Definition

A localized or systemic fungal infection caused by the environmental yeast Cryptococcus spp, most commonly C. neoformans and C. gattii.

Pathophysiology

• C. neoformans-grows in bird droppings and decaying vegetation; soil disturbance increases risk of infection.
• Dogs and cats inhale the yeast and a focus of infection is established, usually in the nasal passages; smaller dried, shrunken organisms may reach the terminal airways (uncommon). There may be colonization or subclinical infection of the nasal passages that spontaneously resolves.
• Stomach and intestinal infections suggest that primary GI entry can occur.
• Dissemination-hematogenously spread via macrophages from the nasal passages to the brain, eyes, lungs, and other tissues; by extension to the skin of the nose, eyes, retro-orbital tissues, and draining lymph nodes.

Systems Affected

• Cats-mainly upper respiratory signs affecting the nose and sinuses; skin; nasal planum; nasopharynx; CNS; eyes.
• Dogs-mainly the head and brain, nasal passages, and sinuses; skin over the nose and sinuses; mucous membranes; draining lymph nodes; eyes; periorbital areas; occasionally lungs and abdominal organs.

Incidence/Prevalence

• Dogs-rare in United States; prevalence 0.00013%.
• Cats-7–10 times more common than in dogs; most common systemic mycoses of cats.

Geographic Distribution

• Worldwide.
• Some areas of southern California and Australia have an increased incidence and an outbreak has occurred on Vancouver Island in British Columbia, Canada.
• C. gattii grows well on eucalyptus trees.

Signalment

Signs

Causes

Exposure to cryptococcal organisms and inability of the immune system to prevent colonization and invasion into tissues.

Risk Factors

• Exposure to disrupted soil
• Prior infection with FeLV or FIV

Differential Diagnosis

CBC/Biochemistry/Urinalysis

• Mild anemia in some cats
• Eosinophilia occasionally seen
• Chemistries usually normal

Other Laboratory Tests

• Latex agglutination or ELISA-detect cryptococcal capsular antigen in serum or CSF; highly sensitive assay; most infected animals have measurable capsular antigen titers; magnitude of titer correlates with extent of infection.
• Antigen assay may be less sensitive in dogs.
• May be positive when only colonization but antigen titers of 1:32 or greater are seen with fungal invasion.

Imaging

• Nasal radiographs (cats)-soft tissue density material filling the nasal passage; occasional bone destruction of the nasal dorsum.
• Contrast-enhanced CT or MRI best for identifying brain and nasal lesions.
• Thoracic radiographs-not indicated, unless signs of lower respiratory tract disease.

Diagnostic Procedures

Pathologic Findings

• Gross lesions-gray, gelatinous mass produced by the polysaccharide capsule; usually found in the nose, sinuses, and nasopharynx of cats; skin lesions are usually ulcerative.
• Neurologic lesions-usually seen in dogs; diffuse or fungal CNS granulomas.
• Chorioretinitis with or without retinal detachment or optic neuritis-dogs and cats.
• Histologic response-usually pyogranulomatous; inflammatory cell infiltrate may be mild because the polysaccharide capsule interferes with neutrophil migration; organism characterized by capsulate yeast with narrow-neck budding.

Appropriate Health Care

• Outpatient if stable.
• Neurologic signs-may initially require inpatient supportive care.

Nursing Care

Cats-nasal obstruction influences appetite; encourage patients to eat by offering palatable food.

Activity

No restrictions in most cases.

Diet

• No special diet.
• Patients treated with itraconazole-give medication in fatty food (e.g., canned food) to improve absorption.

Client Education

• Inform client that this is a chronic disease that requires months of treatment.
• Reassure client that the infection is not zoonotic.

Surgical Considerations

Remove granulomatous masses in the nasopharynx to reduce respiratory difficulties.

Drug(s) Of Choice

• Fluconazole-preferred for ocular or CNS involvement because it is water-soluble and better penetrates the CNS; cats, 50 mg PO q12–24h; dogs, 5 mg/kg PO q12h, most economical drug choice.
• Itraconazole capsules-give with a high-fat meal to maximize absorption; cats, 10 mg/kg PO daily; dogs, 5 mg/kg PO q12h; pellets in the capsule can be mixed with food; no apparent adverse taste. Itraconazole liquid: better absorption on empty stomach; compounded itraconazole: variable absorption and not recommended.
• Amphotericin B may have some advantage in severe disease at an intravenous dose of 0.5 mg/kg every 48 hours given over 3–4 hours. Monitor renal function closely.
• Terbinafine at a dose of 5 mg/kg q12h has been effective in treatment of cats with resistant infections.

Contraindications

Caution with steroid use.

Precautions

• Triazoles-hepatotoxicity; anorexia signals problems; monitor liver enzymes after first 3–4 weeks of treatment.
• Terbinafine-monitor for hepatic toxicity and anorexia.
• Amphotericin B-nephrotoxicity; caution if patient is azotemic but not an absolute contraindication if the infection is life-threatening.
• Itraconazole-ulcerative dermatitis (differentiate from the skin lesions of cryptococcosis); new skin lesions after the disease is much improved should be considered a drug reaction.

Alternative Drug(s)

• Cryptococcal organisms are prone to becoming resistant to antifungal treatment.
• Amphotericin B (intravenous)-dogs and cats that do not respond to a triazole; monitor creatinine closely for evidence of renal damage.

Patient Monitoring

• Monitor liver enzymes monthly (especially early in treatment) in patients receiving a triazole antifungal agent.
• Improvement in clinical signs, resolution of lesions, improvement in well-being, and return of appetite measure the response to treatment.
• Capsular antigen titers-after 2 months of treatment, the titers should decrease substantially if treatment is effective; if ineffective, try the terbinafine, because the organism can become resistant.
• Continue monitoring antigen titers every 1–2 months during treatment and after discontinuing treatment to identify recurrence of disease.
• Ideally treat until the cryptococcal antigen titers reach zero (can be >2 years of treatment).

Prevention/Avoidance

The organism is ubiquitous and cannot be avoided.

Possible Complications

Patients with neurologic disease may have seizures and permanent neurologic changes.

Expected Course and Prognosis

Treatment-anticipated duration 4 months–1 year plus; patients with CNS disease may require life-long maintenance; median time of successful treatment with fluconazole was 4 months; median time for itraconazole treatment was 8 months.

Associated Conditions

N/A

Age-Related Factors

N/A

Zoonotic Potential

• Not considered zoonotic, but possibility of transmission through bite wounds.
• Inform client that the organism was acquired from the environment and that he or she could be at increased risk, especially if immunosuppressed.

Pregnancy/Fertility/Breeding

N/A

Abbreviations

• CNS = central nervous system
• CSF = cerebrospinal fluid
• CT = computed tomography
• ELISA = enzyme-linked immunosorbent assay
• FeLV = feline leukemia virus
• FIV = feline immunodeficiency virus
• FIP = feline infectious peritonitis
• GI = gastrointestinal
• MRI = magnetic resonance imaging

Client Education Handout Available Online