Are allergies causing you a lot of pain? Someone is a thousand times more unlucky than you | International Allergy Day

In the past, when materials were not abundant, it was difficult for people to understand the behavior of some people who "didn't eat this or that". If you were allergic to very common foods, such as watermelon or chopped green onions, you might easily be seen as "weird", "pretentious" or "making excuses because you don't like it". Later, allergies became more and more common, and relevant knowledge became widely popular, and people gradually became accustomed to various allergies. However, there are still some rare allergic reactions that make patients' lives difficult.

Written by | Xiaoye

"The shade of green trees is thick and the summer is long; the reflection of the pavilion is reflected in the pond" describes the comfort of ancient poets who escaped the scorching sun in the cool pavilion. However, for some people, the pavilion can also save their lives because they are allergic to sunlight. This is a relatively rare allergy and belongs to the category of photodermatitis[1]. In fact, allergy is an inappropriate reaction of our body's immune system to normally harmless substances. Common reactions include nasal congestion, sneezing, itching, etc., and severe reactions can even be fatal. Common allergens include pollen, dust mites in the house, food, animal hair, insect bites, and some medicines.

July 8th of each year is the International Allergy Day, which is designated by the World Allergy Organization (WAO) and allergy agencies of various countries. Let us take this opportunity to learn about rare allergies besides common allergies.

No more sunshine

Alice Sanders was a young girl who loved outdoor running. Sunshine, breeze and exercise can help relieve anxiety and regulate emotions. Seven years ago, she suddenly found that every time she finished running, she would have a large rash on her hands, arms, shoulders and legs, but it disappeared in less than an hour. At that time, she didn't pay much attention to it, thinking that it might be because the exposed skin came into contact with pollen on the road and caused a small rash. Until one day, she went to swim in an open-air swimming pool and felt hot and itchy all over her body. Later, when she took a shower, she found that the skin on the part of her body covered by the swimsuit was normal, while the exposed skin became red and swollen. At the same time, she began to feel dizzy and fell to the ground. Her friends and swimming pool staff rushed to rescue her. Fortunately, the situation was not serious. In the end, Sanders put on her clothes with the help of her friends, but the scene made her extremely depressed.

Diagnosis of stinging nettles on the arm by James Heilman, MD | Source: Wikipedia

Afterwards, Sanders went to the hospital for treatment and was diagnosed with solar urticaria (SU), which is generally referred to as an allergy to sunlight. Every time she told others that she couldn't stay in the sun, they would often laugh. But for Sanders, this was no joke, because her skin would indeed be "burned" by the sun, and the symptoms were unpredictable. Sometimes it was just a small rash, and sometimes it was a rash all over the body. In addition, allergies do not necessarily occur when the sun is the strongest. For Sanders, as long as the UV index is high, she will inevitably have an allergy when she goes out. This was like a time bomb, which had a great impact on her psychology: she began to be afraid to go out. The sunnier it was outside, the more depressed she felt. Sometimes she would even feel her skin itching and burning when she saw photos of swimming pools, beaches, and coconut trees. [2]

Unfortunately, solar urticaria is a rare, immunoglobulin E (IgE)-mediated, chromophore-dependent, photodermatosis, and there is no precise data on its incidence. However, according to some clinical reports, the clinical incidence of solar urticaria is approximately 2.3% to 17.8% [3, 4]. In 2004, a retrospective study in Singapore evaluated 21,974 cases of urticaria in Singapore over a 10-year period, of which solar urticaria accounted for only 0.08% [5]. In most cases, the age of the first onset of the disease was between 20 and 40 years old, while related cases have also been reported in newborns, infants, and the elderly.

