Allergies in Utah and Around the World-A Historical Perspective

The history of allergies is like any good story—full of triumphs and tragedies. Treatment approaches have ranged from the practical to the absurd. Allergies have been around long before Utah existed as a state. In fact, allergy-like symptoms have been around since recorded antiquity. However, it has not been until relatively recently that science has had a clear understanding of what the ailment is, and reliable ways of treating it. In fact it has only been the last hundred years that there was even a commonly used name for the symptoms, now known as allergies. In spite of its ancient origins, allergies do seems to be on the rise. Some have described allergies as “the epidemic of the 21st century”. The prevalence has more than doubled in just the last 20 years. In most developed countries, about 40% of the population has the predilection for developing allergies (also known as atopic), while up to 1 in 3 individuals have active allergy symptoms of one sort or another. Theories for the increasing “epidemic”, range from environmental pollution to simply increased awareness. It is likely a combination of several factors. One of the earliest reports of an allergic disorder is that of King Menses of Egypt. He was reportedly killed a wasp sting around 3500 BC. Another report from ancient history is that of Britannicus, son of the Roman Emperor Claudius. Britannicus seemed to have an allergic reaction to horses. Reportedly his eyes would swell to the extent that he could not see where he was going. Therefore the honor of riding by horseback at the head of the young patricians (a title given to high court officials or societal elites) fell to Claudius’s adopted son Nero, who allegedly threw Christians to the lions and eventually killed Britannicus. Perhaps if Britannicus did not have this horse allergy, the bloodthirsty Nero never would have eventually gained the advantage over Britannicus, nor been able to enforce his cruelty. Sir Thomas More gives another account of allergies causing mayhem. He claimed that King Richard III used his allergy to strawberries to good effect by arranging the murder of Lord William Hastings. The King secretly ate some strawberries just prior to giving an audience to Hastings, as expected he promptly developed acute symptoms. He then falsely accused Hastings of putting a curse on him. Using the “proof” of his symptoms, the king was able to demand the head of Hastings on a plate. The Roman philosopher, Lucretius also noted that some people had adverse reactions to common substances. He said, “What is food for some may be fierce poisons for others”. However, it wasn’t until 1565, that a man named Leonardo Bottallo gave the first known modern description of seasonal allergy disorder. The modern era of allergy study didn’t start in earnest until the 1800s. In 1819 a doctor by the name of John Bostock described a classic case of hayfever based on his own symptoms. We actually still use the term “hayfever” coined by Bostock, although allergies aren’t directly related to hay, or fever, as we know it today. In old English the word fever just meant feeling unpleasant. In fact, early pioneers in the field did not know exactly what was causing this “unpleasant” malady. The answers took over 70 years to discover. In 1872 Morrill Wyman, an American physician, published a report identifying ragweed as a cause of what was then known as the ‘autumnal catarrh’. In 1873 Charles Blackley recognized that pollen grains were the causative agent. A year later, Blackley published his observation that hayfever was caused by grass pollen. The study of this disorder continued into the next century. In 1902 Charles Richet and Paul Portier invented the word ‘anaphylaxis’ when in the course of other immunization research they discovered a life threatening response to medications and some protein substances. Anaphylactic shock occurs when within minutes after allergen exposure. The body tissues begin to swell, sometimes causing vomiting, cramps, a sudden drop in blood pressure, or even a loss of consciousness. It most often occurs in people who are severely allergic to penicillin, stinging insects, shellfish, peanuts or tree nuts. About 10 years after Utah first became a state, a doctor, Clemens Von Pirquet, coined the term ‘allergy’ in the year of 1906 in Vienna, Austria. He first became aware of allergies when he observed that some diphtheria patients developed non-disease related symptoms when treated with a horse serum antitoxin. The meaning of the term comes from the Greek word words ‘allos’ (other) and ‘ergos’ (activity). Pirquet eventually became director of Universitats Kinderklinik (University Children’s Clinic) and Professor or Pediatrics in 1911. To date, one must be board certified in either pediatrics or internal medicine, before a physician can even begin to train as an allergist. Now that scientists knew some of the causes of allergy symptoms, they still needed to figure out how to treat the disorder. The study of modern allergies was in its infancy around the world as well as in Utah. As with any new field of research, there were many more questions than answers. However there were promising treatments that were discovered early in the 20th century. In the same year that Pirquet coined the term allergies, 1911, early allergists John Freeman and Leonard Noon used a new method to successfully treat pollen sensitive patients. As founding fathers in the field of immunology, they injected patients with grass pollen extracts in order to desensitize them. Noon worked at St Mary’s Hospital in London, when he began tests with subcutaneous injections of pollen extracts. Freeman and Noon administered increasing doses of crudely prepared whole allergen extracts to allergy patients until their symptoms were successfully lessened. These experiments