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High LDH, recurring fever and enlarged mesenteric lymph nodes - PLEASE HELP
My daughter in 5 years old. She was born in the USA and we can back to India in Oct 2007. She was fine until Dec 2008 when she had the first episode of fever. We gave her Paracetomol and she was okay. Then the fever came back after 21 days. Since then she has been having fever every 15 to 20 days. This has been going on from Dec 2008. She was admitted in the hospital 3 times. After then every time she gets fever we give her Paracetomol(5ml of Crocin 125mg or P250) and the fever goes down after 3 to 4 days. She had fever 15 days ago also. She also complains of abdominal pain around the naval which lasts for half an hour. We did an ultrasound and CT scan of her abdomen and the doctors mentioned that she has multiple mesenteric lymph nodes. The first ultrasound mentioned Parailiac and mesenteric lymphnodes. The second ultrasound mentions that the parailiac nodes are not there and the mesenteric nodes are still present. The CT scan also mentions the same. We just completed the third ultrasound which shows that the lymph nodes are 1.9cm, 1.7cm, 1.5 cm and 1.4 am.
We did a bone marrow test in March 2009 and it was thankfully negative.
We just did a biopsy in May 2009, and it says"Non-specific hyper placia". During the laproscopy, they only found nodes 5mm by 5mm and hence did a biopsy on that. They did not see the 1.9cm node. Is that okay
The LDH level in May 2009 was 649 while the lab range in 460. Also, in the LFT, alkaline phosphatase is 172 while the lab max is 140.
We did another ultrasound of the abdomen after 3 months in Sept 2009, and the lymph nodes are still the same. The LDH after 3 months is 662. I'm am struggling for answers. One pediateric infectious disease doctors says it could be periodic fever syndrome. We have been experiencing this for 9 months now as very very concerned. Any help and advice
We did a bone marrow test in March 2009 and it was thankfully negative.
We just did a biopsy in May 2009, and it says"Non-specific hyper placia". During the laproscopy, they only found nodes 5mm by 5mm and hence did a biopsy on that. They did not see the 1.9cm node. Is that okay
The LDH level in May 2009 was 649 while the lab range in 460. Also, in the LFT, alkaline phosphatase is 172 while the lab max is 140.
We did another ultrasound of the abdomen after 3 months in Sept 2009, and the lymph nodes are still the same. The LDH after 3 months is 662. I'm am struggling for answers. One pediateric infectious disease doctors says it could be periodic fever syndrome. We have been experiencing this for 9 months now as very very concerned. Any help and advice
COMMUNITY LEADER
hi, Matt. Sorry for the delay.
1) No, my guess is not that the body response is giving up. That connotes a bad turn, which is likely not true. My guess goes like this: a fever normally has a good purpose, which is to help defeat an infection.The microbes cannot survive well in the hotter environment. So when the fever does not occur, that seems good and probably is good because the body senses it doesn't need such a powerful response anymore - yet it might also mean that the underlying condition does not get defeated so readily. It's almost a paradox. And of course it's just simply my guessing.
2) if the pain is indeed caused by swelling of the lymph nodes then I would try the pred or the antihistamine, yes. E.g., nodes in the neck or armpit can be tender or painful when swollen as part of an immune response. That's merely another guess.
3) or to compare like to like - IOW pain periods to pain periods, but also non-pain to non-pain
4) if a node divides, then they resulting two would be adjacent. Is there any reason to believe that exists? My guess would be no, because a sono might not be able to differentiate two adjacent nodes versus one big node. An MRI probably would. A node wouldn't divide and then the two parts migrate away from each other.
5) I think that is prudent, Matt. Let's say that you wanted to see if the overall level of the ocean was rising or falling. You'd have to compare high tide to high tide, and low tide to low tide. Taking measurements at arbitrary intervals wouldn't tell much at all.
I'm glad that I might be of some small help. Good luck and (from the west) Happy New Year :)
1) No, my guess is not that the body response is giving up. That connotes a bad turn, which is likely not true. My guess goes like this: a fever normally has a good purpose, which is to help defeat an infection.The microbes cannot survive well in the hotter environment. So when the fever does not occur, that seems good and probably is good because the body senses it doesn't need such a powerful response anymore - yet it might also mean that the underlying condition does not get defeated so readily. It's almost a paradox. And of course it's just simply my guessing.
2) if the pain is indeed caused by swelling of the lymph nodes then I would try the pred or the antihistamine, yes. E.g., nodes in the neck or armpit can be tender or painful when swollen as part of an immune response. That's merely another guess.
