Orellanine Mushroom Toxicity

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Orellanine Mushroom Toxicity

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Cortinarius orellanus, the poznan cort mushroom, is one of the few types of mushrooms that can cause fatal poisonings. Of the thousands of mushroom species that are increasingly studied and collected by amateur mushroom hunters, about 100 can cause serious illness, but only about 10 cause death.

People become sick after ingesting mushrooms for several reasons. They may have ingested toxin-containing mushrooms or mushrooms that cause Antabuse-type reactions to alcohol; they may experience difficulty digesting large amounts of mushrooms or have immunologic reactions to mushroom derived antigens.

Cortinarius species (corts) that may contain the orellanine toxin include the following:

The most common of these in North America is probably C gentilis, although C orellanus and C speciosissimus are most often implicated in documented exposures. Presence of C orellanus in North America remains unconfirmed.

Orellanine is the major toxin found in these mushrooms. Orellanine (3,3′,4,4′-tetrahydroxy-2,2′-bipyridine-1,1′-dioxide) is a colorless, crystalline, nephrotoxic compound. [1, 2]  Orelline is a possibly toxic product of orellanine.

Three other polypeptides have been identified: cortinarin A, cortinarin B, and cortinarin C. At least two of those appear to be nephrotoxic in experimental animals.

Mushroom identification is beyond the scope of this text, but existence of corts is one of the many reasons not to eat little brown mushrooms (LBMs).

Patients with orellanine exposure may experience early symptoms because of other components of the mushroom; orellanine appears to be renal specific. Inhibition of alkaline phosphatase decreases production of adenosine triphosphate and disrupts cellular metabolism. Reaction is specific to the epithelium of cells in the proximal tubules and results in tubulointerstitial nephritis and renal failure, with concomitant symptoms and complications. Orellanine seems to cause almost no reaction in glomeruli, although in an animal model, elimination of orellanine was almost exclusively by glomerular filtration. [3]

Studies of orellanine poisoning in rats have shown no signs of acute toxicity apart from renal failure, but a study of orellanine poisoning in mice showed tubular necrosis as well as effects on other organs, as follows [4] :

However, a study of 28 patients with orellanine poisoning noted that no signs of acute damage were present in any other organ.except the kidney. [5]

In 2017, no exposures of orellanine-containing mushrooms were reported to the American Association of Poison Control Centers’ (AAPCC) Toxic Exposure Surveillance System. [6]  A range of 0-8 exposures per year have been reported over the past 14 years. The reports by year can be found at the APPC site.

Unknown mushroom type makes up most mushroom exposures each year, usually accounting for well over 80% of mushroom exposures (eg, 4911 in 2017). However, deaths in this group remain remarkably low (0-2 per year since 1996). [6]

A study published in May 2000 that used data from the National Center for Health Statistics found no difference when compared with AAPCC data in numbers of deaths caused by mushroom exposures. [7]

No accurate global database exists, but mushroom gathering is more common in Eastern and Western Europe than in North America. Most documented cases of orellanine toxicity are from Europe.

A short latent period before onset of illness and renal injury portents more severe renal insult and prolonged period of renal failure than delayed onset of illness. Relatively mild degrees of renal insufficiency may resolve within weeks to months. Some may be treated expectantly without need for hemodialysis. In more severe cases, renal failure can persist months to years requiring chronic hemodialysis or renal transplant. [5]

Few data are available to estimate incidence of orellanine poisoning. Most reported cases of renal failure are from Europe. The AAPCC last reported a recognized Cortinarius exposure with a major effect in outcome (ie, exposure resulted in life-threatening signs or symptoms or resulted in significant residual disability) in 1999. Since 1999 no outcomes have occurred in the major category and only 3 total in the moderate class (ie, signs or symptoms more pronounced, more prolonged, or more systemic in nature than minor symptoms usually indicating the need for some form of treatment, but the patient had no residual disability).

General education regarding dangers of foraging for and ingesting unknown mushrooms is important.

For excellent patient education resources, visit eMedicineHealth’s First Aid and Injuries Center. Also, see eMedicineHealth’s patient education articles Poisoning and Activated Charcoal.

Herrmann A, Hedman H, Rosén J, Jansson D, Haraldsson B, Hellenäs KE. Analysis of the mushroom nephrotoxin orellanine and its glucosides. J Nat Prod. 2012 Oct 26. 75(10):1690-6. [Medline].

Dinis-Oliveira RJ, Soares M, Rocha-Pereira C, Carvalho F. Human and experimental toxicology of orellanine. Hum Exp Toxicol. 2016 Sep. 35 (9):1016-29. [Medline].

Najar D, Haraldsson B, Thorsell A, Sihlbom C, Nyström J, Ebefors K. Pharmacokinetic Properties of the Nephrotoxin Orellanine in Rats. Toxins (Basel). 2018 Aug 17. 10 (8):[Medline]. [Full Text].

Anantharam P, Shao D, Imerman PM, Burrough E, Schrunk D, Sedkhuu T, et al. Improved Tissue-Based Analytical Test Methods for Orellanine, a Biomarker of Cortinarius Mushroom Intoxication. Toxins (Basel). 2016 May 21. 8 (5):[Medline]. [Full Text].

Hedman H, Holmdahl J, Mölne J, Ebefors K, Haraldsson B, Nyström J. Long-term clinical outcome for patients poisoned by the fungal nephrotoxin orellanine. BMC Nephrol. 2017 Apr 3. 18 (1):121. [Medline]. [Full Text].

Gummin DD, Mowry JB, Spyker DA, Brooks DE, Osterthaler KM, Banner W. 2017 Annual Report of the American Association of Poison Control Centers’ National Poison Data System (NPDS): 35th Annual Report. Clin Toxicol (Phila). 2018 Dec. 56 (12):1213-1415. [Medline]. [Full Text].

