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Ricin Poisoning

Ricin is a potent toxin most commonly due to ingestion of castor oil beans and can cause fatal toxicity. It is often mentioned as a potential biological weapon and cases of poisoning by injection or inhalation have been documented. Clinical presentation includes the appearance of nonspecific gastrointestinal or respiratory symptoms, depending on the route of exposure. The diagnosis is made through patient history, while treatment includes supportive measures.


Presentation

Symptoms of ricin poisoning vary significantly depending on the route of exposure. In the case of gastrointestinal intoxication due to ingestion of castor beans, nonspecific GI symptoms appear approximately within ten hours and include abdominal pain, diarrhea that can sometimes include blood and profuse vomiting [3]. In the case of inhalation, symptoms appear slightly sooner (within the first 4-8 hours in most reported cases) and include dyspnea, cough, development of pulmonary edema and eventual respiratory distress [7]. Following ingestion as well as inhalation, the accompanying constitutional symptoms such as malaise, fatigue, generalized weakness and fever may be present. After the appearance of initial symptoms, patients can rapidly deteriorate, develop hypotension, hypovolemic shock, and life-threatening multi-organ failure. For these reasons, prompt identification of the causative agent and appropriate supportive treatment should be initiated and they can be life-saving.

Constitutional Symptom
  • Following ingestion as well as inhalation, the accompanying constitutional symptoms such as malaise, fatigue, generalized weakness and fever may be present.[symptoma.com]
Vomiting
  • The case history is reported of a patient with ricin poisoning who presented with nausea and vomiting following ingestion of Korean castor bean.[ncbi.nlm.nih.gov]
  • The oil is also used as a laxative and purgative in clearing the digestive tract and why taken by a spoonful, it can induce vomiting.[standardfirstaidcourses.ca]
  • Symptoms include vomiting, diarrhea, abdominal pain and severe dehydration, or significant breathing difficulties and cough, depending on whether ingestion or inhalation of ricin occurred.[symptoma.com]
  • Symptoms after ingestion (onset within 12 hours) are nonspecific and may include nausea, vomiting, diarrhea, and abdominal pain and may progress to hypotension, liver failure, renal dysfunction, and death due to multiorgan failure or cardiovascular collapse[ncbi.nlm.nih.gov]
  • If a patient may have ingested ricin and is not vomiting, a single dose of activated charcoal should be given as soon as possible. Gastric lavage is an option if it can be done within 1 hour after ingestion of the ricin.[cidrap.umn.edu]
Nausea
  • The case history is reported of a patient with ricin poisoning who presented with nausea and vomiting following ingestion of Korean castor bean.[ncbi.nlm.nih.gov]
  • Breathing the dust of ricin can cause nausea, difficulty breathing, cyanosis, coughing, weakness, muscle aches and chest pain. Just like with any form of poisoning, proper measures must be carried.[standardfirstaidcourses.ca]
  • Fever, chest tightness, cough, nausea, and joint pain may occur. Ricin can cause cell death in the respiratory system and eventual respiratory failure.[science.jrank.org]
  • Symptoms after ingestion (onset within 12 hours) are nonspecific and may include nausea, vomiting, diarrhea, and abdominal pain and may progress to hypotension, liver failure, renal dysfunction, and death due to multiorgan failure or cardiovascular collapse[ncbi.nlm.nih.gov]
  • Ricin-related symptoms include fever and nausea, which progresses to severe abdominal pains and fits. Victims die from multiple organ failure and there is no known antidote or vaccine.[theguardian.com]
Diarrhea
  • Symptoms after ingestion (onset within 12 hours) are nonspecific and may include nausea, vomiting, diarrhea, and abdominal pain and may progress to hypotension, liver failure, renal dysfunction, and death due to multiorgan failure or cardiovascular collapse[ncbi.nlm.nih.gov]
  • Symptoms include vomiting, diarrhea, abdominal pain and severe dehydration, or significant breathing difficulties and cough, depending on whether ingestion or inhalation of ricin occurred.[symptoma.com]
  • A possible clue to an attack involving ricin inhalation would be that a number of people who had been close to each other suddenly developed fever, diarrhea, cough, and excess fluid in their lungs.[www1.nyc.gov]
  • It may cause abdominal pain, nausea, vomiting, and bloody diarrhea. Eventual complications include cell death in the liver, kidney, adrenal glands , and central nervous system .[science.jrank.org]
  • In moderate to severe illness due to ricin ingestion, vomiting and diarrhea typically lead to dehydration and possibly to hypovolemic shock. There is no specific antidote for ricin, and it cannot be removed by dialysis, according to the article.[cidrap.umn.edu]
Abdominal Pain
  • Symptoms after ingestion (onset within 12 hours) are nonspecific and may include nausea, vomiting, diarrhea, and abdominal pain and may progress to hypotension, liver failure, renal dysfunction, and death due to multiorgan failure or cardiovascular collapse[ncbi.nlm.nih.gov]
  • Symptoms include vomiting, diarrhea, abdominal pain and severe dehydration, or significant breathing difficulties and cough, depending on whether ingestion or inhalation of ricin occurred.[symptoma.com]
  • If foods contaminated with ricin or castor oil are accidentally eaten, it can cause internal bleeding, vomiting, nausea, abdominal pain , liver and kidney failure, circulatory failure and a rapid heartbeat.[standardfirstaidcourses.ca]
  • It may cause abdominal pain, nausea, vomiting, and bloody diarrhea. Eventual complications include cell death in the liver, kidney, adrenal glands , and central nervous system .[science.jrank.org]
  • Ricin-related symptoms include fever and nausea, which progresses to severe abdominal pains and fits. Victims die from multiple organ failure and there is no known antidote or vaccine.[theguardian.com]
Seizure
  • The person may receive intravenous fluids, medications to control seizures , and stomach flushing if ricin was ingested.[webmd.com]
  • Effects on the central nervous system have been reported to include seizures.[theguardian.com]
  • The victim may experience hallucinations, seizures, and bloody urine. Eventually (usually after several days) the liver, spleen, and kidneys could fail. Death would result from organ failure.[thoughtco.com]
  • Other signs or symptoms may include seizures, and blood in the urine. Within several days, the person’s liver, spleen, and kidneys might stop working, and the person could die.[parveyfrankel.com]
  • If ingested in large enough amounts, ricin causes bloody diarrhea and vomiting, which lead to severe dehydration and low blood pressure, followed by seizures.[medicaldaily.com]

