S. Rutherfoord Rose, PharmD

Poisons have been a threat to the health and well-being of humankind for millennia. The word toxin is derived from the ancient Greek word 

meaning "poison into which arrowheads are dipped" (in reference to Hercules' use of arrows dipped in the venom of the Hydra to slay the centaur Nessus).

Over the ages, poisons have played a considerable role in human affairs. Whether speaking of Socrates and his cup of hemlock, of those condemned to the "penalty of the peach" (administration of peach pits that contain amygdalin, which is metabolized to cyanide), or of the gas chamber (sulfuric acid mixed with sodium cyanide pellets in an enclosed area), poisons have been employed over the ages as an effective means of execution.

The use of toxins in a less than judicial role litters the course of human history as well. Arsenic, referred to as the 

 (the powder of succession), helped ambitious princes secure thrones. Poisoning as a means of political gain is even evident in the recent dioxin poisoning of Victor Ushenko, the newly elected president of Ukraine. Poisons have also been employed throughout history as weapons of war and terror. Hannibal's sailors catapulted pots full of venomous snakes onto the decks of the opposing fleet. Members of the Aum Shinrikyo cult killed fellow countrymen after releasing sarin gas in a Matsumoto neighborhood and on Tokyo subway trains in 1994 and 1995, respectively. And certainly in the post-9/11 environment, chemicals employed as weapons of mass destruction and terror remain a concern of the ongoing national security debate.

But to focus solely on the more deceitful aspects of poisons is to miss the broader scope of their influence in the lives of our patients. We live in a world of toxins and potential toxins, and thus we are often just a misstep away from a toxic exposure and its consequences. Even that which is meant to cure can kill. As Paracelsus, the 16th-century German-Swiss physician and alchemist, said, all substances are poisons; there is none which is not a poison. The right dose differentiates a poison and a remedy. The truth in his words echoes today: exposure to the wrong dose of a medication (whether accidental or not) remains a common form of toxic exposure.

Medications are only one example of potential toxins in the home. Household cleaners and other chemicals are common sources of intentional and unintentional poisoning. Chemicals used to improve our lives or environment--such as herbicides, pesticides, fertilizers, and hydrocarbon fuels used in agriculture or industry--are potentially harmful if improperly used.

From the massive toxic gas release from Mount Vesuvius in ad 79 to the release of methyl isocyanate gas in one of the greatest civilian toxic disasters in modern history in Bhopal, India, in 1984, natural or industrial toxic releases remain a potential threat to health.

 Given the ubiquitous nature of potential poisons, exposure to a toxin should be included in the differential diagnosis of patients with unexplained illnesses or unusual presentations.

The American Association of Poison Control Centers--whose 62 participating poison centers service the population of the 50 states and the District of Columbia--has compiled poisoning data since 1983 and created the Toxic Exposure Surveillance System (TESS). According to the TESS 2004 annual report, US poison centers reported a total of 2,438,644 human exposure cases. Sixty-five percent of reported exposures were in children; of those pediatric exposures, 51.3% of all exposures occurred in children younger than 6 years. Patients younger than 13 years were predominantly male. However, this gender predominance was reversed in teenagers and adults.

Most toxic exposures were unintentional (84.1%) and involved a single toxic substance (91.4%). Most exposures occurred at the patient's residence or another residence (89.7% and 3%, respectively). Ingestions (76.8%) were by far the most common route of exposure; dermal exposure and inhalation ranked second and third (7.5% and 5.9%, respectively).

Most patients were treated at the site of exposure and received only poison center support. Some were treated and subsequently released from a health care facility (11.6%). Only 6.8% were admitted to a health care facility for further examination and treatment.

You will have taken the first step in correctly diagnosing a toxicologic illness or injury by entertaining that possibility in your differential diagnosis. A good history--one that concentrates on uncovering possible toxic exposure--provides you with the means to zero in on the offending agent or agents and focus your physical examination.

