In a country where more than 9% of adults have diabetes, Alexander Reyzelman, DPM, discusses the implications for those who also have peripheral vascular disease. He describes how to efficiently distinguish PAD – an underdiagnosed, undertreated problem – from other conditions; explains how to classify claudication; and clarifies when intervention is needed. Finally, hear why the UCSF Center for Limb Preservation focuses on speedy delivery of care that integrates podiatry and vascular surgery.
Uh, my name is Alex Raiselman. I'm a co-director of UCSF Center for Limb Preservation and a professor of the California School of Pediatric Medicine. My passion in, in the 20 plus years of my career has been taking care of patients with PAD and and the complications of diabetes, lower extremity complications of diabetes. This is a very large topic. There's a lot to talk about, so, Um, I had to condense into the next 25 to 30 minutes, and please go ahead and ask questions towards the end, would love to interact. This is a very significant problem that I think majority of, uh, providers don't really realize how severe this is, and I hope to shed some light on this problem in the next 20 minutes or so. So when we look at PAD, uh, what we call a cardiovascular epidemic, there are significant facts that we just need to know, uh, about the epidemiology. PAD afflicts 8 to 12 million Americans and carries an atherosclerosis risk similar to symptomatic coronary disease. It's increasing as a result of aging US population, and smoking, diabetes, and a bunch of other factors, and frequently is the first sign of cardiovascular disease. Studies have demonstrated that PAD is underdiagnosed and undertreated. Important implications for both life and limb. So somebody with PAD is 2 to 6 times fold increase for heart for heart disease and stroke, and it leads to severe disability or even limb loss. We know that in the United States, there are more than 80,000 major amputations performed per year, affecting 1.4 million Americans living with major limb loss. Just for lower extremity PID are very evident. And I'm gonna go over some of these. If you're less than 50 with diabetes, and you have one additional risk factor such as smoking, dyslipidemia, hypertension, or hyper homocystinemia, you're at risk. If you're aged between 50 to 69 and history of smoking or diabetes, you're at risk for PAD. If you're over 70 years of age without any other comorbidities, you're at risk for PAD. People with leg symptoms with exertion, suggestive of claudication or ischemic rest pain, clearly are risk factors for PAD. Abnormal lower extremity pulse exam is an obvious one. And known atherosclerotic coronary artery or renal artery disease places you at risk for PAD. I think it's important to understand that PAD, CAD, uh, carotid disease, renal disease, they're all the same disease. It's macrovascular disease. So, if you're treating somebody with history of carotid endarterectomy, Somebody who's had an MI, there's a should be a high index of suspicion for PAD and vice versa. When we're seeing patients with PAD, we have to be mindful that the same patient may be having CAD or carotid disease, and we may be able to prevent MI's and strokes if we get these patients appropriate workup sooner. There are different methods of assessing for arterial insufficiency or PAD. Um, many of these are what we employ in our clinics. You may know some of them, ankle and toe pressures or ABI. This is a big screening tool that some of you may have done, or may be doing it now. Uh, segmental Doppler pressures, pulse volume recordings, these are all non-invasive arterial studies. We put them in this category. We also perform tissue perfusion tests with TCPO2, which is transcutaneous pulse oximetry. We have skin perfusion pressure devices, and hyperspectral tissue oxygenation devices to really assess non-invasively, whether somebody has arterial disease. And of course, we have anatomic imaging such as ultrasound, CTA, MRA, and then angiography. This is just a a schematic of a typical ABI where we measure ankle pressure and uh systolic pressure in the arm, and then the ankle over brachial pressure gives us the index, and a normal index is really between 0.9 to 1.1. Anybody that falls below 0.9, by definition, has PAD. The lower they are, if it's 0.6, 0.5, then the more severe PAD is. So, If you're if you're performing these, great. If you're not, you should refer these patients to a center that is able to do these tests. This is just an example of how we do it. It's a simple uh blood pressure cuff that's put around the ankle, and then we use pulse oximeter to put around the distal tip of the toe, and we're able to get waveforms, hence, we're able to get the pressure of um uh of the ankle as well as the toe. This is an example of transcutaneous eximetry. Uh, this particular device is a very expensive device, usually only used in the vascular surgery clinics or wound care centers. Now, when we talk about