Two weeks ago I saw a 20 year-old young man complaining of “allergies.” His mother accompanied him to the appointment to fill in the history of his hazy pre-adolescent and teenage years as well as to relate the recent testing results. A friend of the family had seen me in the past, had done very well on allergy shots, and had recommended me for a second opinion. For years my new 20-year-old patient would become sick at the change of seasons. His family doctor would prescribe an antibiotic, which usually helped somewhat. The young man described severe nasal congestion with thick purulent nasal secretions that could be blown into the tissue and would often drain into his throat causing a harsh cough and laryngitis. Usually he needed to get a second- or third-course of antibiotics to finally get better. His doctors tried various allergy medications to help, but he felt only the Sudafed or Afrin was actually doing anything for him. Also, about once a year bronchitis would accompany his sinus infection.

A chest x-ray had been normal. A sinus CT scan had showed some mild thickening of the sinus membranes but no surgically treatable abnormalities. He had seen an ENT surgeon following the CT scan and had some unusual allergy testing that involved a series of 150-200 injection tests. The tests were read as positive for multiple allergens, and he had been offered allergy drops or shots afterwards; however, his mother decided to get another opinion after hearing from the family friend.

His family history was notable for rhinitis and sinusitis in both parents. His younger sibling was unaffected. He did not have any other history of infection problems like pneumonia, skin infections, or meningitis. His exam was fairly normal since he had just finished 21 days of a strong antibiotic. We decided to skin test him using proper prick test technique to see if allergies were indeed contributing to his difficulties. He was not allergic to any of the types of dust, dander, pollen, or mold spores that we tested, which was a relief to him since that meant no allergy shots. We also did a pulmonary function test with results showing normal for his height and age.

Next, we ordered a complete blood count, immunoglobulin levels, and a test of complement level and function called a CH50. The results came back a couple of days later. All the tests were normal except for a very low IgA level. His level was undetectable (< 5 mg/dl). We repeated it and confirmed the result. He had IgA deficiency, not allergies.

Specific IgA deficiency (SIgAD) is the most common immune deficiency in the adult population. It is estimated that more than 250,000 people in the United States have this condition. In the general population this number works out to be about 1 in 500 people. However, in allergic populations, the risk rises to 1:100 people.

Since IgA moves from the bloodstream into the mucous, the infections that deficient people have are for the most part mucosal-based infections. The nose, throat, bronchioles, and GI tract all have increased risk of infection for people with SIgAD. The risk of having this condition is transmitted genetically but can skip generations. Some medications and some infections can trigger a temporary IgA deficient state, so rechecking levels is recommended before making a permanent diagnosis.

Having very low IgA can also increase the risk of an allergic reaction to a blood transfusion. For that reason I urge my patients with SIgAD to have a medic alert bracelet or a note in their wallet, which would alert ER docs or trauma surgeons to the condition so that proper screening can be done in an emergency.

SIgAD has no treatment. If a SIgAD patient also has allergies, we do treat the allergies in order to help with nasal/sinus or chest symptoms. If significant swelling has occurred, surgical procedures to open the sinuses or to ventilate the eardrums can help, too. Proper nutrition and exercise are encouraged to promote general health. Prompt treatment of bacterial infections of the sinuses, ears, chest, or intestines is helpful; however, overuse of antibiotics could have other effects, including development of medication allergies or antibiotic resistance.

My patient had pure Selective IgA Deficiency and thus needed no treatment for allergies. Seeing an Allergy Immunology trained doctor turned out to be extremely helpful since we provided him with answers for his condition. There is no substitute to being properly diagnosed.

Unfortunately, in this case, I had no specific treatment that could restore him to normal. He was introduced to saline nasal washes (distilled water only), encouraged in his overall health practices, and told to call when getting sick to be screened for antibiotic need. No surgery was indicated at this point in his life.

