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Table 5-1. Major Fungal Infections Commonly Found in the United States
Disease
Causative Organism
Candidiasis
Sporotrichosis
Chromyoblastomycosis
Eumycotic mycetoma
Pathogenic fungal infections
Coccidioidomycosis
Histoplasmosis
Blastomycosis
Paracoccidioidomycosis
Opportunistic fungal infections
Cryptococcal meningitis
Malassezia fungemia
Aspergillosis
Zygomycosis (phycomycosis)
Candidiasis, systemic and local
Exophiala werneckii
Malassezia furfur
Dermatophytes (Microsporum,
Trichophyton, Epidermophyton)
Candida
Sporothrix schenckii
Fonsecaea, Phialophora, Cladosporium
Pseudallescheria boydii, Madurella
Coccidioides immitis
Histoplasma capsulatum
Blastomyces dermatitidis
Paracoccidioides brasiliensis
Cryptococcus neoformans
Malassezia furfur
Aspergillus fumigatus, Aspergillus sp.
Mucor, Absidia, Rhizopus, Rhizomucor
Candida albicans, Candida sp.
Candida vaginitis
Diabetes, leukemia
Rhinocerebral mucormycosis
Fungemia (Candida or
Malassezia)
Urinary catheter
AIDS
AIDS
Severe neutropenia
Pulmonary symptoms
Urinary candidiasis
Esophageal candidiasis
Cryptococcal meningitis,
Histoplasma or coccidioidal
meningitis, Candida cerebritis
Aspergillus central nervous
system infection
Cryptococcal meningitis (chronic)
Invasive Aspergillosis
Pneumocystis pneumonia
Histoplasmosis, coccidioidomycosis
Alcoholism (urban)
Sporotrichosis (pulmonary)
Hemoptysis
Previous lung damage, especially Aspergilloma
cavities
Endocarditis
Intravenous drug abuse
Candida or Aspergillus
endocarditis
Enteritis (often with anal
Antibiotic use
Candida enteritis (irritable bowel
pruritus)
syndrome)
Whitish covering in mouth Premature infants, children on
Candida thrush
antibiotics
Corners of mouth sore
Elderly suffering from
Perlche
malnourishment
Sore gums
Dentures
Denture stomatitis or allergy to
antifungal used in treatment of
denture stomatitis
Skin lesions;
Indwelling catheter
Candidemia
endophthalmitis
o Cultures of normally sterile parts of the body (such as CSF), with cultures
identified by germ tube (sprouts formed from the yeast cells) formation
and morphologic and chemical tests
o Serologic testing demonstrating high levels of Candida precipitins or antigens
o Chromatographic methods to detect fungal products
Forms of candidiases
o Oral thrush
is a yeast infection of the oral mucocutaneous membranes.
manifests as white curd-like patches in the oral cavity.
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occurs in premature infants, older infants being treated with antibiotics,
immunosuppressed patients on long-term antibiotics, and AIDS patients.
o Vulvovaginitis or vaginal thrush
is a yeast infection of the vagina that tends to recur.
manifests with a thick yellow-white discharge, a burning sensation, curdlike patches on the vaginal mucosa, and inflammation of the peritoneum.
is predisposed by diabetes, antibiotic therapy, oral contraceptive use, and
pregnancy.
o Cutaneous candidiasis
involves the nails, skin folds (visible as creamy growth), or groin.
may be eczematoid or vesicular and pustular.
is predisposed by moist conditions.
o Alimentary tract disease
is usually an extension of oral thrush and may include esophagitis and,
ultimately, the entire gastrointestinal tract.
is found in patients with AIDS or other immunosuppressive disorders,
particularly those patients on long-term antibiotic therapy.
is reduced in highly susceptible populations by fungal prophylaxis.
o Candidemias or blood-borne infections
occur most commonly in patients with indwelling catheters or
gastrointestinal tract overgrowth; these infections are manifested by fever,
macronodular skin lesions, and endophthalmitis.
o Endocarditis
occurs in patients who have manipulated or damaged valves or in IV drug
abusers.
o Bronchopulmonary infection
occurs in patients with chronic lung disease; it is usually manifested by
persistent cough.
o Cerebromeningeal infection
may occur in compromised patients.
o Chronic mucocutaneous candidiasis
is a chronic, often disfiguring infection of the epithelial surfaces of the
body.
is diagnosed microscopically and by the lack of cell-mediated immunity
(anergy) to Candida antigens.
