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Cryptococcosis Clinical Presentation

  • Author: John W King, MD; Chief Editor: Pranatharthi Haran Chandrasekar, MBBS, MD  more...
Updated: Feb 29, 2016


The principal site or sites of infection (ie, pulmonary, CNS, disseminated disease) dictate the medical history of patients with symptomatic cryptococcal disease. Factors that are especially important include the presence of coexisting conditions associated with immunosuppression (eg, steroid use, malignant disease, transplantation) or HIV infection. Other key factors in the history often relate to organ-specific problems (eg, cough, headaches, focal neurological defects, skin rashes).

Cryptococcus has become an increasingly common infection among patients who have received solid organ transplants and is now among the 3 most common invasive fungal infections in the posttransplant period. Cryptococcus infections in solid organ transplant recipients usually occur 1-2 years after transplantation. However, a study identified a subset of patients who developed invasive cryptococcal disease within the first 30 days.[11] In 2 patients, invasive cryptococcal disease occurred in the first posttransplant day. The source of these infections are most likely unrecognized pretransplant infections or donor-derived infections. Most of the patients in this report were liver transplant recipients.

Pulmonary cryptococcosis

The pattern of cryptococcal pulmonary disease varies greatly, ranging from asymptomatic saprophytic airway colonization to acute respiratory distress syndrome, which affects immunocompromised hosts (eg, patients with AIDS, organ transplant recipients). On occasion, cryptococcal pulmonary disease may even manifest as a slowly progressive mass that may compress thoracic structures such as the vena cava.

A patient with pulmonary cryptococcosis may present with mild-to-moderate symptoms, including fever, malaise, cough with scant sputum, pleuritic pain, and hemoptysis (rare). Unusual findings include rales or pleural rub. Pleural effusions may be present but are uncommon.

Cavitation and hilar lymphadenopathy are uncommon.

Calcification and pulmonary fibrosis or stranding are usually absent.

Although chronic infection can occur, immunocompetent patients usually have spontaneous regression of both clinical and radiological manifestations.

Among patients who are HIV positive and have a pulmonary cryptococcal infection, 5%-25% present with cough and dyspnea.

Adult respiratory distress syndrome may ensue.

Pulmonary disease is more likely to progress in immunocompromised patients and to require antifungal therapy.

Pulmonary disease may occur in the absence of extrapulmonary disease. Conversely, extrapulmonary disease (eg, meningitis) may develop in the absence of identifiable pulmonary pathology.

CNS cryptococcosis

Meningitis and meningoencephalitis are the most common manifestations of CNS cryptococcosis and are usually subacute or chronic in nature.

This form of infection is invariably fatal without appropriate therapy; death may occur from 2 weeks to several years after symptom onset.

The clinical presentation and course of cryptococcal meningitis vary, relating in part to underlying medical conditions (eg, diabetes, sarcoidosis, glucocorticoid use) and the immune status of the host.

The most common symptoms are headache and altered mental status, including personality changes, confusion, lethargy, obtundation, and coma.

Nausea and vomiting are common and are often associated with increased intracranial pressure, whereas fever and stiff neck, symptoms associated with a more aggressive inflammatory response, are less common.

Some patients who are HIV positive may have minimal or nonspecific symptoms at presentation. Patients are often afebrile or have a mildly elevated temperature.

Symptoms such as blurred vision, photophobia, and diplopia may result from arachnoiditis, papilledema, optic nerve neuritis, or chorioretinitis.

Other findings include hearing defects, seizures, ataxia, aphasia, and choreoathetoid movements.

Dementia is a potential sequela and may indicate the presence of hydrocephalus as a late complication.

Cryptococcosis in other sites

After lung and CNS infection, the next most commonly involved organs in disseminated cryptococcosis include the skin, prostate, and the medullary cavity of bones.

Cutaneous manifestations occur in 10%-15% of cases and usually take the form of papules, pustules, nodules, ulcers, or draining sinuses.

Umbilicated papules in patients with AIDS may resemble molluscum contagiosum.

Cellulitis with necrotizing vasculitis is reported in patients who undergo organ transplantation.

