Something Stinks
Want to know poisoning is often mistaken for an allergic reaction? What you risk by eating barracuda? What causes Foreign Accent Syndrome when a person suddenly starts speaking in another language?
This is the Pick Your Poison podcast. I’m your host Dr. JP and I’m here to share my passion for poisons in this interactive show. Will our patient survive this podcast? It’s up to you and the choices you make. Our episode today is called Something Stinks. Want to know poisoning is often mistaken for an allergic reaction? What you risk by eating barracuda? What causes Foreign Accent Syndrome when a person suddenly starts speaking in another language? Listen to find out!
The last episodes dealt with some heavy topics, so I wanted to change it up and cover some lighter toxins in the next few episodes.
Today we start in the emergency department. Your resident flags you down in the hallway to tell you about a patient he’s concerned about in room 9. As you walk down the hall towards the room, he presents the case. It’s a 30-year-old man with a rash and itching after eating fish. The resident is concerned about anaphylaxis, though the patient has no prior history of allergies. He tells you he's treated the man with IV steroids, Benadryl and famotidine, brand name Pepcid.
The patient is awake and alert scratching his extremely bright red skin. His vital signs are as follows temperature 98.5 Fahrenheit or 36.9 Celsius. His heart rate is 105 bpm, blood pressure is 110/60. His respiratory rate is 20 and he's satting 100% on room air.
The patient essentially tells you the same thing as the resident. He works as a clerk on a MedSurg floor in the hospital and was fine this morning. He went to the cafeteria for lunch, ordering the daily special, sushi. He has no history of food or other allergies. Before even finishing the meal, he developed a metallic taste in his mouth and tingling in his tongue. This was followed by rapid development of the red, itchy rash. He became concerned about an allergic reaction to the fish and checked in.
He denies other new exposures, like new laundry detergent, lotions, medicines, over the counter drugs or supplements. He says he feels better already with the treatment ordered by the resident. You examine him, specifically noting no facial or tongue swelling. His lungs are clear to auscultation, without wheezing. His skin exam is notable for bright red flushing across this face, chest and extremities. Basically, he’s beet red with no other findings.
You agree with the resident’s assessment, likely an allergic reaction to fish and advise the patient to avoid it in the future. You tell the resident to watch him for a few hours to make sure the symptoms don't return, and when ready for discharge to prescribe an EpiPen in case of a more severe reaction in the future.
True or False. You can have an allergic reaction to something on the first exposure. Generally, this is false. In a classic anaphylactic reaction, you need IgE, to over react and cause release of histamine from mast cells. Histamine then causes many of the symptoms, including rash, swelling, etc. IgE is an antibody produced by your immune system on the first exposure, then causes the allergic reaction on a subsequent exposure.
There are other types of reactions that can occur on the first exposure. These are often anaphylactoid reactions. Morphine and IV vitamin K are classic causes. These drugs cause direct stimulation of mast cells, and can cause allergic reactions without the immune system, no IgE involved, or prior exposure. This is actually an adverse drug effect, rather than a true allergic reaction. Patients often get hives on their arm after IV morphine, I don’t worry about anaphylaxis if they get it again, because this is a side effect, not a true allergy.
What defines anaphylaxis, rather than just an allergic reaction? Urticaria ie hives, or other skin changes, along with either respiratory symptoms, low blood pressure, or end-organ dysfunction like loss of consciousness. Or two severe symptoms plus gastrointestinal symptoms, like cramping, vomiting or diarrhea.
The patient is improved, and satisfied with wrapping up the case quickly and efficiently, you move on to other patients.
About 20 minutes later, the intern pulls you into a room 3. The patient is also having an allergic reaction. She’s a 42-year-old woman also with no prior history of allergies. Shortly after a lunch of sushi, she turned red, became extremely itchy. Her vital signs are notable for a mildly low blood pressure at 90/60 but are otherwise normal. Like the last patient, her skin is very red. Though as with him, you don't notice any raised skin, meaning hives or wheals. The intern asks how to treat her. You recommend the same treatment the resident gave the other patient intravenous fluids, steroids, antihistamines, and famotidine.
As you pull the curtain shut behind you on the way out, the resident grabs you and said I've got another allergic reaction in four.
OK. What is happening?
This is a pretty big coincidence, three people with allergic reactions in an hour. The third patient works as a nurse at the hospital. She too went to the hospital cafeteria and had sushi during her lunch break. Her vital signs are unremarkable. Her skin is also extremely red and flushed.
Question 1. What physical exam finding is a clue that our patients are not having an allergic reaction like anaphylaxis?
