USMLE Forum Archives - USMLE Step 3 - FUNGAL INFECTIONS
FUNGAL INFECTIONS
meduploader - 05-12-09 06:08
Candidiasis
Superficial infection is especially common among diabetics.
Risk factors for deep or disseminated infection include immune compromise (HIV, malignancy, neutropenia, or steroids), multiple or prolonged antibiotic treatment, and invasive procedures. C. albicans is the most common cause.
Candiduria: Yeast in urine usually represents colonization and not infection.
Seen in patients with Foley catheters or antibiotic use. Diagnose infection by detecting pyuria or yeast in urine casts; treat if the patient is symptomatic or neutropenic, has undergone renal transplant, or is awaiting urinary tract procedures.
Intertrigo (“diaper rash”): Pruritic vesiculopustules rupture to form macerated or fissured beefy-red areas at skin folds. Satellite lesions may be present. Seen in both immunocompetent and immunosuppressed patients.
Oral thrush: Presents with burning sensations of the tongue or mucosa with white, curdlike patches that can be scraped away to reveal a raw surface. Seen in patients with AIDS or malignancy or in those who use inhaled steroids for asthma. Diagnosis can be confirmed with KOH prep or Gram stain.
Candidal esophagitis: Presents with dysphagia, odynophagia, and substernal chest pain. Seen in patients with AIDS, leukemia, and lymphoma. Diagnosed by the endoscopic appearance of white patches or from biopsy showing mucosal invasion. May occur concurrently with HSV or CMV esophagitis.
Candidemia and disseminated candidiasis: Diagnose through cultures of blood, body fluids, or aspirates. Mortality is 40%. Candidemia may lead to endophthalmitis (eye pain, blurred vision), osteomyelitis, arthritis, or endocarditis.
All patients with candidemia should have an ophthalmologic exam to rule out candidal endophthalmitis.
Hepatosplenic candidiasis: Presents with fever and abdominal pain that emerge as neutropenia resolves following bone marrow transplant. Associated with a high mortality rate. Diagnosed by ultrasound or CT imaging showing abscesses. Blood cultures are frequently –IVE
Rx: Candiduria: Most cases do not need treatment.
Intertrigo and oral thrush: May be treated with topical antifungals (nystatin, clotrimazole or miconazole creams, or nystatin suspension swish and swallow).
Esophagitis and other deep or disseminated infections: Systemic therapy with fluconazole, amphotericin, voriconazole, or caspofungin.
Replace vascular catheters at a new site (do not exchange over a wire!).
C. albicans is usually susceptible to fluconazole and can be distinguished from other etiologic agents within several hours by a + germ tube test
(i.e., the yeast grows a germ tube or pseudohyphae). Patients who have been on fluconazole prophylaxis may have resistant C. albicans or nonalbicans species (e.g., C. glabrata, C. krusei).
Patients with persistent candidemia after catheter removal may have peripheral septic thrombophlebitis or septic thrombosis of the central veins.
Aspergillosis
Aspergillus fumigatus and other species are widespread in soil, water, compost, potted plants, ventilation ducts, and marijuana.
Allergic bronchopulmonary aspergillosis (ABPA): Presents with episodic bronchospasm, fever, and brown-flecked sputum. Seen in patients with underlying asthma or CF. CXR shows patchy, fleeting infiltrates and lobar consolidation or atelectasis. Labs show eosinophilia, elevated serum IgE, and + serum IgG precipitins.
Aspergilloma of the lungs or sinus: May be asymptomatic or present with hemoptysis, chronic cough, weight loss, and fatigue. Seen in patients with previous TB, sarcoidosis, emphysema, or PCP. CXR and CT may show an air-crescent sign or a rim of air around a fungus ball in a preexisting upper lobe cavity. Labs show + serum IgG precipitins.
Invasive aspergillosis:
Presents with dry cough, pleuritic chest pain, and persistent fever with a new infiltrate or nodule despite broad-spectrum antibiotics. Seen in patients with prolonged neutropenia, advanced AIDS, diabetes, and chronic granulomatous disease as well as in those on high-dose steroids
or immunosuppressants.
Imaging: CXR and CT may show wedge-shaped lesions from tissue infarction, an air-crescent sign from cavitation of a necrotic nodule, or a halo sign of a necrotic nodule with surrounding hemorrhage.
Labs: The Aspergillus galactomannan assay is approved for diagnosis in patients with hematologic malignancies and following bone marrow transplant. IgG precipitins and blood cultures are rarely +. In high-risk patients, + sputum or bronchial washing cultures are strongly suggestive, but definitive diagnosis requires a biopsy demonstrating tissue invasion.