Start with the usual: question the patient, parents, and/or others involved in the patient's care to develop a complete understanding of the constellation of acute complaints. Ask specifically about any temporal associations with these complaints. Establish a timeline of your patient's complaints. 

Next, determine whether anyone in the patient's family or school, or among their other regular contacts is experiencing the same or similar symptoms.

 Ask the parents about any medications the child may be taking (both prescription and over-the-counter).

 What vitamins or nutritional supplements does the patient take?

 Does the patient take any herbal or nontraditional remedies?

stop with the patient's medications: who else's medications are reasonably available to the patient in his or her home environment?

 Could the patient be ingesting (inadvertently or intentionally) a family member's medications, supplements, or remedies?

 Does the patient consume any unusual foods that might have a toxic effect, either acutely or of a more cumulative nature?

 Does the patient consume any natural or organic foodstuffs?

 Is there any reason to suspect that the patient may be consuming any food that may be contaminated with herbicides, pesticides, or other toxic chemicals?

 Ask the parents about the particulars of the patient's home. The age and type of structure can provide valuable clues about materials that might reasonably be found in that residence. For example, was the patient's home built before the 1978 US ban on lead in new paints? If so, the home has a greater likelihood of containing lead-based paints.

 What type of heating and cooling devices are used in the home?

 Does the home have an old furnace in disrepair that potentially leaks carbon monoxide throughout the house?

 What household chemicals are stored or used in the house or outlying structures?

 Does the patient have access to these stored chemicals? 

 Is the patient's home supplied by a city water system or by a separate, well-based system?

 If the source is a large city water system, is there reason to suspect contamination--perhaps with hydrocarbons or other industrial chemicals?

 If well water is the source, is there reason to suspect agricultural runoff, herbicides, or pesticides as possible contamination?

 Where does the patient attend school? How long has he been attending that school?

 What material(s) does the patient handle at work or school?

 Are there any materials or procedures that require specific safety precautions or equipment? If so, does the patient use appropriate personal protective equipment?

 Is the patient exposed to any confined or poorly ventilated spaces throughout the day?

 Is there any ongoing or recent construction or repairs to the patient's school?

 Are there centers of agriculture or industry nearby?

 Does the patient engage in any hobbies or leisure activities that might present an increased risk of toxic exposure? 

Our patients lead interesting and complex lives. When you suspect a possible toxic cause for their presenting complaints, you must try to develop a comprehensive picture of the world in which they live. A thorough and detailed history that explores all potential sources of toxic exposures is perhaps the most important element of making an accurate diagnosis of poisoning.

A head-to-toe examination should be performed on every patient who presents with multiple acute complaints--especially those that are vague or nonfocal. Focus on vital signs and organ systems often affected by potential toxins in an effort to assess your patient for a toxicologic syndrome, or "toxidrome" (listed in the 

 Look at your patient globally. Does he appear acutely ill or uncomfortable? Does the general appearance fit with your review of vital signs? Is he especially warm or cool?

 Do the vital signs represent a pattern consistent with any common toxidrome (anticholinergic, sympathomimetic, or other)?

 Dermatologic findings (including mucous membranes): Is the patient dry or diaphoretic? Flushed or pale? Is he cyanotic? Are there any rashes or discrete lesions evident? Is the patient salivating? Lacrimating? Is rhinorrhea present?

 Neurologic findings: Is there altered mental status, nystagmus, or myoclonus? Is there hyper- or hyporeflexia?	

 Ophthalmologic signs: Is there miosis or mydriasis? Are the pupils equal, round, and reactive to light?

 GI signs: Are bowel sounds hyperactive or reduced? Is there evidence of incontinence?

 Genitourinary signs: Can you palpate the bladder (consistent with urinary retention)? Is there evidence of incontinence?

