Aspergillus spp. are a weird fungus in that we have never seen the yeast form. Even when they are in the human body, they will form the hyphael structures, with no yeast cells. The mold form is made of septate hyphae that branch off at acute angles. When looking at a slide, and you’re trying to identify fungi, scan the whole slide and if you see several branches that look less than 90-degree angles, then you can guess Aspergillus spp. Another structure that might help with identification is the reproductive structure which are conidia that release spores.
There are many Aspergillus spp. that can cause disease in humans, but the most common is Aspergillus fumigatus.
This is also a fungal species that produces catalase, which means that patients with Chronic Granulomatous Disease (which are more susceptible to infections with catalase-positive organisms) are more susceptible to acquiring infection with this organism. Patients with Cystic Fibrosis, AIDS, and/or asthma are also more susceptible to this infection.
Typically, this infection is transmitted to humans by the inhalation of the conidia. In immunocopetent people, this is no problem because their alveolar macrophages clear the fungal spores before they germinate. Immunocompromised people have trouble with the clearance, and therefore the spores germinate in their lungs, forming the hyphael structures within their lung tissues.
The most likely manifestation of aspergillosis is the formation of granulomatous nodules in the lung tissue. These nodules mimic tuberculosis, but might also have the “halo sign” which is an area of ground-glass opacities around the nodule. This is widely asymptomatic, but might have a chronic, dry cough as well.
Another manifestation is Chronic Pulmonary Aspergillosis which is a long-term development of cavitary lesions within the lung tissue and will present as fever, chest pain, cough, dyspnea, and hemoptysis as the lesions development.
Sometimes, growth on the walls of these cavities will break off into the lumen of the cavity and begin to grow as a fungal ball or aspergilloma. These are made of hyphal structures, fibrin, mucus, and cellular debris. They will present with fever and hemoptysis. They also will present after the formation of cavities in the lung tissue caused by other infections like tuberculosis. One really cool thing about aspergillomas is they are literally a ball of gunk bouncing around in a cavity, so if you take imaging of the patient standing up and then take an image of them lying down, the aspergilloma will appear to move locations.
One interesting manifestation is called the Allergic Bronchopulmonary Aspergillosis which occurs primarily in patients with asthma or Cystic Fibrosis. These patients are first colonized by Aspergillus spp. which on top of being a hyphal fungal infection, produce fungal spores in the tissues. These patients develop a Type-I Hypersensitivity reaction against these fungal spores causing bronchospasms, fever, mucus impaction, granuloma formation, and pulmonary infiltrates. This of course exacerbates the problem in both asthmatic patients and Cystic Fibrosis patients. Because of the Type-I hypersensitivity, these patients will also have a high level of IgE and peripheral eosinophilia. This does look *a lot* like an allergic reaction to fungal spores. I looked everywhere for why this condition isn’t just considered an allergy to fungal spores, but has it’s own name and categorization, but I couldn’t find an answer, so if you know the answer let me know!
Occasionally in immunocompromised patients the hyphael structures will invade the blood vessels of the lung. This is called angioinvasive aspergillosis. It’s possible that this local invasion of the lung tissue can cause a hemorrhagic infarction and/or necrotizing bronchopneumonia. If the hyphae disseminate, it can cause problems in the organs that are seeded including: kidney failure, endocarditis, ring-enhancing lesions in the brain, and necrosis of the nasal cavity among others. This has a mortality rate of over 60%, so it is imperative that early diagnosis of aspergillosis and appropriate treatment is started immediately before the hyphae become invasive.
There are a few molecules that are produced in some Aspergillus spp. like the alfatoxins which can cause damage to the liver. Alfatoxins are usually ingested by eating crops that have collected alfatoxins from molds in the environment. Normally, humans just consume a small dose of alfatoxins causing subclinical symptoms and chronic liver damage and inflammation. However, any patient that has chronic inflammation it can lead to the development of hepatocellular carcinoma. Children are particularly susceptible to presenting with liver necrosis due to alfatoxin ingestion, and therefore the FDA has regulated that all grain storage be tested for alfatoxin contamination.
Some Aspergillus species also have citrinin and ochratoxin which are nephrotoxins and cause damage to the kidney. These are also tied to the consumption of grains contaminated with the products, and are often found together. They is a common cause of endemic nephropathy, which is an acquired, chronic nephropathy culminating in kidney failure.
Diagnosis is typically clinical, but bronchoaleolar lavage and biopsy samples can easily culture the organism for identification. Patients with Allergic Bronchopulmonary Aspergillosis and Cystic Fibrosi might have a difficult time collecting the causative agent. You can however use serologic testing to test for high anti-Aspergillus IgE antibodies, to identify the syndrome. You can also do an ELISA test for several sugar molecules found in many of the Aspergillus spp.
