Unmask the hidden complexities behind rheumatoid arthritis with renowned rheumatologist, Dr Alan Zalkowitz from the Kayal Orthopedic Center, in this thought-provoking conversation. We trace Dr Zalkowitz’s journey in the medical field, before diving into the depths of rheumatoid arthritis – a systemic, inflammatory condition that affects millions worldwide. From understanding its risk factors to discerning its symptoms, we leave no stone unturned.
As we journey further into uncharted territories, we explore the intricacies of diagnosing and assessing rheumatoid arthritis. Dr Zalkowitz guides us through the physical exams and the nuanced signs that often escape the untrained eye. We also delve into the world of imaging modalities and laboratory tests that are vital in confirming a diagnosis. The importance of early detection and treatment is emphasized, as we unveil how it can alter the course of this debilitating disease.
Finally, we navigate through the maze of treatment options and understand the significance of combination therapy. We compare the roles of rheumatologists and orthopedic surgeons, highlighting the value of their collaborative effort in managing chronic diseases. From understanding joint deformities to discussing the potential cure of rheumatoid arthritis, this episode is a goldmine of information. Join us as we embark on this enlightening journey with Dr Zalkowitz, whose expertise brings a wealth of knowledge to our multi-specialty practice.
Unmask the hidden complexities behind rheumatoid arthritis with renowned rheumatologist, Dr Alan Zalkowitz from the Kayal Orthopedic Center, in this thought-provoking conversation. We trace Dr Zalkowitz’s journey in the medical field, before diving into the depths of rheumatoid arthritis – a systemic, inflammatory condition that affects millions worldwide. From understanding its risk factors to discerning its symptoms, we leave no stone unturned.
As we journey further into uncharted territories, we explore the intricacies of diagnosing and assessing rheumatoid arthritis. Dr Zalkowitz guides us through the physical exams and the nuanced signs that often escape the untrained eye. We also delve into the world of imaging modalities and laboratory tests that are vital in confirming a diagnosis. The importance of early detection and treatment is emphasized, as we unveil how it can alter the course of this debilitating disease.
Finally, we navigate through the maze of treatment options and understand the significance of combination therapy. We compare the roles of rheumatologists and orthopedic surgeons, highlighting the value of their collaborative effort in managing chronic diseases. From understanding joint deformities to discussing the potential cure of rheumatoid arthritis, this episode is a goldmine of information. Join us as we embark on this enlightening journey with Dr Zalkowitz, whose expertise brings a wealth of knowledge to our multi-specialty practice.
Hello and welcome to another edition of the Kale Ortho podcast. Today, our special guest is our very own Dr Alan Zalkowitz, the chief of rheumatology at the Kale Orthopedic Center. Welcome to the podcast, dr Zalkowitz. Thank you so much. It's such an honor and privilege to have Dr Zalkowitz with us today. Dr Zalkowitz is a renowned rheumatologist and we're so privileged to have him practice with us at the Kale Orthopedic Center, servicing the community of patients in Northern New Jersey and New York. Before we get started, why don't you tell us a little bit about your education, training and your family life as well?
Alan Zalkowitz, MD:Yes, hi, I'm Dr Alan Zalkowitz and I started the rheumatology fellowship program at Mounds-Sinai Medical Center in New York City many years ago and helped run the arthritis clinics at Mounds-Sinai in autoimmune disorders, rheumatoid arthritis, lupus. When I came to Northern New Jersey I was the only board-certified rheumatologist from the Delaware Water Gap to the George Washington Bridge. Needless to say, that was a herculean task to cover all of the many, many patients who refer to me, from physicians who used to send in to New York or to Philadelphia. I remember that the highlight of my becoming a rheumatologist takes me back to my last year at Yale, new Haven. At that time an advertisement came out in the New England Journal of Medicine that there was a new position, a new fellowship that was being started at Mounds-Sinai funded by the National Institute of Health. I went for the interview along with 200 others and met the chief there, dr Harry Spira, and he took me.
Alan Zalkowitz, MD:I was the sixth interview. He took me down the hallway and showed me a mail about 30 years of age, bent over, and he said to me Alan, make a diagnosis. And I did and I said he has ankylosing spondylitis. And he said you have the position of the first fellow at Mounds-Sinai. I then entered a group of all Mounds-Sinai doctors there was one, I think, from Albert Einstein. We were all subspecialists and I divided my time mainly between several hospitals and taught at the medical center. I would leave the office at about 8 o'clock at night, having started at 6.30 in the morning, and then go to other hospitals to do consultations. My wife, who has been with me over 50 years and helped put me through medical school. She brought up my three sons till they all left for college and I'm very appreciative of all the work that she's done to do that.
Robert A. Kayal, MD, FAAOS:Wow, thank you so much for that history. I've had the privilege of knowing you for probably close to 30 to 40 years potentially. I had the privilege of growing up with your three boys. I graduated high school with Howard. I was very, very good friends with Howard during my childhood years and high school years. I have fantastic memories of that relationship with Howard. In addition, I remember working at a gym in Wyckoff and you and your wife would very frequently work out in that gym in Wyckoff called the gym, where I worked behind the desk and as a trainer, and I have very fond memories of those years.
Robert A. Kayal, MD, FAAOS:In fact, like I've told you many, many times, forever be indebted to you for your advice and wisdom, guidance and direction in helping me maybe get into medical school and actually land my first hospital privileges at Valley Hospital in Ridgewood, writing my letters of recommendation from medical school and programs that I would wish to matriculate in, and I'm just forever indebted and grateful for all of that and feel so honored and privileged to have you here with us today. Your wisdom and expertise fund of knowledge and experience is just indescribable and just so happy to have you with us today to talk to us all and educate our community of patients about this very important condition called rheumatoid arthritis. Rheumatoid arthritis is very different from other forms of arthritis, and it's very, very important to distinguish between rheumatoid arthritis and other forms of arthritis. So, dr Zalcowicz, why don't you tell our community of listeners and viewers why it's important to distinguish between the different types of arthritis, and then we'll get into focusing on rheumatoid arthritis.
