L15: Fungal Disease Pt.2 (Specht)

Question 1

Where is blasto found?

Answer 1

• Mississippi, Missouri, and Ohio River valleys
• Mid-atlantic states
• Southern Canada
• areas of high humidity/fog
• sandy, acidic soils near H2O

Question 2

Blasto trans. And animals affected

Answer 2

Transmission: inhalation +/- contamination of puncture wounds or open sores

Dogs: large breed, young, male

Cats: young males (roaming behavior)

Question 3

Pathophys. Of Blasto

Answer 3

• causes granulomatous to pyogranulomatous inflammatory response**
• cell-mediated immunity
• transforms to yeast in lungs –> hematogenous or lymphatic spread

Question 4

CS of Blasto

Answer 4

• resp/non-specific signs common: cough, dyspnea, exercise intolerance, anorexia, weight loss
• ocular disease: anterior uveitis, endophthalmitis, optic neuritis
• Skin dz: cutaneous/SC nodules +/- draining tracts
• Misc: fever, lymphadenopathy, CNS signs, lameness, splenomegaly, depression
• CATS may have above +/- GI dz, UT dz, pleural or abd. Effusion

Question 5

Dx of Blasto

Answer 5

• Definitive dx requires cytology, histo, or culture**
• Serology: Ab only develop in some exposed animals (false negatives common). Ag testing better
• thoracic rads abnormal 85% of the time
• rads of bone lesions
• MDB has no specific findings

Question 6

CBC/Chem of Blasto

Answer 6

CBC: non-regenerative anemia, lymphopenia, neutrophilic leukocytosis (+/- left shift)

Chem: hypoalbuminemia and hyperglobulinemia +/- hypercalcemia

Question 7

Radiographic findings with blasto

Answer 7

Thoracic:

• diffuse, miliary to macro-nodular interstitial pulmonary pattern
• single masses, alveolar patterns, pleural effusion, etc. possible

Bone lesions: usually lytic with periosteal reaction surrounding and soft tissue swelling (looks similar to OSA but less proliferative)

Question 8

Cytology and histo of Blasto

Answer 8

Cytology:

• concurrent granulomatous/pyogranulomatous inflammation
• use sputum, cutaneous exudates, FNA of lesions, ocular fluid, etc.
• may have false -

Histo:
concurrent granulomatous/pyogranulomatous inflammation with organisms observed in tissue samples

Question 9

Tx of blasto

Answer 9

• Itraconazole first choice if no CNS or ocular involvement
• other choices: fluconazole, terbinafine, ketoconazole, amphotericin B
• treat at least 60-90 days or continue at least 1-2 months past resolution or measurable signs**
• median duration of tx = 8-9 months
• tx is expensive
• controversial if should used anti-inflammatory steroids at beginning of therapy to avoid severe inflammation from death of fungal organisms

Question 10

Prognosis of Blasto

Answer 10

• poor if CNS involved
• guarded w/ severe pulmonary involvement
• may have to remove eyes if in eyes
• good otherwise w/ 80% cured
• tx relapses w/ 2nd full course of anti-fungals (resistance uncommon)

Question 11

Causative organism of Cryptococcosis

Answer 11

Cryptococcus neoformans

• a dimorphic fungus
• pathologic form = extra-cellular, thin-walled, narrow-budding yeast w/ very thick capsule
• yeast in animal AND the environment*

Question 12

Causative agent of Blastomycosis

Answer 12

• Blastomyces dermatitidis, a dimorphic fungus that is a saprophyic mycelial spore-producing form in soil and yeast form in the body
• pathologic form is extra-cellular yeast
• yeast has broad-based budding with thick, refractile, double contoured wall

Question 13

Distr. And transmission of Crypto**

Answer 13

• worldwide, esp. In S. California and E. Australia
• found in bird excrement
• Trans: inhalation (nasal and pulmonary infection most common)

Question 14

Most common systemic fungal disease in cats**

Answer 14

Crypto (usually

Question 15

What age dogs more commonly get crypto?

