Fungi

Question 1

Histoplasma capsulatum (Histoplasmosis)

Answer 1

Key:

• endemic mycoses
• “Histo belt” southeastern near Miss & Ohio rivers
• dimorphic (yeast in vivo)
• small calcified granulomas (nodules) in lung CT
• mediastinal fibrosis (rare)

Extra:

• predominantly in caves and bird roosts due to association with bird and bat droppings
• aersolized mycelia spore -> inhalation -> replicates as yeast inside macrophages -> lymph nodes (hilum and mediastinum) -> T cell activate macrophage digestion and granuloma containment
• small inoculate (asymptomatic with CT infiltrate), large inoculate/weak immune (organ dissemination
• pneumonia, TB-like

Question 2

Coccidoides immitis (Coccidoidomycosis)

Answer 2

Key:

• dimorphic endemic mycoses
• southwestern U.S. - San Joaquin Valley, CA - “valley fever”
• barrel-shaped arthrospores, spherule yeast in vivo
• erythema nodosum & eosinophilia

Extra:

• arthrospores aersolized (dust storms) -> inhalation -> lung infection -> spherule form -> hypersensitivity rxn (erythema nodosum on anterior lower legs -> possible dissemination
• spherule form contains endospores
• dark skinned, pregnant women > men > women: dissemination (2 yrs < greater–immunocompromised)

Question 3

Blastomyces dermatiditis (North American blastomycosis)

Answer 3

Key:

• dimorphic endemic mycoses
• southeast U.S. (low prevalence) beaver habitats
• large yeast, refective cell wall, attached bud
• pyogranulomatous
• lung infection (tumor) + chronic painless plaques/ulcers

Extra:

• similar lung -> lymph node -> dissemination occurs
• pyogranulomatous - PMN leukcytes form microabcesses in addition to granulomas
• can present without a fever

Question 4

Sporothrix schenckii (sporotrichosis)

Answer 4

Key:

• dimorphic endemic mycoses
• worldwide, gardening/outdoor exposure of broken skin
• non-healing, inflamed, unresponsive to ABs
• string of red nodular lesions

Extra:

• absent fever
• broken skin -> exposure to fungus (moss, wood, straw, roses) -> inflamed non-healing nodule -> lymphatic spread: lympho-cutaneous sporotrichosis
• pulmonary trochosis from inhalation ( 1 or more cavitary lesions)
• joint trichosis without site of infection

Question 5

Cryptococcus neoforman (Cryptococcosis)

Answer 5

Key:

• opportunistic yeast with polysaccharide capsule made of glucoronoxylomannan
• tropical bird droppings
• small nodules or dense lobar consolidations
• CNS target - chronic/acute meningitis

Extra:

• lab test for the polysaccharade capsule - antigen
• aerosolized soil inhalation -> lung infection -> low granulomatous and inflammation response -> rare dissemination
• TH1 & IFN-gamma are key responses

Question 6

Candidiasis

Answer 6

Key:

• opportunistic yeast, produce pseudohyphae
• thrush, esophagitis
• tx: need reconstution of immunity and mucosal integrity
• superficial: T cell-defect, ABs
• invasive: neutropenia, mucosal injury (small purpura)
• (rare) chronic mucocutaneous candidiasis

Extra:

• normal inhabitants of the mouth, GI, vagina controlled by bacterial flora, cellular immunity, granulocytes, and mucous membrane
• ABs, steroids, chemotherapy can cause infection by altering flora, neutropenia, and mucosal damage.

Question 7

Aspergillus fumigatus

Answer 7

Key:

• opportunistic mycelia, conidia spores
• chronic sinusistis or lung disease (allergic response to colonization)
• granulocytopenia & corticosteroids major risk factor
• hemorrhagic skin lesions, hemoptysis (low platelets)

Extra:

• spore inahaltion -> lung ingection -> nodules, cavities, infiltrates -> brain/skin dissemination
• blood vessel invasion
• in the absence of immune reconstitution its always fatal
• skin infections arise from lungs

Question 8

Murcomycosis

Answer 8

Key:

• opportunistic mycelia
• hyphae are broad, short, and form right angles
• risk: neutropenia, steroids, *deferoxamine-iron release, *severe diabetes
• eye bulging, blindness, mucosal eschars

Question 9

Phaeohyphomycosis (Black Fungi)

Answer 9

Key:

• skin and soft tissue infection: chromoblastomycosis (Madura foot), mycetoma- sinus granule draining lesions
• darkly pigmented
• tropical and sub-tropical

Extra:

• chromoblastomycosis- speading, verrucous, scaly skin lesions with histologic sclerotic bodies
• rare brain abcess
• Cladophialophora bantiana

Question 10

Polyenes (Amphotericin)

Answer 10

• bind to and disrupt fungal cell membrane
• broad spectrum, high toxicity

Question 11

Azoles

Answer 11

• inhibit ergosterol synthesis in cell membrane
• mainly fungistatic, numerous drug interactions

Question 12

Echinocandins

Answer 12

• inhibit fungal cell wall synthesis
• limited: Candida cidal, Aperigillis static
• toxic free

Question 13

Pyrimidine inhibitors (5-fluorcytosine)

Answer 13

• inhibts DNA replication
• limited: Crypt & Candida (must be synergized to prevent resistance)
• bone marrow, liver

Question 14

Drug choice

Answer 14