Alan Zalkowitz, MD:Arthritis is an inflammation of a joint or joints like the knees, the hips, the hands, the feet. This leads to inflammation and stiffness and pain in those joints. It may be years before the actual inflammation and joint pain developed. Unfortunately, there are about a hundred different types of arthritis, from infectious arthritis, of which most of you heard about Lyme disease, to degenerative wear and tear arthritis, which is unfortunately about 33 million Americans have where caught lids and bone breaks down and a lot of orthopedists see the stages of it where one may need to have a joint replacement to the other. Inflammatory arthritis is different and the most common symmetrical polyarthritis is rheumatoid arthritis that affects approximately 1% of the population. That means about one and a half million people in the United States. It's a progressive arthritis left untreated that can cause deformity and severe morbidity.
Robert A. Kayal, MD, FAAOS:So, just to elaborate on what Dr Zalcowicz was mentioning, there's different forms of arthritis. Obviously, the most common form is degenerative wear and tear arthritis, but there are other forms as well. Dr Zalcowicz alluded to the fact that there could be infectious arthritis, what we call septic arthritis, where an infection can get into the joint and destroy the joint as well. There's another condition called post-traumatic arthritis, where trauma can destroy the joints, but in today's podcast we're going to focus our attention on inflammatory arthritis, where there's inflammation in the joint which can also destroy the joint. And in the realm of inflammatory arthritis there's different forms of inflammatory arthritis, but today's podcast will focus on a specific autoimmune condition called rheumatoid arthritis.
Alan Zalkowitz, MD:So in rheumatoid arthritis this is usually a newness of women, three to one over men, and it usually happens at 30 to 60 years of age is the major peak, and one of the reasons may be that you have a preponderance of women is that in this condition male hormones can cause a pro-inflammatory effect which causes there to be a larger amount of rheumatoid disease in women and men. We find that in rheumatoid arthritis that after 60, the incidence of the disease is about equal male and female, because the hormone level in women decrease. The causes of rheumatoid arthritis, which is really caused by the white blood cells that normally secrete proteins and enzymes and inflammatory cells that usually protect the system from infection and inflammation, goes out of whack and these inflammatory what we call cytokines, cause an inflammation on the joints or on the muscles or on the tendons or ligaments, causing systemic problems that can affect not only joints. But in rheumatoid arthritis it can affect the heart and therefore in rheumatoid arthritis you have an increased risk of heart disease and heart attacks and stroke. And if you control the rheumatoid arthritis you eliminate that increased risk of heart attacks and stroke.
Alan Zalkowitz, MD:It can affect the eyes, where you get dry eyes, uveitis, which is inflammation of the eyes. It can affect the lungs, in about 10% of people, where they get problems with breathing. It can affect the skin where you get nodules, in about 15% of patients by the elbows. So rheumatoid arthritis is ubiquitous in terms of affecting most joints. We want to suppress the inflammatory condition. We want to suppress the cytokines, we want to suppress certain cytokines that are called leukotrienes and prostaglandins, and we can do that with medication. We can do that with certain changes in our lifestyle.
Robert A. Kayal, MD, FAAOS:So just to further elaborate on what you just discussed, dr Zalkowicz, I think the take-home message is that, unlike degenerative wear and tear arthritis, rheumatoid arthritis is a systemic disease. It's important to remember that rheumatoid arthritis is an autoimmune disease that really affects the entire body. It can result in damage to organs, like you mentioned the heart, the lungs, and so it's important to distinguish between other forms of arthritis, like post-traumatic arthritis, septic arthritis, degenerative wear and tear arthritis and, most importantly, be able to identify those patients that are suffering from a systemic disease like rheumatoid arthritis, and get them in the hands of a board-certified fellowship trained rheumatologist like Dr Alan Zalkowicz. Let's take this opportunity to just explain to our audience what exactly is happening in this condition called rheumatoid arthritis. We already discussed that this is an autoimmune condition where the patient's immune system is essentially attacking itself. We've discussed that it can attack organs. We discussed that it can attack even systems like the cardiovascular system and the pulmonary system and other systems of the body. But specific to the joints, what's happening inside that joint?
Alan Zalkowitz, MD:What's happening is that the inflammatory condition causes certain enzymes and hormones and cytokines to develop what we call osteoclasts, and they eat up the bone and the cartilage and therefore destroy the joint. In addition, there's an inflammatory layer of tissue that forms that is called panace and that causes the bones again to become inflamed and to deteriorate.
Robert A. Kayal, MD, FAAOS:Yeah, so it's primarily affecting the synovial lining of the joint correct.
Alan Zalkowitz, MD:Yes, the synovial lining of the joint is affected and then it goes eventually to cartilage and to bone and erodes the bone and therefore in a significant case of rheumatoid arthritis one develops erosions. When one sees erosions as a rheumatologist and you see a patient for the first time and they have them, you know that we have failed to prevent that. It used to be that one of the hallmarks of rheumatoid arthritis and making the differential diagnosis is erosions. But if you see erosions, we've not been successful in preventing them because those are very difficult to reverse, if at all.
Robert A. Kayal, MD, FAAOS:So, dr Zolkowitz, what are some of the risk factors when considering the diagnosis of rheumatoid arthritis in our patients? Are there some risk factors that put patients at increased risk for getting diagnosed with rheumatoid arthritis?
Alan Zalkowitz, MD:Yes, there are Myself and some of the other rheumatologists that are part of Dr Kale's organization. We often emphasize that one must stop smoking. Smoking causes inflammation to a great degree. In addition to smoking, we often make a great effort to have someone get down to their ideal weight. It's very interesting that there are certain inflammatory markers in people overweight called leptins, and these leptins are those cytokines that travel in the blood system and can land in a heart and therefore lead you to more heart disease, and heart attacks can lead to the joints and possibly cause you to have more joint pain. So the takeaway is to be lean, not smoke, and to exercise regularly. Exercise is a very important thing. Even in people who have wear and tear arthritis. They should exercise under the physician's guidance or someone from physical therapy, because that's very helpful.
Robert A. Kayal, MD, FAAOS:It's so interesting to hear all this because when you're in medical school, they don't really teach us at least not back when I attended medical school that autoimmune conditions like rheumatoid arthritis are associated with smoking and obesity and even exercise. So, dr Zolkowitz, how does the typical patient present to your office? What is their chief complaint usually when they're being seen and you ultimately diagnose them with this condition called rheumatoid arthritis?
