Hello, my name is Dr. Mark Davis. I'm a dermatologist at the Mayo Clinic in Rochester, Minnesota. I'm professor and chair of the department here, and my subject today is an approach to atypical skin ulcerations. So I'm from Ireland originally, and so anybody that's familiar with Ireland might know that it's divided into four provinces, and that's Leinster, Munster, Connacht, and Ulster. And my patients in Ireland used to say, I'm here with me Ulster doctor. So I'm going to talk about ulcers on the skin today, the ulcers on the skin. So one clinical tip that I would share with you that I want you to take away here is that don't think of ulcerations as being a final diagnosis. Think of them as being a clinical sign. And as a clinical sign, just like redness of the skin or swelling of the skin, it's a very nonspecific sign, which have multiple possible etiologies. And of course, we all think of ulcerations as a clinical sign, which can indicate underlying vascular disease or neuropathic disease. The vascular causes, as outlined here on the left side, include venous ulcerations, which are thought to account for 70 to 80% of all ulcerations, arterial ulcerations, arteriolar ulcerations, small vessel disease, lymphatic disease, and then the ulcerations may be neuropathic. But as dermatologists, we also have to be specialists in recognising unusual causes of ulceration. Perhaps not so unusual is trauma to the skin leading to ulcerations. But infections, particularly atypical infections, can cause ulcerations. Malignancies can cause them. Inflammation, connective tissue disease, drug-induced causes, hematologic causes, and pyodermic anginosome, one of the very unusual causes of ulcerations we have to think about. So once again, think of ulcerations as a clinical sign with multiple possible etiologies. And really, my talk today is to illustrate this slide with different presentations of ulcers that were due to different underlying etiologies. And of course, why do we have to know the underlying etiology? It's because the management of each etiology is entirely different. So what's the clinical approach to atypical ulcers when we see it's making the correct diagnosis, that's critical. And how do we do that? By history, physical examination and testing. Now, often our testing can include a skin biopsy, which may include skin biopsy culture for bacteria, mycobacteria and fungi, doing lab tests as appropriate and also doing vascular tests. Vascular testing can include invasive or non-invasive arterial studies, venous studies or lymphatic studies. And of course, depending on the etiology, then the best treatment for the ulceration becomes apparent. So our treatments can vary from compression of the affected area to revascularization, to offloading, to behavioral modification, to antimicrobials, to anticoagulants, to stopping medications, starting medications, starting systemic immunosuppression, doing surgery, to using chemotherapy, depending on the cause. So I want to share some atypical ulcers that I have seen and discuss with you how would we approach making the right diagnosis and ask you, what do you think is the best treatment for the following ulcers? And let's go through different ones. So case number one is a patient presenting with these pinpoint ulcerations on the legs and feet. You can see that they're very, very small. They're surrounded by kind of stellate type scars. And that you can see here where they've healed up, and also they have a kind of a lividoid color. So what do you think is the diagnosis here and what would be the best treatment? Well, I want to share with you a skin biopsy from an affected area of this ulceration, and we see a biopsy with the dermis stuffed with the small blood vessels, stuffed with clots like we see here. So this is a clotting disorder of the skin, which is called lividoid vasculopathy. And the right treatment of this ulceration is to unclot or to use to use things that would prevent clots. So aspirin, diperidamol, and the use of some of the newer anticoagulants are all usable in this situation. So this is lividoid vasculopathy leading to pinpoint skin ulcerations, which are agonizingly painful. And the way we treat this one is that we use aspirin or anti-clotting agents. Let's talk about case number two, atypical ulcer. A patient has this ulceration on the ankle. Now, the interesting thing about this ulceration is that this is an ulcer in a patient with a history of myelofibrosis, who has this agonizing skin ulceration for the past year. And actually, it turned out that it was a priest who was unable to wear shoes. He was unable to sleep with the pain of this ulceration. He had normal pulses, so this is not an arterial ulcer. And his arterial and venous studies were all normal. And he was getting intensive wound care that was not working. So what do you think was going on here? Was it an arterial ulcer, a venous ulcer, a medication-associated ulcer, a neuropathic ulcer, or a factitious ulcer? Well, it actually turned out to be a medication-associated ulcer. For his myelofibrosis, he was on what drug? Hydroxyurea. And hydroxyurea is known to cause leg ulcerations. And it can be years, patients can be on the hydroxyurea for years before the ulcerations develop. And so the treatment for his ulceration was to stop the