AUTHOR AND EDITOR INFORMATION

Section 1 of 12  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Acknowledgments
• Multimedia
• References

INTRODUCTION

Section 2 of 12  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Acknowledgments
• Multimedia
• References

Background

Ricin is a potent toxin that has potential to be used as an agent of biological warfare and as a weapon of mass destruction (WMD). Ricin is widely available, easily produced, and derived from the beans of the castor plant (Ricinus communis).

In attempting to evaluate and discuss agents that can be used as WMDs, the question, "What can cause a maximum credible event?" is hopefully answered. A maximum credible event is one that could cause a large loss of life in addition to disruption, panic, and an overwhelming use of civilian healthcare resources. For an agent to be considered capable of causing a maximum credible event, it should be highly lethal, inexpensively and easily produced in large quantities, stable in aerosol form, and have the ability to be dispersed (1-5 µm). The ideal agent also is communicable from person to person and has no treatment or vaccine.

When ricin's characteristics are applied to this model, its use appears limited but should not be underestimated. Ricin is produced easily and inexpensively, is highly toxic, is stable in aerosolized form, and has no treatment or approved vaccine. Its toxicity when compared to living replicating biological agents limits ricin's use. A large amount of ricin is necessary to produce the desired effect of a WMD. For example, the amount of ricin necessary to cover a 100-km² area and cause 50% lethality, assuming aerosol toxicity of 3 mcg/kg and optimum dispersal conditions, is approximately 4 metric tons, whereas only 1 kg of Bacillus anthracis is required. Ricin, however, would have efficacy as a disabling agent. Its use as a food and water contaminant easily could incapacitate many and overwhelm local healthcare resources. Thus, its use as a food and water contaminant is a major concern because of ricin's ease of availability.

Ricin can be disseminated as an aerosol, by injection, or as a food and water contaminant.

Pathophysiology

Ricin is a widely available potential toxin that is produced easily. It is a potent protein derived from the beans of the castor plant (R communis). Castor beans are used in the production of castor oil, a brake and hydraulic fluid constituent. The aqueous phase of the process, termed the "waste mash," is 5-10% ricin. Separating this 66,000-dalton protein requires chromatography, a common undergraduate chemistry skill. Ricin's ease of availability and its lethality make it an attractive agent for use in biological warfare and for potential use as a WMD. Routes of exposure are respiratory (inhaled aerosol), gastrointestinal (GI [ingested]), and parenteral (injected). Clinical manifestations depend on the route of exposure and the amount of absorption.

Ricin is composed of 2 hemagglutinins and 2 toxins. The toxins RCL III and RCL IV are dimers of approximately 66,000 daltons in molecular weight. The toxins have an "A" and a "B" chain, which are polypeptides and joined by a disulfide bond. The B chain binds to cell surface glycoproteins and affects entry into the cell by an unknown mechanism. The A chain acts on the 60S ribosomal subunit and prevents the binding of elongation factor-2. This inhibits protein synthesis and leads to cell death. This basic structure of ricin is similar to those of the botulinum toxin, cholera toxin, diphtheria toxin, tetanus toxin, and insulin.

Frequency

United States

From 1991-1997, 3 cases were related to ricin. In 1991 in Minnesota, 4 members of the Patriots Council, an extremist group that held antigovernment and antitax ideals and advocated the overthrow of the US government, were arrested for plotting to kill a US marshal with ricin.¹ The ricin was produced in a home laboratory. They planned to mix the ricin with the solvent dimethyl sulfoxide (DMSO) and then smear it on the door handles of the marshal's vehicle. The plan was discovered, and the 4 men were convicted. In 1995, a man entered Canada from Alaska on his way to North Carolina.¹ Canadian custom officials stopped the man and found him in possession of several guns, $98,000, and a container of white powder, which was identified as ricin. Lastly, in 1997, a man shot his stepson in the face. Investigators discovered a makeshift laboratory in his basement and found agents such as ricin and nicotine sulfate.

Three US Senate office buildings were closed February 3, 2004, after ricin was found in the mailroom that serves Senate Majority Leader Bill Frist's office. No injuries were reported.

International

In December 2002, 6 terrorist suspects were arrested in Manchester, England; their apartment was serving as a "ricin laboratory."¹ Among them was a 27-year-old chemist who was producing the toxin. Later, on January 5, 2003, British police raided 2 residences around London and found traces of ricin, which led to an investigation of a possible Chechen separatist plan to attack the Russian embassy with the toxin; several arrests were made.²

Mortality/Morbidity

Mortality and morbidity depend on the route and amount of exposure.

