From Capsicum Pepper Problems to Multiple Chemical Sensitivity

After my skin prick test results came back negative for capsicum pepper allergy, the allergist I consulted with had no further interest in my case or advice about how to deal with my symptoms: extreme GI upset after even small ingestion exposures, and cough strong and continuous enough to prevent breathing after inhalation exposures (see My Story). She assured me that I didn’t have an allergy to peppers so she had no idea why I thought I was having symptoms. So it was up to me to try to figure out what was going on.

I began my research by looking into the incidence of capsicum pepper allergy. I stress the word capsicum here because these peppers are  from the Solanacea family, also related to tomatoes, potatoes, and eggplant, and are of New World origin. They have large, fleshy fruits that can be green, red, yellow, orange, or purple when ripe, and sweet to very hot in taste. They are completely unrelated to black pepper, or Piper nigrum, which is from the Piperacea family, related to Piper betle, a plant whose leaves are traditionally used to wrap betel nuts. Black peppers are quite small fruits that grow on vines of South Asian origin. I have no problems consuming black pepper in any form, but the tiniest bit of a sweet bell pepper is guaranteed to make me ill.

It turns out that capsicum pepper allergy is not very common, but not unheard of, either. One population where it is known to turn up is with workers in greenhouses that grow peppers. In a survey of 472 greenhouse workers, 53.8% reported “work-related symptoms” (Groenewoud et al., 2002). RAST testing showed 35.4% showed sensitization to bell pepper plants (Groenewoud et al., 2002). In an 8-year follow-up study of a subset of the same population, it was found that atopy [odds ratio (OR) 5.60] and smoking (OR 11.85) were significant risk factors for developing sensitization to bell pepper pollen (Patiwael et al., 2010). Spice mill workers exposed to chili pepper (and incidentally, co-exposed to garlic, onion, and other spice powders) also have been reported to be at increased risk of developing asthma (van der Walt et al., 2010) or rhinitis (Nam et al., 2012). In the general, non-occupationally exposed population, severe reactions to peppers have motivated several case reports, such as the case of a 17-month child (Jimenez and Zacharisen, 2011) or a 38-year old woman with premenstrual asthma (Dikensoy et al., 2001).

Several facts in these articles called out to me. The first was that the only one of those articles that mentioned a positive skin test result for capsicum peppers was the one describing the case of the small child (Jimenez and Zacharisen, 2011). Allergy testing in the greenhouse workers had been with RAST (Growenewoud et al. 2002). RAST, or the radioallergosorbent test, relies on blood analyses, and may be more an indicator of exposure than immune reaction. The spice mill worker with rhinitis triggered by pepper had a negative skin prick test result to capsaicin (Nam et al., 2012). No allergy testing was mentioned in the article describing the woman with premenstrual asthma (Dikensoy et al., 2001). So maybe my own negative skin prick tests for pepper weren’t that anomalous after all–other patients were also showing significant reactions to pepper exposure even if they didn’t have positive skin prick tests.

What was different in my case, though, was the type of symptoms being described. In the case of the small child (Jimenez and Zacharisen, 2011), there was urticaria (hives), facial swelling, and conjunctivitis, all classic immune-mediated allergic symptoms, in addition to severe cough, which was the only symptom I had in common with this case. The papers describing people with occupational exposures to peppers mentioned rhinitis (Growenewoud et al., 2002; Nam et al, 2012). But none of these papers mentioned the severe gastric upset I experienced, or the headaches. At this point, I decided the allergist was probably right after all–not only did I not have positive skin prick tests for pepper allergies, but my symptoms simply didn’t fit the mold for an allergy. Now what?

The ingredient that gives chili peppers their bite is capsaicin or 8-methyl-N-vanillyl-6-nonenamide. Different kinds of peppers have differing amounts of capsaicin. They also have other substances that are very similar in structure that have been capsaicinoids. Even sweet peppers can contain capsaicin as well as other capsaicinoids (Reilly et al., 2001).

Searching “capsaicin”  and “allergy” in PubMed turned up some interesting material. The ability of capsaicin to reliably induce coughing is so well known that it is used as a research tool for studying various aspects of respiratory diseases. Researchers will expose volunteers to differing concentrations of capsaicin in controlled environments and record the lowest concentration of capsaicin required to induce two (C2) or five (C5) coughs. The usual finding in this research is that people with some sort of inflammation show an increased “capsaicin cough response.” For instance, people with allergic rhinitis have been shown to have an increased capsaicin cough response (Pecova et al., 2008). So have children with asthma (Jasenak et al., 2009), adults with asthma (Couto et al., 2013),  patients with chronic obstructive pulmonary disease–COPD, (Terada et al., 2009), patients with upper airway cough syndrome (Yu et al. 2010), children with upper respiratory tract infections (Plevkova et al., 2006), and people with chemical sensitivity (Johansson et al., 2002, 2006; Ternesten-Hasséus et al. 2002). Similarly, people with functional dyspepsia show an increase in symptoms after oral capsaicin exposure (Hammer et al., 2008), and people with multiple chemical sensitivity (MCS) show a hyperalgesic (increased pain) response to topical capsaicin exposure (Tran et al., 2013).

