NIH CLINICAL CENTER GRAND ROUNDS
Episode 2010-14
Time: 1:01:56
Recorded April 14, 2010
Contemporary Clinical Medicine: Great Teachers
Mysterious Cases
Mark C. Henderson, MD
Residency Program Director
Department of Internal Medicine
Associate Dean for Admissions
University of California-Davis, School of Medicine
ANNOUNCER: Discussing Outstanding Science of the Past, Present and Future - this is NIH Clinical Center Grand Rounds.
(Music establishes, goes under VO)
ANNOUNCER: Greetings and welcome to NIH Clinical Center Grand Rounds, recorded April 14th, 2010. Today, a special "Contemporary Clinical Medicine: Great Teachers" Grand Rounds. We'll hear from Dr. Mark C. Henderson, residency program director and associate dean for admissions at the University of California-Davis School of Medicine, who will discuss "Mysterious Cases."
We take you to the Lipsett Ampitheater at the NIH Clinical Center in Bethesda, Maryland for today's presentation.
HENDERSON: It's an honor and pleasure to be here. I appreciate the effort given to me this morning. Dr. Homan taught me about stat 1 mutation deficiency. So I learned a lot already today. So hopefully this will be my approach to try to share my thoughts as I think through these cases. I'm a baseball fan and if you hit 333, you're a great hitter. So if I get 1 out of 3 I’m going to feel like an all-star. I appreciate Dr. Cohen's hospitality and thank you for inviting me. I don't have any disclosures. That's normally what I have to do at this point.
So objectives today. I think that my goal really would be to just try to demonstrate some aspects of a systematic approach to clinical thinking to solve patients that are unknown to the clinician. And I’ll talk a little about some clinical reasoning concepts but this will be embedded into my comments.
A 32-year-old man was brought into the emergency department after a head on automobile collision. There was no obvious significant trauma. He said he felt well except he was shaken up and a little bit dazed. So I guess the only comment I would make here is when you think about somebody who has a collision that's presented to an internist, you have to think about or ask yourself why did he have the collision? So I would start thinking in my mind a little bit about things that would cause someone who is driving to have sudden loss of consciousness. So I would be thinking about seizure, I would be thinking about arrhythmia and so I would be thinking about those kind of medical causes rather than just he got hit by somebody. Texting, there you go. In California it's illegal to text. So but we have drivers of subways that is still continue to text and cause accidents. So it's quite a problem any way. So I would be wondering about if he had other cardiac symptoms prior to the event. So I would be focusing on that.
On physical exam, his temp was 37.3, blood pressure was 134 over 86, pulse rate 97 and respiratory rate of 18. He had no evidence of head trauma. Pupils were equal, round and reacted to light and accommodation. On cardiac exam he had rapid rate and no murmur was heard. On the lung exam he was clear. His abdominal exam was soft and nontender and no masses and bowel sounds were normal. On skin examination he had bruises on his chest and seatbelt distribution. So in terms of thinking about the physical exam not much here. What I would want to know more about is a neurologic exam. I know that's an uncommon entity these days. I would love to see that if that was done. I would also like to ask him what happened. But I guess -- I don't know if we skipped over that because you're hiding that from me.
On neurological exam he was alert and oriented. Cranial nerves were normal and no neurological finding. In terms of the motor vehicle accident he was driving on the road and he did not pass out. Did not have or experience chest pains. He was completely quote/unquote, normal, and somebody from the head on swerved and hit him.
Okay. So that throws out my prior theory. So, hmmm. Somebody hit him and never lost consciousness and never had any tonic colonic movements. All right. So I think what I would sort of focus on at this point is a brief look at potentially exacerbations of something. So he's completely normal, and does he remember the event?
Yes. He can tell you start to finish? Yes.
Alright. I think this just lays a little bit of the groundwork. Because I haven't found a chief complaint. He doesn't have a chief complaint. So okay. That's why I'm struggling a bit here. When you look at cases I think most diagnoses are made if you look at the literature, but 70% of the time the diagnosis can be made in the clinical history. That's why we emphasize the present illness and only teach medical students how to take a history. It's not great data but half or more of cases can be summed up in the history. That's why it's so important. I'll get to the chief complaint later.
So he had laboratory work up done and had hemoglobin of 14.2. WBC 9.7 with normal differential. Platelet count was 500,000. He had an alt elevated at 948. And his total bilirubin was elevated. All other chemistries were unremarkable and a urinalysis done was normal as well. So, I'm assuming you're not going to give me a chief complaint.
