Fungal Infections Flashcards by Luke Lloyd

Candida Albicans

Very common dimorphic yeast

_ form – commensal

_form – pathogen

ability of the yeast to undergo transformation to hyphal form under appropriate conditions, producing germinative or “germ” tubes

yeast form – commensal

hyphal form – pathogen

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Whether candidiasis develops, and the severity of the disease itself, appears to depend on at least three factors

The host immune status

The oral mucosal environment

The virulence of the candidal strain

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spectrum of Candida infection

_ state
_
localized invasive candidiasis and disseminated candidiasis uncommon

carrier state

superficial oral mucosal/cutaneous infection

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oral candidiasis presentations

_ _ _

pseudomembranous candidiasis

erythematous candidiasis

hyperplastic candidiasis

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_ Candidiasis
White, curdled milk or cottage cheese-like plaques; can be wiped-off

 Common sites: buccal mucosa, palate or tongue

 May be asymptomatic, but burning or unpleasant taste occasionally noted

Pseudomembranous Also known as “thrush”

not the most common but the most recognized

removable white plaque
Underneath the plaque - only invade very superficial
Underneath epi is okay - might be a little erythrothema

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_candidiasis

area of redness, variable borders

 tongue (posterior dorsal) is common site; may involve palate, oral commissures, perioral skin

Erythematous candidiasis

Acute atrophic candidiasis (“antibiotic sore mouth”)  Central papillary atrophy  Denture stomatitis?  Angular cheilitis  Perioral candidiasis  Chronic multifocal candidiasis

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_candidiasis

diffuse atrophy of dorsal tongue papillae, particularly after broad-spectrum antibiotics

acute onset

typically associated with “burning” sensation

Acute atrophic candidiasis aka “antibiotic sore mouth”

Become smooth and flat - as papilla become atrophic - goes from whitish to ball red surface of tongue

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Probably referred to as “median rhomboid glossitis” in the past

 Most are due to chronic candidiasis

 Well-defined area of redness, mid-posterior dorsal tongue

 Usually asymptomatic

Central Papillary Atrophy candidiasis

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Often referred to as “chronic atrophic candidiasis”
 Not much evidence to support this concept
 Denture is often contaminated with candidal organisms, but no invasion of mucosa is seen
 Erythema of palatal denture-bearing area - typically asymptomatic

Denture Stomatitis

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Usually related to candidiasis, but may have other cutaneous bacterial microflora admixed
 Redness, cracking of corners of mouth
 Often waxes and wanes
 Typically responds well to topical antifungal therapy

Angular Cheilitis

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Often associated with lip-licking or chronic use of petrolatum-based materials
 Usually related to candidiasis, but may have other cutaneous bacterial microflora admixed
 Redness, cracking of cutaneous surface

 Typically responds well to topical antifungal therapy

Perioral Candidiasis

looks like red lipstick all over

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Patient will have angular cheilitis, central papillary atrophy and a “kissing lesion” of the posterior hard palate

Chronic Multifocal Candidiasis

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_ Candidiasis

Also known as “candidal leukoplakia”
 White patch that cannot be rubbed off
 Uncommon; generally anterior buccal mucosa
 May be problematic because a true leukoplakia may have candidiasis superimposed on it
 Should resolve with antifungal therapy

Hyperplastic Candidiasis

less common clinically

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rare candidal infection

associated with specific immunologic defects related to how the body interacts with Candida albicans

Chronic Mucocutaneous Candidiasis

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rare candidal infection

seen in situations of severe uncontrolled diabetes mellitus or immune suppression

Invasive Candidiasis

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how to Dx Candidiasis

Sometimes clinical signs and symptoms are sufficient

 Culture - may not distinguish between carrier and infection

 Exfoliative cytology

 Biopsy - usually not necessary

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Histopathologic Features

 Variable host response to the organism
 Microabscesses may be seen in the superficial epithelium
 Chronic inflammation of the C.T.
 Acanthosis is often present
 In almost all cases, the candidal hyphae never penetrate deeper than the keratin layer

Candidasis infection

acanthosis - increased thickness of epi

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Px of candidiasis infection

In general, oral candidiasis is a nuisance that may present in normal patients, patients who have localized predisposing oral conditions, or immunosuppressed patients

 Good prognosis in normal patients

 Fair to poor prognosis, depending on degree of immune suppression

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Candidiasis - Treatment ?

Depends on the severity of the infection

 Superficial oral mucosal infections can usually be treated with one of the milder topical or systemic antifungal agents

 Life-threatening infections usually require intravenous amphotericin B

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Imidazole antifungal agent
 No significant systemic absorption or side effects
 Pleasant-tasting lozenges (troches)
 Disadvantage – dosing schedule (should be dissolved in mouth 5 times per day)

Clotrimazole (Mycelex)

Mycelex Oral Troches
Disp: fifty (50) Sig: dissolve i slowly PO 5x/day for 10 days

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Developed during the 1950’s - still used
 Not absorbed systemically - must be in contact with the organism in order to be effective
 Disadvantages: taste (bitter to many), multiple dosing schedule, patient compliance

Nystatin (Mycostatin

for RPD tx - Nystatin Oral Suspension (100,000 u/ml)
Disp: 240 ml Sig: soak denture overnight for 10 days in enough liquid to cover.

