Diagnostic Considerations

The following are other causes of intracranial mass lesions and infections:

Pyogenic abscess
Nocardial abscess
Aspergillus abscess
Hemorrhages
Lymphomas
Other neoplasms
Mycoses
Meningeal metastases
Chronic, benign lymphocytic meningitis
Mycobacterium tuberculous infection
Histoplasma capsulatum infection
Acne

Differential Diagnoses

Workup

Anderson DJ, Schmidt C, Goodman J, Pomeroy C. Cryptococcal disease presenting as cellulitis. Clin Infect Dis. 1992 Mar. 14(3):666-72. [QxMD MEDLINE Link].
Orsini J, Nowakowski J, Delaney V, Sakoulas G, Wormser GP. Cryptococcal infection presenting as cellulitis in a renal transplant recipient. Transpl Infect Dis. 2009 Feb. 11(1):68-71. [QxMD MEDLINE Link].
[Guideline] Saag MS, Graybill RJ, Larsen RA, Pappas PG, Perfect JR, Powderly WG, et al. Practice guidelines for the management of cryptococcal disease. Infectious Diseases Society of America. Clin Infect Dis. 2000 Apr. 30(4):710-8. [QxMD MEDLINE Link].
[Guideline] Kaplan JE, Masur H, Holmes KK. Guidelines for preventing opportunistic infections among HIV-infected persons--2002. Recommendations of the U.S. Public Health Service and the Infectious Diseases Society of America. MMWR Recomm Rep. 2002 Jun 14. 51:1-52. [QxMD MEDLINE Link].
[Guideline] Perfect JR, Dismukes WE, Dromer F, Goldman DL, Graybill JR, Hamill RJ, et al. Clinical practice guidelines for the management of cryptococcal disease: 2010 update by the infectious diseases society of america. Clin Infect Dis. 2010 Feb 1. 50 (3):291-322. [QxMD MEDLINE Link].
Busse O. Ueber parasitare zelleninschlusse und ihre zuchtung. Zentralbl. Bakterial. 1894. 16:175-80.
Buschke A. Ueber eine durch Coccidien Hervergerufene Krankheit des menschen. Deutsche Med. Wochenschr. 1895. 21 (3):14.
Vélez N, Escandón P. Distribution and association between environmental and clinical isolates of Cryptococcus neoformans in Bogotá-Colombia, 2012-2015. Mem Inst Oswaldo Cruz. 2016 Oct. 111 (10):642-648. [QxMD MEDLINE Link].
Nyazika TK, Hagen F, Meis JF, Robertson VJ. Cryptococcus tetragattii as a major cause of cryptococcal meningitis among HIV-infected individuals in Harare, Zimbabwe. J Infect. 2016 Jun. 72 (6):745-52. [QxMD MEDLINE Link].
Fink JN, Barboriak JJ, Kaufman L. Cryptococcal antibodies in pigeon breeders' disease. J Allergy. 1968 May. 41 (5):297-301. [QxMD MEDLINE Link].
Panackal AA, Wuest SC, Lin YC, Wu T, Zhang N, Kosa P, et al. Paradoxical Immune Responses in Non-HIV Cryptococcal Meningitis. PLoS Pathog. 2015 May. 11 (5):e1004884. [QxMD MEDLINE Link].
Goldman DL, Khine H, Abadi J, Lindenberg DJ, Pirofski La, Niang R, et al. Serologic evidence for Cryptococcus neoformans infection in early childhood. Pediatrics. 2001 May. 107 (5):E66. [QxMD MEDLINE Link].
Macdougall L, Fyfe M, Romney M, Starr M, Galanis E. Risk Factors for Cryptococcus gattii Infection, British Columbia, Canada. Emerg Infect Dis. 2011 Feb. 17(2):193-9. [QxMD MEDLINE Link].
Bratton EW, El Husseini N, Chastain CA, Lee MS, Poole C, Stürmer T, et al. Approaches to antifungal therapies and their effectiveness among patients with cryptococcosis. Antimicrob Agents Chemother. 2013 Jun. 57 (6):2485-95. [QxMD MEDLINE Link].
Perfect JR, Bicanic T. Cryptococcosis diagnosis and treatment: What do we know now. Fungal Genet Biol. 2015 May. 78:49-54. [QxMD MEDLINE Link].
Alanio A. Dormancy in Cryptococcus neoformans: 60 years of accumulating evidence. J Clin Invest. 2020 Jul 1. 130 (7):3353-3360. [QxMD MEDLINE Link].
Rittershaus PC, Kechichian TB, Allegood JC, Merrill AH Jr, Hennig M, Luberto C. Glucosylceramide synthase is an essential regulator of pathogenicity of Cryptococcus neoformans. J Clin Invest. 2006 Jun. 116(6):1651-9. [QxMD MEDLINE Link]. [Full Text].
Beardsley J, Wolbers M, Kibengo FM, et al. Adjunctive Dexamethasone in HIV-Associated Cryptococcal Meningitis. N Engl J Med. 2016 Feb 11. 374 (6):542-54. [QxMD MEDLINE Link].
Hagen F, Ceresini PC, Polacheck I, et al. Ancient dispersal of the human fungal pathogen Cryptococcus gattii from the Amazon rainforest. PLoS One. 2013. 8 (8):e71148. [QxMD MEDLINE Link].