A. flushed skin.
B. Urticaria or hives
C. Blood pressure
Answer: B. Urticaria, the medical term for hives. Patients with anaphylaxis will have hives, I’m sure you’ve seen this or experienced it yourself. That’s missing here. The skin is red, but without a raised rash.
You send the intern back to patient number two to ask where she ate lunch. You guessed it, the hospital cafeteria.
Uh oh this is not good.
Is this food poisoning? Yes, it’s obviously a foodborne illness. But it's not the classic diarrheal illness we think of related to bacterial food poisoning. First, none of our patients have GI symptoms, second the onset after exposure to bacterial endotoxins can be quick, but not this quick just 15 minutes after exposure.
So what could it be? There are foodbourne toxins not produced by bacteria. We’ve discussed a few like tetrodotoxin from puffer fish. What do you think? No, the patients would be paralyzed which our patients don't have and hopefully won't develop. In addition, pufferfish is a delicacy and a bit too fancy for our hospital cafeteria. In fact, you’re surprised they have sushi. Sounds like they shouldn’t. I’ll tell you the truth, I’ve never been to the hospital cafeteria in most of the institutions I’ve worked in. We ED doctors rarely get to leave the ED.
We've also talked about seafood contaminated with algae, for example paralytic shellfish poisoning due to domoic acid. The poison that inspired Alfred Hitchcock’s The Birds. Other types include amnestic, diarrhetic and neurotoxic shellfish poisoning. Listen to the Amnesia episode for more, but none of those fit here. Improperly cooked fish can transmit tapeworms, but again not right here.
Ciguatera is a fishborne illness and one of the most commonly food borne illnesses reported worldwide. Patients get gastrointestinal upset, dizziness, numbness and tingling, among other nonspecific symptoms. It causes one very strange symptom. Specific and weird.
Question 2. This is a tough one. Ciguatera causes which of the following?
A. Cold allodynia - reversal of hot/cold sensations
B. Foreign accent syndrome - when a person suddenly starts speaking a different language
C. Alice in Wonderland syndrome - believing the head, hands and feet have become distorted in size
D. Fish Odor Syndrome - when the sweat smells like fish
Answer: A. Cold allodynia. The other answers are fascinating medical problems due to other causes. Foreign accent syndrome can occur after a stroke, Alice in Wonderland syndrome, perception of distorted hands and feet, along with distortions in the perception of time can be caused by migraines. Fish odor syndrome is caused by trimethylaminuria, a metabolic disturbance where the body can’t break down that compound, resulting in a fishy smell. Ciguatera causes cold allodynia. It’s a really bizarre symptom, things that are hot taste cold, and things that are cold, taste hot.
Ciguatera is caused by a toxin produced by dinoflagellates, like paralytic and amnesic shellfish poisoning. In this case tho, it’s not from a algal bloom or overgrowth as the cause. It’s due to bioaccumulation. The dinoflagellate is eaten by smaller fish, as larger fish eat the smaller fish, the dinoflagellates accumulate into to dangerous amounts. Barracuda is a classic case, the reason the CDC advises against eating it. Many communities in the US, especially Caribbean ones eat it anyway. Generally, the symptoms resolve in a few days though about 20% of patients have persistent symptoms. Another bizarre fact is symptoms can be retriggered by eating more of the same fish, or things like alcohol or caffeine.
Anway, back to our patients. They don’t have ciguatera. They basically only have symptoms of an allergic reaction.
Question 3. Time to pick your poison. Our patients have which of the following?
A. Scombroid
B. Hepatitis A
C. Giardia
D. Listeria
Answer: A scombroid. Hep A is common in seafood, classically oysters, but it causes liver failure. Giardia is a parasite, common after drinking mountain stream water. Listeria is a bacterial infection. Both cause GI distress, vomiting and especially diarrhea.
Our patients all have scombroid and this is a classic outbreak. Unfortunately, the hospital cafeteria seems to be the culprit. Scombroid is so named because it often happens in fish from the Scombridae, the family of fish including tuna and mackerel, though it's not limited to these species. Scombroid is the name of the disease, but what it is actually is histamine poisoning. Histamine causes allergies, the reason allergy medicine is antihistamines. Histamine is inside your mast cells and gets released during an allergic reaction, from simple seasonal allergies all the way up to true anaphylaxis and anaphylactic shock. In the case of scromboid, however, histamine isn't being released by the patient's body because this is not an allergic reaction.
Rather, histamine is being ingested by the patient because it's on the fish they consumed. How does it get on the fish? It happens if the fish is improperly stored, specifically if it doesn't stay refrigerated. Bacteria on the unrefrigerated fish convert histidine to histamine which you then ingest. These gram negative bacteria, like Klebsiella and E.coli, live in the fish’s gills and GI tract. If the fish are exposed to temperatures above 40 Fahrenheit (or 4 Celsius), it’s warm enough for the bacterial to generate histamine. Once formed, it’s resistant to breakdown by heat, meaning cooking the fish doesn’t prevent the disease.
