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Pediatric Histoplasmosis Clinical Presentation

  • Author: James S Hagood, MD; Chief Editor: Russell W Steele, MD  more...
Updated: Jan 14, 2015


Clinical presentations of histoplasmosis vary depending on the size of the inoculum, the host's immune status, and the presence of underlying lung disease. Overt symptoms occur in 5% of individuals after low-level exposure, but the rate of a clinical disease exceeds 75% after heavy exposure in healthy hosts. The incubation time of acute histoplasmosis in previously nonimmune individuals is 9-17 days.

In a description of a recent large outbreak associated with disturbing soil during school hours at a high school, 77% of all students and staff tested demonstrated evidence of recent infection, and 68% of these developed symptoms of acute pulmonary histoplasmosis. Peak onset of illness occurred 14 days after presumed exposure.[2, 3]

In 80% of patients, symptoms are nonspecific and include fever, chills, myalgias, nonproductive cough, and chest pain. This acute syndrome can range from mild (lasting 1-5 d) to severe (lasting 10-21 d); the latter is associated with weight loss, fatigue, and night sweats. Fatigue may persist for weeks after the acute symptoms resolve.

  • Syndromes in immunocompetent hosts
    • Severe acute pulmonary syndrome: After exposure to a large inoculum, patients may develop severe acute pulmonary syndrome, which is characterized by a flulike prodrome with severe fever, chills, fatigue, cough, and chest pain followed by dyspnea and hypoxemia. This hypoxemia may progress to an adult respiratory distress syndrome (ARDS)–like illness (see the image below).
      Acute pulmonary syndrome in a 16-year-old female a Acute pulmonary syndrome in a 16-year-old female adolescent.
    • Histoplasmoma: Histoplasmosis occasionally manifests as a single pulmonary parenchymal nodule, which is observed as a coin lesion on chest radiographs. This nodule is often asymptomatic.
    • Mediastinal obstructive syndromes (granulomatous mediastinitis)
      • Mediastinal lymph node enlargement occurs in most patients with histoplasmosis (see the image below).
        Hilar lymphadenopathy in an 11-year-old child. Hilar lymphadenopathy in an 11-year-old child.
      • In 5-10% of patients with acute pulmonary syndromes, these nodes may be large enough to obstruct contiguous structures, such as airways, esophagus, and large blood vessels. Airway obstruction can lead to a dry or productive cough and dyspnea. In rare cases, erosion of infected nodes into airway walls can lead to hemoptysis, air leak syndromes, broncholithiasis, or lithoptysis.
      • Esophageal obstruction can cause dysphagia. Airway-esophageal fistulas are reported complications of mediastinal involvement with histoplasmosis. Obstructed pulmonary arteries can produce symptoms of mitral valve obstruction.
      • Fibrosing mediastinitis is a late complication of mediastinal granuloma, in which sustained and exaggerated fibrosis entraps and impinges on mediastinal structures (see the image below), which may result in venous obstruction.
        Fibrosing mediastinitis with mediastinal widening Fibrosing mediastinitis with mediastinal widening and tracheal deviation.
      • Fibrosing mediastinitis represents a fibrotic response to a previous episode of histoplasmosis, and some suggest that certain individuals are predisposed to excessive fibrotic responses to Histoplasma antigens. Nonresponses to antifungal treatment and rare isolations of H capsulatum tissue samples indicate that ongoing infection is not likely to play an important role. Presenting symptoms can include cough, dyspnea, wheezing, hemoptysis, dysphagia, and superior vena cava (SVC) obstructive syndrome. In a subset of patients, the process is progressive, leading to death from cor pulmonale or respiratory failure.
    • Pericarditis: Pericarditis usually results from inflammation in contiguous lymph nodes rather than from fungal infection of the pericardial space and occurs in as m any as 10% of patients with symptomatic acute disease.[4] Pericarditis with true infection of the pericardium occasionally occurs in disseminated histoplasmosis.
    • Rheumatologic syndrome: A syndrome of arthritis, arthralgias, and erythema nodosum is observed in as many as 10% of patients with acute infection. This syndrome is much more common in women than in men. Joint symptoms can persist for months. In an epidemic in the Midwestern United States that occurred in the 1980s, 24 of 381 (6.3%) patients with symptomatic histoplasmosis had rheumatologic symptoms, primarily arthritis or arthralgia.[5] Of these, 46% had erythema nodosum.
  • Syndromes in hosts with an underlying illness or immunodeficiency
    • Chronic pulmonary histoplasmosis (CPH): CPH most commonly occurs in adults with underlying lung disease (eg, chronic obstructive pulmonary disease [COPD]) and represents 10% of symptomatic cases. Concurrent neoplasia is not uncommon. CPH is rare in children. The presentation of CPH is similar to that of pulmonary tuberculosis. Most patients have productive cough, dyspnea, or chest pain. Systemic symptoms, such as fatigue, fever, and night sweats, are common. The clinical course of untreated CPH is progressive, with spread to contiguous lung. Complications, such as hemoptysis and bronchopleural fistulae, may ensue. Other infections, such as mycobacterial and other fungal infections (eg, aspergillosis), can coexist.
    • Progressive disseminated histoplasmosis (PDH)
      • PDH can occur in infants who are immunocompetent but is most likely to affect patients with underlying disorders of cell-mediated immunity. In endemic areas, histoplasmosis accounts for 5% of opportunistic infections among individuals with AIDS and may account for 25% in hyperendemic areas.[6] The incidence of histoplasmosis among individuals with AIDS in the United States has declined because of widespread use of antiretroviral therapy. Disseminated histoplasmosis in a patient with HIV can be an AIDS-defining illness. PDH also occurs in individuals with Hodgkin disease or lymphoreticular malignancies or in those receiving immunosuppressive therapy.
      • In children, the incidence of disseminated histoplasmosis appears to have decreased over the past 3 decades. The onset of PDH can be insidious, with low-grade fever, weight loss, malaise, and oropharyngeal ulcerations. In patients with severely impaired cellular immunity, the presentation of PDH may be acute and rapidly progressive. Presenting symptoms include severe fever, GI symptoms, hepatosplenomegaly, and pancytopenia. In patients with underlying rheumatic disease, this may mimic Felty Syndrome.
      • Multiorgan system failure and coagulopathy can rapidly ensue. Adrenal involvement is common in PDH (80-90% of patients), and 15% of patients have overt adrenal insufficiency.[7]
    • Local manifestations of disseminated disease: Histoplasmosis may include genital ulcers, epididymitis, phimosis, orchitis, cystitis, cholecystitis, pancreatitis, soft-tissue nodules, nodular myositis, panniculitis, carpal tunnel syndrome, osteomyelitis, arthritis, and hypercalcemia. The occurrence of ocular histoplasmosis is controversial because this clinical entity is described in patients who reside exclusively in areas where histoplasmosis in not endemic.[8]
    • CNS histoplasmosis: Meningitis is a complication in 10% of patients with disseminated disease but occasionally occurs in patients who are immunocompetent.[4, 9, 10] Symptoms are usually indolent and chronic; examples include fever, headache, and changes in mental status. Seizures and focal neurologic deficits can occur. Localized lesions in the brain occur in one third of patients with CNS involvement, and isolated spinal cord lesions have been reported.
    • Adrenal disease: This may occur as a manifestation of relapsing histoplasmosis several years after the initial episode. Concurrent CNS involvement is common in patients with adrenal involvement. Histoplasmosis should be excluded in all patients with adrenal insufficiency or adrenal masses, and CT scanning to examine the adrenal glands should be considered in patients with disseminated histoplasmosis.
    • Endocarditis: This is reported in 4% of patients with disseminated histoplasmosis, and mostly presents with embolic episodes.[4]


