Geographic Fungi/Opportunistic Fungi

Question 1

Candida clues and treatment:

Answer 1

Thrush, HIV, central venous catheter, dissemination

Treatment: fluconazole

Question 2

Aspergillus clues and treatment:

Answer 2

Bone marrow transplant, cavitary lung lesion, sinusitis, galactomannan
Treatment: voriconazole, caspofungin or amphotericin (NOT fluconazole)

Question 3

Cryptococcus clues and treatment:

Answer 3

Meningitis in an AIDS patient, pneumonia in the immunocompromised, CrAg
Treatment: Amphotericin B + flucytosine followed by fluconazole

Question 4

Mucormycosis clues and treatment:

Answer 4

Burrowing necrotic sinus lesion, diabetes, iron overload, biopsy
Treatment: Surgery and posaconazole

Question 5

Histoplasma clues and treatment:

Answer 5

Self-limited pneumonia, Mississippi and Ohio river valleys, urine antigen
Treatment: Fluconazole

Question 6

Blastomycosis clues and treatment:

Answer 6

Bilateral pneumonia, pulmonary nodule, histoplasma region and further north
Treatment: Fluconazole

Question 7

Coccidioides clues and treatment:

Answer 7

Self-limited pneumonia, pulmonary nodule, eosinophilia, AZ and CA.

Question 8

Dimorphic fungi:

Answer 8

Fungi that exist in two forms: molds (in the environment) and yeasts (within the body). All geographic fungi are dimorphic fungi.

Question 9

Histoplasmosis pathology:

Answer 9

Intracellular growth of tiny years within macrophages, leading to a GRANULOMATOUS reaction.
May produce mild flu-like illness with primary infection. Reinfection leads to acute pulmonary infiltrates.
Chronic pulmonary infection leads to nodular apical infiltrates, which cavitate.
Disseminated disease resembles miliary TB.

Question 10

Histoplasmosis diagnosis:

Answer 10

Culture (fruiting bodies).
Histopathology (macrophages with small yeast)
Histoplasma urine antigen in active disease.

Question 11

Histoplasmosis therapy:

Answer 11

Not all infections require treatment.
For severe infection, AMPHOTERICIN B.
For patients with abnormal immunity, AZOLES (Itraconazole)

Question 12

Blastomycosis pathology:

Answer 12

Extracellular yeast (but may be seen within macrophages).
Thick-walled yeast with BROAD-BASED BUDS.
Non-caseating loose granulomas with neutrophils (PYOGRANULOMAS).
Causes pulmonary infection, rarely cutaneous lesions, BONE LESIONS, and disseminated infection.

Question 13

Blastomycosis diagnosis:

Answer 13

Stain of pus/tissue

Culture

Question 14

Blastomycosis treatment:

Answer 14

For serious disease, AMPHOTERICIN B.

For non-meningeal disease of moderate severity, ITRACONAZOLE.

Question 15

Coccidioidomycosis pathology:

Answer 15

Inhalation of arthrospores, pulmonary infection, possible hematogenous dissemination.
Granulomatous response. Endospores in characteristic spherules of varying size.
Produces primary pulmonary illness (valley fever), may be associated with EOSINOPHILIA, Erythema nodosum. May disseminate to bone, skin, meninges.

Question 16

Coccidioidomycosis diagnosis:

Answer 16

Serology, complement fixation, immunoprecipitin, ELISA
Culture (VERY HAZARDOUS)
Histopathology (visible endospores)

Question 17

Coccidioidomycosis treatment:

Answer 17

Most primary disease is not treated.

AMPHOTERICIN B for progressive primary disease or immunosupressed patients. Intrathecal AMPHOTERICIN B for meningitis.

Question 18

Sporotrichosis pathology:

Answer 18

Worldwide distribution. Local inoculation, frequently of the upper limb, with a pyogranulomatous response and LYMPHANGITIC spread.
Causes cutaneous lymphangitis with nodules. Rarely systemic symptoms. Pulmonary lesions can cavitate. May disseminate in the immunosuppressed.

Question 19

Sporotrichosis diagnosis:

Answer 19

Culture

Histopathology (“cigar-shaped” yeast hard to find)

Question 20

Sporotrichosis treatment:

Answer 20

Potassium iodide
Local heat for cutaneous lesions
ITRACONAZOLE

Question 21

Immune defenses against Candida:

Answer 21

Mainly neutrophils (can damage pseudohyphae). Also, monocytes, macrophages, eosinophils, lymphocytes. The role of antibody and complement is uncertain.

Question 22

Candidal infections:

Answer 22

1) Thrush (common). Plaques are pseudomembranes of fungus, PMNs, and epithelial debris. Risk factors are: inhaled steroids, dentures, cancer, antibiotics, HIV
Diagnosis: clinical appearance, KOH prep, Gram stain.
2) Esophagitis. Painful swallowing, substernal chest pain.
Risk factors: AIDS, chemotherapy
Diagnosis: endoscopy, biopsy
3) Vulvovaginitis (common). Thick, creamy discharge, intense itching and redness.
Risk factors: Diabetes, HIV, antibiotic therapy, pregnancy
Diagnosis: Exam and wet mount or KOH prep.
4) Cutaneous lesions (intertrigo, diaper rash, balanitis).
5) Candidemia. Spectrum from mild fever to sepsis.
Risk factors: Immunocompromised, ICUs, central IV catheters.
Diagnosis: Blood culture
6) Disseminated Candidiases. May effect: kidney, brain, myocardium, and eye. Diffuse microabscesses with acute suppurative and granulomatous reaction. AIDS PATIENTS RARELY GET DISSEMINATED CANDIDA.
Candida in the urine of a hospitalized person is rarely symptomatic and rarely indicates infection.
7) Candida cystitis. Causes pyuria, fever. Rarely disseminates.
8) Upper UTI. Usually a complication of disseminated disease, but may occur via ascending route.
Risk factors: diabetes, candidemia, anatomic or functional abnormalities.