Alan Zalkowitz, MD:They usually present with polyarthritis, joint pain, swelling of their hands and feet. You can have other joints involved. What's most important is in comparison to some degenerative processes of the hands. It affects the large knuckles and the medium-sized knuckles and rarely ever affects the distal knuckles, which is much more common in osteoarthritis. And they present with stiffness. That's a key here stiffness a gelation phenomenon that usually is over an hour and sometimes even longer than that. It's hard for them to get out of bed. The morning is the worst time for them and as the day progresses they get a little bit, a little bit better. We normally use 15 to 30 minutes as a mock-off to determine inflammation. More than 30 minutes to a few hours. Non-inflammation less than 30 minutes. Usually five to 15 minutes to determine whether it's inflammatory or not. These patients can have significant fatigue. Fatigue may be overwhelming and that's a part of therapy that only the most recent biologics have addressed. They often can have nodules by their elbow. They may have their joints not being able to be straightened.
Robert A. Kayal, MD, FAAOS:So yeah, I agree with you. When I'm taking a history in my office and talking to patients, I definitely inquire about morning stiffness especially. These patients are typically in the prime of their life. These are usually diagnosed more in women than men in the prime of their life. When they start complaining about morning stiffness that's prolonged, like you're describing. It's very concerning and that's when we'll often refer them to you for a rheumatological evaluation. In addition to that, because it is a systemic disease, an autoimmune disease, very often these patients will have systemic symptoms. Sometimes they'll have aches and chills fever, sometimes they'll be lethargic. They'll be tired a lot during the day as well. Are these some of the things you look for?
Alan Zalkowitz, MD:Yes, we look for them In rheumatoid arthritis to the adult. If you have fever, that's a little unusual. It can happen and there is a condition called stills disease, which is rheumatoid arthritis of the adult. That's of a juvenile pattern where the type of fever, whether it's two or three times a day, gives away the diagnosis. It's one of the pearls that rheumatologists like myself use to make that diagnosis. But if we have fever we start to look towards infection and other types of autoimmune disorder, like lupus, like vasculitis. They often are lethargic and fatigued. For a woman who has children, it may keep them in bed for such a long time that they have real difficulty taking care of their children. They have real difficulty holding a job and there's a greater risk of those patients going on disability because they cannot do it, because this overwhelming systemic effect affects every part of their body.
Robert A. Kayal, MD, FAAOS:So, Dr Zalkowicz, I think it's very important to note everything you just described because it's very different when patients present with the typical degenerative wear and tear arthritis. A lot of the patients will complain of stiffness with degenerative wear and tear arthritis, but often that stiffness is isolated specifically to the joint that's being evaluated. They'll say, Dr Kale, my knee is stiff, my hip is stiff, my shoulder is stiff. But in rheumatoid arthritis they'll very often complain of diffuse stiffness in their joints and typically in a symmetrical pattern and in typically the smaller joints of the body right, Like the ankle, the elbows, the shoulders, joints that aren't as often involved in the more ubiquitous condition called degenerative wear and tear osteoarthritis. Is that correct?
Alan Zalkowitz, MD:That's certainly correct. The thing that haunts these young women again, they're three times as likely than men is their hands, wrists, feet, as mentioned, have really stopped them from being able to function in business and at home with swelling of their joints. These joints become swollen, warm and hot.
Robert A. Kayal, MD, FAAOS:So, yeah, everything you're mentioning, dr Zalkowicz, a lot of these things are not present in the typical orthopedic patient complaining of a painful joint. They may complain of stiffness, but again, it's not a systemic problem, it's typically not involving multiple joints and it's typically not associated with other systemic complaints. So now, dr Zalkowicz, you've taken an adequate history. You've begun to establish a differential diagnosis in your own mind that perhaps this patient is suffering from an inflammatory arthritis, maybe rheumatoid arthritis. What's next? What do you do on physical examination to try to really hone in on that diagnosis and really confirm that we're dealing with a patient that probably has rheumatoid arthritis?
Alan Zalkowitz, MD:When we do the examination we look very carefully at the skin. Something that has become much less frequent are nodules by the elbows. They're usually non-tender, they're usually mobile. We used to see them in New York at Mount Sinai, frequently, because we saw only the worst patients. Now we don't see them very frequently because patients are treated, even by their primary care, with medications and therefore those medications interfere with inflammation.
Robert A. Kayal, MD, FAAOS:So specifically in rheumatoid arthritis. Dr Zalkowicz, what do you typically find when you're focused on examining the joints of these patients?
Alan Zalkowitz, MD:So we're looking for inflammation, swelling of the joints, warmth of the joints, difficulty, inflection or extending the joints. And sometimes we find that some of the joints form some abnormalities where they can look like swans the joints. They're called swan neck deformities. And then there are others that are called boutonniere deformities, that are specific for rheumatoid disease. We don't see that much as we did 30 years ago because of a lot of the medications for example methotrexate, in my own view has revolutionized the treatment. But we look for whether patients can straighten their joints, whether there's any warmth to the joints, whether there's any tapering of the joint, whether the patient feels in the small joints this symmetrical attack on their joints of their hands and their feet.
Robert A. Kayal, MD, FAAOS:Furthermore, a lot of these patients can have physical deformities of the fingers, something we call like a boutonniere deformity or a swan neck deformity, which we'll see sometimes in the hand. These are not common conditions in the orthopedic community. So you had mentioned, dr Zalkowicz, that when rheumatoid arthritis affects the hands it typically involves certain joints in the hands. Can you demonstrate for our viewing audience at least what part of the hands are typically involved, which joints are involved typically with rheumatoid arthritis and which joints are more commonly involved with the typical degenerative wear and tear osteoarthritis?
Alan Zalkowitz, MD:In the hand, for example. We look at these joints called the metacopal phalangeal joints and we look at the proximal phalangeal joints. The distal and phalangeal joints are usually not involved and what we look for is swelling, tapering warmth, and we look to see whether they can fully flex and extend their joints.
Robert A. Kayal, MD, FAAOS:So yeah, I agree with you wholeheartedly, dr Zalkowicz. When I see patients in the office and I see swelling around this joint right here, these joints, the metacopal phalangeal joints, I very much think of a rheumatological condition. Very often these patients will have what's called an ulnar deviation deformity at the metacopal phalangeal joints as well, where those fingers will be ulnarly deviated towards the ulna bone. So when we start to see a combination of these conditions like the swelling, redness and warmth in the metacopal phalangeal joints, the ulnar drift in those joints, possibly a boutonniere deformity or a swan neck deformity, our antennas go up and that's when we really want to refer that patient to Dr Zalkowicz and our other physicians at the Kale Rheumatology Center to make sure we're not dealing with an autoimmune systemic disease such as rheumatoid arthritis.