Patients are often severely ill, and empiric antifungal therapy may be reasonable in high-risk patients.
Rx: ABPA: Systemic corticosteroids plus itraconazole × 8 months improves lung function and ↓ steroid requirements.
Aspergilloma: Surgical excision for massive hemoptysis. Antifungals play a limited role.
Invasive aspergillosis: Voriconazole, amphotericin, or caspofungin.
COMPLICATIONS
ABPA: Bronchiectasis, pulmonary fibrosis.
Aspergilloma: Massive hemoptysis; contiguous spread to the pleura or vertebrae.
Invasive aspergillosis: High mortality, especially in bone marrow and liver transplant patients.
Cryptococcosis
Cryptococcus neoformans encapsulated budding yeast found worldwide in soil, bird (pigeon) droppings, and eucalyptus trees. C. neoformans is the most common fungal infection in AIDS patients
(usually associated with a CD4 count < 100) and is the most common cause of fungal meningitis in all patients.
Meningitis: Mental status changes, headache, nausea, cranial nerve palsies. HIV patients usually lack obvious meningeal signs.
May also cause atypical pneumonia (pulmonary infection is usually asymptomatic) or skin lesions (umbilicated papules resembling molluscum contagiosum), or may involve the bone, eye, or GU tract.
Dx: LP: Patients often have high opening pressure, low glucose, high protein, and lymphocytic pleocytosis. Patients with more advanced immunosuppression may have a bland CSF profile even with meningitis. India ink or Gram stain of CSF may show budding yeast with a thick capsule (both
are <50% sensitive).
Cryptococcemia (a +serum CrAg or blood culture) indicates disseminated disease even with a normal LP.
Unlike what is typically seen in bacterial meningitis, HIV patients with cryptococcal meningitis often have minimal symptoms and a bland CSF.
Polysaccharide cryptococcal antigen (CrAg) in serum or CSF: Serum CrAg is > 99% sensitive in AIDS patients with meningitis but is less sensitive in non-AIDS patients. CSF CrAg is only 90% sensitive. A serum CrAg titer of > 1:8 indicates active disease.
Serum CrAg titers are not useful for monitoring treatment response of meningitis in immunosuppressed patients. CSF CrAg titers should ↓ during successful treatment.
Fungal culture of blood, CSF, urine, sputum, or bronchoalveolar lavage.
CT or MRI may show hydrocephalus or occasionally nodules (cryptococcomas).
Rx: HIV-+ive patients: For mild to moderate lung disease, treat with oral fluconazole for 6–12 months. For meningitis, cryptococcemia, or severe lung disease, treat with amphotericin plus 5-flucytosine for 2 weeks followed by oral fluconazole 400 mg/day for at least 10 weeks.
HIV -ive patients:
For mild to moderate lung disease, treat with fluconazole 200–400 mg/day.
For severe lung disease, treat with amphotericin until symptoms are controlled followed by fluconazole.
For meningitis, give induction/consolidation therapy with amphotericin plus 5-flucytosine - 2 weeks followed by oral fluconazole 400 mg/day - 10 weeks.
Patients with HIV need long-term maintenance therapy with oral fluconazole 200 mg/day. It may be reasonable to stop prophylaxis if the CD4 count ↑to > 100–200 for > 6 months in response to antiretrovirals.
Repeat LP until symptoms resolve in patients with coma or other signs of elevated ICP.
COMPLICATIONS
A poorer prognosis for meningitis is seen in patients with abnormal mental status, those 60 years of age, and those with evidence of high organism load or lack of immune response (as indicated by cryptococcemia, high initial CrAg titer in CSF or serum, high CSF opening pressure, 20 WBCs in CSF,
low glucose, and + India ink).
Coccidioidomycosis
Coccidioides immitis- arid southwestern United States, central California, northern Mexico, and Central and South America. outbreaks occur after earthquakes or dust storms.
1° infection (“valley fever,” “desert rheumatism”): Usually presents with self-limited flulike symptoms, fever, dry cough, pleuritic chest pain, and headache, often accompanied by arthralgias, erythema nodosum, or erythema multiforme.
CXR may be normal or may show unilateral infiltrates, nodules, or thin-walled cavities. Some patients may develop chronic pneumonia, ARDS, or persistent lung nodules.
Disseminated disease (1%): Chronic meningitis, skin lesions (papules, pustules, warty plaques), osteomyelitis, or arthritis.
