A patient arrives at your hospital complaining of fever, malaise, and cough. You think nothing of it – until you notice the thirty other patients who have appeared in the waiting room with the same symptoms. A sudden flu outbreak? You realize with concern that it’s not flu season….

Clinicians must be trained to be watchful for the red flags of a biological or chemical terrorist attack. Although rare, the astute diagnosis of a biochemical weapon causing a patient’s symptoms can provide lifesaving treatment in the nick of time.

The following are classified as high risk potential agents of terrorism because they can be quickly disseminated, and would likely cause widespread societal panic and require sweeping public health actions to contain.

Anthrax (Bacillus anthracis): When you think anthrax, think sheep, as in woolsorter’s disease – the anthrax spores are picked up by herds of grazing sheep and passed along to their handlers. To take the mental connection further, think of a herd of black sheep. Anthrax is named after its Greek root anthrakitis (anthracite), a reference to the coal black skin lesions of cutaneous anthrax. These blackened craters are usually called eschars, meaning an ulcer with a blackened center. The easiest way to distinguish an anthrax eschar from another skin lesion? Though it looks frightful, it is nontender. Cutaneous anthrax is fairly curable, given proper treatment, though it can be fatal if untreated. The truly frightening type of anthrax is inhalational. Nonspecific fever, malaise, fatigue, and cough rapidly spiral down into all-out respiratory failure and shock within 24-48 hours. This syndrome includes “metastatic infection” – 50% of cases reportedly progress to meningitis. Inhalational anthrax may cause cloudy infiltrates to appear on imaging studies, but it is a mediastinitis (infection of the mediastinum, the body cavity which contains the heart), not a pneumonia.

Plague (Yersinia pestis): Like anthrax, plague generally manifests on the skin or in the lungs. It also shares with anthrax its close association to the color black. Some might surmise that the Black Plague was known as such due to the death and destruction it caused – black times indeed! However, others argue that the blackness of Black Plague is physiologic, and occurs in late stages of the disease through purpura (dark violet stains on the skin) and gangrene of the tips of body parts. The disease courses towards a swift, dramatic death, either through pneumonic plague (a virulent pneumonia with a bloody cough) or through septicemic plague (gram negative sepsis). Septicemia typically develops from cutaneous plague, the infamous ‘bubonic’ plague, which caused infestations of ‘buboes’ -enlarged lymph nodes, after bites of fleas to the typically wet and warm body areas where they hide.

Botulism (Clostridium botulinum): Characterized in the late 1700s in Germany, botulism was named after the Latin word botulus for sausage, since a group of early botulism victims had died after a meal of blood sausage. Despite its meaty etymology, botulism is classically known in medicine to result from improper preserving of honey. The toxin causes a group of gastrointestinal symptoms, including nausea, vomiting, abdominal pain, and distention. For a more severe toxin exposure, the expected presentation would be symmetric, descending paralysis (referred to as “floppy baby” in infant botulism). This occurs due to the action of botulism in preventing acetylcholine release into the synaptic cleft by blocking exocytosis, and is the property exploited by cosmetically inclined patients who prefer a floppy face to a wizened one. Botulism can be treated with an antitoxin or immune globulin.

Smallpox (Variola virus): One of mankind’s greatest achievements was the eradication of smallpox thirty years ago. Unfortunately, “eradication” does not mean that we finally have one fewer thing to study. Smallpox still exists in high security caches and could potentially be weaponized. It is an orthopoxvirus, along with cowpox, monkeypox, and Vaccinia, the virus used in the smallpox vaccine. Like other well known poxes, it causes disseminated vesicle formation on the skin with an appearance in which “the skin seems studded with grains of rice”. Spread by droplet inhalation, it would require a rapid activation of a mass vaccination program if unleashed as a part of a terrorist plot. Since vaccination has not been required since 1972 in the United States, most people under the age of 36 would be vulnerable to an initial attack.

Radiation: Ionizing radiation results from the decay of radionuclides, such as alpha and beta particles, gamma rays and X-rays, and neutrons. Radiation has its own quirky system of units, with the amount of energy in an exposure expressed in “rads” (radiation absorbed dose), and the “rem” (radiation equivalent in man” representing the biological impact of an exposure. Many patients who fear medical radiation through imaging do not realize that they are exposed to about 300-350 mrem annually of background radiation, an additional 16000 rem annually if they smoke a pack a day, and an additional 5mrem each time they board a transcontinental flight. Most mild effects such as nausea and vomiting (“the GI syndrome”), or erythema of the skin that looks like thermal burns, result at acute doses of 100-600 rads. From 500-1000 rads, a pulmonary syndrome of pneumonitis, respiratory failure, and lung fibrosis results. 900-1700 rads will cause a cerebrovascular syndrome, and 1000 rads is considered the maximum survivable dose with aggressive treatment. Radiation sickness is characterized by lymphopenia and anemia. Providers should maintain a high level of suspicion for concurrent radiation exposure with any other biochemical terrorism injury.

Nerve gas: Similar to bioterrorism vectors such as bacteria and viruses, chemical terrorism could occur by either spraying (i.e. from planes or missiles) or droplets dispersed in similar strategies. Chemical warfare is forbidden by international convention, but unfortunately, terrorists do not represent sovereign states and are not bound by these treaties. One of the chemical entities to be aware of is nerve gas, which includes Sarin gas and VX. Like botulism, these chemicals exert their effects at the all-important synaptic cleft. They inactivate acetylcholinesterase and cause the buildup of acetylcholine; in other words, they are cholinergic agents causing symptoms such as salivation, lacrimation, urination, and GI distress/diarrhea. With exposure to high concentrations, patients will experience seizures and respiratory arrest within minutes. Just one drop of sarin is lethal, and a fraction of a drop of VX on the skin can kill. Luckily, VX is quite difficult to synthesize, but sarin has been used in several high profile cases, such as the Iraqi attacks on Kurds under Saddam Hussein.

Cyanide: Cyanide exposure can be encountered in a number of more common settings, not just terrorist attacks. Cyanide toxicity can result from smoke inhalation or other chemical exposures. It acts by halting oxidative phosphorylation and thus causing global hypoxia and switch to cellular anaerobic metabolism. This eventually results in the cyanosis, or bluish discoloration of the skin, for which cyanide was named. Cyanide also classically has the odor of ‘bitter almond’, which is apparent to most humans, except a few who are genetically unable to smell it. Cyanide toxicity can be treated by amyl nitrite, which also happens to cause a mild euphoric state and is otherwise used recreationally – most likely the only therapy for poisoning that could be classified as enjoyable. More commonly used is the Cyanokit, which involves small amounts of amyl nitrite, sodium nitrite, and sodium thiosulfate.

Terrorist attacks, whether they involve biologic or chemical substances, can be nerve-wracking entities to treat for medical personnel who may not initially be aware of the exposure. For patients who appear to have been exposed to a substance such as a powder, oil, or spray, the key is to decontaminate them by removal of all clothing and by thorough showering prior to attempting to treat them and potentially exposing staff to toxic entities. Awareness of potential toxicities and symptom constellations caused by biologic and chemical weapons can save lives, since most have antidotes or effective treatments that must be given quickly for best effect.