B. Malassezia furfur septicemia
is a blood-borne infection caused by the lipophilic skin organism M. furfur.
occurs in patients (primarily neonates) who are on IV lipid emulsions.
is diagnosed by culturing blood on fungal medium that is either lightly overlaid with
sterile olive oil or has lipids incorporated into the medium.
may resolve by halting the lipid supplements.
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C. Cryptococcal meningitis
is the most common clinical form of cryptococcal infection. (Cryptococcal pneumonia is
generally only seen in pigeon breeders who are assumed to be exposed to high levels of C
neoformans).
is caused by C neoformans.
Cryptococcus neoformans
o is a yeast that possesses an antigenic polysaccharide capsule.
o may be isolated from fruit, milk, vegetation, soil, and pigeon feces.
o is considered to be an opportunist in the presence of underlying disease in patients
with Hodgkin's disease, leukemias, or leukocyte enzyme deficiency diseases.
Clinical presentationcryptococcal meningitis or meningoencephalitis
o presents most commonly with a headache of increasing severity, usually with
fever, followed by typical signs of meningitis.
o is the most common meningitis occurring in AIDS patients.
o also occurs in diabetic patients and patients with Hodgkin's disease.
Laboratory diagnosis
o Detection of cryptococcal capsular material in the CSF by the cryptococcal
antigen latex-particle agglutination test
o Demonstration of encapsulated yeast in CSF sediment on a wet mount in nigrosin
or India ink (However, this technique misses approximately 50% of the culturally
proven cases of cryptococcal meningitis.)
o Confirmation by isolation of C neoformans in culture of CSF
D. Aspergilloses
are a variety of infections and allergic diseases that are caused by Aspergillus fumigatus
and a variety of other species of Aspergillus.
Aspergillus fumigatus
o is a ubiquitous filamentous fungus (one of our major recyclers) whose airborne
spores (conidia) are constantly in the air.
o is recognized both in tissue and in culture by its characteristic septate hyphae with
dichotomous branching and an acute branching angle.
o is an opportunistic organism.
Forms of aspergilloses
o Allergic bronchopulmonary aspergillosis
is an allergic disease in which the organism colonizes the mucous plugs
formed in the lungs but does not invade lung tissues.
is diagnosed by the finding of high titers of IgE antibodies to Aspergillus.
o Aspergilloma
is a roughly spherical growth of Aspergillus in preexisting lung cavities;
growth does not invade the lung tissues.
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presents clinically as recurrent hemoptysis.
is diagnosed by radiologic methods; an air sign shift will be seen
with a change in the position of the patient.
o Invasive aspergillosis
occurs most commonly during severe neutropenia in leukemia and
transplant patients.
E. Zygomycoses
are also known as phycomycoses or mucormycoses.
are infections most commonly caused by the genera Rhizopus, Absidia, Mucor, and
Rhizomucor, which belong to the phylum Zygomycota (the nonseptate fungi).
Zygomycota
o have nonseptate hyphae.
o grow rapidly.
o have a predilection for invading blood vessels and the brain.
Rhinocerebral infection
o is the most common form of zygomycosis; it occurs in patients with acidotic
diabetes.
o presents with facial swelling and blood-tinged exudate in the turbinate bones and
eyes, mental lethargy, and fixated pupils.
o must be diagnosed rapidly, usually by a KOH mount of necrotic tissue or exudates
from the eye, ear, or nose.
o is rarely treated successfully; treatment consists of control of diabetes, surgical
dbridement, and aggressive treatment with amphotericin B.
