Merck Manual Chapter 151 Fungi

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Infections in patients whose host defense mechanisms are compromised

range from minor to fatal and often are caused by organisms that

normally reside on body surfaces. In the hospital setting, they

frequently result from colonization by antibiotic-resistant

organisms and from use of catheters and mechanical devices.

Nosocomial infections in the newborn are discussed under Neonatal

Infections in Ch. 260. Opportunistic infections in AIDS are

discussed in Ch. 163.

Host defense mechanisms--physiologic, anatomic, or immunologic--may

be altered or breached by disease or trauma or by procedures or

agents used for diagnosis or therapy. Infections in this setting,

often called opportunistic infections, occur if antimicrobial

therapy alters the normal relationship between host and microbe or

if host defense mechanisms have been altered by age, burns,

neoplasms, metabolic disorders, irradiation, foreign bodies,

immunosuppressive or cytotoxic drugs, corticosteroids, or diagnostic

or therapeutic instrumentation.

The underlying alteration predisposes the patient to infections from

endogenous microflora that are nonpathogenic or from ordinarily

harmless, saprophytic organisms acquired by contact with other

patients, hospital personnel, or equipment. These organisms may be

bacteria, fungi, viruses, or other parasites; the precise character

of the host's altered defenses determines which organisms are likely

to be involved. These organisms are often resistant to multiple

antibiotics.

Drug Therapy and Impaired Host Defense Mechanisms

Antibiotics alter the normal microflora of the skin, mucous

membranes, and GI tract and may result in colonization by new

organisms. Colonization is harmless unless followed by

superinfection, which refers to invasion by indigenous or

environmental organisms resistant to the administered antibiotic.

Factors predisposing to superinfection include extremes of age,

debilitating diseases, and prolonged treatment with antibiotics,

especially broad-spectrum ones. Superinfections usually appear on

the 4th or 5th day of therapy and may convert a benign, self-limited

disease into a serious, prolonged, or even fatal one. The diagnosis

of superinfection by a normally commensal organism is certain only

when the organism is recovered from blood, CSF, or body cavity fluid.

Cytotoxic drugs enhance the susceptibility to infection through

leukopenia and thrombocytopenia; depression of the immune response,

particularly cell-mediated immunity; and altered inflammatory

response. Most opportunistic infections result from the leukopenia.

Corticosteroids alter many aspects of host defenses; one of the most

important is inhibition of the movement of neutrophils, monocytes,

and lymphocytes into the inflammatory exudate. Corticosteroids may

reactivate quiescent pulmonary TB, histoplasmosis,

coccidioidomycosis, and blastomycosis. Patients receiving

corticosteroid treatment (especially in high dose) for RA,

ulcerative colitis, asthma, sarcoidosis, SLE, pemphigus, or

Cushing's syndrome have increased susceptibility to infection from

usual and unusual bacteria and tend to develop infections with

Aspergillus, Candida, Cryptococcus, Mucor, or Nocardia.

Nosocomial (Hospital-Acquired) Infections

These infections are acquired from the hospital environment or

personnel (eg, inadequately sterilized equipment or insufficient

hand washing). They usually occur when a susceptible patient has a

portal for infection from altered anatomic barriers (see below) or

has been given broad-spectrum antibiotics. They are commonly due to

Staphylococcus, Enterobacter, Klebsiella, Serratia, Pseudomonas,

Proteus, Acinetobacter, Aspergillus, or Candida.

Alterations of Anatomic Barriers

Patients with extensive burns or those undergoing diagnostic or

therapeutic procedures that breach normal anatomic barriers to

infection (eg, tracheostomy, inhalation therapy, urinary tract

instrumentation, indwelling urethral or IV catheter placement,

surgery, and surgical prostheses application) are vulnerable to

infection by endogenous or exogenous antibiotic-resistant organisms.

