Histoplasmosis differential diagnosis

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Associate Editor(s)-in-Chief: Prince Tano Djan, BSc, MBChB [2], Aravind Kuchkuntla, M.B.B.S[3]


Patients with acute and chronic pulmonary histoplasmosis present with features similar to pneumonia. Therefore it must be differentiated from conditions presenting with cough, fever and dyspnea such as tuberculosis, sarcoidosis and other fungal infections.

Differentiating Histoplasmosis from other Diseases

The following table is a list of diseases presenting with similar features of histoplasmosis such as cough and fever:

Pathogen Disease Geographic distribution High risk Groups Differentiating features Microscopic findings
Physical exam Laboratory findings
Fungal Histoplasmosis Mississippi and Ohio River valleys
  • Cave dwellers
  • Soil that contains bird or bat dropping[1]
  • Urine antigen testing
Yeast are typically smaller, with narrow-based budding, found intracellularly within macrophages
Coccidioidomycosis Southwestern US region Opportunistic infection seen in AIDS Serologic tests( enzyme immune assay )more sensitive Characteristic spherule appearance
Paracoccidioidomycosis[3] Central and South america Opportunistic infection seen in AIDS
  • Elevated liver enzymes
Smaller fungi with thin cell walls, forming mariner wheel appearance, circumferentially surrounding the parent cell.( Captain wheel appearance )
Sporotrichosis Ubiquitous Gardeners [4] + Sporotrichin skin test Finger or cigar shaped yeast.
Aspergillosis[5] Ubiquitous Cell wall detection using galactomannan antigen detection, Beta-D-glucan detection test. Septated hyphae with acute angle branching
Bacterial Anthrax Ubiquitous Live stock handlers NonmotileGram-positiveaerobic or facultatively anaerobicendospore-forming, rod-shaped bacterium
Legionella Ubiquitous Chronic lung disease

Building water systems

  • + Urine Antigen
Gram negative bacterium
Tuberculosis Asia,Africa Ill contact individuals Aerobicnon-encapsulatednon-motileacid-fast bacillus
Listeriosis Ubiquitous Pregnant women [8]

Adults > 65


flagellatedcatalase-positive, facultative intracellularanaerobicnonsporulatingGram-positive bacillus

Mexico, South and Central America

People who take unpasteurized dairy products Gram-negative bacteria,non-motile, encapsulated coccobacilli.
Scrub typhus Asia-Pacific region



  • Indirect immunofluorescence
Gram-negative α-proteobacterium  intracellular parasite
Leptospirosis Temperate, tropical climates. People who work with animals
  • Antibodies labelled with fluorescent markers positive for leptospires.
Spiral-shaped bacteria with hooked ends on dark-field.
Cat scratch fever Ubiquitous cat licking a person's open wound, or bites or scratches a person[11]
  • enzymatic immunoassay positive for antibody to B henselae
  • lymphocytosis
Gram-negative bacteria. facultative intracellular parasites
Viral Chickenpox
  • Spots appearing in two or three waves
Whole infected cell (wc) ELISA for IgG.
Coxsackie A virus Children attending day care[13] Painful blisters in the mouth, palms and on the feet.

Rash, appears after episode of high fever.

Clinically diagnosed
Others Primary lung cancer Age >65 CT guided bronchoscopy + for malignant cells


  1. Information for Healthcare Professionals about Histoplasmosis. Centers for Disease Control and Prevention. 2015. Available at: http://www.cdc.gov/fungal/diseases/histoplasmosis/health-professionals.html. Accessed February 2, 2016.
  2. Brown J, Benedict K, Park BJ, Thompson GR (2013). "Coccidioidomycosis: epidemiology". Clin Epidemiol. 5: 185–97. doi:10.2147/CLEP.S34434. PMC 3702223. PMID 23843703.
  3. Marques SA (2013). "Paracoccidioidomycosis: epidemiological, clinical, diagnostic and treatment up-dating". An Bras Dermatol. 88 (5): 700–11. doi:10.1590/abd1806-4841.20132463. PMC 3798345. PMID 24173174.
  4. Mahajan VK (2014). "Sporotrichosis: an overview and therapeutic options". Dermatol Res Pract. 2014: 272376. doi:10.1155/2014/272376. PMC 4295339. PMID 25614735.
  5. Sherif R, Segal BH (2010). "Pulmonary aspergillosis: clinical presentation, diagnostic tests, management and complications". Curr Opin Pulm Med. 16 (3): 242–50. doi:10.1097/MCP.0b013e328337d6de. PMC 3326383. PMID 20375786.
  6. Hicks CW, Sweeney DA, Cui X, Li Y, Eichacker PQ (2012). "An overview of anthrax infection including the recently identified form of disease in injection drug users". Intensive Care Med. 38 (7): 1092–104. doi:10.1007/s00134-012-2541-0. PMC 3523299. PMID 22527064.
  7. Schuetz P, Haubitz S, Christ-Crain M, Albrich WC, Zimmerli W, Mueller B (2013). "Hyponatremia and anti-diuretic hormone in Legionnaires' disease". BMC Infect. Dis. 13: 585. doi:10.1186/1471-2334-13-585. PMC 3880094. PMID 24330484.
  8. Lamont RF, Sobel J, Mazaki-Tovi S, Kusanovic JP, Vaisbuch E, Kim SK, Uldbjerg N, Romero R (2011). "Listeriosis in human pregnancy: a systematic review". J Perinat Med. 39 (3): 227–36. doi:10.1515/JPM.2011.035. PMC 3593057. PMID 21517700.
  9. Zhou YH, Xia FQ, Van Poucke S, Zheng MH (2016). "Successful Treatment of Scrub Typhus-Associated Hemophagocytic Lymphohistiocytosis With Chloramphenicol: Report of 3 Pediatric Cases and Literature Review". Medicine (Baltimore). 95 (8): e2928. doi:10.1097/MD.0000000000002928. PMC 4779037. PMID 26937940.
  10. Iroh Tam PY, Obaro SK, Storch G (2016). "Challenges in the Etiology and Diagnosis of Acute Febrile Illness in Children in Low- and Middle-Income Countries". J Pediatric Infect Dis Soc. 5 (2): 190–205. doi:10.1093/jpids/piw016. PMID 27059657.
  11. Gouriet F, Lepidi H, Habib G, Collart F, Raoult D (2007). "From cat scratch disease to endocarditis, the possible natural history of Bartonella henselae infection". BMC Infect. Dis. 7: 30. doi:10.1186/1471-2334-7-30. PMC 1868026. PMID 17442105.
  12. De Paschale M, Clerici P (2016). "Microbiology laboratory and the management of mother-child varicella-zoster virus infection". World J Virol. 5 (3): 97–124. doi:10.5501/wjv.v5.i3.97. PMC 4981827. PMID 27563537.
  13. Flett K, Youngster I, Huang J, McAdam A, Sandora TJ, Rennick M, Smole S, Rogers SL, Nix WA, Oberste MS, Gellis S, Ahmed AA (2012). "Hand, foot, and mouth disease caused by coxsackievirus a6". Emerging Infect. Dis. 18 (10): 1702–4. doi:10.3201/eid1810.120813. PMC 3471644. PMID 23017893.