Respiratory fungal disease (Aspergillus, Cryptococcosis, Histoplasmosis, Blastomycosis, Coccidiosis, Pheohyphomycosis)

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Causes:

• Cryptococcus neoformans , Aspergillus spp, Blastomyces dermatitidis , Coccidioides immitis , Histoplasma capsulatum , Rhinosporidium seeberi , phaeohyphomycosis.

Signs:

• Mainly nasal for cryptococcosis , rhinosporidiosis , phaeohyphomycosis , and aspergillosis ; lower airway signs from pneumonia with histoplasmosis, blastomycosis, coccidioidomycosis and disseminated aspergillosis.

Diagnosis:

• Serology, cytological or histopathological identification.

Treatment:

• Itraconazole, ketoconazole, fluconazole, amphotericin B, surgical excision of nasal polyps.

• Nasal discharge.
• Epistaxis.
• Sneezing.
• Sterterous breathing.
• Tachypnea, dyspnea.
• Skin nodules.
• Weight loss.
• Fever.
• CNS signs.
• Ocular signs.

Histoplasmosis

• Transient pyrexia and cough.
• Dyspnea, tachypnea.
• Inappetence and eventual cacchexia.
• Insidious onset: granulomatous interstitial pneumonia and hilar lymphadenopathy, chronic coughing.
• Conjunctivitis, eyelid nodules, chorioretinitis, blindness.
• Diarrhea, vomiting, anemia, icterus, hepatosplenomegaly.
• Lymphadenopathy.
• Cutaneous nodules, ulcerations.

Blastomycosis and Coccidioidomycosis

• Tachypnea, dyspnea.
• Conjunctivitis, chorioretinitis, blindness.
• Anorexia, fever, depression, weight loss.
• Lameness.
• Lymphadenopathy.
• Cutaneous nodules, ulceration.
• CNS signs.

Cryptococcosis

• Nasal discharge, sneezing.
• Skin nodules.
• Uveitis, blindness, chorioretinitis.
• CNS signs, eg circling, head pressing, head tilt, seizures.
• Paresis, paralysis.
• Cranial nerve deficits.
• Dyspnea, sterterous breathing.
• Regional lymphadenopathy.
• Renal failure.

Phaeohyphomycosis

• Nasal discharge, sneezing, stertor.
• Visible nasal mass.
• Anorexia, weight loss.

Aspergillosis

• See aspergillosis.

Rhinosporidiosis

• Nasal discharge, sneezing, wheezing, stertor.
• Nasal mass.
• Epistaxis.

• Most cats are not acutely ill, but have a gradual onset of either respiratory or systemic signs.

• Histoplasma capsulatum , Coccidioides immitis , Blastomyces dermatitidis  - enzootic in some areas of North America and Central America.
• Cryptococcus neoformans  - worldwide.
• Aspergillus spp. - ubiquitous.
• Rhinosporidium seeberi  - worldwide with scattered endemic areas.

• Histoplasmosis: <4 years.
• Aspergillosis: < 2 years.

• Siamese : cryptococcosis.

• Expensive to treat systemic infections.

• Moderate to diagnosis the disease.

• Aspergillus spp.:
  • Aspergillus fumigatus.
  • Aspergillus terreus.
  • Aspergillus deflectus.
  • Aspergillus flavipes.
  • Aspergillus niger.
  • Aspergillus nidulans.
  • Aspergillus flavus.
• Blastomyces dermatitidis.
• Coccidioides immitis.
• Histoplasma capsulatum.
• Cryptococcus neoformans.
• Rhinosporidium seeberi
• Phaeohyphomycosis: dematiaceous fungi.

• Access to source of spores - usually external environment, soil, bird (especially pigeon) guano.
• Immunosuppression from feline leukemia virus, feline immunodeficiency virus, etc.
• Prior treatment with corticosteroids.

Coccidiomycosis

• Hot dry summer months encourages inhalation of spores via dust.
• Cats are fairly resistant to this disease. Many exposed cats develop only transient respiratory signs.

Cryptococcosis

• Cryptococcus neoformans var. gattii - access to eucalyptus trees when shedding bark (organism carried in bark).
• Cryptococcus  neoformans var. neoformans - access to soil rich in pigeon droppings.
• Most common systemic fungal infection in cats.

Blastomycosis

• Access to organism in soil.
• Cats are more resistant to this disease than are dogs.

Histoplasmosis

• Access to organism in soil rich in bird or bat guano.
• Disease is more common in cats than in dogs.
• Many cats are exposed, but do not develop overt clinical disease.

Aspergillosis

• Inhalation of spores causes focal nasal infections in most affected cats.
• Inhalation of spores in immunosuppressed cats may result in disseminated disease.

Rhinosporidiosis

• Often requires contact with standing or stagnant water
• Rare disease in cats.

• Environmental exposure  inhalation  localization in respiratory tissue wider dissemination in body (variable).
• Fungal agent  inhaled  either:
  • Localized, mild, subclinical infection.
  • Local spread in nasal and facial tissue.
  • Severe pulmonary disease.
  • Systemic infection.

Blastomycosis

• 5-12 weeks.

Coccidiomycosis

• Weeks to years.

Others

• Several weeks

• See individual microorganisms.

• Nasal discharge.
• Pyrexia.
• Tachypnea, dyspnea.
• Anorexia, weight loss, depression.
• Lymphadenopathy

• Anorexia.
• Weight loss.
• Abnormal breathing.
• Nasal discharge.