Fifteen-year-old Jharell Dillard from Lawerenceville, Georgia, died last week when he accidentally ate a cookie with peanuts. He had been shopping with his aunt at a local Wal-mart when he ran out to their car in the parking lot for a snack. When he realized the cookie had traces of peanut he ran to a nearby McDonalds to rinse his mouth out. He also took Benadryl, an over-the-counter antihistamine, but did not have his self-injectable epinephrine or Epipen. Reports indicate his tongue and throat swelled significantly before emergency services arrived. He was rushed to Walton County Medical Center and ultimately flown to Childrens Healthcare of Atlanta at Egleston where he passed.

Although Jharell and his family donated seven of his organs and have already helped save many lives, we’d like to help other individuals with food allergy avoid such a tragic outcome. Unfortunately, we are not in time for Tyler Davis, a 20-year-old student at Kennesaw State University who we just learned died also last week after ingesting a food he may have been allergic to.

Here are some important facts to remember about food allergy:

1. Teenagers and adolescents tend to be noncompliant with medical recommendations and have historically been poor about regularly carrying their life-saving, self-administered epinephrine.
2. Studies show that the earlier epinephrine is given for an acute reaction following an accidental ingestion the more likely it will be life-saving. Delayed administration of epinephrine may result in more severe and prolonged episodes of anaphylaxis.
3. Benadryl does not treat anaphylaxis!
4. Non-deadly food-induced anaphylaxis is the most common type of severe allergic reaction.
5. Food allergy needs to be accurately diagnosed, which involves expert interpretation of  a patient’s clinical history, skin tests, blood tests, and occasionally, food challenge.
6. No available cure is available for food allergy, so avoidance of culprit foods is key.
7. Patients at the highest risk of death from a food-induced anaphylactic reaction are teenagers with a history of asthma who already know what they are allergic to.
8. Close follow-up with an allergist is helpful.

Luckily, food-induced anaphylaxis resulting in death is relatively rare, claiming approximately 50 deaths per year in the United States. All-cause mortality from anaphylaxis is not accurately known but is likely around 1%.

At the Atlanta Allergy & Asthma Clinic we see patients with food allergy—and patients who think they have food allergy–on a daily basis. The diagnosis is not always simple and often requires our doctors to use a good clinical history, skin tests, blood tests, and food challenges to accurately advise patients on what foods to avoid.

If you or your friend or loved one has a food allergy, please make sure they see an allergist to ensure they are best prepared to avoid any culprit foods . . . and to treat themselves in case of an accidental exposure.

I am an allergist who has personal interest in food allergy. Most of my patients know that I am allergic to shrimp and that my 13-year-old son is severely allergic to pine nuts. We do not live in fear and do not let food allergies dictate our lives. We go out to eat, shop at grocery stores and eat packaged foods. Like all other food allergy patients, we have learned to read labels and discuss our allergies with restaurant staff. In spite of this, we have had three reactions in restaurants to pine nuts and one to shellfish. Accidents happen even if you follow proper precautions. However, we always have injectable epinephrine and are prepared to use it. In fact, both my son and I have used our EpiPens, which resulted in immediate improvement in our symptoms. The most important message I try to give my patients is this: don’t leave home without it and don’t be afraid to use it. This is the lesson that has been well illustrated by the two recent deaths in Atlanta. These unfortunate young men knew they were allergic but did not have their injectable epinephrine. Timely use of epinephrine could have saved their lives.
As a woman I am not particularly challenged by the task of keeping an EpiPen with me. I keep it in my purse at all times. I do worry about my son, though, who keeps his in his backpack and at school. When he goes out without me, we are challenged with the best way for him to carry it because it doesn’t always fit easily in a pocket (and he’s very reluctant to use a fanny pack). To parents out there, stay on your teenagers to carry an EpiPen at all times. They are at the highest risk to die because they often do not read labels, forget their EpiPen and are more likely to dismiss symptoms. Teach their friends how to recognize symptoms and how to use the EpiPen. Having and using an EpiPen during a reaction can mean the difference between life and death.