hydroxyurea and the ulcers resolved. This has been well described. Now, lots of medications can cause ulcerations, not only hydroxyurea, but methotrexate can cause ulcerations. Pentazocine, which is a form of injected narcotic medication, which was used back in the 1960s, can also cause ulcerations. And maybe potent topical corticosteroids, if excessively used, have been noted to cause ulcerations. I wanted to show you a few more atypical ulcers here. This was a woman who'd had mesotherapy to reduce the fat in her buttocks and on her legs. But everywhere she got these injections, she got ulcerations. And what's used in mesotherapy are agents which dissolve the fat, which are used to for to reduce the fat in these areas. And unfortunately, in this patient, this led to ulcerations. Now, why did these ulcerations occur exactly? We don't exactly understand. One thing that's been described in association with mesotherapy is that the injected liquid is contaminated with atypical mycobacteria. But that was not the case in this patient. We put this patient on an anti-inflammatory oral doxycycline for a few months, and these areas of ulceration cleared up interestingly. So just an interesting presentation here that mesotherapy can cause ulcerations. And conversely, this was another woman who had had who presented with these very unusual ulcers on the legs. And you can see the way her legs are a little bit look kind of deformed in this area. This was actually the true outline of her legs here. And when we took the history here, she was from Brazil and she had had injections of something into her buttocks to make her buttocks look actually bigger rather than the previous case, which I showed where the patient wanted smaller buttocks. And it turned out that it was mineral oil that was injected into the buttocks and the buttocks actually bulked up. But then after a time, the entire lower extremity started to swell and then she developed these ulcers. And it turned out that when we biopsied the skin in these areas in the fat, we could see the mineral oil interrelating between the in the fat there. So this turned out to be mineral oil induced and ulcerations on the feet. So this is an example of ulcerations secondary to the mineral oil that was injected into the buttocks, which migrated down into the legs. So, again, very unusual. So the pearl is here that other injected things can cause ulcerations. For example, deoxycholic acid in the first one injected as mesotherapy and then mineral oil in the second instance, as I showed you here. So I think you would agree, very interesting, unusual ulcers. So case number three, I wanted to share here. This is a patient we saw in the hospital who suddenly had been noted to develop ulcerations on the buttocks. And what do you think that these were due to? Well, it actually turned out that they were due to herpes simplex. Of course, whenever we hear about ulcerations on the buttocks, we think about pressure ulcerations. But these were discrete lesions which were grouped on the buttocks and not in specifically in pressure areas. And when we swabbed them, they were due to herpes simplex type two. This is actually surprisingly common. There's been a couple of studies showing that herpes ulcers can occur on the buttocks and are not uncommon. And the way to treat these was then with antiviral agents and rather than managing them as an other causes of ulcerations. So these were herpetic ulcerations. Then this was another patient who presented to us with a question of pyoderma gangrenosum was on huge doses of corticosteroids and other immunosuppressants, but the ulcerations kept on occurring. And what we decided to do was well, actually, the patient had been sent to us for an amputation of the leg and was admitted to the hospital late in the evening, having flown for a long distance. And they asked dermatology to come along and see this patient before the amputation, which had been prearranged the previous day by phone call. But dermatology came along to see this patient and we noticed that the patient had these huge ulcerations on the legs. But we also noted was that there were ulcerations in skip areas along the eyes. So what do you think is going on here? Is this typical of pyoderma gangrenosum? Well, the answer is no. There were extensive ulcerations on the legs occurring despite high dose immunosuppressive medications. And then there were other ulcerations occurring along the skin, overlying the lymphatic drainage of the limb. And this is called sporotrichoid spread clinically. And when we did a biopsy of the affected area of the thigh, we found that there was sporotrix there. So this patient had sporotrichosis. So what was really needed is not an amputation of the leg, but antimicrobial agents that would work for sporotrichosis. This patient was put on itriconazole for nine months and did extremely well and was able to walk again. And I'll show you some more closer ups of this patient. So again, what we're seeing here is at the edge of the ulcerations, what looks like pyoderma gangrenosum on the leg. But then we see these skip lesions with ulceration overlying the lymphatic drainage. This is consistent with sporotrichosis. There's a number of antimicrobial, sorry, of microbial infections that can cause this type of ulceration. But