See the list below:

  • Syndromes in immunocompetent hosts
    • Severe acute pulmonary syndrome: Physical findings are similar to those of diffuse pneumonitis and include increased work of breathing, nasal flaring, accessory muscle use, and diffuse fine crackles. Pleural involvement can present with pleural friction rub or with diminished breath sounds and dullness to percussion.
    • Mediastinal obstructive syndromes: Obstruction of central airways can produce inspiratory and expiratory wheezes, which may be monophonic and localized. Findings in SVC syndrome include facial swelling, distension of the veins of the neck and upper chest wall, conjunctival injection, and loss of venous pulsations. Pulmonary venous occlusion produces findings consistent with mitral valve stenosis, including a low-pitched diastolic apical murmur.
    • Pericarditis: Physical findings include chest/abdominal pain, pericardial friction rub, and fever. Signs of hemodynamic compromise can be observed in 40% of patients.[4]
    • Rheumatologic syndrome: In a subset of patients, symmetric polyarticular arthritis and erythema nodosum may be seen.
  • Syndromes in hosts with an underlying illness or immunodeficiency
    • CPH: Crackles, wheezes, and diminished breath sounds may be heard. Other physical findings are similar to those observed in chronic lung disease. Examples are cyanosis and digital clubbing.
    • PDH: Patients usually have respiratory distress, inanition, cachexia, pallor, and hepatosplenomegaly. Subcutaneous nodules may be present, as may signs of localized infection in almost any tissue or organ.


