Pediatric Histoplasmosis Treatment & Management
- Author: James S Hagood, MD; Chief Editor: Russell W Steele, MD more...
Medical Care
Most acute forms of histoplasmosis in immunocompetent hosts resolve without specific treatment. Systemic antifungal treatment is indicated for severe acute pulmonary histoplasmosis, chronic pulmonary histoplasmosis (CPH), progressive disseminated histoplasmosis (PDH), and any manifestation in an immunocompromised patient. Specific therapy recommendations vary with the presenting syndrome.
- Syndromes in immunocompetent hosts
- Localized disease: Antifungal therapy is unnecessary in patients with localized disease. However, oral itraconazole is recommended for 6-12 weeks in patients whose symptoms have not improved after 3-4 weeks of observation.
- Severe acute pulmonary syndrome: Antifungal therapy (amphotericin B) is indicated for patients presenting with clinically significant dyspnea or hypoxemia. After discharge from the hospital, itraconazole should be used to complete a 12-week course of antifungal therapy. Patients with relatively mild manifestations can be treated with only itraconazole, and treatment should be continued for 3 months. Corticosteroids have also been used for short-term therapy (tapered over 2 wk); however, these agents always should be used with caution in fungal infections because of the risk of impaired cell-mediated immunity with prolonged use.
- Mediastinal obstructive syndromes: For patients with clinically significant, symptomatic obstructive symptoms, antifungal treatment should be started. Reports describe successful treatment with oral (eg, itraconazole, ketoconazole) and systemic (amphotericin B) antifungal agents. Surgical resection should be considered for life-threatening obstruction or if a patient's condition fails to improve after 4-6 weeks of antifungal treatment. Surgical interventions do not prevent progression to fibrosing mediastinitis. Although reports mention successful surgical management of fibrosing mediastinitis, the surgical mortality rate is high, and surgeons inexperienced in managing this disorder should not attempt such interventions. Medical management with antifungal agents should be attempted first unless the obstruction is life threatening.
- Pericarditis: Anti-inflammatory treatment with nonsteroidal anti-inflammatory drugs (NSAIDs) or corticosteroids is the mainstay of management. Progression to constrictive pericarditis is described but rare.
- Rheumatologic syndrome: Rheumatologic syndrome often resolves without treatment or with a brief course of NSAIDs.
- Syndromes in hosts with an underlying illness or immunodeficiency
- CPH: Without antifungal treatment, CPH is progressive, causing loss of pulmonary function in most patients and death in up to half. Amphotericin B has been used most successfully and is effective in 59-100% of cases, but most patients can be treated with itraconazole or ketoconazole for at least 3 months.[4] Relapse rates are 10-15% with the last 2 agents; fluconazole is less effective. The preferred treatment is amphotericin B followed by itraconazole for 12-24 months.
- PDH
- Amphotericin B substantially reduces the mortality rate of PDH. A cumulative dosage of at least 35 mg/kg should be administered to prevent relapse. Liposomal preparations may be substituted to reduce toxicity but may have poor renal penetration.
- Many patients have been treated successfully with a change to oral agents after their symptoms initially improve with amphotericin B. Itraconazole is the preferred oral agent, with a 6-month to 18-month course of treatment. Patients who cannot tolerate itraconazole should use fluconazole. After an initial 12-week intensive phase with amphotericin B to induce a remission, patients with AIDS require chronic life-long maintenance therapy to prevent relapse. Amphotericin B once or twice a week is effective but inconvenient and not well tolerated.
- Azoles are highly effective in most cases, but relapse may occur. Treatment with fluconazole is discouraged because of its reduced efficacy as long-term maintenance therapy for histoplasmosis. Echinocandins should not be used.
- Local manifestations of disseminated disease: Endocarditis is very difficult to treat and may require resection of the affected valve and systemic antifungal treatment.
