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Male Speaker: We're going to bring up Dr. Matrona Giakoumis, who is a faculty at the New York College of Podiatric Medicine in the Department of Surgery and she's going to talk about Heel Pain using Injection Steroids, PRP and Amniotic tissue.
Dr. Matrona Giakoumis: Good afternoon everyone. Thanks for sticking around and I will be talking about something that we probably see all the time and treat very frequently. And that is this idea and concept of heel pain but more specifically for this lecture, we'll be focusing on treatment modalities, which include injections and some more of the new orthobiologics which are becoming a little bit more mainstream now. And that's platelet-rich plasma and amniotic tissue. I'll also try to catch us back up on time a little bit because we are running a little bit behind. I have no financial relationships to disclose.
So we have four main objectives for our lecture today. We're going to discuss the various entities of heel pain and as we know there are numerous things that can cause heel pain but we'll eventually narrow down to sub-calcaneal heel pain with specifically the diagnosis of plantar fasciitis because that's where these injection therapies will come into play. We want to understand how these injection therapies work, when they can come into play, and then we want to look a little bit at the literature and see what is actually being seen, what works, what doesn't work and what's the level of evidence for using these therapies.
So at its core, when we talk about heel pain, that is calcaneodynia. So if we look at the Miller-Keane Encyclopedia & Dictionary of Medicine, Nursing, & Allied Health, basically it's describing this condition in which weight-bearing, which is important, on the heel causes pain but to various degrees in severity. And so, what we know is that the heel is a very complex anatomic structure and so really pinpointing the ideologies of pain and function has been difficult to kind of understand. And that's why we have all these different treatment modalities, but nothing has really been set in stone as to being the gold standard for treating heel pain.
And now we can also break down the different ideologies into different subgroups and one of the subgroups is neurologic ideologies. And just looking at this brief little chart, there are at least eight different neurologic components of heel pain. The one that I really want us to focus on is the one about the first branch of the lateral plantar nerve involvement. So this is also known as Baxter's Nerve. Baxter's Nerve is actually typically found about four to five centimeters proximal to the distal calcaneus or just distal to the medial calcaneal tuber. So a lot of times when these patients come and you're trying to differentiate what type of heel pain they're having, if you compress this portion they will often kind of describe this burning pain that will travel to the distal lateral portion of their foot. And interestingly enough, there was a study that looked at plantar fasciitis on MRI and they found that about 52.8% of patients actually concomitantly had this entrapment of the first branch of the lateral plantar nerve. And the way that they saw this was that the abductor digiti quinti was atrophied, which represented this chronic compression of the nerve.
So if we want to break down these different entities, we can break them down into subgroups by the anatomic position on the heel. So if we look at posterior heel pain, different entities can be from the Achilles tendon, also superficial calcaneal bursa, you can have posterior and pigment or os trigonum and even calcaneal apophysitis. If weâre swinging around to the medial heel, patients can be complaining about heel pain but it can be related to the tibialis posterior tendon and sheath or even the PT nerve in the tarsal tunnel. Along the lateral aspect of the heel, patients may complain about pain but it can be related to the sinus tarsi or even the subtalar joint.
And then once we work our way around and we focus on the sub-calcaneal heel pain which is really where our focus will be today, we can break down the entities into two groups. We can have skeletal component and a soft tissue component. Among the skeletal causes, patients can have a calcaneal stress fracture. It can be from apophysitis of the calcaneus, osteomyelitis or even inflammatory arthropathies. So one of the more common but still rare causes will be the calcaneal stress fracture. So, typically these patients present complaining of this diffuse heel pain, itâs present primarily on weight-bearing activity but eventually progresses to pain off weight-bearing and at rest. They usually have pain along the medial and lateral posterior aspects of the calcaneus and it can be listed by this squeeze test that we talk about often.
And then among soft tissueâ¦
â¦we could have a fat pad atrophy, contusion, plantar fascia rupture and really what we're going to be focusing on for the rest of the lecture is plantar fasciitis. Plantar fasciitis has also been differentiated from fat pad atrophy. Especially with the aging population, we're seeing more causes from fat pad atrophy and basically this is thought to be due to decreased water, elastic fibers and collagen as patients get older. But these patients will specifically complain of this deep intense pain right over the central plantar aspect of the calcaneal tuber.