Although solar urticaria is rare, its history can be traced back more than 100 years. In 1904, French doctor P. Merklen first described the symptoms of solar urticaria in his four-volume book "Dermatological Practice: On Applied Dermatology" [6]. In 1924, American doctor WW Duke published a paper in the JAMA journal (Journal of the American Medical Association), formally coining the term "Urticaria Solaris" (urticaria means hives, and solar means sunlight) [7], referring to the rash caused by light. In 1928, German doctor Wucherpfennig first induced a rash reaction under experimental conditions through a series of light tests with different wavelengths [8]. In the 1950s and 1960s, dermatologists from various countries conducted different studies to trace the cause of solar urticaria and attempted to classify it. With the advancement of action spectrum detection technology, Dr. Colin A. Ramsay of the London Institute of Dermatology in the 1980s divided solar urticaria into three types according to the main action spectra: UVB type (290-320nm), UVA type (320-400nm) and broad-spectrum type (290-700nm) [9]. Sanders underwent spectrum testing after the onset of the disease, hoping to determine the spectrum range that would cause him to be allergic and the range that would not cause him to be allergic.

Although the research on solar urticaria has a long history and a large number of studies, its pathogenesis still needs to be further verified and clarified. Some experts hypothesize that a certain precursor molecule in the dermis absorbs light and is activated to form an immunologically active photoallergen, producing specific IgE antibodies, leading to an antigen-antibody reaction. Subsequently, mast cells are stimulated by allergens to expel the pre-formed granules from the body (a process called "degranulation"), releasing chemical mediators that act on dermal blood vessels to form erythema, wheals, and itching [10]. In addition, some experts have proposed, based on serum transfer experiments, that circulating serum factors cause the patient's mast cells to degranulate, ultimately leading to the appearance of a rash [11]. With the development of modern medical technology, scientists have a deeper understanding of the molecular dynamics of skin mast cells, and may soon be able to clarify the specific pathogenesis of solar urticaria.

Solar urticaria has a long course of disease, and a considerable number of patients will continue to have it for life, making it difficult to cure. Therefore, physical methods combined with drugs are often the only way to control symptoms, such as wearing long sleeves and long pants, holding an umbrella, wearing a wide-brimmed hat, and applying sunscreen when going out. At the same time, under the guidance of a professional doctor, taking a certain dose of antihistamines or other immunosuppressive and regulatory drugs, and using anti-IgE biological agents therapy will have a certain effect on symptom control. In addition, ultraviolet light therapy can also be used to increase the body's tolerance to light by gradually increasing the light dose in a regular manner, thereby achieving a "desensitization" effect [12]. In some extreme cases, doctors will consider performing plasma exchange therapy on patients. Once successful, the patient's photosensitivity will decrease, and they can continue to receive desensitization treatment. However, this treatment is very risky. If you are not careful, it may cause the patient to suffer anaphylactic shock or be infected by other people's blood, threatening their life safety.

I will never eat pork, beef or mutton (red meat) in my life

In 1987, Australian doctor Sheryl van Nunen received a strange patient in the middle of the night. Van Nunen is a well-known allergist in Australia and has seen all kinds of mysterious allergic symptoms. However, this midnight visitor is not an ordinary allergy patient, because most allergic reactions will occur immediately after contact with the allergen, rather than appearing until bedtime late at night. She checked whether the patient had been in contact with obvious irritants, and the result was negative. Then she thoroughly examined the patient's medical history, asked about everything he had eaten and touched a few hours before going to bed, and performed a skin test. The only potential allergen that tested positive surprised her very much: red meat eaten for dinner.

This was the first time Van Nunen had ever seen a patient who had allergic symptoms triggered by eating red meat. In the 1990s, she saw six other patients with the same allergy problem; by 2003, she had seen at least 70 patients with red meat allergies, which she diagnosed as "mammalian meat allergy" (in nutrition, red meat refers to meat that is red before cooking, and the red color comes from the myoglobin contained in mammalian meat). However, she had no idea what the specific cause of the symptoms was. [13]

Van Nunen told his colleagues about his findings. Similarly, his colleagues found it hard to believe at first that humans could have allergic reactions to the meat of mammals. Subsequently, these curious scientists investigated 25 patients who came to the clinic between 2003 and 2007. All of them reported clinical allergic reactions after eating red meat (including beef, lamb, and pork). Symptoms included urticaria, angioedema, respiratory distress, and syncope. Among them, 17 had particularly severe symptoms. After skin prick tests and/or fluorescent enzyme immunoassays were performed on the patients, it was found that they all had IgE-mediated allergic reactions.

