Sjogren syndrome is an autoimmune disorder that has a somewhat unusual presentation. In addition to having arthralgias, patients often develop dry mouth and dry eyes. Symptoms can vary from person to person. Sjogren syndrome also commonly mimics other medical conditions, and this may account for its typically delayed diagnosis. Like most other autoimmune diseases, the exact cause isn't known, but Sjogren syndrome is treatable. In this podcast, we review the presentation of Sjogren syndrome, how to establish a diagnosis and how patients with the condition should be managed. Our guest is Alicia M. Hinze, M.D., M.H.S. , from Mayo Clinic Rheumatology.
Rheumatologic problems are some of the most common health conditions we see as primary care professionals. They can become frustrating for both the provider and the patient, as in many cases it may take months and sometimes even years to establish a correct diagnosis. There are a variety of new tests available to help us confirm a diagnosis, as well as multiple new and effective treatment options. This episode is part of a seven-episode miniseries on Mayo Clinic talks dedicated to rheumatologic health problems to aid in the recognition, diagnosis, and treatment of your patients. Please find these additional episodes where you listen to podcasts or on CE.mail.edu. This is Mayo Clinic Talks, a curated weekly podcast for physicians and healthcare providers. I'm your host, Darl Chatka, a general internist at Mayo Clinic in Rochester, Minnesota. Sjogren's is an autoimmune disorder that has a somewhat unusual presentation. In addition to joint pains, patients often develop a dry mouth, dry eyes, as well as extreme fatigue, and symptoms can vary from person to person. It also commonly mimics other medical conditions, and this may account for its typically delayed diagnosis. It's named after the physician who initially identified the syndrome in 1933, Doctor Hendrik Sjogren. And like most other autoimmune diseases, the exact cause isn't known, but Sjogren's is treatable. In today's podcast, we'll review the presentation of Sjogren's, how to establish a diagnosis, and how patients with the condition should be managed. Our guest is Doctor Alicia Hins from the division of Rheumatology at the Mayo Clinic. You're listening to Mayo Clinic Talks. Alicia, thank you for joining me today. And this should be an interesting discussion because I don't see a lot of Sjogrens, and I think back over my career, and I certainly have seen a lot more other autoimmune diseases, and I don't know, maybe I was the reading I was doing suggested that it takes sometimes 4 years to establish a diagnosis of Sjogren's from the first symptoms, and maybe I've seen it and didn't recognize it, but how common is this condition? So, it's fairly uncommon. So if we were to look at Sjogren's syndrome and look at some of our other autoimmune conditions, it's probably along the lines is as common of lupus, probably even just a little less common than lupus and far less common than our most common, which is RA. So certainly, if you think of New cases, we see maybe 4 new cases per 100,000 people, whereas in, in RA, which is our most common condition, that can be about 30 per 100,000 new cases. So it's certainly not as common as some of our others, and it does. You're right. It has this very insidious on. of symptoms that is not as recognizable sometimes, or patients may not bring it up to their physicians immediately as it's not as recognizable initially. Well, let's talk about typical course of Sjogren's and some of those atypical presenting symptoms. How do most patients present? Most patients do present with dry eyes and dry mouth. And so it can be a varying degree. Sometimes patients do notice a little bit more of a dry eyes and dry mouth, and, and often it may not get articulated exactly as I have dry eyes. But it may be this onset, uh, a really good question actually to ask is, is there a gritty or sandy sensation in the eye? That's actually one that tends to bring out these features of dry eyes, more than even asking just your eyes dry. And dry eyes actually in and of itself is relatively common. So if patients are seeing the optometrist or ophthalmologist often, they might get told that they have a little bit of a dry eye. And really only about 10% of patients that do have underlying dry eye syndrome actually have Sjogren's. It's hard to know which patients should we go on to evaluate and to test further and which may just be kind of an idiopathic dry eye, but often patients do also have those symptoms of dry mouth. Often you can even pick this up sometimes during visits with your patients is they're the ones with the water bottle with and after 15 minutes, they're taking sips of water just because they've learned how to almost manage those symptoms by trying to continue to keep their mouths a little bit more with water, just so they can get through talking. Well, I'm sure this varies from person to person, but when do the joint symptoms typically develop? Is it quickly or can patients have the dry eyes and dry mouth for months to years? Patients can have dry eyes, dry mouth for months to years, and, and not everybody does develop joint symptoms. There's different kind of phenotypes of Sjogren's syndrome. There's Patients that really have symptoms that are limited to the dry eyes and dry mouth. There's another subset of patients that will get more of the arthralgias, those joint pains, some muscle pains, and, and a lot of fatigue and association with the syndrome. And there's probably actually a lot of overlap with fibromyalgia too, that we see with Sjogren's syndrome as well. There's actually another subset of patients that may actually not present initially with dry eyes and dry mouth, but may present with other things such as neurological complications. And