amplification of the signal by the immune system effectsYOU’RE OVERREACTING: IMMUNITY OUT OF BALANCE
Flip is a rock musician, a skilled guitarist who called me in a panic one day, wailing, “I’ve become allergic to my guitar! This is the end of my career. You’ve got to help me.”
I saw him in my office the same day. He wasn’t exaggerating. His fingertips were oozing and weeping, covered with a red, scaly rash where they made contact with the metal strings on his guitar. The diagnosis was immediately obvious: he had developed a condition called allergic contact dermatitis, and the fact that stainless steel guitar strings provoked the reaction made it likely that he was reacting to nickel, which is alloyed to iron in producing stainless steel.
Nickel is one of the most common contact allergens in the world. People with nickel allergy react with a red, scaly, blistering rash when their skin makes contact with the metal, which is found in stainless steel products like costume jewelry, watch casings, and kitchen utensils. The diagnosis can be confirmed by a patch test, in which a small piece of paper containing a nickel solution is applied to the skin. The development of nickel allergy requires skin exposure to nickel and is increased in people with stainless steel earrings that pierce the skin.1
Surprisingly, nickel is also found in many foods. It occurs naturally in whole grains and beans and some fruits and vegetables; it’s also found in most canned goods, as nickel from the stainless-steel can penetrates the food. People who are nickel sensitive may react to the nickel present in food with skin rashes and with gastrointestinal symptoms such as abdominal pain. This reaction is called systemic nickel allergy syndrome (SNAS).2 For more information on nickel levels in food, visit www.drgalland.com.
Flip had been playing rock guitar since the age of 10, so I wanted to understand why he had become allergic to nickel suddenly at the age of 30. I noticed that he had a gold earring in his left ear and asked him if that was new; I didn’t remember seeing it before. Yes, he told me. He’d had a steel earring inserted a few months earlier, but the puncture site got inflamed, so he had it removed and replaced with a gold stud. I also noticed that he’d lost weight and asked him whether he’d changed his diet. Yes, he said, he’d been trying to get healthy, so he’d cut out refined grains and meat and started eating whole wheat and brown rice and alfalfa sprouts a few weeks earlier.
My analysis indicated a three-step process that had produced Flip’s life-altering nickel allergy:
The program I suggested had two components: First, Flip was to avoid all skin exposure to nickel for three months. He limited his guitar-playing to acoustic guitar with nylon strings and did not wear a watch or jewelry. Second, he was to follow a low-nickel diet. The skin on his fingertips improved within a few days on this diet, but he maintained it for three months anyway.
Over the next several months, Flip’s nickel allergy totally abated. He was able to play rock guitar and eat a whole-foods diet with no skin rash. If he wanted to wear jewelry or an earring, I insisted that it be sterling silver or 14-karat gold, so that he would avoid any undue persistent skin contact with nickel. He’s been fine now for six years.
What Is an Allergic Reaction?
An allergic reaction is a self-amplifying chain reaction that begins with a trigger and ends with a series of effects that include the symptoms you experience and the signs a doctor finds on examination. The trigger can be minuscule, and the effects can vary from subtle to catastrophic. If your immune system supplies the amplification, the reaction is considered to be allergy. Whatever the details, the fundamental pattern of allergy is:
Exposure to a trigger amplification of the signal by the immune system effects
The trigger is called an allergen or an antigen. You do not experience an allergic reaction on your first exposure to an allergen. The allergic response requires that a memory of the allergen already be imprinted on your immune system. It’s like recognizing a face: you have to have seen the face before. The allergic reaction will show itself only on subsequent exposures—sometimes the second exposure, sometimes not until multiple exposures have occurred.
Allergens come in all shapes and sizes and can be present in anything you breathe, eat, or touch. Allergens initiate the allergic cascade when they attach to a receptor on an immune cell that activates the immune amplification response. Some allergens produce such an overwhelming immune reaction that an amount too small to measure can trigger a life-threatening allergic reaction. This is the case with peanut allergy, which can trigger fatal reactions (see “Peanut Allergy”).
The Conductors of Your Immune System
Allergic reactions are commonly thought of as misguided or overreactive responses of the immune system, but I believe they are due to a lack of function of key immune cells, so they can actually be thought of as resulting from immune deficiency rather than immune excess.
Most people think of immunity as if the immune system were a radio, with the main control over its output being the volume dial: louder or softer, stronger or weaker. But your immune system is much more like an orchestra. There are many sections, and the output from each section must be synchronized with the output from every other section. When you want more from the strings, you have to quiet the horns or the strings will be drowned out. Organizing the synchronicity of immune responses is the job of a group of white blood cells called lymphocytes. They’re the conductors of the body’s immune system orchestra.
