Histoplasmosis
Histoplasmosis: Excerpt from The 5-Minute Pediatric Consult
Julian L. Allen, MD
Histoplasmosis - BASICS
Histoplasmosis - description
- Spectrum of illness, ranging from primary pulmonary to disseminated infection:
- Pulmonary
- Extrapulmonary
- Disseminated
- Caused by the dimorphic fungus Histoplasma capsulatum
- Acute or chronic
- Primary or reactivation
Histoplasmosis - general prevention
- Investigate common source of infection in outbreaks. Limit exposure to soil and dust from areas contaminated with bat and bird droppings.
- For occupational exposure to H. capsulatum–contaminated soil:
- Wetting agents to prevent aerosolization of contaminated dust
- National Institute for Occupational Safety and Health (NIOSH)-approved respirators, e.g., N95, gloves, and dispensable clothing (see NIOSH Web site in Bibliography)
- Isolation of the hospitalized patient: Standard precautions recommended
Histoplasmosis - epidemiology
- Most common systemic fungal infection in US
- Organism found in nitrogen-rich soil contaminated by animal droppings, especially those of bats and birds
- Outbreaks reported in pigeon breeders or cleaners of chicken coops, explorers of caves with bats, and populations living close to construction
- Endemic in eastern and central US, specifically in the St. Lawrence, Mississippi, and Ohio River valleys, the Rio Grande, Texas, Oklahoma, Kansas, Pennsylvania, Maryland, and Virginia
- No human-to-human or animal-to-human transmission
- Incubation period variable, 1–3 weeks
Histoplasmosis - incidence
Severity of symptoms depends on immunologic status of the host and size of inoculum:
- Asymptomatic in up to 95% of cases
- With heavy inoculum, 50–100% develop symptoms. Of these, 80% develop flulike symptoms, lasting about a week; 10–20% develop pericarditis, arthritis, or erythema nodosum, resolving after a few weeks
Histoplasmosis - prevalence
80–90% of adults in endemic areas are skin test– positive
Histoplasmosis - risk factors
Risk factors for severe disease (progressive disseminated histoplasmosis) include very old and very young (<2 years) and cellular immunocompromise.
Histoplasmosis - etiology
- Inhalation of H. capsulatum spores
- The dimorphic fungus exists in mycelial form in the environment at 25°C and in yeast form in tissues at 37°C.
Histoplasmosis - DIAGNOSIS
Histoplasmosis - signs & symptoms
Histoplasmosis - history
- Environmental exposures (pigeon breeding, construction, cave exploration, travel in endemic areas): Epidemiologically suggestive of histoplasmosis
- Upper respiratory symptoms, low-grade fever, cough, pleuritic chest pain: Suggestive of mild disease lasting 1–5 days
- Arthritis, more severe chest pain, skin lesions, pericarditis, or pleural effusion: Suggestive of moderate disease lasting ~15 days
- High fever, night sweats, weight loss, cough, chest pain, shortness of breath, hoarseness lasting >2–3 weeks: Suggestive of disseminated disease and underlying immune suppression
- Chronic cough, dyspnea, disabling respiratory dysfunction: Suggestive of chronic cavitary pulmonary disease
Histoplasmosis - physical exam
- Flulike signs and symptoms are common presentations in mild disease; physical examination may be normal.
- Less usual manifestations suggest moderate or disseminated disease:
- Hepatosplenomegaly
- Adenopathy
- Pneumonitis
- Skin lesions (erythema nodosum)
- Pericardial friction rub
- Pallor, petechiae
- CNS findings
Histoplasmosis - tests
Histoplasmosis - lab
- Culture of the organism in sputum, tissue specimens, peripheral blood, or bone marrow:
- Definitive, but requires 2–6 weeks
- Sputum cultures are negative in most patients with mild disease.
- Cultures are positive in 2/3 of patients with cavitary disease and 1/3 of patients with noncavitary disease.
- In progressive disseminated histoplasmosis in patients with AIDS, bone marrow and blood cultures are positive in 80–90% of patients, and bronchoscopic cultures are positive in 80–90% of patients with abnormal chest radiographs.
- Identification of organism by microscopy:
- Histologic identification from sputum, blood, bone marrow, biopsy specimens, and/or CSF
- Staining methods: Hematoxylin and eosin, Wright, Giemsa, periodic acid–Schiff; Gomori methenamine silver more likely to detect sparse organisms
- Skin testing:
- Skin tests not available in the US; no longer recommended
- Positive delayed hypersensitivity reaction (48 hours) to the histoplasmin test may become reactive 2–6 weeks after infection.