Let's talk about the liver tests. So if you think about this, the striking abnormality here really is the liver test abnormalities which I would describe as a mixture of hepatocellular damage with an AST of nearly 1,000 and cholestasis. Now my initial thought would be, he had trauma. He had injury to the abdomen. The seatbelt around his liver could easily cause that. That bothers me a little bit that that would explain all of this because alkaline phosphatase is an enzyme and needs to be induced. You can't immediately raise your phosphatase from a traumatic injury.
So I guess I would be thinking along the lines of, does this gentleman have some type of underlying liver disease-causing this, not just explained by trauma. So I guess my next step might be again besides asking him questions like has he turned yellow, does he have itching, any signs or symptoms of chronic liver disease, I would want to know that. Subsequently, I would then want to proceed to some type of imaging of his liver, I think would be the next step, I would undertake.
So the next step, liver ultrasound was done along with a 3-phase ct scan of the abdomen. Both were unremarkable. The patient was then admitted for overnight observation. He was initially lethargic but steadily improved throughout the admission. On the following day he had repeat liver tests done. When the alt improved to 676 and AST improved to 474.
So the reason we do ultrasonography when we evaluate someone with liver dysfunction has to do with wanting to understand whether there is obstruction. It appears there is not. We want to be looking for intraductal dilatation or extra ductal dilatation. He has neither. It's not completely sensitive for all kinds of liver abnormalities. But now this makes me think about a couple of things, things that where profusion is interrupted of the liver and rapidly reestablished, ischemic hepatitis. You can get transaminases in the 1000s which rapidly reduce over the subsequent few days as profusion as reestablished to the liver. I think about viral hepatitis. Although again, I don't know what this has to do with this motor vehicle accident. And again, I still worry about the spots as representing some type of other chronic long-standing liver disease. What would I do next? His lethargy I would want to know if this could be a reflection of hepatic failure, if this could be hepatic encephalopathy. His liver function was normal, if I recall so unlikely to be that. But you can have hematic encephalopathy with acute liver failure.
I would think about acetaminophen, and ask him if he is taking Nyquil, which has 5 grams of acetaminophen. Those are the kind of things I would be thinking about. So he was not taking any specific medicines.
He was then discharged on the following day for follow-up with a GI consultant. Approximately a week later, he presented to the GI consultant complaining of malaise, dark urine, light clay-colored stool, had yellow sclera. On repeat biochemical examination had alt of 1300 and AST of 1400 and a total bilirubin of 7.2.
So he didn't get better. I guess my suspicioning is there may have been some type of chronic liver disease is probably correct. It appears there is some abnormality -- again I would describe this as cholestatic jaundice or abnormalities. The differential diagnosis, when I see this above 1,000, I think of a short list here, when you think about clinical thinking, I think that's one way to do a differential diagnosis, take the abnormality that has the shortest list of possibilities.
So when I think of transaminase over 1,000, I think viral. Hepatitis b, hepatitis a can cause transaminase in the 5-10,000. I think ischemic, that makes no sense with this because he's back to normal, his blood pressure is normal, the trauma is gone. I think about actually biliary disease. If you have a large common duct stone or an obstructing stone that for some reason is expulsed into the duodenum, if there is obstruction, you can have transaminasees go up to 2-3,000 and rapidly fall to normal. We ruled that out by ultrasound. He doesn't have that.
The last thing I think about is two more things, toxins, acetaminophen. And mushrooms in northern california where we have certain people who like to eat wild mushrooms. I think about the aflatoxin of which we haven't seen a lot of cases recently, that's becoming less common. That doesn't make sense with the story here. I would want to ask him about, is he a guy who eats herbal -- is he a health food nut?
And then the final thing I would think about in a young person with this is autoimmune. Hepatitis. Autoimmune hepatitis can cause transaminasees in this range. So I would be thinking about the idea this could be a reflection of a chronic illness or autoimmune disorder like hepatitis.
So further history. He is currently single. Not sexually active. No alcohol history. No tobacco history. He is recently graduated from Yale law school suma cum laude. Don't know if that helps.