For people with allergies, one particular type of lymphocyte seems to be the weak link. These are the regulatory T-cells, or T-regs, which limit inflammation by turning off unwanted immune responses. Numerous studies have shown that in people with allergies, the T-regs are not functioning properly. This leads to the unwanted immune responses that are the hallmark of allergy.
Scientists in Norway studied immune responses in children with allergy to cow’s milk who outgrew their allergy and compared them with the responses of children who remained allergic to milk.3 All the children in the study followed a totally dairy-free diet for an average of six months. Their prior symptoms, which included diarrhea, vomiting, and eczema, cleared quickly.
Milk was then reintroduced into their diets, slowly and cautiously, building up to four ounces a day. About half the children no longer showed any adverse reaction to milk, but the other half experienced a return of symptoms and milk had to be stopped. A week later, all the children’s blood was tested. The major immune difference between the two groups was that the children who had outgrown their allergy had a higher level of T-regs in their blood. Further testing demonstrated that the T-regs were responsible for preventing the allergic response.
The Process of Allergy
The effects of allergy—the symptoms that make you sick—are created by cells called effector cells and by the specialized chemicals they release, which are called mediators. The two major types of allergy effector cells are mast cells and eosinophils, or Eos. Most of the drugs used to treat allergies work by blocking the effects of mast cell mediators; antihistamines are the best-known example. Steroids work in part by killing off Eos. This book offers a different approach: a way to identify and avoid the hidden triggers of allergy and turn down the immune amplification process.
Effector cells produce the effects that we call an allergic reaction. But the first thing to know about these cells is that they do not exist to make you sick; they play an essential role in wound healing and tissue regeneration and also protect your body from infection and toxicity.4
Mast cells, for example, are activated by bee venom to produce the swelling and pain associated with bee stings. Eos play an important role in killing parasites. In the current epidemic of allergy sweeping the world, allergy effector cells have been hijacked by allergens and tricked into doing more harm than good.
Mast cells supply most of your body’s histamine—one type of chemical mediator—and are the effector cells of the initial, or early phase, allergic response. They are an ancient type of cell, found even in primitive animals like sea squirts, where they function as mainstays of the immune system.5 In humans they are large cells sparsely distributed throughout all tissues of the body. The chemical mediators that they make, store, and release not only cause the symptoms of allergy, but also attract other cells, especially Eos, that create the late-phase allergic response.
Eos circulate in your blood but readily wander into your tissues, where they release an array of unique mediators of their own. The best studied of these are enzymes that cause considerable damage to cells of all types.6 Invasion of tissues by Eos is a major feature of chronic allergic diseases including asthma, sinusitis, and gastrointestinal disorders. Eos also shift your immune response pattern in the direction of greater sensitivity. Activation of Eos initiates a vicious cycle, a feed-forward loop in which allergy induces more allergy.
Mast Cell Mediators
Mast cells produce about 200 mediators that create the signs and symptoms of allergic reactions. Most drug treatment of allergy works by suppressing the synthesis or blocking the activity of these mediators.
The best-known mast cell mediators are:
The Four Types of Allergy
The term allergy was coined by a Viennese pediatrician, Claude von Pirquet, in 1906, to explain the sneezing of children exposed to pollen. The clearest translation of its meaning is “altered reactivity,” and it soon became clear that allergy involves excessive and abnormal activation of the immune system.
During the 20th century, scientists identified four types of immune activation that lead to allergic reactions.7 All four types can occur in people with allergic disorders.8 Each type requires that your immune system recognize a specific allergen because of a previous exposure to it. In the first three types, that previous exposure caused your immune system to make antibodies directed against the allergen. The usual function of antibodies, which are proteins made by cells of your immune system, is to create immunity, helping you resist infection; allergy turns this protective effect into a harmful one. The fourth type of allergy, the type that occurs with nickel dermatitis, does not require antibodies to produce its effects.
Type 1 Allergy
Type 1 allergic reactions, the most common form, result from formation of an antibody called IgE (immunoglobulin E). When IgE attaches to an allergen, it stimulates mast cells to release mediators like histamine into your tissues with explosive force. Standard blood tests for allergies look for the presence of IgE antibodies directed against specific allergens. Skin tests for allergies attempt to measure the swelling produced in your skin when IgE antibodies attach to an allergen that’s being injected.
Type 1 is the kind of allergic reaction that occurs with anaphylaxis, eczema, hives, hay fever, and allergic asthma. It has two phases, early and late. Symptoms of the early phase allergic response are caused by the release of mast cell mediators. They can occur within seconds of exposure to an allergen and may last for a few hours. Some mast cell mediators also attract Eos to the inflamed tissues.
