Clinical Features

The clinical picture in intoxicated victims would depend on the route of exposure. After aerosol exposure, signs and symptoms would depend on the dose inhaled. Accidental sublethal aerosol exposures which occurred in humans in the 1940s were characterized by acute onset of the following symptoms in 4 to 8 hours: fever, chest tightness, cough, shortness of breath, nausea, and joint pain. The onset of profuse sweating some hours later was commonly the sign of termination of most of the symptoms.

Although lethal human aerosol exposures have not been described, the severe affects seen in the animal respiratory tract, including necrosis and development of fluid in the lungs, are probably sufficient to cause death from ARDS and respiratory failure.

Time to death in laboratory animals is dose dependent, occurring 36-72 hours post inhalation exposure. Humans would be expected to develop severe lung inflammation with progressive cough, shortness of breath, cyanosis (bluish discoloration of the skin and mucous membranes) and pulmonary edema.

By other routes of exposure, ricin is not a direct lung irritant however, intravascular injection can cause minimal pulmonary edema due to vascular injury. Ingestion causes necrosis of the gastrointestinal lining, local hemorrhage, and liver, spleen, and kidney necrosis. Intramuscular injection causes severe local necrosis of muscle and regional lymph nodes with moderate visceral organ involvement.

Diagnosis

An attack with aerosolized ricin would be primarily diagnosed by the clinical and epidemiological setting. Acute lung injury affecting a large number of geographically clustered cases should raise suspicion of an attack with a pulmonary irritant such as ricin, although other pulmonary pathogens could present with similar signs and symptoms. Other biological threats, such as SEB, Q fever, tularemia, plague, and some chemical warfare agents like phosgene, need to be included in the differential diagnosis.

Ricin-induced pulmonary edema would be expected to occur much later (1- 3 days post exposure) compared to that induced by SEB (about 12 hours post exposure) or phosgene (about 6 hours post exposure). Ricin intoxication would be expected to progress despite treatment with antibiotics, as opposed to an infectious process. There would be no swelling or inflammation of the esophagus as seen with inhalation anthrax.

Toxin Characteristics

Ricin can be produced relatively easily and inexpensively in large quantities in a fairly low-technology setting. Ricin can be prepared in liquid or crystalline form, or it can be lyophilized to make a dry powder. It could be disseminated as an aerosol, injected into a target, or used to contaminate food or water on a small scale.

Ricin is stable under ambient conditions, but is detoxified by heat (80°C for 10 min., or 50°C for about an hour at pH 7.8) and chlorine (>99.4% inactivation by 100 mg/L FAC in 20 min.). Low chlorine concentrations, such as 10 mg/L FAC, as well as iodine at up to 16 mg/L, have no effect on ricin.

Ricin's toxicity is inferior to other toxins, such as botulinum and SEB (incapacitating dose). An enemy would need to produce it in large quantities to cover a significant area on the battlefield, thus potentially limiting large-scale use of ricin by an adversary.

Mechanism of Toxicity

Ricin is very toxic to cells. It acts by inhibiting protein synthesis. The B chain binds to cell surface receptors and the toxin-receptor complex is taken into the cell; the A chain has endonuclease activity and extremely low concentrations will inhibit DNA replication and protein synthesis. In rodents, aerosol exposure is characterized by necrosis of respiratory system, causing tracheitis, bronchitis, bronchiolitis, and pneumonia. There is a latent period of 8 hours after inhalation exposure before lesions are observed in laboratory animals. In rodents, ricin is more toxic by the aerosol route than by other routes of exposure.

Medical Management

Management of ricin-intoxicated patients depends on the route of exposure. Patients with pulmonary intoxication are managed by appropriate respiratory support (oxygen, intubation, ventilation, and circulation monitoring) and treatment for pulmonary edema, as indicated.

Gastrointestinal intoxication is best managed by washing out the stomach with sterile water or a salt-water solution and purging the bowels with magnesium citrate. Superactivated charcoal is of little value for ricin. Replacement of GI fluid losses is important. In percutaneous exposures, treatment would be primarily supportive.

Preventative Measures

A surgical mask is effective in preventing aerosol exposure.