Robert A. Kayal, MD, FAAOS:I think that's important when we're assessing patients. When these patients are complaining of a symmetrical nature of their joint pains and swelling, we definitely get concerned about an inflammatory autoimmune condition. And in addition, these conditions often affect the smaller joints of the body right, the joints like the ankles, the elbows, the shoulders, much more commonly than the typical degenerative wear and tear osteoarthritis. In our profession, in orthopedics, we see way more patients suffering from knee arthritis and hip arthritis as opposed to ankle arthritis, for instance, or elbow arthritis or even shoulder arthritis. And so when we start seeing a patient with multiple joints involved, with pain and bone on bone deformity in the smaller joints especially, we very much get concerned about inflammatory arthritis and that this patient may possibly be suffering from an autoimmune condition and it's really very important that we refer those patients for rheumatological evaluation.
Alan Zalkowitz, MD:That's very true. These patients have to be picked up early. If it's very early, there is a possibility within several weeks of preventing the memory T cells. But the early you treat, before you have further damage and what we call panis, which is a thickening of the tissue by a joint, the more that you can reverse this and put patients into remission.
Robert A. Kayal, MD, FAAOS:So, dr Zalco, what else can you do on physical examination to help support the diagnosis of rheumatoid arthritis?
Alan Zalkowitz, MD:So we actually do a full examination, the rheumatologist with the Kale group and we look in particular at the lungs.
Alan Zalkowitz, MD:We're listening for what we call dry-course rals, to suggest that the rheumatoid is one of the 10% of patients who may have inflammation of their lungs which require special therapy.
Alan Zalkowitz, MD:We look at their eyes to see if they have dry eyes, to see if they have any inflammation called iritis or uveitis which require a two minute-cross factor. That's different than other medications to treat them, whereas it also treats their eyes. We listen to their heart to see if they have any sign of any cardiac involvement of the heart, in particular whether they have something called pulmonary hypertension that we can pick up on auscultation of the heart and an echocardiogram. We look to see if they have on abdominal examination and enlarged spleen and that is something that we see infrequently but it can happen. And, most importantly, we look at the nervous system, the nerves, and we do check for whether these people have a peripheral neuropathy, because if we catch a peripheral neuropathy due to rheumatoid disease and we are able to confirm that with an EMG nerve conduction, then there is medication to control that. But it also signifies to us to look for underlying inflammatory disorder called vasculitis.
Robert A. Kayal, MD, FAAOS:Wow, that was so helpful, dr Zalcow. So at this point it sounds like you've taken an adequate history. The patient's chief complaint, their history of their present illness, their physical examination are all pointing and suggesting rheumatoid arthritis as a diagnosis. What other objective tests can you do to further support that diagnosis?
Alan Zalkowitz, MD:One of the things that we do are joint films, specifically hand involvement, wrist involvement, but then again we're not likely to find significant findings. In today's age we rarely see erosions Again. If they're present, you have a general diagnosis and the patient hasn't been treated correctly. What we look for is swelling of the joints. What we look for is something where there's some inflammation of the side of joints, called periostitis. We often see on the proximate phyllo angio joints that I showed in the metacopal phyllo angio joints we may see some signs of some osteopenia. That means thinning of the joints on either side of the joint.
Robert A. Kayal, MD, FAAOS:Sometimes you can see a subluxation of the joints as well, which can contribute in the diagnosis correct.
Alan Zalkowitz, MD:Yes, we see them on occasion Again, not as often as we did 20, 30 years ago.
Robert A. Kayal, MD, FAAOS:Because you're diagnosing and treating them sooner With better medications. As far as other imaging modalities, what else can you employ to assist in the diagnosis?
Alan Zalkowitz, MD:Well, this is very key. We want to treat early to prevent panis formation and prevent erosions that we see on a regular film. That's by ultrasound and MRI. We try ultrasound first because it's very simple. In a skilled person who does ultrasound they can pick up tino-synovirus, inflammation of the tendons and the synovium of the joint and possibly some early erosions before they appear on the x-ray. More and more. To me and to most remittages, the gold standard is the MRI. Again, what we're looking for is edema. Even something as simple as edema will lead to erosions. If I see edema on an MRI, that would get me to use a biologic on a patient. If I saw tino-synovirus, certainly very aggressive. If I saw erosions on an MRI, all guns would be used to try and prevent further erosions and try and see if we can get some of those erosions to reverse, which happens on occasion. Again, the key is regular x-ray ultrasound MRI the key for a rheumatologist.
Robert A. Kayal, MD, FAAOS:Absolutely. It sounds like to me the key here is the early diagnosis and treatment. Really, nothing's better in early diagnosis than MRI, especially in this condition. The MRIs are so sensitive. It'll show that edema. It'll show that early erosions around the joint inflammation that we cannot appreciate on plain radiograph. I think it's a very, very important point that you've just made. Now that we've made the diagnosis, you've done the history, physical examination, you've looked at some of these imaging studies, are there any labs that you can order to support that diagnosis as well?
Alan Zalkowitz, MD:Yes, laboratory work for a rheumatologist is the bane of patients. Of course it means we take a lot of blood. We take a lot of blood often when we follow the patients because they need recurrent visits to see how they're doing and making adjustments in their medication. The test that we use for inflammation in general is called a sedrate and a seroactoprotein. They're elevated in inflammatory arthritis but can be elevated in infection as well, so we have to be very careful. But in degenerative osteoarthritis they're not elevated or borderline.
Robert A. Kayal, MD, FAAOS:What about the rheumatoid factor serology test?
Alan Zalkowitz, MD:So the rheumatoid factor testing is the latex fixation and the CCP antibody. One of the specific inflammatory markers in rheumatoid disease is called a Vectra D, which is rather more specific for inflammation. The testing that we do is we can do a latex fixation for rheumatoid arthritis that is positive in about three quarters of the patients with rheumatoid arthritis. It's not as specific as we would like because you can see that in people who have hepatitis and arthritis, tuberculosis and arthritis, sarcoidosis and arthritis, the test that we use more is called an ACP, an anti-citrullin peptide antibody. The anti-citrullin peptide antibody is found mainly in rheumatoid arthritis. It has a specificity of anywhere from 95 to 97 percent. So if you have someone who looks they have rheumatoid arthritis clinically and there's some edema on MRI or you see some tinocephalitis on an ultrasound and if you have a positive CCP antibody, you've made the diagnosis of rheumatoid arthritis. Moreover, the CCP antibody is those patients that develop the more severe type of crippling rheumatoid arthritis that you want to be most aggressive with. The small percentage of rheumatoids that have CCP negative rheumatoid arthritis you treat the same. They don't respond to biologics quite as well but they have a better prognosis. The higher the level of the CCP antibody, the worse the prognosis. So if you have a CCP antibody that's mildly elevated, that's much better than so now as a strongly elevated CCP antibody.
