Hi. My name is Alex Dittrich. I'm from Nova Scotia, Canada. I'm in Halifax there. I'm an R5 in Respirology. So I'm going to begin today's talk. So thanks for all being here. I have no financial disclosures. So today's objectives are really to just form a differential for cavitary lung lesions and then identify visceral manifestations of pyoderma gangrenosum, which I realize I give my case away, but that's OK. So I'll start off with our referral. So we had a 58-year-old gentleman who was referred to us for progressive cough and dyspnea. And this was in the context of a recent CT after presenting to the emergency department, which showed multiple cavitary lesions. Just in terms of his relevant past medical history, so this was when he was referred to Respirology. He doesn't really have much in the way of past medical history, aside from some GERD. And then he also had recurrent epistaxis from previous cocaine use. But apart from that, really nothing else. I will note that he had prior incarceration, but that was about four years prior. And he'd had TB skin testing that had been up to date up to this point. He wasn't really on any medications at all. So in the Respirology office, we determined that he had this three-month history of progressive malaise, productive cough, shortness of breath, some night sweats, and sinus infections. And then he also had some weight loss as well. No rash or hearing loss, nothing really to indicate any systemic manifestations of these cavitary lesions. And he hadn't really had any dental procedures recently or no travel. So the differential at this time for us was really knowing that he had these cavitary pulmonary lesions included infections such as your usual bacterial pathogens like staph, strep, TB, NTM, the usual culprits, and then some dimorphic fungi was also, of course, on our differential. Malignancy and then inflammatory causes as well, which I'll get into. So this here is his CT thorax. And this was right before he was referred to us. So you can see in the coronal and axial cuts that he has multiple nodules. And some of them were cavitating and others speculated, mainly on the right side. We didn't really see anything on the left. So I'm going to just take you through a timeline of his course here. So CT was T equals 0. And then about two weeks after his initial CT scan and after seeing us in clinic, we had decided to do a bronchoscopy with BAL. And at that time, he grew staph and strep. And so the patient was started on levofloxacin and metronidazole for antibiotic choice. And then ultimately, we decided to do a repeat CT scan about nine weeks later to see if any of these lesions had cleared up with his antimicrobial therapy that he had received. But in fact, at the CT scan nine weeks later, he actually had new lesions that had shown up and new cavities as well. So at this point in time, we actually opted to bring him into hospital and facilitate a CT guided core needle biopsy. And the biopsy actually showed some organizing pneumonia. And the patient was started on steroids with a plan to taper. And he had done pretty well with the steroid taper plan. He had been discharged from hospital. And a lot of his pulmonary symptoms had started to resolve. But this brings us to T18. So this is at 18 weeks. While he was on his steroids and the tapering for his lung lesions, he actually started to develop these very painful extensive cutaneous leg lesions. And so ultimately, he was admitted to hospital for that at that point. And dermatology was consulted. They ended up performing a biopsy, which showed features in keeping with pyoderma gangrenosum on the histopath. And so at that point, we ultimately decided to do a workup to look at different etiologies of pyoderma gangrenosum, which included extensive serology of autoimmune, inflammatory, and vasculitic causes. Dermatology at that point also decided to start him on systemic steroids to help with clearing up some of these leg lesions, as that is often first line. So I'm just going to talk here for a moment before I bring up the rest of my timeline here. So he was discharged home from hospital and had been doing okay from a steroid taper plan. But then at about 35 weeks or so, he was actually readmitted because the leg lesions got worse after he started to taper. And so dermatology was quite worried about this being a malignancy as an underlying process, given we had done extensive serology and ruled out other causes. And so at that point, they ultimately wanted us to initiate or talk to thoracic surgery to initiate a wedge biopsy to see if we could rule out malignancy definitively before other steroid sparing agents were started. So he had his wedge biopsy, which showed atypical findings for GPA, but it was actually felt to be most in keeping with pyoderma gangrenosum with the visceral involvement in his lungs. I should mention simultaneously, he was actually started on cyclosporine, IVIG, and IV steroids given the extensity of his leg lesions and also his severe symptoms. He was not doing well at home and actually failing to cope. And so at that point, the cyclosporine and IVIG had been started and he actually did really well from that for the first bit, which brings us to 45 weeks. So at that point in time, he was doing quite poorly at home. The leg lesions started to reappear despite the cyclosporine and IVIG as well as his steroid taper. And so dermatology had seen him in clinic and ultimately decided to start him on infliximab, which is one of the treatments that can be