Activation of Eos creates the late phase allergic response. The most potent mediators released by Eos are enzymes that damage cells. They’re capable of killing parasites and can inflict the same kind of damage on your own tissues. The late phase reaction may last for days and can cause long-lasting changes to your tissues and your immune system: damaged tissues may heal with scarring, and your immune system may shift so that your lymphocytes further increase their production of IgE antibodies. It’s a dangerous cascade that can allow allergies to spin out of control.
If you suffer from allergic eczema, you can see the difference between the early and late phase responses in your own skin. When you eat a food to which you’re allergic, your skin becomes red, somewhat swollen, and very itchy. Once this early phase reaction subsides, your skin becomes thickened and scaly, still red and itchy but with less intensity. That’s the late phase response, and if it lasts long enough, your skin does not readily return to normal.
Type 2 and Type 3 Allergy
Type 2 and Type 3 allergy depend upon another class of antibody, called IgG (immunoglobulin G), to amplify the allergic signal. IgG is the main class of antibodies circulating in your blood. IgG is essential for a normal immune response, and its deficiency predisposes people to recurrent or chronic bacterial infections. Type 2 and 3 reactions are the main mechanisms involved in drug allergies and may occur in some people with food allergy, especially when migraine headache, abdominal pain, or arthritis are the allergic symptoms.9
Two factors make Type 2 or Type 3 allergy to foods or drugs hard to detect. First, IgE antibodies are not involved, so standard allergy tests, which measure IgE, will not detect this kind of allergy. Second, the onset of the allergic reaction is often delayed, sometimes occurring 24 hours or more after exposure to the triggering allergen. You have to be a really good detective to track down these reactions. The same is true for Type 4 allergy, which is known as delayed hypersensitivity.
Type 4 Allergy
Type 4 allergic reactions do not require antibodies. The triggering allergens directly activate immune cells called helper lymphocytes, which amplify the response themselves, attracting so-called killer lymphocytes to the area where the antigen is found. Killer cells are just as effective as Eos at causing tissue damage.
Type 4 reactions occur in a number of infectious diseases, such as tuberculosis, where they help to control the spread of the infection. They also contribute to the damage that occurs in several autoimmune disorders, including rheumatoid arthritis, Crohn’s disease, type 1 diabetes, multiple sclerosis, and Hashimoto’s thyroiditis.
The most common allergic disorder employing the Type 4 mechanism is poison ivy, an allergic skin rash caused by exposure to oils from plants in the genus Toxicodendron. Allergic contact dermatitis (like Flip’s allergy to nickel, for example) usually involves a Type 4 reaction. For some people, Type 4 reactions may cause asthma. As I describe in Chapter 12, up to 15 percent of asthmatic reactions may occur because of Type 4 allergy. Food allergy may also be caused by Type 4 reactions, especially when the allergic reaction affects the gastrointestinal tract or the skin.
Anaphylaxis: Allergy That Can Kill
The term anaphylaxis was coined in 1901 by the French scientist Charles Richet, who received the Nobel Prize for his research in 1913. Richet coined a new word for what he believed to be a new concept: hypersensitization, or, as he expressed it, “the opposite of a protective response.”
With an anaphylactic reaction, your body is flooded with chemicals that cause instantaneous, massive swelling of the affected tissues, dilation of blood vessels, contraction of the smooth muscles that line your airways or intestines, and irritation of nerve endings. If the reaction involves your tongue, throat, or respiratory tract, you may be unable to breathe. If it involves your circulatory system, your blood pressure can drop profoundly, producing anaphylactic shock. Swelling of your face, your lips, your eyes, or any part of your skin, as well as wheezing, abdominal cramps, and diarrhea, are other symptoms that may occur with anaphylaxis.
The usual triggers for anaphylaxis are insect stings, specific foods such as peanuts, or medication such as penicillin. Emergency treatment is essential and starts with an injection of adrenaline, which raises blood pressure, constricts blood vessels and dilates bronchial tubes.
Anyone with a history of anaphylactic reactions should carry a device for rapid self-injection of adrenaline at all times and have an emergency action plan worked out with his or her personal physician.
The incidence of anaphylactic reactions has doubled over the past decade, with an estimated 1,500 fatalities a year in the United States, yet most patients receiving emergency treatment for anaphylaxis at U.S. hospitals do not receive an adrenaline auto-injector or an allergist referral when discharged, a missed opportunity for preventing further reactions.10
Studies in many different countries have all reached the same conclusion: people prone to anaphylaxis are not adequately armed with adrenaline. As severe as it is, life-threatening anaphylaxis is still underdiagnosed, underreported, and undertreated.11
Peanut allergy is one prevalent cause of anaphylaxis. Peanuts contain at least 12 allergenic proteins, two of which can cause anaphylaxis in sensitive individuals.12 A telephone survey of more than 4,000 U.S. households in 1997 concluded that peanut or tree nut allergies affected 1.1 percent of those surveyed (which translates to about three million people in the U.S. population).13 A follow-up study five years later found a doubling of peanut allergy among children.14 By 2007 the prevalence of peanut allergy among schoolchildren in the United States had tripled, and researchers were using the term epidemic to describe the increase.15 A British study documented a tripling in the rate of allergic skin-test reactivity to peanut extract among schoolchildren during the 1990s and a doubling of clinical allergic reactions to peanuts.16
The reasons for the increase in peanut allergy are not clear. Most children with peanut allergy get sick immediately on their first known exposure to peanuts. For this to happen, the child must already have been exposed to peanuts, so that his immune system became sensitized to peanut allergens.