Serologic tests (complement fixation assays); titers ≥ 1:32 indicate more severe disease and a higher risk of dissemination.
Histology may show giant spherules in infected tissues.
Cultures of respiratory secretions or aspirates of bone and skin lesions may grow the organism (alert the laboratory if the diagnosis is suspected; Coccidioides is highly infectious to lab workers).
Rx: Treatment may not be necessary for acute disease but may be reasonable in patients at risk for dissemination.
Fluconazole, itraconazole, or amphotericin for disseminated disease.
Histoplasmosis
Histoplasma capsulatum is found in the Mississippi and Ohio River valleys.
The organism is found in moist soil and in bat and bird droppings. Risk factors include exploring caves and cleaning chicken coops or attics.
1° infection: Most patients are asymptomatic. However, patients may present with fever, dry cough, and substernal chest discomfort. CXR may show patchy infiltrates that become nodular or exhibit multiple small nodules and hilar or mediastinal adenopathy. Some patients may develop
chronic upper lobe cavitary pneumonia or mediastinal fibrosis (dysphagia, SVC syndrome, or airway obstruction).
Disseminated disease: Presents with hepatosplenomegaly, adenopathy, painless palatal ulcers, meningitis, and pancytopenia from bone marrow infiltration. Patients with HIV may develop colonic disease (diarrhea, perforation or obstruction from mass lesions).
Dx: Urinary antigen test is most useful in HIV/AIDS patents with disseminated disease.
Histology with silver stain of bone marrow, lymph node, or liver.
Cultures of blood or bone marrow are + in immunosuppressed patients with disseminated disease.
Serologic tests (complement fixation and immunodiffusion assays) are often + in immunocompetent patients.
Rx: Treatment is not needed for acute pulmonary disease. Itraconazole or amphotericin for chronic cavitary pneumonia, mediastinal fibrosis, or disseminated histoplasmosis.
Blastomycosis
Blastomyces dermatitidis is found in the central United States (as is Histoplasma) as well as in the upper Midwest and Great Lakes regions.
Risk factors include exposure to woods and streams.
Acute pneumonia. May lead to warty, crusted, or ulcerated skin lesions or to osteomyelitis, epididymitis, or prostatitis.
Dx: Microscopy and culture of respiratory secretions; biopsy or aspirate material shows large yeast with broad-based budding.
Rx: Itraconazole or amphotericin for all infected patients.
meduploader - 05-12-09 06:08
Candidiasis
Superficial infection is especially common among diabetics.
Risk factors for deep or disseminated infection include immune compromise (HIV, malignancy, neutropenia, or steroids), multiple or prolonged antibiotic treatment, and invasive procedures. C. albicans is the most common cause.
Candiduria: Yeast in urine usually represents colonization and not infection.
Seen in patients with Foley catheters or antibiotic use. Diagnose infection by detecting pyuria or yeast in urine casts; treat if the patient is symptomatic or neutropenic, has undergone renal transplant, or is awaiting urinary tract procedures.
Intertrigo (“diaper rash”): Pruritic vesiculopustules rupture to form macerated or fissured beefy-red areas at skin folds. Satellite lesions may be present. Seen in both immunocompetent and immunosuppressed patients.
Oral thrush: Presents with burning sensations of the tongue or mucosa with white, curdlike patches that can be scraped away to reveal a raw surface. Seen in patients with AIDS or malignancy or in those who use inhaled steroids for asthma. Diagnosis can be confirmed with KOH prep or Gram stain.
Candidal esophagitis: Presents with dysphagia, odynophagia, and substernal chest pain. Seen in patients with AIDS, leukemia, and lymphoma. Diagnosed by the endoscopic appearance of white patches or from biopsy showing mucosal invasion. May occur concurrently with HSV or CMV esophagitis.
Candidemia and disseminated candidiasis: Diagnose through cultures of blood, body fluids, or aspirates. Mortality is 40%. Candidemia may lead to endophthalmitis (eye pain, blurred vision), osteomyelitis, arthritis, or endocarditis.
All patients with candidemia should have an ophthalmologic exam to rule out candidal endophthalmitis.
Hepatosplenic candidiasis: Presents with fever and abdominal pain that emerge as neutropenia resolves following bone marrow transplant. Associated with a high mortality rate. Diagnosed by ultrasound or CT imaging showing abscesses. Blood cultures are frequently –IVE
Rx: Candiduria: Most cases do not need treatment.
Intertrigo and oral thrush: May be treated with topical antifungals (nystatin, clotrimazole or miconazole creams, or nystatin suspension swish and swallow).
