Systemic Mycoses

Schaechter’s Chapter 47
Lange Chapter 49
 Systemic Mycoses

Inhalation of the spores of dimorphic fungi that have

their mold forms in the soil.
Within the lungs, the spores differentiate into yeasts or
other specialized forms.
Most lung infections are asymptomatic
some persons - disseminated disease develops in
which the organisms grow in other organs, cause
destructive lesions, and may result in death.
Infected persons do not communicate these diseases
to others.
 COCCIDIOIDES IMMITIS

Disease: Coccidioidomycosis.
Properties:
dimorphic fungus
exists as a mold in soil and as a spherule in
tissue.
(arthrospores) cells at the tip of the hyphae
differentiate into asexual spore which
germinate in the soil to form new hyphae
if inhaled the arthrospores differentiate into
spherules in tissue.
 COCCIDIOIDES IMMITIS
Transmission: Arthrospores are very light and
carried by the wind. Inhaled and infect the lungs.
Pathogenesis:
Lungs - arthrospores form spherules (large with a
thick, doubly refractive wall, filled with endospores).
Upon rupture of the wall, endospores are released and
differentiate to form new spherules.
Organism spreads via the bloodstream.
Granulomatous lesions can occur in virtually any
organ but are found primarily in bones and the
central nervous system (meningitis).
 COCCIDIOIDES IMMITIS: Dissemination
Occurs in people who have a defect in cell-mediated
immunity.
- One way to determine whether a person has
produced adequate cell-mediated immunity to the
organism is to do a skin test.
can occur in almost any organ; the meninges, bone,
and skin are important sites.
incidence of dissemination in persons infected with C.
immitis is 1%, although the incidence in Filipinos and
African Americans is 10 times higher.
Women in the third trimester of pregnancy also have
a increased incidence of dissemination.
 COCCIDIOIDES IMMITIS: Skin Test
• In infected persons, skin tests with fungal extracts (coccidioidin or
spherulin) cause at least a 5-mm induration 48 hours after injection
(delayed hypersensitivity reaction).


• positive skin test - reaction has developed sufficient immunity to prevent

disseminated disease from occurring.


• Skin Test becomes positive within 2—4 weeks of infection and remain
so for years but are often negative (anergy) in patients with
disseminated disease.


• serologic tests - IgM and IgG precipitins appear within 2—4 weeks of
infection and then decline in subsequent months.


• Complement-fixing antibodies occur at low titer initially, but the titer rises
greatly if dissemination occurs.
•
• Not used to diagnose acutely ill patients, but rather to determine whether
a person has been exposed to Coccidiodes in the past.
•
COCCIDIOIDES IMMITIS: Clinical Findings:
• Infection of the lungs is often asymptomatic and is
evident only by a positive skin test and the
presence of antibodies.


• Some infected persons have an influenzalike illness

with fever and cough.


• 50% have changes in the lungs as seen on x-ray, and

10% develop erythema nodosum. This syndrome
is called “valley fever” or “desert rheumatism” it
tends to subside spontaneously.
 COCCIDIOIDES IMMITIS: Erythema
nodosum (EN)
•
• red, tender nodules on extensor surfaces such
as the shins.
• delayed (cell-mediated) hypersensitivity is an
indicator of a good prognosis.
• no organisms in these lesions; they are not a sign
of disseminated disease.
• EN is not specific for coccidioidomycosis; it
occurs in other granulomatous diseases, eg,
histoplasmosis, tuberculosis, and leprosy.
 Coccidioides immitis

•
•


•Genus/Species: Coccidioides immitis •Title: Lesion on knee

•Image Type: Clinical Presentation •Disease(s): Coccidioidomycosis

•Legend: Lesion on knee resulting from dissemination from the lungs.

Erythema Nodosum
 Coccidioides immitis

•
•


•Genus/Species: Coccidioides immitis •Title: Erythema nodosum

•Image Type: Clinical Presentation •Disease(s): Coccidioidomycosis

•Legend: The rash is a immunologic response to the fungus. It is most commonly seen in caucasion women.
 COCCIDIOIDES IMMITIS:
Laboratory Diagnosis
• In tissue specimens, spherules are seen
microscopically.
• Cultures on Sabouraud’s agar incubated at 25 0C
show hyphae with arthrospores.
• Cultures are highly infectious; precautions against
inhaling arthrospores must be taken.
• In infected persons, skin tests with fungal extracts
(coccidioidin or spherulin) cause at least a 5-
mm induration 48 hours after injection (delayed
hypersensitivity reaction).
• Serology is used today instead of culture:
complement fixation test.
 COCCIDIOIDES IMMITIS:

 Treatment:
• Amphotericin B is used for persisting lung lesions
or disseminated disease. Nephrotoxicity and
magnesium and potassium wasting.