so sometimes we see patients, for example, that are being worked up for a small fiber neuropathy or a polyneuropathy that doesn't seem to have an underlying cause and Labs will get done, and we may see a positive SSA, and, and we may evaluate those patients a little bit further to try to understand if Sjogren's may be an underlying associated syndrome with it, or whether maybe it is just idiopathic, and we can't always make a diagnosis based on labs alone. And so, it often is putting the pieces of the puzzle together. Well, but it is obvious why it can often take such a long time to establish a diagnosis in these patients. So once a patient has established Sjogren's, how does this progress? Is it like rheumatoid arthritis where patients may get intermittent flares, or does it gradually progress or do people just stay stable for many years? All of the above. So some patients really can have those stable symptoms of dry eyes and dry mouth. And there may be some fluctuations in that. Sometimes even just simple things like allergy season, and they took some additional antihistamines, and we might see a little dryness in that context. But the patients certainly can have a little bit of a waxing waning course where sometimes the symptoms do seem to be worse in terms. Of the dry eyes and dry mouth, and sometimes it can seem like things are have kind of stabilized out a little bit. We do see a lot of extra glandular features too, and I think this often, if we we're thinking of sort of flares and disease activity, it's often these extra glandular features that we're seeing kind of flares. So sometimes we see inflammatory arthritis with Sjogren's syndrome. And certainly we can see flares and inflammatory arthritis occur. We can see Raynaud's phenomenon, which tends to, I, I wouldn't necessarily call it a flare, but it can be triggered with cold temperatures, for example. We can also see cutaneous vasculitis, for example, which can present as palpable purpura or rash, and those kinds of symptoms certainly may flare as well too. So, it really kind of depends on actually the manifestations that a patient experiences in association with the the Shogren's, that may also determine the course in the future, and flares and such things. Sometimes people do also With more of the glandular features, if we focus on that, have some flares in parotid gland enlargements which can crop up. Certainly, if it's more prolonged or, or if it's unilateral, you know, if it's unilateral, we are wanting to make sure that we're not missing an infection there. If it's prolonged, then we, we do have to think about other things too that can occur in patients with Sjogren's such as lymphoma. So what's the potential long term outlook for patients with Sjogren's? What kind of complications might they get into and does this condition just kind of burn out or does it stay active throughout one's lifespan? I would say once a patient does experience the glandular features, they don't often just resolve. We do have medications that certainly can help those symptoms quite a bit. But like most of our autoimmune diseases, unfortunately, we don't have an absolute cure for them. So they do stick around. I'm not certain that I would quite use the term burnout, but some can remain very stable. Over time, some of these extra glandular features can accumulate. So I think there is one study using a fairly large cohort, and One of the things that they said is probably 30% of these patients did accumulate over time different extraglandular features. So maybe that's neuropathy, maybe that's some findings of interstitial lung disease. So there is a portion that may remain stable, but some patients do end up developing some additional extra glandular complications. Well, I know, as with other autoimmune diseases, we don't know the cause of this, but are there thoughts? Do we have some ideas of what might be causing Sjogren's? You're absolutely right. With most of our autoimmune diseases, unfortunately, we don't know the exact cause. So, we hypothesize that there's probably some environmental trigger that's occurring in patients with certain genetic susceptibilities. Sjogren's syndrome, in terms of the pathogenesis, we see a lot of lymphocytic infiltrates in the glands themselves. So there is some degree of auto-reactive B cells that are probably driving the process, but really what trigger this, we don't have that answer. Who's more likely to get this? Are there known risk factors for Sjogren's? Uh, we see it more commonly in women. It's probably about 9 to 1 male that will actually develop Sjogren's syndrome. Common ages would be in 40s or so, 40s, 50s is the, the general age group. So, female in their 40s and 50s is general, but we can see in males as well too. We can see it in younger ages. So, so it's not restricted to that population. And you mentioned a genetic component to this as well? So that's the theory that there is some genetic component to Sjogren's syndrome, more as a susceptibility standpoint. There's been some research into HLA haplotypes that may be a little bit more predisposed to Sjogren's syndrome, but we generally can't just pick one gene that would cause it. Usually it's more than just one gene. There's probably some other factors into these particular autoimmune conditions. Well, let's talk about how we establish a diagnosis, and I suspect the history is extremely important. Anything on physical exam that may help us? So some things that can be helpful on physical exam is, is really to make a good ocular exam as well as an oral examination. Initially, when I'm evaluating a patient for Sjogren's, I am looking at the parotid glands. Well, not everybody will have enlarged parotid glands, there are many patients that will have some enlargements, um, bilaterally of their parotid glands. I do a