F. Pneumocystis pneumonitis and pneumonia
are infections caused by Pneumocystis carinii.
Pneumocystis carinii
o is considered a fungus, based on molecular biologic techniques such as ribotyping
and DNA homology.
o is an obligate parasite of humans (cannot be grown in vitro) but is extracellular,
growing on the surfactant layer over the alveolar epithelium.
o colonizes most humans early in life, without apparent disease.
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Table 5-4. Symptoms and Clues to Diagnosis of Fungal Diseases in Generally Healthy
Patients With Superficial, Cutaneous, Mucocutaneous, Subcutaneous, or Allergic Fungal
Diseases*
Most Common
Presenting Symptoms
Possible Disease
Clues
Fungal Agent
Hyperpigmented or
Pityriasis versicolor
hypopigmented skin
macules with little
inflammation, generally on
trunk of body
Cutaneous lesions with
Tineas
various degrees of
inflammation
Candidiasis of skin
Mucocutaneous lesion
Candidiasis
(vaginitis, diaper rash)
Subcutaneous lesions
Sporotrichosis
following lymph nodes or
Dermatophytes:
Epidermophyton,
Trichophyton,
Microsporum
KOH: pseudohyphae Candida albicans and
and yeasts
related species
KOH: pseudohyphae Candida albicans and
and yeast
related species
KOH: cigar-shaped Sporothrix schenckii
yeast in tissue
(most likely in the
solitary nodule
Examination of skin scrapings or other tissue mounted in and cleared with potassium hydroxide
(KOH) and examined microscopically.
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Table 5-5. Symptoms and Clues to Diagnosis of Fungal Diseases in Generally Healthy
Patients With Systemic Symptoms
Most
Common
Presenting Symptoms
Possible Disease
Clues
Fungal Agent
Acute pulmonary disease Histoplasmosis
(cough, fever, night sweats)
Blastomycosis
Exposure to soil/dust
Histoplasma
contaminated with bird
capsulatum
(especially chicken and
starling) or bat feces
Environmental form or
25C culture: hyphae with
microconidia and large
tuberculate macroconidia
Endemic region: Ohio,
Mississippi, Missouri
riverbeds
Tissue: small, intracellular
yeast
Exposure to rotting wood Blastomyces
Environmental form or
dermatitidis
25C culture: hyphae with
microconidia
Endemic region: as for
Histoplasma plus
southeastern seaboard of
the U.S.
Tissue: large, budding yeast
with double refractile wall
Coccidioidomycosis
Review Test
1. A florist presents with a subcutaneous lesion on the hand, which she thinks resulted from a jab
wound she received while she was making a sphagnum moss-wire frame for a floral wreath. The
lesion has not healed despite use of antibacterial cream and has begun to spread up her arm with
the lymph node raised and red and beginning to look like it might ulcerate, like the original
lesion. The lymph node above is also beginning to redden and is slightly raised. What is most
likely to be an appropriate treatment for this infection?
(A) Oral itraconazole or potassium iodide
(B) Miconazole cream
(C) Cortisone cream
(D) Oral griseofulvin
(E) Penicillin
View Answer
1A. This is a classic case of lymphocutaneous sporotrichosis in which a gardener or florist is
infected via a puncture wound. The drug of choice is either itraconazole or potassium iodide
(administered orally in milk). Topical antifungals are not effective, and the cortisone cream
would probably enhance the spread of the disease. Griseofulvin localizes in the keratinized
tissues and would not halt the subcutaneous spread of this infection. Penicillin would have no
effect because Sporothrix is not a bacterium.
2. What would you expect to see in the above patient's tissue biopsy?
(A) Lots of hyphae
(B) Long, branching hyphae with acute angles
(C) Yeasts with broad-based buds
(D) Cigar-shaped yeasts
(E) Yeast with multiple buds (mariner's wheel)
View Answer
2D. Sporothrix schenckii is dimorphic; the tissue form is cigar-shaped yeasts.
