Oral Implications of Nutritional Deficiencies PDF

So let's first start with a couple systemic issues that can have oral implications, if you will. The first would include nutritional deficiencies. So many of us eat a varied diet and me, I eat a very diet and extra. So as long as ice cream is in the food group, I'm good. But in any case, we eat a ve...

So let's first start with a couple systemic issues that can have oral implications, if you will. The first would include nutritional deficiencies. So many of us eat a varied diet and me, I eat a very diet and extra. So as long as ice cream is in the food group, I'm good. But in any case, we eat a very diet and so we have a diversity of nutrients and imagining a nutritional deficiency may be outside of our thinking. However, it is not uncommon for some of us to encounter either patients or even our own selves to have nutritional deficiencies despite eating a varied diet. So for various reasons, right. So a very common deficiency in that you will encounter in your clinical endeavors is iron deficiency anemia. Now the most it is the most common cause of anemia. Here in the US. There's lots of reasons why you could have iron deficiency anemia. It could be because of excessive blood loss, including menstruation. It could be decreased. Sorry, an increased demand for RBCs, say such as during pregnancy or other states where you are needing more RBCs, meaning red blood cells, Right. Decreased iron intake, maybe just dietary sources. You are not choosing a diet or your patient is not choosing a diet that has high iron foods and then decreased absorption because of systemic issues. And you may remember back from when you looked at red blood cells and iron deficiency anemia and kind of pathology courses on cytology. If you look at a blood smear of a patient with iron deficiency anemia, the red blood cells are smaller than you would expect and they're paler than you would expect. So we call that hypo chromic microfluidic. But that's just just to remind you what they look like. I'm not going to ask you what they look like. It's just a just so you know, I will tell you that in patients who have iron deficiency, you really can see clinical manifestations in your practice. And some of the clues that you might see in a patient who is deficient in iron includes a vulnerability to a condition called angular colitis. I actually just saw a patient this week in my clinic with this condition. So if you maybe you've ever you've had this happen to you before, right at the corners of your mouth, you know, it's very common as we become more seasoned and maybe get a little wrinkle at the corner of the mouth. It is dark, it is moist, and it's a great place for organisms to kind of overgrow. And so you can get a little scaling, erythema, fingering right at the labial call mature. And we call that angular colitis. Patients can have that condition outside of iron deficiency anemia. It is just that it is a little more common in patients who are deficient in iron. Atrophic loss situs is another feature. What does that mean? It means the tongue is bald. Right. So you know that we have hundreds of hair like projections on the surface of the tongue. These are fully formed papillae. They belong there. You know about them. They're normal structures. These are the structures that can be accessibly coated with keratin. Right? If we have dry mouth or a soft diet or we smoke, well, you can also see loss of papillae, diffuse loss of papillae, a balding of the tongue, if you will. We call that atrophic loss situs. And that can be seen in actually a number of conditions, one of which is iron deficiency anemia. So keep that in your differential. If your patient sticks out their tongue and it is bald and red, generalized mucosal atrophy. So what does that mean? Well, normally the thickness of the skin of the mouth is a certain thickness, right? The stratum, Spinoza, the thickness of the epithelium is kind of universal in various parts of the oral mucosa. If it gets thinner, what will you see clinically? Just intellectually think about it. If we talk about what can make a white lesion look white, it's anything that keeps your eye from seeing the blood vessels, right. And the underlying connective tissue that can make something look white. Well, what could make it look If it were atrophic, what would it look like? More red, right? It would be erythematosus because the epithelium is thinner. So now it's easier to see the blood vessels, right? So if mucosal atrophy would present as kind of diffuse erythema of the oral mucosa. There is a kind of a syndrome, if you will, in which patients who have iron deficiency anemia have kind of a constellation of symptoms, a very severe iron deficiency anemia can cause glossiness sort of atrophic loss sites that we mentioned, kind of mucosal burning irritation and dysphasia. That means difficulty swallowing, right? So this is something called Plummer Vincent syndrome, and that is a condition in which patients who have iron deficiency anemia present with a couple of other contributing symptoms. All right. Now, I have seen patients with iron deficiency anemia in my clinical practice. I will tell you a quick story about one particular patient. She had been in a motor vehicle accident and was otherwise healthy. But during the accident, she had a an injury to her esophagus. And I think at the seat belt, something happened and it it caused the esophagus status post treatment for this traumatic injury. Her esophagus no longer kind of had a straight anterior sort of inferior sort of orientation, if you will, superior inferior. It kind of had a curlicue in it. Right. So that it had a contour defect and it meant it was difficult for her to swallow certain foods. And so she had a very restrictive diet. And so when she came to see me, she sat in my chair complaining of some kind of burning in the mouth and some trouble with her mucosa. And then she kind of started to doze. And it's kind of interesting because usually patients who come to see us, especially me, because they