- Not recommended for diagnostic purposes in adults; very often indicative of past infection
- In children <5 years, only 0.5% from endemic areas are skin test–positive.
- 50% of immunocompromised patients may have false-negative skin tests
- False-positives occur in blastomycosis and coccidiomycosis.
- Skin testing can falsely elevate antibody levels in 15–25% of patients.
- Radioimmune and hemagglutinin assays for H. capsulatum antigen:
- Radioimmunoassay: Specific, sensitive, and rapid for diagnosing progressive disseminated histoplasmosis, but low sensitivity for acute pulmonary histoplasmosis in immunocompetent patients
- May cross-react with coccidiomycosis and blastomycosis antigens
- Hemagglutinin found in urine or blood in 50–90% of patients with progressive disseminated histoplasmosis (urine more sensitive) and in bronchoalveolar lavage fluid in 70% of AIDS patients with pulmonary histoplasmosis
- Antigen tests generally useful only in 1st month of infection, but can persist for much longer in AIDS patients
- Antigen levels decrease with treatment and can increase again with relapse.
- DNA probes increasingly used
- Serologic studies for antibodies:
- Titers become positive 4–6 weeks after infection, peak at 2–3 months, and decline over a period of 2–5 years.
- Positive titers in 90% of patients with symptomatic disease
- False positives in patients with coccidiomycosis, blastomycosis, tuberculosis, or paracoccidiomycosis
- False negatives in immunocompromised patients with progressive disseminated histoplasmosis
- Complement fixation:
- Single titer 1:32 (1:8 in nonendemic areas) is diagnostic; 4-fold increase in titers is diagnostic.
- More sensitive than immunodiffusion test, which is more specific
- Precipitating antibodies by immunodiffusion:
- H band suggests active infection.
- M band is less specific.
- Presence of H and M bands is highly diagnostic.
- Evaluation for meningitis:
Relative sensitivities:
| Stain of CSF | <10% |
| Culture CSF | 20–60% |
| Antigen CSF | 40–70% |
| Antibody CSF | 60–80% |
| Meningeal or brain biopsy | 50–80% |
Histoplasmosis - imaging
Chest radiograph:
- Normal in 75% of patients with histoplasmosis, 25–50% of immunocompromised patients with disseminated disease
- Most common radiologic changes include:
- Small 2–5-mm infiltrates in lung bases
- Lobar or diffuse infiltrates
- Enlarged or calcified hilar nodes
- Buckshot calcifications seen in patients with large inoculum
- Cavitary lesions
- Pleural effusions in 10% of chest radiographs in adults
- Calcified nodules in liver and spleen
Histoplasmosis - differencial diagnosis
- Infections:
- Pneumonia (viral, bacterial)
- Influenza and other viral syndromes
- Tuberculosis
- Other fungal diseases:
- Aspergillosis
- Blastomycosis
- Coccidiomycosis
- Sarcoidosis
- Malignancy
- Can be difficult to distinguish between active disease and previous exposure in patients from endemic regions
- May be confused with tuberculosis and other fungal diseases
- Isolated pulmonary nodule on chest radiograph may be difficult to distinguish from malignancy.
Histoplasmosis - TREATMENT
Histoplasmosis - medication
- Uncomplicated cases of primary histoplasmosis of the lungs may not require drug therapy.
- Treatment should be considered for patients with pulmonary symptoms lasting >4 weeks or with obstructing granulomatous adenitis.
- Patients with more severe or disseminated disease or the immunocompromised require treatment with antifungal agents. Treatment regimens vary. Amphotericin B, 0.5–1.0 mg/kg/d IV for 4–6 weeks (or 35 mg/kg total). Recommended for disseminated disease or patients with respiratory compromise and hypoxemia. Alternative treatment in children: Amphotericin for 2–3 weeks, followed by oral itraconazole for 3–6 months.
- Milder disease: For the following drugs, interactions with other drugs are common; consult drug interaction database or reference before prescribing. Limited or no information about use in newborn infants, and, in the case of ketoconazole, children <2 years:
- Ketoconazole:
- 3.3–6.6 mg/kg/d PO (400 mg/d initially, then 200 mg/d is maximum dose) for 3–6 months
- Should be used with caution in patients receiving HLevels can also be reduced by rifampin and phenytoin.
- Fluconazole or itraconazole are generally preferred due to fewer side effects (hepatotoxicity, anaphylaxis, thrombocytopenia, hemolytic anemia, other GI).