used for pyoderma as a steroid sparing treatment. And then at 52 weeks, he had another outpatient follow-up, and this was about seven weeks after his infliximab start, and he had complete resolution of his skin lesions, which is pretty impressive. He'd also had a few follow-up CT scans at that point, and his pulmonary lesions had actually resolved in terms of the cavitations. And then he just had some post-inflammatory residual nodules that had either decreased in size or had completely gone away. So pyoderma gangrenosum, it's very rare, or not rare, it is rare, but it's ulcerating, and it's a neutrophilic dermatosis. It's usually associated with inflammatory causes like inflammatory bowel disease, inflammatory arthropathies, and malignancy, but we only actually get the underlying etiology about 50% of the time. And our patient underwent extensive workup for this, so he had autoimmune markers sent, inflammatory vasculitic. He even had ANCA-negative vasculitic panels sent to our mitogen lab in Calgary, and that had all come back negative. And of course, he had his malignancy was ruled out. Visceral involvement can occur. Pulmonary is actually the most common, but you can have other viscera involved, including vulvar and rectal involvement, and occasionally sinus involvement as well. First line therapy is systemic steroids. However, steroids bearing agents are often required, and it depends really on the underlying etiology, and in this case, he certainly needed them. Pulmonary pyoderma, so it is quite rare, but like I said, it is one of the more common visceral involvements if we do see it. And then symptoms from pulmonary pyoderma can be asymptomatic to having fevers, dyspnea, cough, chest pain, and hemoptysis, so it's really a spectrum. Cavitate and lesions are found on radiography, which can make the diagnosis quite challenging, and to diagnose it, you really need to rule out those other causes first, which included what I had already mentioned. So in summary, my cavitary conundrum, so this is a pyoderma gangrenosum, which is a rare dermatosis, and it usually presents with skin inflammation and ulceration. Extracutaneous manifestations are quite rare, but pulmonary is the most common, like I mentioned, and you really need to exclude other cavitating lung diseases first. So my case really just gives attention to the rare diagnosis, and it really highlights the importance of having a comprehensive evaluation of patients with cavitary lung lesions. These are my references. Thank you. Really interesting case. Any questions from the audience? Yes, please. Alex, would you comment on the finding of organizing pneumonia, and do you think that that was a major hindrance in this case to getting to the actual problem? Yeah, that's a great question. I think it probably did, because I think that those findings were really nonspecific in terms of the organization process, and the core needle biopsy I don't think was our gold standard for getting a tissue, so I think it probably did delay his care a little bit further, although I really think that having him develop the skin lesions is really what helped us kind of progress to the diagnosis later down the line. You don't often see pulmonary pyoderma as the first presenting symptom, and so I think that really put a wrench in the diagnostic process initially. That was a great presentation. Thank you. I've never seen this before, so I'm curious. Obviously, the name pyoderma means skin involvement, right? So what was it about the biopsy that made them think that this was directly related to what was going on in the skin? Yeah, I didn't actually put up the histopathology, because I didn't have enough time, obviously, to go through with my presentation, but I'm not a pathologist by any means. But the way they described it is there were features that were suggestive of a vasculitic process, but they said it was very atypical for it being like GPA, because that was one of our differentials as well. And I think it was just the way that the neutrophils were organized on the biopsy and in conjunction with his leg lesions. That's why I think they went that way with their top differential. One other quick question. Usually, you think of this as being involved with ulcerative colitis, right? So I'm wondering if this could precede that, and maybe you masked it by treating it. Have you thought about that, or has he developed any bowel symptoms or anything like that? Yeah, that's a great point. So luckily, dermatology was on the ball with that as well, and we had ordered a fecal cal, and there was talks of doing a scope with him as well. He'd never had any previous GI symptoms before, and it hasn't to date either. But you're right, it certainly could have masked it, and maybe he's just doing really well because he's on immunosuppressants. But we did do an extensive history, and there was no family history or preceding illness suggestive of that. Cool case. Thanks. Yeah, I agree. Excellent presentation and a really good case. So thank you very much. Thank you. Thanks very much, everybody, for being here today. My name is Tim Rowe. I'm a third-year fellow at Northwestern in Chicago. I do not have anything to disclose. I do want to take a second and just thank my co-authors on this case presentation, and particularly my mentor, Dr. Esposito, who's in the audience today, as well as our fabulous pathologist, Anjana Yaldandi, and our fearless leader, Dr. Tamadi. So lesson objectives today, pretty simple. First, I just want to review a differential