get kind of anxious to see someone who's a pathologist, it sounds like disease and kind of intimidating, worrisome. And so instead of having elevated blood pressure and being very anxious and focused, she actually was getting tired just sitting in my chair. And so I had her pull down her eyelids just so I could peek at the color of the conjunctiva. And it was pale. And when I looked in her mouth, I have never seen the mucosa so pale in all my life. It was instead of being pink as you'd expect, it was almost white. It was so pale. And that was, again, you know, she's anemic and very tired. Right? The oxygen carrying capacity of her blood was not up to par. And so we determined this was the most likely issue. And she was seen by her primary physician who did hematologic studies to assess for iron levels. And she ended up having iron infusions and improving. But so, you know, you can run into this in your practice and not only from, you know, patients who maybe have dietary choices that are different or who are avoiding certain foods that are high in iron or maybe have absorption issues, but also even status post an injury that's that's causing a change in dietary choices. But anyway, this is a patient just demonstrating two features that you can see in iron deficiency anemia. The first is angular colitis. If you notice right at the labial comissioners, right where the maxillary and mandibular vermilion border kind of join, you see there's kind of an ulcer and redness right at the corner that is angular colitis. Again, not unique to iron deficiency anemia. It's often a sign of fungal infection sometimes and anatomic folding and moist environment that allows bacteria and fungal organisms to overgrow. It's just you're more vulnerable to it, right, when you have iron deficiency anemia. And then look at the patient's tongue. It is bald and it is beefy red. And so that is a supporting feature in a patient with iron deficiency anemia. Another example, look, you can see similar features. Another retractor in there so we can see a little better. All right. So that's iron deficiency anemia. Again, patients should have a history that would help support that thinking, especially, say, in a test setting, but in your clinical practice. More importantly, if you encounter a patient with loss of form papillae, history of fatigue. Angular colitis, beefy, bald, red tongue. Think about nutritional deficiencies. Another one that can present that way is B12 deficiency. So pernicious anemia is a situation in which patients can have a deficiency in the intrinsic factor that facilitates the uptake of B12. And when this occurs, B12 looks different just for your interest. Again, not from a test setting, but just so because I think you might like to know the hematology. If you look at a blood smear of a patient with B12 deficiency, the red blood cells look very different. They have they're much bigger than you'd expect. We call it macro acidic anemia. And so tests can be done to assess the pathogenesis of the deficiency, whether it's a dietary deficiency or whether it's an issue with this intrinsic factor that's preventing, no matter how much B12 a patient takes in, they just can't convert it properly because they don't have the intrinsic factor. So patients with B12 deficiency have, similar to iron deficiency, a burning sensation of the oral mucosa, mucosal erythema and mechanical atrophy. This patient has kind of patchy loss of papillae of the tongue. And interestingly, when you are trying very hard to make red blood cells because you need greater oxygen carrying capacity, sometimes your body will make more red blood cells, right? Because the ones you have are not doing enough for you. And so you will find new places to make new red blood cells. So your jawbones that usually don't really do a whole heck of a lot of hematopoiesis we don't usually see, you know, hematopoietic bone marrow elements. You can, but not to a great extent in the in the jaws by the time we are formed. You can go back to producing he, you know, blood cell precursors in your jawbones and you will that will be reflected by this kind of altered trabecular pattern in and that is a feature in patients with very chronic B12 deficiencies. All right. So just a couple examples in which nutritional deficiencies can manifest with oral findings. And if a patient such as that should show up in your clinical practice, just think about that possibility. And then the the responsibility is simply for you to suggest that the patient see their physician for some routine blood work to rule out that possibility and then the physician can take over the management of the nutritional deficiency. And once that's stabilized, the oral changes result. All right. All right. This next condition is a condition called Addison's disease. Now, Addison's disease is an endocrine abnormality in which there are two possibilities in which patients can develop this condition. Either there's problems with the the adrenal glands that sit, as you know, on top of our kidneys, primary hypo adrenal criticism in which the adrenal glands don't produce enough adrenal corticosteroid hormones because of usually inflammatory destruction of the adrenal cortex. And so it is a primary hypo adrenal criticism, secondary causes for Addison's disease. If the, you know, the adrenal glands are perfectly fine, would be a pituitary gland malfunction. And the result is that patients develop diffuse bronzing of the skin because this tends to stimulate melanin production and so patients can have diffuse bronzing of the skin and you can acquire multifocal macular, meaning flat brown pigmented lesion of the oral mucosa. Um, and you know, there are tests that can be done in order to kind of cinch the diagnosis and confirm the etiology, whether it's a pituitary issue or whether it is from primary hypo adrenal criticism. So this is a patient who a Caucasian patient, fair skinned patient with diffuse bronzing of the skin as a result of untreated and as yet undiagnosed Addison's disease. You can see diffuse melanocytes