Speed B, Dunt D. Clinical and host differences between infections with the two varieties of Cryptococcus neoformans. Clin Infect Dis. 1995 Jul. 21(1):28-34; discussion 35-6. [QxMD MEDLINE Link].
Lewis JL, Rabinovich S. The wide spectrum of cryptococcal infections. Am J Med. 1972 Sep. 53(3):315-22. [QxMD MEDLINE Link].
Sun HY, Alexander BD, Lortholary O, et al. Unrecognized pretransplant and donor-derived cryptococcal disease in organ transplant recipients. Clin Infect Dis. 2010 Nov 1. 51(9):1062-9. [QxMD MEDLINE Link].
Gazzoni AF, Oliveira Fde M, Salles EF, Mayayo E, Guarro J, Capilla J, et al. Unusual morphologies of Cryptococcus spp. in tissue specimens: report of 10 cases. Rev Inst Med Trop Sao Paulo. 2010 May-Jun. 52 (3):145-9. [QxMD MEDLINE Link].
Lahmer T, Brandl A, Rasch S, Schmid RM, Huber W. Fungal Peritonitis: Underestimated Disease in Critically Ill Patients with Liver Cirrhosis and Spontaneous Peritonitis. PLoS One. 2016. 11 (7):e0158389. [QxMD MEDLINE Link].
Fiore M, Leone S. Spontaneous fungal peritonitis: Epidemiology, current evidence and future prospective. World J Gastroenterol. 2016 Sep 14. 22 (34):7742-7. [QxMD MEDLINE Link].
Baddley JW, Perfect JR, Oster RA, Larsen RA, Pankey GA, Henderson H, et al. Pulmonary cryptococcosis in patients without HIV infection: factors associated with disseminated disease. Eur J Clin Microbiol Infect Dis. 2008 Oct. 27(10):937-43. [QxMD MEDLINE Link].
Lindsley MD, Mekha N, Baggett HC, Surinthong Y, Autthateinchai R, Sawatwong P, et al. Evaluation of a newly developed lateral flow immunoassay for the diagnosis of cryptococcosis. Clin Infect Dis. 2011 Aug. 53(4):321-5. [QxMD MEDLINE Link]. [Full Text].
Rivet-Dañon D, Guitard J, Grenouillet F, Gay F, Ait-Ammar N, Angoulvant A, et al. Rapid diagnosis of cryptococcosis using an antigen detection immunochromatographic test. J Infect. 2015 May. 70 (5):499-503. [QxMD MEDLINE Link].
Ogundeji AO, Albertyn J, Pohl CH, Sebolai OM. Method for identification of Cryptococcus neoformans and Cryptococcus gattii useful in resource-limited settings. J Clin Pathol. 2016 Apr. 69 (4):352-7. [QxMD MEDLINE Link].
Pappas PG, Perfect J, Larsen RA, et al. Cryptococcus in HIV-negative patients: analysis of 306 cases [abstract 101]. 36th Annual Meeting of the Infectious Diseases Society of America (Denver, CO). Alexandria, VA: Infectious Diseases Society of America; 1998.
Lortholary O, Fontanet A, Mémain N, Martin A, Sitbon K, Dromer F. Incidence and risk factors of immune reconstitution inflammatory syndrome complicating HIV-associated cryptococcosis in France. AIDS. 2005 Jul 1. 19(10):1043-9. [QxMD MEDLINE Link].
Sungkanuparph S, Filler SG, Chetchotisakd P, Pappas PG, Nolen TL, Manosuthi W, et al. Cryptococcal immune reconstitution inflammatory syndrome after antiretroviral therapy in AIDS patients with cryptococcal meningitis: a prospective multicenter study. Clin Infect Dis. 2009 Sep 15. 49(6):931-4. [QxMD MEDLINE Link].
Bisson GP, Molefi M, Bellamy S, Thakur R, Steenhoff A, Tamuhla N, et al. Early Versus Delayed Antiretroviral Therapy and Cerebrospinal Fluid Fungal Clearance in Adults With HIV and Cryptococcal Meningitis. Clin Infect Dis. 2013 Feb 6. [QxMD MEDLINE Link].
French N, Gray K, Watera C, Nakiyingi J, Lugada E, Moore M, et al. Cryptococcal infection in a cohort of HIV-1-infected Ugandan adults. AIDS. 2002 May 3. 16 (7):1031-8. [QxMD MEDLINE Link].
Jarvis JN, Harrison TS, Lawn SD, Meintjes G, Wood R, Cleary S. Cost effectiveness of cryptococcal antigen screening as a strategy to prevent HIV-associated cryptococcal meningitis in South Africa. PLoS One. 2013. 8 (7):e69288. [QxMD MEDLINE Link].
Meya DB, Manabe YC, Castelnuovo B, Cook BA, Elbireer AM, Kambugu A, et al. Cost-effectiveness of serum cryptococcal antigen screening to prevent deaths among HIV-infected persons with a CD4+ cell count < or = 100 cells/microL who start HIV therapy in resource-limited settings. Clin Infect Dis. 2010 Aug 15. 51 (4):448-55. [QxMD MEDLINE Link].
Smith RM, Nguyen TA, Ha HT, Thang PH, Thuy C, Lien TX, et al. Prevalence of cryptococcal antigenemia and cost-effectiveness of a cryptococcal antigen screening program--Vietnam. PLoS One. 2013. 8 (4):e62213. [QxMD MEDLINE Link].