• Dermal exposure
• • Dermal exposure of ricin is of little concern because the absorption amount is insignificant.
  • To be absorbed dermally, ricin must be enhanced with a strong solvent such as DMSO.
  • Dermal symptoms depend on the type of solvent and length of exposure. Dermal exposure probably is unable to achieve toxicity.
• Gastrointestinal exposure
• • The LD50 (lethal dose for 50% of exposed population) for GI exposures is 30 mcg/kg.
  • Ricin's lethality is diminished when ingested secondary to poor absorption.
  • In the past, castor bean ingestions were reported to be fatal, but multiple case reports prove otherwise. Many documented cases are related to ingestions of multiple seeds and voluntary ingestion of ricin without fatality.
  • If ingested in sufficient amounts, ricin can cause severe gastroenteritis, GI hemorrhage, and hepatic, splenic, and renal necrosis. Death may occur secondary to circulatory collapse.
• Parenteral exposure
• • Parenteral exposures can be rapidly fatal, with an LD50 similar to aerosol exposure.
  • The highly publicized case of Georgi Markov is evidence of the rapidly fatal nature of parenteral exposure. Markov, an exiled Bulgarian broadcaster, was waiting for a bus in 1978 when he was jabbed with an umbrella in the lower extremity.¹ He then developed severe gastroenteritis and high fevers and died 3 days later. At autopsy, a small 1.5-mm metallic sphere was found at the wound site. It had 2 tiny holes and could hold a volume of 0.28 mm³. No toxin was isolated. Because of the small volume and rapid demise of the patient, ricin was believed to be the only capable inciting agent. The coroner recreated the scenario by injecting a pig with a similar dose of ricin. The pig died in a similar manner 26 hours later.
  • Ricin, if injected, can cause severe local necrosis of muscle and regional lymph nodes with organ involvement and death.
• Aerosol exposure
• • The LD 50 for aerosol exposure is 3 mcg/kg.
  • Aerosol exposure causes weakness, fever, cough, and pulmonary edema within 18-24 hours and severe respiratory distress and death within 36-72 hours.
  • In rodents, aerosol exposure is characterized by necrotizing airway lesions causing tracheitis, bronchitis, bronchiolitis, and interstitial pneumonia with perivascular and alveolar edema.

CLINICAL

Section 3 of 12  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Acknowledgments
• Multimedia
• References

History

• In the case of an isolated attack such as an assassination attempt, no historical markers may be present.
• A victim may relate the pain of an antecedent injection, but this may be overlooked during the history.
• A patient is unlikely to be aware of contamination of ingested foods or beverages.
• If a number of patients are affected simultaneously, by either ingestion or inhalation, the subsequent cluster of patients presenting with similar symptoms over a brief time may alert an astute clinician to the possibility of an intentional act. This is especially true in the case of an inhalation incident (ingestion initially may mimic food poisoning).

Physical

Perform a complete physical examination with any exposure.

• In parenteral exposure, inspect the site for induration, erythema, and the possibility of a retained foreign body. These physical findings may be present prior to or at the time of systemic manifestations.
• In aerosol exposure, the presentation is that of a rapidly progressive acute lung injury, with findings consistent with the stage of progression from a physical examination with normal findings through hypoxia, cyanosis, labored breathing, tachypnea, tachycardia, and progressive respiratory failure.
• In GI exposure, physical examination should be consistent with that for gastroenteritis and volume depletion. If the dose was sufficient and the disease had progressed, frank hematemesis and/or bloody diarrhea or melena may be present.

DIFFERENTIALS

Section 4 of 12  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Acknowledgments
• Multimedia
• References

Other Problems to be Considered

Pneumonic plague
Salmonella
Shigella
Cholera
Necrotizing fasciitis

WORKUP

Section 5 of 12  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Acknowledgments
• Multimedia
• References

Lab Studies

• Obtain baseline laboratory information. Useful testing includes a complete blood count (which may reveal leukocytosis), electrolytes, BUN, creatinine, glucose, prothrombin time, activated partial thromboplastin time, international normalized ratio, type and screen, fibrinogen, liver enzymes, amylase, and lipase. An arterial blood gas may reveal hypoxemia.
• Specific enzyme-linked immunosorbent assay (ELISA) testing on serum and immunohistochemical techniques for direct tissue analysis are under development.
• Collect acute and convalescent serum to determine measurements of antibody response.

Imaging Studies

• Chest radiography
• • A chest radiograph may reveal infiltrates or an acute respiratory distress syndrome (ARDS) picture.
  • Radiography may also be useful in parenteral exposures to evaluate for retained foreign body.

Procedures

• Bronchoscopy: If performed, bronchial aspirate may be rich in protein compared to plasma, as observed in any condition causing high-permeability pulmonary edema.

