Allergic rhinitis diagnosis and treatment

- [Voiceover] How does somebody get diagnosed with allergic rhinitis? Well, allergic rhinitis is actually a very common disease, and most clinicians are very used to seeing it, and so far and away, the most common way to get diagnosed is actually by history and exam. If a person is displaying all the symptoms, then the diagnosis of allergic rhinitis can be very easy. For example, if they have nasal congestion, if they have nasal discharge, if they have watery, itchy eyes, if they have sneezing. It becomes even easier if you can show that those symptoms are seasonal or a person actually can show that they react to a specific allergen. In these situations, allergic rhinitis is easy to diagnose, and oftentimes, they'll be treated successfully from this point on, but what if there's still a question? What if, for example, they don't have a seasonal component, or they only have watery eyes and sneezing? In that case, more information is needed. Oftentimes, the next go-to test is something called skin testing. Now, skin testing may sound a little barbaric when I describe it, but it's actually the most sensitive and probably the most specific way, other than history, to get at the diagnosis of allergic rhinitis. In order to undergo skin testing, the patient has to have a relatively large patch of skin available for the test. Usually this is done on the patient's back. This can also be done on the arm or any other large area, but the important thing is that the person has enough room to place multiple tiny little pricks on the skin, and each one of these pricks contains an allergen. In other words, each one of these contains something that the person might be allergic to. Here, I'm going to draw a few out on this patient's back, and usually the person that's performing this test will number these with a Sharpie or a ballpoint pen just so they can keep them straight so they know exactly what it is that's going on. After the allergens are placed on or actually within the skin, 15 minutes is allowed to pass. At this point, the skin has had enough time to react to any of those allergens that a person might be allergic to. For instance, if this person has a skin wheal here and a skin wheal here, the person that performed the test knows one particular allergen here and one particular allergen here are potential culprits. Now, yes, this will leave the patient with an itchy, red, inflamed patch of skin, but it usually doesn't last that long, and this can give valuable information into what might be causing the patient's symptoms. For instance, in the scenario that I've drawn, if the person has a cat at home, it may be that the cat is what's causing the patient's symptoms, or it could be as simple as taking a different route walking to work and avoiding that patch of grass which is currently distributing pollen into the air. Now, sometimes nothing that the patient has been exposed to reacts, or there's another question about what could possibly be going on, and the skin test is equivocal, or perhaps the patient wouldn't tolerate having the skin testing, is either very young or has a skin condition that would preclude putting these allergens down. In those situations, you might need to go on to blood testing. Blood testing can be performed by almost anybody. Yes, it involves a needle stick. Yes, people don't like having these types of tests, but it might be preferable to the skin testing option. Sometimes also, it may be that you're worried that there could be a dangerous reaction to the skin test, and the blood test needs to be performed instead. Blood tests in the setting of allergies basically all look for the same thing. They all want to know are there specific antibodies to any of these allergens in the patient's blood, and the specific antibody that we're looking for in the case of allergic rhinitis and most allergies is called immunoglobulin or IgE. Now, your body makes a whole lot of different IgE molecules or proteins, and each IgE is specific for a certain thing. In other words, each antibody will bind to a specific allergen, so a person that's allergic to cat dander, for instance, would have IgE circulating in their blood that would bind to cat dander. Now, the first one of these tests to be developed was called a RAST test, or R-A-S-T, and RAST stands for radioallergosorbent test, and I'll write that out here. Now, we won't go into too much more detail because RAST tests have essentially been completely replaced by a newer and more sensitive test that uses fluorescence, or alternatively, another test that uses enzymes. The enzyme test is also known as an ELISA test, or enzyme-linked immunosorbent assay, and it's worth spending a second on what these tests actually do because they're kind of interesting. There are various companies that have developed these tests, and the general idea is that they provide a solid substance, and within that substance are embedded certain allergens. In this case, let's say it's pollen. This might be in a test tube or on a little plate, and usually a number of different allergens are tested at once, but once you've got your allergen embedded in a solid substrate, you wash it with the patient's serum. Within the patient's serum are those IgE molecules that we're talking about. IgE molecules are shaped like little "y"s, and they bind the allergen or potentially bind the allergen, so the serum is washed away at this point, and you're left with your solid substrate, your bound allergens, and your IgE molecules. The next step is that the manufacturer provides another antibody, but this antibody