Kimaro GD, Mfinanga S, Simms V, Kivuyo S, Bottomley C, Hawkins N, et al. The costs of providing antiretroviral therapy services to HIV-infected individuals presenting with advanced HIV disease at public health centres in Dar es Salaam, Tanzania: Findings from a randomised trial evaluating different health care strategies. PLoS One. 2017. 12 (2):e0171917. [QxMD MEDLINE Link].
Coelho C, Casadevall A. Cryptococcal therapies and drug targets: the old, the new and the promising. Cell Microbiol. 2016 Jun. 18 (6):792-9. [QxMD MEDLINE Link].
Beardsley J, Wolbers M, Kibengo FM, Ggayi AB, Kamali A, Cuc NT. Adjunctive Dexamethasone in HIV-Associated Cryptococcal Meningitis. N Engl J Med. 2016 Feb 11. 374 (6):542-54. [QxMD MEDLINE Link].
Eriksson U, Seifert B, Schaffner A. Comparison of effects of amphotericin B deoxycholate infused over 4 or 24 hours: randomised controlled trial. BMJ. 2001 Mar 10. 322(7286):579-82. [QxMD MEDLINE Link]. [Full Text].
Imhof A, Walter RB, Schaffner A. Continuous infusion of escalated doses of amphotericin B deoxycholate: an open-label observational study. Clin Infect Dis. 2003 Apr 15. 36(8):943-51. [QxMD MEDLINE Link].
Perfect JR, Dismukes WE, Dromer F, Goldman DL, Graybill JR, Hamill RJ, et al. Clinical practice guidelines for the management of cryptococcal disease: 2010 update by the infectious diseases society of america. Clin Infect Dis. 2010 Feb 1. 50 (3):291-322. [QxMD MEDLINE Link].
Pfaller MA, Rhomberg PR, Messer SA, Jones RN, Castanheira M. Isavuconazole, micafungin, and 8 comparator antifungal agents' susceptibility profiles for common and uncommon opportunistic fungi collected in 2013: temporal analysis of antifungal drug resistance using CLSI species-specific clinical breakpoints and proposed epidemiological cutoff values. Diagn Microbiol Infect Dis. 2015 Aug. 82 (4):303-13. [QxMD MEDLINE Link].
Pettit NN, Carver PL. Isavuconazole: A New Option for the Management of Invasive Fungal Infections. Ann Pharmacother. 2015 Jul. 49 (7):825-42. [QxMD MEDLINE Link].
Wiederhold NP, Kovanda L, Najvar LK, Bocanegra R, Olivo M, Kirkpatrick WR, et al. Isavuconazole Is Effective for the Treatment of Experimental Cryptococcal Meningitis. Antimicrob Agents Chemother. 2016 Sep. 60 (9):5600-3. [QxMD MEDLINE Link].
Thompson GR 3rd, Rendon A, Ribeiro Dos Santos R, Queiroz-Telles F, Ostrosky-Zeichner L, Azie N, et al. Isavuconazole Treatment of Cryptococcosis and Dimorphic Mycoses. Clin Infect Dis. 2016 Aug 1. 63 (3):356-62. [QxMD MEDLINE Link].
Pastick KA, Nalintya E, Tugume L, Ssebambulidde K, Stephens N, Evans EE, et al. Cryptococcosis in pregnancy and the postpartum period: Case series and systematic review with recommendations for management. Med Mycol. 2020 Apr 1. 58 (3):282-292. [QxMD MEDLINE Link].
Rahul Nayak & Jianping Xu. Effects of sertraline hydrochloride and fluconazole combinations on Cryptococcus neoformans and Cryptococcus gattii. Mycology. 2010. 1:2:[Full Text].
Zhai B, Wu C, Wang L, Sachs MS, Lin X. The antidepressant sertraline provides a promising therapeutic option for neurotropic cryptococcal infections. Antimicrob Agents Chemother. 2012 Jul. 56 (7):3758-66. [QxMD MEDLINE Link].
Smith KD, Achan B, Hullsiek KH, McDonald TR, Okagaki LH, Alhadab AA, et al. Increased Antifungal Drug Resistance in Clinical Isolates of Cryptococcus neoformans in Uganda. Antimicrob Agents Chemother. 2015 Dec. 59 (12):7197-204. [QxMD MEDLINE Link].
Treviño-Rangel Rde J, Villanueva-Lozano H, Hernández-Rodríguez P, Martínez-Reséndez MF, García-Juárez J, Rodríguez-Rocha H, et al. Activity of sertraline against Cryptococcus neoformans: in vitro and in vivo assays. Med Mycol. 2016 Mar. 54 (3):280-6. [QxMD MEDLINE Link].
Rossato L, Loreto ÉS, Zanette RA, Chassot F, Santurio JM, Alves SH. In vitro synergistic effects of chlorpromazine and sertraline in combination with amphotericin B against Cryptococcus neoformans var. grubii. Folia Microbiol (Praha). 2016 Sep. 61 (5):399-403. [QxMD MEDLINE Link].
Rhein J, Morawski BM, Hullsiek KH, Nabeta HW, Kiggundu R, Tugume L, et al. Efficacy of adjunctive sertraline for the treatment of HIV-associated cryptococcal meningitis: an open-label dose-ranging study. Lancet Infect Dis. 2016 Jul. 16 (7):809-818. [QxMD MEDLINE Link].