Gram-negative bacteria, particularly Pseudomonas and Serratia, and

other multiply resistant organisms, alone or in combination with

staphylococci, cause soft tissue infections and bacteremia in

severely burned patients. Significant bacteriuria develops in

patients with indwelling urethral catheters, increasing the risk of

cystitis, pyelonephritis, and bacteremia with gram-negative bacilli.

Sepsis from IV catheter sites, due to staphylococci, gram-negative

bacilli, or Candida, may cause local suppuration or severe and

sometimes fatal systemic infections. Patients with endotracheal

tubes or tracheostomies and others who require repeated tracheal

suctioning or inhalation therapy with equipment containing a

reservoir of nebulization fluid may develop bronchopulmonary

infection, usually with nosocomial gram-negative organisms.

Impaired Cellular or Humoral Host Defense Mechanisms

Neoplastic and immunodeficiency diseases such as leukemia, aplastic

anemia, Hodgkin's disease, myeloma, and HIV infection are

characterized by selective defects in host resistance. Patients with

hypogammaglobulinemia, myeloma, macroglobulinemia, or chronic

lymphocytic leukemia tend to have deficient humoral immune

mechanisms and to develop pneumococcal and Haemophilus pneumonia

(see also Pneumonia in the Compromised Host in Ch. 73) and

bacteremia. Patients with neutropenia due to leukemia, intensive

immunosuppressive therapy, or irradiation frequently develop gram-

negative bacteremia from infections acquired through the mucous

membranes or secondary to pneumonia (see Ch. 135). Severely

immunosuppressed patients and those with Hodgkin's disease and HIV

tend to have depressed cellular immune mechanisms; serious

infections with mycobacteria, Aspergillus, Candida, Cryptococcus,

Histoplasma, Mucor, Nocardia, or Staphylococcus are frequent. Herpes

zoster, cytomegalovirus, Pneumocystis, and Toxoplasma infections

also occur. AIDS often leads to infections caused by atypical

mycobacteria, herpes simplex, Giardia, Cryptosporidia, Isospora, and

many others. (AIDS is discussed in Ch. 163, and other specific

immunodeficiency diseases are discussed in Ch. 147.)

Prophylaxis

Awareness of the patterns of infection that occur in the compromised

host helps in early recognition of infections and initiation of

appropriate therapy. Awareness of the specific site of breached

defense, the type of defense system that has been weakened or lost,

and the characteristics of organisms prevalent in a particular

institution, based on continuous hospital surveillance, is also

helpful.

Antibiotic prophylaxis (see also Antimicrobial Chemoprophylaxis in

Ch. 153) is indicated for some conditions, including rheumatic fever

and bacterial endocarditis, TB exposure, recurrent UTIs and otitis

media, bacterial infections in granulocytopenic patients, and some

types of Neisseria infections. Prophylaxis with antibiotics is also

indicated after vaginal or abdominal hysterectomy; colonic, rectal,

cardiac, joint, or vascular surgery; prostatectomy in patients with

previous UTIs; and pneumocystis in AIDS patients (see Pneumonia

Caused by Pneumocystis Carinii in Ch. 73). However, use of broad-

spectrum antibiotics, massive doses of any antibiotic, or

prophylactic use of systemic antibiotics may ultimately result in

infection with resistant bacteria. Patients receiving antibiotics

should be watched for signs of superinfection.

The hematopoietic growth factors, granulocyte colony-stimulating

factor and granulocyte-macrophage colony-stimulating factor, can

accelerate hematopoietic recovery after chemotherapy. They are

useful in preventing infections from agents that cause transient

neutropenia. Their broader use to prevent or treat other infections

is under investigation.

Active or passive immunization helps prevent some types of

infections. Active immunization can prevent influenza, Haemophilus

influenzae type b, meningococcal, and pneumococcal infections.

Pneumococcal vaccination is effective for chronically ill, asplenic,

and elderly patients and those with sickle cell and HIV disease.

