 So I'm going to be talking today about a disease called ocular cicatricial pampagoid, also known as mucus membrane pampagoid, depending on the literature that you read. I found these were used pretty synonymously. So I'll start with a case presentation. This is a 58-year-old male who presented to the VA with a chief complaint of eye redness and irritation. And basically, this has been going on for a long time for many years. But it was a worsening over the past year. He was also noticing some blurred vision that was getting worse over the past year and some skin growths that he mentioned over both eyes that were slowly enlarging. And interestingly, asking about his ophthalmic history, he originally didn't recall really any specific history of procedures on his eyes or any specific treatments. I'm talking about his medical history. The main thing that he did mention was back in 97. He was raising sheep at home. And he was talking about some procedure he did where you have to shove a tube down the sheep's throat. And I'm not sure what it was for, but he cut his finger while doing this and ended up developing this infection called ORF, which is a zoonotic viral infection. And reading about it usually resolves on its own over a few weeks. In his case, a short time after developing this, his whole body started to break out in these blisters. And he says originally they looked like chicken pox. Eventually they developed into a little bit larger Ebola. And they involved the left eye, the medial canthus of left eye. And the skin source, he remembers they were eventually treated. He doesn't remember exactly how. But the gross in his eye never really went away. They persisted. He denied. Since then, he hasn't had any other skin problems. He hasn't had any other problems with mucous membranes anywhere else. He does have a history of depression. Medications, he was on vitamin D, satalaprim, and Ambien. His parents and brother had diabetes. He had a brother with rheumatic heart disease, but no other history of inflammatory or autoimmune conditions. He was a 20-pack year smoker. He raised sheep at home and had pretty recently lost his job. So on exam, he was seeing 2060 and 2070 pinhold to 2040 in both eyes. His pressures were normal. Pupils were reactive. His motility was full. And visual fields were normal. On SLLAMP exam, he did have mild conjunctival injection in the left eye more than the right. And you can see here, he did have bilateral teridia. And in the left eye, he had this anchoring component binding the teridia to the palpiroconjunctiva. His anterior chamber was deep and quiet. His iris was normal. His lens was clear. He did have decreased tear film in both eyes consistent with his complaints of some dry eye symptoms. His fundoscopic exam was normal. So this patient initially was worked up and was consented for trigemiccision. When he presented on the day of surgery, he kind of remembered being in similar situation before. His memory was kind of jogged, I guess he could say. And all of a sudden, he remembers that he's had some sort of procedure on his eye. He was looked up in the Moran records and he was found to be in our system. Or back in 97, he had had a conjunctival biopsy which was consistent with OCP. And he'd been treated for a year with cyclophosphamide. And then after that, he had basically been lost a follow-up and you hadn't been seen since then. So I'm gonna talk a little bit about the disease and then I'll go back to our patient, kind of his course in management. So mucous membrane, Pemphagoid. Again, it's kind of used synonymously in the literature with ocular cicatricial Pemphagoid. It's a rare disease that affects mucous membranes, as you might guess. It leads to blisters and erosions that eventually rupture and then scar and then can contract and lead to tissue damage. This is a rare disease, again, one in 8,000 to one in 46,000. It's hard to know the exact incidents because it's a rare disease and it's tricky to diagnose. Females do tend to get it twice as often as males. There's a mean age of 70. It's pretty rare actually to get it under 60 years old and it is associated with HLA-DR4 and DQ-W3. It's usually bilateral but as we saw, one eye can be more extensively involved. So pathogenesis, this is a type two hypersensitivity which, if you recall, is direct interaction of antibodies against target antigens. And in this case, the target antigens include BPAG2 or bolus-pemphagoid antigen 2 and a pilgrim or laminin 5, those are the main two. This is usually IgG but can be IgA. Then I mentioned this study here. Back in 2002, there was this group that showed that if you had mice that were deficient in mast cells and complement, they still would have this blistering condition if you gave them anti-laminin 5 antibodies so they said that kind of show that this was a direct interaction of those