• Nasal discharge.
• Nasal mass.
• Increased respiratory noise.
• Weight loss, emaciation.
• Ocular changes.
• CNS signs.
• Vomiting, diarrhea (histoplasmosis).
• Lameness.
• Lymphadenopathy

Thoracic Radiography

• See thoracic radiography .
• Hilar lymphadenopathy.
• Nodular interstitial patterns.
• Increased bronchial markings and alveolar patterns.

Cytology in search of organism

• Impression smears of cutaneous lesions.
• Fine needle aspirate  of lymph nodules, cutaneous lesions, masses, vitreous.
• Examination of bronchial washes and transtracheal aspirates.
• Cerebrospinal fluid analysis.

Biopsy

• Isolate and identify agent from nasal mass, biopsy of affected turbinates, gastrointestinal tract (histoplasmosis), cutaneous masses, peripheral lymph nodes, bone, etc.

Serology

• Agar gel immunodiffusion and complement-fixation tests for blastomycosis and coccidiomycosis.
• False negative and positive results are common with histoplasmosis. Serology is unreliable for this disease.
• Latex cryptococcal antigen agglutination test (LCAT).
• AGID, ELIZA and counter immunoelectrophoresis for aspergillosis.

Mycology

• Required for definitive diagnosis of the species involved in aspergillosis and phaeohyphomycosis.

Other

• Rhinoscopy with visualization of fungal colonies, fungal granulomas or mass formation.
• Endoscopy of upper or lower gastrointestinal tract for histoplasmosis.
• Radiography of limbs to look for bony involvement.

• History.
• Signs.
• Radiography.

• Serology.
• Cytology.
• Histopathology .
• Mycology.

• Most systemic mycotic infections cause a pyogranulomatous inflammation that may be widespread or focal in affected tissues.

• Fix transverse nasal sections, trachea, lung, regional lymph nodes.
• Make touch preps (cytology/immunology etc) from suspected lesions, save some fresh tissue for culture.
• Some immunohistochemical stains are available to identify the species of fungi involved, so consult laboratory for fixing procedure.
• Periodic Acid Schiff (PAS), and silver stains may be used to search for fungi.

• Other causes of rhinitis.
• Nasal neoplasia.
• Pneumonia .
• Pulmonary neoplasia .
• Lymphosarcoma.
• Other causes of CNS disease.
• Bacterial osteomyelitis.

(Drugs are listed in the order of efficacy or historical choice)

• Coccidiomycosis
  • 1. Ketoconazole 5-15 mg/kg PO BID .
  • 2. Itraconazole 5 mg/kg PO BID .
  • 3. Fluconazole 2.5-5.0 mg/kg PO or IV qd .
• Blastomycosis, histoplasmosis
  • 1. Itraconazole 5 mg/kg PO BID
  • 2. Ketoconazole 5-15 mg/kg PO BID
  • 3. Fluconazole 2.5-5.0 mg/kg PO, IV qd
  • 4. Amphotericin B 0.25 mg/kg IV in 5% dextrose/water .

 Amphotericin B is nephrotoxic.

• Cryptococcosis
  • 1. Fluconazole 50 mg Po BID
  • 2. Itraconazole 5 mg/kg PO BID
  • 3. Amphotericin B 0.25 mg/kg IV in 5% dextrose/water

 Amphotericin B is nephrotoxic.

• 4. Flucytosine 25-50 mg/kg PO QID .
• 5. Ketoconazole 5-15 mg/kg PO BID
• 6. Surgical debulking for isolated granulomas.
• Aspergillosis
  • 1. Itraconazole 5 mg/kg PO BID
  • 2. Ketoconazole 5 mg/kg PO BID
  • 3. Fluconazole 50 mg PO BID
  • 4. Possible topical enilconazole or clotrimazole for nasal disease.
• Rhinosporidiosis
  • 1. Surgical removal of the nasal mass.
• Pheohyphomycosis
  • 1. Itraconazole 5 mg/kg PO BID.
  • 2. Amphotericin B 0.25 mg/kg IV in 5% dextrose/water.

 Amphotericin B is nephrotoxic

• 3. Surgical removal of isolated nasal granulomas.

• Monitor complete blood count and liver enzymes in all cats receiving the imidazole compounds.
• Measure renal function prior to each dose of amphotericin.
• The only serologic titer than can be used to evaluate response to treatment is the LCAT titer for cryptococcosus.

• Most systemic fungal infections require long-term treatment (minimum of 2 months).
• Cryptococcosus may require treatment for > 12 months.
• Coccidioidomycosis and histoplasmosis may require therapy for > 10 months.
• Treat for at least 30 days beyond resolution of all clinical signs.
• Disseminated aspergillosis is commonly fatal, even with treatment.

Cryptococcus

• Fair to good if treated aggressively.
• Relapses may occur once therapy is stopped.

Blastomycosis

• Fair if survive first 7-14 days of  treatment.
• Overall prognosis is poor.

Coccidiomycosis

• Good with localized infections.
• Fair for disseminated disease.

Histoplasmosis

• Grave if disseminated.
• Fair to good for localized infections.

Pheohyphomycosis

• Fair to good.

Rhinosporidiosis

• Good, but recurrence of the nasal mass may require repeated surgeries.

Aspergillosis

• Grave with disseminated disease.
• Fair to good with nasal disease.

• Resolution of clinical signs.

• Immunodeficiency.
• Dissemination with debilitation.
• Poor response to antifungal agents.
• Inadequate dose or length of treatment.
• Premature termination of therapy due to expense.

• Tennant K et al (2004) Nasal mycosis in two cats caused by Alternaria species. Vet Rec. 155, 368-370.

• Mr David Morgan BVetMed BSc MRCVS
• Dr Elizabeth Rozanski DVM DACVIM DACVECC

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