PAD, I think the way to think about it is the PAD is a spectrum. It's not that one day patient wakes up with PAD. Patient develops PAD in terms of their severity over many years. So, they may come in with mild disease, then progress to moderate disease, and eventually progress to severe disease. So, we break down PAD in several categories. Number 1, 50% of patients with PAD are asymptomatic. They're walking around without knowing that they have PAD. 30% of PAD is atypical leg pain, so patients don't even know that it's related to PAD but they have some form of pain in the leg. 20% of PAD is classic intermittent claudication, which we'll talk about in just a second. And only 2 to 3% of PAD is critical limb ischemia, which is end-stage PAD, which is the very severe form of PAD, which we'll talk about in a minute as well. History, physical exam, non-invasive physiologic studies established the diagnosis in the majority of cases, but you have to have an index of suspicion. So what is intermittent claudication? Sometimes, uh, we, we get confused and we don't really know what that means, but in simple terms, Intermittent claudication is pain in the muscle, big muscle groups, such as uh buttock, uh, thigh musculature, or calves, uh, or even the arch of the foot, the intrinsic muscles of the foot. The intermittent claudication, by definition, has to be pain in the muscle group during exercise or during activity. Most of these patients, they're not exercising, they're walking. They're having difficulty walking 12, or 3 blocks. What happens is the typical history is Patient describes pain in their calves when they're walking. And the pain is so severe that they have to stop. And it's not truly a cramp. Um, it's pain in the muscle that makes them stop. Once they stop, they rest, pain goes away, because more blood flow comes back to the musculature, the pain goes away, they're able to walk. But what's interesting about intermittent claudication, it is repetitive. It's consistent, meaning that if you have one block claudication, you will have it every single block. You're not gonna have a patient comes in and says, I'm gonna, I walk 1 block today, and I have pain, but tomorrow, or a week ago, I walked 34 blocks, and I didn't have pain. That inconsistency is not intermittent claudication. Intermittent claudication has to have same block pain, every 2 blocks, every 3 blocks, every block, and it doesn't vary from one week to another. Usually, the disease is the segment above where the muscle is. So, if the pain is in the calf, usually the arterial disease is going to be in the popliteal artery segment above. If the disease is in the thigh, the the arterial if the pain is in the thigh, arterial disease is gonna be a segment above, probably in the iliofemoral area. Not all leg is PAD. We have to have a differential diagnosis. Very common. With spinal cord disease or spinal stenosis, mimic intermittent claudication. The difference between spinal compression or narrowing of the spinal cord is that that disease is not consistent. It's not every block, week to week, or every 2 blocks week to week. One day it's gonna be 3 blocks. One day, the patient's gonna be able to walk 1 block, but it's not consistent. So, that's a usual clinical way of differentiating. Peripheral neuropathy is another differential diagnosis. Osteoarthritis of the hip or knee, muscle spasm or cramps, and I have to spend just a second to tell you that cramps at night, typically patients have cramps at night. That is not PAD. OK. When you really have that true uh uh severe cramp in your muscle that many of us have experienced, that just happens haphazardly, that is not PAD. PAD is pain in the muscle group during walking or exercise. Restless leg syndrome is another differential, and sometimes venous disease um uh with varicose veins could mimic uh PAD or intermittent claudication. Now, as we jump into chronic limb-threatening ischemia, this is the end-stage PAD. Intermittent claudication is more moderate, and chronic chronic limb-threatening ischemia is more severe. This is when we're having patients develop ischemic rest pain. This is where the patient will complain. I have to dangle my feet at night in order to get rid of the pain. So they wake up because of the pain, cause there's lack of blood flow coming to their feet. Now that ischemia that's created in the foot is causing pain. So, what happens is These patients have to dangle their feet, allow gravity to overcome their occlusions in their arteries, and that increased blood flow with gravity helps to overcome their pain. That is true ischemic crest pain, and this is pre-gangrenous stage. Also, uh, chronic illness-threatening ischemia can come with tissue loss. So, if you have a toe ulcer, a foot ulcer, uh, gangrene, all of these are end-stage PAD. More severe compromise of circulation, which carries with it a high risk of amputation if not treated. So, if somebody comes in with a typical ischemic ulcer or gangrene, these