Workup

Because symptoms of ricin poisoning are nonspecific and can mimic various gastrointestinal and pulmonary infections, the diagnosis primarily relies on patient history [14]. Recent exposure to this agent should be investigated, with eventual suspicion for intentional poisoning, if circumstances point to this mode of intoxication. This information is critical for making the initial diagnosis, as there is no widely available test to confirm ricin as the causative agent.

Physical examination can also be of diagnostic significance as it can reveal injection sites if ricin was administered via injection. However, the overall status of the patient should be evaluated through a complete examination, so that appropriate therapeutic measures can be initiated.

Treatment

Current treatment strategies in patients with ricin poisoning include only supportive measures, as there is no antidote or another form of therapy. Recent studies have evaluated the use of nanosecond pulsed electric fields (nsPEFs), which induce inactivation of some parts of this toxin in animal models, but its effects in humans remain to be seen [15].

The majority of patients will present with symptoms that can very rapidly progress to multi organ failure, which is why rapid measures, such as blood pressure and heart rate monitoring, maintaining adequate ventilation and oxygen saturation, as well as correction of fluids and electrolytes are vital in preventing further deterioration. Drugs that could be of use include activated charcoal if ingestion of ricin is established, but only if symptoms such as vomiting are absent [8], while gastric lavage is also indicated if ingestion occurred very shortly prior to admission [16]. Because respiratory distress and lung failure may occur, assisted ventilation may be indicated.

Prognosis

Studies that have reviewed cases of ricin poisoning established a mortality rate of slightly over 8% in patients who were untreated and less than 1% in treated patients [8]. Mortality significantly depends on the mode of poisoning, since inhalation of ricin is deemed to be much more potent than ingestion. The lethal dose for adults is estimated to be around 5-10 µg/kg in case of inhalation or direct injection, with fatal effects ensuing within hours [13]. The lethal dose in case of ingestion is estimated to be significantly higher [8], which could explain why inhalation of ricin poses much more risk. However, significant toxicity is reported to occur from ingesting only a few castor beans.

Etiology

Ricin is a 60-65 kDa protein composed of A and B subunits, similar to the pertussis and cholera toxin [4]. It is derived from the castor oil plant (Ricinus communis) and is isolated from its bean, which can be recognized by their light brown color and dark brown spots. The initial discovery of ricin was made at the end of the 19th century [5], but the mechanism of action and effects were not clearly established up to the 1980s [6]. This compound belongs to a group of ribosome-inactivating proteins (RIPs), which can be completely harmless to humans and animals, as they are not able to enter cells (type I RIPs). However, ricin belongs to type II RIPs, which are distinguished by being attached to a galactose-binding lectin (the main function of B subunit), making this heterodimeric toxin able to bind to human cells and reach the cytosol [4] [6]. Once the toxin enters the cells, the A subunit exerts its cytotoxic effects and causes significant cell damage.

