Today, we have guest speaker Dr. Brett Kettelhut. Dr. Kettelhut is board certified in pediatrics, allergy and immunology. He is currently practicing allergy and immunology at Boys Town, Neb., and is an adjunct clinical professor in the College of Medicine at the University of Nebraska Medical Center. Dr. Kellelhut also serves as the president of the Nebraska Academy of Allergy, Asthma and Immunology.
Today, we have guest speaker Dr. Brett Kettelhut. Dr. Kettelhut is board certified in pediatrics, allergy and immunology. He is currently practicing allergy and immunology at Boys Town, Neb., and is an adjunct clinical professor in the College of Medicine at the University of Nebraska Medical Center. Dr. Kellelhut also serves as the president of the Nebraska Academy of Allergy, Asthma and Immunology.
IG Living Advocate
Episode 8
PI and Allergies
Hello, and thank you for joining us today. My name is Abbie Cornett, and I am the patient advocate for IG Living magazine. This podcast is brought to you by IG Living magazine to give readers an opportunity to hear from healthcare experts on topics important to them.
In this episode, we will be talking about immunodeficiencies and allergies.
Today, we have guest speaker Dr. Brett Kettelhut. Dr. Kettelhut is board certified in pediatrics, allergy and immunology. He is currently practicing allergy and immunology at Boys Town, Neb., and is an adjunct clinical professor in the College of Medicine at the University of Nebraska Medical Center. Dr. Kellelhut also serves as the president of the Nebraska Academy of Allergy, Asthma and Immunology.
Abbie: Good morning, Dr. Kettelhut, and thank you for joining me today. I frequently get questions about allergies and primary immunodeficiencies (PIs). Having PI and allergies on the surface seems a little illogical since PI is caused by a weakened immune system or compromised immune system, whereas allergies are the result of an overactive immune system. However, PI patients frequently suffer from allergies. Can you please explain this disconnect?
Dr. Kettelhut: Well, thank you, Abbie, for inviting me to be on your podcast this morning. In regards to your question about allergies and PI, the first thing we have to recognize is that the prevalence of allergies is far greater than PI. It's estimated that 30 even 40 percent of the general population have some sort of allergy, whereas in PI, while patients do have symptoms, it is not as prevalent as the occurrence of allergies. It's not a very common illness that we have to deal with. In fact, the most common of the immune deficiencies is selective IGA deficiency and that only occurs in at most one in a hundred to one in a thousand patients.
With the high prevalence of allergy, it would not be expected to have patients with both allergies and PI confusing the distinction between the two. Another factor that complicates the identification of PI is that, in my opinion, antibiotics are overprescribed for allergies, so the recognition of PI is not considered. Also, as typically healthcare is now fragmented and many patients are treated by different providers for the same complaints, it makes it difficult to connect that there could be a PI. Finally, as PI is rare and is not typically considered as the underlying cause of most infections, in particular sinusitis, bronchitis and other respiratory infections. My personal experience is that most PI patients who I've diagnosed actually were referred to me for evaluation for allergies. And that's why I think there's confusion between allergies and PI.
Abbie: You know, that brings an interesting question: We know that there's frequently a long time between someone demonstrating symptoms of a PI and their actual diagnosis. Where do you see most of your patients being referred to from? Is it ear nose and throat doctors or primary care?
Dr. Kettelhut: When we talk about referrals from subspecialists, I think the two subspecialists who will refer are the otolaryngologists, the ENTs, and the pulmonary physicians. Of course, they're dealing with different organ systems. The ENT of course is dealing with sinusitis. The pulmonologist is dealing with recurrent pneumonias and bronchitis. I would say those are the two most likely referral sources for evaluation for recurrent infections. Although, as I mentioned, I think most of my referrals have been by primary care for difficult-to-control allergy symptoms, meaning recurrent sinusitis and potentially bronchitis.
Abbie: You know, that's interesting when you talked about that a lot of times there's a disconnect between the number of providers who a patient is seeing. If you were going to recommend to our patients who suspect they might have something besides allergies, how do you recommend they gather all that information together from the different doctors?