In addition, these people all had one thing in common. It was this commonality that revealed the source of red meat allergy: they all lived in the northern beaches area of ​​Sydney, where ticks are active and bites are common. Twenty-four of the patients had been bitten by ticks and had severe local reactions. The team ultimately concluded that there is a correlation between tick bites and red meat allergy. The paper was published in the Medical Journal of Australia in 2009 [14]. This article made the world realize for the first time that there are people in the world who cannot eat red meat.

Left: Adult male lone star tick; Right: Adult female lone star tick. 丨Source:
https://entnemdept.ufl.edu/creatures/urban/medical/lone_star_tick.htm

So, which tick causes humans to be allergic to red meat? Based on the geographical distribution pattern of allergies, Professor Thomas Platts-Mills' team from the Department of Allergy at the University of Virginia School of Medicine found the culprit for red meat allergy: the lone star tick (Amblyomma americanum) [15]. In fact, as early as 2006, when Platts-Mills' team was investigating the accidental severe allergic reaction to the colorectal cancer drug cetuximab, they discovered α-galactose, an important molecule that causes red meat allergy symptoms. This is a substance produced by many mammals but not by humans and some other primates, and the saliva of the lone star tick also contains this sugar molecule. Therefore, after being bitten by a lone star tick, once the α-galactose molecule appears in the human body, the immune system will regard it as an invader and launch an immune attack, resulting in an immune response. In 2008, Platts-Mills' team published an article in the Journal of Allergy and Clinical Immunology[16], stating that α-galactose-specific IgE antibodies from mammals such as beef, pork, lamb, and milk were found in 24 patients with red meat allergy. Since then, red meat allergy has an official name: α-galactose syndrome. From 2010 to 2018, more than 34,000 cases of α-galactose syndrome were reported in the United States.

The unfortunate truth is that once you are bitten by the lone star tick, you are confined to mammalian products for life. Pork, beef, mutton, venison, and rabbit are all off-limits for people with alpha-galactosidase syndrome. But for those who are more sensitive to the alpha-galactose molecule, even dairy products can trigger an allergic reaction. And for the tiny minority of super-sensitive people, avoiding alpha-galactose means looking for mammalian byproducts hidden in the most unexpected places: drug capsules and candies (which may contain gelatin), face creams (collagen), and lip balms (lanolin). Even wool sweaters can cause some people to break out in hives.[17]

So far, prevention is the only way to prevent α-galactosidase syndrome. If you are going to places where ticks are prevalent, it is recommended to wear long sleeves, long pants, long socks and long boots, tie all openings of clothing tightly, and wear a protective hat. If you find that you are bitten by a suspected tick, please avoid eating red meat. If you unfortunately develop acute symptoms of red meat allergy, please seek treatment immediately. Commonly used drugs include epinephrine, oral antihistamines, oral or injectable hormones, and intravenous rehydration [18].

So, will the poor patients with α-galactose syndrome never have the chance to eat red meat again? That’s not absolute. In 2022, The Atlantic magazine reported that Revivicor, a US xenotransplantation company, had cultivated a pig that does not contain α-galactose[25]. They quietly sent frozen packages of α-galactose-free bacon, ham, minced pork, ribs and pork shoulder to the α-galactose syndrome patient group for free. In 2020, the US Food and Drug Administration (FDA) stamped the approval seal on Revivicor’s galactose-safe strain of pigs. Although it is currently only supplied to a small range of α-galactose syndrome patients and has not yet been commercialized, it may become a safer alternative meat product in the future, allowing more patients with red meat allergies to eat meat again.

