕见的危及生命的疾病，其特征为骨髓细胞减少和全血细胞减少。它通常与免疫介导机制相关，需要免疫抑制治疗（IST）或造血干细胞移植（HSCT）。感染，尤其是侵袭性真菌感染，如毛霉菌病和曲霉病，是SAA患者发病和死亡的主要原因。包括穿孔素（PRF1）多态性在内的遗传易感性可能通过损害免疫功能使疾病预后更加复杂。
我们描述了一例36岁女性SAA患者，由于无法获得匹配的同胞供体进行HSCT，考虑对其进行IST。患者出现发热症状，影像学检查发现深部颈部间隙脓肿，由侵袭性曲霉病引起。为优先控制感染，推迟了IST并开始进行脓肿引流的抗真菌治疗。然而，尽管进行了积极及时的治疗，曲霉病仍进展，最终导致败血症、多器官功能衰竭和死亡。此外，尸检确诊为毛霉菌病。基因检测发现两个杂合多态性（c.272C>T和c.900C>T），这可能导致了免疫失调和真菌播散。
本病例突出了SAA管理与侵袭性真菌感染治疗之间复杂的相互作用，侵袭性真菌感染仍是免疫受损患者死亡的主要原因。后者强调了及时诊断和针对性治疗以减轻感染相关并发症的重要性，同时保持对血液系统疾病的连续护理。多态性的检测引发了关于它们在免疫调节和疾病进程中的意义的问题，强调了该领域进一步研究的必要性。
