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Disseminated Aspergillosis

Disseminated aspergillosis is an emerging disease that mainly afflicts patients who are severely immunocompromised or are seriously ill. The entry site for the infection is often the respiratory tract, and if the disease becomes invasive in the lungs, it can spread to various organs via the circulation. Disseminated aspergillosis progresses quickly and is often fatal.


Presentation

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]
  • This diagnosis should be considered when neutropenic patients show abdominal pain and distention with fever.[ncbi.nlm.nih.gov]
  • According to international consensus, infection was categorized as probable (two host factors: deep neutropenia for 10 days and refractory fever for 96 h; major clinical criteria of lower respiratory tract and CNS invasive fungal infection; positive results[ncbi.nlm.nih.gov]
  • Three days after discharge, the patient was readmitted with hemorrhagic cystitis, persistent thrombocytopenia, and bilateral pulmonary consolidation, although no fever was present. The ANC at the time of readmission was 3,500.[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]
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]

Workup

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].

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]
White Matter Lesions
  • In our experience, these nonenhancing white matter lesions were most conspicuous on proton density–and T2-weighted images.[ajnr.org]

Treatment

  • Initial clinical manifestations were suggestive of hepatitis, and steroids and antibiotics were used in the treatment. This therapy may have fostered the onset of an opportunistic mycosis.[ncbi.nlm.nih.gov]
  • Skin lesions healed without any surgical treatment. The infant was discharged in good health. Long-term follow-up at three years of age revealed normality of all neurodevelopmental and cognitive parameters.[ncbi.nlm.nih.gov]
  • BmGT was detected in two serum samples obtained prior to intravenous antifungal treatment, which was then reduced after voriconazole treatment was started.[ncbi.nlm.nih.gov]
  • Shortly following the completion of treatment symptoms developed suggestive of tumour recurrence. At post mortem the cause was identified as disseminated aspergillosis with extensive cerebral involvement.[ncbi.nlm.nih.gov]
  • Disseminated aspergillosis after stem cell transplantation has a high mortality despite treatment with amphotericin B or one of the azoles.[ncbi.nlm.nih.gov]

Prognosis

  • Disseminated aspergillosis is very rare in immunocompetent hosts and is typically associated with a poor prognosis.[ncbi.nlm.nih.gov]
  • Taek Soo Kim Kyoung-Ho Song Se Joon Woo Eu Suk Kim Kyoung Un Park Hong Bin Kim Article First Online: 29 May 2015 292 Downloads 7 Citations Abstract Disseminated aspergillosis is very rare in immunocompetent hosts and is typically associated with a poor prognosis[link.springer.com]
  • Prognosis is generally poor, although early diagnosis and treatment may result in recovery 3-4.[radiopaedia.org]
  • Prognosis CNPA has a significant mortality of up to 40%, even if promptly recognised and treated. It is easy to miss and, in such cases, carries a worse prognosis.[patient.info]
  • Despite aggressive treatment, the visual prognosis is poor because of frequent macular involvement. Final visual acuity is usually less than 20/200. Hariprasad SM, Mieler WF, Holtz ER, et al.[aao.org]

Etiology

  • The latter etiologic mechanism was suggested once before. Neither of these patients showed other underlying disease.[neurology.org]
  • Initial cutaneous lesions may appear in the form of either macules, papules, nodules, or plaques. [4] Although rare, cases of primary cutaneous infection with Aspergillus have been described in immunocompetent patients. [5, 6] Etiology Aspergillosis is[emedicine.medscape.com]
  • Etiology ABPA is found in people with asthma and/or CF who are allergic to Aspergillus . The thick mucus found in the airways of these patients may make clearing inhaled Aspergillus spores difficult.[emedicine.medscape.com]
  • The Etiology of Ring Lesions on Diffusion-Weighted Imaging. Neuroradiol J, 2014; 27(3):280–7. pmid:24976194 View Article PubMed/NCBI Google Scholar 32. Osborn AG. Diagnostic Cerebral Angiography. Lippincott Williams & Wilkins; 1999. 491 p. 33.[journals.plos.org]

Epidemiology

  • With studies suggesting that the incidence of this disease is increasing, and with relatively few epidemiological data available in this population, we evaluated cases of disseminated aspergillosis identified at autopsy over a one-year period on a 31-[ncbi.nlm.nih.gov]
  • This book summarizes the current knowledge about Aspergillosis, covering: Epidemiology Pathogenesis Clinical manifestations Diagnosis Treatment Prevention Written by internationally respected authors, the information presented in this book adds for a[books.google.de]
  • Trends in the postmortem epidemiology of invasive fungal infections at a university hospital. J Infect. 2010;61:259–65. CrossRef PubMed Google Scholar 5. Cook DJ, Achong MR, King DE. Disseminated aspergillosis in an apparently healthy patient.[link.springer.com]
  • […] symptoms after near drowning during the tsunami, 3 and meningitis of pregnant women receiving anesthesia for Caesarean section at the hospitals affected by the tsunami, have suggested an association between tsunamis and Aspergillus infections. 4 Further epidemiological[rc.rcjournal.com]
  • Aspergilloma Epidemiology Aspergilloma has a variable prevalence depending on the amount of cavitating lung disease affecting a population.[patient.info]
Sex distribution
Age distribution

