Pulmonary Fungal Infections 2: Opportunistic Mycoses Flashcards by Paul Shanley

What are the five major human opportunistic mycoses?

Candidiasis
Cryptococcosis
Aspergillosis
Mucormycosis
Fusariosis

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What is the MOST IMPORTANT PREDISPOSITION to opportunistic mycoses?

Prolonged neutropenia

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What organism most commonly causes Candidiasis?

Candida albicans

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What are the most common diseases caused by Candida infection?

Thrush, vaginitis (yeast infection), diaper rash, mucocutaneous candidiasis

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What are microscopic features that can help in the Dx of Candidiasis?

Oval yeast w/ single bud, but may also appear as pseudohyphae, or hyphae

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What is the Dx? In what situations is it almost always seen?

Thrush; HIV+ patients not on HAART

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What diseases (other than thrush) that can be caused by Candida overgrowth?

Vaginitis (“Yeast Infection”), Skin overgrowth, Folliculitis

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What is the Dx? What is typically associated with it?

Disseminated Candidiasis; T cell immunity or IL-17 deficiency, possibly underlying malignancy

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What type of cardiac pathology occurs with disseminated candida infection?

Right-sided endocarditis

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Microscopy reveals gram-positive mixture of budding yeasts, pseudohyphae, and hyphae. What is the Dx?

Candida

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When culturing candida, what is a vital step that must be performed?

Antifungal susceptibility testing (make sure the drug will work!)

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What is the general trend for Candida infection Tx for Thrush? Skin? Vaginitis? Dissemination?

Fluconazole
Azoles
Azoles
Amphotericin B or Fluconazole

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If you have any suspicion of disseminated Candida what should you do?

Start Tx immediately

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Why are Candida abscesses important to drain?

Abscesses get poor bloodflow and therefore antifungal Tx will not reach the abscess

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What is the bug that causes Cryptococcosis? What condition is it notorious for causing?

Cryptococcus neoformans; Cryptococcal meningits

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By what route do patients acquire cryptococcus?

Inhalation of pigeon droppings

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What is absolutely diagnostic for cryptococcus?

Sample stained with India Ink revealing wide capsules

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Describe the pathogenesis of cryptococcosis in immunosuppressed patients

Patient inhales organism
Yeasts disseminate
Patients deficient in helper T cells cannot activate macrophages.
Macrophages become Trojan horses
If patients also lack Abs to the capusle, bare yeast are free to roam

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What are physical exam findings that are helpful in diagnosing disseminated Cryptococcus infection?

Hx of steroid use, malignant disease, transplantation, HIV

Skin lesions

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What is unique about the body’s response to Cryptococcosis infection? Why?

There is very little inflammation and therefore minimal fever and stiff neck and therefore presentation is typically late in disease

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What are typical lab findings that are suggestive of Cryptococcosis?

Spinal Tap with India Ink stain
Biopsies stained with Methenamine silver, periodic acid-Schiff, or mucicarmine
Culture
Serology - test for “crag” (Cryptococcal antigen)

What will routine bloodwork show for a cryptococcal infection?

Very possibly will be normal because of very little inflammatory processes

What is the general Tx for cryptococcosis? AIDS patients? Prostate Infection?

Amphotericin B plus flucytosine initially
For AIDS patients fluconazole for long-term suppression
Protstate/Pneumonia - Fluconazole or Itraconazole

Microscopy reveals the following image. How would you describe it? What is the Dx? What is the most common bug that causes this?

Septate hyphae with V-shaped branches; Aspergillosis; Aspergillus fumigatus

What are the four syndromes involving Aspergillus

1. Allergic bronchopulmonary aspergillosis (ABPA) 2. Aspergilloma 3. Chronic necrotizing pulmonary aspergillosis 4. Invasive Aspergillosis

What is ABPA? In what patients is it typically found?

Allergic bronchopulmonary aspergillosis - Hypersensitvity to infection of bronchi by aspergillus; Asthmatics and CF patients

What is an aspergilloma and how does it form?

Fungus ball that forms when aspergillus invades pulmonary cavitations originally caused by TB or CF

What is CNPA? What is the general pathogenesis?

Chronic necrotizing pulmonary aspergillosis; Aspergillosis can invade lungs causing pneumonia w/ hemoptysis and granulomas

What is invasive aspergillosis? What is it a fairly common cause of?