Epidemiology

One of the uses of castor oil is in car manufacturing, but this plant is ubiquitous, as Ricinus communis is distributed throughout the world. Cases of ricin poisoning have been documented worldwide. Ricin appears as a white powder soluble in water. It is stable in wide ranges of pH and requires high temperatures, especially when in powder form, to be neutralized [7]. Until the 1990s, about 400 cases of intoxication with this compound were described [8], while several criminal cases connected with ricin have been published in earlier decades [9] [10]. Consequently, it was established that ricin poisoning not only occurs through ingestion of castor beans but also through inhalation and direct inoculation of the poison through injection. Since ingestion is accidental in most cases, this disease is observed in adults and in children. Because of relatively easy ways of growing Ricinus communis and castor beans, together with the fact that ricin is a very potent toxin to human cells, the Center for Disease Control (CDC) has classified ricin as a category B agent [1].

Sex distribution
Age distribution

Pathophysiology

Ricin, as mentioned previously, is a heterodimeric ribosome-inactivating toxin (RIP) composed of two subunits - the A chain which binds to the ribosomal units and causes inhibition of protein synthesis - and B chain, which is able to bind to surface glycoproteins and glycolipids due to the presence of β-1,4 linked galactose residues [11]. Once the B chain binds to the surface of the cell, the toxin enters the cytosol through endocytosis. Although the majority of the toxin is expelled from the cell through exocytosis or undergoes degradation in lysosomes, a certain number reaches the Golgi apparatus and eventually the endoplasmic reticulum. Because the two subunits are bound by disulfide bonds, the A subunit breaks from the B subunit through cleavage of these bonds and is able to reach the cytosol, where ribosomes are present [12]. The exact location at which ricin inhibits protein synthesis is the 28S rRNA of the 60S subunit, where it removes adenine from the RNA chain [7]. The end-result is inability of the newly formed genetic material to bind elongation factor (EF), which is an essential component of protein synthesis, which is also seen in patients with Corynebacterium diphtheria infection, where EF is inhibited by diphtheria toxin, thus producing similar effects. Through these effects, ricin is able to significantly impair formation of new DNA and cause cell death.

Prevention

Since ricin poisoning most commonly occurs following ingestion of castor beans that contain this toxin, avoiding castor beans is a preventive measure that can significantly reduce the rates of this poisoning. In addition, various studies have investigated potential candidates for the development of a vaccine [17] [18], although these studies are still in the phase of animal testing and their efficacy in human subjects are still not determined.

Summary

Ricin poisoning is a condition that occurs after introduction of ricin, a toxin derived from the beans of the castor oil plant (Ricinus communis) into the body, most commonly through ingestion of the beans. Because of its potency and relative stability in nature, ricin is often discussed as a potential weapon of biological warfare and is classified as category B agent characterized by relatively easy means of dissemination and moderate morbidity rates [1]. Although the most common form of poisoning occurs through ingestion, inhalation and injection methods have also been documented. Because of very scarce reports of ricin poisoning, the exact number of cases worldwide is unknown but sporadic reports of both accidental and intentional poisoning have been documented in various parts of the world [2] [3]. Ricin exerts its effects through inhibition of protein synthesis through deactivation of ribosomes, which can lead to very rapid development of irreversible cell damage and eventual cell death, which is why symptoms appear within hours after exposure. Clinical presentation depends on the mode of introduction. Ricin ingestion through castor beans manifests as a nonspecific gastrointestinal illness, with symptoms such as diarrhea, abdominal pain and vomiting, while inhalation of this toxin produces symptoms such as cough, dyspnea and development of pulmonary edema.Constitutional symptoms may be present, such as malaise and generalized weakness. Regardless of the mode of toxicity, patients may develop severe hypotension and progressive multi-organ failure together with shock, which may be life-threatening. Despite significant challenges in making the diagnosis, appropriate patient history may reveal events that can lead to ricin poisoning as a possible cause of symptoms, such as ingestion of suspicious beans or presence of similar symptoms in other individuals in the same environment. Current treatment includes only supportive measures, including control of fluids, establishing adequate ventilation and hemodynamic monitoring, as there is no cure or antidote for this compound.