• Ketoconazole is also effective in lung disease.



 Prevention:
 There are no means of prevention except avoiding
travel to endemic areas.
Temp. (F)– Children 0-3 months: 99.4
Children 3-6 months: 99.5
Children 6 months to 1 year: 99.7
Children 1 year to 3 years: 99.0
Children 3 years to 5 years: 98.6
Children 5 years to 9 years: 98.3
Children 9 years to 13 years: 98.0
Children 13 year to adult: 97.8 - 99.1
Normal body temperature varies over a narrow range of 36°C (98.6°F) to 37.5°C (99.5)

HR – newborn infants; 100 to 160 beats per minute

children 1 to 10 years; 70 to 120 beats per minute
children over 10 and adults; 60 to 100 beats per minute
well-trained athletes; 40 to 60 beats per minute

pH – 7.35-7.45
WBC - 4500-11,000/mm3
BP – 120/80
pCO2 – 33-45 mmHg
RR – 20 breaths/min.
pO2 – paO2 of 60 to 80 mm is labeled as mild hypoxia < 60 is moderate and < 40 mm of
Hg is labeled as severe hypoxia.
SaO2 - > 70% is acceptable. Saturation is probably more useful than the pO2
Geographic Location is Important for
these three
 Left Shift
• an acute bacterial infection, will cause an increase in both the
total number of mature neutrophils and the less mature
bands or stabs to respond to the infection.
• "shift to the left" This term is a holdover from days in which
lab reports were written by hand.
• Bands or stabs, the less mature neutrophil forms, were written
first on the left-hand side of the laboratory report. Today,
the term "shift to the left" means that the bands or stabs
have increased, indicating an infection in progress.
• For example, a patient with acute appendicitis might have a
"WBC count of 15,000 with 65% of the cells being mature
neutrophils and an increase in stabs or band cells to 10%".
This report is typical of a "shift to the left", and will be taken
into consideration along with history and physical findings,
to determine how the patient's appendicitis will be treated.
Memory Tool: The Coyboy “cocks” his gun in the
old Southwest and “HItS” and “BLASTs” the
Mississippi River Valley.
 HISTOPLASMA CAPSULATUM

 Disease: histoplasmosis.


 Properties: H capsulatum is a dimorphic

fungus that exists as a mold in soil and as
a yeast in tissue.
 HISTOPLASMA CAPSULATUM:
 It forms two types of asexual spores:


 (1) Tuberculate macroconidia: with typical

thick walls and fingerlike projections that
are important in laboratory identification


 (2) Microconidia: which are smaller, thin,

smooth-walled spores that, if Inhaled,
transmit the infection.
 HISTOPLASMA CAPSULATUM:
 Transmission: Inhalation of airborne
asexual spores (microconidia)


 Pathogenesis & Clinical Findings:

• Inhaled spores are engulfed by
macrophages and develop into yeast
forms.
• In tissues H capsulatum occurs as an oval
budding yeast inside macrophages!!!!
Histoplasma
Histoplasma spreads widely throughout
the body
• liver and spleen
• most infections remain asymptomatic, and the small
granulomatous foci heal by calcification.
• With intense exposure (eg, in a chicken house or bat-
infested cave), pneumonia may become clinically
manifest.
• Severe disseminated histoplasmosis develops in a small
minority of infected persons, especially infants and
individuals with reduced cell-mediated immunity, such
as AIDS patients.
• In AIDS patients, ulcerated lesions on the tongue are
typical of disseminated histoplasmosis.
 Histoplasma capsulatum

•
•


•Genus/Species: Histoplasma capsulatum •Title: Histoplasmosis

•Image Type: Clinical Presentation •Disease(s): Histoplasmosis

•Legend: Discoloration of the skin caused by the fungus.

