Introduction
It is a rare pulmonary infection caused by Cryptococcus neoformans. It is a potentially life-threatening fungal disease affecting humans and animals worldwide. It is more commonly seen in immunocompromised patients, such as in human immunodeficiency virus (HIV) patients. The patients usually present with severe pneumonia. However, immunocompetent patients rarely get infected with the infection and may show mild symptoms. The fungal spores are usually found in soil contaminated by avian droppings. The method of entry of the fungus is usually through the respiratory tract causing pulmonary infections. It may disseminate to any organ, most commonly the central nervous system and skin, and rarely may cause isolated pulmonary disease. Pulmonary infection is difficult to diagnose and majorly goes undiagnosed. It can often mimic lung cancer, tuberculosis, pneumonia, and other pulmonary mycoses clinically and radiologically.
Cryptococcosis is an opportunistic systemic mycosis caused by two environmental yeast species, Cryptococcus neoformans, and Cryptococcus gattii. Cryptococcus neoformans is distributed worldwide and causes opportunistic diseases associated with many immunocompromised states, predominantly HIV infection. Cryptococcus gattii is a primary pathogen, mainly in the tropics and subtropics. It may cause more frequent neurological complications as compared to the neoformans infection. It is also very difficult to treat due to reduced sensitivity to antifungal therapy compared to neoformans infection. Therefore, a more aggressive approach is required to treat such infections.
Who Can Get Cryptococcal Infections?
It is most commonly seen in patients with weak immune systems. It is most commonly seen in
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Patients with human immunodeficiency virus.
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Patients who have undergone an organ transplant.
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Patients who are taking immunosuppressive drugs such as corticosteroids.
What Are the Signs and Symptoms of Cryptococcal Infections?
Pulmonary cryptococcus does not present with specific clinical manifestations.
The clinical presentation is variable, from being asymptomatic in some individuals to presenting with mild symptoms such as
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Low-grade fever.
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Cough.
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Expectorations.
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Chest-tightness.
What Are the Diagnostic Tests to Be Carried Out?
The most common radiological features are solitary or multiple pulmonary nodules and segmental or lobar consolidations. The main diagnostic methods include
1. Sample Culture: The sample can be collected from blood, cerebrospinal fluid, and sputum. Samples for culture should be placed on Sabouraud dextrose agar at 30 degress Celcius for seven days, in aerobic conditions, and observed daily. Cryptococcus appears as creamy mucoid colonies. C.neoformans are identified generally as smooth colonies, while C.gattii mostly appears as mucoid colonies.
2. Imaging Tests: The most common radiographic finding is nodule formation. The nodules are often multi-pulmonary, well-defined with smooth borders, and usually less than ten mm in diameter. They usually involve less than ten percent of the lung parenchyma and are mostly distributed peripherally in the middle and upper lobes. Sometimes, large cavities may be seen as an unusual presentation. Rare appearances of pulmonary cryptococcus include calcifications, "tree in bud" appearance, lymphadenopathies, and pleural effusions.
- Chest X-Ray: It may reveal diffuse lung infiltration. But sometimes, the findings are often seen as a lung mass that may be confused with lung cancer. Therefore, a correct diagnosis is required for appropriate treatment planning.
- Computed Tomography (CT) Scan: It may be present as:
a) Clustered nodular form.
b) Solitary nodule or mass with or without cavitation.
c) Diffuse nodules.
d) Peribronchovascular consolidation.
3. Positron Emission Tomography: It may show a spiculated mass with high fluorodeoxyglucose uptake resembling lung cancer mass.
4. Lung Biopsy: It is the best diagnostic method for negative sputum or bronchoscopy specimens. There are several methods of lung biopsy, including percutaneous lung biopsy, trans-bronchial lung biopsy, video-assisted thoracoscopic (VAT) biopsy, and open lung biopsy.
5. Histological Staining: Most commonly, hematoxylin and eosin (H& E), Grocott or Gomori methenamine silver (GMS), and periodic acid-Schiff (PAS) are used to detect cryptococcus that appears as little budding yeasts (4-10 μm), usually surrounded by thick capsules in the lung tissue. To display the capsule, tissue sections can be processed with alcian blue or mucicarmine.
6. Antigen Detection Test: The types of cryptococcal antigen (CrAg) detection tests available are the latex agglutination test (LAT), the enzyme-linked immunoassay test (EIA), and the lateral flow immunoassay (LFA). These methods are rapid, sensitive, and specific but have not been standardized for respiratory specimens such as bronchoalveolar lavage, pleural fluid, or sputum. Capsular polysaccharides of cryptococcus can be detected and quantified from body fluids such as serum, cerebrospinal fluid, bronchoalveolar lavage, and urine using specific anti-C.neoformans antisera. The sensitivity and specificity of cerebrospinal fluid CrAg are very high. False negative serum CrAg is commonly associated with pulmonary cryptococcal infection, probably because of the low fungal burden outside the lung or the capsule-deficient strain of cryptococcus. However, it may be positive in the case of disseminated cryptococcus with lung involvement.
What Is the Management of Pulmonary Cryptococcus?
The management of the disease primarily depends upon the host's immune status and the predilection of the disease, whether it is present as a localized mass in the lungs or has disseminated.
In cases of mild to moderate infections, the drug of choice is Fluconazole.
The most common drug of choice in case of severe cryptococcal infection is Amphotericin-B with Flucytosine.
How Can Cryptococcal Infections Be Prevented?
Cryptococcal infections are most commonly found in the environment. People can easily breathe in the fungi, but it remains undiagnosed in healthy individuals. However, in individuals with a weak immune system, it may remain dormant for some time and may cause the infection only after some time when the body's immune response is too low. This creates a window period from the time of exposure to the infection and when a test can reliably detect that infection. This allows early detection and treatment of the infection before symptoms develop.
Conclusion
Cryptococcosis is the most common opportunistic fungal infection in immunocompromised patients. Pulmonary cryptococcosis usually remains undiagnosed and leads to severe disseminated disease involving the central nervous system and skin. Most lesions involved the periphery of the lower lung lobes with a halo sign. It is most commonly asymptomatic but, in severe cases, may cause respiratory distress. The most common CT findings are multiple pulmonary nodules with ill-defined margins. The diagnosis is based on isolating cryptococcus or detecting cryptococcal antigen, pulmonary sample, and pertinent clinical radiological and histopathological findings. Treatment usually involves antifungals such as Amphotericin B along with Flucytosine.