diagnosis for a rather common CT finding, right, diffuse ground-glass opacities, but specifically in the case of an individual with multiple myeloma. And then I want to discuss one rather uncommon pulmonary complication of multiple myeloma itself. So our patient presentation. This was a 69-year-old who was a former tobacco user, had quit about 20 years previously. He already had a diagnosis of IgG lambda multiple myeloma, had been diagnosed a few years previously. And he presented to our care, unfortunately, after about a year of subacute progressive dyspnea and exertion associated with a dry, nonproductive cough, and unfortunately progressing to the point of needing supplemental oxygen. He had had a couple of emergency room and urgent care presentations, sort of variable workups treated with steroids, antibiotics, transient improvement in symptoms, but record distance of symptoms shortly thereafter. His exercise tolerance had decreased to the point where he could only walk a couple of blocks at a time without having to take a break. So unfortunately, quite symptomatic at the time that we saw him. And just talking a little bit about his myeloma, it had been diagnosed a few years previously in 2017. His marrow at that time showed 80% cellularity. He did have nephrotic range proteinuria, but fortunately had normal indices of renal function. And at the time that we encountered him, he had been on maintenance therapy with lenalidomide for a couple of years. So as you can see, his examination is fairly unremarkable, really only notable for his oxygen requirement. His laboratory profile also relatively unremarkable, pretty normal indices of renal function. The referring physician had already done some autoimmune serology, so ANA with reflex panel was negative. Ankylserologies were negative, and they had also done a local HP panel there, which was negative as well. A little bit more data for him. So he's restricted. He has a moderate to severe reduction in his diffusing capacity. His six-minute walk distance is below his predicted total of 550 meters, and he did desaturate to 74% on his two liters of oxygen. With that, his echo, remarkable mostly for some moderate pulmonary hypertension, a little bit of LVH and mild diastolic dysfunction. He actually did get a right heart cath before presenting to us, which showed normal left-sided filling pressures in context of that, which will become important later. And he already had a bronchoscopy at the time he saw us, so it was a little bit of a bloody sample, monocyte predominant. Infectious evaluation was negative on that. They did not take any biopsies with that. So here's where I cross my fingers and hope that the CT plays. I'm just going to, before I play this, I'm just going to point out, maybe after I play, there is a left-sided sort of multinodular thyroid there that is known and is unrelated to his presentation, just in case that gets distracting for you. So as we come down, you can see that we have diffuse bilateral, I'm sorry guys, ground glass infiltrates, not really much of an axial gradient, not much of an apobasilar gradient. Importantly, no interlobular, intralobular septal thickening, a little bit of paraceptal, sorry, paraceptal and centrolobular emphysema, especially as you get towards the apices, and then his mediastinal windows. Other than that, thyroid is unremarkable, so no adenopathy noted, no pleural disease. Okay, so putting together a differential diagnosis with the data that we have so far, we have the 69-year-old former smoker who has known multiple myeloma. He's been on therapy for a couple of years, and importantly, he's been on therapy while he's developed these symptoms over the last 12 to 14 months. He's unfortunately had non-resolution after treatment with steroids and antibiotics. He's had a kind of an unrevealing bronchoscopic evaluation, and importantly, in the context of these bilateral ground glass infiltrates, he has a right heart cath that was performed with normal left-sided filling pressures. So at that point, we felt we had sort of more or less excluded some of the more sort of common or atypical infectious causes with the bronchoscopy, as well as the chronicity of his symptoms. Of course, the normal left-sided filling pressures in the context of this illness makes a sort of cardiogenic pulmonary edema less likely as a differential consideration. So our kind of focus differential, he's been on this drug, lenalidomide, for a while. This is known to cause pneumonitis. It can also cause eosinophilic pneumonia, as well as organizing pneumonia, and importantly, it does not necessarily need to occur at the onset of treatment. This can occur weeks, months, even, in some cases, years into therapy. Of course, in the context of his myeloma, we presumed it to be relatively well controlled, but plasmacidic infiltrative disease or another sort of lymphangitic spread of a malignancy was another differential consideration, as well as was an inflammatory ILD, you know, based on the radiographic pattern, potentially a cellular NSIP versus a hypersensitivity pneumonitis. And then finally, although less common, infiltrative disease like amyloidosis was another consideration, as well. And so we are going to cut to the chase here in this histopathology slide, and particularly in panel B on the right here, you can see Congo red staining, which is positive for birefringent deposits, which were revealed to be amyloid deposition. And this was subjected to liquid chromatography and revealed to be AL