Wow. Nothing is coming to me about the law school. So and it sounds like he's not an herbal guy. Doesn't take supplements. He isn't a bodybuilder taking androgenes. He is not. When you think about cholestatic liver disease, medications are really a very common cause and we always have to make sure that we go to the mat and ask multiple times what the medication history is. Try as we might to figure out whether it could be something that could be contributing. So in the absence of that, what else are you going to tell me?
He is not on any medications and nor did he have any recently.
So viral hepatitis, exclude that.
He had a viral serology done. All were negative including a negative hepatitis AGM. And negative for antibodies of hepatitis b core and negative for hepatitis c antibody. He did have a positive anti hepatitis b surface antibody, and he was HIV-negative as well.
So as hopefully all of us in the room are hepatitis b surface antibody positive. So this reflects the immunization of which consists of the surface antigen essentially recombinant. I was talking to some students the other day about the hepatitis b vaccine that I received the one that all the young people receive. Back in the day, it was pooled serum from many, many people and patients and caused all kinds of problems. But now it's recombinant technology, an advance of modern medicine.
So he doesn't have viral hepatitis. He probably got vaccinated and I still would be thinking in my mind about autoimmune hepatitis. That's a tough diagnosis to make sometimes. Antinuclear antibodies – we always think about antismooth muscle body as being associated with that illness. Both of those tests are not sensitive for autoimmune hepatitis. 60% maybe on the ana smooth muscle even less.
So you have to think about –I would order those two tests. The most sensitive test for autoimmune hepatitis is the s hep. So 60% will have a polyclonal gammopothy. So I would start with those tests at this point. I would also think about a liver biopsy. I would love to give a liver biopsy, depends on what rapidity you can attain that study. More extensive history. I always like that.
So some additional information. After further probing, he admitted to daily heroin injections since the age of 14. And more recently, he started injecting with a new person.
Wow. So surprising. But again, so I suppose this is a medication of sorts. Heroin. I'm not familiar with the idea that heroin could cause liver failure or cholestasis. It's just not ringing a bell for me but I would look that up and figure out if it's possible since it seems like- he's a daily injector. When I think about chronic heroin use, I think about nephropathy. He didn't have any perineuria. So I'm still not buying that this is from heroin.
I still like an autoimmune disorder of some type of young person. In a young person. So I'm assuming you wouldn't have done a liver biopsy without me knowing. Let me know. Let me think about what tests. I'm going to guess on the serology. The other possibility as we think about this could be he could have primary biliary cirrhosis although he didn't have any ductal abnormalities in the ultrasound. I'll go with autoimmune hepatitis. So I guess it is an antismooth muscle antibody, positive.
So he had hepatitis ccpr done and was positive for virus in serum. So the diagnosis was acute hepatitis c.
if you think about hepatitis c, we think of that as a chronic intermittent hepatitis which doesn't cause such a high degree of this.
So identification of acute hepatitis c infection is often rare as oftentimes patients are asymptomatic. The antibody itself is only positive in approximately 50% of patients. And patients who are presenting with acute hepatitis c infection because serial conversion incurs 8 weeks after infection. A lot of times the alt will peak before the presence of
Antibodies of hepatitis s.
Treatments and response rates are different. And acute patients that are treated with interferon, 90% obtain a sustained virologic response when treated before 16-18 weeks whereas once chronicity occurs after 6 months, the response rate is 55%.
This is analogous to the hiv serum conversion syndrome. So acute hep cv infection is not -- I think we probably missed this. We don't see it. And that's why I missed it. But this is a great case.thank you.I know I'm two minutes over. That's 21 minutes. So I'll take the next hypothetical situation from the speaker.
QUESTION: [OFF MIC]
HENDERSON: The question was, could the thrombocytosis -- he had a platelet count of 513, could that be inflammation. And I would say chronic inflammation, although acute inflammation could also cause that. But again I was thinking along the lines of a chronic inflammatory condition. Not really an acute one. Once in my head, eliminated hep b and hep a, and this is all about pattern recognition. If you have hepatitis c, acute infection on your list of things that causes acute hepatitis, which I tend to put that lower down. AST at 200, 300, 400, I might have thought about it but 1,500 is why I put that down lower. So yes, thrombocytosis, inflammation, mostly.
Any other questions or comments? Anybody else seeing this kind of acute hepatitis c? Alt of 1,500? Impressive. Thank you.