patients are at very high risk for below the knee. Or above the knee amputation. And also, these patients are increased risk for cardiovascular morbidity and mortality, OK. How do we treat PAD? Uh, typically, if you're, if you have asymptomatic disease, it's risk factor management and surveillance. There's no role for prophylactic revascularization, and I think this is an important part. You, some of you may have seen this where patients are getting stented, they're getting angioplasties performed, yet they don't really have any foot ulcers, they don't have gangrene, so it's more prophylactic. There is no prophylactic revascularization because it's a risky procedure. And many times we see patients who undergo prophylactic procedures, and they burn bridges. They have problems with uh With um showering emboli down the leg, which then causes some major issues. So we have to be very careful. Not all PAD deserves intervention. Intermittent claudication treatment is typically risk factor management, exercise, and pharmacotherapy. Exercise has shown evidence has shown that if you have the patient walk consistently every day with history of intermittent claudication, their intermittent Medication improves. So, if they were a two-block cloudin, they may become a 3-block cloudicin or a 4-block cloudin, but that takes time. So, it's consistent daily routine of pushing themselves and exercising the muscle that increases angiogenesis, opens up collaterals, and the pain tends to improve. Uh, sometimes we do interventions with stenting or angioplasties if intermittent claudication becomes disabling, and that's really the operative word here is disabling. What do we mean by disabling? Well, let's say that you have a mail carrier. Who is not able to do his route of 5 blocks, and he's able to walk only 2 blocks. And he gets pain, and is not able to finish their job or to do his job adequately. That's disabling to that particular individual. That may need to be intervened on. We may need to work this patient up and and uh perform a balloon angioplasty, maybe a stent. However, If you have an 80 year old with two-block claudication that doesn't walk much and is able to get to her supermarket that's a block away, that's not really disabling for that individual. Hence, intervention may not be necessary. And as we move into critical ischemia, This is where we absolutely have to intervene. Without intervention, these patients will lose their legs. Worse yet, they may develop cardiovascular problems, such as MI and strokes. So, Effective revascularization is really important. Um, fast, uh, workup, quick intervention is really important, and that's the only way that we can prevent amputation in this, uh, high-risk, um, uh, part of PAD. Now, we'll move into diabetes. Uh, diabetes, in and of itself is a major problem, and I think it's important to understand the magnitude of diabetes in the United States. And I don't know how many of you know these statistics, but I think some of them are pretty staggering. More than 30 million patients with diabetes in the United States, which makes up about 9.4% of the US population, over 300 million worldwide, and this continues to increase. Nearly 70% of amputations in the United States are performed in patients with diabetes. Age adjusted risk for amputation is 28-fold higher. So if patients, patients with diabetes are 28 times higher risk for developing an amputation. It is estimated there is a diabetic undergoing lower extremity amputation every 20 to 30 seconds around the globe. Diabetic foot ulcer is a strong predictor for limb loss. And among patients with a diabetic foot ulcer that heal, up to 80% of them will have a recurrence within 1 year. 1 out of 3 diabetics older than age 50 have PAD, and diabetics with PAD are at significantly increased risk for mortality and limb loss. It's a huge, huge public health expenditure and growing rapidly. Here's a chart of the number and percentage of US population with diagnosed diabetes. If you look from 1960 to 1997, it's been growing at a steady state. But then in 1997, it has a significant spike. From 1997 to 2015, there's been a tremendous increase in diabetes, and it continues to increase today. Now what about in California? What's happening in our own backyard? In California, this is a fair, this is fairly recent data um that's that was published 2 years ago, uh I think it's been 2 years ago now. Greater than 15.5 million adults, which make up about 55% of all Californians, have prediabetes or diabetes. Greater than 1/3 of adults of color have prediabetes, and in California, lower limb amputations has increased by greater than 31% between the years of 2010 and 2016. We can further divide and break this down based on counties. And if you look at the richest county in the United States, which is Marin County, amputations has increased from 32% between 2010 and 2016. San Francisco County by 16%, Alameda County 7%, Santa Clara County by 19%, and San Joaquin County, a