represented the beginnings of the development of ‘desensitizing immunotherapy’. Noon also made the first attempt at standardizing allergen doses and established the ‘Noon unit’ based on weight. This desensitizing approach, at first only experimental, has now been scientifically validated. Scientists now recognize that several beneficial immunologic changes occur during immunotherapy. With the help of knowledgeable allergists, hay fever (allergic rhinitis) and some asthma patients can be effectively immunized against house dust, animal dander, and pollens. Interestingly enough, this early treatment turned out to be one of the longest lasting and most valid. Shortly after in 1916, R.A. Cooke wrote a landmark paper on human allergies where he described the inheritance pattern of allergic hypersensitivity. Cooke also helped established the standardization of allergens by nitrogen content as determined by the Kjeldahl method, which is still in use today. He described ‘blocking antibodies’ and in doing so provided one of the earliest logical suggestions for the clinical improvement of allergen immunotherapy. Finally, Cooke introduced intra-dermal skin testing. Even now, his philosophies are still prevalent in the United States. A major advance in allergy studies came in 1921 when Prausnitz and Kustner described a ‘skin sensitizing factor’ that can be transferred to the skin of a nonsensitised individual and confer the sensitivity of the original antigen. They also developed the ‘PK test’ to identify the presence of this factor in a serum. In 1923 Coca coined the word atopy, which means “out of place”, to describe the hereditary, familial predisposition in a person to produce an allergic response to ordinarily harmless materials such as pollen, dust, and animal dander. This response was mediated by an antibody, which was then referred to as “reagin”. This antibody response was associated with the standard allergy syndromes of asthma, hay fever, hives, and eczema. Reagin was found to be circulating in nature, which means it was able to sensitize or attach itself to skin and mucous membranes, inactivated by heat, transferable to serum, non-precipitating, and unable to cross the placental barrier. The first physician in Utah who showed a special interest in the treatment of allergic disorders was Dr. J. Mercer Anderson, who began practicing dermatology and allergy in Utah in 1928. Doctor Anderson is considered one of Utah’s pioneer allergists. He practiced here in Utah for nearly forty years. In 1937 Daniel Bovet developed the very first antihistamine drug. He and his colleagues found that antihistamines not only blocked the effects of the chemical histamine, but also protected against some anaphylaxis symptoms. Even today’s antihistamine drugs have been found quite effective in the treatment of the “hayfever” symptoms of sneezing, runny nose, along with itchiness, swelling hives, and other allergic symptoms. In 1943 the Society for the Study of Asthma and Allied Conditions merged with the American Association for the Study of Allergy to become the American Academy of Allergy, which changed its name to the American Academy of Allergy and Immunology in 1982, and again in 1995 to the American Academy of Allergy, Asthma & Immunology (AAAI). In 1948 Philip Hench and Edward Kendall discovered corticosteroids and introduced them regular clinical medicine. These drugs were found to be effective in the treatment of asthma and many types of allergic reactions, and are still used to date. In 1949 Dr. G. Harlow Richards arrived in Utah with a serious interest and some training in allergy treatment, he later became a board-certified allergist. The 1950s brought more board-certified allergists to the state including doctors, Dean Moffat and George Peck. They were followed in the late fifties and early sixties by Doctors John Baukol and Virginia Lanier. All of these early board certified allergists helped set a high standard for allergy care in Utah. One of the most significant advances in the standard treatment of Allergies occurred during the 1950s with the introduction of cortisone derivatives. Many asthmatics were spared premature death by the use of this new drug. Unfortunately, this drug was soon found to produce significant side effects, especially when used carelessly. Cortisone however, did add a substantial measure of relief and control to severe asthma, hives, eczema, and allergic rhinitis. However, not all treatments proved to be as equally effective. Practitioners and patients alike have often jumped to the wrong conclusions about the best way to treat the condition. Another popular treatment method in Utah, at its height during the 1950s, was the use of autogenous bacterial vaccines. These vaccines were cultures of the patients own respiratory tract bacteria, which were then grown, filtered, and reinjected back into the patients. The original idea was that those with suffering from allergy symptoms were “allergic” to their own bacteria. This hypothesis was later proven to be false, and the erroneous practice was abandoned. Another questionable treatment was giving patients gammaglobulin injections, which was very widely used during 1950s and 1960s. Gammaglobulin injections are usually given in an attempt to temporarily boost a patient’s immunity against disease. The popular theory was that the same effect could be achieved with allergy symptoms. The whole nation, but especially Salt Lake City, widely used this new alternative treatment for some time. Parents and physicians thought it might offer a quick solution for a child’s “cold like symptoms”. Critical examination later proved this method to be largely ineffective for treating allergies and was subsequently abandoned. Another drug, a steroid called Kenalog, was found to be capable of relieving allergy symptoms for up to several weeks, although it suppressed the adrenal