eMedicine Specialties > Pulmonology > Infectious Lung Diseases
Histoplasmosis: Treatment & Medication
Updated: Aug 14, 2009
- Overview
- Differential Diagnoses & Workup
- Treatment & Medication
- Follow-up
Treatment
Medical Care
Most infections in individuals who are immunocompetent are self-limiting and do not require therapy. In cases of prolonged infection, cases of systemic infection, or those involving individuals who are immunocompromised, medical treatment is recommended.
- Acute pulmonary histoplasmosis
- No treatment is required for individuals who are asymptomatic.
- Monitor mild symptoms (without treatment).
- In patients with prolonged symptoms (>4 wk) or those with overwhelming pulmonary involvement, initiate medical therapy with itraconazole for 6-12 weeks.
- Patients with severe infection should be treated with amphotericin B; once the patient is stable, amphotericin B may be changed to itraconazole and should be continued for 1 year.12
- Chronic pulmonary histoplasmosis
- This often is fatal if not treated; the mortality rate may be as high as 50% without treatment, compared with a mortality rate of 28% with treatment.3
- Patients may have a progressive loss of pulmonary function.
- Patients with cavitary lesions must be treated, in most patients itraconazole is sufficient and should be given for one year.
- Persistent cavitations despite multiple courses of medical treatment warrant surgical consideration.
- Progressive disseminated histoplasmosis and meningitis
- Initiate medical therapy for all patients with progressive disseminated histoplasmosis and meningitis.
- Hemodynamic and respiratory compromise from pericardial and pleural involvement warrants immediate procedural intervention. Perform thoracentesis or pericardiocentesis in patients with severe pleural effusions and pericardial tamponade, respectively.
- Cutaneous and rheumatologic histoplasmosis: Lesions are self-limiting. Therapy is indicated only for prolonged episodes or in individuals who are immunosuppressed.
- Ocular histoplasmosis: Treat extensive maculopathy in presumed ocular histoplasmosis with steroids.
- Mediastinal histoplasmosis
- Treatment for mediastinal granuloma is not recommended in asymptomatic patients; for symptomatic patients, itraconazole may be used for 6-12 weeks, although clinical trials to support this are lacking.12
- Antifungal therapy is not effective for fibrosing mediastinitis; corticosteroids and nonsteroidal anti-inflammatory drugs (NSAIDs) also are ineffective. Surgery is not recommended.
- Antifungals are not recommended for pericarditis because it is an inflammatory reaction.
Surgical Care
Use surgical procedures for diagnostic purposes when other modalities are unrevealing. Intervention is also required when medical therapy is insufficient to alleviate the effects of progressive fibrosis, calcification, and scarring.
- Thoracic surgery
- In rare cases when serologic and procedural modalities cannot indicate a definitive diagnosis, consider obtaining sufficient tissue samples using thoracoscopy or by performing an open lung biopsy.
- Surgical resection of pulmonary cavitary lesions is required when repeated relapses or progressive disease occurs despite repeated intensive medical therapy.
- Progressive fibrosis of the mediastinum can produce traction or invade into adjacent structures and cause a distorted anatomy. Surgery with spiral vein grafts or vascular stents may be necessary to treat SVC syndrome associated with fibrosing mediastinitis. Surgery may also be required to alleviate scarring, to retain structural integrity, and to alleviate symptoms. The possibility of extensive adhesion and distortion associates surgery with high mortality rates.
- Mechanical compression by mediastinal and hilar granulomatosis may require surgical excision. However, surgery is risky because of the possibility of spilling necrotic material into the mediastinum and initiating further fibrotic reaction. Patients may develop extensive symptoms from compression of pulmonary, vascular, and rarely, esophageal structures.
- Cardiac surgery
- Pericardial window placement may be needed when pericardiocentesis is insufficient to alleviate pericardial tamponade.
- Endovascular histoplasmosis may result in infected valves and aneurysm formation, which requires surgical excision of infected valves and aneurysm repair. Treating endovascular histoplasmosis with medical therapy alone is rarely curative.
- Ophthalmologic treatment
- Laser photocoagulation treatment may be needed in patients with active neovascular membrane formation due to choroiditis.
- Overgrowth may result in progressive vision loss.
Consultations
Obtain consultations when complications of histoplasmal infection compromise organ systems. Seek out a specialist to perform diagnostic procedures if other modalities do not provide adequate information to make a diagnosis.
- Pulmonary specialist
- Bronchoscopy may be needed for diagnostic purposes.
- Bronchial washings and aspirates are sent for culture and analysis.
- Transbronchial tissue biopsy provides specimens for histiologic examination.
- Cardiology specialist: Pericardiocentesis is required to restore hemodynamic stability in patients with pericardial tamponade.