Hepatitis B vaccine should be given to patients who repeatedly

receive blood products as well as to medical and nursing personnel

and others at risk. Passive immunization can prevent or ameliorate

herpes zoster, hepatitis A and B, measles, and cytomegalovirus

infection in selected immunosuppressed patients. Severe

hypogammaglobulinemia requires maintenance with immune globulin.

Barriers help control and prevent infection. Strict asepsis should

be maintained in diagnostic and therapeutic manipulative procedures.

Attendants should wear sterile gloves during endotracheal or

tracheostomy suctioning, and suction catheters should be sterile,

disposable, and used only once. Masks, tubing, nebulizer jars, and

other respiratory therapy equipment connected directly to a

patient's airway should be sterilized by steam or gas before use and

should be changed daily. When steam or gas sterilization is not

possible, the equipment should be disinfected with a 2%

glutaraldehyde or 2% acetic acid wash, followed by thorough rinsing

and drying. Alternatively, nebulization of 0.25% acetic acid through

the equipment, followed by thorough rinsing, is usually satisfactory

for daily cleaning of a ventilator that is in use. Care should be

taken to ensure that the gas jets have been completely cleaned.

Urethral catheters must be connected to closed sterile drainage bags

and the system kept closed. IV catheters should be inserted

securely, covered with a sterile protective dressing, and removed

after 48 to 72 h or at the first sign of phlebitis. An ointment of

neomycin, polymyxin B, and bacitracin or an iodine ointment (eg,

povidone-iodine), applied daily to the cannulation site and the

emerging catheter, may help prevent infection. Thrombophlebitis

usually responds to catheter withdrawal and local application of hot

compresses, but antibiotic therapy for specifically identified or

presumed causative organisms may be necessary.

Treatment

Opportunistic infections are difficult to treat once established

because the organisms tend to be resistant to most commonly used

antibiotics. Short-term therapy tends to merely suppress infection

temporarily unless the underlying condition can be corrected (eg,

urethral or IV catheters removed or tracheostomy closed); thus,

treatment often must be longer than usual. Cultures and possibly

tissue biopsy should be performed before starting or altering

antibiotics, but therapy may need to be started while awaiting

laboratory results on the basis of clinical-bacteriologic diagnosis

and knowledge of the organisms known to be prevalent in a particular

institution and their presumptive sensitivity. If possible,

corticosteroid dosage and immunosuppressive chemotherapy should be

reduced while treating opportunistic infections. Patients with

severe agranulocytosis who have documented infection may benefit

from granulocyte transfusions.

Other Fungal Opportunists

Many yeasts and molds can cause opportunistic, even life-threatening

infections in immunocompromised patients. They only rarely affect

persons with intact host defenses. Yeasts tend to cause fungemia as

well as focal involvement of skin and other sites. Trichosporon

beigelii and Blastoschizomyces capitatus particularly affect

neutropenic patients. Candida (Torulopsis) glabrata can cause

fungemia, urinary tract infections, and, occasionally, pneumonia or

other focal lesions and tends to be more resistant to azoles or

amphotericin B than C. albicans. Infants and debilitated adults

receiving lipid-containing IV hyperalimentation infusions are

susceptible to Malassezia furfur fungemia. Penicillium marneffei was

recognized as an opportunistic invader in Southeast Asian AIDS

patients, and cases have been recognized in the USA. P. marneffei

skin lesions may resemble molluscum contagiosum. Especially in

neutropenic patients, various environmental molds can cause focal

vasculitic lesions mimicking invasive aspergillosis, including

species of Fusarium and Scedosporium. Specific diagnosis requires

culture and speciation and is crucial because not all of these

organisms respond to any single antifungal drug. For example,

Scedosporium sp are typically resistant to amphotericin B. Optimal

regimens of antifungal therapy for each member of this group of

fungal opportunists still must be defined.

Histoplasmosis

A disease caused by Histoplasma capsulatum, causing primary

pulmonary lesions and hematogenous dissemination.

Histoplasmosis occurs worldwide. The endemic areas in the USA are in

the Ohio-Mississippi river valleys extending into parts of northern

land, southern Pennsylvania, central New York, and Texas, but

microfoci have been noted in other states, such as Florida.