whopping 41%. And this is here in California. And as we go further out, closer to Central California, it gets even worse. Now, how does this happen? Why do diabetic patients develop Um, ulcers and subsequent amputation. It's really the triad between neuropathy, vasculopathy, and immunopathy. And what this means is neuropathy is, um, is the loss of sensation that develops in patients with diabetes over many years. Now, if you've had diabetes for 10 years or greater, your risk of having neuropathy is probably 50 to 75%. So first, what happens is patients slowly lose sensation. They develop pins and needles, burning, eventually numbness, and eventually their sensation in the foot goes away. And we call that loss of, I, I always tell my patients, this is where they, they lose the gift of pain, because pain is really the protective mechanism that we have. But these patients lose that gift, and now they're walking around without feeling on the bottom of their feet. So if they step on a nail, If they develop a callus, if they wear a shoe that's a little bit too tight, they will not feel the blister, they will not feel the damage that's occurring to their skin. So now the callous is is becoming more of an issue. There's injury underneath the skin, and then that tissue breaks open. If you add vascular disease on top of that, that makes it even more difficult for that wound to heal. And then, we already know that patients with diabetes have immunopathy. They have poor defense, and poor ability to fight infections. So when you put them all together, that leads to a major problem, which eventually leads to infection and subsequent amputation. Uh, this is a stairway to amputation that was published, uh, maybe 5 to 10 years ago. And this is again an easy way to think about this, and how does, how do we get to amputation? We first have diabetes. Diabetes leads to neuropathy. Neuropathy opens the door to the ulceration, which is the break in the skin. Ulceration gets infected. When you add vascular disease on top of that, that leads to the bad outcome of an amputation. Why is this important? Because the stairway, we can intervene and mitigate certain risk factors. We, we can't reverse diabetes. We can't reverse neuropathy, but we can, we can prevent ulcers, we can treat infections, and we can, we can catch vascular disease with proper intervention, timely intervention. Probably my favorite slide um to present. To my non-podiatry colleagues. Because if you look at, we talk about amputations, but we also should talk about mortality. And when we think about five-year mortality rates, we typically talk about cancers, right? We know that cancer is, is, is the, is what everybody is afraid of. Why? Because of mortality. Because it's, it's some of the cancers lead to significant mortality. But what about diabetes and the complications that occur in the foot? And what is, what about PAD? How does that affect mortality rate? So, if we look at breast cancer, 5-year mortality rate, you can see that it's fairly low. If you look at a diabetic foot ulcer, which is this bar, the red bar right here, diabetic having a foot ulcer. patient that you see with a foot ulcer carries at least a 30% 5 year mortality rate, which is much higher than breast cancer and higher than colon cancer. OK, and higher than usually higher than non-Hodgkin's lymphoma. If you have Charcot, which is a complication of diabetes where the arch collapses and the bones collapse, mortality rate is pretty high. When you have a minor foot amputation, such as missing a toe or part of the toe, or part of the foot. The 5 year mortality rate approaches 50%. If you have a patient with chronic limb threatening ischemia, 5-year mortality rate is greater than 50%. And then if you have a patient with a below the knee amputation. Where 5-year mortality rate is very high as well. So the only cancers that have a higher 5-year mortality rate than the majority of the foot problems with PAD and diabetes really are lung cancer and pancreatic cancer. Why is this important? Because I think we need to switch the way that we think about these. When a patient walks in with PAD, when the patient walks in with diabetic foot ulcer, or Charcot, or part of the toe is missing, we need to think about these people as having cancer, because only then will we have the same diligence and care, and plug them in appropriately. Otherwise, we don't really think about it that way. So, I think it's really critical for us to think of patients. With diabetes and lower extremity complications, as though they have a very aggressive cancer. Why is this a problem for us? Well, number one, there's a low level of public and community MD awareness. We have poor classification and staging systems that complicate management and communication between providers. There are multiple providers, and the care is extremely fragmented and delayed. And why is that? Well, sometimes patients go to a podiatrist, sometimes patients go to a vascular