3) or to compare like to like - IOW pain periods to pain periods, but also non-pain to non-pain
4) if a node divides, then they resulting two would be adjacent. Is there any reason to believe that exists? My guess would be no, because a sono might not be able to differentiate two adjacent nodes versus one big node. An MRI probably would. A node wouldn't divide and then the two parts migrate away from each other.
5) I think that is prudent, Matt. Let's say that you wanted to see if the overall level of the ocean was rising or falling. You'd have to compare high tide to high tide, and low tide to low tide. Taking measurements at arbitrary intervals wouldn't tell much at all.
I'm glad that I might be of some small help. Good luck and (from the west) Happy New Year :)
Hi TonyBob
Please find my answers to your questions:
1) OTOH: is the duration of the pain period occurring over more days in the recent attack? IOW, if the fever was necessary to defeat some recurrence of *actual infection*, then the lack of fever might mean that the infection flareup lasts longer. Did it last longer the most recent time?
Ans: The abdominal pain is occuring more frequently than before. It is almost everyday, but the duration of the pain is about 20 to 30 minutes everytime for the last year. The exception to this was twice - July 17th and Nov 21st when the stomach pain lasted for two days each. You had mentioned that the lack of fever means that the infection flareup lasts longer - can you please kindly elaborate on this - does this mean that the infection is growing and that the body response is giving up? Please help us with your valuable thoughts
2)did you try the prednisone or antihistamine during the November attack?
Ans: We did not use any medication as there was no fever during the Nov attack. Would you suggest that we try prednisone even for the stomach pain.
3). You are right when saying that we took the ultrasound during different times - with and without the attack. But comparing the sonogram report taken during the attack at different times, once in May 23rd and then in Nov 21st, we find that the lymph nodes then were two or three at any given place but this time it is six in one place. This is what is worrying us. Your point is well taken and we will compare the sonogram report during the pain only.
4) One thing is that the size has decreased but the number has increased - could this be a division of the nodes. You had said no, but you have also mentioned that it is possible for the nodes to divide itself - and that means danger. - This is what is worrying us the most - there are more number of nodes in the same area which are smaller in size, which were previously, smaller in number but larger in size. Would this mean that there is a division on nodes - I appologize for asking this again as you know how concerened we are.
5). You have highlighted a very important point which we did not consider so far. The tests, be it blood test or sonograms, were taken when we visit the doctor or when there is fever/stomach pain. From now on we wll taken it at regulated periods - during and 3 days after the attack and this will help us compare better.
I hope that I have been able to answer your questions to the best possible. We are still grappling with what is causing these problems - it more than one year and the pain that she has undergone is unexplainable.
But as always, we have been lucky to find kind people as you helping and guiding us. Thanking you again - Matt
Please find my answers to your questions:
1) OTOH: is the duration of the pain period occurring over more days in the recent attack? IOW, if the fever was necessary to defeat some recurrence of *actual infection*, then the lack of fever might mean that the infection flareup lasts longer. Did it last longer the most recent time?
Ans: The abdominal pain is occuring more frequently than before. It is almost everyday, but the duration of the pain is about 20 to 30 minutes everytime for the last year. The exception to this was twice - July 17th and Nov 21st when the stomach pain lasted for two days each. You had mentioned that the lack of fever means that the infection flareup lasts longer - can you please kindly elaborate on this - does this mean that the infection is growing and that the body response is giving up? Please help us with your valuable thoughts
2)did you try the prednisone or antihistamine during the November attack?
Ans: We did not use any medication as there was no fever during the Nov attack. Would you suggest that we try prednisone even for the stomach pain.
3). You are right when saying that we took the ultrasound during different times - with and without the attack. But comparing the sonogram report taken during the attack at different times, once in May 23rd and then in Nov 21st, we find that the lymph nodes then were two or three at any given place but this time it is six in one place. This is what is worrying us. Your point is well taken and we will compare the sonogram report during the pain only.
4) One thing is that the size has decreased but the number has increased - could this be a division of the nodes. You had said no, but you have also mentioned that it is possible for the nodes to divide itself - and that means danger. - This is what is worrying us the most - there are more number of nodes in the same area which are smaller in size, which were previously, smaller in number but larger in size. Would this mean that there is a division on nodes - I appologize for asking this again as you know how concerened we are.
5). You have highlighted a very important point which we did not consider so far. The tests, be it blood test or sonograms, were taken when we visit the doctor or when there is fever/stomach pain. From now on we wll taken it at regulated periods - during and 3 days after the attack and this will help us compare better.
I hope that I have been able to answer your questions to the best possible. We are still grappling with what is causing these problems - it more than one year and the pain that she has undergone is unexplainable.
