 Good morning. I'll be presenting two cases on uncommon but important causes of pediatric uveitis. So the first case is a 10-year-old boy that was referred into us with a diagnosis of pan-uveitis after a proceeding upper respiratory illness. He was noted to have optic nerve swelling and anterior chamber inflammation in both eyes. The inflammation would improve with topical steroids, but then recur shortly after being tapered. He did not have a past medical history that was contributory, but he did have a pretty impressive travel history. His parents were ambassadors to the US, and he was currently living in China. And he had also lived in these various countries in his short 10 years on Earth. In addition, parents admitted that he was exposed to stray cats, rodents, as well as unclean drinking water. So he had sought care on while in China and got a pretty extensive laboratory workup, which just showed some non-specific inflammatory markers, such as elevated ESR and amylamemia, and then very disturbing to the parents were these recurrent episodes of fever, arthritis, diarrhea, and some weight loss over the last several months. On presentation to us, the visual acuity has slightly diminished to 2040 in the right eye, 2025 in the left, with normal low pressures. And sit-lamp exam was remarkable for a moderate amount of anterior chamber inflammation in both eyes, as well as posterior sneaky eye and a little bit of atritus. So Color Fundus photos here, we can appreciate a little bit of a hazy view and marked optic nerve swelling in both eyes. So our plan was to expand the workup, including a lot of infectious etiology is given his exposures. And then we started topical steroids and encycloplegia. So the laboratory results revealed an elevated beta 2 microglobulin in the urine. And so I have the normal range is free there in black, and then his value is in red. We can see the beta 2 microglobulin ratio to creatinine was very elevated at 1,500. And of note, the serum creatinine was normal, and he had a normal CBC. So if we're just checking routine labs with the CMP and CBC, you would miss this diagnosis. Oh, a pathology slide, that's never a good sign. Don't worry, I didn't enucleate a 20-20 eye. This is a pathology slide of a kidney biopsy. So this is a kidney biopsy showing chronic interstitial nephritis and with the predominance of lymphocytes and some scattered plasma cells and eosinophils around the tubules. There's also focal areas of tubular atrophy. So this is consistent with a tubular interstitial nephritis and with our known uveitis gives us a diagnosis of tinu. So tinu is rare, comprises less than 2% of all comers of uveitis. But if we're looking at just acute anterior uveitis that's bilateral, simultaneous, and onset, it's at 10% patients. And greater than 30% of these are in patients under 20 years old. There's an increased female to male ratio but this is changing the literature with more males being reported recently. It can occur in all ages, the median age of onset is 15 years old. And typically the kidney involvement happens before the uveitis but in 20% of cases the uveitis can happen first. And then, so the hallmark feature of tinu is the systemic symptoms. They can have arthritis, weight loss, fever, fatigue. The renal manifestations vary from just a sterile pyruria to proteinuria, actual kidney dysfunction, patients can report frequency of urination of urination at nighttime. And then inflammatory markers like ESR, CRP, and a mild anemia. So in some cases the tubular interstitial nephritis can resolve without treatment. However, the renal prognosis is variable with some cases having permanent renal dysfunction even with treatment. So there's quite a variety for the kidney disease. And it's unclear in the literature if the severity of the uveitis correlates to the nephritis. So our patient was treated with oral prednisone. He had the kidney biopsy done by their pediatric nephrologist and they started mycophenolate. His beta-2 microglobulin in the urine normalized within a couple of months and he remained 20, 20 in both eyes. So the second case, this is a five-year-old male that came to us with a known syndrome. Just some questions. Does this tend to recur? So usually when you get an episode suppressed in one of the odds that this is that it's going to work. For the uveitis or the nephritis? For both. For both. So the patients we've treated here have done well on systemic therapy without recurrence and then withdrawn after two to three years without recurrence that may have not. And is there, I mean, anything I've been out with is there is no clear idea what is the cause of this, right? Right, right, exactly. Is it felt as likely an autoimmune type thing? It's autoimmune driven, yep. Possibly also one of these is kind of a viral illness. Exactly, maybe some hand hygiene exposure that happens and then there's probably some genetic predisposition as well. We're actually involved in a genetic study with looking specifically at that. Oh, to see if there may be a genetic risk associated with this. So remember when we, I remember a long time ago, when we call it idiopathic, remember that