See the list below:

  • The spores of H capsulatum (microconidia) become airborne when soil is disturbed.
  • High numbers of spores are present in microfoci of soil heavily contaminated with bird or bat droppings, such areas as under bird roosts or in caves (see the image below).
    Starling roost in Alabama. Starling roost in Alabama.
  • Urban and suburban outbreaks in endemic areas are often associated with large-scale construction or cleaning projects in which soil is disturbed. A recent large outbreak at a high school was associated with roto-tilling soil under a known bird roost during school hours. [2]
  • The microconidia (1-5 µm in diameter) are easily inhaled and deposited in distal air spaces.
  • At body temperature, proliferation of the yeast (infective) form of the organism occurs within 3-5 days.
  • Histoplasmosis can occur in almost all mammals. Although the fungus thrives in bird droppings, birds are not infected. However, bats can be infected with H capsulatum. Direct animal-to-human or human-to-human transmissions are not thought to occur.
Contributor Information and Disclosures

James S Hagood, MD Professor of Pediatrics and Chief, Division of Respiratory Medicine, Department of Pediatrics, University of California, San Diego, School of Medicine and Rady Children's Hospital of San Diego

James S Hagood, MD is a member of the following medical societies: American Thoracic Society

Disclosure: Nothing to disclose.


Gulnur Com, MD Pediatric Pulmonologist, University of Arkansas for Medical Sciences Children's Hospital

Gulnur Com, MD is a member of the following medical societies: American Academy of Pediatrics, American Thoracic Society, Cystic Fibrosis Foundation

Disclosure: Nothing to disclose.

Asad Ansari, MD, MPH Attending Physician, Pediatric Pulmonology and Infectious Diseases, Memorial Children's Hospital

Asad Ansari, MD, MPH is a member of the following medical societies: American Academy of Pediatrics, American College of Chest Physicians, American Thoracic Society, Infectious Diseases Society of America, Pediatric Infectious Diseases Society

Disclosure: Nothing to disclose.

Specialty Editor Board

Mary L Windle, PharmD Adjunct Associate Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Nothing to disclose.

Larry I Lutwick, MD Professor of Medicine, State University of New York Downstate Medical School; Director, Infectious Diseases, Veterans Affairs New York Harbor Health Care System, Brooklyn Campus

Larry I Lutwick, MD is a member of the following medical societies: American College of Physicians, Infectious Diseases Society of America

Disclosure: Nothing to disclose.

Chief Editor

Russell W Steele, MD Clinical Professor, Tulane University School of Medicine; Staff Physician, Ochsner Clinic Foundation

Russell W Steele, MD is a member of the following medical societies: American Academy of Pediatrics, American Association of Immunologists, American Pediatric Society, American Society for Microbiology, Infectious Diseases Society of America, Louisiana State Medical Society, Pediatric Infectious Diseases Society, Society for Pediatric Research, Southern Medical Association

Disclosure: Nothing to disclose.

Additional Contributors

Glenn Fennelly, MD, MPH Director, Division of Infectious Diseases, Lewis M Fraad Department of Pediatrics, Jacobi Medical Center; Clinical Associate Professor of Pediatrics, Albert Einstein College of Medicine

Glenn Fennelly, MD, MPH is a member of the following medical societies: Pediatric Infectious Diseases Society

Disclosure: Nothing to disclose.

  1. Lo MM, Mo JQ, Dixon BP, Czech KA. Disseminated histoplasmosis associated with hemophagocytic lymphohistiocytosis in kidney transplant recipients. Am J Transplant. 2010 Mar. 10(3):687-91. [Medline].

  2. 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. 2004 Oct. 23(10):909-14. [Medline].

  3. McKinsey DS, McKinsey JP. Pulmonary histoplasmosis. Semin Respir Crit Care Med. 2011 Dec. 32(6):735-44. [Medline].

  4. Wheat LJ, Kauffman CA. Histoplasmosis. Infect Dis Clin North Am. Mar 2003. 17(1):1-19, vii. [Medline].

  5. Rosenthal J, Brandt KD, Wheat LJ, Slama TG. Rheumatologic manifestations of histoplasmosis in the recent Indianapolis epidemic. Arthritis Rheum. 1983 Sep. 26(9):1065-70. [Medline].

  6. AETC. Clinical Manual for Management of the HIV-Infected Adult. AETC National Resource Center [serial online]. Available at Accessed: January 11, 2007.

  7. Mandell GL, Bennett JE, Dolin R. Histoplasmosis. Principles and Practice of Infectious Diseases. 6th ed. Oxford, England: Churchill Livingstone; 2004.

  8. 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. 2012 Feb. 119(2):327-32. [Medline].

  9. Wheat LJ, Musial CE, Jenny-Avital E. Diagnosis and management of central nervous system histoplasmosis. Clin Infect Dis. 2005 Mar 15. 40(6):844-52. [Medline].