and bronzing of the skin. Now, in patients who have Addison's disease, you can acquire these macular, flat brown pigmented lesions of the oral mucosa. So, you know, if if you see a patient and there is someone in the room, Rachel, who you may want to keep this in your differential for that case, we've been kind of discussing if an adult patient presents with newly acquired melan, acidic pigmentation of this nature, then it is a part of our responsibility to have the patient seen by their physician to rule out an endocrine abnormality. All right. You know, if you were to biopsy one of these pigmented lesions, you would not see any melanocytes ATP. This is not concerning for melanoma. You would just see more pigment in the basal layer than you'd ordinarily expect. Right. So this is an oral manifestation of a systemic condition, right? An endocrine abnormality. And here is diffuse pigmentation of the tongue in a patient with Addison's disease. All right. Any questions about that? All right. Now. There is a another kind of jumping now to another thing that we're going to talk about today, and that is a very particular kind of inflammation. So first I have to clarify terminology. So sit tight. All right. You have learned about an entity in which there's a non vital tooth. And at the apex of that tooth, you see a radial. And we've always said it's either a periodical cyst or a peripheral granuloma, right. That term granuloma in that context is just a short way, a shortened form, a kind of vernacular for saying granulation tissue, granulation tissue is new blood vessels and in this case, inflammation. Right. So when we use the term periodical granuloma, we're talking about granulation tissue. Today. All right. We're going to talk about what a real granuloma is. All right. So a periodical granuloma is granulation tissue when we use that term. That's what we mean today. We're talking about something else completely different, a different kind of inflammation. And it is called a granuloma. Okay. And there are a few conditions in which you might see that very particular kind of inflammation. All right. Inflammatory bowel diseases can present with associated what we call granulomatous inflammation. It's a very particular kind of inflammation. These include ulcerative colitis and Crohn's disease. Now. Crohn's disease and for example, is a condition that involves the entirety of the GI tract with certain areas more likely to show this very particular kind of inflammation. It's not unusual for the first manifestation to be the mouth, the oral mucosa and lips, and then patients will complain of GI issues like diarrhea and such. So. We will talk about. All right. So this is a patient. So we'll start with this. We'll start by talking about Crohn's disease. So Crohn's disease is a very particular inflammatory condition in which the, you know, the entirety of the GI tract can be affected. But the distal small bowel and proximal colon of the lower GI tend to be affected and the oral cavity can be affected. All right. So this is a patient who is presenting with oral manifestations of Crohn's disease. It's kind of nonspecific, right? We see the gingiva is focal erythematosus and ulcerated. You have this kind of irregular ulcerative lesion on the gingiva. Kind of nonspecific, I agree. But look how the gingiva is kind of boggy and enlarged. And then this to me is the classic presentation for oral manifestations of Crohn's. If you find this in your patient, honestly, you are doing them a huge favor because catching it early is so helpful and it's not unusual for oral lesions to proceed. GI lesions. I have seen many patients who present in this fashion. All right, so the first place I want you to look is the vestibule, the gutter. It's a great place to see these lesions. All right. Patients develop these kind of redundant tissue folds that remind me of hyperplastic tissue that you see when a denture doesn't fit. Well, just these kind of folds of tissue, linear folds of tissue that are ulcerated. Okay. And you see that here? Do you see in the back? If I have one of those pointers, let's see if it'll work right there. Do you see these linear folds of tissue? It's very subtle. Classic, classic. All right. And then you see all this kind of creamy yellow exudate. These are all ulcerative lesions, very superficial, ulcerative lesions. Here's another example down here below. And you can see that pseudo membrane right in that patient. So patients develop these kind of multifocal ulcerative lesions, but always look in the vestibule and look for these kind of redundant folds of tissue. Also, Crohn's disease tends to come along early on when a patient is a teenager, early 20s, that's usually when the diagnosis is established. So seeing this in a younger patient is highly suggestive of a granulomatous inflammatory condition. Specifically, think about Crohn's. Okay. This was my patient. He's 24 years old at this time. I had been following him for a bit. He has a known diagnosis of Crohn's disease and he was seeing me about the persistent labial fullness. Now in patients with Crohn's disease, the you get it's an inflammatory disorder and the inflammation is characterized by these aggregates of his sites. These are macrophages that are activated and they come together in these little clusters, sometimes with multi nucleotide giant cells. And so we call that epithelium sites activated macrophages, we call those aggregates Granulomatous. Okay, So in Crohn's patients develop this granulomatous inflammation where there you can develop this firm persists and swelling. So when you palpate this gentleman's lips, they were woody firm hard. When I took the picture up top, I went to reflect his maxillary labial and mucosa. And think about if you were to kind of retract your upper lip, it would kind of be very supple and kind of his lip moved as one mass. It was that firm and his buckle mucosa is very firm because it is teeming with granulomas in the underlying connective tissue, these collections of his sites, it's very inflamed and when you