H. capsulatum grows as a mold in nature or when cultured at room

temperature but converts to a small (1 to 5 µm in diameter) yeast

cell at 37° C (98.6° F) and when invading host cells. Infection

follows inhalation of mold conidia (spores) in soil or dust

contaminated with bird or bat droppings. Severe disease is more

common after heavy, prolonged exposure and occurs often in men,

infants, or those with compromised T-cell-mediated immunity.

Symptoms and Signs

The disease has three main forms. Acute primary histoplasmosis is

usually asymptomatic. If symptoms develop, they are usually

nonspecific, with fever, cough, and malaise of varying severity.

Acute pneumonia sometimes is evident on physical examination and

chest x-ray.

Progressive disseminated histoplasmosis follows hematogenous spread

from the lungs that is not controlled by normal cell-mediated host

defense mechanisms. Characteristically, generalized involvement of

the reticuloendothelial system, with hepatosplenomegaly,

lymphadenopathy, bone marrow involvement, and sometimes oral or GI

ulcerations occurs, particularly in chronic cases. In general, the

course is usually subacute or chronic, with only nonspecific, often

subtle symptoms such as fatigue, weakness, malaise, or, in HIV-

positive patients, an unexplained worsening in condition. 's

disease is an uncommon but potentially serious manifestation and

must be distinguished from other causes of adrenal insufficiency

such as TB, sarcoidosis, lymphoma, or leukemia. Severe

manifestations occur most often in infants and immunocompromised

patients.

Progressive disseminated histoplasmosis is one of the defining

opportunistic infections for AIDS. Patients with AIDS may develop

severe acute pneumonia with hypoxia suggestive of Pneumocystis

carinii infection as well as hypotension, mental status changes,

coagulopathy, or rhabdomyolysis.

Chronic cavitary histoplasmosis is characterized by pulmonary

lesions that are often apical and resemble cavitary TB. The

manifestations are worsening cough and dyspnea, progressing

eventually to disabling respiratory dysfunction. Dissemination does

not occur.

Another chronic but rare form of histoplasmosis is fibrosing

mediastinitis, ultimately causing circulatory compromise.

Histoplasmosis may be a cause of blindness in presumed ocular

histoplasmosis syndrome (see Ch. 98); however, organisms are not

present in lesions, antifungal chemotherapy is not helpful, and the

link to H. capsulatum infection has not been established with

certainty.

Diagnosis

Culture of H. capsulatum from sputum, lymph nodes, bone marrow,

liver biopsy, blood, urine, or oral ulcerations confirms the

diagnosis. Lysis-centrifugation or culture of buffy coat improves

the yield from blood specimens. Microscopic histopathology can

strongly suggest the diagnosis: Tissue specimens that are specially

stained (Gomori's methenamine silver, PAS, Gridley's silver stain)

may reveal characteristic clusters of small, oval yeast cells within

macrophages, blood monocytes, or neutrophils. In AIDS patients with

extensive infections, intracellular yeasts may be seen in 's-

or Giemsa-stained peripheral blood or buffy coat specimens. H.

capsulatum antigen can be detected in serum, urine, CSF, or

bronchoalveolar lavage samples by an enzymatic assay or

radioimmunoassay. Although the test for H. capsulatum antigen is

reportedly sensitive and specific, rare cross-reactivity with other

fungi has been noted (Coccidioides immitis, Blastomyces

dermatitidis, Paracoccidioides brasiliensis, Penicillium marneffei).

However, the Histoplasma antigen test is currently only available

through the Histoplasmosis Reference Laboratory in Indianapolis, and

results have not yet been duplicated in other laboratories. Positive

cultures should always be sought as definitive confirmation of

histopathologic or immunoserologic diagnoses.