Patient Information

Ricin is one of the more potent toxins that can be encountered worldwide and is found in the beans of the castor oil plants, known as Ricinus communis, which is ubiquitously distributed. Ricin poisoning almost exclusively occurs after ingestion of castor beans that grow on this plant, because they are the only part of the plant which contain the toxin. Castor beans can be encountered as ornamental items (for. e.g in bracelets, necklaces or prayer beads) or in maracas, which may be a possible source of accidental exposure. However, this compound has been frequently mentioned as a potential biological weapon, because it is easy to grow, as well as the fact that it is widely available. Several assassinations as well as criminal cases have been documented in which ricin was used. Consequently, inhalation of ricin, which occurs naturally in the form of a white powder, or even injection have been described as potential modes of intoxication. Ricin is able to enter the human cells and causes inhibition of protein synthesis, which ultimately prevents formation of DNA and induces cell death. It does so quite rapidly, with symptoms appearing within 10 hours after ingestion and within 4-8 hours after inhalation. Symptoms include vomiting, diarrhea, abdominal pain and severe dehydration, or significant breathing difficulties and cough, depending on whether ingestion or inhalation of ricin occurred. In either case, ricin can cause rapidly progressive failure of several organs, which is why immediate supportive treatment can be life-saving for the patient. Because symptoms are nonspecific and mimic various infectious diseases, but also other poisons, the diagnosis significantly relies on the information provided by the patient or those individuals who were with the patient prior to hospital admission. No specific test is available to confirm that ricin is the causative agent, nor is there an antidote for this poison. Therefore, treatment includes adequate rehydration through administration of fluids, together with blood pressure and heart rate monitoring, as well as maintaining normal breathing and oxygen content in the body. This toxin can cause organ damage that can be fatal, which is why avoiding castor beans is strongly recommended. As this poison can cause life-threatening intoxication, significant steps toward development of a vaccine are being made.

References

Article

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  2. AL-Tamimi FA, Hegazi AEM. A Case of Castor Bean Poisoning. Sultan Qaboos Univ Med J. 2008;8(1):83-87.
  3. Schier JG, Patel MM, Belson MG, et al. Public Health Investigation After the Discovery of Ricin in a South Carolina Postal Facility. Am J Public Health. 2007;97(1):S152-S157.
  4. Moshiri M, Hamid F, Etemad L. Ricin Toxicity: Clinical and Molecular Aspects. Rep Biochem Mol Biol. 2016;4(2):60-65.
  5. Stillmark, H. Uber Ricin, eines gifiges Ferment aus den Samen von Rtcinus communis L. und anderen Euphorbiacen. Inaugural Dissertation, University of Dorpat, Estonia. 1888
  6. Lord JM, Roberts LM, Robertus JD. Ricin: structure, mode of action, and some current applications. FASEB J. 1994;8(2):201-208.
  7. Audi J, Belson M, Patel M, et al. Ricin poisoning: a comprehensive review. JAMA. 2005;294(18):2342-2351.
  8. Challoner KR, McCarron MM. Castor bean intoxication: review of reported cases. Ann Emerg Med. 1990;19:1177–1183.
  9. Gibson J, Drociuk D, Fabian T, Brundage S, et al. Investigation of a ricin-containing envelope at a postal facility—South Carolina, 2003. MMWR Morbid Mortal Wkly Rep. 2003;52:1129–1131
  10. Crompton R, Gall D. Georgi Markov--death in a pellet. Med Leg J. 1980;48(2):51-62.
  11. Lord MJ, Jolliffe NA, Marsden CJ, Pateman CS, Smith DC, Spooner RA, Watson PD, Roberts LM. Ricin. Mechanisms of cytotoxicity. Toxicol Rev. 2003;22(1):53-64.
  12. Sandvig K, Grimmer S, Iversen TG, et al. Ricin transport into cells: studies of endocytosis and intracellular transport. Int J Med Microbiol. 2000;290(4-5):415-420.
  13. Bradberry SM, Dickers KJ, Rice P, Griffiths GD, Vale JA. Ricin poisoning. Toxicol Rev. 2003;22(1):65-70.
  14. Palmer ME, Betz JM. Plants. Nelson LS, Lewin NA, Howland MA, et al, eds. Goldfrank's Toxicologic Emergencies. 9th ed. New York, NY: McGraw-Hill; 2010.
  15. Wei K, Li W, Gao S, et al. Inactivation of Ricin Toxin by Nanosecond Pulsed Electric Fields Including Evidences from Cell and Animal Toxicity. Scientific Reports. 2016;6:18781.
  16. Behrman RE, Kliegman RM, Jenson HB. Nelson Textbook of Pediatrics. 17th ed. Philadelphia: WB Saunders; 2003.
  17. Olson MA, Carra JH, Roxas-Duncan V, Wannemacher RW, Smith LA, Millard CB. Finding a new vaccine in the ricin protein fold. Protein Eng Des Sel. 2004;17(4):391-397.
  18. Zhang T, Yang H, Kang L, et al. Strong protection against ricin challenge induced by a novel modified ricin A-chain protein in mouse model. Hum Vaccin Immunother. 2015;11(7):1779-1787.

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Last updated: 2018-06-22 09:58