But as always, we have been lucky to find kind people as you helping and guiding us. Thanking you again - Matt
COMMUNITY LEADER
> One thing is that the size has decreased but the number has increased - could this be a division of the nodes
no, AFAIK division means cancer, and your daughter does not have cancer.
but with either infection or else the false alarm of an auto-immune response, I'd guess that the nodes will wax and wane. There might not be any clear pattern as to which nodes decide to flare up and which nodes don't.
Here's one thing that occurs to me: are you correlating test results according to when tests were taken vis-a-vis her cycling pattern? E.g., at one point her LDH was down. Let's say arbitrarily that was 5 days after an attack. Have her other LDH test been taken also at around 5 days after an attack? IOW, I'd think that all results should be thought of in terms of when they were taken vis-a-vis the peak point of an attack.
Let's take the opposite example: say she gets LDH tested on the first day of every month, but her syndrome cycles every 20 days or so. In such a case, the LDH tests occur at different points in the cycle, and they can't be compared to each other.
Please let me know if I was clear in saying that.
no, AFAIK division means cancer, and your daughter does not have cancer.
but with either infection or else the false alarm of an auto-immune response, I'd guess that the nodes will wax and wane. There might not be any clear pattern as to which nodes decide to flare up and which nodes don't.
Here's one thing that occurs to me: are you correlating test results according to when tests were taken vis-a-vis her cycling pattern? E.g., at one point her LDH was down. Let's say arbitrarily that was 5 days after an attack. Have her other LDH test been taken also at around 5 days after an attack? IOW, I'd think that all results should be thought of in terms of when they were taken vis-a-vis the peak point of an attack.
Let's take the opposite example: say she gets LDH tested on the first day of every month, but her syndrome cycles every 20 days or so. In such a case, the LDH tests occur at different points in the cycle, and they can't be compared to each other.
Please let me know if I was clear in saying that.
COMMUNITY LEADER
hi, Madhan. Here are my guesses, if that might help any:
It's probably good that the fever hasn't returned. That might mean that her immune response is lessening. She stills gets node enlargement and the accompanying pain - and the most recent episode is pretty much on schedule, except maybe a little delayed. This all would apply if the recurrent syndrome was *auto-immune*. The auto-immune response is now less severe because some symptoms develop but not the fever.
OTOH: is the duration of the pain period occurring over more days in the recent attack? IOW, if the fever was necessary to defeat some recurrence of *actual infection*, then the lack of fever might mean that the infection flareup lasts longer. Did it last longer the most recent time?
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did you try the prednisone or antihistamine during the November attack?
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> the ultrasound done on Nov 21st shows that there are 6. I do not know if the pain is linked to the lymph nodes.
I'd guess that the pain results in the same way that pain results when people get swollen lymph nodes from an immune response.
I'd also figure that since she had a sonogram actually during a period of attack, that's why more show up as enlarged on that sonogram. If others sonograms showed fewer nodes as being enlarged, then is that because those sonograms were not taken actually during an attack?
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This is my guess as to the situation: there is a chronic infection or else a chronic auto-immune condition. Either of those results in a state where some nodes are enlarged. The only difference is whether the immune response is occurring due to an actual infection or to a misguided response by her immune system to a threat which is not real.
Periodically, her immune system becomes even more activated. That's when more nodes get enlarged, and maybe some get even extra big. That's also when fever occurs, and fever of course is part of the response of the immune system. So the nodes wax and wane. Hopefully, the trend will be towards lessening - as it seems to be (except if the period of bad pain occurred over more days in the November attack).
It's probably good that the fever hasn't returned. That might mean that her immune response is lessening. She stills gets node enlargement and the accompanying pain - and the most recent episode is pretty much on schedule, except maybe a little delayed. This all would apply if the recurrent syndrome was *auto-immune*. The auto-immune response is now less severe because some symptoms develop but not the fever.
OTOH: is the duration of the pain period occurring over more days in the recent attack? IOW, if the fever was necessary to defeat some recurrence of *actual infection*, then the lack of fever might mean that the infection flareup lasts longer. Did it last longer the most recent time?
------
did you try the prednisone or antihistamine during the November attack?
-------
> the ultrasound done on Nov 21st shows that there are 6. I do not know if the pain is linked to the lymph nodes.
I'd guess that the pain results in the same way that pain results when people get swollen lymph nodes from an immune response.
I'd also figure that since she had a sonogram actually during a period of attack, that's why more show up as enlarged on that sonogram. If others sonograms showed fewer nodes as being enlarged, then is that because those sonograms were not taken actually during an attack?