surgeon, sometimes patients go to an orthopedic surgeon. Sometimes they go to a primary care physician, endocrinologist. They're all over the place. Therefore, the care is fragmented. There's no one center that can take care of this big problem. Diagnostic and therapeutic approaches are highly variable, and the quality measures are not standardized. So, in order to be successful, what we need to do is have rapid recognition and treatment of these advanced stages in order to get clinical success. What we usually say is time is tissue. The reason that a lot of these people lose their feet is because they delay their care, or we don't pick them up soon enough. So, when we see these patients, we need to jump on them right away. We need to be able to diagnose them. We need to be able to intervene appropriately. And the longer time goes by, the more time that goes by, The more tissue we lose. We also realize that close follow-up and serial assessment is very important for progress. Once you have had an ulcer, as I mentioned earlier, up to 80% will re-ulcerate within within one year. If you have PAD and you've had an intervention, there's a high rate of restenosis in these patients, so their surveillance becomes very important. In order to combat this problem, we set up a center at UCSF about 12 years ago now. Uh, which we call Center for Limb Preservation and Diabetic Foot. This was the first of its kind in the Bay Area, because we provided the multidisciplinary care. We realized that in order to save limbs, in order to make a dent, we have to combine. Uh, expertise. And we've, we're the first center of its kind to combine vascular and podiatry, and then use other services such as endocrinology, orthotics, and prosthetics, uh, plastic surgery to, to help us treat these patients and get them what they need. So, we established the center in 2011. Uh, our center treats patients with foot ulcers, peripheral arterial disease, and those at risk for developing these conditions. We're dedicated to functional preservation of limb, which means we're not just thinking of preserving the limb, which we're thinking of how do we keep these patients active? How do we make sure that they maintain ambulatory status? We have a highly uh in a close coordinated effort between outpatient and inpatient setting, which we believe is very important. The same team that treats the patient on inpatient side is the same team that follows these patients on outpatient side. We have a 92% limb salvage rate. Uh, we take consults 24/7. We typically see patients within a 48 hour period, depends on the urgency of the situ urgency of the situation, and it's very important for us that we communicate to our referral sources and to our partners in the community. The conditions that we typically treat are diabetic foot ulcers, uh, Charcot feet, pressure ulcers, venous ulcers, patients with Buerger's disease, uh, with Raynaud's syndrome, uh, peripheral neuropathy, and of course, any other vascular, uh, condition, uh, which could be aortic disease or carotid disease, or dialysis access as well. One of the best parts of our center is that we consider ourselves a one-stop shop. When a patient comes to see us, we're able to do everything. We're able to see the patient in a combined fashion. A vascular surgeon, a podiatrist sees this patient, and we're able to do non-invasive arterial studies in the same setting. So, we tend to assess the problem, and then develop a treatment plan as a team. This is just a slide showing that we have different tools in our toolbox, um. Intervention for PAD has evolved over the years. There are all kinds of interesting tools and devices. Uh, there are all kinds of different balloons, there are drug-coated balloons, there are all kinds of atherectomy devices, uh, there are all kinds of different stents, and of course, uh, we still do, uh, the mainstay for many of these patients is the open bypass procedure. This is a guide, an amputation risk and screening guide that we will provide to all of you, because I think this is an easy, um, easy, uh, guide to look and see how, what kind of risk are the patients and, and how fast should we refer this patient. So, we developed this a couple of years ago, and basically, it, it, it works like this. If you are a diabetic patient, and you don't have any symptoms, and you don't have any foot ulcers, and you don't have neuropathy, You're a low risk for amputation. This is a patient that should be screened annually by either primary care, or if the primary care wants to refer him to a podiatrist, that would be acceptable. If the patient now develops numbness, tingling, burning of their toes, which are signs of peripheral neuropathy, now they have moderate risk of amputation. This is a patient that but for sure needs to be seen by a podiatrist, at least once a year to assess for PAD and for peripheral neuropathy, and for risk for developing ulceration. And then, if the diabetic patient develops an ulcer, has a history