One of my patients with a significant history of allergies who had been repeatedly late for her weekly allergy shot asked me the other day in clinic whether we also offered sublingual immunotherapy or SLIT, the liquid allergy drops patients place under their tongue and then swallow. More and more allergy and ENT practices are making this alternate form of allergy immunotherapy available. Unfortunately, the FDA has not yet approved SLIT for use in the United States, although this method of allergy desensitization is commonly being used in Europe. Some doctors in the United States have been using the same allergy extract regularly approved for injections for sublingual treatments, although the doses administered sublingually are much higher.

And here lies the rub. Current studies on SLIT, most done in Europe, don’t delineate the precise, effective dose necessary for treatment success. In the U.S., such doses are regularly agreed upon for our much more commonly prescribed allergy shots. Further, most SLIT studies in Europe focus on patients who are mono-sensitized or allergic to only one allergen. Here in the U.S., patients are largely multi-sensitized or allergic to multiple different allergens. Most of our allergy shot patients are therefore prescribed allergy extract that consists of many different allergens, such as cat, dog, dust mite, tree, grass, mold and weed—not just grass extract alone, for example. We’re not sure yet whether mixing many different allergens together for SLIT would be as effective in treating multi-sensitized patients as one sublingual extract is in treating patients only allergic to one allergen. The one SLIT study done so far in the United States that looked at treating patients with multiple allergies revealed that mixing the allergens together blunted their efficacy.

Nonetheless, SLIT will likely become a commonly prescribed allergy treatment in the future. Like allergy shots, SLIT has been shown to be effective for treating allergic asthma and nasal and ocular allergies. Unlike allergy shots, SLIT can be administered at home and has a low risk for anaphylaxis, although serious allergic reactions have occurred. Recent evidence has even shown that both shots and sublingual drops might also help treat allergic patients with eczema or atopic dermatitis. As with allergy shots, SLIT has been shown to have long-lasting benefits, remaining effective years after patients have stopped the drops. Again, these promising results apply to mono-sensitized patients treated with allergic extract containing only one type of allergen and not necessarily to the multi-sensitized patient who predominates in the U.S.

Future SLIT studies will hopefully reveal how doctors can appropriately dose and mix relevant allergens to achieve the best treatment outcomes. Until that information is known, patients should understand that SLIT for patients with multiple allergies is in an investigational stage. Because SLIT is not FDA-approved it is not currently covered by insurance. Therefore doctors who provide this therapy do so off-label and so often charge cash. For all these reasons, the Atlanta Allergy & Asthma Clinic does not yet offer SLIT. As more information becomes available we may change our views, but for now, we prefer the tried and true.

We have so many different oral antibiotics available today, who cares if you are penicillin allergic? To treat your next sinus or ear infection your doctor can instead prescribe clarithromycin (Biaxin) or levofloxacin (Levaquin) or azithromycin (Zpak) or doxycycline or even cefdinir (Omnicef), a cousin of penicillin. For the most part, these alternative antibiotics work well and often suffice. Unfortunately, using them, especially the broader spectrum drugs like Levaquin, a member of the quinolone family of antibiotics, may actually increase your chances of developing a future infection with harder-to-treat, penicillin-resistant, bacteria. Doctors prefer to keep the big guns, the broadest spectrum antibiotics, in their holsters for just such situations. But if the big guns are used up-front and over and over again for common infections, chances are you will ultimately develop a resistant bug hopefully susceptible to an IV antibiotic, which may require you to be hospitalized for treatment. Such situations can be life-threatening.