good or Examination. One of the things that you can look for is whether there is salivary pooling. So, if you have some 4x4s or some gauze in the clinic office, if you just have them open their mouths, kind of blot the existing saliva in the mouth, and just go wait a minute. Are they accumulating any saliva or are they not? If they're not accumulating any saliva in a minute, then that's abnormal. And would be pretty indicative of dryness. If they're accumulating copious amounts of saliva, then it's probably not what we're thinking on along the lines of Sjogren's syndrome. Another thing that's helpful is sometimes patients will tell you about a burning tongue or or their taste is different. It's important really to look at the tongue itself. Sometimes we can see uh an kind of an atrophic glossitis, or that could be actually indicative of uh candidiasis or erythematous uh regions on the hard palate and soft palate that may clue us in actually to candidiasis as well. So, usually, when we're thinking of candidiasis or at least as I was originally thinking of candidisis, you think of plaques in the mouth. But this can actually really present with more of a erythematous look to it, not necessarily white plaques, but really that erythema glossy tongue that has a loss of papillae. So that can be some signs there. Angular cheitis is actually pretty common as well too. And you can always kind of just take a look at the eyes, whether they look irritated. Some patients will actually have some conjunctival irritation. It's pretty easy to do a Sherber's test at the bedside, so you can get these little litmus paper, can put it in the corners of the eyes, and then for 5 minutes, pull some of the tears down. If it's less than 5, that would be indicative of some dry eyes as well too. So some easy bedside things that you can do and and further evaluation, but ultimately, we often really engage our colleagues in ophthalmology or optometry to do a lot more of the dry eye testing for further evaluation. Let's talk about the testing that we can use to help establish a diagnosis. I know there's some blood tests that might be helpful. What tests should we be ordering? There's actually quite a bit of workup. We often do when we're evaluating patients for Sjogren's, but at least when we're thinking about autoimmune serologies, some of the things that we do obtain is an ANA by immunofluorescence. We wanted to obtain an SSA and an SSB antibody. Those are also called anti-ro and anti-law in some labs. We also want to obtain a rheumatoid factor because this is positive in some patients with Sjogren's as well too. Sometimes they have positive ANA and a positive rheumatoid factor, but may not have the SSA and SSB. We'll also be thinking also in our differentials, could they have a manifestation. Of another autoimmune disease too, because there can be uh quite a bit of overlap with Sjogren's with some of our other autoimmune diseases like lupus. So, we'll often get it some additional autoantibodies, a double stranded DNA, we may get an RNP antibody that describes some of our overlapping conditions. We'll often get a complement, a C3 and C4, as we often do see it in some sets of Sjogren's actually, that the complement will be low. And it can be somewhat prognostic of risks of lymphoma later. We often see a hypergamma globular anemia, so something like an SPEP usually picks that up. We do look for things like leukopenia, anemia, or thrombocytopenia that we can see in association. Always checking kidney function as well too, with a BMP. Renal tubular acidosis is one of the sort of extra glandular features we can see in Sjogren's. So we're really looking at a low potassium and low bicarb on those panels. Other things. We can see an association is autoimmune liver disease with Sjogren's. So usually getting a hepatic function panel can be very helpful just to really give that good overall look for any other organs or other diseases that might be associated. I think also one of the things that we want to think about is, is there anything else that can be explaining their dryness? And of course, you know, at this point, you've probably done that history, really assessed to make sure that there's not any anticholinergic medications on board that might explain the dryness or other medical history, you know, maybe they're on diuretics and things like that. But other conditions, medical conditions that we can see is actually some infections like hepatitis C and HIV can cause some Of these glandular symptoms, hemochromatosis is another one. So simple iron studies can usually pick that up. Uh, other conditions like sarcoidosis can actually be a mimic in a patient that maybe has new asthma or shortness of breath, getting that chest X-ray, maybe getting that 125 hydroxy vitamin D just to kind of further for any evidence of sarcoidosis, for example. IgG4 is another one that can cause a lot of glandular symptoms, IgG4 related diseases. We generally have to have a pretty high index of suspicion for that. You can get an IgG 4 serum level. I have to caution about that one just Cause it's not diagnostic in and of itself, but certainly, if you did have a really high IgG4, you may do some further investigations, things like wanting to do a salivary gland biopsy, for example. The arthritis that goes along with Sjogren's, is it an erosive inflammatory arthritis like rheumatoid arthritis and would joint images be of any help? There are some patients that do get inflammatory arthritis with Sjogren's syndrome. We also see some overlaps. So sometimes it's hard to say this is purely Sjogren's or is it Sjogren's overlapping with rheumatoid arthritis. There's necessarily rules about whether it's corrosive or not. Certainly, if we see inflammatory arthritis, which we can often pick up on on our examinations. Then we would