Media Gallery

Axial T2-weighted magnetic resonance image shows clustered hyperintensities in the left caudate; these are consistent with enlarged Virchow-Robin spaces caused by small cryptococcomas.

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Author

Pradeep Kumar Mada, MD, MRCP(UK) Consulting Physician in Infectious Diseases, Comanche County Memorial Hospital

Disclosure: Nothing to disclose.

Specialty Editor Board

Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Received salary from Medscape for employment. for: Medscape.

John W King, MD Professor of Medicine, Chief, Section of Infectious Diseases, Director, Viral Therapeutics Clinics for Hepatitis, Louisiana State University School of Medicine in Shreveport; Consultant in Infectious Diseases, Overton Brooks Veterans Affairs Medical Center

John W King, MD is a member of the following medical societies: American Association for the Advancement of Science, American College of Physicians, American Federation for Medical Research, American Society for Microbiology, Association of Subspecialty Professors, Infectious Diseases Society of America, Sigma Xi, The Scientific Research Honor Society

Disclosure: Nothing to disclose.

Chief Editor

Pranatharthi Haran Chandrasekar, MBBS, MD Professor, Chief of Infectious Disease, Department of Internal Medicine, Wayne State University School of Medicine

Pranatharthi Haran Chandrasekar, MBBS, MD is a member of the following medical societies: American College of Physicians, American Society for Microbiology, International Immunocompromised Host Society, Infectious Diseases Society of America

Disclosure: Nothing to disclose.

Additional Contributors

Jeffrey D Band, MD, FACP, FIDSA Professor of Medicine, Oakland University William Beaumont School of Medicine; Health System Chair, Healthcare Epidemiology and International Medicine, Beaumont Health System; Former Chief of Infectious Diseases, Beaumont Hospital; Clinical Professor of Medicine, Wayne State University School of Medicine

Disclosure: Nothing to disclose.

Meredith L DeWitt, MD Fellow, Department of Internal Medicine, Section of Infectious Diseases, Louisiana State University Health Sciences Center

Meredith L DeWitt, MD is a member of the following medical societies: Infectious Diseases Society of America

Disclosure: Nothing to disclose.

Folusakin O Ayoade, MD Assistant Professor of Clinical Medicine, Division of Infectious Diseases, Department of Medicine, University of Miami, Leonard M Miller School of Medicine; Attending Physician in Infectious Diseases, Jackson Health System; Attending Physician in Infectious Diseases, University of Miami Hospital

Folusakin O Ayoade, MD is a member of the following medical societies: American College of Physicians, American Federation for Medical Research, American Medical Association, Infectious Diseases - International Research Initiative, Infectious Diseases Society of America

Disclosure: Nothing to disclose.