palpate it, it is not soft, it is nodular and firm. I also want to clue you in on a secret feature. Whenever you suspect Crohn's disease, you look for the kind of redundant folds of tissue in the vestibule. With ulcers, we call that pie stomatitis vegetarians and then palpate for kind of nodular look for labial fullness. Look at Wharton's duct, Wharton's duct has this tail tail sign in a lot of patients, when they have granulomatous inflammation, we say it's staghorn. So the the orifice of Wharton's duct, you get these kind of little horn like protuberances at Wharton's duct. That's also very classic for Crohn's. So these are key clinical features you can use when you are examining your patients to assess for potential granulomatous inflammation. This is another example of the kind of punctuate ulcerative lesions that you can see in Crohn's. Again, the term is you PIO, stomatitis vegetarians, whatever. It's they call it snail track pustules. If you've ever seen a snail kind of leave it snotty goo along after it's moved away. That kind of they have this kind of subpages or snaky looking trails of teeny tiny little punctuate areas of ulceration. And that's what what we're illustrating here. And again, with these grooved corrugated areas, you're looking at the buckle mucosa. Do you see how it has these kind of fishery grooves to it? That's also very suspicious for Granulomatous inflammatory disorder. Again, with the snail track pustules. All right. And this is the patient post treatment. So what is a granuloma look like? All right. So this is a picture of a biopsy of a patient who had suspected, you know, granulomatous inflammatory condition like Crohn's. And in the biopsy, you see, no matter where you're sitting, you can see there's an aggregate here of these tiny little small round blue cells. These are lymphocytes. But inside this aggregate are these cells with larger, more eosinophilic cytoplasm, maybe a little multi nucleated giant cell. This structure, if you will, inflammatory structure is called a granuloma. It is a collection of epithelial adhesive sites, often with multi nucleated giant cells. Here's another one. Look, see the multi nucleated giant cells and these kind of pale cells here in the inflammatory infiltrate are all Hestia sites. Now, Crohn's disease is not the only condition in which you can see this particular peculiar inflammation. All right? You have to have other things in your differential. And another possibility is a condition called sarcoidosis. Sarcoidosis is a granulomatous disease. We don't really know what causes it, but it is probably related to an overreaction to antigens that that are being presented. And. Sarcoidosis predominantly affects the lungs and the glandular tissue like salivary gland tissue. It can also affect the eyes and lymph nodes. All right. Yes. Sorry. Yes. Back. Yes, right there. Sure. Absolutely. So there are two lurking in this picture. This one and this one. Oh, you can't. I'm sorry. Here. I don't know what else they have. Green. Can you see that? Sorry. Thank you. Any other questions? But you see them now, right? Okay. This one's a really good one. Okay, I'm ready for action now. All right. So sarcoidosis, you can see the same kind of granuloma. There will be collections of epithelium at historic sites, sometimes with little multi nucleated giant cells. And that pattern of inflammation can be seen in this other condition. But unlike Crohn's, that tends to affect the GI tract, this tends to affect salivary glands, lungs, eyes and lymph nodes. So here's the patient presenting with bilateral facial enlargement with the right side more significantly involved slightly in my opinion. And you can see some changes in the sclera of the eye, some kind of enlargement of the tissue, the soft tissue, and then we have a biopsy of the salivary gland tissue. So the salivary you're looking at salivary glands, globules of salivary glands. Let me show you here. You can see that they kind of maintain their lobular architecture, right? There's a lobular, there's a oh, is it going to. It only works for a second. Up top there's a lobular. But within the salivary gland tissue, the glandular units have been overrun by granulomas. I'm just going to point. I'm sorry. You know, it's kind of rude to step in front, but I don't know how else to do so. These are normal arsenal units, normal salivary gland tissue. And on the right, you'll notice it looks kind of smudgy. Like I put my thumb on it and pushed. Right. It looks softer. It's harder to define the assignee. It's kind of messy. And if you look more closely, there are some collections of multi nucleated giant cells here. There's a big one up there. Okay? And they're kind of this pale cells that that kind of clump together. All right. So let's zoom in on an area. All right. And so here you see in the upper right hand corner, this swirl, you all see the multi nucleotide giant cell right here. I just make sure there's one here and there's also one over there. But these are collections of epithelial sites and they tend to make these little nodules or little balls of cells. And they are it is just a particular kind of inflammation. All right. It's a collection of history sites, often with multi nucleotide giant cells. In this case, these are non necrotizing granulomas. Later in the course, we will talk about infectious conditions like tuberculosis and other conditions, things we get when cats scratch our face and things like that, you can get a certain bacterial infections and so forth that can cause granulomatous inflammation as a response, but usually there's necrosis in the middle. In this case, these are just collections of epithelial adhesive sites now, because it's involving the salivary gland tissue. Our index of suspicion is higher that this might represent sarcoidosis because sarcoidosis does have a tendency to cause granulomatous inflammation in glandular tissue. Now, what if, you know, you've you can't seem to find an explanation. I've never had GI issues. I've had a colonoscopy and everything is normal. They