Prognosis and Treatment

The acute primary form is almost always self-limited, although very

rare fatalities after massive infections have been reported. Chronic

cavitary histoplasmosis can cause death from severe respiratory

insufficiency. Untreated progressive disseminated histoplasmosis has

a fatality rate > 90%, yet the diagnosis is often missed because the

findings are nonspecific, a particular problem in AIDS patients, who

more frequently develop rapidly fatal infections.

Acute primary histoplasmosis requires no antifungal therapy except

in rare cases of severe pneumonia. In the chronic form, treatment

may cause culture to become negative and progression may be halted

or slowed, but fibrotic lesions do not improve. Amphotericin B or

itraconazole may be effective, but relapse is common. Amphotericin B

is the treatment of choice for severe disseminated histoplasmosis.

Itraconazole can be used to treat less severe cases. In AIDS

patients, indefinite chronic therapy with itraconazole is used to

prevent relapse because the best duration of therapy is not known.

Fluconazole appears to be less effective. Intermittent doses of IV

amphotericin B can be used for chronic suppression in azole-

intolerant AIDS patients.

Coccidioidomycosis

(Valley Fever; San Joaquin Fever)

A disease caused by the fungus Coccidioides immitis, usually

occurring in a primary form as an acute benign asymptomatic or self-

limited respiratory infection, occasionally disseminating to cause

focal lesions in skin, subcutaneous tissues, lymph nodes, bones,

liver, kidneys, meninges, brain, or other tissues.

Coccidioidomycosis is endemic in the southwestern USA, including the

central valley of California, Arizona, parts of New Mexico, and

Texas west of El Paso. The area extends into northern Mexico, and

foci occur in parts of Central America and Argentina. Infections are

acquired by inhalation of spore-laden dust. Because of travel and

delayed onset of clinical manifestations, symptomatic infections

sometimes may become evident outside endemic areas.

Once inhaled, C. immitis conidia (spores) convert at 37° C (98.6° F)

to form large tissue-invasive spherules (about 30 to 100 µm in

diameter). As spherules enlarge and then rupture, each releases

multiple small endospores that may form new spherules. The pathology

is characterized by an acute, subacute, or chronic granulomatous

reaction with varying degrees of fibrosis. Intact spherules usually

are surrounded by lymphocytes along with plasma, epithelioid, and

giant cells, but neutrophils are often present at sites of rupturing

spherules along with eosinophils. In infected lungs, lesions may

cavitate or form granulomatous coin lesions.

Symptoms and Signs

Primary coccidioidomycosis is usually asymptomatic, but nonspecific

respiratory symptoms resembling influenza or acute bronchitis

sometimes occur or, less often, acute pneumonia or pleural effusion.

Symptoms, in decreasing order of frequency, include fever, cough,

chest pain, chills, sputum production, sore throat, and hemoptysis.

Physical signs may be absent or limited to scattered rales with or

without areas of dullness to percussion over lung fields. There is

usually a leukocytosis and, sometimes, eosinophilia. Some patients

develop hypersensitivity to the localized respiratory infection,

manifested by a desert rheumatism syndrome, with arthritis,

conjunctivitis, erythema nodosum, or erythema multiforme. Primary

pulmonary lesions sometimes resolve, leaving nodular coin lesions

that must be distinguished from neoplasms and TB or other

granulomatous infections. Sometimes, residual cavitary lesions

develop that may vary in size over time and often appear thin-

walled. Although dissemination does not occur from these residual

foci, a small percentage of these cavities fail to close

spontaneously. Hemoptysis or the threat of rupture into the pleural

space may occasionally necessitate surgery.

Progressive coccidioidomycosis may develop a few weeks, months, or

occasionally years after primary infections, which may occur long

after leaving endemic areas. Progressive disseminated

coccidioidomycosis is more common in men than women and is more

likely to occur in association with HIV infection, immunosuppressive

therapy, the second half of pregnancy or postpartum, advanced age,

and certain ethnic backgrounds (Filipino, African-American, native

American, Hispanic, and Oriental in decreasing order of relative

risk).

