Although Aspergillus is ubiquitous in the environment, immunocompetent people do not usually develop aspergillosis unless very sick. Risk factors for the disease are neutropenia, immunosuppression (either by disease or by pharmacological intervention), cytotoxic chemotherapy, allogeneic hematopoietic stem cell transplantation, and solid organ (such as lung) transplantation [1]. Neoplasms are also risk factors, mainly those of hematopoietic or lymphoreticular origin [2].

Invasive infection can spread to the systemic circulation and be carried to various organs. The portal of entry is often the lung and less commonly the skin, and the gastrointestinal tract [3] [4] [5]. Other, less usual entry sites have been reported, for example, a peritoneal dialysis [6]. As Aspergillus reaches the circulatory system, it can cause hemorrhage and infarction [7] and invade other organs: the brain, heart, kidneys, liver, spleen and gastrointestinal tract [4]. The brain is a frequently affected end organ; most cases of brain aspergillosis originate from lung infection [7].

Many patients have respiratory problems, such as fever, cough, hemoptysis, tracheobronchitis [8], and pleural friction rub, which may indicate hemorrhagic infarction of the lung [4]. Central nervous system aspergillosis manifests as nonspecific neurological symptoms, which are often dramatic [4], presenting as seizures, cerebral infarctions, intracranial hemorrhage, meningitis and others [8].

Other tissues affected by hematogenous dispersion of the organism are the eye, the heart (although cardiac surgery remains the leading cause of aspergillosis in the heart), the skin, the gastrointestinal tract where perforation, bleeding or ischemia may follow; the kidneys, and ribs where infections mainly in children with chronic granulomatous disease may occur [4].

• Fever

  Clinical and pathologic findings in a 65-year old woman with fever of unknown origin are described in this report. Generalized aspergillosis with endocarditis was demonstrated at autopsy. [ncbi.nlm.nih.gov]

  After stabilization, he developed persistent fevers with worsening mental status. Imaging of the brain revealed multiple hemorrhages with impending brain herniation. [journals.lww.com]

• Goiter

  An ultrasound revealed moderate goiter of left lobe prevalence with parenchymal hypoechogenicity and heterogeneous structure, changes in the left lobe: solid-cystic heterogeneous nodular lesion 27 x 16 x 23mm, thick peripheral hypoechoic halo without [revistanefrologia.com]

• Low Back Pain

  An immunocompromised patient presented with chronic low back pain as the initial symptom and a subcutaneous abscess as the initial sign of disseminated aspergillosis. [ncbi.nlm.nih.gov]

  back pain as the initial symptom and a subcutaneous abscess as the initial sign of disseminated aspergillosis. [mdedge.com]

• Back Pain

  An immunocompromised patient presented with chronic low back pain as the initial symptom and a subcutaneous abscess as the initial sign of disseminated aspergillosis. [ncbi.nlm.nih.gov]

  pain as the initial symptom and a subcutaneous abscess as the initial sign of disseminated aspergillosis. [mdedge.com]

• Mental Deterioration

  She gradually developed dyspnea and mental deterioration after admission, which was followed by sudden cardiac arrest at 7:00 am on March 12. [rc.rcjournal.com]

• Apraxia

  Western blots were performed for genes associated with double-stranded DNA breakage repair, and they were normal for: ATM (ataxia telangiectasia), NBS (Nijmegen breakage syndrome), FANCD2 (Fanconi anemia), APTX (ataxia-oculomotor apraxia syndrome), Artemis [aspergillus.org.uk]

Many authors remark that diagnosis of invasive and disseminated aspergillosis is difficult [1] [8] [9], yet because of the high mortality, diagnosis must be prompt to allow quick and aggressive treatment [10]. Ambiguity in the description of the disease, such as distinguishing ‘proven’ aspergillosis from ‘probable’ and ‘possible’ disease, is one reason for the difficulty [10] [3]. Colonization and invasion by Aspergillus are also not easily distinguished [11]. The standard methods of culturing the fungus and identifying its characteristic hyphae in the microscope from sputum or bronchoalveolar lavage (BAL) are not sensitive enough [1] [3]. Invasive procedures such as thoracoscopic biopsy may be needed for conclusive diagnosis.

Chest computed tomography (CT) frequently shows nodules and a characteristic “halo sign”, which can be used as an indication of invasive aspergillosis in neutropenic patients [1].

Laboratory tests for the early detection of aspergillosis have been developed; an assay detects galactomannan (GM) [9], which is released from the hyphae of Aspergillus. GM can be detected in the serum or BAL, days before radiological signs are seen; however, the sensitivity of the test may not be consistent between different laboratories [1]. Another cell wall component beta-d-glucan is tested for the levels in serum samples [12] in an assay that is regarded as very sensitive for detecting early fungal infections [1]. Another promising technique is the polymerase chain reaction (PCR), performed on BAL and blood samples [11] [13].

Characteristics of imaging patterns for cerebral aspergillosis have been described [14]: these include decreased CT attenuation and ring-enhancing lesions in multiple areas. The most typically affected brain areas are the basal nuclei and thalami [7]. This reflects the spreading of the disease through the lenticulostriate and thalamoperforator arteries. The radiologic appearance of disseminated aspergillosis in the brain is characterized by the appearance of early infarcts and hemorrhages followed by the later spreading into surrounding tissue and is different from metastases [7]. Any of the above findings, or an increase in the size or number of the lesions in immunocompromised patients, should be a strong enough indication for starting antifungal therapy [7].

• Mural Thrombus

  A thoracic CT revealed mycotic aneurysm of the ascending thoracic aorta, including mural thrombus. [elsevier.es]

• Bowel Distention

  CT findings were a diffuse, small-bowel distention with a thickened, distal, ileum wall. Emergency surgery was performed with resection and immediate anastomosis of the distal ileum. [ncbi.nlm.nih.gov]

• Thrombocytosis

  A patient with idiopathic thrombocytosis developed sudden loss of vision in his left eye secondary to endophthalmitis caused by Aspergillus flavus. [ncbi.nlm.nih.gov]

• Toxoplasma Gondii

  Vitreous was also sent to the NMC and Toxoplasma gondii PCR was performed with a negative result. [elsevier.es]

• Hepatic Necrosis

  Three patients with subacute hepatic necrosis died of clinically unrecognized disseminated aspergillosis. All of the patients had pulmonary aspergillosis and Aspergillus infections of the CNS. [ncbi.nlm.nih.gov]

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