What are the other Names for this Condition? (Also known as/Synonyms)

• Busse-Buschke Disease
• European Blastomycosis
• Torular Meningitis

What is Cryptococcosis? (Definition/Background Information)

• Cryptococcosis is a potentially fatal fungal infection mainly involving the lungs and brain. In the lungs, it manifests as pneumonia, and in the brain as meningitis
• When the lungs are infected, the symptoms usually include difficulty breathing, chest pain and fever. When the brain is infected, the symptoms may include headache, fever, neck pain, nausea and vomiting, light-sensitivity, and altered behavior
• The complications of Cryptococcosis may include raised intracranial pressure, failing eyesight, and immune reconstitution inflammatory syndrome (IRIS)
• Cryptococcosis is most commonly caused by the fungi Cryptococcus neoformans, or less commonly by Cryptococcus gattii. It is acquired by breathing in the spores from the air and can be spread by contact with pigeon droppings, unwashed raw fruit, or via infected individuals
• Cryptococcosis usually affects individuals who have reduced/impaired immunity. These include individuals with HIV infection or AIDS, those undergoing cancer chemotherapy, and organ transplant recipients
• Individuals with Cryptococcosis are typically treated with anti-fungal medications. With early diagnosis, cryptococcal infections (involving the brain) and disseminated infections, are generally amenable to therapy. Cryptococcal meningitis is normally fatal unless treated appropriately and promptly

Who gets Cryptococcosis? (Age and Sex Distribution)

• Cryptococcosis typically occurs in individuals with a weakened immune system
• Generally, adults aged 40-60 years of age are affected the most
• Both males and females are affected, with males being affected more often than females. 
• The condition is observed in settings where access to healthcare resources is limited, specifically sub-Saharan Africa and parts of Asia

 What are the Risk Factors for Cryptococcosis? (Predisposing Factors)

The risk factors for Cryptococcosis may include:

• HIV infection
• Corticosteroid and/or immunosuppressive therapies
• Solid organ transplantation (who are on immunosuppressant drugs)
• Rheumatologic diseases
• Diabetes mellitus
• Malignant and lymphoproliferative disorders
• Sarcoidosis
• Treatment with monoclonal antibodies (such as etanercept, infliximab, and alemtuzumab)
• Idiopathic CD4+ lymphopenia
• Chronic liver disease
• Renal failure and/or peritoneal dialysis
• Hyper IgM syndrome and hyper IgE syndrome

It is important to note that having a risk factor does not mean that one will get the condition. A risk factor increases one’s chances of getting a condition compared to an individual without the risk factors. Some risk factors are more important than others.

Also, not having a risk factor does not mean that an individual will not get the condition. It is always important to discuss the effect of risk factors with your healthcare provider.

What are the Causes of Cryptococcosis? (Etiology)

Cryptococcus neoformans and Cryptococcus gattii are fungi that cause Cryptococcosis

• Both types of fungi are found in soil. Breathing in the fungus can lead to a lung infection. The infection may resolve on its own, or sometimes remain in the lungs. It may even spread throughout the body (disseminate infection) 
• C. neoformans lives in the environment throughout the world. The fungus is typically found in soil, on decaying wood, in tree hollows, or in bird droppings. C neoformans infection is most often seen in people with a weak immune system. The infection is not contagious

What are the Signs and Symptoms of Cryptococcosis?

Generally, individuals with a healthy immune system may present no significant signs and symptoms. Patients who are immunocompromised may have varying signs and symptoms based on the severity of the infection in the body.

The signs and symptoms of Cryptococcosis affecting different organs may include:

• The signs and symptoms related to brain infection may include:
  • Fever and headache
  • Neck stiffness
  • Nausea and vomiting
  • Blurred vision or double vision
  • Confusion
• The signs and symptoms related to lung infection may include:
  • Difficulty in breathing
  • Cough
  • Chest pain
• Other symptoms may include:
  • Bone pain or tenderness of the breastbone
  • Fatigue
  • Skin rash, including pinpoint red spots called petechiae, ulcers, or other skin lesions
  • Sweating that is unusual and often excessive at night
  • Swollen glands
  • Unintentional weight loss

How is Cryptococcosis Diagnosed?

