Cryptococcosis

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Classification according to ICD-10
B45 Cryptococcosis
ICD-10 online (WHO version 2019)
Cryptococcosis of the lungs

The cryptococcosis (also Busse-Buschke's disease according to the Erstbeschreibern Otto buses and Abraham Buschke ) is a fungal infection that primarily by Cryptococcus neoformans is caused. The infection usually proceeds primarily without any symptoms. A disease occurs in humans, especially in immune deficiency before, especially in the final stage of HIV disease infection (AIDS). Another Cryptococcus species, Cryptococcus gattii , which until recently was considered a variety of C. neoformans , is becoming increasingly important . With a mortality rate of 25 percent, C. gattii is more dangerous than C. neoformans and has recently appeared in a variant that is even more virulent and can also infect healthy people and domesticated animals such as dogs, cats and sheep. Infections by other Cryptococcus species are a rarity.

Occurrence

Cryptococci can be detected in the soil on tree bark or on grass and vegetables. Pigeon droppings and dust emanating from them are of particular importance in the transmission for humans. The more virulent pathogen Cryptococcus gattii seems to occupy an ecological niche in eucalyptus trees . C. gattii is typically found in the tropics and subtropics. At the end of the last century, however, the pathogen spread to humans and animals in the northwest of the American continent.

According to current estimates, around one million cases of cryptococcal meningoencephalitis are diagnosed annually worldwide in people with HIV infection alone, and more than 600,000 people die from the disease each year.

Diagnosis

To establish the diagnosis, the detection of cryptococci from otherwise sterile body tissues and fluids is necessary. Cryptococcus can be detected by light microscopy in an ink color . The non-staining polysaccharide capsule are characteristic. For the inexperienced examiner, leukocytes or lipid artifacts can simulate cryptococci. Evidence is possible from blood and nerve water . The light microscopic test can be false negative if the number of pathogens is low. Antigens from the polysaccharide capsule can also be detected in blood or nerve water. A quick test strip is now available for this purpose . The cultivation of pathogens from blood or nerve water is more time-consuming but just as diagnostic. The typical nerve fluid findings in cryptococcal meningitis show increased protein values ​​and the presence of lymphocytes and monocytes . With isolated lung involvement, blood and nerve water are often negative for the test for the fungal capsule antigen.

Disease emergence

In humans, C. neoformans mainly affects the lungs through inhalation of spore-containing dust, then other organs are also infected with cryptococci via the bloodstream ( hematogenous ). The infection of the meninges (meninges) and possibly the brain parenchyma (cryptococcal meningitis or - meningoencephalitis ) rarely causes granulomas in the brain . Infection of the skin or bone tissue is possible, but less common. In HIV patients with permanent immune deficiency, the prostate appears to be a reservoir of pathogens.

Signs of illness

Pulmonary cryptococcosis manifests itself as a cough that produces mucus. Only a minority of complaints with lung involvement show fever. The skin involvement in cryptococcosis can result in typical fungal growth patterns of central reddening with a rim wall, but can also result in completely uncharacteristic reddening of the skin or the formation of small tumor-like skin manifestations. Patients with central nervous system involvement show signs of chronic meningitis. Often there is a gradual process lasting several weeks. It starts with a headache, fever, and lethargy . The typical signs of meningism such as neck pain are often absent. With advanced brain tissue infestation, paralysis, visual disturbances, but also mental and cognitive deficits up to full dementia appear .

treatment

The antimycotics amphotericin B and flucytosine as well as the group of azoles ( fluconazole , voriconazole , posaconazole , itraconazole and others) are available for treating the disease . Due to its mechanism of action, amphotericin B is regarded as fungicidal and fluconazole as fungistatic. Amphotericin B carries the risk of kidney damage . This can be avoided by giving the much more expensive liposomal dosage form. The choice of drug, dosage form and duration of treatment depend on the patient's immune status and the spread of the disease. In the case of CNS involvement or severe involvement of the respiratory tract, inductions with amphotericin B and possibly flucytosine are recommended for several weeks. This is followed by maintenance therapy, usually lasting months or years, with an azole preparation in tablet form. Corticosteroids can be considered as supportive treatment in severe respiratory tract involvement in terms of ARDS . However, they should be avoided in the case of CNS involvement. For refractory relapses, treatment with an antifungal agent in combination with interferon can be considered. In patients with cryptococcal meningitis, the intracranial pressure often has to be lowered by punctures or the creation of a shunt to avoid permanent brain and nerve damage. A disease of the immune system that is restricted to the lungs can be treated with fluconazole as monotherapy for several months.

In untreated AIDS patients who simultaneously have CNS infestation from cryptococcosis, a worsening of neurological symptoms can be triggered by restoring the immune system by starting antiretroviral therapy . Whether this is a reason to interrupt antiretroviral therapy if necessary and only treat cryptococcosis at first is controversial.

Prospect of healing

Cryptococcosis caused by C. neoformans is always life-threatening for immunosuppressed people: if left untreated, it is usually fatal and even with adequate treatment, the risk of death for HIV patients is almost 20%. Neurological deficits that are triggered by meningitis often no longer regress. Relapses are very common in people with permanently immunocompromised and can also occur in people with healthy immune systems. Predictive factors for a complicated course are high intracranial pressure, high multiplication of pathogens in the nerve water with only a low inflammatory reaction. The multiplication of pathogens can be estimated from the lowering of the sugar level in the nerve water or the high antigen titre. Likewise, patients who can be detected by light microscopy from blood or nerve water are to be regarded as patients at high risk.

prevention

HIV patients with advanced disease should be treated prophylactically with an azole in tablet form as long as they have T cell counts below 200 / µl.