Dr. Kettelhut: Because it requires a certain understanding of PI, I think in general if a patient requires antibiotics two, three, four times a year, or if they have unusual infections like pneumonias or any sort of odd infections, deep-seated infections, that should raise in their mind that this is not an allergy problem but may have to do with their body's ability to fight off infections.
Abbie: Thank you. The next question I wanted to ask you is: Can you explain to our listeners how the immune system reacts to an allergen and what some of the symptoms are?
Dr. Kettelhut: OK, well you know the immune system, I like to make it rather simplified, although it is not simple by any means. But the way I like to discuss this is, I look at a coin that has two sides (of course all coins have two sides; I've never seen a three-sided coin, but nonetheless I digress). One side relates to overactivity or autoimmunity; the other side is related to providing protection from infections. As long as that's balanced, everything's fine. But if the coin is not balanced, let's say it leads more to autoimmunity, of course then patients will develop autoimmune disease, which actually is not uncommon in common variable immunodeficiency (CVID). But that's another subject. And then the other side of the coin is the side of the coin that protects us from infections, primarily by making antibodies. The antibodies that protect us from infection are typically IgG and IgA. The antibody IgE, though, is the antibody that in most cases causes allergies. When our immune system encounters a protein which is not us, it will normally respond by producing IgG and IgE antibodies. This is the purpose of immunization such as the COVID and influenza vaccinations — to produce these protected antibodies. In some instances, the antibiotic produces IgE, which can trigger an allergy in the future such as hay fever in the fall or food allergies such as peanut or shrimp. Also, in this case, it's the genetics of the individual which seems to play a significant role in how IgG is produced and how IgE ultimately affects them.
Abbie: We've all heard the term immune deficiency and we've all heard the term autoimmune and allergies. Instead of saying immune deficiency, because a lot of times it's more like a dysregulation of the immune system where you have too little in one and then you have too much of another when they have the allergies?
Dr. Kettelhut: Well, there's kind of a disconnect I think at times. I don't think I understand the question correctly. Maybe you should repeat that question so I can make sure I understand it.
Abbie: A lot of times our PI patients also present with other diseases that are more autoimmune in nature or allergic in nature. So besides it just being an immune deficiency, there's also some type of a dysregulation in the immune system.
Dr. Kettelhut: Well, you're absolutely correct because the immune system has multiple components. The antibody component is from our B cells, and the autoimmune component is from our T cells. And T cells are thought to be like the conductor of the orchestra. The orchestra members are the B cells. But, sometimes, the T cells react in an abnormal fashion, and it's the T cells which drive our body to produce autoimmune disease. So there are different components of our immune system which account for primary immune deficiency versus that of autoimmune disease. And, unfortunately, many of our CVID patients have both. They have poor antibody response and they actually even have some abnormal antibody response caused probably by the T cells in some degree because just like autoimmune cytopenias, autoimmune thrombocytopenia, autoimmune neutropenia, those are your more common autoimmune cytopenias that affect your blood cells.
Abbie: Thank you very much, Dr Kettelhut. It's my understanding that correctly diagnosing an allergy in PI patients can be difficult because the patients are more prone to infection. And allergic reactions manifest similar to infections at times. In fact, allergies are frequently suspected as an underlying cause of repeated infections. And I know you touched on that a little bit earlier. But because allergies are far more common than PI, when should you look for that diagnosis?
Dr. Kettelhut: Well, the diagnosis of allergy is not difficult in our PI patients. But as you mentioned, the recognition of allergies may not be straightforward. Seasonal allergies are pretty easy to recognize such as a typical hay fever in the fall — symptoms of itchy eye, sneezing runny nose, nasal congestion. The year-round allergies, or perennial allergies, are more difficult because typically those present with chronic nasal and sinus symptoms of congestion and postnasal drainage that are often considered or confused with sinus infections. And in particular, in the case of recurrent infections, the real issue is: How often does the patient require antibiotics, and what's the response? You know, allergies are not treated by antibiotics; infections are. And one of the things you see in these patients is that they're on multiple antibiotics throughout the year. They get better, but then the symptoms come back thereafter, and it's related to the frequency of the antibiotics improving the symptoms — not seasonal allergy or perennial allergies. And sometimes, you get very unusual infections. I had one patient who I diagnosed with CVID and her presenting complaint was recurrent urosepsis, which is basically bacterial infections of the bloodstream. Did I answer your question for you?