Alan Zalkowitz, MD:Now I will do other blood work. I will do a serum protein electrophoresis to see if these patients have early signs of what we call a monoclonal gemopathy. That can lead to an illness called amyloidosis or multiple myeloma, which rheumatoids are more prone to develop. I will do blood work for other autoimmune disorders like lupus and vasculitis, and I will do blood work if they have another type of genetic disease called HLAB27 arthritis, like psoriasis or ankylosing spondylitis. I might do parvoviral titers and if they have a high IgM titer I will tell them that they probably have parvoviral disease. I will do a hepatitis level and profile on them and I'll do a test for tuberculosis because if they're going to go on methotrexate or biologic they have to be TB negative. If they have had TB you can treat them, if they, with biologics and methotrexate, if their TB is dormant and the blood tests will tell you that.
Robert A. Kayal, MD, FAAOS:Do all patients that have rheumatoid factor always test positive for the latex test and or the anti-CCP test?
Alan Zalkowitz, MD:So patients who have rheumatoid factor or latex fixation don't necessarily have to have rheumatoid arthritis. As I mentioned, it's a non-specific test. You can have it in hepatitis, you can have it in other inflammatory disorders. The CCP antibody test is specific for rheumatoid disease. What most people have to understand is they can have a positive latex fixation or rheumatoid factor or a CCP for years and not have rheumatoid arthritis develop. It can take up to four and a half years for them to develop the inflammation, the stiffness, the symmetrical polyarthritis of the hands and feet and other joints. But when we test for it, if that's positive, it would mean we are going to be very aggressive in treatment.
Robert A. Kayal, MD, FAAOS:Could it work the other way, where they do have the diagnosis but don't have positive latex tests and or anti-CCP tests?
Alan Zalkowitz, MD:Yeah, so latex is positive 75% of the time. So you can have a latex positive and have hepatitis. You can have it with viral arthritis, which, by the way, is in a differential and usually is gone within six to eight weeks, whereas rheumatoid lasts longer. So latex is not specific. Ccp antibody is rather specific for rheumatoid disease, especially if they have history compatible with it, positive vector positive C-reactive protein and sedrate, and if they have on MRI edema or tino sinavitis on ultrasound. The seronegative patient that has negative CCP antibodies and has a negative latex has a much milder disease and you can have people have a latex fixation that's negative and have rheumatoid disease, or a latex fixation that's positive and not have rheumatoid disease. I think that with CCP antibody if you have the test positive you have rheumatoid arthritis. If it's negative then the chance of having rheumatoid arthritis is remote, possible, but only by a few percentages of patients.
Robert A. Kayal, MD, FAAOS:The common culprit in a lot of medical conditions is inflammation these days.
Alan Zalkowitz, MD:There are several other things that a lot of my patients take that can affect inflammation. First are the turmeric and curcumin that a lot of people take on their own. It is anti-inflammatory. It has approximately the same anti-inflammatory effect as some of the non-steroidal anti-inflammatory drugs, like Celebrex, for example. I just want to spend one moment on Celebrex because it does not affect the platelet and therefore does not interfere with coagulation like the other anti-inflammatories ibuprofen, aliv, naprison. Therefore, it's one of the medications that one can use, if one has to, in people who have conditions where they're taking a blood thinner.
Alan Zalkowitz, MD:But turmeric you have to be careful of, and over the counter preparations you have to really Google the side effects. For example, it can cause oxalate formation. So if you've had a kidney stone, we don't recommend that you take it. If you have iron deficiency anemia, we don't suggest that you take it because it can interfere with iron absorption. If you're on a blood thinner, we don't recommend that you take it. Something else that's very important are omega-3 fatty acids. Omega-3 fatty acids are very anti-inflammatory and have been used in the past in patients who have heart disease to help with their cholesterol profile. We know that they're anti-inflammatory, whereas omega-6 and omega-9 fatty acids have the opposite effect. But again, if you're going to go to surgery to get a hip or a knee replacement, you must stop that, as well as any non-steroidal or turmeric, before you're going to go to surgery for about a week at least, because it can cause some bleeding.
Alan Zalkowitz, MD:Other things that people have taken are conjoitan and glucosamine that have a beneficial effect on cartilage, whether it's in inflammatory disorders or degenerative disorders. It too can have an effect on a medication, cumidin. If you're taking it, most people come in and they talk about having ginger tea, which has an anti-inflammatory effect. I do recommend that. But in degenerative wear and tear arthritis, the Scandinavians have shown clearly that rose hip tea or by mouth has a beneficial effect on arthritis of the knees and of the hands. In addition, in Shrewsbury, massachusetts, a large study showed that if you take Jell-O it will help the arthritis of someone in their knees. There are a lot of things that you can do, but most importantly to reduce inflammation is watch your weight, don't smoke and get down to an ideal weight. What is the best diet? The best diet generally is a Mediterranean diet. In people who have an inflammatory disorder that's very painful, called gout, which is by a different mechanism of elevated uric acid. We usually have people on a low purine diet.
Alan Zalkowitz, MD:In terms of inflammation, we have changed over the last 30 years the prognosis in rheumatoid arthritis and in most of the inflammatory autoimmune conditions by using disease-modifying anti-inflammatory drugs and what we call biologics. The biologics can affect the basic cause of the disease. In rheumatoid arthritis there are three different mechanisms that we attack. One is called tumor necrosis factor. That is made in the system to fight and prevent tumors. But we also note that in rheumatoid arthritis and in most inflammatory disorders, like psoriatic arthritis, which about 3 million people in the world have and is one of the differential diagnoses from rheumatoid disease and is a non-symmetrical arthritis, whereas rheumatoid arthritis is usually symmetrical, the major things that we attack are different. In rheumatoid arthritis we try and attack tumor necrosis factor. We try and attack something called interleukin 6 and interleukin 1. So we have now medications that will specifically attack those pathways and cause people to go into remission.