As we all know, sub-calcaneal heel pain is very common. It's actually the most common reason to foot and ankle specialist. It affects over two million Americans and it accounts for about one million visits to foot and ankle specialist. The most common diagnoses for plantar or sub-calcaneal heel pain as we said is plantar fasciitis or fasciosis as we will talk about and normally peaks around 40 to 60 years of age and it's multifactorial. Meaning that we know that there's this mechanical stress and increased tension along the plantar fascia and it's been attributed to different things such as Aquinas which we talked about a pronated foot type, obesity. And we know that it actually starts off as an inflammatory process but through recent papers such as Lamont & R, which was published in [Indecipherable] [06:30] in 2003, we know that as this process becomes more chronic, it becomes more of a degenerative process.
So these features of inflammatory versus degenerative process are important when we talk about our treatment modalities because certain things will work better in the acute phase versus the chronic phase. And as we know there's a variety of treatment options and modalities that exist out there. Unfortunately, the results are inconsistent and as we will see through our little short literature review it continue to be inconsistent.
So as we have mentioned before, there are various treatment modalities that are present, but there is no gold standard. So if patients present to you with heel pain, regardless of any of the entities that we talked about, most of your initial treatments will be the same for all of them. Those include rest, ice and said some sort of either prefabricated or custom orthotic, stretching physical therapy that's pretty universal. But then how do we get rid of that pain for those percentage of patients who aren't responding to those conservative measures? Well, that's where these following treatment modalities come into play. And so more specifically, we'll be talking about steroids, platelet-rich plasma and amniotic tissue.
Now going back to this inflammatory versus degenerative process, where do these modalities fit into play? If we're really believing that plantar fasciitis is a degenerative process and is really fasciosis then the chronic form of it would be more amendable to platelet-rich plasma and amniotic tissue therapy. But the acute phases will be responsive to steroids. So as a quick review, as we all know, steroids are our class of medications that reduced inflammation. And the most commonly injected steroids into the body tissues and the ones that are approved by the FDA are dexamethasone phosphate, triamcinolone, betamethasone and methylprednisolone, which I'm sure all of you have used one or more of these to some degree.
Now we're all familiar with this pathway and the interesting thing about corticosteroids is we know that it affects the anti-inflammatory as well as the anti-immunosuppressive pathways. And it's very complex but the thing about it is that it affects the pathway very early on. So it has its effect on several levels of this pathway and so it ultimately what it does is it prevents these prostaglandins and inflammatory mediators from being released by the body and that's how it decreases inflammation and how we can clinically see it as this decreased, when itâs decreased swelling, decreased pain?
The concern with steroids obviously, the main one is the rupture of the fashions actually been reported to be about 2.4% in the literature. Other common side effects are thinning of the fat pad, discoloration of surrounding tissue, increased pain due to the cortisone flare and infection. And so even though we'll see that steroids do help, there's this increasing concern about the side effects. Platelet-rich plasma is autologous bone and it is fractionated plasma with these increased levels of platelets above baseline. So basically, it can be done intra-operatively or even in your office, it just requires a machine which some people buy or rent out and basically
you collect about 30 to 40 milliliters from the cubital vein. And then it spun down on a machine and it forms this three-layer in your test tube or your centrifuge tube and you have your buffy coat which is the white blood cells, you have your plasma which is your platelets and then you have your other red blood products such as your red blood cells. And from there, your platelets are taken out and then re-injected back into the site of an injury. And theoretically, this could be done in the office or in the OR. The problem with this is that the actual procedure in the way that the blood is collected or how many times it's spun down can actually affect its efficacy. So there's no standardized way or standard amount of blood that's collected and how many platelets are taking from 30 ml of my blood might be different from how many platelets are taken out of your blood and so we may have different responses because of that.
So here is this on picture and basically on the top left corner you see a platelet granule. So when the platelet granule is activated, it releases these lysosomes dense granules and these alpha granules and we're primarily interested in the alpha granules. Because once these get activated, basically we have this fibroblastic migration and proliferation and vascularization and collagen reparative process that goes on. So we have this tissue healing cascade that gets initiated.