antibodies. So this is kind of just a schematic of the basement membrane with underlying connective tissue and the basal keratinocytes. And you can see laminin 5, it's one of these proteins that anchors the basement membrane to underlying connective tissue. And this BP180, that's the same thing as BPAG2 and that kind of binds the basal keratinocyte to the basement membrane. So either of those can be targeted by these antibodies. As far as staging this disease and clinical presentation, I think it's important to keep in mind that staging is a useful way to be able to communicate where a patient's at with this disease, but it does not necessarily guide treatment. There hasn't been any data or studies that showed it. For this stage, this treatment works best. But it's more dependent on how a patient's progressing over time. So in stage one, it can be pretty subtle, but you'll see subothelial fibrosis and you'll see redness, pain and tearing. In stage two, the hallmark of stage two disease is foreshortening of the fornices. And this can be graded from 2A to 2D depending on how much the conjuring type of fornices are shortened. You can also get goblet cell loss and tear deficiency, mostly due to scarring and closure of lacrimal ducts. Stage three, you get sym blepharone formation, which is basically a fibrous adhesion between palpyro and bulbar conjuring tiva. Or in our case, it was between that teridium and the palpyro conjuring tiva. And stage four disease is when it gets severe to the point that you start to get some ankle or blepharone or some partial fusion of the eyelids, you get frozen. You can get a frozen or fixed globe and you get pretty severe corneal damage. So here's just a picture of some of the foreshortening. You can see on this lower leg, you can see foreshortening and quite a bit of scarring under the epithelium. And again, this is our patient again, but you can see the sym blepharone, which is right here. And again, you might also see it in a lot of other patients, you'd see it kind of just connecting conjuring tiva here. And ankle or blepharone, you can see a little bit of starting to fuse of the temporal eyelids there. And then other sites can be involved. In fact, in mucous membrane temphagoid, the mouth, the oral mucosa is most commonly involved and the eye is second common. People that have ocular involvement, it's about 15 to 50% will also have oral involvement. But it can affect the pharynx, the esophagus, and eventually leads to scarring and contraction of these, which can obviously lead to pretty severe problems. And the skin can be involved. You can get vesicles or Ebola that can hemorrhage. As far as the differential, there's kind of four main categories that your differential's gonna include. Post-infectious problems can cause a similar picture as well as some allergic conditions like atopic carotide, conjunctivitis, or Stevens-Johnson. As far as autoimmune problems, there's quite a few that can have a really similar picture. And there's a few miscellaneous things like severe rosacea or medication-induced. There are a few glaucoma medications that can cause a similar picture, pylocarbin, Timalol, and a few other drops. So to make the diagnosis, we need to use our brains. I thought this was applicable to us at the Moran Eye Center. So really the way to, that was my mid-presentation attention-getter. Hope you enjoyed that one. So this is differentiated. No, I didn't. So this is the way to make the diagnosis. It's basically using the signs and symptoms I mentioned before. You need to pay really close attention for those. And then also with the conjunctival biopsy. And often direct immunofluorescence and indirect immunofluorescence will be done. So basically the way that you differentiate it from other autoimmune problems is this one specifically causes pretty significant scarring. And some of the other autoimmune problems such as classic bulls, pimpagoid, pimpagosin, one ear, IgA, don't cause nearly as much scarring. Also pseudo-pimpagoid or drug-induced pimpagoid, basically the way to differentiate it from that is if you think it's drug-induced, you stop the drug and see if it resolves. If it doesn't, then it's, there's a good chance it's this. And then conjunctival biopsy. So direct immunofluorescence is gonna show a linear band right along that basement membrane under the epithelium and you'll see IgG, IgA or C3. And indirect immunofluorescence can also show circulating autoantibodies against the basement membrane zone. And this is often tested on salt split skin. And depending on, I pointed out those antigens, but depending on where these autoantibodies bind on the salt split skin, you can kind of have an idea of which antigen is being targeted. So here's a picture of a H&E stain of a conjunctival biopsy showing subepithelial Bola formation and underneath you can see there's a scarred and