Symptoms often are nonspecific, including low-grade fever, anorexia,

weight loss, and weakness. Extensive pulmonary involvement may cause

progressive cyanosis, dyspnea, and discharge of mucopurulent or

bloody sputum. Extrapulmonary lesions are usually focal, involving

one or more tissue sites in bones, joints, skin, subcutaneous

tissues, viscera, brain, or meninges. Draining sinus tracts

sometimes connect deeper lesions to the skin. Localized

extrapulmonary lesions often become chronic and recur frequently,

sometimes long after completion of seemingly successful antifungal

therapy.

Diagnosis

The diagnosis can be established by culturing infected body fluids

or tissue specimens or by visualizing C. immitis spherules in

sputum, pleural fluid, CSF, exudate from draining lesions, or silver

or PAS-stained biopsy specimens. Intact spherules are usually 20 to

80 µm in diameter, are thick-walled, and are filled with small ( 2

to 4 µm in diameter) endospores. Endospores released into tissues

from ruptured spherules may be mistaken for nonbudding yeasts.

Complement fixation for IgG anticoccidioidal antibodies remains the

most useful test. Titers >= 1:4 in serum are consistent with current

or recent infection, and higher titers (>= 1:32) signify an

increased likelihood of extrapulmonary dissemination. However,

immunosuppressed patients may have low titers. Titers should decline

during successful therapy. The presence of complement fixing

antibodies in CSF is diagnostic of coccidioidal meningitis and is

crucial because cultures are positive in only a few cases.

Other antibody tests include newer, more sensitive and specific

immunoassays, but these have not been shown to reflect prognosis and

are less useful. Delayed cutaneous hypersensitivity to coccidioidin

or spherulin usually develops within 10 to 21 days after acute

infections in immunocompetent patients but is characteristically

absent in progressive disease. Because this test is positive in most

persons in endemic areas, it is of primary value for epidemiologic

studies rather than for diagnosis.

Prognosis and Treatment

Untreated disseminated coccidioidomycosis is usually fatal,

uniformly so if meningitis is present. Mortality in HIV-infected

patients exceeds 70% within 1 mo of diagnosis; it is uncertain

whether treatment can alter this.

Treatment for primary coccidioidomycosis is unnecessary in low-risk

patients. High complement fixation titers indicate spread, which

requires treatment. Mild to moderate nonmeningeal extrapulmonary

involvement should be treated with >= 400 mg/day fluconazole or 400

mg/day itraconazole. IV amphotericin B is preferable for severely

ill patients and is continued until total dose reaches 1 to 3 g

depending on the degree of infection. As with histoplasmosis,

patients with AIDS-associated coccidioidomycosis require maintenance

therapy to prevent relapse; 200 mg/day of an azole usually is

sufficient, and weekly IV amphotericin B may suffice for azole-

intolerant patients.

If amphotericin B is used for patients with meningitis, intrathecal

injections either intraventricularly via a subcutaneous reservoir or

intracisternally are needed. However, fluconazole has replaced

amphotericin B as the drug of choice for most cases of coccidioidal

meningitis. Doses > 400 mg/day may be more effective and > 800 to

1200 mg/day have been tried experimentally, but the optimum regimen

still must be defined. Treatment for meningeal coccidioidomycosis

must be continued for many months, probably lifelong. Surgical

removal of involved bone may be necessary to cure osteomyelitis.

Blastomycosis

(North American Blastomycosis; Gilchrist's Disease)

A disease caused by inhalation of mold conidia (spores) of

Blastomyces dermatitidis, which convert to yeasts and invade the

lungs, occasionally spreading hematogenously to the skin or focal

sites in other tissues.

In the USA, the endemic area for blastomycosis includes the

geographic distribution of H. capsulatum, but extends further into

middle Atlantic and southeastern states, the northern Midwest,

upstate New York, and southern Canada. Cases also have been

identified in the Middle East and Africa. The incidence and severity

of blastomycosis seems to be increased in immunocompromised

patients, but it is a less common opportunistic infection than

histoplasmosis or coccidioidomycosis.