3. A patient presents with paranasal swelling and bloody exudate from both his eyes and nares,
and he is nearly comatose. What is the most likely compromising condition underlying this
infection caused by Rhizopus, Mucor, or Absidia (phylum Zygomycota, class Phycomycetes)?
(A) AIDS
(B) Diabetes (with patient in ketoacidosis)
(C) Neutropenia
(D) B-cell defects
(E) Chronic sinusitis
View Answer
3B. Zygomycota are aseptate fungi that cause serious infections, primarily in ketoacidotic
diabetic patients and cancer patients. Fungal infections common in AIDS patients include
Candida infections (ranging from oral thrush early to fungemias later), cryptococcal meningitis,
and disseminated histoplasmosis and coccidioidomycoses. Severely neutropenic patients are
most likely to have invasive Aspergillus infections.
4. What type of fungal skin lesions would show only hyphae and possible arthroconidia in a
biopsy?
(A) Blastomycosis (disseminated)
(B) Chronic mucocutaneous candidiasis
(C) Coccidioidomycosis
8B. The fungal subunit, called a hypha, is a filamentous structure with or without cell walls.
9. Which of the following oral antifungal agents inhibits microtubule formation and may be used
to treat dermatophytic infections?
(A) Amphotericin B
(B) Griseofulvin
(C) Ketoconazole
(D) Miconazole
(E) Nystatin
View Answer
9B. Griseofulvin, which localizes in the keratinized tissues, inhibits the growth of
dermatophytes by inhibiting microtubule assembly.
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10. A 15-year-old dirt biker visiting southern California has pneumonia caused by an organism
whose environmental form consists of hyphae that break up into arthroconidia, which become
airborne. What is the agent?
(A) Aspergillus fumigatus
(B) Blastomyces dermatitidis
(C) Coccidioides immitis
(D) Histoplasma capsulatum
(E) Sporothrix schenckii
View Answer
10C. Coccidioides immitis is found in desert sand, primarily as arthroconidia and hyphae.
11. Which of the following inhibits ergosterol synthesis, is important in treating Candida
fungemias, and is used orally to suppress relapses of cryptococcal meningitis in AIDS patients?
(A) Amphotericin B
(B) Fluconazole
(C) Griseofulvin
(D) Miconazole
(E) Nystatin
View Answer
11B. Fluconazole is an imidazole; all imidazoles inhibit ergosterol synthesis. Fluconazole has
become the mainstay in the treatment of serious candidal infections, and it is used to prevent
relapse of fungal central nervous system infections in compromised patients. Miconazole, also an
imidazole, is available in topical or intravenous preparations and has been largely replaced by the
oral fluconazole.
12. A patient has splotchy hypopigmentation on the chest and back with only slight itchiness.
What is most likely to be seen on a potassium hydroxide (KOH) mount of the skin scraping?
(A) Yeasts, pseudohyphae, and true hyphae
(B) Filaments with lots of arthroconidia
(C) Clusters of round fungal cells with short, curved, septate hyphae
(D) Darkly pigmented, round cells with sharp interior septations
(E) Cigar-shaped yeasts
View Answer
12C. Malassezia furfur is seen in tissues as clusters of round fungal cells with short, curved,
septate hyphae (spaghetti and meatballs) and is the causative agent of pityriasis or tinea
versicolor; M furfur overgrowth causes pigmentation disturbances.
13. A patient has a dry, scaly, erythematous penis. Skin scales stained with calcofluor white show
fluorescent blue-white yeasts and a few pseudohyphae. What is the causative agent of this
dermatophytic look-alike?
(A) Candida
(B) Trichosporon
(C) Trichophyton
(D) Malassezia
(E) Microsporum
View Answer
13A. Candida may cause skin infections that resemble some dermatophytic infections. The
patient described in the question has Candida balanitis. In tinea cruris, the penis is not usually
involved.