Surgical Care
- Surgical consultation is indicated for patients with infections complicated by fistulas, hemoptysis, or broncholithiasis. The surgical management of mediastinal obstructive syndromes is somewhat controversial because they may improve with observation or medical therapy. Severe obstruction of the airways or large blood vessels may be life threatening, and immediate intervention may be required.
- In general, unroofing and debridement of large granulomas is preferable to excision. Fibrosing mediastinitis is especially difficult to manage because normal structures are encased in collagenous connective tissue. Surgeons in endemic areas often are well versed in the management of these surgically challenging problems.
Consultations
- Infectious disease specialists can assist in the differential diagnosis, in planning appropriate workup, and in choosing therapeutic regimens, particularly for immunocompromised patients.
Lo MM, Mo JQ, Dixon BP, Czech KA. Disseminated histoplasmosis associated with hemophagocytic lymphohistiocytosis in kidney transplant recipients. Am J Transplant. Mar 2010;10(3):687-91. [Medline].
Chamany S, Mirza SA, Fleming JW, Howell JF, Lenhart SW, Mortimer VD, et al. A large histoplasmosis outbreak among high school students in Indiana, 2001. Pediatr Infect Dis J. Oct 2004;23(10):909-14. [Medline].
McKinsey DS, McKinsey JP. Pulmonary histoplasmosis. Semin Respir Crit Care Med. Dec 2011;32(6):735-44. [Medline].
Wheat LJ, Kauffman CA. Histoplasmosis. Infect Dis Clin North Am. Mar 2003;17(1):1-19, vii. [Medline].
Rosenthal J, Brandt KD, Wheat LJ, Slama TG. Rheumatologic manifestations of histoplasmosis in the recent Indianapolis epidemic. Arthritis Rheum. Sep 1983;26(9):1065-70. [Medline].
AETC. Clinical Manual for Management of the HIV-Infected Adult. AETC National Resource Center [serial online]. Available at http://www.aids-ed.org/aetc?page=cm-515_histoplasmosis. Accessed January 11, 2007.
Mandell GL, Bennett JE, Dolin R. Histoplasmosis. In: Principles and Practice of Infectious Diseases. 6th ed. Oxford, England: Churchill Livingstone; 2004.
Cionni DA, Lewis SA, Petersen MR, Foster RE, Riemann CD, Sisk RA, et al. Analysis of outcomes for intravitreal bevacizumab in the treatment of choroidal neovascularization secondary to ocular histoplasmosis. Ophthalmology. Feb 2012;119(2):327-32. [Medline].
Wheat LJ, Musial CE, Jenny-Avital E. Diagnosis and management of central nervous system histoplasmosis. Clin Infect Dis. Mar 15 2005;40(6):844-52. [Medline].
Rangel-Castilla L, Hwang SW, White AC, Zhang YJ. Neuroendoscopic Diagnosis of Central Nervous System Histoplasmosis with Basilar Arachnoiditis. World Neurosurg. Nov 7 2011;[Medline].
Wheat LJ. Antigen detection, serology, and molecular diagnosis of invasive mycoses in the immunocompromised host. Transpl Infect Dis. Sep 2006;8(3):128-39. [Medline].
Swartzentruber S, LeMonte A, Witt J, Fuller D, Davis T, Hage C, et al. Improved detection of Histoplasma antigenemia following dissociation of immune complexes. Clin Vaccine Immunol. Mar 2009;16(3):320-2. [Medline].
Wheat LJ, Garringer T, Brizendine E, Connolly P. Diagnosis of histoplasmosis by antigen detection based upon experience at the histoplasmosis reference laboratory. Diagn Microbiol Infect Dis. May 2002;43(1):29-37. [Medline].
O'Shaughnessy EM, Shea YM, Witebsky FG. Laboratory diagnosis of invasive mycoses. Infect Dis Clin North Am. Mar 2003;17(1):135-58. [Medline].
Maubon D, Simon S, Aznar C. Histoplasmosis diagnosis using a polymerase chain reaction method. Application on human samples in French Guiana, South America. Diagn Microbiol Infect Dis. May 15 2007;[Medline].