[New case study] this case is called a pain in the back. It’s about a 42-year-old man who presented to the emergency room with severe upper back pain and difficulty walking for 2 days. He noted leg weakness and numbness in his right leg greater than left and difficulty maintaining balance. One day before the onset of his pain, he had lifted a heavy piece of furniture. He also noted mild right shoulder weakness.
So, the comment about back pain, how common is back pain? Wow. I mean, in your clinic, you see low back pain every day. It's extremely common clinical condition and I think the big question when you take a look and you try to diagnosis someone with back pain, 80% of the time back pain is going to be due to -- anybody know? Musculoskeletal strain. Ligamentous strain, mechanical low back pain. Those are group of diagnosis where it's not really anatomic but it's a soft tissue injury. The question is, what are the warning signs that something else is going on? Something more sinister?
We know there are systemic illnesses that present as low back pain and then there are neurologic illnesses.so the key element to keep in your mind is this going to be one of those unusual causes of back pain? When you're in cpc or in this format, the prevalence of unusual causes is higher. But I want you to know in clinical practice, most cases of low back pain you don't do anything except reassure them because 80-90% resolve after 4-6 weeks. Even disc herniation. So you need to have in your mind warning signs or features and there are several. One is age. Age, the older the patient is the more likely they are – a third category is metastatic disease of spine. I won't mention that here because he's not that old. But the other two sorts of infections can present with low back pain and then neurologic catastrophes.
So when I think about the warning signs to me are fever, if he doesn't report one. Injection drug use like our last guy. I would certainly want to ask. People who use injection drugs have a much higher likelihood of developing complications of staph, in this case it would be a vertebral abcess. So I always want to know about fever, injection drug use, immunocompromised HIV infection or risk factors and then finally, neurologic symptoms. So if I look at this history, I see numbness in the right leg verses left leg, difficulty maintaining balance. Right shoulder weakness. We have multiple neurologic complaints. It's going to be a case where there is a more sinister cause of back pain.
And so I would want to clearly focus on the exam on the neurologic exam. I'd also want to ask about bowel and bladder in continents. I think about a cord compression and losing function over the next 1-3 days, you need to intervene and evaluate patients very quickly. So I would do a careful neurologic exam quickly and proceed to imaging quickly. Which is not usually what I say. But in this case -- go ahead.
So he did not complain of urinary in continence or urinary retention. He complained of constipation for two days. He had no fever and had no recent fever. He had experienced a 2 kilogram weight loss over the past few days and increasing abdominal distention and discomfort. He denied any respiratory symptoms or chest pain. No headache and no visual changes and I will reiterate his back pain was in the upper back.
So I should add to my list of red flag that is I mentioned last is that when people have mid thoracic or upper back pain, everything I said previously pertains to lower back pain. That's most of the literature on how to assess back pain has to do with lower back pain. When you think about thoracic, the prevalence of sinister causes is much higher. Two kilogram weight loss. So that's 5 pounds over a few days? I don't know what to make of that. Interesting. No cough just chest pains. His age is 40? 42. So, again I'm thinking about a neurologic disorder. The absence of fever while reassuring in a sense that the likelihood of a bacterial infection involved in the spine is lower, it's certainly not sensitive. You can have vertebral abscess without fever and you can have all kinds of other fun organisms as many as are around today. All kinds of organisms can be involved and not cause fever. I would be looking at the physical exam, neurologic exam and I'm going palpate the spine because there is some diagnostic value vertebral tenderness for vertebral osteomyelitis. It has some specificity for increasing the likelihood of vertebral osteomyelitis. So I'm going to palpate his back and do a physical exam.
His past medical history -- injection drug use! He had untreated hypertension. He said that he was HIV-negative one year before. He had a history of a gunshot wound to the left knee. He was injection drug user for many years but had stopped using injection drugs since he enrolled in a methadone program 18 months before. He drinks a 6 pack of beer per day and he was a truck driver who is intermittently employed on no medication.
Except for the methadone, right? So I think here again, active injection drug use would be a predisposing factor for organisms that live on the skin, staph and strep, to cause infectious complications like osteomyelitis involving the spine, vertebral abscess, et cetera. It's hard to postulate that if he was really abstinent or clean for 18 months that would be what is going on. But I'm going to not dismiss it. I guess you know, in thinking about his risk factors, I would still be very concerned about that history and so I would be very paying a lot of attention and looking for infectious complications of the spine.