The nice thing about platelet-rich plasma is because it's coming from you. There's no concern for immunogenic reaction and there's no disease transmission. There are no side effects that have been reported in the fob. Interestingly, this has been used for many years particularly in cardiac surgery. And prior to 1997, they did see these coagulopathies that would happen in patients who received it but they noted that this happened on patients where the platelet-rich plasma was directly put on to an open wound. And it's also the dosage was a lot higher than what's injected into feet. So for instance, they received over 10,000 units whereas in the foot, it's less than 200 units. So since this has been standardized by drug companies, there haven't been any more reported cases after 1997 or the foot either.
And finally amniotic tissue. Amniotic tissue is multipotent stem cells and factors which promote regeneration of tissue and down regulate inflammation. So similar to platelet-rich plasma, the idea is to form this reparative tissue response in the body. And basically these are harvested from already pre-selected mothers prior to cesarean sections and so they give consent prior to the case and normally the amniotic tissue is discarded after surgery, so instead of it being discarded it's collected and separated out for this process. And that there are no common side effects reported with amniotic tissue either.
The reason why amniotic tissue and platelet-rich plasma are thought to work in this degenerative plantar fasciitis situation is that, what we have seen through cadaveric studies is that the proximal portion of the plantar fascia through time becomes hypo vascular and so there's decreased blood flow getting to that area. And so the idea is by injecting these products to the sites, you're getting this hyper vascularization that's occurring which is thought to hasten the healing response by putting all these cytokines and growth factors into the area directly.
So the amniotic tissue was originally used in the early 20th centuries directly on chronic wounds. So back then, they actually took it right away from the operating room and put it on these chronic wounds particularly burn victims and they found that these patients did really well. And it's actually been used in ophthalmology surgery for at least 20 years, but it's actually just making its way into orthopedics in the more recent years. So this is an image of the fetal tissue and fetal tissue contains two layers; we have your amnion layer and your chorion layer. And the interesting thing about the amnion layer is that it contains no blood vessels, no lymphatic vessels. There's no nerves in there, but it's responsible for maintaining the fetal tissue and so the different layers, the epithelium, the basement membrane, compact layer and the fibroblastic layer are the layers thatâ¦
â¦contain the collagen types one, three, four, five and seven which are known to be important for this healing cascade.
The extracellular matrix has also contained specialized proteins, fibronectin, laminins proteoglycans and glyclocenomen. And growth factors EGF, TGF, beta FGF and PDGF.
Okay, so now we want to look at the literature and see what this literacy say because we're all training towards this evidence-based medicine. And we really want to practice evidence-based medicine. So this was a recent study published in 2016 in May and the aim was to evaluate if corticosteroid injections were more effective than other interventions and so basically they compared corticosteroid to placebo, which is generally saline injection, platelet-rich plasma or Tenoxicam which is an NSAID injection. And they looked at it in the short-term and long-term of plantar fasciitis.
So basically, this review article, their results concluded that the corticosteroid was not more effective. So there was a non-inferiority that was shown for platelet-rich plasma and the Tenoxicam, but these were all based on level 2 and level 3 studies. And as we know, the level 1 studies are really the ones that are the highest level of study. And this following article, also published in 2016, the author Mahinda [phonetics] and all were interested in comparing platelet-rich plasma, corticosteroid in placebo. Now we get into more interesting studies because instead of comparing a treatment modality to placebo, now we're comparing two treatment modalities to placebo. So we can really do more of a head-to-head study.
So this was a well done study, was a prospective, randomized, double-blind placebo control study, they enrolled 75 patients with chronic plantar fasciitis. And basically, they randomized some of them to receive platelet-rich plasma, some of them received corticosteroids and the rest of them received placebo, which was a saline injection. Now unfortunately, their follow-up study was kind of short. They evaluated the patients at three weeks and three months post injection. Their primary outcome measure was pain and the way they measured this was by using the Visual Analogue Scale score as well as the AOFAS ankle and hind foot score. At three weeks and three months, they found that there was significant improvement to both scores in both groups. So they both were equally good at decreasing pain based on AOFAS score and a VAS score, but the PRP group was slightly better but it was not significantly better.
This was a little review chart that they had in their study and basically they kind of pulled all of the articles that use platelet-rich plasma treatment for chronic plantar fasciitis. And as you can see on the right chart, the conclusion was that both the steroid and the platelet-rich plasma were pretty much effective in their treatments.