Pathophysiology

  • While Aspergillus also disseminates to the CNS hematogenously, most commonly but not exclusively from the lung (1), the pathophysiology is often different.[ajnr.org]
  • The pathophysiology of tsunami lung is thought to involve not only chemical or mechanically induced inflammation, but also bacterial infection, the chief pathogens of which include Aeromonas species, Burkholderia pseudomallei, Chromobacterium violaceum[rc.rcjournal.com]
  • Pathophysiology Cutaneous aspergillosis is caused by infection with ubiquitous soil- and water-dwelling saprophytes of the Aspergillus genus.[emedicine.medscape.com]
  • Pathophysiology In a healthy, immunocompetent individual, macrophages and neutrophils normally defend against the inhaled fungus.[patient.info]
  • Pathophysiology Aspergillus causes a spectrum of disease, from colonization to hypersensitivity reactions to chronic necrotizing infections to rapidly progressive angioinvasion, often resulting in death.[emedicine.medscape.com]

Prevention

  • Special attention is given to the prevention and treatment of these diseases found in developing countries as well as the latest findings about new antimicrobial agents, gram-negative infections and their management, and recommendations for immunization[books.google.de]
  • This book summarizes the current knowledge about Aspergillosis, covering: Epidemiology Pathogenesis Clinical manifestations Diagnosis Treatment Prevention Written by internationally respected authors, the information presented in this book adds for a[books.google.de]
  • Centers for Disease Control and Prevention Aspergillosis (Medical Encyclopedia) Aspergillosis precipitin (Medical Encyclopedia) Pulmonary aspergilloma (Medical Encyclopedia) [ Read More ][icdlist.com]
  • […] it is recommended to start treatment when symptoms appear. 9 Voriconazole, the most used and most effective drug for treating invasive aspergillosis, 2,8 inhibits the activity of cytochrome P450-3A4; as such, the tacrolimus dose should be adjusted to prevent[revistanefrologia.com]
  • Centers for Disease Control and Prevention (November 21, 2015 updated.) Histoplasmosis. Available online at . Accessed August 27, 2016. Centers for Disease Control and Prevention (February 13, 2014 updated.) Pneumocystis Pneumonia.[labtestsonline.it]

References

Article

  1. Segal BH, Walsh TJ. Current approaches to diagnosis and treatment of invasive aspergillosis. Am J Respir Crit Care Med. 2006 Apr 1;173(7):707-717.
  2. Smith JM, Hampton JR, Webb RW. Disseminated aspergillosis, Cushing's syndrome, and oat cell carcinoma of the lung. Chest. 1979 Jul;76(1):112-113.
  3. Walsh TJ, Anaissie EJ, Denning DW, et al, Infectious Diseases Society of America. Treatment of aspergillosis: clinical practice guidelines of the Infectious Diseases Society of America. Clin Infect Dis. 2008 Feb 1;46(3):327-360.
  4. Procop GW, Pritt BS, eds. Pathology of Infectious Diseases: A Volume in the Series: Foundations in Diagnostic Pathology. Philadelphia, PA: Elsevier Saunders; 2015.
  5. Alderson JW, Van Dinter TG Jr, Opatowsky MJ, Burton EC. Disseminated aspergillosis following infliximab therapy in an immunosuppressed patient with Crohn's disease and chronic hepatitis C: a case study and review of the literature. MedGenMed. 2005 Sep 21;7(3):7.
  6. Ross DA, Anderson DC, Macnaughton MC, Stewart WK. Fulminating disseminated aspergillosis complicating peritoneal dialysis in eclampsia. Arch Intern Med. 1968 Feb;121(2):183-188.
  7. DeLone DR, Goldstein RA, Petermann G, Salamat MS, Miles JM, Knechtle SJ, Brown WD. Disseminated aspergillosis involving the brain: distribution and imaging characteristics. AJNR Am J Neuroradiol. 1999 Oct;20(9):1597-1604.
  8. Soubani AO, Chandrasekar PH. The clinical spectrum of pulmonary aspergillosis. Chest. 2002;121:1988–1999.
  9. Meersseman W, Lagrou K, Maertens J, et al. Galactomannan in bronchoalveolar lavage fluid: a tool for diagnosing aspergillosis in intensive care unit patients. Am J Respir Crit Care Med. 2008 Jan 1;177(1):27-34.
  10. Garnacho-Montero J, Amaya-Villar R, Ortiz-Leyba C, et al. Isolation of Aspergillus spp. from the respiratory tract in critically ill patients: risk factors, clinical presentation and outcome. Crit Care. 2005 Jun;9(3):R191-199.
  11. Lugosi M, Alberti C, Zahar JR, et al. Aspergillus in the lower respiratory tract of immunocompetent critically ill patients. J Infect. 2014 Sep;69(3):284-292.
  12. De Vlieger G, Lagrou K, Maertens J, Verbeken E, Meersseman W, Van Wijngaerden E. Beta-D-glucan detection as a diagnostic test for invasive aspergillosis in immunocompromised critically ill patients with symptoms of respiratory infection: an autopsy-based study. J Clin Microbiol. 2011 Nov;49(11):3783-3787.
  13. Buchheidt D, Baust C, Skladny H, et al. Detection of Aspergillus species in blood and bronchoalveolar lavage samples from immunocompromised patients by means of 2-step polymerase chain reaction: clinical results. Clin Infect Dis. 2001 Aug 15;33(4):428-435.
  14. Ashdown BC, Tien RD, Felsberg GJ. Aspergillosis of the brain and paranasal sinuses in immunocompromised patients: CT and MR imaging findings. AJR Am J Roentgenol 1994;162:155–159.

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Last updated: 2019-07-11 20:26