On exam, he was 97.6 and blood pressure was 142 over 101. Oxygen saturation of 99%. He appeared older than his stated age and he was in mild distress and pain. His exam was normal. His pupils were equal. His cardiac and pulmonary exams were normal. On abdominal exam he was distended and normal bowel sounds and mild generalized tenderness with no rebound or guarding. No palpable liver edge or spleen tip. He had suprapubic illness to percussion and no peripheral edema.
I guess what I would say on this is the suprapubic illness could be a sign of urinary retention. So I would be concerned about that and really want to examine this.
He had no skin rashes. He had shotty bilateral adenopathy. He had marked tenderness over the lower cervical and upper thoracic spine and his cranial nerves were normal but he had mild proximal right upper extremity weakness and moderate left lower extremity weakness, proximal and distal and profound right lower extremity weakness. Both proximal and distal. He had saddle anesthesia and diminished rectal tone. His deep tendon reflexes were normal in the upper extremities in the lower extremities he was hyperreflexic. His right plantar reflex was upgoing and was equivical on the left.
So we could talk all day about this exam. So, clearly the things that jump out to me, the adenopathy, less than one centimeter, that's not a concern. It's very common. It's not necessarily pathologic. We'll think about it as we think about lymphoma as a potential cause. Because certainly that could present in the spine as well. The tenderness over the spine really suggests to me or makes me worry that as I said earlier, about vertebral osteomyelitis. If within the vertebral body, you percuss the spine and get tenderness. It's cervical and upper thoracic spine and process system. So that's going to make me jump to imaging of that area very quickly. The rest of the exam, the most concerning thing to me is anesthesia, signs and symptoms of basically of a neurosurgical emergency. So I think you're talking about losing very critical function if there is some involvement of the sacral area. With that, it can be caused by infection involving the cord. Usually the cause is metastatic tumor but it's a neurosurgical emergency. So again, hyperflexion in the lower extremities. This implies to the cord lesion. I'm going to jump to imaging MRI of the spine. And I would probably image top-to-bottom because he's got cervical tenderness, thoracic tenderness and then this sacral. This could be a reflection of a higher lesion. So if I was going to have to pick -- I'm sure to MRI the whole spine but I'm most worried about the higher up stuff. This could be accounting for everything.
His white blood cell count was 8.8. Hemoglobin 11.7, platelets 220. Creatinine 11.12. 15 was 35.5 both elevated. AST was 238. Alt92, alkphos155. Albumin was 2.7. His urinalysis had 3 red blood cells and 20 white blood cells. So as I look at this he has a mild anemia. Not too excited about this. Low albumin. Probably a sign of chronic inflammation. It's a very common finding the problem with SED rates is they are very nonspecific. However there is a little bit there to suggest that a rate of above 100 has some diagnostic value in terms of thinking about a couple of illnesses, mainly deep-seated bone infections or deep seated vascular infections. So endovascular infections like osteomyelitis and then TB classically causes very elevated SED rates when it involves the bone. The urine, pyuria makes me think of a couple of things. I'm going back to vertebral osteomyelitis. If you think about most cases, they originate either from injection drug use or in a non-injection drug user, the urinary tract. So they are seated from a urinary tract infection, local extension to the spine causing vertebral abscess.
The other possibility to me, I think about endocarditis, if the guy is still using drugs he could have that with a complication of embolic, essentially infection, metastatic infection involving the spine. Almost all of those patients have abnormality urinary tract issues. So I'm thinking about endocarditis, vertebral osteomyelitis. My next step would be MRI of the spine, blood cultures, and I would get a neurosurgical consultation. We need to hurry up in terms of therapy. Sometimes we can't wait to make a diagnosis. This is one of those cases in which you can't wait to make this diagnosis. You have to hurry.
So here is the mr. So the MRI was from top-to-bottom. MRI of the t spine showed epidural collection extending from t3-t5 with spinal cord compression. A section lesion causing mild spinal stenosis and cold compression from T9-T10.