TREATMENT

Section 6 of 12  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Acknowledgments
• Multimedia
• References

Prehospital Care

Strictly adhere to universal precautions at all times, although secondary dermal absorption to prehospital providers is not expected. The risk of secondary aerosolization is minimal. Use protective masks, which are effective in preventing toxicity, when an overt aerosol attack is suspected.

Emergency Department Care

• Management
• • ED management begins with universal precautions and the ABCs. Add a "D" for decontamination (including the removal of garments). If ingestion is possible, based on the history and presenting findings, consider gut decontamination as well.
  • Management also involves the ability to recognize, diagnose, and treat a possible biological event.
• Decontamination
• • Decontamination begins by removing garments and cleaning with soap and water.
  • If available, use a 0.5% sodium hypochlorite solution with a contact time of 15 minutes. Do not instill this solution into open abdominal, brain, or spinal cord injuries or into the eyes. It can be instilled into noncavity wounds and then removed via suction into disposable containers. This discarded solution is neutralized and nonhazardous in 5 minutes. To make a 0.5% sodium hypochlorite solution, mix 1 part bleach and 9 parts water. Make it fresh daily with a pH in the alkaline range. In the absence of this solution, copious amounts of soap and water may be used.
• Diagnosis
• • Diagnosis of an aerosolized attack or food and water contaminant with ricin is similar to that of any of the biological or chemical agents that serve as WMDs. It primarily depends on the clinical and epidemiologic setting. In cases of isolated injection, the diagnosis is extremely difficult.
  • The clinical presentation of acute lung injury in a large number of patients in a particular area should suggest a pulmonary irritant. The clinical presentation of severe gastroenteritis or hemorrhagic gastroenteritis in a large number of patients in a particular area should suggest a food and water contaminant.
  • Include ricin and other agents (eg, staphylococcal enterotoxin B, Q fever, tularemia, pneumonic plague, inhalational anthrax, chemical agents such as phosgene) in the differential diagnosis.
  • Ricin is expected to progress despite antibiotic therapy. Chest radiograph exhibits no evidence of mediastinitis, as would be expected with pulmonary anthrax.
  • Staphylococcal enterotoxin B does not progress to a life-threatening syndrome, and phosgene produces ARDS, which is mediated by exertion. Phosgene also has the characteristic odor of newly mown hay or grass and is quite irritating to mucous membranes in lethal amounts.
• Diagnostic testing: Diagnostic testing is of limited value (see Workup).
• Treatment
• • Treatment and toxicity depend on the route of exposure. Treatment is supportive, and no antidote is available for ricin.
  • Emergency department employees should obey strict universal precautions at all times.
  • For dermal exposure, a weak sodium hypochlorite solution (0.1%) and/or soap and water suffice to decontaminate the skin.
  • For GI exposure, include gastric decontamination with superactivated charcoal, volume replacement, and H2 blockers in treatment. Include chemistry panels, complete blood count, liver function panel, BUN and creatinine, urinalysis, and type and screen in the laboratory evaluation.
  • For percutaneous exposure, base treatment on excision of the injection site, if possible, within the shortest amount of time. Obtain baseline laboratory information, including arterial blood gas and fibrinogen. Although antibiotics serve no role in the treatment of ricin, withholding such therapy in an acutely septic-appearing patient would be difficult. Antibiotics may serve to prevent infection resulting from the percutaneous mechanism. Update tetanus immunization status if unknown.
  • For aerosol or pulmonary exposure, provide standard critical care treatment directed toward acute lung injury and pulmonary edema. Maintain a low threshold to secure the patient's airway and ensure adequate oxygenation and ventilation. Obtain a chest radiograph, which may show infiltrates. The clinical course progresses despite antibiotic therapy.
  • The only effective treatment for ricin toxicity is prevention. Current investigations are underway with candidate vaccines and ricin inhibitors as antidotes or to facilitate immunotoxin treatment. Pteroic acid, neopterin, pterin tautomer, and guanine tautomer are particularly useful.
• Disposition: Admit and monitor any symptomatic patient and perform aggressive volume resuscitation.

Consultations

Surgical consultation for local excision and removal is warranted for parenteral exposures when a retained foreign body is located.

MEDICATION

Section 7 of 12  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Acknowledgments
• Multimedia
• References

Update tetanus status if unknown. If exposure is via parenteral route, antibiotics may be helpful in preventing secondary bacterial infection.

Drug Category: Antibiotics

With regard to ricin toxicity, the only possible indication for antibiotics is for the parenteral mechanism of exposure. Direct the choice of antibiotic to cover skin flora.

Drug Category: Vasopressor agents

Perform adequate volume resuscitation of patients with isotonic fluids and packed red blood cells prior to using or in conjunction with these agents; do not use in place of volume resuscitation. Choice of agent usually is determined by physician preference.