Penicillin allergy also increases your risk of being allergic to another, related group of antibiotics, the cephalosporins. To further confuse the issue, these cephalosporin antibiotics are divided further into different “generations”: first, second, third, and now even a fourth. Allergists generally believe that patients with penicillin allergy will be more likely to be allergic to first generation cephalosporins like cephalexin (Keflex) because the two drugs share similar chemical structures. We think penicillin allergic patients are less likely to be allergic to third generation cephalosporins like cefdinir (mentioned above) as the chemical structure of the two drugs differ more. Truly penicillin allergic patients are thought to be allergic to all cephalosporins about 2-8% of the time, but those unfortunate and rare patients with the allergy to both can experience life-threatening reactions. So while many primary care doctors still prescribe Omnicef to patients with a history of penicillin allergy, they do so uncomfortably. Some doctors won’t test the waters, leaving you with fewer antibiotic options.

A few allergists joined forces with allergy extract maker ALK to help patients avoid the above scenarios by reintroducing the key component to penicillin skin testing that had been taken off the market in 2004. Pre-Pen, the major breakdown product of penicillin and the key to accurate penicillin skin testing is back. Now allergists across the country can better assess whether their patients are truly allergic to penicillin. This testing proves especially useful given most patients who think they are allergic, in fact, aren’t. Of all patients who say they are allergic only 10% actually are. Even those patients who truly once were allergic, lose their allergy over time—as many as 80% of patients lose their allergy after 10 years.

Without skin testing, even allergy experts have a difficult time figuring out whether you ever were or still might be allergic to penicillin. Skin testing assesses for the presence of penicillin-specific immunoglobulin E or IgE, the type of antibody also responsible for allergies to peanuts, tree pollen, dog dander, mold . . . . etc. An IgE-mediated allergic reaction to penicillin might cause symptoms of hives, itching, throat closing, wheezing, shortness of breath, light-headedness, nausea, etc . . .all of which are characteristic of severe allergic reactions or anaphylaxis. These symptoms generally appear within minutes to 2 hours after ingestion and usually occur after a patient has been previously exposed to penicillin. Unfortunately, patients don’t always remember in detail their allergic symptoms, especially when their reaction occurred years ago or as a child.

Patients may develop other types of rashes after penicillin ingestion which clouds the clinical picture even more. These other rashes are not usually life-threatening and not usually associated with development of the IgE antibody. For instance, patients may develop a red, rough, bumpy rash after penicillin ingestion which is often termed “maculopapular” by health professionals. These rashes are common in children taking penicillin and may occur even 7-10 days after completing the penicillin treatment course. In patients who develop these delayed rashes to penicillin, only 10-13% will actually develop another rash if re-exposed to the drug. In some cases, a viral infection, often mistaken by our medical community as bacterial and thus treated with antibiotics, may cause rashes by their own accord, unfairly implicating the patient’s antibiotic. It’s also been shown that some antibiotics interact with viral infections to create a rash, as occurs when patients infected with viral mononucleosis are given amoxicillin.

Other very severe, life-threatening penicillin drug reactions, such as Stevens-Johnson syndrome, are also not IgE mediated and so fail to register a positive reaction on standard skin testing. These reactions often involve a severe, diffuse rash with blistering of the mucous membranes and internal organ involvement. If these patients survive their drug allergy, they rarely have to be told to avoid all penicillin drugs in the future.

So penicillin allergy is not always straight-forward but determining whether you are currently at risk for a life-threatening penicillin reaction can be accomplished. Bottom line: if you think you are penicillin allergic you might not be. Speak to your local allergist to see if you might be a candidate for skin testing.