When aspergillus rapidly invades blood vessels in severely IC patients involving infarction, hemorrhage, and necrosis; Often causes death of severely IC patients

A CXR is shown below. "Grape cluster" and "hand in mitten" morphology is shown. The patient was constantly coughing up brownish bronchial plugs. What is the Dx?

Allergic bronchopulmonary aspergillosis

Chest CT shows the following. What is the Dx? What is the sign observed?

Aspergilloma; Air Cresent Sign

What are underlying diseases that are normally associated with CNPA? What is your best diagnostic method?

* Alcoholism, Collagen-vascular disease, chronic granulomatous disease, COPD, long-term corticosteroids * Aspirate from the lungs

A CT scan shows a characteristic halo sign: ground-glass infiltrates surrounding a nodular density. What does this represent? What is the Dx?

Represents hemorrhage; Invasive aspergillosis

What lab tests are useful for Dx Aspergillosis?

1. **Cultures** from sputum, needle biopsy, bronchoalveolar lavage - Visualize with silver stain 2. **Invasive** **Aspergillosis** - Septate hyphae branching at **ACUTE ANGLES**, high serum levels of **galactomannan antigen** 3. **ABPA** - High levels of aspergillus-specific IgE, eosinophilia

What is the Tx for ABPA? Aspergilloma? CNPA? Invasive?

* **ABPA** - Oral corticosteroids, itraconazole * **Aspergilloma** - surgery, oral itraconazole * **CNPA** - Amphotericin B or Voriconazole * **Invasive**

The following microscopic analysis is shown. What is the likely diagnosis? What is characteristic of this bug?

Mucormycosis; The hyphae branch at 90^o

Describe the pathogenesis of Mucormycosis

1. Inhaled/ingested spores 2. Invade tissues of patients w/ reduced immunity (diabetes, burns, leukemia) 3. Proliferate in walls of blood vessels 4. Cause necrosis of paranasal sinuses, lungs, gut

Why is it worrisome when a patient with Mucormycosis shows Syx?

Patients will soon drop dead

A patient presents with unilateral retro-orbital headache, facial pain, numbness, fever, vision loss, and black pus. What is the likely Dx?

Rhinocerebral Mycormycosis

What are useful lab tests in the Dx of mucormycosis?

* **Bloodwork** - reveals neutropenia, possibly diabetic acidosis, iron overload * **Biopsy** - **NONseptate hyphae** w/ broad irregular walls and branches at **RIGHT ANGLES** * **Culture** - colonies w/ spores contained in sporangium. Difficult to culture

What are the useful antigen tests and CSF findings for mucormycosis?

There are none! HA!

What is the primary defense against mucormycosis?

Neutrophils

What is the major bug that causes Fusarium infection?

Fusarium solani

How are fusarium identified microscopically?

Identified microscopically by banana-shaped macroconidia

What are the three presentations of Fusarium?

1. Mycotoxicosis -\> Trichothecene mycotoxins 2. Immunocompetent local infection - Skin, Cornea, Allergic sinusitis 3. Aggressive disseminated infection

What is the primary risk factor for fusarium infection?

Neutropenia

What are fusarium virulence factors?

* Immunosuppressive mycotoxins * Collagenases * Proteases * Adherence to prosthetic materials

Describe the pathogenesis of disseminated fusarium

1. Usually invades from sinus or wound site 2. Fungemia 3. Invasion of eye, sinus, pneumonia, skin lesions

What process is must be performed to get a Dx of fusarium?

1. Take samples from several sites for **Multiple cultures** 2. Fusarium is ubiquitous in the environment and a single positive result is probably due to contamination 3. **Histology** - yeast form must be present along with the acute branching hyphae 4. PCR available

What is the Tx and Px for fusarium?

**NOTE:** Fusarium is more resistant to antifungals 1. Surgical Excision 2. **Try** Amphotericin B with natamycin or voriconazole Px in disseminated disease is **POOR**

What is the process for Fusarium prevention?

Keep patient in HEPA-filtered room at a **POSITIVE PRESSURE** with filtered water and scrubbed-down showers

What is vital in the pre-op workup for Hematopoietic Stem Cell Transplant?

Screen for fusarial infection. Patient will become immunosuppressed and can contract disseminated fusarium