amyloid deposits, thereby sort of helping us make the diagnosis of alveolar septal amyloidosis as a complication of his multiple myeloma. And so I wanted to take a minute just to talk about amyloidosis associated with myeloma. You know, as we all know, myeloma is not an uncommon disease. It's responsible for about one in five hematologic malignancies in adults. It tends to present in the sixth to seventh decade of life, and amyloid is actually not all that uncommon either. In terms of clinically manifest disease, we see it in about 10 to 15% of patients, but based off of autopsy studies, it's actually probably more like 20 to 25% of patients. And then one in four patients who have AL amyloidosis will have pulmonary disease. You may be thinking this is not necessarily the pulmonary manifestation of amyloid that I'm used to seeing or I'm thinking about seeing, and you're right about that. You know, here's a more typical example of amyloid deposition in the lung. So it tends to cause parenchymal nodular disease. Important to note, it can also cause tracheobronchial nodular disease. It can cause pleural deposits. It can cause diaphragmatic deposits. It can be a cause of isolated hyaluronidic adenopathy. It's much less common, only about 3% of cases that we see. This is kind of another representation of an alveolar septal pattern. So the diffuse alveolar septal pattern is only seen in about 1% to 3% of cases, so much less common to see. And as you can see, the sort of diffuse and really impressive dense ground glass opacities that we saw in ours is not even really the typical pattern that you would necessarily see in that case. It's also worth mentioning that, you know, as goes pulmonary involvement with AL amyloidosis, so goes cardiac involvement. So seeing pulmonary amyloidosis as a manifestation of multiple myeloma is exceedingly uncommon to see without cardiac involvement, as was the case for us. The median survival, unfortunately, with this particular variant of amyloidosis is poor. So median survival is less than two years. So I want to get back to our patient and then continue the discussion a little bit here. So based off of the histopathology, which was reviewed by our pathologist, the diagnosis of alveolar septal amyloidosis with solitary pulmonary disease was made. It warrants mentioning that in addition to involving the alveolar septal interface, there was also evidence of vascular involvement in our case, perhaps providing an explanation for the pre-capillary pulmonary hypertension that we observed in this individual. We don't have a cardiac MRI, which, as you probably know, is the gold standard for excluding the diagnosis of an infiltrative cardiomyopathy. However, there wasn't a suggestion necessarily of significant LV involvement based off of the transthoracic echo. And the right heart cath did not show physiologic evidence of infiltrative cardiomyopathy. So we presume him to not have that involvement. After discussion with the patient, he was started on bortezomib-based chemotherapy. So I didn't have enough time to discuss this in detail here. But really, the evidence basis for use of bortezomib for treatment of AL amyloidosis is based off a case series. The rationale for treatment with bortezomib is you kind of stop the hematologic malignancy in its tracks, and it prevents further amyloid deposition. So it's important to think about when we're counseling our patients that this is not something that would be expected necessarily to reverse disease, but hopefully to stop it in its tracks. Unfortunately, he did not show a clinical or radiographic response to treatment, and he's currently seeking a third opinion at another institution for stem cell transplantation. Now stem cell transplantation, I have not seen it specifically reported for this process, but it warrants mentioning that the initial evaluation by the institution that he referred himself to basically noted that he has such a poor performance status from his lung disease that he's not likely to be a candidate for that. So thank you for coming through this with me and talking about this with me, but this is sort of a common sequela of multiple myeloma, but a rather uncommon manifestation of AL amyloidosis in the lungs. It's important to note, I think, some takeaway points here. Although one in four patients with AL amyloidosis will have pulmonary involvement, and it's not a particularly uncommon manifestation of myeloma, it's rather uncommon to see pulmonary involvement absent cardiac involvement. And so I think the takeaway there is if you see pulmonary involvement with your patients, you should have a low threshold to do some sort of a cardiovascular assessment. Whether that's cardiac MRI, if the patient has evidence of pulmonary hypertension, whether that's a right heart cath, some sort of evaluation is likely warranted in that case. And so unfortunately, this is a variant of this illness that carries a very poor prognosis, and effective therapies for do not really exist. So these are my references, and thank you very much for your attention. Any questions from the audience? So I have a quick question. If you were to have gotten a cardiac MRI and found evidence of cardiac amyloid, would that have changed your management in any way? That's a good question. So I think the biggest thing that it would have would be sort of prognostic significance and really, you know, talking about the morbidity of disease with the patient. Unfortunately, I think the thing that's likely to limit his