this turned out to be sporotrichosis and the patient responded to antimicrobials. This was the biopsy showing the sporotrix here in the biopsy specimen. So the patient was able to tolerate debridement after a time and engraftment, which hadn't worked before. And after itriconazole for nine months, was able to walk again. So that is an unusual cause of an ulceration. So case number four, I wanted to share with you here, this was a patient who presented with progressive painful ulcerations involving the groin and the perianal area. And you can see what this looked like here. They were in the groin here. And biopsies by 12 had all been nonspecific, but it was noted on the biopsy specimens that they saw some candida, but that was felt to be a contaminant. And the patient had been tried multiple times at oral fluconazole, but that had not worked. We tried lots of different things to treat these ulcerations, but none of them worked except for one of the following agents. And what do you think was the thing that worked for this patient? Was it prednisone, caspofungin, bexarotene, methotrexate or excision of the affected area? Well, I put up that list there because we did actually try all of these for this patient, but there's one thing that actually worked and that turned out to be caspofungin. And why? Because this turned out that it turned out that when we actually sent the biopsy. For culture and antimicrobial susceptibility, specifically looking at that candidiasis, it turned out that this was resistant, the candidiasis was recalcitrant to fluconazole, and the only thing that it was sensitive to was caspofungin, and we admitted the patient to hospital, gave caspofungin and the ulcers healed, started to heal within a few days. And you can see that the ulcer is completely healed up, as you can see in this patient here. So again, always be conscious that that infection can cause ulcerations and it may be very subtle infection and think about could it be antimicrobial susceptibilities as being important here. In this case, it was candidiasis, which was recalcitrant to fluconazole. So the pearl is here, infection can cause ulcerations, and I've shown you viral infections, herpes simplex and fungal infections with deep fungal infections and also recalcitrant candidiasis causing ulcerations. All right, case number five, I wanted to share with you. This was a patient that I saw in the vascular center. The patient had what was thought to be a venous ulcer and was receiving excellent wound care. But despite that, the ulcerations were continuing and getting larger. And why would you think that that's the case in this patient? Well, as you might suspect clinically, the edges of this ulcer appear rolled and they don't appear normal here. And whenever we see rolled edges, that's reminiscent of the so-called rodent ulcers of basal cell carcinoma. And sure enough on biopsy, this turned out to be a basal cell carcinoma on the extremity, which was the reason that the ulcer wasn't healing with excellent care for venous ulcer, which was compression. So what was required here was actually surgery to remove the basal cell carcinoma and then the ulcer healed. So whenever you see a recalcitrant venous ulcer or any ulcer, always think about biopsy to look for malignancy. And here's a giant basal cell carcinoma on somebody's lower back. And again, showing the rolled edge reminiscent of basal cell carcinoma. We've seen a number of malignancies causing ulcerations, including melanoma, clear cell sarcoma, basal cell carcinomas, lymphoma, they can all cause ulcerations. Case number six, why do you think this patient had an ulceration on their leg? Well, I think when we examined the leg closely, we see this ulceration here and it has a kind of gray metal type edge that we can see here at the edges here. And that raises a lot of possibilities. But then when we look around the leg, we're seeing a lot of these red papules consistent with palpable purpura. So actually this turned out to be ulceration secondary to vasculitis. And this patient actually had Henoch-Schoenlein vasculitis. The ulcers were sudden in onset and they were coincident with the appearance of these palpable purpura on the legs. And really the best treatment for sudden onset of vasculitis causing ulcerations on the legs is oral prednisone. And this patient responded very well to that. Of course, whenever we see a patient with vasculitis, we have to think what's underlying the vasculitis and the commonest underlying causes are bugs and drugs, that's infection and medications, but also connective tissue disease can cause vasculitis, malignancy can be underlined, and often it's idiopathic. All right, case number seven. When we see an agonizingly painful ulcer, especially in the hospital setting like this, what do we think of? Well, I think calciflax is the immediate thing that comes to mind. What we are seeing here is not infarctive areas, which now have become crusted on the skin, but also ischemic areas of the skin as exemplified by these violations patches here that we see scattered on the legs. So this is consistent with, you know, something very ischemic slash infarctive involving the skin. Characteristically, you walk in the room and if you go to look as if you're even going to touch this patient, they almost jump off