So I would want to involve the neurosurgeons at this point to see if this would be treated surgically. In terms of outcome, it tends to be improved with early decompression. So you would do a therapeutic and diagnostic procedure together which would be a laminectomy or some looking at the spine, incising the area, looking for an abscess and then -- you said the cord -- there is pressure on the cord. I would be thinking about an infection. He doesn't seem sick enough to have staph. I would think of a different organism, a more indolent organism, although I think staph is a strong possibility. Again TB involves the spine. If you think about presenting CPC. If you don't say TB, it will be an error. Because it's one of those diseases that is can involve the spine. This is very consistent with TB of the spine. I am trying to think of what else I would add. Other bacteria. Hopefully the blood cultures were done and maybe they are cooking. I will point out on the MRI that there was no bone involvement. There was just epidural collection. Again epidural abscess, same bacteriology. And that is what it appears to be. It doesn't look like a tumor. Although I could guess in a young person I would always want to keep lymphoma on my mind. Especially with shotty nodes.
Was other imaging done? Is there intraabdominal or thoracic? Thoracic is eventually other imaging. The diagnostic procedure is probably some type of aspiration of the epidural space or perhaps a surgical IND. One of those two things. So I have to put my nickel down here, what I think it is, right? Or do I have another chance. Do I? All right give me another chance.
[LAUGHTER]
So the patient underwent emergent laminectomy and cord decompression and in the t2-t5 ep during space there was a collection of thick gray fluid which was debrided and he was placed on triaxon and vancomycin.
Blood cultures? This is still hospital day one so they were drawn and pending.
So in terms of organism I'm thinking about organisms that perhaps present subclinically so I'm still liking TB. This could be a number of bacteria. Again, I don't know how I would
Sort of tell. I'm trying to think about – did you go back and ask them about the injection drug use? Is he still using?
there were some elements of history on which he was not entirely clear. So he may have still been using.
I mean, there is a whole host of infections that could cause this. And I'm trying to think of what I would put my dime down on. I still think the most likely suspect is strep and staph or some skin organism that has been injected into the circulation and involving the spine. But that's usually not the answer in a conference like this. So I'm going to go with TB. Okay.
So diagnosis was made. And the grandstand -- you did say lymphoma. Grandstand of the collection revealed no organism. Cultures were negative. Pathologic review of the collection revealed high grade b-cell lymphoma and turned out to have been HIV positive with cd4 count of 157. He also had chronic hepatitis b and c. So that's a classic high grade lymphoma associated with HIV infection in the early years. There is a lot of that around. It has to do with epstein bar virus or maybe --
So in the hospital course, he had a staging ct which showed retro peritoneal mask with abdominal retro peritonealopothy. He had right urethral obstruction. He had mild right nephrosis, narrowing of the ascending colon and deep venous thrombosis of the common temporal vein. His bone marrow biopsy was negative. He began radiation therapy from the thoracic spine and given anticoagulation for his thrombosis. His inr bounced around but was generally subtherapeutic. On day 9 he developed acute left eye blindness and later in the day, collapsed with cardiac arrest as hemoglobin had during the resuscitation was found to have gone from 12 to 5.one. He died after multiple efforts at resuscitation. There was no autopsy but it was thought that he may have had an acute hemorrhage on anticoagulation. Just briefly about epidural lesions in patients with aids. In one series of 55 patients with aids and neurologic symptoms and abnormal mris, 15 out of 55 had lymphoma. So as you mentioned, it's not an uncommon diagnosis in patients with HIV.
So, again, I have to get this last one to get my 333.
Let's see, again the teaching points are relatively straightforward. When you have neurologic symptoms and signs and back pain, you need to be very aggressive and move quickly. Lots of diseases we don't have to do that. It sounds like in this case that was done very appropriately and an unfortunate outcome. This is a very difficult tumor, very poor prognosis even though we know how to treat lymphoma, it's a poor prognosis no matter you what do.
The anticoagulation issue is interesting to me. There is an emerging literature. We know about the association between cancer and thrombosis. It's very, very well-worked out. But there is also, if you look at the literature, there is also an association with bleeding. So patients on anticoagulants who have cancer are more likely to bleed than those who do not. So it's a double edged sword when you treat thrombosis with cancer. They have a very high risk and higher bleeding rates. So something to be really cautious and careful about. We tend to use initially intravenous heparin because we can turn it on and off. Although that is going away. Everybody is looking liquid heparin which is great. It's been associated with lower mortality from thrombosis in cancer. The problem? Once you give it, it's harder to turn off and it lasts. So any way. I got keep going. Sorry, fire away.