The following are reasonably available to the office-based provider:

15-year-old boy, who has been your patient for over 6 years, comes to your office with an approximately 6- to 7-day history of what he describes as flu-like symptoms. These are characterized predominantly by generalized fatigue and malaise with nausea and vomiting (1 or 2 episodes of nonbloody, nonbilious emesis per day). The patient attributes these symptoms to the especially cold weather over the past couple of weeks. He denies any chest pain, palpitations, or shortness of breath. There is no cough, nasal discharge, sinus pressure, or congestion. He denies any diarrhea or additional GI symptoms. He denies dysuria and other genitourinary complaints.

He describes a generalized difficulty in thinking and concentrating on tasks at home and at school over the past few days. He describes no focal neurologic deficits, but he has had mild intermittent headaches during this time without neck stiffness, photophobia, or additional complaints that he can attribute to these headaches. His symptoms are worse in the morning and then improve throughout the day or during periods away from home.

The patient has no past medical history and until the past week or so his family has been quite healthy. He does not smoke or drink, and he denies illicit drug use. He lives with his mother, father, and younger sister--all of whom have been experiencing similar symptoms during the same period.

The patient says that he lives in a home built in the mid-1980s. He does not know the particulars or current condition of the heating and air conditioning systems, but he knows that his furnace burns oil. The home is supplied with city water. The family has not received notification of any water contamination issues. He has not noticed any appreciable disruption in the water supplied to his home, nor any alteration in odor, color, or clarity.

The patient's home is located within a large area zoned for residential use. He can think of no agricultural or industrial sites within at least 10 miles, and no fumes or odors from industry have been noticed around his home. There are no railways, highways, or waterways nearby, and no reports of recent accidents involving hazardous materials transportation vehicles near his home or school.

The patient takes no medications, vitamins, nutritional supplements, or nontraditional remedies. The patient's parents each take a daily multivitamin. The patient eats a variety of fruits and vegetables purchased at a local supermarket, which are washed thoroughly before preparation.

After school, the patient works as a courier in a large office building that was built in the past 5 years. He attends a newly constructed local high school. There is no ongoing construction or renovation. Various classmates have experienced symptoms that are similar to the patient's own; these are generally attributed to "that crud going around the school this time of year."

The patient's hobbies include tennis and card games with friends at their homes. He does not spend any appreciable time in a toolshed, basement, or other enclosed work area for hobbies or entertainment. He does help his parents with yard maintenance projects during the summer, including applications of various pesticides and herbicides.

 Oral temperature 98.9ºF (37.2ºC); heart rate, 102 beats per minute; blood pressure, 138/86 mm Hg; respiration rate, 18 breaths per minute; oxygen saturation, 99% on ambient air.

 Mildly ill appearing, but alert and cooperative.

 Pupils equal, round, and reactive at 4 mm bilaterally. Anicteric sclerae without conjunctival injection or lacrimation. No rhinorrhea or nasal drainage. No oropharyngeal erythema. Moist mucosal membranes without excessive salivation or lymphadenopathy.

 Warm, anicteric skin with normal turgor, and without flushing, diaphoresis, pallor, piloerection, or cyanosis. No rashes or discrete lesions.

 Lungs clear to auscultation bilaterally.

 Tachycardia, though regular rhythm. No murmurs, rubs, gallops. Point of maximum intensity is nondisplaced.

 Soft, nontender, nondistended, no rebound or guarding. Normoactive bowel sounds auscultated in 4 quadrants. No palpable bladder.

 No clubbing, cyanosis, or edema. Pulses symmetric and within normal limits. No lymphadenopathy, including in groin and axilla.

 Oriented to person, place, and time. Motor and sensory examination symmetric and within normal limits bilaterally. Normoreflexive. No asterixis or evidence of myoclonus. Results of Romberg and Babinsky tests negative.

Results of the basic metabolic panel are as follows:

Results of electrocardiography are as follows:

The differential diagnosis includes an upper respiratory tract infection, a viral syndrome, and carbon monoxide poisoning.

Articles

Poisons have been a threat to the health and well-being of humankind for millennia. Given the ubiquitous nature of potential poisons, exposure to a toxin should be included in the differential diagnosis of patients with unexplained illnesses or unusual presentations.

S. Rutherfoord Rose, PharmD

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