Alan Zalkowitz, MD:Years ago we used aspirin and we used drug called penicillamine and we used gold and we had very little benefit. Now what I've noticed over my career is that we've made such a great difference in rheumatoid arthritis that we rarely see now someone who has crippling disease, and the reason for that mainly is when the drug methotrexate, which was used for hundreds of years to treat tumors and malignancy, was utilized to treat rheumatoid arthritis once a week by mouth and if you go into higher doses, subcutaneously by injection, and that by itself, without anything else, has caused one in three rheumatoids to go into remission. When that is not enough, we then usually add other oral agents, a drug called hydroxychloroquine or plaque. We know that's had a lot of play in the literature in COVID, where it may not play a role and may not be beneficial, but in rheumatoid arthritis and especially lupus, it is life-saving and has changed the whole lifestyle of patients with systemic lupus, and their average age would be up to 55. Now I have patients with lupus who are in their 70s 80s and have had lupus for over 40 years with the use of plaque, venal and methotrexate and other disease modifying biologics. We sometimes use even a drug called a sulfidine or sulfasalazine, which is used in people who have inflammatory bowel disease and in people who have bladder infections over the course of years. In fact, in Europe it was the drug of choice for many years in terms of treating rheumatoid disease, until they too learned from us here in America that methotrexate was the drug of choice. I would venture to say that all of our rheumatologists in the Kale organization and we have a large experience over 80 years between the several who are in the group will all start a patient with rheumatoid disease and most inflammatory arthritis with methotrexate. We're not certain how it works actually, but it may have an effect on folic acid metabolism of inflammatory cells and therefore we don't want patients to become folate deficient, which is a vitamin B like B12. So we give them folic acid along with the methotrexate. When we have patients who do not respond well enough to methotrexate, possibly using hydroxychloroquino and sometimes using azulfidine, which is a triple therapy which was used now for about 25 years rather successfully, then we go on to use biologic. There are some people, myself included, who use a biologic much earlier.
Alan Zalkowitz, MD:There's some evidence that if you use methotrexate or a biologic within the first few months, first 14 to 16 weeks of rheumatoid arthritis, that perhaps you stop the T cells. Remember that we've learned from COVID that there are B cells. The body makes two types of lymphocytes that help with inflammation in a positive manner and in inflammatory disorders in a negative manner. One are called B cells and the other are called T cells or thymus derived the cells. If you give medication early in rheumatoid arthritis, you can prevent the T cell from forming memory cells and memory antibodies. If you prevent the memory cells from developing and you treat a patient early enough, you may be able to cure them in a long run. Other than that, you can only hope to put patients into remission. Now that's something that was unheard of 20 to 30 years ago when the first biologic came out and we first started using methotrexate, often together.
Alan Zalkowitz, MD:The biologics that we use now are multiple, depending on whether we think someone has tumor necrosis factor as the primary cause of their rheumatoid disease, or interleukin six or interleukin one. The tumor necrosis factor inhibitors that we know of and use today the most common one is umira, which is now has biosimilas, so it's made the cost much, much cheaper and it's given subcutaneously every two weeks. One that I like a great deal is called remicade, which is an intravenous and one of the oldest, so I have a long history of the side effects of remicade and umira as well, and you have more play with that. In umira you give the same dose to someone who's skinny or someone who's heavy. Again, you want to be not heavy In remicade. You have the ability to alter the dose and alter the timeframe that you give the medication. This is now that affect the interleukin six system are drugs called ectemora and kevzara.
Alan Zalkowitz, MD:What I'd like to spend a moment and get off rheumatoid disease is that at age 60, I mentioned that men are as frequently involved with rheumatoid diseases as women because the restrogen level decreases. Age 60 and above we find another condition that has muscular and joint involvement, called polymyadromatica. Perhaps we'll have a session just on that, but over 60, it's just as frequent as rheumatoid arthritis. One of the things that the rheumatologists at the Kale centers have shown is that we can now treat polymyadromatica and we have biologics for that. Those biologics are the ones that inhibit interleukin 6. So when you have someone over age 60, especially if it's a female, you need to look for polymyalgia as part of your differential from rheumatoid arthritis. It's treated very similarly but not quite the same.
Alan Zalkowitz, MD:In addition, you have to make certain that you're not missing some other types of arthritis that are very common. One would be infectious arthritis. I mentioned Lyme disease early and we're in the time period where you have Lyme disease, usually spring, summer and fall. It's usually done by a spirochete that gives you a bite that you can't see the spirochete. It's usually under the armpit, by the groin, by the backside.
Alan Zalkowitz, MD:Then you get a certain type of erythema, this reddish rash that clears in the center. Then you get usually one joint, usually a knee, but it could be an ankle or a wrist. Rarely does it cause a polyarthritis like you get in rheumatoid disease and doesn't usually affect small joints, hands and feet, as rheumatoid arthritis does. But there's also Parvo virus. Moms will know that and teachers will know that because it's called fifth disease amongst children and it's very common. And in children you get a big red rash on the face and they can develop arthritis and fever. In adults you don't get any rash, you just develop a polyarthritis and a certain percentage of those patients go on to form rheumatoid arthritis and lupus and are treated often the same. Why is it important to know and to test for Parvo virus? Because often it will get better by itself with time and that's very reassuring to a patient.
Robert A. Kayal, MD, FAAOS:So I know, dr Zalkowicz, that you mentioned some of the medical therapies for the treatment of rheumatoid arthritis, but I think it's so important for our viewing audience to understand the difference between treating symptoms and actually modifying the course of disease in this medical condition. Some of the medications that you mentioned are called DMARDS, which are actually disease modifying anti-rheumatoid drugs which actually positively affect the ultimate outcome for these patients. They can actually cause this condition to stop progressing and actually go into remission and sometimes, as you've indicated, actually be curative if you can diagnose them and treat them early enough. But disease modifying anti-rheumatoid drugs such as methotrexate and hydroxychloroquine also the biological disease modifying anti-rheumatoid drugs that you've mentioned, like Humera, actually have this effect on these medical conditions, like rheumatoid arthritis and others that you've mentioned.