lifespan will be the pulmonary involvement, just because this specific variant carries such a poor prognosis. But I do think that when we think about the patient's morbidity and what's driving his symptoms, it may have helped us to kind of describe that a little bit more effectively. I do think that we felt that with the physiologic assessment he had with the right heart cath, that it would not add significant additional value. I agree. I just wanted to bring that point out. Thank you. So thank you for this opportunity to speak today. My name is Sarah Mett. I'm a second year fellow at a pulmonary critical care fellow at the University of Nebraska Medical Center, and I have nothing to disclose. So these are my learning objectives that are listed on the slide. To begin, we have a 64-year-old female with seropositive rheumatoid arthritis who is noted to have bilateral pulmonary nodules noted on chest CT in 2018. At that time, she was asymptomatic from a respiratory standpoint, and she denied any prior or current tobacco use. Regarding her rheumatoid arthritis, she was diagnosed in 1989 with a positive rheumatoid factor. Her symptoms included joint pain of her hands, elbows, and shoulders. She also reported morning stiffness that typically lasted about one hour every day. Unfortunately, at that time, her symptoms were poorly controlled despite being on multiple medication regimens for her RA. These medication regimens consisted of etanercept, methotrexate, and adalimumab, tofacitinib, and then intermittent steroid use for acute flares. So regarding her imaging, I'm going to – she had significant bilateral pulmonary nodules, but for simplicity, I'm going to just show the upper lobe nodules and lower lobe nodules chronologically over a few years, and you will see that they progress from solid lesions to cavitary lesions over time. So starting in August, you can see that it is solid, but then starts to cavitate along the development of a new one in the left upper lobe. And now to the lower lobe, you see again it is solid and then begins to cavitate and evolve over time. So during this period, she was worked up to the various, for various causes of cavitary lesions. And when I think about the differential diagnoses for cavitary lesions, I divide them into two groups, infectious versus non-infectious etiologies, which are outlined in this slide above. Regarding her workup, you can see that she had an elevated ESR and a positive rheumatoid factor, but a negative ANA, ANCA, and glomerular basement membrane antibody. She also had her fungal and viral serological workup was negative, along with blood cultures and sputum cultures, both bacterial and AFB and fungal. She underwent bronchoscopy with BAL, which demonstrated the following cell differential. She had negative fungal androgen testing, along with a negative PCR panel and negative bacterial, AFB, and fungal cultures. She was then proceeded to get a CT-guided biopsy of one of her right upper lobe nodules, which just demonstrated necrotizing granuloma, which is fairly nonspecific. So they decided to proceed with a surgical wedge biopsy of one of her left upper lobe nodules, which demonstrated necrotizing granuloma with fibrosis, along with surrounding palisading histiocytes, which I'm trying to show you with the cursor, but it's not showing up. So hopefully you can see that. It's almost like a fence-like architecture surrounding the necrotizing granuloma. So given the fact that that histological pattern was consistent with rheumatoid nodules, the fact that she was still developing new nodules, along with evolution of her preexisting nodules, she was referred to us for further management in trying to get her symptoms under control. So when she presented to us, her symptoms were still poorly controlled, including her joint pain. But one key thing to note at that time, she now had new subcutaneous nodules along the radial aspect of her right wrist, which should note that this presented four years after her initial pulmonary nodules, which is atypical from what's currently in the literature. After review, we found that her tofacitinib was transitioned to liflutamide in 2020, and she was trialed on abatacept, which was later transitioned to cerulamab. So when she presented to us, her current regimen consisted of liflutamide, cerulamab, and prednisones for a few months, for which I thought was an acute flare. We discussed her case at our multidisciplinary conference, which consists of specialists in pulmonary, rheumatology, radiology, and pathology. And after a thorough review of her symptoms, medical history, physical manifestations, workup, and biopsy, it was confirmed that the diagnosis was consistent with cavitary pulmonary rheumatoid nodules. So just a little overview regarding pulmonary rheumatoid nodules. It's an uncommon extra-articular manifestation of RA. The prevalence of solid pulmonary nodules can vary anywhere from .4% to 32%, depending on the study that you're looking at. But cavitary nodules are even more rare, with only a few case reports documented over the last 30 years. And typically, most patients present with pulmonary nodules have longstanding disease, and concomitant subcutaneous nodules, which is key in our patient, because she actually developed pulmonary nodules prior to the development of subcutaneous nodules. Regarding pathophysiology, the idea is that it's usually a result of the underlying disease. However, there is some literature to suggest an association with RA treatment regimens, including