inflamed substantia propria. Immunofluorescence, this isn't path from our patient, but this is what you'd expect to see. So this is where you can see those linear deposits of IgG lining up along the basement membrane. So treatment, the goals are to prevent further damage, basically, you want to stop further scar formation, treat dry eye and maintain normal anatomy and eyelid and eyelash position. So basically all patients that have ocular involvement are high risk and need treatment and careful followup. And again, treatment's based on the speed of development of disease and the speed of scarring and not necessarily on the stage. So someone with stage four disease that you see over many years is not progressing at all, will be treated differently from someone with stage one who over the course of a few weeks is getting worse. So basically you treat mild disease with slow progression with DAPSome. Again, this shouldn't be used in G6PD deficiency and can cause some hemolysis. For more extensive rapid progression, prednisone is often used as well as these immunomodulators, methotrexate, azathioprine and mycophenylate. Cyclophosphamide is used for severe inflammation or corneal involvement. And again, this is what our patient was originally treated with. And a lot of times when people present, they'll be started on prednisone on cyclophosphamide just to stop the blister formation and get the disease under control. Couple of treatments, IVIG has been used in some small studies, but there's no long-term data showing it's safety. And topical vitamin A has been shown in some studies as well to decrease or reverse keratinization. But it's not available as an ophthalmic prep. It's important to keep in mind with the anti-apilagran subtype, there's an increased risk for malignant tumors. So some screenings should be done. Surgical correction can be done. The thing to keep in mind is it's extremely important to have the disease under very good control. If not, you're gonna just induce that much more inflammation, it's gonna lead to that much more damage. And then keratoprocesis or tarserae, if you can be indicated. And communication is really important. So talking to our patient, he actually felt really bad that he hadn't been followed up in so many years. And he felt like it was not made known to him the magnitude of this condition potentially. I think he was pretty fortunate to have not progressed a lot more. But he felt like he should have been explained a little bit more about how a disease can progress and really the importance of good follow-up. There is a lot of prognostic uncertainty. It's basically chronic and progressive with exacerbations but patients can go a long time with remissions. So for our patient, looking back to his records, he had had a biopsy with direct immunofluorescence that did show intense linear deposits of IgG, IgA and C3 along the basement membrane. Then indirect immunofluorescence also did show an IgG basement membrane antibody that adhered on the epidermal and dermal side of the split skin. So kind of binding to both of those. And a weak presence of IgA adhering to the epithelial side. And the doctor that read the path, dermatologist Dr. Zone, said that this is most likely representative of anti-epilagrine type, secretion of pentagoid. So he was started on DAPSome and set up an appointment to follow up with dermatology and a consult was placed with immunology. He was started on FNL. And a week later, he was seen again. He was tolerating the treatment well. His eye was feeling much more comfortable. His visual acuity in the left eye had improved to 2050. So basically this is a rare disorder with chronic scarring. Diagnosis is tricky. It requires kind of clinical judgment as well as histological and immunopathologic studies. And this is treated with steroids and immunomodulators and the prognosis is widely variable. So any questions? Dr. Morshedi, I think systemic malignancies. I couldn't find specific ones, but just general, I think, systemic malignancies. That was what eventually led to the diagnosis, actually. He eventually, he presented with that, almost worked up and had these biopsies and that's when he started on cyclophosphamide. He kind of just thought of it as treatment for the skin condition and didn't really think of it as an eye problem. So that's kind of how he was not followed up for so long. He kind of thought it was taken care of and treated. And so that is what I read too. It's one of the more rare signs. So I thought it was interesting that he had that as well. I think so. I couldn't quite figure out or I was trying to decide if maybe that led to some systemic inflammatory response that was too, I don't know if that sensitized him and led to this or if that was just kind of a red herring, like he said, buccamiflame. From what I read, the sensitivity of that was 80, around 80%.