L15: Fungal Disease Pt.2 (Specht) Flashcards
Where is blasto found?
- Mississippi, Missouri, and Ohio River valleys
- Mid-atlantic states
- Southern Canada
- areas of high humidity/fog
- sandy, acidic soils near H2O
Blasto trans. And animals affected
Transmission: inhalation +/- contamination of puncture wounds or open sores
Dogs: large breed, young, male
Cats: young males (roaming behavior)
Pathophys. Of Blasto
- causes granulomatous to pyogranulomatous inflammatory response**
- cell-mediated immunity
- transforms to yeast in lungs –> hematogenous or lymphatic spread
CS of Blasto
- 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
Dx of Blasto
- 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
CBC/Chem of Blasto
CBC: non-regenerative anemia, lymphopenia, neutrophilic leukocytosis (+/- left shift)
Chem: hypoalbuminemia and hyperglobulinemia +/- hypercalcemia
Radiographic findings with blasto
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)
Cytology and histo of Blasto
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
Tx of blasto
- 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
Prognosis of Blasto
- 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)
Causative organism of Cryptococcosis
Cryptococcus neoformans
- a dimorphic fungus
- pathologic form = extra-cellular, thin-walled, narrow-budding yeast w/ very thick capsule
- yeast in animal AND the environment*
Causative agent of Blastomycosis
- 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
Distr. And transmission of Crypto**
- worldwide, esp. In S. California and E. Australia
- found in bird excrement
- Trans: inhalation (nasal and pulmonary infection most common)
Most common systemic fungal disease in cats**
Crypto (usually
What age dogs more commonly get crypto?
1-7 years
Purebreds over represented
Pathophys. Of crypto
- 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
Why is phagocytosis against crypto ineffective?
thick polysaccharide capsule inhibits multiple components of immune dz
CS of crypto in CATS
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
CS of Crypto in DOGS
- nasal, CNS, and ocular manifestations most common
- wt. loss, lethargy
- skin, kidney can also be affected
Differentials for severe nasal ulceration in dogs
Immune mediated dz
Crypto
Asper
Dx of Crypto
- 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)
CBC, UA abnormalities possible with Crypto that may aid in dx
CBC: monocytosis, non-regenerative anemia
UA: organisms may be present on sediment in dogs
Tx of crypto
- 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
Crypto vs. Blasto: which develops resistance to antifungals?
CRYPTO
-may need to switch antifungal in middle of tx, or do antifungal sensitivity testing
Causative agent of histoplasmosis
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
Distr. And transmission of Histo
- 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
Pathophys. Of histo
- 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
CS of histo
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
Dx of Histo
- 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
CBC/Chem of histo patient
(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
Findings on abdominal imaging of histo patient
- dec. detail due to poor body condition
- hepato/splenomegaly; effusion
- thickened/irregular GI wall w/ contrast
- lymphadenomegaly/opathy
Tx of histo
- 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
Causative agent of Coccidioidomycosis
Coccidioides immitis:
- dimorphic fungus with mycelial form and pathologic spherule form
- spherule is large, round, double-walled, and contains multiple endospores
Distr. and trans. of coccidio
- 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
Pathophys. Of coccidio
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
CS of coccidio in DOGS
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
CS of coccidio in CATS
- Skin lesions even w/o underlying bone lesions
- fever, anorexia, wt. loss
Dx of coccidio
- 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
CBC/Chem/UA changes of coccidio patient
CBC: normocytic, normochromic non-regen. Anemia, leukocytosis or leucopenia, and/or monocytosis
Chem: hyperglobulinemia (polyclonal), hypoalbuminemia, and/or renal azotemia
UA: proteinuria
Challenges of serology for coccidio (S.O.)
- 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
Tx of coccidio
- 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