the bed because it's so agonizingly painful, these areas of ischemic skin. And calciflax is one of the most difficult things we see. So the most likely diagnosis in this case is calciflaxis. And of course, what is calciflaxis? Well, as you would expect clinically, we've got infarction and ischemia of the skin going on here. So what would you expect to see in the blood vessels? Particularly in the fat, we see blood clots, and that's associated with the deposition of calcium in the blood vessel wall, which gives calciflaxis its name. But I think it's important to think about calciflaxis not only as the deposition of calcium in the blood vessel wall, but also critically this clot that is formed, which is causing infarction of the distal skin. So this is what we see at high magnification. When we biopsy the fat, we see blood vessels in the fat, which have calcium in the blood vessel wall and clots centrally causing distal infarction. Of course, on this lower power view, you can see that blood vessels distally are blocked, and that's why we're seeing ischemia and infarction of the overlying skin. And then this view is showing the coagulative necrosis of the skin as a consequence of this calciflaxis, evident clinically as those purple patches, and then also as the infarction of the skin. When calciflaxis is extensive, or even if it's limited, it does lead to mortality, predominantly because of infection. And of course, it is one of the worst ways to die because your skin is agonizingly painful. Many of these patients elect to go on palliative care because the pain is so actually severe and recalcitrant. Case number eight is a patient presenting with these ulcerations on the legs. This was a patient I saw in the wound care center and was being marvelously managed for venous leg ulcers, but the ulcers were not healing. And why do you think that might be? Well, when we examined this leg, what we see is ulcers that look like they're linear, here, like this. And of course, what causes linear leg ulcerations? There's only one thing that can cause that, and that's external trauma. And it turns out that despite the use of UNA boots on this patient, the patient was managing to put a scratch stick down inside the UNA boot and scratch the skin and continue to cause these longitudinal ulcers on the legs and admitted to it finally. And we were able to get some help with regard to that, and then the ulcers healed up. So whenever you see linear ulcerations on the legs, you have to think factitial or traumatic ulcers of the legs. Of course, trauma can come in multiple ways, not only scratching of the skin, but also external trauma from external injury from other things. So this is an example of a patient who has obviously got erythromelalgia of the feet. They're bright red and hot. And to cool them down, characteristically patients with erythromelalgia soak their feet in cold water and ice. And do they do that sometimes 24-7? And that leads to external trauma, maceration of the skin and any mild trauma will lead to ulcerations of the legs here. So these ulcerations on the feet in this patient that are evident here are primarily due to the maceration of the feet and the constant immersion of the feet in cold water and ice. They're not due to the erythromelalgia itself, they're due to the behaviors to relieve the pain of the erythromelalgia. And it's important that we recognize this as healing of these ulcerations would be critically dependent on trying to get away from that habit of cooling down the feet in iced water. So the pearl is here that trauma and excoriations can cause ulcerations. And in fact, external injury of any kind to the skin can cause this. And I've shown you examples of the immersion foot associated with erythromelalgia. Another example is pressure ulcers, which are direct trauma to the, for example, buttocks, lying in bed all the time, especially when those areas get wet can cause those pressure ulcers. Case number nine of atypical ulcers that I wanted to show you are patient, this patient who presented with ulcerations at the breasts. What was unusual about this patient was that she had received breast reduction surgery. And then following the breast reduction surgery kept on getting abscesses and then which then ulcerated on her breasts and kept on being readmitted through the ER. First of all, to infectious disease for IV antibiotics. And then secondly, to the original plastic surgery service for incision and drainage of these ulcers. And the ulcers seemed to heal, start healing up and then they would restart and she'd represent the ER. And this went on for a few months before they finally called for a dermatology consultation. And what was it that we thought was going on? Let's just go over the story again. This was actually a 53-year-old nurse who'd had breast reduction surgery, subsequent admissions for breast abscesses and ulcerations. And then had had multiple hospitalizations for IV antibiotics and surgeries for incision and drainage. But it actually turned out to be a pyodermic gangrenosa. The ulcers have overhanging edges here which are violations in color and very typical of pyodermic gangrenosa. And turned out that she had a distant history of ulcerative colitis. We started her on systemic corticosteroids for this and the ulcers went from