don't see any evidence of Crohn's. But I still have an unequivocal granulomatous inflammation only in my oral cavity. My chest x ray was negative, so nothing like sarcoidosis. So we have a diagnosis of exclusion. If you've ruled out systemic causes of granulomatous inflammation like sarcoidosis and Crohn's, then it might be this condition called oral facial granuloma. Ptosis. All right. Oral facial granuloma ptosis, we say, is a diagnosis of exclusion because if you biopsy a patient and you see granulomatous, you do need to rule out systemic causes for granulomatous inflammation. If you can't find it, then this is the diagnosis you make. It only affects the oral cavity. Again, we don't know what causes it, why we develop granulomatous inflammation, but it is likely an overreaction of our immune system. Some patients may have a genetic predilection for the disease. For this condition there may be there's handwaving that maybe it's an overreaction to a viral protein or a bacteria, but we don't know. And that's the bottom line. Okay. And so you can see oral facial granuloma ptosis all by itself. Oftentimes you might see accompanying fingering of the tongue and enlargement of the tongue as a result, sort of figuring an enlargement, which is a what we might call Melkersen Rosenthal syndrome. So here is a patient presenting without any systemic involvement, chest x ray, negative, salivary gland involvement, negative. And yet the patient has firm, palpably firm, swelling, nodular swelling of the lips. That's persistent. Okay. Here's another patient presenting similarly kind of just nonspecific, palpably firm enlargement of the lips. You'll notice that the lips fissured. And there's also the scale crust. Don't be distracted by that. If your lip was swollen, it would probably not be unusual for you to moisten it with saliva because it feels weird to you. Right? And that's exactly what people do. If you have an enlarged lip, it's not unusual to kind of moisten it with saliva. And that's the worst thing we can do, right? Just so you know, a dry lip is technically a healthy lip. We're not supposed to moisten our lips with saliva. And if we do, the saliva evaporates and then it gets drier, and then you'll get scale crusting and figuring you can secondarily colonize with oral flora bacteria and candida, which is a fungal organism. So in any case, don't be distracted by that scale crust and fissure that you see here. That's the patient is probably, I'm assuming, moistening their swollen lip. And if you palpate it, the reason I keep pointing out that what it's going to feel like to you clinically, it's really important because granulomatous inflammation has texture to it. It's not spongy. It's usually kind of firm and nodular. So I would expect that. And also it tends to kind of come and stay. So instead of kind of waxing and waning, it generally kind of comes and gets larger and larger and then just kind of sits there. All right. So this is a patient, a case that was shared with me. A patient. I'm going to show you his profile. And it's more dramatic when he turns to the side, but he's presenting with enlargement of the lip. Biopsy showed non necrotizing granulomatous inflammation. All right. And he had negative endoscopies and also no signs of sarcoidosis. So the diagnosis was presumed to be oral facial granuloma ptosis, which, as I said, is a diagnosis of exclusion. Yes. Okay. Oh, whether they will have zero Estonia, they may. But, you know, that's kind of tricky. And I'll tell you because. Oral dryness is is kind of ubiquitous in my experience. I feel like many patients have oral dryness as a complaint. Right now I have oral dryness. I don't think I've had anything today but coffee and so many and many patients who take a number of medications will also have medication associated hypo salivation. Right? So dryness is something you'll hear about with some frequency. So if a patient has involvement of their salivary glands with granulomatous inflammation, it is true that it is damaging that inflammation is damaging healthy alveoli, alveolar structures that ordinarily would astroneer structures, rather that would be producing saliva. But it's kind of subjective. You know, you have it doesn't efface the entire gland and you have lots of help from supporting minor glands and other major glands that will will kind of step up. So it's kind of a hard to say, but it's true that those that particular Asner unit that I was showing you isn't healthy. Right. And it's not able to produce saliva as effectively. But whether a patient will really notice or endorse hypo salivation as a result is kind of hard to say. It's probably subjective and that's just the truth, right? Because they have other glandular structures that will be producing saliva and whether that's enough to make a difference, you know, we're in a microscopic level, zoomed in on a few Asner units that are damaged by this pattern of inflammation. So I suppose if it's caught early enough, then its treatment can be initiated. And it may be that that there really isn't much of a difference. It's a good question, though. As I am sure. Sometimes that is a logical allergic reaction. Yes. We will get to that in a moment, if you don't mind. It's actually the last thing I talk about, but that's okay. You're just ahead of me, that's all. So the reason that we would so that's part of the reason why I keep making a big deal about palpation so that your colleague I don't know if everyone heard but pointed out that allergic reactions, hypersensitivity reactions specifically angioedema, causes enlargement of the lip. And we're going to talk about that in just a second. But that enlargement is soft, it's palpably soft, and it's often of acute onset. This fellow has been like this for a bit and when you palpate his lip, it is nodular and it's kind of and that my my patient, it was like palpating this desk really firm so texturally and then the history will probably send you down a different path. All right. So. Yes. It is not typically painful, however, not just to to