A diagnosis of Cryptococcosis may involve the following exams and tests.

• Complete physical examination and medical history evaluation, including past and travel history
• Assessment of presenting signs and symptoms that may include checking for:
  • Abnormal breath sounds
  • Fast heart rate 
  • Fever
  • Mental status changes
  • Stiff neck that can be a sign of meningitis (inflammation of the brain coverings)
• Blood culture to differentiate between the two fungi and help provide a definitive diagnosis
• Sputum culture and stain
• Chest X-ray
• CT scan of the head
• Lung biopsy
• Bronchoscopy and bronchoalveolar lavage
• Lumbar puncture to evaluate the cerebrospinal fluid (CSF) for evidence of cryptococcal meningitis
• Cryptococcal antigen test in CSF: It is the most appropriate test for diagnosis of cryptococcal meningitis in terms of sensitivity

Other rapid diagnostic methods may include:

• Latex agglutination test
• Lateral flow immunochromatographic assay (LFA)
• Enzyme immunoassay (EIA)
• Polymerase chain reaction (PCR) analysis

Many clinical conditions may have similar signs and symptoms. Your healthcare provider may perform additional tests to rule out other clinical conditions to arrive at a definitive diagnosis.

What are the possible Complications of Cryptococcosis?

Cryptococcosis is known to be associated with the following complications:

• Chronic pulmonary infections may cause the following medical issues:
  • Large masses in the lobes of the lungs 
  • Segmental pneumonia (involving parts of lungs)
  • Pleural effusions (fluid in the lungs)
• Central nervous system infections complications may include:
  • Hydrocephalus (abnormally large head)
  • Failing eyesight
  • Seizures
  • Hearing loss
  • Brain damage
• Side effects and complications from treatment with amphotericin B may include:
  • Kidney damage
  • Muscle and joint pain
  • Fever
  • Nausea and vomiting
  • Thrombophlebitis: An inflammatory process that causes a blood clot to form and block one or more veins, usually in the legs

How is Cryptococcosis Treated?

Individuals infected with Cryptococcosis need to take antifungal medications for at least 6 months, often longer than 6 months.

• There are generally two phases of treatment. One is termed the initiation phase (shorter duration) and the other, the maintenance phase (of a longer duration).
• The type of treatment usually depends on the severity of the infection and the parts of the body that are affected.

Some of the medications administered may include:

• Amphotericin B (that can present severe side effects)
• Flucytosine
• Fluconazole

Moreover, treatment to address the signs and symptoms and complications is also provided.

How can Cryptococcosis be Prevented?

The following measures may be undertaken to decrease the risk for Cryptococcosis:

• Avoiding exposure to soil in areas with high risk of fungal spores
• Avoiding or minimizing contact with individuals who have infections
• Washing hands frequently with suitable hand sanitizer
• Having a healthy lifestyle with good food control to keep diabetes under check
• Promptly diagnosing and adequately treating diseases and conditions that increase one’s risk for Cryptococcosis
• Maintaining long-term follow-up to watch out for infections, especially in immunocompromised individuals

Early screening for Cryptococcosis in susceptible individuals can be done to prevent complications of the disease. The World Health Organization (WHO) recommends cryptococcal antigen screening in HIV-infected persons with CD4<100 cells/μL.

• Cryptococcal antigen can be found in the body weeks before symptoms of meningitis. Individuals who test positive for cryptococcal antigen should take suitable antifungal medicine
• When antigen screening is not available, fluconazole (antifungal medicine) should be taken prophylactically in adults living with HIV infection, with a CD4 cell count <100 cells/mm³ 
• Screening and primary prophylaxis are not recommended for children, given the low incidence of Cryptococcal Meningitis in this age group

What is the Prognosis of Cryptococcosis? (Outcomes/Resolutions)

• In most cases, the prognosis of Cryptococcosis is favorable, with early diagnosis and treatment
• The condition can be fatal if left untreated, particularly in immunocompromised patients, especially when the central nervous system is involved

Additional and Relevant Useful Information for Cryptococcosis:

The following DoveMed website link is a useful resource for additional information:

https://www.dovemed.com/diseases-conditions/infection-center/