Robert A. Kayal, MD, FAAOS:There are other treatments for rheumatoid arthritis as well which do help with the symptoms of arthritis. We already discussed that arthritis is associated with a tremendous amount of inflammation, and inflammation is the main culprit here. In this autoimmune disease, it is in fact our body's immune system which is attacking ourselves. The immune system is attacking not only the joints in rheumatoid arthritis but, as we've mentioned previously, it's affecting our organs as well the heart, the lungs, the vascular system and others. Anti-inflammatory medications are very, very helpful in this condition. As we've mentioned, some are disease modifying anti-inflammatory medications, like the ones we've previously mentioned, but there are others that treat the symptoms but do not actually modify the prognosis and outcome. What are some of those other anti-inflammatories? Some are over the counter and some are prescription strength.
Alan Zalkowitz, MD:So we do use non-steroidal anti-inflammatories. They've been around for many years. Some are over the counter, like ibuprofen and Aleve. Most of the ones that I use are by prescription. Interestingly enough, the one that I use most is a drug called Celebrex. It's a sulfur preparation, so you have to be careful in those people who are allergic to sulfur. And the reason that I use that, as I mentioned, it does not interfere with anyone who is on a blood thinner. In addition, in a large study in the Cleveland Clinic comparing Celebrex to patients who have heart disease with ibuprofen and naprason, it showed less morbidity and less mortality. So I use that as my go-to.
Alan Zalkowitz, MD:For other's. Dichlofenac or Voltaren is probably the strongest, although most rheumatologists would say that most of the anti-inflammatory drugs are interchangeable in terms of their potency. I should mention that both orthopedists and rheumatologists use a drug like Voltaren, dichlofenac, in a cream form or anointment form that we apply to a knee, for example, or a joint that's typically giving more difficulty. I would mention again that if you're on a blood thinner especially, you should make certain that your physician is knowledgeable enough to know that not all nonsteroidals are the same in terms of causing an increase of bleeding problem, and that I do recommend, if you're not allergic to sulfur, that you talk to them about using Celebrex.
Alan Zalkowitz, MD:We have used nonsteroidal anti-inflammatories for many years. They're both by prescription and over-the-counter. I should caution that they're great drugs but they have potential for side effects on kidney and the cardiovascular system. So it should be under the care of a physician and you should have blood work monitored. We also use steroids. That's a form of prednisone or medrol that we use often to suppress inflammation, either in a pulse we give it for a short period of time or a longer period of time if we need it. Those are great medications. They take away the inflammation in their hands and the feet and the joints of patients with inflammatory disorders. However, we're trying to get away from steroidals because steroidals have an effect in raising the blood pressure, glaucoma, diabetes and osteoporosis. Again, if you're on corticosteroid, that needs to be under the care of a physician that has a lot of experience with it.
Robert A. Kayal, MD, FAAOS:Yeah, absolutely. In my field of orthopedics I definitely poo-poo the usage of steroids as much as possible because we are the ones that see and appreciate and treat the dreaded complication of steroids called avascunocrosis, where the AVN or avascunocrosis can deleteriously lead to the death of the bone in the joint, leading to collapse, arthritis and the need for hip, knee, shoulder or ankle replacement. I think it's so important to emphasize once again that, now that we're talking about joints, when we definitively treat these patients and treat their joints that have been destroyed by this inflammatory autoimmune condition, we are not yet done treating the patient. As opposed to an osteoarthritis, degenerative wear and tear arthritis, for instance we talked about hip and knee arthritis are so common. When we replace those joints, we've cured essentially that patient of that arthritis in that hip or in that knee or in that shoulder or in that ankle.
Robert A. Kayal, MD, FAAOS:That is not the case with inflammatory autoimmune diseases such as rheumatoid arthritis. These patients may ultimately still require a hip replacement, a knee replacement, a shoulder replacement or an ankle replacement, but we're not done treating that patient. That patient can still get arthritis or inflammation in that joint due to the autoimmune condition because the synovial lining is still there. If the patient suffers a flare up of their underlying autoimmune condition, they can still get inflammation, swelling and pain in that joint. Yes, we get rid of most of the pain from the bone-on-bone erosions that occurred secondary to the inflammatory arthritis by doing the hip or knee or shoulder ankle replacement, but we do not get rid of the synovial lining or tissue and so they can still get symptoms. That's why it's incumbent upon us to distinguish between typical degenerative osteo-wear and tear arthritis from an autoimmune condition, because that patient will more than likely require a lifelong treatment by an expert such as Dr Zalkowitz, so that we can continue to suppress the autoimmune condition, so it doesn't continue to affect other joints of the body. Do you agree with that, dr Zalkowitz?
Alan Zalkowitz, MD:Yes, I certainly do. Some of the information has suggested that about 25% of patients can get off the medication over a period of time. But of those 25%, about half of those flare within a year or two and then when you reapply the medication, unfortunately it doesn't work as well. What we try and do is get patients off two minicross factor inhibitors or other interleukin inhibitors and see if they still do. Well, get them off of a methotrexate if we can. We certainly make an effort to get these patients off of steroids because they're the ones that have a long-term effect, not only in vascular crosis but in cardiovascular problems and cataracts and in healing. In some patients who are fortunate and able to look like they're in remission. That means they have no stiffness, swelling, no joint pain, they have full flexion extension and there's no active inflammatory process going on clinically and their laboratory work, namely their sedrate and their seroactoprotein, are normal.
Alan Zalkowitz, MD:We try and wean these patients down or for medication. We certainly start with corticosteroids. That means prednisone, medrol. We try then wean them off of that slowly and progressively and look to see if there's any sign clinically of them worsening. Next we try and wean them off their two men across his factor inhibitor, or their interleukin-6 or interleukin-1 inhibitor, their biologic. That may be by using a biologic like umira that's used every two weeks, going to every three weeks or every four weeks or even further, and then when we're satisfied there being able to withstand being off the biologic, then we will wean down the methotrexate slowly. This can take a year or so to do. And when they're off methotrexate then we try and see if we can wean them down or maybe keep them on just some hydroxychloroquine, perhaps one a day or one every other day, having their eyes looked at every six months by an ophthalmologist.
Alan Zalkowitz, MD:If we're fortunate and we're able to get some patients off probably about 25% over the course of time, about half of those a few years later will have a flare of activity and that flare of activity can be just as they presented originally, with swelling of their small joints of their hands and feet and their purple other joints, and can be accompanied by stiffness, swelling, pain and difficulty, straightening joints, their sedraton seroactive protein and their blood goes up. And those patients we put back on medication and unfortunately only about half of those respond. The other half will have significant difficulty and will be difficult to treat thereafter. So what a lot of us do is wean off cortisone that's an absolute and try and wean them off nonsteroidals or they can stay on a nonsteroidal if their kidney function is, and blood pressure, reasonably normal. We then try and wean them off a biologic.