gland for several months. Litigation against physicians who failed to obtain informed consent from patients, or fully disclose the very serious possible side effects, has led to it no longer being a standard treatment for allergy symptoms. Around this same time period, a new form of skin testing became available where a small amount of the patient’s blood could be drawn and transferred to the skin of a non-allergic volunteer. The volunteer was paid a fee to allow himself or herself to be skin-tested at these artificially sensitized sites. The passively transferred antibodies, known as reagin or IgE, then attached themselves to the mast cells in the recipient’s skin where the allergens could be identified. The possible benefit of this type of testing was that the individual receiving the tests were not likely to have a seriously adverse allergic reaction, as only a small area of the body was sensitized to the allergens. This practice was understandably abandoned as awareness of blood-transmitted diseases, like HIV, became more prevalent. Even though controlled allergen serums for skin testing were available for order from commercial laboratories, many allergists (including some in Utah) preferred to extract some of their own antigens from flora and fauna indigenous to their respective areas. Sometimes the allergists’ children would be sent out into the fields of weeds and grasses, during the highest pollen count seasons, in order to collect the raw materials. They allergist would then extract the allergens themselves. In 1953, researches James F. Riley and Geoffrey B. West discovered that the mast cell granule was the major source of histamine in the body. An experimental subject named Judy aided this fundamental contribution to the understanding of inflammatory and allergic reactions. This ten-year-old cocker spaniel surely did her part in furthering allergy research. Another long-awaited breakthrough in the field occurred in 1965-1966 when Teruko and Kimishige Ishisaka working in Denver, CO discovered that reagin was in fact IgE or Immunoglobulin E. Concurrently, in Sweden, Hans Bennich and S. Johansson also identified a strange protein in a multiple myeloma patient that was typically elevated in allergic patients. The World Health Organization (WHO) established in 1968, that the two new proteins and “reagin” were actually all the same thing. These researchers furthered the understanding of the allergy process by discovering the role of IgE class antibodies, which were found to be an important factor in the allergic reaction. This newly discovered process was shown to involve a response to repeated exposure to an allergen such as dust mites or ragweed, at which point the allergic individual produces IgE antibodies, which then attach to mast cells. These researchers found that after repeated exposure, allergens cross-link IgE antibodies on the surface of the mast cells. It is this process that triggers the release of histamine and other mediators, which causes allergy symptoms. Now allergists, physicians, and other medical professionals had a better understanding of what they were dealing with. IgE is naturally produced by all individuals, but in greatly increased quantities by those who are atopic, or susceptible to allergies. The production of the antibody appears to be genetically related. IgE is responsible for the majority of allergy symptoms such as anaphylaxis, hay fever, pollen asthma, and some types of urticaria, eczema, insect allergy, and drug allergies. The discovery and subsequent research of IgE helped the field of allergy study to evolve from a guessing game into the well-understood and accepted immunologic science that it is today. Only a year after the discovery of IgE, the same Swedish scientists, Bennich, Johansson and a colleagues, developed the first in-vitro tests known as RAST (radioallergosorbant test) and commercially marketed it as ‘Phaedebas-RAST’ in 1970. This test was widely used to help identify and quantify the amount of IgE in a patient’s serum specific for the antigen in the same manner the skin test identified the ‘reagin’ in the skin. Later in the 1970’s Richard Fadal and Donald Nalebuff (an otolaryngologist) modified the original test and its’ scoring to make it even more user-friendly. This new blood test could identify specific circulating IgE antibodies directed toward allergens. While the RAST test is still useful in certain clinical situations, its widespread availability led to many non-certified physicians becoming “overnight allergists” without any proper training. Many local physicians did not really understand the science behind the testing or useful applications. Nevertheless, many “pseudo-allergists” embraced the opportunity to participate in a new specialty without adequate background or training. Some much-needed changes occurred in 1974 when the Conjoint Board of Allergy and Clinical Immunology was established as a subspecialty of the boards of both pediatrics and internal medicine. The new requirements allowed only physicians who were already boarded in pediatrics or internal medicine to become certified as allergists by the conjoint board. These boards recognized the necessity of requiring a certified allergist to have a broad background in the field. Even today the standard for board certification as an allergist requires certifications in pediatrics and/or internal medicine, on top of that the certified allergist must complete two years of specialization in allergy and clinical immunology. These new requirements helped stem the tide of untrained pseudo-professionals claiming to be allergists, whose lack of knowledge could potentially harm patients. In the early 1980s Professor Bengt Sameulsson received the Nobel Prize in Medicine/Physiology for identifying leukotrienes as the little understood ‘slowing reacting substance of anaphylaxis’ which had been