Bone lesions develop in 5%-10% of patients and are usually osteolytic or resemble cold abscesses. These lesions may be confused with tuberculosis or neoplasm.

Other less common forms of cryptococcosis include the following:

  • Chorioretinitis
  • Hepatitis
  • Renal abscess
  • Prostatitis (Prostatic foci of cryptococci may persist after therapy for CNS disease and may act as a reservoir for relapse in men with AIDS.)
  • Myositis
  • Adrenal involvement


The physical findings of patients with cryptococcal infection primarily depend on the patient’s immune status prior to infection and the site or sites involved. Because the inflammatory responses to encapsulated cryptococci are blunted, tissues may be extensively involved before the patient presents for medical care. Furthermore, the limited inflammatory response associated with the encapsulated yeast can result in mild clinical findings, further complicating diagnosis.

Pulmonary cryptococcosis

Although C neoformans most often infects patients via the pulmonary route, less than 15% of patients present with a clinical picture of pneumonia. On occasion, isolation of Cryptococcus from sputum may represent colonization rather than true infection, especially in patients with chronic obstructive pulmonary disease (COPD) or bronchiectasis.

One third of immunocompetent patients who develop pulmonary infection are asymptomatic or have symptoms so mild that they do not seek medical care.

When symptoms develop in immunocompetent hosts, they include cough (54%), cough with the production of scant mucoid sputum (32%), and pleuritic chest pain (46%). Low-grade fever, dyspnea, weight loss, and malaise may also be present.

Night sweats, as observed in tuberculosis, are uncommon in cryptococcal pulmonary disease but may occur with disseminated or CNS disease.

In immunocompromised patients who do not have HIV infection, cryptococcal pulmonary infection is associated with an accelerated course, often with early dissemination. As many as 83% of these patients present with constitutional symptoms (eg, fever, malaise).

Patients co-infected with HIV and Cryptococcus present with fever (84%), cough (63%), dyspnea (50%), headache (41%), and weight loss (47%). Often, patients with co-infection have cryptococcal antigens and cultures that are positive in cerebrospinal fluid (CSF), blood, and urine. Any part of a lung may be involved, and infiltrates may be bilateral, unilateral, multilobar, or lobar.

CNS cryptococcosis

Although C neoformans enters the body via the lungs, the CNS is the main site of clinically evident infection in both immunocompetent and immunocompromised hosts. Following pulmonary infection, cryptococci disseminate widely and may infect any organ. The organs most often involved include the CNS, bones, prostate, eyes, and skin. Prior to the discovery of amphotericin B in 1955, 80% of patients with CNS involvement died within 2 years of diagnosis.

Cryptococcal CNS infections usually involve both the brain and meninges, causing diffuse disease. Immunocompetent hosts may present with either meningitis or focal cryptococcomas. Meningitis manifests with diffuse nonfocal findings (eg, altered mental status, vomiting), whereas cryptococcomas often manifest with focal neurologic defects.

Cryptococcal skin infection

Approximately 10%-15% of patients infected with C neoformans develop skin involvement. In immunocompetent hosts, the skin may be the only site of infection; however, immunosuppressed patients, especially those with AIDS, have skin involvement that must be considered evidence of disseminated disease.

Cutaneous lesions include nodules, ulcers, papules, and vasculitic lesions.

Cryptococcal osteomyelitis

Bone involvement is documented in 5%-10% of patients with cryptococcal infection.

Bone lesions are usually osteolytic and may be misinterpreted as neoplastic lesions or osseous tuberculosis.

Other sites of cryptococcal infection

The eyes and prostate are often involved. Eye involvement often manifests as vision loss caused by optic neuritis or endophthalmitis. Rapid diagnosis and treatment are essential to preserve the patient's sight.

In men, eradication of cryptococci from the prostate is often difficult, and prostatic foci of infection can act as a reservoir for relapse of systemic infections.