want to treat uh accordingly with appropriate medications. Uh, X-rays certainly are helpful. A lot of joint pain does happen with, with Sjogren's, which may be inflammatory and, and may not be. So X-rays certainly could be helpful. OK, so it's it's a great masquerader, it really is. What's the role of a salivary gland biopsy? Do you do those? To occasionally. It's important to have a discussion with the patient as to what we're going to do with management if we do this. Some patients will come in, they've got dry eyes, dry mouth. They have positive serologies for Sjogren's syndrome, and the picture fit. Now, there's a lot of sort of classification criteria, probably don't have the, the luxury of time to get into all of that. But we do generally like to at least see some serological criteria and with compatible symptoms. But I might use a salivary gland biopsy in situations in which the picture may not be as clear. For example, they may have an ANA. Some dry mouth symptoms, but may not have that SSA or SSD or investigating some other symptoms, extraglandular, that we might approach differently. I might consider a salivary gland biopsy in that particular situation as well too. I'd say practice patterns do differ quite a bit here. I think it's important if it's just glandular features that you do have that discussion with the patient that we will still treat your symptoms, dryness and what you're experiencing. If the salivary gland biopsy isn't confirmatory, there's still things to do to help relieve your dryness, and if it is confirmatory, we're going to take a lot of the same approaches if it's just the dryness. Well, let's talk about management now, and Sjogren's is somewhat unique in that you're dealing with glandular manifestations and dry mouth, dry eyes, which I'm sure patients really are troubled by, but then the underlying autoimmune disorder. So, how do you approach a patient for treatment? So we really begin by trying to understand what the systems are affected. If the symptoms of Sjogren's for a patient is really the dry eyes and dry mouth. Unfortunately, while it is caused by, it is an autoimmune disease, we have not found that our immune medications, or immune suppressing medications, actually modulates or changes the symptoms of dry eyes and dry mouth or changes the course. So if it's restricted to the Andular symptoms, we actually don't use immune suppressing medications. Now, that doesn't mean that we don't have treatments. So we really, we have a lot of treatments that we're focused on to try to relieve those symptoms. So I will recommend a lot of over the counter products initially for dry mouth. So there's a lot of dry mouth products that can be very helpful to patients. We really emphasize that good oral care, seeing the dentist, at least every 6 months, good fluoride toothpaste to try to really protect the teeth. There's also some other secretagogues that we will try, or cholinergic medications that can really help increase the production of saliva and do provide benefits to patients. If we're talking about, I guess, some of the other manifestations, such as joint pain, you know, if we're seeing inflammatory. Arthritis and you'll often use some of the medications that we would utilize for rheumatoid arthritis, for example. If it's joint pain in the absence of inflammation, then we may target a little bit more with NSAIDs or analgesic type medications um to try to relieve some of the pain. So it's very individualized depending on what's really giving the symptoms. Absolutely. Some of the immunosuppressants the same as in other inflammatory arthritis? We do use some of the same medications. So, again, if inflammatory arthritis is a component, then we'll often use hydroxychloroquine, for example. We may use methotrexate as a couple of our initial medications that can be used to try to help that process. If we're seeing things like cryoglobulinemic vasculitis that's also impacting the kidneys, we're bringing out medications such as rituximab. So we really run the the spectrum of what we might use in the context of Sjogren's syndrome, really based on what manifestations they're experiencing. Well, Alicia, you've really described Sjogren's quite well. Can you summarize everything with maybe 2 or 3 key points? Well, certainly, it's important to do a thorough history and anybody that is presenting with Sjogren's syndrome, making sure that there's no other causes or medications on board or other conditions that could be causing it, cause overall, it is a fairly rare condition. When you are suspicious for Sjogren's syndrome, there's several tests that can be performed. Not any one of them is diagnostic in and of itself, and we always have to keep a broad differential and make sure that we're not missing another autoimmune disease, for example, that can have the same markers. But overall, there's a lot of symptomatic treatments that we can offer our patients that can really improve quality of life. And the other thing I know, we didn't talk too much yet about this, but patients are at increased risk of lymphoma. So if you or any of your patients do present with symptoms of fevers or weight loss or things like that, then we do want to do a pretty thorough look for any evidence of lymphoma in this patient's subset. We've been discussing Sjogren's syndrome with rheumatologist Doctor Alicia Hins from the division of Rheumatology at the Mayo Clinic. Alicia, thank you so much for sharing your expertise with us today. Thank you so much for the invitation to join you on this show. You can now listen to over 100 different medical topics developed for primary care providers on Mayo Clinic Talks podcasts. Find them at c.mail.edu or your favorite podcasting app. If you've enjoyed Mayo Clinic Talks podcast, please follow us. Stay healthy and see you next week.