  10. Rangel-Castilla L, Hwang SW, White AC, Zhang YJ. Neuroendoscopic Diagnosis of Central Nervous System Histoplasmosis with Basilar Arachnoiditis. World Neurosurg. 2011 Nov 7. [Medline].

  11. Wheat LJ. Antigen detection, serology, and molecular diagnosis of invasive mycoses in the immunocompromised host. Transpl Infect Dis. 2006 Sep. 8(3):128-39. [Medline].

  12. 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. 2009 Mar. 16(3):320-2. [Medline].

  13. 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].

  14. O'Shaughnessy EM, Shea YM, Witebsky FG. Laboratory diagnosis of invasive mycoses. Infect Dis Clin North Am. Mar 2003. 17(1):135-58. [Medline].

  15. 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. 2007 May 15. [Medline].

  16. Adderson EE. Histoplasmosis in a pediatric oncology center. J Pediatr. 2004 Jan. 144(1):100-6. [Medline].

  17. 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].

  18. Pitisuttithum P, Negroni R, Graybill JR, et al. Activity of posaconazole in the treatment of central nervous system fungal infections. J Antimicrob Chemother. 2005 Oct. 56(4):745-55. [Medline].

  19. 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].

  20. Restrepo A, Tobon A, Clark B, et al. Salvage treatment of histoplasmosis with posaconazole. J Infect. 2007 Apr. 54(4):319-27. [Medline].

  21. Myint T, Anderson AM, Sanchez A, Farabi A, Hage C, Baddley JW, et al. Histoplasmosis in patients with human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS): multicenter study of outcomes and factors associated with relapse. Medicine (Baltimore). 2014 Jan. 93(1):11-8. [Medline].

  22. Antachopoulos C, Walsh TJ. New agents for invasive mycoses in children. Curr Opin Pediatr. 2005 Feb. 17(1):78-87. [Medline].

  23. 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. 1969 Apr. 99(4):Suppl:1-132. [Medline].

  24. George R, Penn R. Histoplasmosis. Sarosi GA, Davies SF, eds. Fungal Diseases of the Lung. New York, NY: Raven; 1993. 39-50.

  25. 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].

  26. Hamilton AJ. Serodiagnosis of histoplasmosis, paracoccidioidomycosis and penicilliosis marneffei; current status and future trends. Med Mycol. Dec 1998. 36(6):351-64. [Medline].

  27. Joseph Wheat L. Current diagnosis of histoplasmosis. Trends Microbiol. 2003 Oct. 11(10):488-94. [Medline].

  28. Keating GM. Posaconazole. Drugs. 2005. 65(11):1553-67. [Medline].

  29. Kumar N, Singh S, Govil S. Adrenal histoplasmosis: clinical presentation and imaging features in nine cases. Abdom Imaging. 2003 Sep-Oct. 28(5):703-8. [Medline].

  30. Kurowski R, Ostapchuk M. Overview of histoplasmosis. Am Fam Physician. 2002 Dec 15. 66(12):2247-52. [Medline].

  31. Levitz SM. Overview of host defenses in fungal infections. Clin Infect Dis. 1992 Mar. 14 Suppl 1:S37-42. [Medline].

  32. Mathisen DJ, Grillo HC. Clinical manifestation of mediastinal fibrosis and histoplasmosis. Ann Thorac Surg. Dec 1992. 54(6):1053-7; discussion 1057-8. [Medline].

  33. Mocherla S, Wheat LJ. Treatment of histoplasmosis. Semin Respir Infect. 2001 Jun. 16(2):141-8. [Medline].

  34. Murray JF, Nadel JA. Histoplasmosis. Textbook of Respiratory Medicine. 4th ed. 2005. 1045-55.

  35. Wheat J. Histoplasmosis. Experience during outbreaks in Indianapolis and review of the literature. Medicine (Baltimore). 1997 Sep. 76(5):339-54. [Medline].

  36. [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. 2000 Apr. 30(4):688-95. [Medline].

  37. Wiedermann BL. Histoplasmosis. Feigin RD, Cherry JD, Fletcher J, eds. Textbook of Pediatric Infectious Diseases. WB Saunders; 1998. 2337-50.

Hilar lymphadenopathy in an 11-year-old child.
Map demonstrates the distribution of histoplasmin skin-test positivity by region. Used with permission from the American Thoracic Society.
Hematoxylin and eosin stain of infected lung tissue. Histoplasma organisms appear to have a false capsule.
Starling roost in Alabama.
Acute pulmonary syndrome in a 16-year-old female adolescent.
Fibrosing mediastinitis with mediastinal widening and tracheal deviation.
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