Other considerations

A CT scan or MRI in patients with cryptococcal infection may reveal diffuse atrophy or cerebral edema with focal, homogenous, or contrast-enhanced areas. These findings may help distinguish cryptococcal infection from other causes of intracranial mass lesions and infections. However, scans are not diagnostic in and of themselves.

Early cryptococcal meningitis may resemble other mycoses, syphilis, tuberculosis, or meningeal metastases. Do not confuse this condition with chronic meningitis caused by other infections or by noninfectious causes (eg, sarcoidosis, chronic benign lymphocytic meningitis).

Pulmonary findings may be indistinguishable from those in patients with acute pneumonia caused by Pneumocystis jiroveci (previously Pneumocystiscarinii), Mycobacterium tuberculous, Histoplasma capsulatum, or other organisms.

Cutaneous lesions are nonspecific and may be mistaken for a large variety of lesions related to other causes, including acne, syphilis, lipoma, tuberculosis, molluscum contagiosum, or basal cell carcinoma.

Bone lesions may be mistaken for tubercular cold abscess or neoplasm.



Infection with either C neoformans or Cgattii causes cryptococcal disease. The most common pathogen of the genus Cryptococcus in immunocompromised patients is C neoformans. Both C neoformans and Cgattii cause disease in immunocompetent patients. Most patients with disease due to C gattii have been reported to be immunocompetent.

Contributor Information and Disclosures

John W King, MD Professor of Medicine, Chief, Section of Infectious Diseases, Director, Viral Therapeutics Clinics for Hepatitis, Louisiana State University Health Sciences Center; Consultant in Infectious Diseases, Overton Brooks Veterans Affairs Medical Center

John W King, MD is a member of the following medical societies: American Association for the Advancement of Science, American College of Physicians, American Federation for Medical Research, Association of Subspecialty Professors, American Society for Microbiology, Infectious Diseases Society of America, Sigma Xi

Disclosure: Nothing to disclose.


Folusakin O Ayoade, MD Clinical Fellow, Division of Infectious Diseases, LSU Health Science Center

Folusakin O Ayoade, MD is a member of the following medical societies: American College of Physicians, American Medical Association, Infectious Diseases Society of America, Society of Hospital Medicine

Disclosure: Nothing to disclose.

Specialty Editor Board

Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Received salary from Medscape for employment. for: Medscape.

John W King, MD Professor of Medicine, Chief, Section of Infectious Diseases, Director, Viral Therapeutics Clinics for Hepatitis, Louisiana State University Health Sciences Center; Consultant in Infectious Diseases, Overton Brooks Veterans Affairs Medical Center

John W King, MD is a member of the following medical societies: American Association for the Advancement of Science, American College of Physicians, American Federation for Medical Research, Association of Subspecialty Professors, American Society for Microbiology, Infectious Diseases Society of America, Sigma Xi

Disclosure: Nothing to disclose.

Chief Editor

Pranatharthi Haran Chandrasekar, MBBS, MD Professor, Chief of Infectious Disease, Program Director of Infectious Disease Fellowship, Department of Internal Medicine, Wayne State University School of Medicine

Pranatharthi Haran Chandrasekar, MBBS, MD is a member of the following medical societies: American College of Physicians, American Society for Microbiology, International Immunocompromised Host Society, Infectious Diseases Society of America

Disclosure: Nothing to disclose.

Additional Contributors

Jeffrey D Band, MD, FACP, FIDSA Professor of Medicine, Oakland University William Beaumont School of Medicine; Health System Chair, Healthcare Epidemiology and International Medicine, Beaumont Health System; Former Chief of Infectious Diseases, Beaumont Hospital; Clinical Professor of Medicine, Wayne State University School of Medicine

Disclosure: Nothing to disclose.

Meredith L DeWitt, MD Fellow, Department of Internal Medicine, Section of Infectious Diseases, Louisiana State University Health Sciences Center

Meredith L DeWitt, MD is a member of the following medical societies: Infectious Diseases Society of America

Disclosure: Nothing to disclose.

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Axial T2-weighted magnetic resonance image shows clustered hyperintensities in the left caudate; these are consistent with enlarged Virchow-Robin spaces caused by small cryptococcomas.
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