Esophagitis and other deep or disseminated infections: Systemic therapy with fluconazole, amphotericin, voriconazole, or caspofungin.
Replace vascular catheters at a new site (do not exchange over a wire!).
C. albicans is usually susceptible to fluconazole and can be distinguished from other etiologic agents within several hours by a + germ tube test
(i.e., the yeast grows a germ tube or pseudohyphae). Patients who have been on fluconazole prophylaxis may have resistant C. albicans or nonalbicans species (e.g., C. glabrata, C. krusei).
Patients with persistent candidemia after catheter removal may have peripheral septic thrombophlebitis or septic thrombosis of the central veins.
Aspergillosis
Aspergillus fumigatus and other species are widespread in soil, water, compost, potted plants, ventilation ducts, and marijuana.
Allergic bronchopulmonary aspergillosis (ABPA): Presents with episodic bronchospasm, fever, and brown-flecked sputum. Seen in patients with underlying asthma or CF. CXR shows patchy, fleeting infiltrates and lobar consolidation or atelectasis. Labs show eosinophilia, elevated serum IgE, and + serum IgG precipitins.
Aspergilloma of the lungs or sinus: May be asymptomatic or present with hemoptysis, chronic cough, weight loss, and fatigue. Seen in patients with previous TB, sarcoidosis, emphysema, or PCP. CXR and CT may show an air-crescent sign or a rim of air around a fungus ball in a preexisting upper lobe cavity. Labs show + serum IgG precipitins.
Invasive aspergillosis:
Presents with dry cough, pleuritic chest pain, and persistent fever with a new infiltrate or nodule despite broad-spectrum antibiotics. Seen in patients with prolonged neutropenia, advanced AIDS, diabetes, and chronic granulomatous disease as well as in those on high-dose steroids
or immunosuppressants.
Imaging: CXR and CT may show wedge-shaped lesions from tissue infarction, an air-crescent sign from cavitation of a necrotic nodule, or a halo sign of a necrotic nodule with surrounding hemorrhage.
Labs: The Aspergillus galactomannan assay is approved for diagnosis in patients with hematologic malignancies and following bone marrow transplant. IgG precipitins and blood cultures are rarely +. In high-risk patients, + sputum or bronchial washing cultures are strongly suggestive, but definitive diagnosis requires a biopsy demonstrating tissue invasion.
Patients are often severely ill, and empiric antifungal therapy may be reasonable in high-risk patients.
Rx: ABPA: Systemic corticosteroids plus itraconazole × 8 months improves lung function and ↓ steroid requirements.
Aspergilloma: Surgical excision for massive hemoptysis. Antifungals play a limited role.
Invasive aspergillosis: Voriconazole, amphotericin, or caspofungin.
COMPLICATIONS
ABPA: Bronchiectasis, pulmonary fibrosis.
Aspergilloma: Massive hemoptysis; contiguous spread to the pleura or vertebrae.
Invasive aspergillosis: High mortality, especially in bone marrow and liver transplant patients.
Cryptococcosis
Cryptococcus neoformans encapsulated budding yeast found worldwide in soil, bird (pigeon) droppings, and eucalyptus trees. C. neoformans is the most common fungal infection in AIDS patients
(usually associated with a CD4 count < 100) and is the most common cause of fungal meningitis in all patients.
Meningitis: Mental status changes, headache, nausea, cranial nerve palsies. HIV patients usually lack obvious meningeal signs.
May also cause atypical pneumonia (pulmonary infection is usually asymptomatic) or skin lesions (umbilicated papules resembling molluscum contagiosum), or may involve the bone, eye, or GU tract.
Dx: LP: Patients often have high opening pressure, low glucose, high protein, and lymphocytic pleocytosis. Patients with more advanced immunosuppression may have a bland CSF profile even with meningitis. India ink or Gram stain of CSF may show budding yeast with a thick capsule (both
are <50% sensitive).
Cryptococcemia (a +serum CrAg or blood culture) indicates disseminated disease even with a normal LP.
Unlike what is typically seen in bacterial meningitis, HIV patients with cryptococcal meningitis often have minimal symptoms and a bland CSF.
Polysaccharide cryptococcal antigen (CrAg) in serum or CSF: Serum CrAg is > 99% sensitive in AIDS patients with meningitis but is less sensitive in non-AIDS patients. CSF CrAg is only 90% sensitive. A serum CrAg titer of > 1:8 indicates active disease.
Serum CrAg titers are not useful for monitoring treatment response of meningitis in immunosuppressed patients. CSF CrAg titers should ↓ during successful treatment.