Drug Category: Toxoids

These agents are used to induce active immunity. Update tetanus status if unknown.

Drug Category: H2 blockers

Reversible competitive blockers of histamine at H2 receptors, particularly those in the gastric parietal cells where they inhibit acid secretion. The H2 antagonists are highly selective, do not affect H1 receptors, and are not anticholinergic agents.

Drug Category: Antidotes

Used to inhibit or reduce absorption of the toxin.

FOLLOW-UP

Section 8 of 12  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Acknowledgments
• Multimedia
• References

Further Inpatient Care

• Perform adequate volume resuscitation of patients. First treat hypotension with isotonic fluids and packed red blood cells as needed. Use a pressor-type agent such as dopamine or norepinephrine when needed.

Deterrence/Prevention

• The only effective treatment or prevention against a biological attack with ricin is prophylaxis; unfortunately, no prophylaxis exists. Currently, investigations are ongoing with candidate vaccines and ricin inhibitors. Human vaccines are under investigation and show promise but are still unavailable at this time. In an aerosol attack, protective masks are effective in preventing toxicity and should be used.

Patient Education

• For excellent patient education resources, visit eMedicine's Bioterrorism and Warfare Center. Also, see eMedicine's patient education articles Biological Warfare, Ricin, and Personal Protective Equipment.

MISCELLANEOUS

Section 9 of 12  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Acknowledgments
• Multimedia
• References

Medical/Legal Pitfalls

• Investigate any ricin exposure that involves multiple victims. Weaponized use of ricin is a reportable offense and mandates reporting to local and federal authorities.

Special Concerns

• Conclusion: Although ricin is not the ideal biological warfare agent, it remains a threat. It is widely available and easily produced. It is not the ideal agent of choice for an aerosol attack, but it is a major concern as a food and water contaminant. With the increasing number of biological threats, hoaxes, and "how to" Internet resources available, this threat has the potential to become reality. Therefore, the emergency physician must be familiar with its characteristics. Treatment is supportive, and no antidote or approved vaccine is available.

ACKNOWLEDGMENTS

Section 10 of 12  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Acknowledgments
• Multimedia
• References

The authors and editors of eMedicine gratefully acknowledge the contributions of previous author, Michael P Allswede, DO, to the development and writing of this article.

MULTIMEDIA

Section 11 of 12  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Acknowledgments
• Multimedia
• References

Media file 1:  Chemical Terrorism Agents and Syndromes. Signs and symptoms. Chart courtesy of North Carolina Statewide Program for Infection Control and Epidemiology (SPICE), copyright University of North Carolina at Chapel Hill, www.unc.edu/depts/spice/chemical.html.
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REFERENCES

Section 12 of 12

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Acknowledgments
• Multimedia
• References

1. CDC and Public Health Training Network. Recognition, Management and Surveillance of Ricin-Associated Illness [Web cast script]. December 30, 2003. [Full Text].
2. CNN.com. Timeline: UK ricin terror probe. January 23, 2003. [Full Text].
3. Balint GA. Ricin: the toxic protein of castor oil seeds. Toxicology. Mar 1974;2(1):77-102. [Medline].
4. Challoner KR, McCarron MM. Castor bean intoxication. Ann Emerg Med. Oct 1990;19(10):1177-83. [Medline].
5. Ellenhorn MJ, Barceloux DG. Ornamental beans. In: Medical Toxicology Diagnosis and Treatment of Human Poisoning. 1988:1225-27.
6. FBI. Federal Bureau of Investigations Web Page. Available at www.fbi.gov. Accessed 2000.
7. Franz D, USAMRIID. Defense against toxic weapons. In: US Army Medical Research Material Command. 1997.
8. Kopferschmitt J, Flesch F, Lugnier A, et al. Acute voluntary intoxication by ricin. Hum Toxicol. Apr 1983;2(2):239-42. [Medline].
9. Kortepeter MG, Parker GW. Potential biological weapons threats. Emerg Infect Dis. Jul-Aug 1999;5(4):523-7. [Medline].
10. Meselson M, Guillemin J, Hugh-Jones M, et al. The Sverdlovsk anthrax outbreak of 1979. Science. Nov 18 1994;266(5188):1202-8. [Medline].
11. Shih RD, Goldfrank LR. Plants. In: Goldfrank's Toxicologic Emergencies. 6^th ed. 1998:1254-55.
12. US Medical Research Institute of Infectious Diseases. Medical Management of Biocasualities Handbook. 1998.
13. Zilinskas RA. Iraq's biological weapons. The past as future?. JAMA. Aug 6 1997;278(5):418-24. [Medline].

Article Last Updated: Feb 14, 2008