Question 23

Candida treatment:

Answer 23

Candidemia/disseminated candida: Removal of infected foreign bodies, antimicrobials (Amphotericin B, Caspofungin, or Fluconazole). Treatment should continue for 2 weeks after last positive culture. If there are persistently positive cultures, look for a nidus of infection.
Cystitis: Remove catheter (usually doesn’t require antifungals). Can use fluconazole or amphotericin bladder wash.
Thrush: nystatin

Question 24

Aspergillus pathology:

Answer 24

Usually acquired by inhaling spores, or via trauma.
Phagocytosis and cell-mediated immunity are required for immune protection. Bronchopulmonary aspergillosis is an allergic reaction.
In the immunosuppressed patient, it may cause: VASCULAR INVASION (leading to infarction, necrosis, edema and/or hemorrhage), invasive sinusitis (acute and chronic), ASPERGILLOMAS, invasive pulmonary aspergillosis, disseminated aspergillosis (can affect any organ), or cutaneous aspergillosis.

Question 25

Aspergillus diagnosis:

Answer 25

Culture of respiratory tract.
Histology (direct visualization).
GALACTOMANNAN test, which detects a component of the aspergillus cell wall. This indicates invasive disease, and is not a primary diagnostic test.

Question 26

Aspergillus treatment:

Answer 26

Surgery (aggressive debridement for sinus disease, brain disease, cutaneous lesions), reduction of immunosuppression.
VORICONAZOLE is first line. Amphotericin B is useful, but toxic. Caspofungin and posaconazole may also be effective.

Question 27

Zygomycosis epidemiology:

Answer 27

Ubiquitous. Found in decaying matter. Inhalation must be a DAILY EXPERIENCE, due to relatively low virulence. Disease only in severe immunocompromised, diabetes, lymphoma, leukemia, and burn victims.

Question 28

Zygomycosis pathogenesis and risk factors:

Answer 28

Enters via respiratory tract. Infection usually due to some defect in macrophages and neutrophils. Once the fungus begins to grow, the hyphae invade tissue with AFFINITY FOR BLOOD VESSELS, resulting in THROMBOSIS and NECROSIS.
Risk factors: diabetes (specifically KETOACIDOSIS), leukemia with neutropenia, IRON OVERLOAD.

Question 29

Zygomycosis presentation:

Answer 29

Rhinocerebral mucormycosis. Acute sinusitis, facial pain, headache, fever, proptosis, and orbital cellulitis. May erode through face and hard palate, causing BLACK ESCARS.
Cerebral abscess, cavernous sinus thrombosis can occur. Often fatal.
Can also cause pulmonary or cutaneous disease.

Question 30

Zygomycosis diagnosis:

Answer 30

Tissue histopathology and culture to differentiate from Aspergillus. Vascular invasion with tissue necrosis.

Question 31

Zygomycosis treatment:

Answer 31

PROGNOSIS VERY POOR.
Surgery is often necessary.
Reversal of underlying problem (hyperglycemia, acidosis).
Medical therapy: AMPHOTERICIN B or POSACONAZOLE.

Question 32

Cryptococcosis epidemiology:

Answer 32

A yeast with a PROMINENT POLYSACCHARIDE CAPSULE, which reproduces by budding.
Found worldwide, associated with pigeons. Symptomatic disease uncommon in normal hosts.

Question 33

Cryptococcosis pathology:

Answer 33

After inhalation, typically asymptomatic. Infection is walled-off by alveolar macrophages. DISEASE IS FELT TO BE DUE TO REACTIVATION. CELL-MEDIATED IMMUNITY IS NECESSARY TO LIMIT DISEASE.
Cryptococcus can disseminate after primary infection, and produces meningoencephalitis. Can also produce a cryptococcoma (mass lesion).

Question 34

Cryptococcosis presentation:

Answer 34

Meningoencephalitis: Insidious to subacute onset. Headache, malaise, impaired memory, behavior changes, CRANIAL NERVE INVOLVEMENT, fever, hydrocephalus.
Respiratory: cough, chest pain, sputum, hemoptysis.

Question 35

Cryptococcosis diagnosis:

Answer 35

CRYPTOCOCCAL ANTIGEN TESTING is the mainstay of diagnosis, via latex agglutination. Titer indicates burden of disease.
ELEVATED CNS OPENING PRESSURE, with low glucose, increased protein, low WBCs.
Stain CSF (or sputum) with India ink or other stains.
Culture (most definitive way to make the diagnosis).

Question 36

Cryptococcosis treatment and prophylaxis:

Answer 36

Improve immune status.
In AIDS, institute anti-cryptococcal therapy prior to antiretroviral therapy to prevent Immune Reconstitution Inflammatory Syndrome (IRIS).
Serial lumbar punctures, or lumbar drain placement, may reduce ICP.
Treatment for mild-to-moderate disease in HIV-negative patient: FLUCONAZOLE.
Gold-strandard treatment: AMPHOTERICIN B + FLUCYTOSINE (induction therapy for 2 weeks) followed by FLUCONAZOLE for 6 weeks.