The final case. I had nothing to do with the title of this. A 30-year-old man was in good health until four months ago when he developed bilateral red eyes with associated photophobia and no change in visual acuity. These symptoms improved but didn't resolve completely with eye drops. He saw an outside ophthalmologist. One month prior to us seeing him, he had migratory joint pain and swelling in shoulders, knees, wrists and small joints of hands. The joint pain and swelling would come on and then be fairly intense for a day or so and then resolve only to reappear in a different joint a few days later. So migratory arthritis. He had noted night sweats. About a 10 pound weight loss over the past month. He had developed skin lesions a few weeks ago mildly tender on his fingertips and elbows. And I'll show you a picture in a moment. And additional history, he had history of chronic sinus problems since he was a teenager. Over the last year he had intermittent nose bleeds. He denies systems pretty much negative, specifically no headaches or abdominal or urinary complaints.
So, here we have a young person with red eye, bilateral red eye, and joint symptoms. As well as some constitutional symptoms. So as I think about this case, whenever I see red eye in a young person, again, most common cause of red eye, conjunctivitis from allergic, sometimes bacterial, but again in a cpc format, it won't be what this is.
So you think about red eye. The more sinister causes of red eye, I think about uveitis. Inflammation in the uvea. Episcleritis. The most urgent would be acute open-angle glaucoma which they tend to have a lot of eye pain which he doesn't have? He has some discomfort but not much.
So with pain or a gritty sensation or eyes getting stuck open or shut could be caused by infections but here I'm thinking in a young person, uveitis. I want to know where the inflammation was and I think about systemic illnesses. Systemic vasculitidies and lupus and rheumatoid arthritis, especially with symmetric migratory arthritis involving small joints and then when you tell me sinus disease, sinus problems, if you think about systemic vasculitis involving sinuses, the most common one would be Wegeners involving the upper and lower respiratory track usually upper in 90% of the cases.
They can have involvement of the eyes, they can have involvement of the ears and they often have involvement of skin. So, I'm thinking about those kinds of illnesses. Autoimmune disorders in young persons. Where would I go from here? I want to know where it is.
Social history it's not terribly revealing. Current meds for the joint pain and steroid eye drops he had been prescribed. One question, sexual history? Reactive arthritis is another one that can present as uveitis. He was sexually active with a girlfriend. Heterosexual with a steady girlfriend. Okay.
Vitals are normal. I'll focus on the abnormalities and the rest is pretty normal. The abnormalities were confined to the eyes and nose so he had bilateral collateral injection. Pupils normally reactive in exam and fundoscopic exam was normal. Nasal mucosa was mild with crusting in the right side. No ulcerations and septum was intact. And remainder of the exam was normal. He had skin lesions which I'll show you pictures of.
So, there is his fingertip lesion there. And there is the picture of his sclera in his eye. So you can see considerable injection of the upper scleral vessels. The sclera part of that has a purplish dark red hew as opposed to white.
So the skin, I think that is sort of on the fingernail there and there, I think about splinter hemorrhages although this is a little bit bigger than a splinter hemorrhage. This sort of a lesion makes me think about embolic disease or something involving the vessels. It's a small vessel vasculitis. So with my prior comments I see these and I think about a small vessel vasculitis. There is a little bit of a laundry list but of the ones mentioned that involve the upper respiratory tract trying to put this with the nasal crusting and I'm going back to wegners as I think about something that would put together this whole clinical picture. What else? Maybe he just has bad allergies. But again, I'm thinking about rheumatoid arthritis, Wegeners, could this be infection an endocarditis? Possible. I can't explain the episclerotitis. Although it can involve the eye. It's usually in the back of the eye. I don't like that as much. So I would proceed with basic labs and looking at ordering a anca and a p anca. If I had to choose -- do I have to choose?
I'll give you some labs. He is from Virginia. So there is his routine lab data. He had a neutrophilic leukocytosis. Elevated platelet count. His chemistry 20 panel which is liver function, and creatine was normal. Urinalysis showed 5-10 rbc/hpf. His rheumatoid factor was elevated at 563 and ana was negative and chest x-ray was normal.
The laboratory abnormalities speak to again, the platelet count, and probably a chronic inflammatory condition. Makes me think about autoimmune diseases. Makes me think about coxia. It's not really right for that from Virginia. I don't know if he traveled. The rheumatoid factor is non specific. You could have rheumatoid arthritis on the list. The urinary tract abnormalities suggest to me he has some type of immune complex or gn. Which could be associated with any of the diseases I mentioned. Anymore labs? I still like the anca. Or I don't know what else could we do?