means it's probably because we're the idiots. So our next case is a five year old that has a syndrome that's known, which I'm withholding at the moment. He was also noted to have anterior chamber inflammation, an optic nerve swelling similar to our other patient. And as we know with that definition from sun classification, that is just anterior uveitis with optic nerve swelling, not pan-uveitis. He had a past medical history notable for a rash starting at age 15 months, as well as arthritis and several joints. He has an extensive treatment history, so obviously already plugged into rheumatology, has been on prednisone and several immunosuppressives. He's currently on topical steroids in both eyes. And so if we're paying attention to the last slide, he has a triad of uveitis, dermatitis and arthritis. Keep that in mind. On presentation vision was good, 20, 25 in both eyes, mildly elevated intraocular pressure in that left eye, possibly from the top of steroids. And he still had some mild anterior chamber inflammation despite QID and prednisone and mild betritus. So this is an optosphoto of the right eye. We can note the marked optic nerve swelling with some peripapillary hemorrhages. It's faint, but there's a few small hypopigmented corioretinal lesions in the macula. We can see one out here as well. So this patient indeed does have pan-uveitis, so anterior chamber inflammation, vitritus and corioretinal inflammatory lesions. The left eye shows optic nerve swelling. We have a macula showing swelling of the optic nerve with fluid extending into the macula. And we appreciate just the glimpse of that optic nerve swelling in the left eye as well. Fluorescine angiography shows a hot nerve and some peripheral fern-like retinobascular leakage in the right eye, similar in the left eye. And then an ICG does show these hypoflorescent spots in the macula on ICG corresponding to the spots we saw on exam. So this is just my quick shout-out to Danielle. All of these photos I showed you were done in clinic on a five-year-old. So no exam under anesthesia. He happened to be a very cooperative five-year-old and we have a great integer, so thank you for that. So what is this? This is called Blau syndrome. It's also known as juvenile systemic granulomatosis. It's an inflammatory disorder comprised of this triad of adermatitis, which typically is the first sign. It's a scaly rash over the torso and the extremities when they're very young. The arthritis is typically a boggy synovitis affecting the wrists, hands and feet. And then the uveitis, it's normally a granulomatous pan-uveitis, which our patient had. And other organs can be affected, like liver, heart, spleen, kidneys, but typically not the lungs like we see in sarcoid. And age of onset is under four years old. So we know this is caused by a mutation in nod 2. This is a codes of protein involved in immune cells such as dendritic cells and monocytes. It's inherited in an autosomal dominant fashion. However, there is a non-familial version, which is known as early onset sarcoidosis. And this happens in those without a family history, but it's a spontaneous mutation in the same nod 2 gene. Do we know what the penetrant says if you have the gene? I don't know. Can you answer? Is it 100%? Yeah. And so this patient actually, it may be early onset sarcoid because he had a biopsy and the gene mutation, but he has no family history of it. So technically, this may be early onset sarcoid rather than blout. So there's some non-specific inflammatory markers to look for, but these can be seen in a variety of other etiologies. And the treatment, like with much of uveitis, is oral steroids and immunosuppression. So our patient was restarted on his oral prednisone when we saw this eye exam. He had recently had his methotrexate added back to the humerus, so we were waiting for that to work. And he remained 20-20 at the last visit as well. And this was his OCT, much improved. And so some take-home points. Not all patients with the extensive travel history we saw end up having infectious uveitis. Remember these syndromes of tinu and vlau in young patients with systemic symptoms. And then don't forget to check the beta 2 microglobulin in the urine, not the serum, and just checking if the CBC and CMP would miss tinu. So I'm assuming vlau syndrome is a lifelong problem. I mean, this is. And overall, with good treatment, I mean, is it a lot like sarcoidosis, as far as the other? But vlau is typically much harder to treat. And the uveitis in vlau, typically, is very difficult to treat. Often with a biologic. In our experience, it's been controllable. But in other people, it's been a lot of trouble. And I've had to use multiple biologics. It's not an easy uveitis to treat. I would imagine there's enough complications associated with all of that, then, that overall survival is probably curtailed, I mean, it's. I think there's that. We don't have any information on that. Turns out that with most immunomodulators, you're not. So to change. So the idea is to reset their immune system by suppressing them long enough so that they're in remission, that's a difficult objective to achieve. Thank you.