Asymptomatic patients do not require any treatment if their only finding is an aspergillus nodule. Pulmonary Aspergillosis requires treatment with itraconazole. Allergic Bronchopulmonary Aspergillosis typically needs itraconazole and oral steroids to combat the allergic inflammation. Aspergillomas are usually removed surgically, but anti-fungal medications prior to and after surgery are necessary in case some hyphal elements break off during removal and seed the area again. Angioinvasive aspergillosis can be complicated with many medications but most include voriconazole in combination with other medications.
A 54-year-old male presented with a productive cough and hemotysis for the last two months. He did not have any fever, chills, night sweats, shortness of breath, or chest pain. Past medical history is significant for pulmonary tuberculosis at age 50 and Type-2 diabetes mellitus. Chest auscultation revealed scattered, right-upper-lung field crackles. Acid-fast bacilli smears were definitively negative, and HIV testing is negative. Chest radiography of the patient upright reveals a mass in the top of the right lobe, and mass in the middle of the top right lobe when the patient is supine. After developing worsening hemoptysis, emergency removal of the upper lobe was performed. Histology of the removed tissue revealed a mass comprised of fungal hyphae with acute-angle branching, fibrin, and mucus with no evidence of tissue invasion. What is the most likely diagnosis?
A. Pulmonary Aspergillosis
B. Aspergilloma
C. Allergic bronchopulmonary aspergillosis
D. Angioinvasive aspergillosis
First, diagnose the patient.
This patient is presenting with a 2 month history of hemotysis. The history of tuberculosis and the presence of a lung mass might make you immediately think tuberculosis, and you totally should that would be my number one pick too. Except they tell us that the testing definitively did not find any acid-fast bacilli, so we can ignore tuberculosis for now.
Imaging found a mass in the upper lobe when the patient was upright, but the mass must have moved slightly to the middle of the lobe when the patient became supine, which suggests that he mass isn’t really anchored into the tissue.
Histological examination of the lung tissue then found hyphal structures consistent with Aspergillus spp. infection, fibrin, and mucus. and no evidence of invasion.
A. Pulmonary Aspergillosis presents with fever, chest pain, cough, dyspnea, hemotysis, and the slow formation of cavitary lesions in the chest. The imaging did not mention any cavitary lesions, but the presence of a mass. Our patient also didn’t present with fever, chest pain, or dyspnea.
B. Aspergilloma is a fungal ball that forms within a previously developed cavitary lesion. These are made of Aspergillusspp. hyphae, mucus, and fibrin. Patients will present with fever, hemoptysis, and cough. The fungal ball often changes position based on the position of the patient.
C. Allergic bronchopulmonary aspergillosis almost exclusively occurs in patients with Cystic Fibrosis or asthma. This would present as uncontrollable exacerbations of symptoms including bronchospasm, peripheral eosinophilia, fever, production of brown mucus and the formation of mucus plugs.
D. Angioinvasive aspergillosis usually presents in immunocompromised patients and would presnt with much more serious organ dysfunction and destruction.
Therefore,
A 43-year-old male presents to the clinic with a three-week history of wheezing, shortness of breath, and productive cough producing rubbery mucus plugs. Chest auscultation revealed widespread audible expiratory wheeze. Serum levels of total IgE were 1454 kU/L (reference range, <81 kU/L) and antibodies against A. fumigatus IgE levels were 40.5 kU/L (reference range, <35kU/L). Serum complete blood count with differential revealed an elevated eosinophil numbers. What comorbidity is most associated with this patient’s diagnosis?
A. Acquired Immunodeficiency Syndrome
B. Chronic Granulomatous Disease
C. Cystic Fibrosis
D. Diabetes Mellitus
First, diagnose the patient.
This patient is presenting with dyspnea, and coughing up mucus plugs. Diffuse lung inflammation, as determined by the widespread wheezing. High levels of total IgE and in particularly IgE against Aspergillus fumigatus, and high peripheral eosinophilia are all signs of Allergic Bronchopulmonary Aspergillosis.
A. Acquired Immunodeficiency Syndrome which is caused by a long-term unregulated infected with Human Immunodeficiency Virus might make patients more susceptible to acquiring angioinvasive aspergillosis, but not allergic bronchopulmonary aspergillosis.
B. Patients with Chronic Granulomatous Disease are more susceptible to acquiring infections with catalase-positive organisms. Aspergillus spp. are catalase-positve so these patients would be more susceptible to acquiring Pulmonary Aspergillosis, Aspergillomas, or Angioinvasive Aspergillosis, but NOT Allergic Bronchopulmonary Aspergillosis.
C. Patients with Cystic Fibrosis or asthma are particularly susceptible to acquiring Allergic Bronchopulmonary Aspergillosis.
D. Diabetes Mellitus does not cause patients to be more susceptible to acquiring this particular syndrome, but it could make patients more susceptible to acquiring Pulmonary aspergillosis since Diabetes Mellitus makes people immunocompromised.
Therefore,
References:
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5412229/
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1745361/pdf/v054p00044.pdf
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4499746/
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5806394/
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