Researchers at Imperial College London attempted to identify factors that separated children with proven peanut allergy from children with other allergies or no allergies. The most significant difference was that children who developed peanut allergy had been rubbed with skin care products containing peanut oil (arachis oil) twice as often as children who did not develop peanut allergy.17 Peanut oil is a common component of skin care and infant care products in the United States as well as the United Kingdom. The list of commonly used topical preparations that contain arachis oil includes Cerumol (for removing earwax), Siopel barrier cream, zinc and castor oil ointment, calamine oily lotion, Dermovate (a potent topical steroid cream used for difficult eczema), and Naseptin cream.18
The British researchers also found that peanut allergy was more likely to occur if other family members ate peanuts.19 Their theory is that exposure to peanut allergens through the skin is the main risk factor for peanut allergy. This theory might explain why children with eczema are at increased risk for developing anaphylaxis from peanuts. The inflamed and broken skin of eczema allows increased absorption of peanut antigens through the skin.
There is at present no specific treatment that can reverse peanut allergy.
The Mystery of Oral Tolerance
How you’re exposed to an antigen in infancy can determine whether you react to it as if it is a friend or a foe. When a child eats a food, especially a large dose of the food, his or her immune system usually recognizes the food as safe and responds to it with a reaction called oral tolerance, a reaction that says “friend.” If the infant is exposed to the same antigen through the skin, oral tolerance does not occur and allergenic sensitization may result. A study of mice found that exposure to peanut protein on the skin produced an allergic response to peanut allergens followed by an even stronger reaction when the mice were subsequently fed peanuts.20
Oral tolerance to food and intestinal bacteria helps to prevent food allergy and intestinal inflammatory disorders like celiac disease, Crohn’s disease, and ulcerative colitis. A critical step in oral tolerance is the development of the specialized lymphocytes called T-regs that we discussed earlier in this chapter, which work to prevent dangerous hypersensitivity responses to antigens.21
Red Meat Allergy Triggered by Tick Bites
A new phenomenon burst into medical journals in 2009. People who had been eating meat their entire lives suddenly developed hives or anaphylaxis after a meal of beef, pork, or lamb but had no reaction to any other food.22 In almost every case, the development of red meat allergy had followed bites by hard-bodied ticks. The initial account came from the University of Virginia, but the same strange syndrome was soon reported from places as far-flung as Australia, Scandinavia, Spain, and China.23
Although most food allergens are proteins, the Virginia researchers found that in affected people, tick bites caused the development of an IgE Type 1 antibody response to alpha-gal, a sugar that is found in red meat but not in human tissues. Hard-bodied ticks also contain alpha-gal and inject it into the skin of people they bite. Recognizing alpha-gal as a foreign substance, the lymphocytes of some people mount an immune response to destroy it. This disrupts the normal response of the body to potential food allergens, which is oral tolerance. The next time that person eats red meat, the misdirected protective response creates an allergic reaction that can include itching, burning, hives, throat swelling, and even anaphylactic shock. Although it’s a Type 1 allergic reaction, which usually starts soon after allergen exposure, the alpha-gal red meat reaction may not occur for several hours after the meat is consumed.24
Tick-bite red meat allergy is another example of skin exposure to an allergen creating an allergic reaction that overrides oral tolerance, your natural defense against food allergy.
Conclusion
This chapter kicked off with the case of the rock musician, Flip, who developed a dramatic allergy to his guitar strings. His case helps us answer the question: what is an allergy? Allergy starts with a trigger, followed by amplification of the signal by the immune system that produces the effects, or symptoms. I introduced the concept of the immune system as an orchestra, where white blood cells called T-regs are like conductors who maintain a balance in the music. In upcoming chapters we will look at many ways of supporting the function of these T-regs to help reduce allergic reactivity.
I also outlined the four types of allergy and drilled down to the cellular level of allergy with a look at effector cells and mast cell mediators. Given the medical nature of this material, it is imperative that you bring these pages with you when you see your doctor. Because allergy is complex and carries the potential of a dangerous allergic reaction, you must follow the professional advice of your doctor.
Now that you understand more about what’s going on in your body when you have an allergic reaction, let’s turn to figuring out what triggers you—because knowing what’s wrong is the first step toward making it right.