The other possibilities for making a diagnosis. We found something to biopsy? Did you?
So the biopsy of the skin showed vasculitis in the vessel being destroyed by inflammatory infiltrate. So he had small vessel vasculitis on the skin biopsy. That was the most accessible thing to biopsy on the first day.
I'm impressed that you got a biopsy. This is consistent with the clinical impression to me of systemic vasculitis involving small vessels. That would explain small to medium. That would explain the skin findings and eye finding. Also I have written here, the joint findings. So I still go with Wegeners. I'll put rheumatoid arthritis second if you're going to make me guess now. He's a little young.
Before we get to skin biopsy, the next thing we did was take a little bit of his urine and look at it under the microscope. I'm impressed! And so, establishing the presence of nephritis. So again, rarely will clinical labs on routine find red cell casts. So we were really concerned to look at fresh urine. So that was the first test. And once we had that, then the next test, you already eluded to is we looked for antipert needs 3 antibodies the auto antibodies seen in the screen. He had a very high titre. It was confirmed. This allowed us to make the diagnosis of Wegeners granulamatosis.
My comment would be -- it's a compilation of symptoms. We could talk about it -- but it's revolutionary. Diagnosis and treatment of disorders come full field. People live and do quite well. And the serologies are interesting. I saw a patient a couple of weeks ago who had the c ancas has excellent sensitivity but not completely specific. So there are some other disorders that can cause it, including rheumatoid arthritis. I was going to say a case I saw of ra that had a c anca which is quite unusual.
Any way, it looks like you're going to summarize. He didn't have pulmonary. I was been thinking about pulmonary disease.
I think we are running out of time so these are just the principle key features of that disease. He had most of them. He didn't have disease of the lung but had we biopsied his nose we would have seen necrotizing granulosis. This is from our cohort. And you can see that in addition to the respiratory tract disease and kidney disease which are in excess of 80-90% of patients, a variety will be involved by small vessel vasculitis or granuloma disease and constitutional symptoms are present in more than half of the patients in this case, I think it was illustrated because the main clinical features that bothered him were not the typical ones. His nasal symptoms were mild at and best. It's really the constitutional features and his eye disease that were the main clinical features of this case that had one not looked closely at his urine and his nose, we could have missed the diagnosis until it was far advanced.
I had a question about – you have a large series here. Have you noticed or observed an increase? We have a much smaller group of patients. But we noticed some really terrible thrombotic complications, pulmonary embolism, and dvt, I don't know if you noticed that here?
Yes, especially people sick and in the hospital. It's hard to separate that out. Most of the patients that I had that complication had been failure of hospitalization or lung biopsy or critical illness. And we had a 19-year-old kid die of pulmonary embolism and his initial presentation was Wegeners and we were trying to look at it again. Any way, again, fabulous case.
How did he do? He did pretty well. Low dose methotrexate and steroids and complete remission. But he did relapse with granulomatous disease behind his eye years later.
At least I got one.
I appreciate it. Thank you for giving me a softball.
[APPLAUSE]
[LAUGHTER]
Again, thank you to all of the residents who we rounded with this morning and took the time to tell me about the patients we saw. I really enjoyed the visit and thank you again to Dr. Cohen. Thank you.
[APPLAUSE]
ANNOUNCER: You've been listening to NIH Clinical Center Grand Rounds recorded April 7, 2010. On today's presentation, Today, we heard a special "Contemporary Clinical Medicine: Great Teachers" Grand Rounds. Our speaker was Dr. Mark C. Henderson, residency program director and associate dean for admissions at the University of California-Davis School of Medicine, who discussed "Mysterious Cases." You can see a closed-captioned videocast of this lecture by logging onto http://videocast.nih.gov -- click the "Past Events" link -- or by clicking the "View Videocast" link on the podcast homepage at www.cc.nih.gov/podcast. The NIH CLINICAL CENTER GRAND ROUNDS podcast is a presentation of the NIH Clinical Center, Office of Communications, Patient Recruitment and Public Liaison. For more information about clinical research going on every day at the NIH Clinical Center, log on to http://clinicalcenter.nih.gov. From America's Clinical Research Hospital, this has been NIH CLINICAL CENTER GRAND ROUNDS. In Bethesda, Maryland, I'm Bill Schmalfeldt at the National Institutes of Health, an agency of the United States Department of Health and Human Services.