Blastomyces dermatitidis grows as a mold at room temperature and in

its natural site in soil enriched with animal excreta and moist,

decaying, acidic organic material. It has been rarely isolated from

soil near beaver dams or where farm animals are kept. It may infect

dogs as well as humans. Inhaled B. dermatitidis conidia convert at

37° C (98.6° F) in the lungs into invasive large yeasts, usually 8

to 15 (but sometimes as much as 30) µm in diameter that form broad-

based buds. The histopathology is characterized by mixed mononuclear

cell infiltrates with giant cells surrounding large yeasts, with

some granuloma formation, necrosis, fibrosis, and, especially in

skin lesions, focal areas of suppuration infiltrated with

neutrophils.

Symptoms and Signs

Acute, self-limited blastomycosis is seldom recognized clinically.

Pulmonary blastomycosis tends to occur as individual cases of

progressive infection requiring therapy. Focal or diffuse

infiltrates may be present, sometimes as a patchy bronchopneumonia

fanning out from the hilum, resembling a neoplasm. Most often, the

infection has an insidious onset and is chronic. Symptoms are

nonspecific and may include a productive or dry hacking cough, chest

pain, dyspnea, fever, chills, and drenching sweats. Pleural effusion

occurs occasionally. Some patients have rapidly progressive

infections, and adult respiratory distress syndrome may develop.

In extrapulmonary disseminated blastomycosis, hematogenous spread

may lead to focal infection in skin, prostate, epididymis, testis,

kidneys, vertebrae, ends of long bones, subcutaneous tissues, brain,

oral or nasal mucosa, thyroid, lymph nodes, bone marrow, and other

tissues. Sometimes areas overlying bone lesions are swollen, warm,

and tender. Some genital lesions present as painful epididymal

swelling, deep perineal discomfort, or prostatic tenderness on

rectal examination. Skin lesions are by far the most common, may be

single or multiple, and may occur with or without clinically

apparent pulmonary involvement. Papules or papulopustules usually

appear on exposed surfaces and spread slowly. Painless miliary

abscesses, varying from pinpoint to 1 mm in diameter, develop on the

advancing borders. Irregular, wartlike papillae may form on

surfaces. As lesions enlarge, the centers heal, forming atrophic

scars. A fully developed individual lesion appears as an elevated

verrucous patch, usually >= 2 cm wide with abruptly sloping,

purplish red, abscess-studded border. Ulceration may occur if

bacterial superinfection is present.

Diagnosis

Culture is definitive, but diagnosis is almost as certain if direct

examination of sputum, pus, or urine specimens reveals

characteristic thick-walled, unencapsulated yeasts that are 8 to 15

µm or more in diameter and form broad-based buds. Histopathology

with Gomori's methenamine silver, Gridley's, or PAS staining also

can differentiate these yeasts from smaller C. neoformans cells,

which form narrow-based buds, and, unlike B. dermatitidis, are

encapsulated and stain with Mayer's mucicarmine or the Masson-

Fontana technique for melanin. Patients with blastomycosis may have

cross-reactive positive assays for H. capsulatum antigen, but

sensitivity of the test is uncertain. No other serologic assays or

skin tests are useful for diagnosis.

Pulmonary blastomycosis must be distinguished from other mycoses,

TB, and neoplasms. Skin lesions can be mistaken for sporotrichosis,

TB, iodism, or basal cell carcinoma. Genital involvement may mimic

TB.

Prognosis and Treatment

Untreated blastomycosis is usually slowly progressive and ultimately

fatal. Oral itraconazole is used for mild-to-moderate blastomycosis.

Fluconazole appears to be less effective. The optimum dose is

undefined, but 400 to 800 mg/day po may be tried to treat

itraconazole-intolerant patients with mild cases of blastomycosis.

IV amphotericin B is the treatment of choice for those with severe,

life-threatening infections and is usually effective.