Answer 15

1-7 years

Purebreds over represented

Question 16

Pathophys. Of crypto

Answer 16

• inhaled particles most often trapped in upper airway –> nasal disease –> hematogenous spread to extra-pulmonary sites
• CNS may occur by direct extension across cribiform plate
• cell-mediated immunity
• granulomatous to pyogranulomatous inflammatory response with ineffective phagocytosis
• not only opportunistic, but actively causes infection and avoids immune system**
• don’t have to be immunocompromised to get it

Question 17

Why is phagocytosis against crypto ineffective?

Answer 17

thick polysaccharide capsule inhibits multiple components of immune dz

Question 18

CS of crypto in CATS

Answer 18

Sneezing and nasal d/c (80%): uni or bilateral, serous to mucopurulent +/- blood tinged
-lesions extending from nares, facial deformity, or ulceration of nasal planum

Cutaneous or SC masses (40-50%)
Ocular inflammatory lesions
Non-specific: anorexia, lethargy
CNS signs
Misc. signs relating to inflammation and organisms in lung, LN, bone, kidney

Question 19

CS of Crypto in DOGS

Answer 19

• nasal, CNS, and ocular manifestations most common
• wt. loss, lethargy
• skin, kidney can also be affected

Question 20

Differentials for severe nasal ulceration in dogs

Answer 20

Immune mediated dz
Crypto
Asper

Question 21

Dx of Crypto

Answer 21

• serology is #1 test in cats (very good Se/Sp)
• cytology (false - possible)
• skull rads/CT/MRI: see increased ST in nasal cavity, nasal bone lysis and deformity, and/or contrast-enhancing mass lesions in CNS
• histopath
• culture (has sensitivity issues)
• MDB non-specific
• thoracic rads usually normal (can see hilar lymphadenopathy and/or diffuse to miliary interstital pulm. Pattern)

Question 22

CBC, UA abnormalities possible with Crypto that may aid in dx

Answer 22

CBC: monocytosis, non-regenerative anemia
UA: organisms may be present on sediment in dogs

Question 23

Tx of crypto

Answer 23

• Itra = 1st choice if no CNS involvement
• tx for 1-2 months past resolution of CS and neg. titers
• mean tx time = 8.5 months
• nasal and cutaneous dz responds better than ocular and CNS dz
• tx CNS dz with amphotericin B, others

Question 24

Crypto vs. Blasto: which develops resistance to antifungals?

Answer 24

CRYPTO

-may need to switch antifungal in middle of tx, or do antifungal sensitivity testing

Question 25

Causative agent of histoplasmosis

Answer 25

Histoplasma capsulatum - dimorphic fungus that has saprophytic mycelial form in env. and yeast form in body - small INTRA-cellular yeast with thick wall and broad-based budding

Question 26

Distr. And transmission of Histo

Answer 26

- around mississsippi, missouri, and ohio river valleys, and southwest and mid-atlantic states - concentrated in bird/bat poop - trans: inhalation (or ingestion?) - more common in young male sporting dogs, and young cats

Question 27

Pathophys. Of histo

Answer 27

- spores transform to yeast at body temp - yeast engulfed by mononuclear phagocytes and undergo further replication by budding --> hematogenous or lymphatic spread - cell mediated immunity usually clears infection unless there is high infective dose or immune deficiency - granulomatous inflammation develops in persistently infected organs

Question 28

CS of histo

Answer 28

DOGS: -anorexia, wt. loss, fever, cough, dyspnea, diarrhea (LI most common) +/- polyarthritis, PLN, chorioretinitis, CNS signs, skin lesions CATS: -similar, but with profound weight loss

Question 29

Dx of Histo

Answer 29

- cytology for definitive dx* (shows granulomatous or pyogranulomatous inflammation, intracellular organism) - MDB: typical inflammatory response - serology unreliable - thoracic rads: 85% have diffuse, miliary or nodular interstitial pattern, hilar lymphadenopathy - Rads of lytic bone lesions - Abd. Imaging