**mild bleeach solution used for complete dentures

 Triazole antifungal agent
 Readily absorbed systemically- no significant degree of side effects (potential drug interactions)
 Daily dosing is convenient
 Relatively expensive

Fluconazole (Diflucan)

Topical Antifungal Agents
Treatment of angular cheilitis or perioral candidiasis:

_- combination of nystatin and triamcinolone

Vytone Cream - combination of iodoquinol and hydrocortisone

Mycolog II Cream - nystatin and triamcinolone

Vytone Cream - iodoquinol and hydrocortisone

Endemic to Ohio and Mississippi River valleys
 500,000 new cases in U.S. annually
 Spores in bird or bat droppings

Histoplasmosis

 Histoplasma capsulatum

Most cases are asymptomatic – calcified hilar lymph nodes seen coincidentally  Acute – may have flu-like illness  Chronic – cavitary pulmonary lesions  Disseminated – elderly, debilitated, or immunocompromised

Histoplasmosis

Oral Lesions  Usually seen in the disseminated form of the disease  Affects tongue, palate, or buccal mucosa  Presents as a chronic variably painful ulcer or granular erythematous plaque  Clinically may be identical to malignancy

Histoplasmosis

Histoplasmosis  Granulomatous inflammation, with or without necrosis  1-2 micron yeasts, usually within macrophages  Best visualized by _

silver stain (GMS) or PAS

Dx of histoplasmosis

Identification of characteristic small yeasts in tissue sections  Culture of the H. capsulatum organism from a suspected lesion  Serologic testing for antibodies or yeastrelated antigens

Histoplasmosis - Treatment

Acute – no treatment is usually necessary  Chronic or disseminated histoplasmosis – may require amphotericin B  Ketoconazole or itraconazole for mild cases or as maintenance therapy

Histoplasmosis - Prognosis

Acute histoplasmosis in an immunocompetent patient – good  Chronic histoplasmosis – fair  Disseminated – poor; mortality rate of 90% if untreated; 7-23% if treated

Endemic to desert Southwest U.S.  100,000 people infected annually in U.S.  “Valley fever” represents a hypersensitivity reaction

Coccidioidomycosis |  Coccidioides immitis

Inhalation of spores  Flu-like illness in 40% of infected patients  Dissemination in <1%  Skin of central face may be affected; oral lesions are rarely described

Coccidioidomycosis

Histopathologically shows large (20-60 micron) spherules that contain endospores  Variable host response, ranging from acute to granulomatous inflammation  Diagnosis can be made by culture or biopsy

Coccidioidomycosis

Coccidioidomycosis tx?

Amphotericin B for disseminated cases  Fluconazole or itraconazole for milder cases  May be more aggressive in persons of color  Generally good prognosis if patient is not immunocompromised

Organism lives in pigeon droppings  Transmitted by air-borne spores  Affects immunosuppressed patients almost exclusively

Cryptococcosis |  Cryptococcus neoformans

Flu-like symptoms with initial pulmonary infection  Disseminates to meninges, resulting in headache, vomiting, neck stiffness  Cutaneous lesions may develop in 10-20%  Oral lesions are rare

Cryptococcosis

Histopathologically, 4-6 micron yeasts with a clear halo (representing a mucopolysaccharide capsule) Organisms may be visualized with mucicarmine, PAS, or silver stain (GMS) Diagnosis based on culture or identification of organisms in tissue sections

Cryptococcosis

Cryptococcosis tx?

Severe cases treated with amphotericin B and flucytosine  Fluconazole for less severe cases and for maintenance  Poor prognosis because most patients are immunocompromised

 Also known as Mucormycosis  Several genera of molds, including Mucor, Rhizopus, and Absidia  Affects severe diabetic or immunocompromised patient  Rhinocerebral form in oral region

Zygomycosis

Nasal obstruction, bloody nasal discharge  Facial pain, swelling, palatal perforation  Black, necrotic lesions  With progression superiorly, visual disturbances and blindness result  Seizures and death occur with intracranial invasion

Zygomycosis

Diagnosis is usually based on histopathologic findings because culture is too slow  Large, branching, nonseptate hyphae with extensive tissue necrosis  Hyphae are often seen plugging small blood vessels

Zygomycosis

Zygomycosis tx? px?

Radical surgical debridement  IV amphotericin B  If patient is diabetic, control of diabetes is important  Poor prognosis

Common; second in frequency to Candidiasis  Several species  Spectrum of disease that includes allergy, localized infection or invasive aspergillosis  Spores in soil, water, decaying organic debris  May be “nosocomial” infection

Aspergillosis

Features vary, depending on immune status and extent of tissue invasion  Allergy- Allergic fungal sinusitis (may trigger asthma)  maxillary sinus fungus ball  Tissue damage - locally invasive  Immunocompromised patient - disseminated

Aspergillosis “Aspergilloma” – max sinus fungal ball

Biopsy shows branching septate hyphae  Occlusion of small blood vessels by hyphae  Granulomatous inflammation if the host is not immune compromised  Little inflammation if immunocompromised  Culture can be done, but may be too slow

Aspergillosis

Treatment and Prognosis Aspergillosis invasive vs non-invasive

Non-invasive disease:  debridement  Invasive disease:  Voriconazole or itraconazole, with or without debridement  Good prognosis if normal immune status  Poor prognosis if patient is immunocompromised

Was approved for topical use in the US, but tastes bitter, and is no longer available  IV form is used to treat life-threatening systemic fungal infections  Nephrotoxicity is significant with standard amphotericin, but newer (expensive) liposomal preparations are relatively non-toxic

Amphotericin B (Fungizone)

First oral antifungal agent that could be absorbed systemically- imidazole  Requires acidic stomach environment  Single daily dose is convenient  Problems with drug interactions and idiosyncratic hepatotoxicity (1 in 12,000)

Ketoconazole (Nizoral

 Approved for treating histoplasmosis  Well-absorbed; daily dosing  Minimal side effects  Quite expensive

Itraconazole (Sporanox)

Triazole compound; IV or oral  Approved for treating Candida, Aspergillus and several other species  Side effects include photosensitivity++  1st line therapy - invasive aspergillosis  Quite expensive ($460)

Voriconazole