Multiple Chemical Sensitivity? I had never heard of that disease before. It seemed to be the same disease that the Johansson group was calling sensory hyper-reactivity or chemical sensitivity. In one paper, the Johansson group described these patients as having “pronounced sensitivity to chemical odours, such as perfumes, flower scents and tobacco smoke” (Johansson et al., 2002). In another paper by the same group, the authors mentioned a pronounced sensitivity to perfumes, cleaning agents, and flower scents. (Johansson et al., 2006). These comments got me thinking. On the one hand, I had never considered myself exceptionally sensitive to these scents. When exposed to them, I found they gave me headaches, which would lead to nausea and achy joints if I didn’t seek fresh air immediately. But I thought that happened to everyone, that it was normal.

But if perfume really gave everyone such equally awful headaches, why would anyone buy it and wear it? And then there was my daffodil problem. I had planted hundreds of daffodils in my yard a few years ago, only to find that when they were in bloom, I couldn’t sit in my yard to enjoy them or cut and bring them in the house for bouquets because they would give me a headache and nausea. When I first connected the headaches to the daffodil blooms, I mentioned this to my friends, and they looked at me funny–they said daffodils didn’t give them headaches at all. I had the same problem with Easter lilies. I loved to look at them, but if I was within 20 feet of one, the smell would give me a pounding headache. Tobacco smoke wasn’t so much of a problem, but thanks to second-hand smoke rules, I was hardly ever exposed to it. Cleaners? Ugh–those gave me a headache, too, so for years, I had only been using unscented products in my home. New carpets–they were another problem. When our local Staples store moved to a new location, the new carpet smell in the store was so intense I got a headache and became nauseated just standing by the front door. I simply couldn’t go inside to shop. It puzzled me how others could blithely enter and browse about the store despite the smell. Could it really be that other people weren’t affected like me? Or could I actually be hypersensitive to chemical scents in some way? And could a hypersensitivity to chemicals somehow be connected to my capsaicin hypersensitivity?

Indeed, between the negative skin prick results and the constellation of symptoms on pepper exposure, especially the severe, inhalation-preventing cough when exposed to steaming pepper vapor (see My Story), I admitted that the allergist was completely right. I had a hypersensitivity to peppers, not an allergy. Years before, I had been diagnosed with environmental allergies through skin prick tests, and my new research had found a connection between environmental allergies and capsaicin hypersensitivity. Thus, my environmental allergies could be one explanation for my capsaicin hypersensitivity. But given how my symptoms from chemical exposures matched those described for multiple chemical sensitivity, I felt I should at least discuss the possibility of MCS with my doctor, to find out what she knew about MCS, and if she thought that might be contributing to my problem with peppers.

I returned to my primary care physician with the results of my skin prick test and my Internet research. I reviewed my capsaicin exposure symptoms with her again, and this time also mentioned my chemical sensitivities to perfumes, flowers, cleaners, and carpets. I pointed out that in my research, I had found mention that there is a TRP channel specific to capsaicin, TRPV-1, found on nerve receptors in both the respiratory and digestive tracts [more on TRP channels and capsaicin in a later post], and maybe this could be a mechanism that would connect both my capsaicin hypersensitivity and my chemical hypersensitivity.

“So what do you think?” I asked her. “Would that be a plausible explanation for my pepper problems? And do you think my chemical sensitivity issues sound at all like multiple chemical sensitivity?”

The doctor stared at me in disbelief, as if I had asked her if my pepper problems stemmed from being bit by a leprechaun. She knit her brow. After a pause, she asked, “Well, let’s check your blood pressure. And maybe we should calculate your BMI as well.”

I swung my arm over so she could adjust the blood pressure cuff. The doctor never answered my questions, however. She just continued with the physical exam as if I had not spoken. It wasn’t until I later, when I had done some more research that I found out why–I had used the term Multiple Chemical Sensitivity in her office. And at least in the United States, Multiple Chemical Sensitivity officially doesn’t exist, so my doctor simply wasn’t going to discuss it with me. I was back in the Do-It-Yourself medicine zone again.

Sources Cited

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Dikensoy, O., Bayram, N., & Filiz, A. (2001). Severe Asthma Attack in a Patient with Premenstrual Asthma: Hot Pepper Is the Possible Trigger Respiration, 68 (2), 227-227 DOI: 10.1159/000050500

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Yu, L., Xu, X., Wang, L., Yang, Z., Lü, H., & Qiu, Z. (2013). Capsaicin-sensitive cough receptors in lower airway are responsible for cough hypersensitivity in patients with upper airway cough syndrome Medical Science Monitor, 19, 1095-1101 DOI: 10.12659/MSM.889118