“I am allergic to all nuts.”
A friend of my wife cornered me at a Christmas party this year and told me her story. Hearing such tales is an occupational hazard for physicians, but I usually take it in good humor and sometimes even learn something myself. She told the story of living through an anaphylactic episode at age 13 after eating a single cashew. As she was chewing it a burning painful itching sensation began suddenly on her tongue and spread to the back of her throat. Next she started itching all over, turned red, felt nauseated and weak, and started to have trouble breathing due to her very tight throat. She was rushed to the emergency room where she had several shots, an iv was placed, and after awhile she felt better and was allowed to go home. Her pediatrician told her and her family at that time to never allow her to eat nuts again.
“Am I really allergic to all nuts?”
She had been wondering whether the advice she was given was true, and she certainly was interested in trying some nuts if it would be safe. Many holiday recipes use nuts to flavor or garnish a dish. Some Christmas cookie recipes use a base of ground up nuts instead of flour. Oriental foods often have peanut or cashews. Mediterranean diets also emphasize nuts as a source of healthy fats and protein.
Cross reactivity is a term used in allergy that describes the body’s ability to have recognition of a food or airborne allergen due to an allergy to a different food or airborne allergen. For example people who are allergic to hickory tree pollen are also allergic to pecan tree pollen due to the similarity of the pollen. People who are allergic to cow’s milk can also be allergic to goat’s milk in some cases. With nuts the case is trickier. Studies of peanut allergic patients have noticed that almost half of them develop allergies to tree nuts. However there seems to be no cross reactivity between tree nuts and peanuts so this represents the development of a new food allergy. However there is some cross reactivity among tree nut families so caution is warranted. We have some information on this through research that involves testing blood serum from tree nut allergic people against all tree nut proteins that are known. Other research involves giving tree nut allergic people oral food challenges with different nuts and observing them for reactions.
For more on this go to (http://foodallergies.about.com/od/nutallergies/p/treenutallergy.htm).
If you want to see some of the science of cross reactivity studies using double immunodiffusion go to http://treenuts.ca/nutallergy.pdf.
“Am I just nuts to do this?”
Seeing the allergy specialist was the right move for her. The new Food Allergy Guidelines certainly advises people with these types of questions to see a specialist for a discussion of testing options. My wife’s friend made an appointment to see me and I skin tested her to all the nuts. She had positives to cashew and pistachio which are known to be cross reactive. She was negative to another family of tree nuts (walnut and pecan). She underwent a food challenge in the office to both and did well. She decided to go ahead and eat these as she was reassured that the risk of reaction was very low. At last report she enjoyed both walnuts and pecans this Christmas season and was thrilled. She continues to avoid cashews, will not eat pistachios, and keeps her epinephrine injector in her purse just in case.

In the world of allergy and asthma, vitamin D is now a hot topic.  Many allergy specialists are wondering whether vitamin D might be used to help control asthma symptoms.  Our attention has turned to vitamin D because of mounting circumstantial evidence that links vitamin D insufficiency with poor asthma control.  The International Study of Asthma and Allergies in Childhood (ISAAC) begun in 1991 first noted a possible link between asthma and vitamin D insufficiency in Westernized countries like Ireland, England, Australia, the United States, and New Zealand which have the highest prevalence of asthma.  Most citizens in these countries spend the majority of their days indoors and so are commonly vitamin D insufficient, as they don’t spend enough time outside in the sun, which promotes vitamin D production in the skin.  In fact, we obtain 80% of our vitamin D from our skin and ingest only a small portion from vitamin D-rich foods like cod liver oil, salmon, cereal, milk,  etc.  Indeed, vitamin D insufficiency, defined as a blood level less than 30, is rampant in these countries, even in the sun-soaked Australia.  One study reports that 48% of the US pediatric population is vitamin D insufficient.  But just because lots of Westernized countries have lots of asthma and vitamin D insufficient patients doesn’t mean the two are related.

Furthering the conspiracy theory that vitamin D might play a role in asthma, African Americans and obese patients are more commonly vitamin D insufficient . . . and both groups are also more likely to have asthma.  And now we’re learning that vitamin D doesn’t just help control our blood calcium levels, which help keep our bones strong and prevent disease like ricketts.  We are beginning to understand that vitamin D does more than just help our intestines and kidneys absorb calcium.  Vitamin D receptors have also been found in the lung and in several immune cell lines like B-cells, T-cells, and dendritic cells.  What might vitamin D do in our immune system or . . . in our lungs?

One study in pregnant women revealed that vitamin D supplementation reduced the chance their future babies would develop asthma by as much as 40%.  The study had been prompted by the view that vitamin D might play a role in the development of the immune system and lungs in utero.  This significant finding has not been reliably reproduced however in subsequent studies.