Question 30

CBC/Chem of histo patient

Answer 30

``` (Usually no specific signs) CBC: -non-regenerative anemia -intracellular organisms in monos, neuts, eos -thrombocytopenia -cats may be pancytopenic ``` Chem: -hypoalbuminemia or inc. LIV enzymes LIV fx tests may be abnormal

Question 31

Findings on abdominal imaging of histo patient

Answer 31

- dec. detail due to poor body condition - hepato/splenomegaly; effusion - thickened/irregular GI wall w/ contrast - lymphadenomegaly/opathy

Question 32

Tx of histo

Answer 32

- Itraconazole 1st choice if no CNS/ocular involvement - others: amphotericin B, fluconazole, terbinafine, ketoconazole - tx >60-90 days or at least 1-2 mo. Past resolution of signs - if relapses, tx with 2nd full course of anti-fungals - anti-fungal resistance uncommon - prognosis excellent w/ only pulmonary involvement, but guarded to fair with dissemination

Question 33

Causative agent of Coccidioidomycosis

Answer 33

Coccidioides immitis: - dimorphic fungus with mycelial form and pathologic spherule form - spherule is large, round, double-walled, and contains multiple endospores

Question 34

Distr. and trans. of coccidio

Answer 34

- regions with dry, warm climates and sandy soil - CA, NM, AZ, UT, NV, and southwest TX - number of cases increases after high rainfall years - trans: inhalation - common environmental exposure - it's everywhere! - young male dogs overrepresented

Question 35

Pathophys. Of coccidio

Answer 35

1) phagocytosis and increased CO2 --> arthroconidia transform to spherules 2) endospores divide w/n spherule (and a protected from immune system) 3) endospores released into tissues and are phagocytized or (if immune system overwhelmed) disseminates to mediastinal/tracheobronchial LN, bones, eyes, heart, pericardium, testes, brain, spinal cord, visceral organs 4) neutrophilic inflammation 5) monocyte, lymphocyte, and plasma cell infiltration 6) resp. Signs develop w/n 1-3 wks, disseminated dz develops w/n 4 months of exposure

Question 36

CS of coccidio in DOGS

Answer 36

DOGS: - cough, weakness, lethargy, anorexia, wt. loss, fever - lameness w/ painful swollen bone lesions - localized lymphadenopathy, ocular and skin lesions - skin lesions often overlay bone lesions - diarrhea, non-specific signs

Question 37

CS of coccidio in CATS

Answer 37

- Skin lesions even w/o underlying bone lesions | - fever, anorexia, wt. loss

Question 38

Dx of coccidio

Answer 38

- Cytology: #1 diagnostic. Done on sputum, lung washes, exudates, or FNA. False - possible. See concurrent inflammation - MDB non-specific inflammatory - Serology: Ab tests only - Thoracic rads: hilar lymphadenopathy, diffuse interstitial, pleural effusion - Bone lesion rads: more proliferative than lytic - Histo/culture: look for gigantic structures

Question 39

CBC/Chem/UA changes of coccidio patient

Answer 39

CBC: normocytic, normochromic non-regen. Anemia, leukocytosis or leucopenia, and/or monocytosis Chem: hyperglobulinemia (polyclonal), hypoalbuminemia, and/or renal azotemia UA: proteinuria

Question 40

Challenges of serology for coccidio (S.O.)

Answer 40

- only Ab tests are Se and Sp enough - fale negs can occur in early infection, cutaneous infection, chronic infection, or rapidly progressing acute infection - false positives can occur due to immune complexes or bacterial contaminants - can cross react with H. Capsulatum and B. Dermatitidis

Question 41

Tx of coccidio

Answer 41

- itra 1st choice - treat for at least 1-2 months past resolution of measurable signs - typical duration of tx = 6-12 mos. - prognosis depends on degree of dissemination - bone infections often incurable - overall recovery rate ~60% - titers can persist months-years after clinical resolution