palpate it. Not really. Although that fellow I showed you my own, my my patient. He did have some discomfort in general because his mucosa was kind of stiff and not pliable. So he kind of spoke generally about mild discomfort, but he wasn't in wincing in pain when I would palpate his lips. Um. All right. All right. So here he is sort of before and after treatment, but it's more dramatic from the side. So you can see before treatment, his upper lip was markedly enlarged. And after with prednisone, systemic prednisone, you can see a reduction in that enlargement. So systemic and intra injections of steroids are sometimes helpful in driving this to kind of a place where it has regressed because steroids are anti-inflammatory medications, right? And so it's sometimes helpful to help us reestablish a more uniform contour. In my patient that I showed you, that young gentleman, I did intra lesion or analog injections for weeks. He would come in every other week and it never really made a big difference. Unfortunately, he was on TNF Alpha inhibitor, which is a newer management strategy for Crohn's and that was actually very well controlled and he was just in the end just decided he would be satisfied with having his GI symptoms controlled. So it's not always perfect. And I will also tell you a story that one of my colleagues told me They had a patient. They were treating for both maxillary and mandibular enlargement for granulomatous inflammation biopsy proved oral facial granuloma ptosis and they did international catalog injections so steroid injections in the lips to bring them back down. And then finally she said, no, that's good enough because she kind of liked that fullness. It was she wanted that was like Angelina Jolie, you know, the kind of you know, so she she kept some of the enlargement. So I thought that was kind of yeah, kind of nice. All right. So again, just to reinforce what what is a granuloma? All right. Just looking at this biopsy, the top what you're seeing is stratified squamous epithelium. Right? Normal epithelium, underlying connective tissue, a few little skeletal muscle fibers, mucus gland, lobular in the lower right corner. And this focus here, this is a granuloma, so it's a collection of epithelial adhesive sites and some lymphocytes. But you see this these pale cells here in the middle. These are actually the sites. They're the ones that are causing all of this hubbub. And here you can see another granuloma with multi nucleated giant cells. Sorry, keep walking. I don't have a good pointer right there. All right. His sites tend to have a little more cytoplasm than a lymphocyte and it's kind of this pale, frothy, can't tell if it wants to be pink or blue cytoplasm. And they come together in these little aggregates. All right. And that is a granuloma. And now to your question, I think that's the last thing I'm talking about. So there are other reasons the lips can swell and not just the lips. All right. So I did want to mention briefly a condition called angioedema. Angioedema can result from a couple of different situations. The first and most typical is as a result of a hypersensitivity reaction. So patients are are sensitized to something, they're exposed to it, and then they initiate an inflammatory cascade that leads to edema. And when that occurs, then you have acute swelling, soft, palpably soft swelling. Often the lips, the lips really are like a sign that there's something wrong. More often than not. So allergic reactions will often cause swelling and erythema of the lips. I sometimes see contact reactions to toothpaste and other things on the upper lip, interestingly. So the lips really are kind of important that way. So Ige mediated hypersensitivity reactions can do it. Contact reactions meaning my fancy toothpaste with all the bells and whistles in it that I just bought might cause a reaction if I'm allergic to an ingredient. Physical stimuli stimuli can do it as well. I may even have a patient who at least she thinks that when she has contact. Just me examining her. She called me to tell her I made her worse because just by performing an intraoral exam, she feels that that initiated the cascade that that led to swelling of her lip. Patients who take Ace inhibitors can have a very dangerous manifestation of angioedema. It does not matter how long you have taken that medication and you can develop angioedema that can not just stop at the mouth, but can also compromise the airway. And the issue with Ace inhibitor associated angioedema is that steroids don't usually help. You have to wait for the medication to clear the system if you're having a significant reaction. And so when that occurs, patients are even sometimes intubated just until they are stable. So that can be actually kind of a serious situation. Sometimes you can have a complement cascade activation that's usually hereditary situation. And when that occurs, the complement cascade is activated and it leads to edema, which is another thing. And then in patients who have antigen antibody, complex disease. So just so you know, sometimes swelling of the lip, if especially if it's acute, you know, this wasn't here yesterday, it's here today, this patient. Notice what they must be doing, all kinds of lip licking or maybe they have a contact reaction to their lip balm. That's very typical. But you see all the scaling and crusting. I'm just trying to show you enlargement of the lip and erythema. And you can see it's full, right? The lip looks kind of full. Here's another patient showing kind of erythema and enlargement of the lip. And then after they have been treated with a topical corticosteroid in this case. All right. Yes, I do have a couple more things to say. So this next thing we'll talk about is exogenous material that can cause similar kinds of inflammatory reactions. The first is to foreign material and then also to things that are native in the body, endogenous material, but it's in the wrong place. So think about if you had a cyst that was filled with keratin, which keratin is an outside kind of