Cryptococcosis is a fungal infection caused by Cryptococcus neoformans and Cryptococcus gandii. The encapsulated organisms are inhaled and survive in the respiratory tract without causing any harm. However, depending upon the immunity of the individual, it may result in several clinical diseases. Cryptococcosis is therefore known as an opportunistic infection. Patients with immune deficiency such as HIV, corticosteroid therapy or reticulo-endothelial malignancy may suffer from the additional debilitating effects of the disease.
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cryptococcus

Image: “Micrograph of cryptococcus. Field stain.” by Nephron – Own work. License: CC BY-SA 3.0


Overview

Cryptococcosis is an infectious disease that is caused by pathogenic encapsulated yeasts that belong to the genus Cryptococcus. The most common causes of cryptococcosis in humans are Cryptococcus neoformans and Cryptococcus gatti. Cryptococcal meningitis is gaining global importance because of a recent increase in its incidence among patients with AIDS.

Types of Cryptococcosis

Cryptococcosis can be differentiated into three types:

  • Cutaneous Cryptococcosis
  • Pulmonary Cryptococcosis
  • Cryptococcal meningitis

Epidemiology of Cryptococcosis

There are more than 50 species of Cryptococcus, but the above-mentioned species are the only ones reported to be pathogenic in human beings. The two species have five serotypes depending upon the antigenic specificity.

Cryptococcus neoformans has serotypes A, D and AD, while Cryptococcus gandii has serotypes B and C. The former is found in the temperate climatic regions, while the latter is more abundant in the tropical and sub-tropical climates.

Cryptococcus neoformans is found in the droppings of old pigeons, while Cryptococcus gandii grows in the litter surrounding certain species of eucalyptus tree.

Immunocompromised individuals, such as those suffering from AIDS, are frequently infected with Cryptococcus neoformans serotype A. Cryptococcus gandii, for reasons unknown, rarely infects them. The other risk factors for cryptococcosis are summarized below:

  • Use of corticosteroid or other immunosuppressive therapies
  • Solid organ transplantation
  • Sarcoidosis
  • History of rheumatoid arthritis or systemic lupus erythematosus
  • Chronic liver disease, especially if decompensated
  • Idiopathic CD4+ lymphoma
  • Diabetes mellitus
  • Hypergammaglobulinemia
  • Renal failure
  • History of peritoneal dialysis

Pathophysiology of Cryptococcosis

Once the organism is inhaled, it reaches the pulmonary alveoli and survives there with the help of an essential factor Glucosylceramide synthase (GCS). Once engulfed by the macrophages, this factor is no longer required.

The encapsulated species are, however, resistant to engulfment by the macrophages. The immune response produced includes both humoral and cell-mediated immunity. An increase in the number of helper T cells is considered a successful response.

A cystic lesion with no inflammatory response or granuloma formation is characteristic of Cryptococcosis. Organ damage and extensive tissue distortion is a feature of end disease. If limited to the airway, these organisms may cause pneumonia. Meningitis occurs as a result of disseminated infection.

Preexisting conditions such as diabetes mellitus or any other medical condition that can result in immunosuppression puts the patient at an increased risk of acquiring cryptococcosis. Moreover, the incidence of Cryptococcus meningitis is increased in patients with AIDS.

Up to 95% of cryptococcal infections are caused by Cryptococcus neoformans serotype A. The remaining cases are caused by other Cryptococcus neoformans serotypes or by Cryptococcus gatti.

Diagnosis and Treatment of Cryptococcosis

History is particularly important in the diagnosis of Cryptococcosis. Immunosuppressive state may point towards it. Investigations such as pan cultures, CT scan brain, bronchoscopy, chest x-ray and CSF analysis are helpful in making a definite diagnosis.

CT scan shows diffuse atrophy of the brain with cerebral edema and focal contrast-enhanced areas. This differentiates Cryptococcus from other mass-occupying lesions of the brain. The CSF leucocyte count may be within normal limits in an AIDS patient whose immune system does not respond appropriately.

Signs and symptoms

cryptococcosis gross pathology

Image: “Gross Pathology of Cryptococcosis.” by Yale Rosen from USA – Cryptococcosis Uploaded by CFCF. License: CC BY-SA 2.0

Commonly seen are:

  • Cough
  • Headache
  • Altered mental state
  • Confusion
  • Focal neurological defect
  • Skin rashes

Pulmonary findings are usually nonspecific to this disease and may not be distinguishable. Similarly, cutaneous lesions do not have any specific findings and may be mistaken for acne, syphilis, tuberculosis, molluscum contagiosum and basal cell carcinoma.

Immune Reconstitution Inflammatory Syndrome

Cryptococcosis has been associated with an abnormal immune response known as immune reconstitution inflammatory syndrome (IRIS). IRIS is more commonly seen in AIDS patient with central nervous system involvement by cryptococcosis and is associated with significant morbidity and mortality.

The current diagnostic criteria of IRIS in patients with HIV is:

  • The onset of symptoms within 12 months after the initiation of antiretroviral therapy
  • The recovery of CD4+ count
  • New appearance or worsening of any of the following:
    1. New contrast-enhancing lesions on computed tomography or MRI in the brain
    2. Cerebrospinal fluid pleocytosis
    3. Increased intracranial pressure with or without hydrocephalus
    4. The presence of pulmonary nodules, cavities, masses or pleural effusions due to cryptococcosis
    5. Lymphadenopathy, cutaneous cryptococcosis, or involvement of the bone and joints
  • Histopathology of one of these lesions show a granulomatous configuration
  • Symptoms occur while on antifungal therapy for cryptococcosis
  • The above symptoms, clinical, and radiological findings should be associated with a negative culture for Cryptococcus “IRIS is an immune dysregulation disorder and not an infectious disease”

Treatment

Antifungal treatment is done if there is any lung lesion or the disease has spread. Regular follow-ups for almost one year are carried out. Amphotericin B, Flucytosine and Fluconazole are the drugs of choice in this infection.

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