Pulmonary cryptococcosis is a subacute or chronic visceral fungal disease caused by Cryptococcus neoformans or Cryptococcus gattii. It primarily affects the lungs and central nervous system but can also involve bones, skin, mucous membranes, and other organs. Infection with this fungus typically triggers only a mild inflammatory response and is more common in immunosuppressed individuals, such as those with AIDS. Approximately 20% of cases occur in immunocompetent individuals.
Etiology
The pathogenic species of Cryptococcus primarily include Cryptococcus neoformans and its gattii variant (currently at least nine species). Cryptococcal cells are typically round or oval, do not form hyphae or spores, and reproduce by budding. Cryptococcus neoformans is a saprophytic yeast that can grow at 37°C and possesses a capsule.
Based on its capsular antigens, Cryptococcus is classified into four serotypes: A, B, C, and D. The geographic distribution of infections caused by different variants and serotypes varies. Serotypes A, D, and AD are globally distributed and are commonly found in soil and pigeon droppings, often associated with immunosuppressed patients (especially those with AIDS). The gattii variant (serotypes B and C) and serotype B are more prevalent in tropical and subtropical regions.
The fungus can be isolated from soil, pigeon droppings, and fruits, as well as from the skin, mucous membranes, and feces of healthy individuals. Environmental pathogens primarily enter the human body via the respiratory tract but may also enter through the skin or gastrointestinal tract, causing disease or establishing colonization. In HIV-infected patients, the incidence of cryptococcosis is close to 10%, ranking as the fourth most common infectious complication. Cryptococcosis can occur at any age, though it is more common in children and adults over 40 years old.
Cryptococcus neoformans does not produce toxins, and infection does not cause tissue destruction, hemorrhage, infarction, necrosis, fibrosis, or calcification. The direct effects of the pathogen on tissues are due to the proliferation of yeast cells, which occupy space and exert compressive effects.
Clinical Manifestations
Pulmonary cryptococcal infections often have an insidious onset. Symptoms may include fever, cough, production of small amounts of white sputum, shortness of breath, chest pain, hemoptysis, weight loss, and diaphoresis. Some patients may be asymptomatic. Chest X-rays often reveal localized small patchy infiltrates in the lungs, which are frequently misdiagnosed as tuberculosis or atypical pneumonia. In some cases, pulmonary lesions may resolve spontaneously without antifungal therapy. However, in other cases, the disease may progress slowly or disseminate.
Chronic inflammation and granuloma formation may develop, leading to nodular or mass-like lesions on chest X-rays, which can be misdiagnosed as lung cancer.
Extrapulmonary infections may occur, and in rare cases, meningitis or other extrapulmonary infections may appear even after pulmonary lesions have resolved.
In immunosuppressed patients, chest X-rays may show multiple patchy consolidations or diffuse interstitial infiltrates in both lungs. Nodules or masses may also be present, sometimes involving the pleura, leading to pleural effusion or pneumothorax, and may be accompanied by hilar lymphadenopathy.
Diagnosis
Cryptococcal growth in sputum cultures is helpful for diagnosing pulmonary cryptococcosis but is not definitive, as the fungus can colonize the respiratory tract without causing disease. A definitive diagnosis requires direct sampling and culture from the lower respiratory tract or lung tissue.
Cryptococci can be identified in cerebrospinal fluid (CSF) using India ink staining, which reveals thick-walled yeast cells with a translucent halo.
Tissue samples stained with methenamine silver or Fontana-Masson stain (FMS) can selectively highlight cryptococcal cells.
The latex agglutination test for cryptococcal antigen is highly valuable for diagnosing cryptococcal infections.
Treatment
Treatment options include fluconazole, itraconazole, and amphotericin B.
For asymptomatic immunocompetent individuals, clinical observation and follow-up may suffice, or oral fluconazole at 200-400 mg/day for 3-6 months may be administered.
For symptomatic patients, a treatment course of 6-12 months is recommended.
For severe cases, especially those with cryptococcal meningitis, combination antifungal therapy is advised, such as amphotericin B combined with 5-flucytosine.
For patients undergoing surgery without prior chemotherapy for pulmonary cryptococcosis, postoperative oral fluconazole at 200-400 mg/day for 2-4 months is recommended.