Hoppe-Roberts JM, Lloyd LM, Chyka PA. Poisoning mortality in the United States: comparison of national mortality statistics and poison control center reports. Ann Emerg Med. 2000 May. 35(5):440-8. [Medline].

Haddad LM, Winchester JF. Clinical Management of Poisoning and Drug Overdose. 2nd ed. WB Saunders; 1990. 581-90.

Lincoff G, Mitchell DH. Toxic and Hallucinogenic Mushroom Poisoning: A Handbook for Physicians. New York: Van Nostrand Reinhold; 1977.

Litovitz TL, Klein-Schwartz W, Caravati EM, et al. 1998 annual report of the American Association of Poison Control Centers Toxic Exposure Surveillance System. Am J Emerg Med. 1999 Sep. 17(5):435-87. [Medline].

Litovitz TL, Klein-Schwartz W, Dyer KS, et al. 1997 annual report of the American Association of Poison Control Centers Toxic Exposure Surveillance System. Am J Emerg Med. 1998 Sep. 16(5):443-97. [Medline].

Litovitz TL, Klein-Schwartz W, Rodgers GC, et al. 2001 Annual report of the American Association of Poison Control Centers Toxic Exposure Surveillance System. Am J Emerg Med. 2002 Sep. 20(5):391-452. [Medline].

Litovitz TL, Klein-Schwartz W, White S, et al. 1999 annual report of the American Association of Poison Control Centers Toxic Exposure Surveillance System. Am J Emerg Med. 2000 Sep. 18(5):517-74. [Medline].

Litovitz TL, Klein-Schwartz W, White S, et al. 2000 Annual report of the American Association of Poison Control Centers Toxic Exposure Surveillance System. Am J Emerg Med. 2001 Sep. 19(5):337-95. [Medline].

Litovitz TL, Smilkstein M, Felberg L, et al. 1996 annual report of the American Association of Poison Control Centers Toxic Exposure Surveillance System. Am J Emerg Med. 1997 Sep. 15(5):447-500. [Medline].

Mitchel DH, Trestrail JH. Poisondex. Micromedex Inc. 1997:94.

Rumack BH, Spoerke DG. Handbook of Mushroom Poisoning Diagnosis and Treatment. 2nd ed. CRC Press LLC; 1994.

Tintinalli JE, Ruiz E, Krome RL. Emergency Medicine: A Comprehensive Study Guide. 4th ed. McGraw-Hill; 1996.

Watson WA, Litovitz TL, Klein-Schwartz W, et al. 2003 annual report of the American Association of Poison Control Centers Toxic Exposure Surveillance System. Am J Emerg Med. 2004 Sep. 22(5):335-404. [Medline].

Watson WA, Litovitz TL, Rodgers GC, et al. 2002 annual report of the American Association of Poison Control Centers Toxic Exposure Surveillance System. Am J Emerg Med. 2003 Sep. 21(5):353-421. [Medline].

Watson WA, Litovitz TL, Rodgers GC, et al. 2004 Annual report of the American Association of Poison Control Centers Toxic Exposure Surveillance System. Am J Emerg Med. 2005 Sep. 23(5):589-666. [Medline].

Yildirim C, Bayraktaroglu Z, Gunay N, Bozkurt S, Köse A, Yilmaz M. The use of therapeutic plasmapheresis in the treatment of poisoned and snake bite victims: an academic emergency department’s experiences. J Clin Apher. 2006 Dec. 21(4):219-23. [Medline].

Reed Brozen, MD Director of Air Transport, Associate Professor, Department of Emergency Medicine, Dartmouth Medical School, Dartmouth-Hitchcock Medical Center

Reed Brozen, MD is a member of the following medical societies: American Academy of Emergency Medicine, American College of Emergency Physicians, New Hampshire Medical Society, Society for Academic Emergency Medicine

Disclosure: Nothing to disclose.

John T VanDeVoort, PharmD Regional Director of Pharmacy, Sacred Heart and St Joseph’s Hospitals

John T VanDeVoort, PharmD is a member of the following medical societies: American Society of Health-System Pharmacists

Disclosure: Nothing to disclose.

Sage W Wiener, MD Assistant Professor, Department of Emergency Medicine, State University of New York Downstate Medical Center; Director of Medical Toxicology, Department of Emergency Medicine, Kings County Hospital Center

Sage W Wiener, MD is a member of the following medical societies: American Academy of Clinical Toxicology, American Academy of Emergency Medicine, American College of Medical Toxicology, Society for Academic Emergency Medicine

Disclosure: Nothing to disclose.

Miguel C Fernandez, MD, FAAEM, FACEP, FACMT, FACCT Associate Clinical Professor, Department of Surgery/Emergency Medicine and Toxicology, University of Texas School of Medicine at San Antonio; Medical and Managing Director, South Texas Poison Center

Miguel C Fernandez, MD, FAAEM, FACEP, FACMT, FACCT is a member of the following medical societies: American Academy of Emergency Medicine, American College of Emergency Physicians, American College of Medical Toxicology, Society for Academic Emergency Medicine, Texas Medical Association, American College of Occupational and Environmental Medicine

Disclosure: Nothing to disclose.

Michael Hodgman, MD Assistant Clinical Professor of Medicine, Department of Emergency Medicine, Bassett Healthcare

Michael Hodgman, MD is a member of the following medical societies: American College of Medical Toxicology, American College of Physicians, Medical Society of the State of New York, and Wilderness Medical Society

Disclosure: Nothing to disclose.

Orellanine Mushroom Toxicity

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Orellanine Mushroom Toxicity

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