14. A recent immigrant from rural Brazil presents with a swollen face and extremely poor dental
hygiene, including loss of an adult tooth, which appears to be the focus of the current infection.
There are two open ulcers on the outside of the swollen cheek. Small yellow grains are
seen in one of the ulcers. Gram stain shows purple-staining fine filaments. What is the most
likely disease?
(A) Actinomycotic mycetoma
(B) Chromomycosis
(C) Eumycotic mycetoma
(D) Sporotrichosis
(E) Paracoccidioidomycosis
View Answer
14A. The disease syndrome is lumpy jaw, which is a form of mycetoma. The presenting signs
seen in this patient suggest actinomycotic mycetoma, a bacterial infection caused by
Actinomyces. (Students: you needed a nonfungal question.) Yeasts will also stain gram-positive.
Remember that Actinomyces is a gram-positive anaerobe that is not acid-fast.
15. A patient who is a recent immigrant from a tropical, remote, rural area with no medical care
is now working with a group of migrant crop harvesters. He has a large, raised, colored,
cauliflower-like ankle lesion. Darkly pigmented, yeast-like sclerotic bodies are seen in the tissue
biopsy. Which of the following is the most likely diagnosis?
(A) Actinomycotic mycetoma
(B) Chromoblastomycosis
(C) Eumycotic mycetoma
(D) Sporotrichosis
(E) Tinea nigra
View Answer
15B. The finding of dematiaceous (dark), yeast-like forms with sharp planar division lines
and the clinical presentation are both characteristic of chromoblastomycosis. Tinea nigra would
show dematiaceous hyphae.
16. A premature baby, now 4 days old, has developed a white coating on her buccal mucosa
extending onto her lips. It appears to be painful. What is the most likely causative agent?
(A) Actinomyces
(B) Aspergillus
(C) Candida
(D) Fusobacterium
(E) Microsporum
View Answer
16C. The disease described is thrush, and it is caused by Candida.
17. Which of the following stains allows differentiation of fungus from human tissue by staining
the fungus a pink-red color?
(A) Calcofluor white stain
(B) Gomori methenamine-silver stain
(C) Periodic acid-Schiff stain
(D) Hematoxylin and eosin stain
View Answer
17C. Calcofluor white stain, Gomori methenamine-silver stain, and periodic acid-Schiff stain
are all differential stains, but only the periodic acid-Schiff stain turns fungi a pink-red color. The
hematoxylin and eosin stain turns fungi a pink-red color also, but does not differentiate between
the fungi and human tissue.
18. A normally healthy 8-year-old boy from Florida is visiting friends on a farm in Iowa during
the month of July. He presents July 28 with a fever, cough, and lower respiratory symptoms (no
upper respiratory tract symptoms). He has been ill for 4 days. His chest sounds are consistent
with pneumonia, so a chest radiograph is obtained. The radiograph shows small, patchy
infiltrates with hilar adenopathy. His blood smear shows small, nondescript yeast forms inside
monocytic cells. What is the most likely causative agent?
(A) Aspergillus fumigatus
(B) Blastomyces dermatitidis
(C) Coccidioides immitis
(D) Histoplasma capsulatum
(E) Pneumocystis carinii
View Answer
18D. Histoplasma and Blastomyces are both endemic in Iowa, but only Histoplasma fits the
description of a facultative intracellular parasite circulating in the reticuloendothelial system.
19. Which of the following is a polyene antifungal agent used for many life-threatening fungal
infections?
(A) Amphotericin B
(B) Griseofulvin
(C) Itraconazole
(D) Miconazole
(E) Nystatin
View Answer
19A. Amphotericin B, a polyene, is the most effective treatment for many life-threatening
fungal infections. Nystatin, also a polyene, is used topically or orally, but is not absorbed.
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20. A logger undergoing chemotherapy for cancer has developed pneumonia and skin lesions.
Biopsy of the skin lesions demonstrates the presence of large yeasts with thick cell walls and
broad-based buds. What is the most likely causative agent?