of calluses that are bleed that have bleeding into them, if they have pain in their feet at night, if they have symptoms of intermittent claudication, or they have had ulcers in the past, this is a high-risk patient for amputation. This is the type of patient that we want to see right away. This is where we would schedule that patient within a week, or probably within a couple of days. And finally, Uh, patient with severe risk for amputation with an active ulcer, spreading infections, cellulitis, uh, gangrene, foot and ankle swelling with or without pain. This is a rapid referral. This is the patient will probably get in within 24 hours, uh, by calling our referral center. In this, in this slide, what I'd like to show you is that how we think about our limb preservation program, uh, and how we partner with our community. Our base is this UCSF proper in San Francisco, where we do complex procedures such as open bypass or or uh foot surgery. However, we have a lot of partners. We have a BOPC which is Berkeley Outpatient Clinic, where we have vascular presence, and we do non-invasive studies in Berkeley. We have Saint Mary's Hospital in San Francisco, where we have our podiatrists and vascular surgeons who are doing the same thing. We have an outpatient post in San Mateo. We have clinics in the North Bay, in the East Bay, where we partner with community podiatrists, who are then able to screen these patients, who are then able to follow these patients, because we're not able to follow all of these patients for their wound care needs on a weekly basis. But we do have partners all over the Bay Area, where where they know how we function, they're able to communicate to us at all times, and they're able to see these patients closer to their home. So, what happens when the patient sees us and for initial evaluation? They undergo a comprehensive pediatric and vascular evaluation at the same time, and complete foot exam, assessment of deformity, assessment of the wound. We, we figure out whether there is a probing to bone, where the bone is exposed. We assess for uh neuropathy, we take foot x-rays, uh, we take pictures, we, we take, uh, we perform a non-invasive arterial study. And then we stage the limb. There is a staging classification called WiFi, wound ischemia and foot infection. And this system basically is like a cancer staging system. We're able to look at the foot and the leg, and assign a risk category from 1 to 4. Risk category 1 is a very low risk for amputation. Risk category 4 carries approximately 40% risk of amputation within a year. So, much like cancer staging, the higher the stage, the worse the prognosis. The same thing with the Wi Fi. The higher the stage, it basically tell us tells us that this patient needs to be seen in a multidisciplinary fashion, and this patient needs to have intervention. Sooner the better in order to to save the limb. Post-discharge, patients are following up with the same team on outpatient basis, uh, or they're following up with our community podiatry partners. Surveillance is key. Uh, these patients will always be plugged into 136 month appointments to assess for recurrence of PAD, assess for restenosis. Um, the need for, uh, offloading and shoes and orthotics is always there, so, these patients are patients for life. And I'll probably end with um We're talking a little bit about our research program. UCSF Center for Limb Preservation is one of 7 centers that were that was recognized by NIH who is currently doing a major, major, um, study on on diabetic foot ulcerations preventions, and this is a consortium of 7 different academic centers across the country, and we're one of them. So, we're always looking for patients to um put in our research programs. Our team is composed of vascular surgeons, podiatrists, uh, 4 nurse practitioners, and a patient care coordinator. Uh, who is, um, Joanna De Long. She's always available. We'll, we'll pass around her cell number, and she's always, uh, ready to answer the phone calls. Our phone numbers, uh, Mike Conti's, my partner, who is the chief of Vasco at UCSF, and myself, we'll make the phone, our phone numbers available. We're really easily accessible. We're happy to take your call or text or pictures and say, what would you do with this patient? We're happy for curbside consults. Um, we're very accessible because we want to be able to decrease the number of amputations, right? And that's really the key for our center. Our foot care partners, we have locations throughout the Bay Area, including Sacramento, anywhere from San Francisco, South Bay, East Bay, uh, Peninsula, uh, North Bay. All of these centers are available to see your patients, to screen your patients, and to be helpful in any way. And this is our team. And without the team, this doesn't work. Uh, it's all about team effort. No single specialty can help can help decrease amputation. It it takes really a team. So with that, I will end and happy to answer any and all of your questions.