Cryptococcosis in the cat

In cats, C. neoformans mainly affects the upper respiratory tract and causes persistent nasal and eye discharge, the formation of granulation tissue in the nasal and paranasal sinuses , melting of the facial cranial bones and tumor-like swellings on the face. Infestation of the skin, the brain or the lungs is less common. Ketoconazole , itraconazole or fluconazole are used for therapy in cats ; the combination of flucytosine with amphotericin B or ketoconazole is also possible.

Research history

The pathogen Cryptococcus neoformans (formerly Torulopsis neoformans, as the causative agent of cryptococcosis, also known as torulosis and European blastomycosis ) was discovered independently at the end of the 19th century. Abraham Buschke and Otto Busse isolated him from a lesion on the shin. The Italian Francesco Sanfelice isolated the mushroom from peach juice. In 1905, meningeal cryptococcosis was first described by David Paul von Hansemann . In the second half of the twentieth century, the American pathologists RD Baker and RK Haugen described the role of the lungs as the portal of entry and primary focus.

Individual evidence

  1. ↑ Dangerous yeast. Image of Science , April 23, 2010, accessed September 9, 2019 .
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  3. ^ DH Ellis, TJ Pfeiffer: Natural habitat of Cryptococcus neoformans var. Gattii. In: J Clin Microbiol. 1990 Jul; 28 (7), pp. 1642-1644. PMID 2199524
  4. ↑ Kausik Datta, Karen H. Bartlett, Rebecca Baer, ​​Edmond Byrnes, Eleni Galanis: Spread of Cryptococcus gattii into Pacific Northwest Region of the United States. In: Emerg Infect Dis. 2009 Aug; 15 (8), pp. 1185-1191. doi: 10.3201 / eid1508.081384
  5. ^ BJ Park et al .: Estimation of the current global burden of cryptococcal meningitis among persons living with HIV / AIDS . In: AIDS . tape 23 , no. 4 , 2009, p. 525-530 , PMID 19182676 .
  6. ↑ a b c d e f Arturo Casadevall: Cryptococcosis. In: Dan L. Longo, Anthony A. Fauci, Dennis Kasper, Stephen L. Hauser, J. Larry Jameson, Joseph Localzo: Harrison's Principles of Internal Medicine. 18th edition. New York 2012, pp. 1648-1651.
  7. Jump up ↑ J. Hansen, ES Slechta, MA Gates-Hollingsworth, B. Neary, AP Barker: Large-scale evaluation of the immuno-mycologics lateral flow and enzyme-linked immunoassays for detection of cryptococcal antigen in serum and cerebrospinal fluid. In: Clin Vaccine Immunol. 2013 Jan; 20 (1), pp. 52–55. doi: 10.1128 / CVI.00536-12 PMID 23114703
  8. ↑ K. Becker, B. Ing, G. Canthomas, H. Herbst, W. Fegeler: Pathogen-related diseases. In: W. Böcker, H. Denk, Ph. U. Heitz, H. Moch: Pathology. 4th edition. Munich 2008, pp. 1192–1193.
  9. ↑ IDSA Guideline: John R. Perfect et al: Clinical Practice Guidelines for the Management of Cryptococcal Disease: 2010 Update by the Infectious Diseases Society of America. In: Clin Infect Dis. (2010) 50 (3), pp. 291-322 doi: 10.1086 / 649858
  10. ^ JF Gibson, SA Johnston: Immunity to Cryptococcus neoformans and C. gattii during cryptococcosis. In: Fungal Genet Biol. 2014 Dec 12, pp. S1087-S1845 (14) 00215-1. doi: 10.1016 / j.fgb.2014.11.006 PMID 25498576
  11. ↑ B. Njei, EJ Kongnyuy, S. Kumar, MP Okwen, MJ Sankar, L. Mbuagbaw: Optimal timing for antiretroviral therapy initiation in patients with HIV infection and concurrent cryptococcal meningitis. In: Cochrane Database of Systematic Reviews. 2013, Issue 2. Art. No .: CD009012. doi: 10.1002 / 14651858.CD009012.pub2
  12. ↑ M. Desnos-Ollivier et al .: Mixed Infections and In Vivo Evolution in the Human Fungal Pathogen Cryptococcus neoformans . In: MBio . tape 18 , no. 1 , 2010, p. e00091 – e00010 , PMID 20689742 .
  13. ^ Albert Weber et al.: Case report: cryptococcosis in a cat. In: Small Animal Practice. 37: 255-258 (1992).
  14. ↑ Chiara Noli, Fabia Scarampella: Practical Dermatology in Dogs and Cats. 3. Edition. Schlütersche, 2013, p. 261.
  15. ↑ Karl Wurm, AM Walter: Infectious Diseases. In: Ludwig Heilmeyer (ed.): Textbook of internal medicine. Springer-Verlag, Berlin / Göttingen / Heidelberg 1955; 2nd edition, ibid. 1961, pp. 9-223, here: p. 213.
  16. ^ TG Mitchell, JR Perfect, TG Mitchell, JR Perfect: Cryptococcosis in the Era of AIDS -100 Years after the Discovery of Cryptococcus neoformans. In: Clin Microbiol Rev. 1995 Oct; 8 (4), pp. 515-548. PMID 8665468

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