- Cardiothoracic or ophthalmologic surgeon: Such surgery may be needed if complications arise or if further diagnostic options are required.
Medication
The goals of pharmacotherapy are to reduce morbidity and to prevent complications.
Antifungals
Their mechanism of action may involve an alteration of RNA and DNA metabolism or an intracellular accumulation of peroxide that is toxic to the fungal cell.
Fluconazole (Diflucan)
Synthetic oral antifungal (broad-spectrum bistriazole) that selectively inhibits fungal cytochrome P-450 and sterol C-14 alpha-demethylation, which prevents conversion of lanosterol to ergosterol, thereby disrupting cellular membranes. Has little affinity for mammalian cytochromes, which is believed to explain its low toxicity. Available as tab for oral administration, as powder for oral suspension, and as a sterile sol for IV use. Has fewer adverse effects and better tissue distribution than older systemic imidazoles.
Adult
400 mg/d PO/IV for CNS histoplasmosis or for prophylaxis in immunosuppressed patients
Pediatric
12 mg/kg/d IV/PO; not to exceed 600 mg/d
CYP450 2C19 and 3A4 inhibitor; levels may increase with hydrochlorothiazide; fluconazole levels may decrease with chronic coadministration of rifampin; may increase concentrations of theophylline, phenytoin, tolbutamide, cyclosporine, glyburide, and glipizide; effects of anticoagulants may increase with coadministration
Documented hypersensitivity
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
Adjust dose for renal insufficiency; closely monitor if rashes develop, and discontinue drug if lesions progress; may cause clinical hepatitis, cholestasis, and fulminant hepatic failure (including death) when taken with underlying medical conditions (eg, AIDS, malignancy) or while taking multiple concomitant medications; not recommended in breastfeeding
Convenience and efficacy of single-dose regimen for treatment of vaginal yeast infections should be weighed against difficulties resulting from higher incidence of adverse reactions reported with oral fluconazole versus intravaginal agents
Itraconazole (Sporanox)
Fungistatic activity. Synthetic triazole antifungal agent that slows fungal cell growth by inhibiting CYP450-dependent synthesis of ergosterol, a vital component of fungal cell membranes.
Can be used as substitute for ketoconazole. Indications are similar. Can be used for mildly symptomatic or prolonged acute pulmonary histoplasmosis. Used to treat cutaneous or rheumatologic manifestations in patients who are immunocompromised and in prolonged courses of illness. Can be used as an alternative to amphotericin B in treatment of chronic pulmonary histoplasmosis or chronic and subacute progressive disseminated histoplasmosis. Unlike ketoconazole, can be used as alternate maintenance therapy after induction with amphotericin B in acute progressive disseminated histoplasmosis.
Adult
200 mg PO qd; not to exceed 400 mg/d; increase in 100-mg increments if no improvement (administer >200 mg/d in divided doses)
3- to 6-wk course in acute pulmonary histoplasmosis; 6- to 12-mo course for all other manifestations of histoplasmosis, as indicated
200 mg PO bid as life-long maintenance therapy after amphotericin B in acute progressive disseminated histoplasmosis
Pediatric
Not established; suggested dose of 100 mg/d PO for systemic fungal infections
Antacids may reduce absorption; edema may occur with coadministration of calcium channel blockers (eg, amlodipine, nifedipine); hypoglycemia may occur with sulfonylureas; may increase tacrolimus and cyclosporine plasma concentrations when high doses are used; rhabdomyolysis may occur with coadministration of HMG-CoA reductase inhibitors (ie, lovastatin, simvastatin)
May increase digoxin levels; coadministration may increase plasma levels of midazolam or triazolam; phenytoin and rifampin may reduce itraconazole levels (phenytoin metabolism may be altered)
Documented hypersensitivity
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
Caution in hepatic insufficiency
Amphotericin B (Fungizone)
Drug of choice for overwhelming acute pulmonary histoplasmosis, chronic pulmonary histoplasmosis, all forms of progressive disseminated histoplasmosis, meningitis, and endovascular histoplasmosis. Can be used as maintenance therapy for acute progressive disseminated histoplasmosis. Treatment with amphotericin alone without surgical intervention in endovascular histoplasmosis rarely is effective. Also used after treatment failure with azoles.