structure, right? But that the cyst ruptured in your connective tissue and then your body could recognize the keratin. You still made that keratin, but your body recognizes that as foreign because it is in a place it doesn't belong. So these are other scenarios in which you can see granulomatous inflammation as a foreign body. Reaction, in fact is the most common cause of non necrotizing granulomatous inflammation because we get all kinds of things in our mouth, right? And so look at that enormous multi nucleotide giant cell. I mean, it's probably the biggest one I've ever seen. It is how many nuclei? It's just huge. Right? Those enormous multi nucleated giant cells very angry about something that it is trying to engulf. Multi nucleated giant cells are very brave. They see an invader and they try and engulf it to protect you. And so that's what these multi nucleated giant cells are doing here. There's some more foreign body type, multi nucleated giant cells, very dramatic. There's many of them in this picture. You see all these nuclei. Again, they're upset about something that doesn't belong there. These are foreign body reactions. Sometimes it's really hard to find the foreign material. So I'm showing you the reaction. But you notice I'm not really saying much about what it is. Sometimes I will polarize under the microscope to try and see if any foreign material is lighting up. And sometimes I don't see it at all. Today I had a foreign body reaction to dermal filler. I see that a lot. People who get these marionette lines like I have. If you could please just deposit some Restylane in there for me or sculptor, I would appreciate it. And then we can biopsy my foreign body reaction. But you develop this, you can develop a foreign body reaction to injectables and other things, but all kinds of things get in there. You know, you can imagine a misadventure, an accident where maybe you fell off your bike and gravel got embedded. Or you can develop a foreign body reaction for all kinds of reasons. But sometimes the foreign material is so tiny, it's hard to see. And sometimes you wonder why it got so upset. This is a as I mentioned, this giant multi nucleated giant cell. But I think this is the foreign material, these two little things. It seems like they made kind of a big deal out of that. All right. And there you can see the foreign material in this case kind of looks a little bit like dental amalgam to me, but it's hard to know. I just see that it's kind of opaque. You see that black blob up there? That's the foreign material. And this is the granuloma in response to that foreign material. There you can see dusky pigmented particles of opaque exogenous material in this giant cell. Right. This stuff might even polarize if it might be refracted while more particles of exogenous material down here at the bottom. All right. So there's another reason you might see a granuloma would be if you had foreign material embedded in your mucosa and your body responded with collections of epithelial adhesive sites. This is what I mean. When we polarize, you probably know that, like when you wear polarizing sunglasses, if you put two pair together and kind of that's what we do under the microscope and it makes foreign material glow in the dark, it's actually really very fun. So you see, this is something that doesn't belong there and it's lighting up and you can see the granuloma around it. Right? All these collections of inflammatory cells that are engulfing this foreign particle. So more little refractory foreign material. All right. And this is this. Yes, this is restolin. So this is like the thing I saw today. So this is a hyaluronic acid based dermal filler. Now, there are other dermal fillers like. El poly acid, lactic acid and other things that are used. Sculpture radius. You know, different. They aren't all hyaluronic acid, but hyaluronic acid has a very distinctive appearance. You get this blue pools of this kind of bluish smudge in the connective tissue. You see, it's kind of blue goo. All right? It's a amorphous acellular. All of this doesn't belong here. It's from outside the body. All right? And you see these very brave, multi nucleated giant cells here who are trying to get around all of this exogenous material. So this is a hyaluronic, acid based dermal filler with a foreign body reaction. It's kind of cool. I actually really like foreign body reactions. Look at that. Isn't that nice? And I know you don't have to love oral pathology, but you do have to love this giant cell. I mean, he's working hard. He's trying to get all this stuff scooped up. All right. So there are you know, there are some reasons why we could have. So we've talked about reasons why you have granulomatous inflammation. Right? We said it could be from a systemic condition like Crohn's disease, which tends to present in younger patients initially, like think teenagers remember those kind of folded fissured areas of the mucosa that kind of remind you of a denture hypoplasia in a dental patient right in the gutters with little punctuate areas of ulceration. The wharton's duct that stag horning palpably firm, nodular to the mucosa and then a complain of GI issues. Right? That's classic for Crohn's. You could see granulomatous inflammation in a patient with salivary involvement, ocular involvement, lung involvement, more consistent with sarcoidosis. Right. And you can also see granulomatous inflammation in a context of a foreign body reaction. And there's all kinds of foreign material that we can see in the mouth. Just anything you want, anything you can put in your mouth, you can have a foreign body reaction to. All right. Any questions about that? And all we mean when we say granuloma, we're talking about a true granuloma, not a granuloma. Right. Which is granulation tissue. A true granuloma is a collection of activated macrophages, often with multi nucleated giant cells. They kind of come together and merge and you get these multi nucleated giant cells and they're responding to something we can't see, but it's likely there's an antigen