Is everyone allergic to mangoes?

Mangoes grown in tropical regions are delicious and can be enjoyed almost all year round. They are rich in nutrients such as vitamin C, A, and fiber, and are known as the "king of fruits." However, there is a saying circulating on the Internet: everyone is allergic to mangoes. Is this true?

In fact, mango allergy is not common clinically. An article published in Medicina in 2021 [19] used keywords such as "mango", "allergic reaction", "contact dermatitis", "cross-reactivity", and "urticaria diagnosis" to count all articles reporting mango allergy in PubMed, Embase, and other scientific research paper databases. In the end, a total of 16 reports involving 37 patients with mango allergy were found. The earliest report can be traced back to 1939, when the world's first paper on mango allergy was published in JAMA: a 29-year-old woman developed acute herpetic dermatitis on her lips and perioral area 24 hours after eating mango [20].

According to various papers, some people develop rashes after contact with mango skin, but are able to safely eat mangoes without allergic reactions, while others have severe allergic reactions to any contact, including stinging urticaria, swelling, and even more severe, life-threatening systemic reactions[21].

According to different clinical manifestations, mango-related allergic reactions can be divided into two types: the first is a chronic allergic reaction, which may occur within a few days (usually 48 to 72 hours) after contact with mangoes, including rashes in and around the mouth, usually contact dermatitis, also known as "mango mouth". The second is an immediate allergic reaction, which occurs within 24 hours after eating mangoes. The severity can range from skin erythema and itching in the mouth to life-threatening (such as difficulty breathing). In 2018, a Polish team reported a relatively rare case of severe allergic reaction to mangoes [22]: A 30-year-old female patient immediately developed systemic urticaria within a few minutes of eating mangoes, followed by facial edema, accompanied by severe stomach pain and watery diarrhea.

A more common condition in life is "mango mouth", which means that the lips and the area around the mouth become red and swollen. In more serious cases, the mouth may swell into "sausage mouth", which is very uncomfortable. However, the culprit for this is not the mango flesh, but the peel. Mango trees belong to the Anacardiaceae family. Their leaves, branches, peels and juice all contain urushiol, a substance that has a certain irritating effect on the skin and mucous membranes. Therefore, experts generally recommend that when eating mangoes, it is best to peel them and cut them into small pieces before putting them in your mouth to avoid contact with the face and causing "mango mouth" [23].

People who are allergic to mangoes mainly have immunological activity against protein allergens contained in the fruit. So far, scientists have characterized two major types of allergens: ① inhibitory proteins Man i1, Man i2, and Man i3 (encoded by the mango profilin gene), and ② chitinase 1, which can cause milk-fruit syndrome and is closely related to childhood asthma[24]. In addition, unripe mangoes also contain aldehydes, which can irritate the skin and mucous membranes and cause allergies[25].

Mango allergens can also cross-react with allergens from other species, meaning that if an allergic person has previously been exposed to similar allergens in other foods and has had an allergic reaction, then eating mangoes may also cause an allergic reaction. Mango allergens have been shown to cross-react with mugwort pollen, birch pollen, poison ivy, poison oak, mugwort, celery, carrots, pistachios, tomatoes, papayas, and bananas.[26]

Compared with adults, children are more likely to be allergic to mangoes. Ge Hongsong, chief physician of the Department of Dermatology at Anhui Provincial Children's Hospital, explained[27] that children often eat fruit in a "face-washing" manner, and fruit juice often stains a large area of ​​the child's mouth and face. Because children's skin is delicate, the probability of skin allergies after being stimulated is much higher than that of adults. Generally speaking, children with mild symptoms will recover in a few days after stopping eating allergenic fruits and washing their hands and faces. However, if the symptoms are more severe, such as large patches of erythema on the lips, mouth, ears, and neck, or even slight edema, you should go to the hospital in time for treatment. Taking and applying anti-allergic drugs under the guidance of a doctor will generally not cause serious adverse consequences.