found in allergic inflammation many years earlier. Leukotrienes are naturally occurring chemicals in the body, which can contribute to asthma attacks. Sameulsson’s work greatly increased the understanding of the biological connection that leukotrienes have as mediators in asthma, allergy and inflammation. In 1986 the Utah Society of Allergy and Asthma was formed to promote the scientific interests of certified allergists and enhance their ability to provide high-quality allergy care, as well as to provide members a forum for the exchange of new ideas, discussion of difficult patients, journal club, etc. Since that time the general population has become more aware and understanding about the various types of allergy afflictions. New legislation has successfully protected allergy sufferers, especially those with severe food allergies. A new food labeling law now requires food manufacturers to disclose in plain language if a product contains any of the top eight food allergens. The Food Allergen Labeling and Consumer Protection Act (FALCPA), which took effect January 1, 2006, mandates that all foods containing milk, eggs, fish, crustacean shellfish, peanuts, tree nuts, wheat, and soy must declare the food in plain language on the ingredient list or clearly state that the product contains the allergen, and it must use its common name. For example, if a product contains “albumin” is must include the common name in parenthesis (egg). Such ingredients must be listed even if they are only present in colors, flavors, or spice blends. Additionally, manufacturers must list the specific nut or seafood that is used. This law will potentially save many lives. While more than 160 foods have been identified as causing allergic reactions, the eight foods listed above cause 90% of all serious food allergy reactions. Today allergies are more common than ever, affecting up to one in 3 people. From asthma to hay fever, eczema to food allergies, and hives to sinusitis, it almost seems like everybody is suffering from one form of allergies or another these days. The good news is that there are a growing number of competent specialists in the field, along with new and improved medications. Several studies and research projects are currently underway to give us an even clearer understanding of how to effectively treat allergies. New medications are constantly under development to offer more relief with few side effects. Today, with the proper treatment, those with allergies can look forward to a bright and healthy future. A Historical Timeline and Summary of Modern Allergy Study 1819 – Dr. John Bostock accurately describes hay fever as a disease that affects the upper respiratory tract. Although of unknown origin, oddly enough it had nothing to do with either hay or having a fever. Hay fever, or in medical terms, seasonal allergic rhinitis, is the most widespread form of allergy, affecting millions of Americans. Symptoms include sneezing, a runny or stuffy nose, itchiness, swollen or watery eyes. 1869 – To investigate his own hay fever, Charles Blakely performed the first skin test by applying pollen through a small break in his skin. His experiment introduced the concept that pollen sensitivity caused hay fever. Today’s skin testing methods vary in the way in which the allergen extract is introduced into the skin; however, the principle remains the same. Blakely found that a positive reaction to a specific allergen could be recognized within twenty minutes by the appearance of “hives” at the tested skin site. 1902 – Charles Richet and Paul Portier invent the word ‘anaphylaxis’ when they discover a life threatening response to medications and protein substances. Anaphylactic shock occurs within minutes after allergen exposure, causing symptoms from swelling of body tissues, to vomiting, to cramps, to a sudden drop in blood pressure or even a loss of consciousness. It often occurs in people who are particularly sensitive to penicillin, stinging insects, shellfish, peanuts or tree nuts and it must be treated as a medical emergency. 1906 – Austrian Pediatrician Clemens von Pirquet first uses the word ‘allergy’ to describe unusual, non-disease related symptoms The word comes from the Greek word ‘alol’, meaning, ‘change in the original state.’ Indeed an allergic reaction is the result of the body’s change when it adversely responds to a harmless substance. 1911-1914 – The work of Leonard Noon and John Freeman helped established the basis for immunotherapy or allergy shots. Immunotherapy involves injecting the allergy sufferer with small, gradually increasing amounts of the substance that is causing the reaction. The idea is that over time, the body’s immune system will become less sensitive to the substance and the allergy symptoms will be reduced or eliminated. 1937 – Daniel Bovet synthesizes the first antihistamine drug. Subsequent antihistamines developed are still used today. 1948 – Philip Hench and Edward Kendall discover corticosteroids. They are found to be quite effective when used correctly, in both the treatment of asthma and allergic reactions. Corticosteroids continue to improve the lives of allergy sufferers today. 1953 – Researches James F. Riley and Geoffrey B. West, with the help of a loyal cocker spaniel test subject, discovered the mast cell granule to be the major source of histamine in the body. 1967 – Kimishige and Teruko Ishizaka and discover IgE class antibodies, and the process that they trigger, which causes allergy symptoms. 1980’s – In the early 1980s Professor Bengt I Sameulsson receives the Nobel Prize in Medicine/Physiology for successfully identifying leukotrienes and their biological role in asthma, allergy and inflammation. Sources include: American Academy of Allergy, Asthma & Immunology The Food Allergy and Anaphylaxis Network Brief History of Allergy, Dae Kim, BDS, MSc (Hons), MRCS, Auckland Allergy Clinic