the glutamide, which the patient was on. And the idea is that they are inducing and are accelerating the pulmonary nodules. However, the mechanism for which this happens is unknown at this time. In order to adequately make this diagnosis, you have to rule out other potential ideologies, including infection, vasculitis, and malignancy. This includes a thorough workup, along with lung biopsy. So that way, you can confirm the histopathological features of the nodules in question. In terms of treatment, you treat the underlying condition. And noting that some of the medications could be contributing to new or evolving lesions, you may need to adjust their medication regimen for the rheumatoid arthritis. And if you have cavitary lesions, you should also be aware of the potential complications, including pleural effusions, hemoptysis, bronchopleural fissures, pneumothoraces, and abscesses. So going back to our case, we thought that there may have been a connection with leflutamide and the progression of her disease as she was initiated on leflutamide in 2020. And that's when her solid lesions became cavitary. So we decided to discontinue this medication. And we initiated her on azathioprine, continued her on cerulomab, and tapered her off her prednisone. She had a follow-up with us in three, six and three-month marks. And at that time, she was successfully weaned off her steroids. She remained on cerulomab and azathioprine with significant improvement in her articular symptoms, along with stabilization of her subcutaneous nodules. We also obtained chest CT during these time intervals, which also demonstrated stabilization of her lung disease with no lesions, which I will demonstrate here. So here's your upper lesions and your lower lesions. So to summarize, I think there is a few aspects to this case that makes it unique. One, pulmonary nodules are uncommon. And the fact that she had cavitary lesions are even more rare. The fact that she developed pulmonary lesions prior to developing subcutaneous lesions is very unique and actually opposite of the literature that's out there right now. The fact that she developed cavitary lesions despite being on multiple medication regimens for her rheumatoid arthritis. And the fact that we were able to identify a potential contributing factor, which may have been the leflutamide, given the timing and the fact that we were able to get her nodules stabilized and her symptoms controlled after switching off that medication. So I thank you for your time, and I'm happy to take any questions. Really interesting case as well. These are great. I have a question for you. Do you think, in retrospect now, or if you had another case like this later, would you biopsy this, or would you stop the leflutamide and follow? I would say the fact that the differentials for cavitary lesions is wide, and I think you have to rule that out, and especially malignancies. So I would go forward with a biopsy because malignancy is something that you would not want to miss, and it would allow you to look at the histopathology to truly confirm that that's what's going on, and then transition her medications after that. Yeah, that's a good question. I mean, we might have a few patients with rheumatoid arthritis who would be reticent to biopsy just because of comorbidity and so on, but it's a difficult differential. Yes. Yeah. Yeah. Well done. Thank you. Thank you. Hello, everyone. I'm Samridhi. I am one of the third-year fellows at Michigan State University. I have nothing to disclose, but disclaimer if somebody can take a picture because my folks are up hiking. And the lesson objectives today are I'll be reviewing the disease processes that lead to cavitation, understanding the image characteristics of autoimmune lung cavities, and learn in detail about the management of cavities in GPA. So it kind of truly ties very well with the rheumatoid arthritis case that was presented before. So here we have a 40-year-old male who had history of rheumatoid arthritis on immunosuppressive therapy with prednisone and adalimumab, and presented with chief complaint of worsening shortness of breath, nonproductive cough, fatigue, night sweats, and about 20-pound weight loss over three weeks. The laps were significant for slightly elevated white count and set rate of 118 with elevated CRP. The CT chest shows pretty thick wall cavities, and I'll be demonstrating that on the slide later. As far as the workup is concerned, the infectious workup was negative with bronchial velar lavage. The autoimmune workup showed elevated Sienka and PR3 with the titers of 1 by 160 for Sienka. The transbronchial biopsy initially showed non-necrotizing granulomas, but the surgical lung biopsy was pursued since the characteristics of the cavity was really thick walled, and it showed necrotizing vasculitis with Kepleritis consistent with GPA. So the clinical course of this patient initially, obviously, was started on broad-spectrum antibiotics since the patient was on immunosuppressive regimen for his rheumatoid, but after lung biopsy, he was started on Ritux and pulsed-toe steroids for three days, and subsequently they were tapered off over a period of a few months. So over a period of six-month follow-up, this is the gradual progression of his cavities, and you can clearly see that they were very thick-walled to begin with, but now the size of the cavity is kind of slowly coming down, and there's also been subjective improvement in his symptoms. And this is the kind of mnemonic that we use for