 HISTOPLASMA CAPSULATUM:
Laboratory Diagnosis
• In tissue biopsy specimens or bone marrow
aspirates, oval yeast cells within macrophages
are seen microscopically.
•
• Cultures on Sabouraud’ s agar show hyphae with
tuberculate macroconidia.
•
• Tests that detect Histoplasma antigens by
radioimmunoassay and Histoplasma RNA with
DNA probes are also useful.
•
• In immunocompromised patients with disseminated
disease, tests for antigens in the urine are
especially useful because antibody tests may be
 HISTOPLASMA CAPSULATUM:
Skin test
• uses histoplasmin (a mycelial extract)
•
• becomes positive, ie, shows at least 5 mm
of induration within 2—3 weeks after
infection and remains positive for many
years.

 HISTOPLASMA CAPSULATUM:

Treatment:

• No therapy needed in asymptomatic or mild primary

infections.
• progressive lung lesions - oral itraconazole
• In disseminated disease, amphotericin B is the treatment of
choice.
• In meningitis, fluconazole - penetrates the spinal fluid well.
• Oral itraconazole - treat pulmonary or disseminated disease,
as well as for chronic suppression in patients with AIDS.



Prevention:
 There are no means of prevention except avoiding
exposure in areas of endemic infection.
 BLASTOMYCES
 Disease: blastomycosis


 Properties:


• B. dermatitidis is a dimorphic fungus that

exists as a mold in soil and as a yeast in
tissue.
• The yeast is round with a doubly refractive
wall and a single broad-based bud.
 BLASTOMYCES
 Transmission: Inhalation of airborne asexual spores.


 Pathogenesis & Clinical Findings:



• Infection via the respiratory tract.

• Asymptomatic or mild cases are rarely recognized.
• Dissemination - ulcerated granulomas of skin, bone, or other sites.


 Laboratory Diagnosis:


• In tissue biopsy specimens, thick-walled yeast cells with single broad-

based buds are seen microscopically.
•
• Hyphae with small pear-shaped conidia are visible on culture.


• Skin test lacks specificity and has little value.



• Serologic tests have little value.


Skin lesion following dissemination
from the lungs.
 BLASTOMYCES:
 Treatment:

• Itraconazole is the drug of choice for most patients.



• Amphotericin B should be used to treat severe

disease.


• Surgical excision may be helpful.



 Prevention:
 There are no means of prevention.
 PARACOCCIDIOIDES BRASILIENSIS

Disease: paracoccidioidomycosis

P brasiliensis is a dimorphic fungus that

exists as a mold in soil and as a yeast in
tissue.

The yeast is thick-walled with multiple buds

(pilot wheel), in contrast to B. dermatitidis,
which has a single bud
 PARACOCCIDIOIDES BRASILIENSIS
Transmission: Inhalation of airborne asexual spores.


Pathogenesis:


• The spores are inhaled, and early lesions occur in the lungs.
• Asymptomatic infection is common.
• Alternatively, oral mucous membrane lesions, lymph node enlargement, and
sometimes dissemination to many organs develop.


Laboratory Diagnosis:


• In pus or tissues, yeast cells with multiple buds (pilot’s wheel) are seen
microscopically.
• A specimen cultured for 2—4 weeks may grow typical organisms.
• Skin tests are rarely helpful.
• Serologic testing shows that when significant antibody titers (by immunodiffusion or
complement fixation) are found, active disease is present.


Treatment: The drug of choice is itraconazole taken orally for several months.


Prevention: There are no means of prevention.




 Important Summary
• Sporothrix schenckii: Rose Gardener’ Disease. Local pustule or ulcer
with nodules along the draining lymphatics; round or cigar-shaped
budding yeasts


• COCCIDIOIDES IMMITIS: Red, tender nodules on extensor surfaces

such as the shins (Erythema Nodosum). Hyphae with arthrospores in
culture; spherules in tissue


• HISTOPLASMA CAPSULATUM: Birds and Bats. Oval budding yeast

inside macrophages.


• BLASTOMYCES: Single broad-based buds are seen microscopically.



• PARACOCCIDIOIDES BRASILIENSIS: yeast cells with multiple buds

(pilot’s wheel)
•
• TINEA: 10% KOH on a glass slide show hyphae under microscopy.
Tinea capitus, Wood’s Lamp.