Adderson EE. Histoplasmosis in a pediatric oncology center. J Pediatr. Jan 2004;144(1):100-6. [Medline].
Johnson PC, Wheat LJ, Cloud GA, et al. Safety and efficacy of liposomal amphotericin B compared with conventional amphotericin B for induction therapy of histoplasmosis in patients with AIDS. Ann Intern Med. Jul 16 2002;137(2):105-9. [Medline]. [Full Text].
Pitisuttithum P, Negroni R, Graybill JR, et al. Activity of posaconazole in the treatment of central nervous system fungal infections. J Antimicrob Chemother. Oct 2005;56(4):745-55. [Medline].
Raad II, Graybill JR, Bustamante AB, et al. Safety of long-term oral posaconazole use in the treatment of refractory invasive fungal infections. Clin Infect Dis. Jun 15 2006;42(12):1726-34. [Medline].
Restrepo A, Tobon A, Clark B, et al. Salvage treatment of histoplasmosis with posaconazole. J Infect. Apr 2007;54(4):319-27. [Medline].
Antachopoulos C, Walsh TJ. New agents for invasive mycoses in children. Curr Opin Pediatr. Feb 2005;17(1):78-87. [Medline].
Edwards LB, Acquaviva FA, Livesay VT, Cross FW, Palmer CE. An atlas of sensitivity to tuberculin, PPD-B, and histoplasmin in the United States. Am Rev Respir Dis. Apr 1969;99(4):Suppl:1-132. [Medline].
George R, Penn R. Histoplasmosis. In: Sarosi GA, Davies SF, eds. Fungal Diseases of the Lung. New York, NY: Raven; 1993:39-50.
Guimaraes AJ, Pizzini CV, De Matos Guedes HL, et al. ELISA for early diagnosis of histoplasmosis. J Med Microbiol. Jun 2004;53(Pt 6):509-14. [Medline].
Hamilton AJ. Serodiagnosis of histoplasmosis, paracoccidioidomycosis and penicilliosis marneffei; current status and future trends. Med Mycol. Dec 1998;36(6):351-64. [Medline].
Joseph Wheat L. Current diagnosis of histoplasmosis. Trends Microbiol. Oct 2003;11(10):488-94. [Medline].
Keating GM. Posaconazole. Drugs. 2005;65(11):1553-67. [Medline].
Kumar N, Singh S, Govil S. Adrenal histoplasmosis: clinical presentation and imaging features in nine cases. Abdom Imaging. Sep-Oct 2003;28(5):703-8. [Medline].
Kurowski R, Ostapchuk M. Overview of histoplasmosis. Am Fam Physician. Dec 15 2002;66(12):2247-52. [Medline].
Levitz SM. Overview of host defenses in fungal infections. Clin Infect Dis. Mar 1992;14 Suppl 1:S37-42. [Medline].
Mathisen DJ, Grillo HC. Clinical manifestation of mediastinal fibrosis and histoplasmosis. Ann Thorac Surg. Dec 1992;54(6):1053-7; discussion 1057-8. [Medline].
Mocherla S, Wheat LJ. Treatment of histoplasmosis. Semin Respir Infect. Jun 2001;16(2):141-8. [Medline].
Murray JF, Nadel JA. Histoplasmosis. In: Textbook of Respiratory Medicine. 4th ed. 2005:1045-55.
Wheat J. Histoplasmosis. Experience during outbreaks in Indianapolis and review of the literature. Medicine (Baltimore). Sep 1997;76(5):339-54. [Medline].
[Guideline] Wheat J, Sarosi G, McKinsey D, et al. Practice guidelines for the management of patients with histoplasmosis. Infectious Diseases Society of America. Clin Infect Dis. Apr 2000;30(4):688-95. [Medline].
Wiedermann BL. Histoplasmosis. In: Feigin RD, Cherry JD, Fletcher J, eds. Textbook of Pediatric Infectious Diseases. WB Saunders; 1998:2337-50.