Fungal culture of blood, CSF, urine, sputum, or bronchoalveolar lavage.
CT or MRI may show hydrocephalus or occasionally nodules (cryptococcomas).
Rx: HIV-+ive patients: For mild to moderate lung disease, treat with oral fluconazole for 6–12 months. For meningitis, cryptococcemia, or severe lung disease, treat with amphotericin plus 5-flucytosine for 2 weeks followed by oral fluconazole 400 mg/day for at least 10 weeks.
HIV -ive patients:
For mild to moderate lung disease, treat with fluconazole 200–400 mg/day.
For severe lung disease, treat with amphotericin until symptoms are controlled followed by fluconazole.
For meningitis, give induction/consolidation therapy with amphotericin plus 5-flucytosine - 2 weeks followed by oral fluconazole 400 mg/day - 10 weeks.
Patients with HIV need long-term maintenance therapy with oral fluconazole 200 mg/day. It may be reasonable to stop prophylaxis if the CD4 count ↑to > 100–200 for > 6 months in response to antiretrovirals.
Repeat LP until symptoms resolve in patients with coma or other signs of elevated ICP.
COMPLICATIONS
A poorer prognosis for meningitis is seen in patients with abnormal mental status, those 60 years of age, and those with evidence of high organism load or lack of immune response (as indicated by cryptococcemia, high initial CrAg titer in CSF or serum, high CSF opening pressure, 20 WBCs in CSF,
low glucose, and + India ink).
Coccidioidomycosis
Coccidioides immitis- arid southwestern United States, central California, northern Mexico, and Central and South America. outbreaks occur after earthquakes or dust storms.
1° infection (“valley fever,” “desert rheumatism”): Usually presents with self-limited flulike symptoms, fever, dry cough, pleuritic chest pain, and headache, often accompanied by arthralgias, erythema nodosum, or erythema multiforme.
CXR may be normal or may show unilateral infiltrates, nodules, or thin-walled cavities. Some patients may develop chronic pneumonia, ARDS, or persistent lung nodules.
Disseminated disease (1%): Chronic meningitis, skin lesions (papules, pustules, warty plaques), osteomyelitis, or arthritis.
Serologic tests (complement fixation assays); titers ≥ 1:32 indicate more severe disease and a higher risk of dissemination.
Histology may show giant spherules in infected tissues.
Cultures of respiratory secretions or aspirates of bone and skin lesions may grow the organism (alert the laboratory if the diagnosis is suspected; Coccidioides is highly infectious to lab workers).
Rx: Treatment may not be necessary for acute disease but may be reasonable in patients at risk for dissemination.
Fluconazole, itraconazole, or amphotericin for disseminated disease.
Histoplasmosis
Histoplasma capsulatum is found in the Mississippi and Ohio River valleys.
The organism is found in moist soil and in bat and bird droppings. Risk factors include exploring caves and cleaning chicken coops or attics.
1° infection: Most patients are asymptomatic. However, patients may present with fever, dry cough, and substernal chest discomfort. CXR may show patchy infiltrates that become nodular or exhibit multiple small nodules and hilar or mediastinal adenopathy. Some patients may develop
chronic upper lobe cavitary pneumonia or mediastinal fibrosis (dysphagia, SVC syndrome, or airway obstruction).
Disseminated disease: Presents with hepatosplenomegaly, adenopathy, painless palatal ulcers, meningitis, and pancytopenia from bone marrow infiltration. Patients with HIV may develop colonic disease (diarrhea, perforation or obstruction from mass lesions).
Dx: Urinary antigen test is most useful in HIV/AIDS patents with disseminated disease.
Histology with silver stain of bone marrow, lymph node, or liver.
Cultures of blood or bone marrow are + in immunosuppressed patients with disseminated disease.
Serologic tests (complement fixation and immunodiffusion assays) are often + in immunocompetent patients.
Rx: Treatment is not needed for acute pulmonary disease. Itraconazole or amphotericin for chronic cavitary pneumonia, mediastinal fibrosis, or disseminated histoplasmosis.
Blastomycosis
Blastomyces dermatitidis is found in the central United States (as is Histoplasma) as well as in the upper Midwest and Great Lakes regions.
Risk factors include exposure to woods and streams.
Acute pneumonia. May lead to warty, crusted, or ulcerated skin lesions or to osteomyelitis, epididymitis, or prostatitis.
Dx: Microscopy and culture of respiratory secretions; biopsy or aspirate material shows large yeast with broad-based budding.
Rx: Itraconazole or amphotericin for all infected patients.
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