Abbie: Yes, you pretty much did. What I am looking at is: When should physicians look at PI as the cause of recurrent infections rather than allergies? And then, also, you mentioned the overuse of antibiotics: What would you consider too many prescriptions of antibiotics over the course of a year before you need to be looking for other causes besides allergies?
Dr. Kettelhut: Well, let's answer the last question first. The number of times I'm personally on antibiotic in a year is never OK. So anytime that a physician is prescribing an antibiotic, the indication ought to be pretty clear that this is a bacterial infection, all right? I think many times, though, this is not the case. Antibiotics are quick and easy to prescribe for symptoms which may or may not be true infections. So if, as a patient, you are being prescribed antibiotics on a frequent basis, even one or two times a year, you have to kind of think: What am I being treated for? Is this truly a bacterial infection or is this a viral infection? About 90 percent or better of antibiotics in this country, I believe, are being prescribed for viral infections. So I think any physician treating a patient when they are prescribing antibiotics should be always thinking about why they are prescribing the antibiotic. What's the reason? For example, most sinus infections that require antibiotics occur after having a viral upper respiratory tract infection that doesn't clear after seven to 10 days. And then again, because of the fragmented nature, a lot of times providers do not go back and look in the records to see, yeah, this is your third or fourth antibiotic this year. Those are red flags, in my opinion, that the physicians ought to at least think about why this patient needs so many antibiotics. Regardless of the etiology. I just think that's good medicine.
Abbie: I completely agree with you. All you have to do is look at the number of times people are prescribed antibiotics a year, and frequently it's way too often. The second part of that question, and this is getting a little bit off the original topic, but when you talk about allergies, how often does an allergic reaction actually turn into a bacterial infection? Because if you have the allergy long enough and you're congested, does that ever turn into an infection?
Dr. Kettelhut: Well, it could, I think. With severe allergy, whether it's seasonal or perennial, that's undertreated and you have nasal and mucosal congestion and changes in the sinuses, especially if the sinuses are obstructed and they cannot drain properly, then you are predisposed to having an infection, especially if you get a virus on top of it. So now you've got a double whammy: You've got the underlying inflammation of your nasal passage and your sinuses from allergy, and now you get the viral inflammation. And the two together then make it more likely for you to develop a secondary bacterial infection. Primary bacterial infections, I think the sinuses would make you think there's some issue going on with the immune system. There's something else that is needed to be looked at.
Abbie: Great, thank you. There are different forms of PI associated with an increased susceptibility to allergies, and there are others associated with specific allergies. For instance, does a patient with hyper IgE syndrome tend to develop more allergies than other PI patients?
Dr. Kettelhut: Well that's an interesting question. I actually took care of one patient with hyper IgE and this is a very unusual immune deficiency; it's not very common. And these patients can have associated eczema. But their real problem is recurrent staphylococcal infections, especially pulmonary infections. So, they may have findings that you consider allergic, but I don't think it's truly allergy. The hyper IgE patients, they produce excessive IgE, but it's more of a general production; it's not necessarily as specific as to an individual with hay fever who has IgE primarily to ragweed. They do make IgE antibodies, but usually that's more toward the bacteria that cause the infections like staphylococcus. The other autoimmune disease that has typically elevated IgE is called Wiskott Aldrich syndrome. It's found in boys. They typically have eczema, and they also can have other findings of allergies and asthma. And they also have what they call small platelets or thrombocytopenia. But again, these are very rare patients who I believe are being picked up in neonatal screening now. What complicates this sometimes is the fact that some of our patients with atopic dermatitis, which is allergy, can have extremely high serum IgE levels. But when you go back and you look at these patients, they're not having recurrent infections. They're having significant eczema that can be associated with food allergy in some instances.
Abbie: That's very interesting. Now that you brought up food allergies, is there also a correlation between PI and food allergies? And if so, is there a specific form of PI that's more susceptible to food allergies than other forms?