At this point we don’t fully understand how vitamin D might function in our lungs or immune system, but we do think that vitamin D increases production of another type of immune cell called T regulatory cells or Tregs.  These cells tamp down immune responses.  So we might imagine that a lack of vitamin D and a resultant lack of Tregs might let the immune system run amok, as we see in various autoimmune diseases like diabetes or multiple sclerosis or inflammatory bowel disease or asthma . . .all of which have been associated with vitamin D insufficiency.  Again, these associations haven’t been proved to be causal at this point, but the vitamin D story certainly is tantalizing.  What more obvious explanation for the increased asthma prevalence in African American patients when compared to Caucasians than color of the skin and its ability to make vitamin D.

In the lung, vitamin D has been shown to increase production of proteins that help fight infections.   This might explain why asthma patients experience more severe lung symptoms when they acquire common, upper respiratory, viral infections.  A re-analysis of a landmark asthma study called the Childhood Asthma Management Program study (CAMP), indeed supports this view that vitamin D insufficient patients are more likely to experience severe, life-threatening asthma exacerbations.   A more rigorous, randomized, controlled study evaluating the effect of supplementing asthma patients with vitamin D has not yet been done so we don’t yet have our definitive answer regarding vitamin D’s effect on asthma.  Maybe sicker asthma patients spend more time indoors and so, by force, have lower vitamin D levels and all of the above is just coincidence.  We’ll find out soon enough.

This week a mother and her 5 year-old son visited me for an opinion on his food allergies. She brought with her a 20 page colorful and flashy printout of labs done a few weeks ago. The testing was quite comprehensive in evaluating antibody response to over 100 foods and 30 environmental allergens. It checked for the presence of other antibodies indicating possible celiac disease and also measured total antibody levels of various types. Many foods were identified as positives and most of them were her son’s favorites. She was in despair as she sought to provide him excellent nutrition, deal with his frustration at being denied some of his beloved foods, and try to make sense of the advice she was given by the nurse at the pediatric office. She had been simply told not to give him any of these foods until she could make an appointment with the allergist.
I asked her why the tests had been run. She stated that her son had had mild to moderate eczema for several years and recently had over a week of hives that led to the test being done. She had no idea he was so allergic to so many foods.
As I reviewed the tests with her it became clear to me that all of the positive tests were of the IgG4 type. These tests are not approved for the detection of allergic response by the body. The serum IgE tests were negative to all foods. Some of the environmental IgE tests were positive such as dust mite and cat dander. The celiac tests were negative as well. I was troubled at the use of testing methods that were not approved for allergy evaluation. I was also troubled by the misuse of such tests to alter diet and lifestyle unnecessarily. No testing was indicated at all by the history and therefore the financial cost and family turmoil could have been avoided.
The National Institute of Allergy and Infectious Disease (NIAID) released the first ever Guidelines for the Diagnosis and Management of Food Allergy last week (http://www.niaid.nih.gov/topics/foodallergy/clinical/Pages/default.aspx). The intent of the guideline is to assist clinicians in properly diagnosing and managing food allergy. The recommendations are based on studies and expert opinion both. They address both recommended and controversial methods of testing for allergy. It addresses dietary advice for both the allergy sufferer and family members. It addresses proper emergency management techniques and medications. Finally the guideline recommends that patients with suspected food allergy see a specialist who can look at all the facets of the problem: the history, the exam, and the testing results. Food challenges can sometimes also be helpful in understanding the relevance of skin or specific IgE blood testing. In early 2011 the NIAID will release a lay person version of the food allergy guidelines. We will post the link here when it is available.

After our lengthy conversation about the facts of food allergy and testing mother and son were excited to have his favorite foods restored to him. After reviewing the facts surrounding his rash we decided that his outbreak of hives was likely due to a cold virus he suffered around the same time. She called the office today to report that he is doing well, eating all his favorite foods, and enjoying being a normal boy again.

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