this to this and then eventually healed up that you can see here. Now, pyodermic gangrenosum is one of the most unusual causes of ulcerations. It's recognized clinically. Ulcers start as a tiny pustule which then rapidly ulcerate and then the ulcers expand very, very quickly. And they have a characteristic appearance at the edge with the violations overhanging edge which sometimes appears necrotic and they can be agonizing. And it's important to recognize these as the treatment really involves immunomodulation or immunosuppression and prednisone is the famous thing that works very well. There are lots of different criteria to help diagnose pyodermic gangrenosum to verify that this is the diagnosis but that's beyond the topic of this presentation today. But think about pyodermic gangrenosum as one of the more unusual causes of ulcerations but it's critical to recognize them as they will respond to prednisone or other immunosuppressive or immunomodulatory medications. I want to stay on the topic of pyodermic gangrenosum for a couple more cases because I think they're very illustrative. We saw that patient with pyodermic gangrenosum of the breasts following breast surgery. This was another patient who presented with multiple ulcers on the legs which started all of a sudden and spread up the legs like this. This patient had been recognized to have pyodermic gangrenosum and was put on high dose steroids. And actually when he came to see us he was on 80 milligrams of prednisone a day but the ulcerations kept on progressing. So the question is, what should we do next with him? Some people said that we should put him on double the dose of steroids. Others said we should switch him to other immunosuppressive or immunomodulatory medications. But before we did that, we thought we should do some other things. And what were those? These are just close-ups of these ulcerations. Just to review this story again, this was a 34-year-old with a history of ulcerative colitis now quiescent clinically. Had had recurrent pyodermic gangrenosum in the past but in the past three weeks had developed the explosive onset of ulcerations on the legs like we see here. This was agonizingly painful and he had been working as a bartender but had to quit his job because of the pain of these ulcerations. And again, he had been on prednisone 80 milligrams a day for two weeks before he came to see us. So what would you say is the next appropriate step here? Do we increase the dose of oral prednisone, add infliximab to the regimen, initiate cyclophosphamide or start intravenous immunoglobulin or none of the above? Well, I would say that none of the above because what we had to do was due diligence here. We had to obtain a skin biopsy, make sure there wasn't something else going on that would imitate pyodermic gangrenosum but also assess for his underlying disease which in his case was ulcerative colitis. And when we did do that due diligence, we found that on a chest X-ray, he had multiple nodules and colonoscopy, he had invasive colon carcinoma and on CT scan, he had lymph node involvement from this colon cancer or colon carcinoma. So in him, the explosive onset of the pyodermic gangrenosum was a clinical sign of metastatic colon cancer. And so what the treatment was to send him to oncology for management of that and with management of his metastatic colon cancer, his pyodermic gangrenosum resolved. So in summary, I think I've shown you that, we all know skin ulcerations, particularly on the extremities, the vast majority of them are due to vascular causes, venous, arterial, small vessel disease, vasculitis, occlusion, neuropathic causes. But we as dermatologists have to be cognizant of the unusual vascular ulcers such as small vessel occlusion, like we saw in levodoid vasculopathy, of inflammation of the blood vessels which we see in vasculitis. Then also to be aware of trauma, infection, malignancy, inflammation, connective tissue diseases, drug-induced causes of ulcerations, and then the unusual causes of pyodermic gangrenosum. And how do we approach management of a typical ulcer? I think by history, what medications is the patient on, what's the history of this ulcer is really critical in formulating the reason for the ulcerations. The physical examination can give you a lot of clues and then we have to do testing and that would include a skin biopsy. Sometimes we have to send that for pan culture for bacteria, mycobacterium fungi, as I've shown you because my atypical infections can cause those ulcerations. We do lab tests as appropriate. And of course, whenever we see what we suspect to be vascular ulcers, we do arterial, venous and lymphatic studies. And then again, our treatments can vary enormously. We can do anything from compression to revascularization to giving them antimicrobials to stopping or starting their medications to immunosuppression as I've just shown you. So with leg ulcers, it's critical to make the right diagnosis, treat the right diagnosis, and all the beautiful things we do for skin wounds are great, but you really have to treat the underlying cause in order for them to heal. And that way you can heal your ulcer. All right, thank you very much.

atypical skin ulcerations

Dr. Mark Davis

Mayo Clinic

diagnosis

treatment strategies

case studies

ulcer management