Conclusion

Today, allergies have been listed by the World Health Organization as one of the six major chronic diseases that require key prevention and treatment in the 21st century. According to statistics from the World Allergy Organization, the incidence of allergic diseases has at least tripled in the past 30 years, and the current global prevalence has reached 22%. The overall prevalence of allergic diseases in my country has now exceeded 20%[28].

It is really hard for most people to empathize with those who suffer from rare allergies, and even feel like they are joking when they say it out loud. But these people are indeed troubled by allergies. I hope that after reading today's article, everyone will have a better understanding of some rare allergies and have more understanding and empathy for patients.

References

[1] https://zh.wikipedia.org/zh-hans/%E6%97%A5%E5%85%89%E6%80%A7%E8%95%81%E9%BA%BB%E7%96%B9

[2] https://www.theguardian.com/commentisfree/2016/apr/07/a-moment-that-changed-me-allergic-sunlight

[3] https://onlinelibrary.wiley.com/doi/10.1111/ddg.12809

[4] https://www.sciencedirect.com/science/article/abs/pii/S0889856113000878?via%3Dihub

[5] https://onlinelibrary.wiley.com/doi/10.1111/j.1600-0781.2004.00083.x

[6] Merklen P. Urticaire. in: ed. 2. La pratique dermatologique: Traité de dermatologie appliquée. vol. 4. Masson & Cie, Paris1904: 728

[7] https://linkinghub.elsevier.com/retrieve/pii/S0190962289701675

[8] Wucherpfennig V. Pathologische Lichtu¨berempfindlichkeit in qualitativer und quantitativer Hinsicht, nebst Untersuchungen zur Pathogenese der Lichtquaddel. Arch Dermatol Syph(Berl) 1928;156:520-44.

[9] https://onlinelibrary.wiley.com/doi/10.1111/j.1365-4362.1980.tb00314.x

[10] https://onlinelibrary.wiley.com/doi/10.1111/ddg.12809

[11] https://www.sciencedirect.com/science/article/abs/pii/S0889856113000878?via%3Dihub

[12] https://onlinelibrary.wiley.com/doi/10.1111/exd.14493

[13] https://www.theguardian.com/news/2018/dec/11/mysterious-allergy-to-meat-alpha-gal-lone-star-tick

[14] https://www.mja.com.au/journal/2009/190/9/association-between-tick-bite-reactions-and-red-meat-allergy-humans

[15] https://news.virginia.edu/content/what-know-about-tick-bites-can-leave-you-allergic-meat

[16] https://www.jacionline.org/article/S0091-6749%2808%2901931-3/fulltext

[17] https://www.theatlantic.com/science/archive/2022/04/alpha-gal-syndrome-tick-meat-allergy/629649/

[18] https://www.bjsjth.cn/Html/News/Articles/24108.html

[19] https://www.mdpi.com/1648-9144/57/11/1240

[20] https://jamanetwork.com/journals/jama/article-abstract/1158920

[21] https://www.verywellhealth.com/mango-allergy-82833#:~:text=Most%20people%20tend%20to%20be,peel%20is%20removed%20for%20you

[22] https://aacijournal.biomedcentral.com/articles/10.1186/s13223-018-0294-1

[23] https://www.dr-skin.com.tw/health/view/291

[24] http://www.zgspws.com/html/2010/2/20100264.pdf

[25] https://www.toutiao.com/article/4308379676/?source=seo_tt_juhe

[26] https://www.spkx.net.cn/fileup/HTML/20170348.shtml

[27] https://www.gov.cn/fuwu/2014-04/23/content_2664611.htm

[28] https://www.zmuhospital.com/Article/17281.html

This article is supported by the Science Popularization China Starry Sky Project

Produced by: China Association for Science and Technology Department of Science Popularization

Producer: China Science and Technology Press Co., Ltd., Beijing Zhongke Xinghe Culture Media Co., Ltd.