Dr. Kettelhut: Well, when you talk about food allergy, the most common food-associated reaction is going to be in patients with selective IGA deficiency. Those patients may have celiac disease. I'm sure you've heard of that. Now, celiac disease is not a true food allergy in my opinion. It's an immunological reaction to the protein called gluten. And that causes inflammation in the small intestine, which then leads to malabsorption. So, it's a food sensitivity if you want to think of it that way, but I don't necessarily think of it as a true food allergy as one would think someone is allergic to peanut or to shrimp. There could be some other intolerances, too, that may be confused with food allergy. One of the most common intolerances, of course, is lactose- or milk- and protein-intolerance, or lactose sugar and milk protein intolerance. So you may have some patients who have this intolerance which is not unusual, and then it gets confused as secondary to their immune deficiency.
Abbie: That's very interesting. What do you suppose is one of the most serious food allergies? Probably peanut allergies?
Dr. Kettelhut: Well, in the general population, in children, it tends to be peanut with nuts, and in adults, it tends to be shellfish. But what makes food allergy dangerous is lack of preparation and lack of immediate treatment when a person does have an exposure to food allergen. Because to date, we don't have a cure for food allergy. All we can do at best is identify what the specific food is, counsel the parent or the patients about how to avoid this and then prepare them for any accidental exposures that may occur in the future. Because the number one reason for a food allergy after it's been diagnosed, of course, is accidental exposure. Nobody in their right mind is going to eat a food that they know they're allergic to.
Abbie: That is very true. I certainly can't eat strawberries; we'll just leave it at that. It's nothing severe, but no, I don't like hives for a week. So, is there a difference in the treatment protocols for PI patients with allergies versus those without allergies? And should immunoglobulin trough levels be checked? Why I'm asking about trough levels is: If you're going to test for allergies after a person has had an immune globulin infusion, should it be done immediately after or before their next infusion or treatment because the levels are so much higher after an infusion than before?
Dr. Kettelhut: Well, again, since we're talking about IgE, not IgG, I am not aware that these immune globulin products have a large amount of IgE.
Abbie: How much IgE do immune globulin products have? And would that affect allergy testing? If it does, when should a patient have the testing done?
Dr. Kettelhut: Let's make the assumption that there is significant IgE, OK? I'm not sure that's the case. There are a lot of different products. But if you're going to ask me, how can we minimize that possibility, I agree a trough level would be one I would draw. But the problem is, as you well know, with the primary way we deliver immune globulin now (subcutaneously), we don't get these peak trough levels anymore. So I think that this is an interesting concept. But, unless you're one of those few patients who are getting monthly infusions, there really isn't a trough level to look at.
Abbie: That's interesting. That question was based on infusions versus subQ, and with subQ, you would have a constant level.
Dr. Kettelhut: So, if they're treated monthly with intravenous infusions, I would go ahead and check right before their next monthly infusion. But if they're on weekly subcutaneous infusions, I don't think it really matters. But like I said, I'm not aware of how much IgE is in these various preparations, and I have no idea what the amounts are. Now if you assume that you are getting a large pool of individuals donating and 30 to 40 percent do have allergies, you could theoretically find IgE in the product. And in that particular case, instead of doing skin testing which is the typical way that I look for IgE-mediated food allergies, I think that an immunocap RAST, which is a blood test, might be more useful because you can quantitate the amount of IgE in the patient's blood. Now, that might help you to determine, along with history, whether or not there's a food allergy. You have to remember the presence of IgE does not prove allergy, proof sensitization. So you have to go back and you have to look at the history. In fact, if the history doesn't suggest food allergy, I don't look because you can get various results and you can get false-positives.
Abbie: That's an excellent point. Well, we're kind of running out of time today, so I wanted to thank you so much for joining us. It's been a real pleasure to have you, and I hope to have you as a speaker again in the future. Is there anything else you'd like to cover before we wrap it up?
Dr. Kettelhut: I just want to thank you for allowing me to participate in your podcast. I think that the service you provide is much needed, and I'm sure it is much appreciated by patients with primary immunodeficiency.
Abbie: Listeners, thank you again for joining us today. Additional information regarding this podcast can be found on our website at www.igliving.com. If you have a question that was not answered, please contact me at acornett@igliving.com.
Look for the next IG Living podcast announcement on our website for the opportunity to submit your questions.
IG Living Advocate is a copywrite production of IG Living magazine, published by FFF Enterprises, the only magazine for the immune globulin community comprised of patients who suffer from chronic illness and their caregivers.