Adult
0.7-1 mg/kg/d IV to a total dose of 35 mg/kg; minimum total dose should be 2 g
If life-long antifungal maintenance therapy is desired in acute progressive disseminated histoplasmosis, induce 0.7-1 mg/kg/d IV to total of 20-25 mg/kg; maintenance therapy of 50 mg IV once per wk
Can use itraconazole as alternate maintenance drug
Although unproven, intrathecal or intraventricular injection for severe meningitis is dosed at 0.5-1 mg/5 mL of CSF 3-4 times weekly
Pediatric
Administer as in adults
Antineoplastic agents may enhance potential of amphotericin B for renal toxicity, bronchospasm, and hypotension; corticosteroids, digitalis, and thiazides may potentiate hypokalemia; risk of renal toxicity is increased with cyclosporine
Documented hypersensitivity
Pregnancy
B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals
Precautions
Monitor renal function, serum electrolytes such as magnesium and potassium, liver function, CBC, and hemoglobin concentrations; resume therapy at lowest level (eg, 0.25 mg/kg) when therapy is interrupted for > 7 d; hypoxemia, acute dyspnea, and interstitial infiltrates may occur in neutropenic patients receiving leukocyte transfusions (separate time of amphotericin infusion from time of leukocyte transfusion)
Nonsteroidal Anti-inflammatory Drugs
Have analgesic, anti-inflammatory, and antipyretic activities. Their mechanism of action is not known, but they may inhibit cyclooxygenase activity and prostaglandin synthesis. Other mechanisms may exist as well, such as inhibition of leukotriene synthesis, lysosomal enzyme release, lipoxygenase activity, neutrophil aggregation, and various cell-membrane functions. Commonly used to alleviate inflammation associated with pericarditis, as in histoplasmal pericarditis.
Ibuprofen (Motrin, Advil)
Inhibits inflammatory reactions and pain by decreasing prostaglandin synthesis.
Adult
400 mg PO q4-6h, 600 mg q6h, or 800 mg q8h while symptoms persist; not to exceed 3.2 g/d
Pediatric
20-70 mg/kg/d PO divided tid/qid; start at lower end of dosing range and titrate; not to exceed 2.4 g/d
Coadministration with aspirin increases risk of inducing serious NSAID-related adverse effects; probenecid may increase concentrations and, possibly, toxicity of NSAIDs; may decrease effect of hydralazine, captopril, and beta-blockers; may decrease diuretic effects of furosemide and thiazides; monitor PT closely (instruct patients to watch for signs of bleeding); may increase risk of methotrexate toxicity; phenytoin levels may be increased when administered concurrently
Documented hypersensitivity; peptic ulcer disease; recent GI bleeding or perforation; renal insufficiency; high risk of bleeding
Pregnancy
B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals
D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus
Precautions
Caution in congestive heart failure, hypertension, and decreased renal and hepatic function; caution in anticoagulation abnormalities or during anticoagulant therapy
Corticosteroids
Have anti-inflammatory properties and cause profound and varied metabolic effects. Corticosteroids modify the body's immune response to diverse stimuli.
Prednisone (Sterapred)
Commonly used to decrease hypersensitivity response to histoplasmal infection. High-dose steroids are used in patients with extensive maculopathy.
Adult
60-80 mg/d PO; taper over 2-3 wk to treat severe hypersensitivity response in all manifestations of histoplasmosis
Pediatric
4-5 mg/m2/d PO bid/qid; alternatively, 0.05-2 mg/kg PO divided bid/qid; taper over 2 wk as symptoms resolve
Coadministration with estrogens may decrease prednisone clearance; concurrent use with digoxin may cause digitalis toxicity secondary to hypokalemia; phenobarbital, phenytoin, and rifampin may increase metabolism of glucocorticoids (consider increasing maintenance dose); monitor for hypokalemia with coadministration of diuretics
Documented hypersensitivity; viral infection; peptic ulcer disease; hepatic dysfunction; connective tissue infections; fungal or tubercular skin infections; GI disease
Pregnancy
B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals
Precautions
Abrupt discontinuation of glucocorticoids may cause adrenal crisis; hyperglycemia, edema, osteonecrosis, myopathy, peptic ulcer disease, hypokalemia, osteoporosis, euphoria, psychosis, myasthenia gravis, growth suppression, and infections may occur with glucocorticoid use
More on Histoplasmosis |
| Overview: Histoplasmosis |
| Differential Diagnoses & Workup: Histoplasmosis |
 Treatment & Medication: Histoplasmosis |
| Follow-up: Histoplasmosis |
| References |
| Further Reading |
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References
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Keywords
histoplasmosis, Histoplasma capsulatum, H capsulatum, Histoplasma species, dimorphic fungus, yeast, bat droppings, bird droppings, acute pulmonary histoplasmosis, pleural effusion, pericarditis, chronic pulmonary histoplasmosis, pulmonary fibrosis, mycelium, macroconidia, microconidia, progressive disseminated histoplasmosis, ocular histoplasmosis syndrome, chronic progressive disseminated histoplasmosis, subacute progressive disseminated histoplasmosis, acute progressive disseminated histoplasmosis