cavity, which is C for cancer, A for autoimmune, V for vascular, I for infection, D for trauma, and Y for youth, which includes congenital cavities and pulmonary sequestration. And out of the autoimmune, the differential includes GPA and rheumatoid arthritis, and here is the radiological appearance of autoimmune cavities. I'll take quite a bit of time to discuss about these cavities and how we manage them, specifically in GPA. So the first slide is the axial CT, which shows cavitary lesion with mild nodular posterior wall due to GPA. The second one is the necrobiotic nodules, which are usually seen in RA. The third one is the coronal CT scan, which shows stage 2 sarcoid cavity, and the fourth one is the CT scan, which shows stage 4 sarcoidosis. Demonstrating the fibrocystic sarcoidosis with intracavitary myosotoma with an arrow. So I'll go through the classification criteria for GPA. This was recently published in 2022 by European Society, and a cutoff point for more than 5 is sensitive of about 92.5% and has a specificity of about 93.8%. The clinical criteria out of these include nasal involvement with bloody discharge giving you 3 points, the cartilaginous involvement giving you 2 points, the conductive or sensory neural hearing loss giving you a point. And the lab criteria, specifically the CENCA and PR3 gives you 5 point off the bat. So that's what this patient had. The pulmonary nodules or cavitation gives you 2 points, and then granuloma gives you 2 points. What subtracts the points for you is the blood eosinophil count if it's more than 1,000, or a positive test for P-ANCA or MPO gives you a negative 1 point. And finally discussing about how we manage ANCA-associated vasculitis. So if somebody comes in with active GPA or MPA, we need to make sure what sort of manifestation they have. Do they have organ life-threatening manifestation or non-life-threatening manifestation? Some examples of life-threatening manifestations include cardiac involvement, CNS or meningeal involvement, pulmonary hemorrhage, and mononeuritis multiplex. And the non-organ life-threatening involvement includes the skin, myositis, or the sinus involvement. So if somebody has organ life-threatening, we start the patient on Ritux or cyclophosphamide. And if they have non-organ life-threatening, the patient is started on Ritux. Our patient did have a 3-day course of pulse steroids and was subsequently started on Ritux. Usually the glucocorticoid regimen is started along with, and it's tapered over a period of 4 to 5 months. And once the patient achieves remission, the patient is followed upon by the expert care center. Maintenance of remission, and I would like to also mention that there is a new drug that has been added to this algorithm, which is Avacopan. It has been also shown in the recent trial in NEJM that was published in 2021 that Avacopan was non-inferior to glucocorticoids. And you can start them off right off the bat once they get diagnosed. The method how Avacopan works is it blocks the C5 receptor that's present on neutrophils. And the C5 receptor is a, it goes through the pathway of alternate complement, and that's mostly involved in neutrophil chemotaxis to the leading to these cavities and capillaritis and vasculitis and GPA. So the study that was published showed or included about 300 patients in which Avacopan at 26 weeks was non-inferior to glucocorticoids for induction of remission. And it was, at 52 weeks, it was superior to glucocorticoids for maintenance of remission. And that's the algorithm. And in conclusion, I would say that if the cavitary lesions are observed in rheumatoid arthritis, we have to keep a broad differential in mind. As rheumatoid arthritis nodules rarely cavitate. And once they do cavitate, we also have to consider malignancy in mind. So biopsy should be obtained for accurate diagnosis. Thank you. Good morning, everyone. My name is Vani Mulcairetti, and I am a second-year fellow at Thomas Jefferson University Hospital. And today I'm going to be discussing a case of eosinophilic angiocentric fibrosis with likely lung involvement. So I'm just going to, well, first I have no financial disclosures. But I'm going to go straight into our case. Our case is of a 55-year-old woman who presented to the hospital with worsening right orbital swelling and diplopia for four months. She had been treated for recurrent episodes of sinusitis with antibiotics. And prior to developing the swelling and diplopia, she was recently also diagnosed with pyoderma gangrenosa. She had a previous 20-pack year smoking history, no other relevant social, family, medical or surgical history. Her physical exam, aside from the right eye proptosis, was unremarkable. So on presentation to the hospital, she ended up getting a CT as well as MRI of her orbit and sinuses. And I have the MRI images here. The red arrow is pointing towards a, about like four into two into three centimeter mass around the right orbit, which is causing significant proptosis, as you can see. And as well as that, it's also involving the optic nerve, as well as the extraocular muscles. There's also extensive paranasal sinus disease as well. So based off of these images, the differential at the time was, you know, some sort of either like an IgG4 related disease, sarcoid, lymphoma, other malignancy or any other immunological condition. So based off of that, she had a full immunological workup. And I've listed all of the positive results, including an elevated ESR, CRP, ANA, C-ONCA, elevated anti-SSA antibodies, PR3. Her