Here's another article, this was also a systematic review and based the authors had an inclusion criteria of a diagnosis for plantar fasciitis with clear details of clinical assessment. So based on their inclusion and exclusion criteria, they found 12 articles that met their criteria which included about 455 patients. And they did a quality assessment of these articles based on the DAD scores for the randomized control trials at the Newcastle-Ottawa Scales for the non-randomized studies.
And here is the articles that they pulled and they did a nice job summarizing it. And if you look more towards like the central area of the chart, these are some of the studies that actually compared platelet-rich plasma to a steroid. And you can see both groups showed improvement even though PRP showed better initial improvement, both groups significantly lower pain, significant difference between the two groups PRP was more effective. At three weeks, all scores were significantly improved. So the general consensus is corticosteroids and PRP can go pretty much head-to-head and they both work pretty well with improving pain. Where they do start to differentiate is, how long are they effective? And so, what we're seeing is that the steroids really are effective but only for a short term. So, just for several months. But if these patients are followed long enough, then the treatment group that fares to do better is the platelet-rich plasma group. So basically their discussion was thatâ¦
â¦factors may be affected by numerous things. The use of ultrasonic guidance. So whether or not you're injecting this blindly versus under an ultrasound, that will affect the results. The injection technique that you're using, peppering versus a direct injection and what we talked about a little bit earlier, the amount of blood collected, method use of preparation, so the centrifuge B, the number of spins, the type of anticoagulant or activating agent. So there are so many variables that it's kind of hard sometimes to really compare these different papers objectively because there's so many different things that can be taken into account.
And basically, their conclusion was that all the selected and reviewed studies showed significant improvement with no evidence or side effect or complications when PRP was used in treating plantar fasciitis. This suggests that PRP could be an effective mode of treatment for plantar fasciitis with promise safety. So basically, they're really looking at the side effects. PRP doesn't have any side effects and so because it has non-inferiority to corticosteroids, then maybe it is better to use on patients. The one thing that they don't really talk about it is the cost component and how does that play a role into these different treatment modalities. The new orthobiologic minimally invasive techniques tend not to be covered by insurances. So a lot of times patients have to pay out of pocket for these kind of treatments.
So now when we look at amniotic tissue, this probably has the least number of studies that have been done on it. I'm pretty much going to talk about, I think, two that have been published that were more higher level articles. So this was an article published that enrolled about 44 patients and their primary outcome measure was pain as well. And they also used the VAS Scale score and they measured these patients at four and 12 weeks post injection. And they found that there was significant reduction by four weeks post injection and the 10 weeks post injection.
And this following prospective, randomized, blinded, comparative study was also a level one study. And basically 45 patients were enrolled and they were randomized into two groups. One group received 1.25CCs of saline, the placebo group and the study group either receive 0.5 or 1.25CCs of the mDHACM, which is micronized dehydrated human amniotic/chorionic membrane. And the things they were interested in looking at was not only pain, but also function and functional health and wellbeing. So these patients were also followed over eight weeks and they found significant improvement observed in both groups.
This following study was also level 1 prospective, randomized, controlled, double-blind, single center pilot study. This included smaller number of participants. There was only 23 participants enrolled in this. And basically, they compared cryopreserved human amniotic membrane to corticosteroids for plantar fasciitis. Their outcome measures included foot health status questionnaire, VAS and verbally reported percentage improvement at six, 12 and 18 weeks post injection. So this is one that they followed them a little longer and they actually did not find a statistical difference between the groups for majority of outcome measures.
So as we can see, sub-calcaneal heel pain due to plantar fasciitis or fasciosis is a common problem. There are many treatment modalities that exist, but no treatment is guaranteed. So even with this review of literature, even though this newer therapies are promising, nothing is really being shown to be completely superior based on a level 1 study to what we already have. We know that corticosteroids provide relief, however, they are shown to be temporary and frequently avoided because of the common side effects that we know can occur with them. There has been promise with the newer agents such as PRP and amniotic tissue, but overall we need further future studies to be directed toward larger clinical trials in order to really formulate a gold standard treatment for plantar heel pain. Thank you.
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