Alan Zalkowitz, MD:Those are the. That's the mainstay. If we can get by with methotrexate and possibly hydroxychloroquine and the patients doing well, we may be satisfied with that. If we can get the methotrexate down to a low dose, so how do you follow these patients?
Robert A. Kayal, MD, FAAOS:Dr Zalkowicz, Once you've made the diagnosis and you began medical therapy, what's the typical follow up for these patients?
Alan Zalkowitz, MD:So there is the use of prednisone, which I told you.
Alan Zalkowitz, MD:We try and get patients off.
Alan Zalkowitz, MD:But we often use prednisone at the beginning as what we call bridge therapy, because it takes methotrexate several weeks, platinol several weeks and biologics several weeks for them to start to kick in.
Alan Zalkowitz, MD:The prednisone, in very small doses, will usually do the trick. The patient will feel better. We'll usually start them on methotrexate either that first visit or quite soon, and then we'll follow them clinically by the amount of stiffness they have in the morning, by looking at their joints for swelling, for whether they have any inflammation of the redness or, and we'll look to see what the sedrate and seroacuprotin they should be coming down. And then we will probably see them every few weeks at the beginning and then, when they're in doing very well or possibly in remission, probably every eight to 12 weeks. I have some patients that I now been in remission for several years that I see every six months to a year and they come to me from all over the country because I put them into remission. So they, I think, feel that if they come to me they're going to stay in remission Even though they have a rheumatologist, either it in Florida or in North Carolina or in Connecticut, or even in South America.
Robert A. Kayal, MD, FAAOS:And how often do you use combination therapy?
Alan Zalkowitz, MD:That's a great question. I always use combination therapy, just like we do in high blood pressure. In fact, I think that the people who use combination therapy and high blood pressure learn from us, the rheumatologists. We always have patients on methotrexate almost always. We often have patients on an antimalarial hydroxychloricin or plaque when we sometimes have them on sulfazalazine, which is a sulfa preparation, and we have them often if they're CCP positive or have on an MRI signs of edema or tinoceinavitis on the biologic.
Alan Zalkowitz, MD:So there are on several medications. Now some of those are on an anasteroidal as well if they're not on prednisone. I really ever use an anasteroidal with the prednisone at the same time because it increases the risk of an NSAID gastropathy. That means inflammation of the stomach that can lead to bleeding and it's silent because if you bleed in the stomach the nerve endings are dulled so it increases the risk of bleeding sevenfold. So rarely ever will I use prednisone or an anasteroidal. Sometimes I'll be able to get by with an anasteroidal as bridge therapy instead of prednisone In a mild patient. Usually you're CCP negative and usually has just some demer or juctar ticolasty process.
Robert A. Kayal, MD, FAAOS:Very interesting.
Robert A. Kayal, MD, FAAOS:Well, dr Zalkowitz, as you know and I've mentioned many, many times I chose to be an orthopedic surgeon because I appreciate instant gratification, I like fixing things that are broken and I get that instant reward for the most part.
Robert A. Kayal, MD, FAAOS:Thank God there are doctors like you who deal regularly with chronic disease, because this is, in fact, a chronic disease, right, it's not like osteoarthritis, like I mentioned, that we can do a hip replacement or knee replacement or a meniscus tear and take care of that surgically, where I fix the problem and the patient gets on with their life.
Robert A. Kayal, MD, FAAOS:This patient is your patient for life and the onus is on you to quarterback the care of that patient, told that patient's hand and manage that patient medically to keep that patient remission their entire lives once that diagnosis has been made, because this is a chronic disease that we had already mentioned is progressive and can go on literally to kill patients, right? So it's so important, because of the cardiovascular involvement and the involvement of other organs, that this condition can literally kill patients. So it's so, so important for the medical community to understand this diagnosis, to identify it and diagnose it early with treatment and refer the patient to a rheumatologist like Dr Zolkowitz, so that he or she can hold their hands their entire lives and keep their condition at bay, to keep them healthy and active and live a long, vivacious life. Do you agree with that, dr Zolkowitz?
Alan Zalkowitz, MD:Yes, there are just a few caveats. I'd like to add. Number one unfortunately we're not making enough rheumatologists. There's usually in most centers a six-month wait for a new patient to be seen, and generally they're seen by a physician's assistant or nurse practitioner who are knowledgeable but don't have the experience of well-trained rheumatologists being in practice.
Alan Zalkowitz, MD:Fortunately, when Dr Kale and I discussed about joining rheumatology and orthopedist, he understood that these are lifelong patients that need a lot more time because they have a lot more underlying pathology and develop infection, heart attacks, a lung involvement, kidney involvement, amyloidosis, multiple myeloma. So they're often followed by five or six other doctors that we as rheumatologists have to look at their notes and see how they're doing. And what's so wonderful about being a rheumatologist in the Kale group is we're allowed the time to deal with these patients, to help them and to help the doctors that are treating them in other fields to know how the rheumatoid arthritis or other autoimmune disorders is playing a role in their patient's heart disease or lung disease or kidney disease or neurological disease, because we know a lot about it, probably more than they do, because we see a lot more of it in our particular field.
Robert A. Kayal, MD, FAAOS:And we're so blessed to have each other in our practice. It's a multi-specialty group, it's a collaborative effort with experts in every field where we're caring for these patients, and I must say this has been a very enlightening discussion. I've learned so much from you once again, dr Zalkowitz, and I appreciate your knowledge, wisdom and expertise. I hope that you have found this to be very informative and helpful in your evaluation and management of your patients and your conditions, and I just want to take this opportunity to say how thankful I am that you're part of our practice caring for our patients all these years. It's just a blessing to have you, dr Zalkowitz, and I look forward to having you come back in the future so we can talk about other rheumatological conditions, and thank you so much for your time and wisdom and expertise.
Alan Zalkowitz, MD:Thank you so much. And remember at tail, as it says on the sign, we'll see you soon. So if you have a rheumatological problem, you're not going to wait six months or six weeks. It's a matter of days before one of the various rheumatologists look at you. We look at you ourselves.
Robert A. Kayal, MD, FAAOS:Amen, thank you, thank you.