- Fluconazole:
- 6–12 mg/kg/d PO (400–800 mg/d is maximum dose) for 3–6 months
- Reduced dose may also be given IV.
- Achieves levels in CSF
- Itraconazole:
- 5–10 mg/kg/d PO (400 mg/d is maximum dose) for 3–6 months
- May also be given IV
- Although not approved for use in children, effective in the treatment of HIV patients with histoplasmosis
- Does not achieve levels in CSF
- In patients with AIDS, lifelong suppressive therapy is recommended.
- Adjunct therapy with corticosteroids may be added in patients with life-threatening airway obstruction secondary to hilar adenopathy.
- Prophylaxis: Considered for patients with AIDS, low CD4 counts and who live in endemic areas
- Pericarditis: Treat with indomethacin
Histoplasmosis - FOLLOW UP
When to expect improvement:
- In mild-to-moderate cases not requiring drug therapy, usually 1–2 weeks
- In cases requiring therapy, improvement usually noted within 2 weeks
- Response to therapy more variable in AIDS patients
Histoplasmosis - prognosis
- In most cases, prognosis excellent.
- 90% mortality within 3 months in patients with acute disseminated histoplasmosis if left untreated
- High relapse in AIDS patients if not treated with chronic suppressive therapy
Histoplasmosis - complications
- In general, complications rare; usually indicate disseminated disease
- Symptoms include:
- Prolonged fever, malaise, cough, weight loss, hepatosplenomegaly, diarrhea
- Patients may also develop disseminated intravascular coagulopathy, adult respiratory distress syndrome, renal failure, endocarditis, or Addison disease.
- Disseminated disease can involve:
- Skin
- Eyes (uveitis)
- Liver
- Spleen
- Adrenal glands (adrenal insufficiency)
- Bone marrow
- Heart
- CNS (meningitis)
- Other complications include:
- Tracheobronchial compression
- Mediastinal granuloma formation or fibrosing mediastinitis
- Fistula formation
- Pericarditis
- Obstruction of superior vena cava, esophagus, or pulmonary arteries
- Chronic cavitary pulmonary disease very similar to tuberculosis
Histoplasmosis - bibliography
American Academy of Pediatrics. Histoplasmosis. In: Pickering LK, ed. Red Book: 2006 Report of the Committee on Infectious Diseases. 27th ed. Elk Grove Village, IL: American Academy of Pediatrics; 2006:371–374.Nania JJ, Wright PF. The Mycoses. In: Chernick V, Boat TF, Wilmott RW, et al., eds. Kendig’s Disorders of the Respiratory Tract in Children. Philadelphia, PA: Saunders Elsevier; 2006:530–542.National Institute for Occupational Safety and Health (NIOSH) Web site: http://www.cdc.gov/niosh/ 97-146.html.- Wheat LJ. Current diagnosis of histoplasmosis. Trends Microbiol. 2003;11:488–494.
- Wheat LJ. Histoplasmosis. Infect Dis Clin North Am. 2003;17:1–19.
Histoplasmosis - CODES
Histoplasmosis - icd9
115.90 Histoplasmosis, unspecified
Histoplasmosis - FAQ
- Q: What are the most common clinical presentations of histoplasmosis?
- A: Asymptomatic, mild primary pulmonary (1–2 weeks), moderate (2–3 weeks), disseminated, and cavitary
- Q: How is histoplasmosis best diagnosed?
- A: Skin test generally not useful; culture and serologic testing recommended
- Q: Does histoplasmosis need to be treated with antifungal therapy?
- A: Mild primary disease—no; more severe or disseminated disease—yes
- Q: How can histoplasmosis be prevented?
- A: Prevention can be achieved only by controlling the environmental factors in the affected areas; there are no vaccines for the prevention of histoplasmosis.
- Q: Do patients with histoplasmosis need to be isolated?
- A: No isolation of infected patients is required.
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Book Source Details
- Book Title: The 5-Minute Pediatric Consult
- Author(s): M. William Schwartz MD; et al.
- Year of Publication: 2008
- Copyright Details: The 5-Minute Pediatric Consult, Copyright © 2008 Lippincott Williams & Wilkins.
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Copyright notice for book excerpts: Copyright © 2008 Lippincott Williams & Wilkins. All rights reserved.
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More About This Book:
Title: The 5-Minute Pediatric Consult
Authors: M. William Schwartz MD; et al.
Publisher: Lippincott Williams & Wilkins
Copyright: 2008
ISBN: 0-7817-7577-9
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