actually binds to those IgE molecules. Again, they're shaped like little "y"s, and the manufacturer has produced these to either have an enzyme, in the case of the ELISA, or to have a little fluorescent molecule on the tip of them here. Using the activity of that enzyme to change a solution's color or by looking at the fluorescence of this little fluorescent molecule, they can actually tell how much IgE is bound, and that can give them the idea that in this particular patient's blood, there was IgE that bound to pollen. That means they're allergic to pollen, or at least potentially it does. Both skin tests and blood tests can have false positives, and they can't be interpreted in a vacuum. It will show that a person might be allergic when they actually aren't, or false negatives, it will show that a person's not allergic when they actually are, but together with a history, and potentially with skin testing, the blood test can be a very useful alternative. Now, because this had to go through a lot of steps and a lot of development, of course, these blood tests are expensive, and that's one of the main drawbacks, in addition, of course, to having to actually get the patient's blood. Let's say a person has gone through this process and at this point, they've nailed down the diagnosis of allergic rhinitis. What's next? The next step is treatment. For discussion of treatment, let's zoom back in to the cellular level. Here, I'm going to draw the nasal mucosal cells again, all lumped together, and I'm going to draw one special cell, and that's our overreactive immune cell. Of course, there are lots of these in the nasal mucosa in a person who is allergic to things, but we're just going to draw in the one. Remember, this cell is usually a basophil or a mast cell. Let's say this particular cell is overreactive and sensitized to this allergen here, which we'll say is pollen. This cell is expressing that IgE molecule, and that pollen is going to go in and be bound up by that IgE. When that pollen binds to the IgE, it signals to the cell to react. Of course, in allergies it's going to be over-reacting. This brings up our first potential treatment. Our first treatment is to avoid the allergen. That will put a block in the process right here. I'll draw that in as a little bar blocking the way for this pollen to get bound up by this IgE molecule. In the case of pollen, it may be avoiding going outside when there's a high pollen count. In severe cases, you may have to relocate to areas where the pollen isn't even there. Sometimes it's impossible to do this, for instance, in the case of a loved family pet, or if you're not exactly sure what the allergen is. It's good that we have other treatments. Let's talk about the next step in this allergic cascade. Well, remember, when this cell overreacts to the pollen, it's going to start to release inflammatory molecules, and it's going to release them to all its neighboring cells, causing them to overreact as well. It's going to allow blood vessels to get leaky and for things to get swollen. It's going to cause these cells to overproduce mucus and all the other things that go along with allergic rhinitis. All those things are a result of these inflammatory molecules that this cell is putting out. The best and most potent next treatment after avoidance is to decrease the inflammation. There's been numerous studies that show that the best way to do this is steroids. In most cases, the steroids are applied directly to the nasal mucosa. Steroids have complex mechanism of action, but the end result is to decrease inflammation. Sometimes, though, it's not enough, and we have to attack other targets in this pathway of inflammation. Remember, this immune cell is overreacting and sending out all these pro-inflammatory molecules. Well, probably the most important one is called histamine. It's one of the major players in causing all of the inflammation, but these cells have to detect the histamine, but they have a little receptor that's sitting here on their membrane that's specifically built to receive histamine and react to cause all this inflammation. This receptor is called an H1, for histamine one receptor, so our next line of attack against this inflammatory pathway are called antihistamines, and that H1 blocker gets right in the way of that process here where the histamine binds to the H1 receptor. In fact, we can draw in boxes everywhere there's a histamine molecule coming in to affect to these cells, but unfortunately, that's not the only pro-inflammatory molecule out there. These cells are producing other molecules that go off and affect the nasal mucosa and the surrounding tissue as well. Another molecule that's involved in this pathway that we have a drug against is called a leukotriene. Just like with histamine, there are little leukotriene receptors as well, sitting on the cell surface. Our next line of treatment, although getting to be kind of last-ditch at this point, are called leukotriene inhibitors. Leukotriene inhibitors actually have a variety of different targets that can work like the H1 blocker right at the site of binding, like this. They can also work inside the cell later on in the pathway of a leukotriene's mechanism of action. We'll draw some blocks here within some of these cells. Most studies have shown that these leukotriene inhibitors aren't quite as effective, but they do give us another way to treat allergic rhinitis, especially if the first two methods aren't working. Once you have your diagnosis of allergic rhinitis, always not doom and gloom, we have an effective treatment regimen that we can put into action.