IgG levels were within normal limits, but kind of on the higher end of normal. And her IgG4 were also within normal limits. So based off a very positive autoimmune workup, there was concern if she had any other systemic or organ involvement. And so a CT chest and abdomen, which was obtained. And this is when the pulmonary team was consulted. The CT chest shows a lesion, which the right arrow, the red arrow is pointing to. The lesion is about maybe four into two centimeters. And it was encasing the right epilobronchus, which was causing significant narrowing of the right epilobronchus as well. No other findings were seen on the CT. And to remind you, at this point, she didn't have any pulmonary symptoms or any findings on exam. So we did a bronchoscopy and E-bus. These are the images from the bronchoscopy. Fairly normal airways except for that middle image, which is of the right epilobronchus, which you can see has significant narrowing likely from like an extrinsic compression. So we biopsied that as well as an enlarged 4R lymph node. Unfortunately, the biopsies were non-diagnostic. However, we did see a background of inflammatory cells. In the meantime, she undergoes a resection of the orbital mass as well as biopsies of the sinonasal disease. The two images on the right are from the sinonasal. And the one on the left is from the orbital mass. The one on the left just shows like an inflammatory infiltrate with eosinophils, plasma cells, lymphocytes. The two on the right kind of show this, if you can imagine, it's like this very concentric onion skin world appearance. And it's basically fibrosis. And it's surrounding a blood vessel. It's much harder to see the blood vessel on these images just given the amount of fibrosis that is seen. They did do IDG4 staining. And that came back. I don't have an image of that. But that did come back with 31 cells per high power field. So quite not suggestive of an IDG4 related disease. So based off of the histopathology findings, a diagnosis was made of eosinophilic angiocentric fibrosis. I will say this is not a very clear cut diagnosis. We had a very robust discussion with the pathologist, the rheumatologist, ENT, ophthalmology, and pulmonology. But based off of that very classical onion skin world appearance, the diagnosis of eosinophilic angiocentric fibrosis was made. She was immediately started on steroids and a very prolonged taper, which she's still undergoing. And then received two doses of rituximab to six months apart. And she had good response to treatment without any complications. We did follow up six months later in the pulmonary clinic. And got a repeat CAT scan, which showed improvement in that lesion that was encasing the right abdominal bronchus. So I just want to talk a little bit about eosinophilic angiocentric fibrosis. It's a fairly rare condition. All the literature out there is mainly based off of case series and case reports. It's an uncommon, tumor-factive, benign lesion with just fibrosis. And it typically involves the orbit and the upper respiratory tract of unknown ideology. It was thought to be first described in 1983 as intranasal granuloma faciale. However, this is now its own identity. In 2011, it was proposed to be in the spectrum of IgG4-related diseases. And this was because a case series of five patients with eosinophilic angiocentric fibrosis. Four out of those five fulfilled the histologic criteria of an IgG4-related disease, meaning elevated IgG4 plasma cells, as well as an IgG4 to IgG ratio greater than 40%. As I mentioned, the ideology is really unknown. There's been a lot of predisposing factors that have been proposed, including ATP, trauma, surgery, and immunological conditions. However, none of this has really been supported by any evidence. A very few cases, maybe a handful, have described lung involvement. A few of those have had peribronchial involvement, while others were just kind of clear-cut masses. And as I mentioned, the diagnosis is really based off of the histopathology. There's two states that we kind of see. The first is an inflammatory state, which is predominant of eosinophils, and then we start seeing more of a fibrotic state. And one of the very classical descriptions is in onion skin fibrosis. Surrounding vessels. Very important to differentiate this from other causes, including like GPA and eosinophilic GPA. And that's where the histopathology as well as immunological workup comes into play. And the best treatment based off of the literature that's out there is complete excision. And then immunosuppressants have been used, including steroids and rituximab, with a favorable response. These patients do have a very high risk of recurrence, and literature has shown up to 70% risk of recurrence. So they do need very close follow-up. So basically, just to sum this up, the case I presented, it's a very rare case, in my opinion, of EAF, and then an even more rare presentation of having pulmonary involvement. It may be a subgroup of IgG4-related diseases if it meets the histological criteria. Diagnosis is based off of histopathology and having a multidisciplinary discussion, I think is key in this case. And then treatment is excision and then immunosuppressants. And these patients need to be followed up very closely because of risk of recurrence. And these are my references. Thank you.

40-year-old male

rheumatoid arthritis

pyoderma gangrenosum

right orbital swelling

diplopia

autoimmune workup

eosinophilic angiocentric fibrosis

onion skin appearance