Question 4. What is the best way to test for scombroid poisoning?
A. Send the patient's blood for histamine levels
B. Check histamine levels in the fish.
C. Check for those bacteria in the fish.
Answer: B check the fish histamine levels. Different countries have different safe levels of histamine allowed on seafood, I believe 50 mg/dL in the US and 100 mg/dL in Europe. Below 100 is defiantly safe and above 200 is definitely dangerous.
Is this the fault of the hospital cafeteria? Possibly, though more often the poor storage conditions come during transport. I wasn't aware until I started the research for this episode that the FDA has really strict regulations for the rapid cooling of fish after they're caught. Starting at the fishing boat, logs have to be kept about the time the fish were caught, the air and water temperatures, the method of cooling and the fish temperature. Amazingly, this has to be recorded every hour. The logs continue until the fish is bought by either a grocery store or a restaurant. A lack of refrigeration for two hours is enough time for the bacteria to produce a toxic level of histamine.
After an outbreak, it’s usually the local health department who tracks down the source, ensuring no one else is exposed. If you live in the US, hopefully your local epidemiologist hasn’t become the victim of budget cuts and still has a job. Otherwise, the outbreak will affect a lot more people.
Exposures have occurred in all sorts of places, including hospital cafeterias, military dinners, school cafeterias, fancy restaurants, and even kindergartens. I got very distracted by a report of one outbreak in a Korean elementary school. Not by the disease but by their lunch. They had rice, seaweed and beef soup, yellowtail steak, sweet-and-sour mushrooms, kimchi, and milk. Not exactly the chicken patties and frozen pizza that I ate for lunch in the US.
The scientific word for poisoning is Ichthyosarcotoxism. The treatment? You guessed it, antihistamines. You can use first generation antihistamines like diphenhydramine ie Benadryl or less sedating second-generation ones like cetirizine and loratadine (ie Zyrtec and Claritin).
The symptoms, even without treatment, are usually self limited, resolving within a few hours. Scombroid can cause asthma exacerbations in patients with a history of asthma. There are very few rare reports of hypotension ie low blood pressure with shock and respiratory distress. Only one death is reported, after exposure from eating crabs.
The true incidence of scomboid is impossible to measure, some people with mild symptoms never present to the emergency department and certainly some are misdiagnosed as a seafood allergy. It's estimated that between 2 to 5 cases per million inhabitants occurs in Europe, with higher rates, as many as 31 cases per million habitants, in Hawaii.
There are a few medicines which can make the reaction worse, interestingly enough. Isoniazid, a drug for tuberculosis or monoamine oxidase inhibitors, an older class of antidepressants, can cause more severe and longer lasting symptoms as these drugs inhibit the metabolism of histamine in the human body.
I mentioned earlier we treated the patients with famotidine, and acid blocker you might’ve taken for heartburn. Why? It also has antihistamine properties. It’s in a category of drugs called H2 blockers, they decrease acid production by blocking H2 histamine receptors in the stomach. They’ve been shown to have some effect on H1, the type of histamine receptors involved in allergic reactions.
Scombroid was first described in the UK in 1799. Histamine was suggested as the cause in the 1940s but it wasn't until 1991 that histamine was proven to be the cause. It’s a nice paper in the New England Journal of Medicine if you're interested by Morrow with a study conducted on medical personnel at Vanderbilt University after an outbreak in their hospital cafeteria.
Back to the ED. It’s swamped over the next hour with red itchy patients concerned about seafood allergies. You resolve never to eat at the cafeteria. You assign the intern to these patients; he successfully treats them all with antihistamines and all make a complete recovery an hour or so after exposure.
You notify the cafeteria and advise them to stop serving the sushi. You call the health department who initiates an investigation, finding, phew, it wasn’t the cafeteria’s fault, but rather a breakdown in the fish transport to their supplier. The investigator pulls the rest of that batch from other restaurants, preventing further exposure.
This is a fictional case, as are all our cases, to protect the innocent. But it is based on real poisonings and real hospital cafeteria outbreaks.
Last question in today’s podcast. Question #5. Once the fish become contaminated with elevated levels of histamine, freezing and canning the fish is a good way to get rid of it.
A. True
B. False
Follow the Twitter and Instagram feeds both @pickpoison1 and you’ll see the answer when I post it. Remember, never try anything on this podcast at home or anywhere else.
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While I’m a real doctor this podcast is fictional, meant for entertainment and educational purposes, not medical advice. If you have a medical problem, please see your primary care practitioner. Thank you. Until next time, take care and stay safe.