there that they're upset about and that's why you have these granuloma. Okay. So just wanted to comment on enlargement of the gingiva. We are clinicians. We do see from time to time patients with Gingival enlargement. All right. And the reason I'm mentioning it now is because about halfway down you notice that granulomatous inflammation can cause gingival enlargement. The gingiva can be involved in these cases of oral facial granulomatous sarcoidosis, Crohn's disease. So why why might a patient's gingiva be enlarged? Your dentist? I'm sure you can think of lots of good reasons like hyperplastic gingivitis, medication associated gingival enlargement. If the patient's taking Dilantin, for example, a hereditary condition in which patients develop gingival enlargement called gingival fibrosis, ptosis granulomatous inflammation. We'll talk later in the course. Do you know that leukemia can present as gingival enlargement? Yeah. So that we'll talk about that. Lymphoma, proliferative diseases, scurvy. Oh my gosh, scurvy. You know, you think about that as pirates back in the day, but scurvy is actually making a comeback. People are avoiding certain foods and in so doing, they are not getting enough vitamin C And vitamin C, as you know, is very important in helping to maintain collagen development production function. And our teeth are retained in our jaws by a collagen bed. Right? And so if we do not have enough vitamin C, the teeth become loose and exfoliate and the gingiva get very erythematosus. We actually had a nice CPK recently at one of my oral path meetings with scurvy, so it's really out there, so you can't forget it. And then there's a condition that is a particular inflammatory condition called Wegener's granuloma ptosis. And so that is another reason why patients might have gingival enlargement. So here's just a couple examples of patients exhibiting diffuse gingival enlargement. This is firm gingival enlargement. This was a patient taking Dilantin and this was a patient, either cyclosporine or a calcium channel blocker. But this kind of medication associated gingival hyperplasia. But again, you'd have to have a good history from your patient, right, in order to narrow down the etiology. Yes. So for the exam. That's a great question. I'm actually really glad you asked that. So the question is, if I were to give you a case on the exam of kind of diffuse gingival enlargement, I would appreciate it if you were specific. I think if you're if you were asking for a full credit for me, you really need to be specific. And by that I mean if I say here's a patient with a seizure disorder who's under the care of their physician for a seizure disorder, we'll say, and they presented with this and you can say, oh, medication associated gingival hyperplasia or gingival enlargement. The reason I'm asking you to be specific is because I also mentioned in a few weeks we're going to learn about leukemia can present this way and or so. Yeah, we can see we can all agree the gingival gingiva are enlarged. It's the why that's the most important thing. And you'll have to get a pretty darn good history or a good reason for it. But thank you. Because I really like it when you get full credit for things. So. Here's another example. This looks kind of dramatic, but again, this was a patient with a medication associated gingival enlargement, interestingly. If you biopsy a patient with medication associated gingival enlargement, it's just more gingiva. It's kind of benign fibrous tissue. The overlying epithelium when you biopsy the gingiva, the are very pointed like this. So that's normal. And then there's just more connective tissue than you would expect. All right. Do you have any questions for me? It was a quick lecture, so we can take just a couple of questions before you run. Yes. So the biopsy is taken intra orally. It is. So this is about that dermal filler question. I like to talk about it. So I don't I don't mind. So oftentimes patients will get dermal filler injections. Let's say here marionette lines, for example, using me as an example. And it will migrate a little bit and intra orally. It's not unusual to feel a palpable nodule. And so for esthetic reasons and also because you can appreciate it as a palpable mass intra orally, it's usually sampled from the mucosa. Any other questions? Well, I hope. Oh, yes. Go ahead. What happens when my. Giant cells are unable to knock off. A foreign body when. Multi nucleated giant cells cannot? I think that's very typical, quite frankly. The question is what happens when the multi nucleotide giant cells are not successful in defeating their enemy? I would say it's that's typical because clearly those multi nucleotide giant cells were not going to be able to gobble up all of that hyaluronic acid. And so they they sit there more may come. It will get more inflamed. There could be fibrosis. You'll get a mass, usually a palpable mass. Nothing more happens. It's just that there's more exogenous material in that case than there is ability for the body to kind of defeat it. Sometimes you'll see granulation tissue come kind of come around it and kind of try and wall it off with lots of inflammation. It often will become evident clinically because of the granulation tissue that's surrounding your body does a pretty good job of walling things off and it often is palpable when there's. And that will prompt the biopsy. Yes. The patient are or always hopeful because the one that you showed the slide where like just one spot. Oh that's okay. The question is about Addison's disease and patients who have oral, you know, oral pigment changes, it can be anywhere, anywhere on the mucosa buckle, mucosa, you know, gingiva, ventral tongue, soft palate. You can have involvement anywhere with melanocytes in patients with Addison's. That was just. Yeah, you're right. It was just one example on the gingiva, I think. Any other questions before you go? I will try to do that thing for those who want to capture your credit for participating today, and I hope you have a nice, long weekend. All right.