-------
This is my guess as to the situation: there is a chronic infection or else a chronic auto-immune condition. Either of those results in a state where some nodes are enlarged. The only difference is whether the immune response is occurring due to an actual infection or to a misguided response by her immune system to a threat which is not real.
Periodically, her immune system becomes even more activated. That's when more nodes get enlarged, and maybe some get even extra big. That's also when fever occurs, and fever of course is part of the response of the immune system. So the nodes wax and wane. Hopefully, the trend will be towards lessening - as it seems to be (except if the period of bad pain occurred over more days in the November attack).
Sorry missed one point. I have read in your other posts that lymphnodes would divide. Could this have happened to my daughter also. Would it be that the two or three nodes existing before have divided into the six or seven. One thing is that the size has decreased but the number has increased - could this be a division of the nodes. - Please advise
Hi TonyBob,
Thank you for your response. Please find below the update.
The last fever occurred on Oct 20th and this has been the longest time and we hope and pray it never returns. We have been graphing the pattern and the fever has been happening every 15 to 25 days for the past year(from Dec 10, 2008). I hope and pray that the fever never returns.
But she has been getting stomach pain constantly. The severe bout happened on Nov 21 - Nov 23rd. Other than that she gets it everyday. It is around the naval and lasts anywhere between 1 minute to 30 minutes. The severe pain happens one or two times during the day when she crouches and catches her stomach. In addition, she usually complains by herself two to three times in the day. The remaining time she just plays and when asked by us she says that her stomach hurts. Either she says or when asked she says that her stomach pains. The pain has been constant. Also, her lymph nodes have gone from 2 in one place 6 which we are very concerned. We looked at all the ultrasounds done so far. So far there have been only two or three lymph nodes in one place but the ultrasound done on Nov 21st shows that there are 6. I do not know if the pain is linked to the lymph nodes. Since the lymph nodes have not gone down in almost one year and the number has increased I'm very scared. Please help us and guide us..Thanking you for your time and help.
Thanking you
Madhan
Thank you for your response. Please find below the update.
The last fever occurred on Oct 20th and this has been the longest time and we hope and pray it never returns. We have been graphing the pattern and the fever has been happening every 15 to 25 days for the past year(from Dec 10, 2008). I hope and pray that the fever never returns.
But she has been getting stomach pain constantly. The severe bout happened on Nov 21 - Nov 23rd. Other than that she gets it everyday. It is around the naval and lasts anywhere between 1 minute to 30 minutes. The severe pain happens one or two times during the day when she crouches and catches her stomach. In addition, she usually complains by herself two to three times in the day. The remaining time she just plays and when asked by us she says that her stomach hurts. Either she says or when asked she says that her stomach pains. The pain has been constant. Also, her lymph nodes have gone from 2 in one place 6 which we are very concerned. We looked at all the ultrasounds done so far. So far there have been only two or three lymph nodes in one place but the ultrasound done on Nov 21st shows that there are 6. I do not know if the pain is linked to the lymph nodes. Since the lymph nodes have not gone down in almost one year and the number has increased I'm very scared. Please help us and guide us..Thanking you for your time and help.
Thanking you
Madhan
COMMUNITY LEADER
thank you for saying that, Matt
if it were me, I'd still have pred on hand to try immediately if the fever returns. If the syndrome goes away on its own, I'd be wondering what it was... so it might set your minds at ease to get as much info on it while it's still here.
Have you been graphing the pattern? Maybe a visual would help you to see a trend. Please let me know what develops, and good luck :)
if it were me, I'd still have pred on hand to try immediately if the fever returns. If the syndrome goes away on its own, I'd be wondering what it was... so it might set your minds at ease to get as much info on it while it's still here.
Have you been graphing the pattern? Maybe a visual would help you to see a trend. Please let me know what develops, and good luck :)
Hi TonyBob
Thank you for your response. Iam grateful to you for taking the time to atleast point us in the direction we should look into. It helps us when we talk to the doctors. Please do continue to support us and provide us with information and thereby help us. Thanking you as always.
Thank you for your response. Iam grateful to you for taking the time to atleast point us in the direction we should look into. It helps us when we talk to the doctors. Please do continue to support us and provide us with information and thereby help us. Thanking you as always.
COMMUNITY LEADER
I'm sorry that I don't know the answers, Matt. My memory is from three years ago, with a chemo patient that I knew online, who was taking cimetidine for the resulting intestinal pain.
Hi TonyBob
Thank you again for your response. How do we find out if the inflammation is from the intestine and not from the nodes. Any advise would be helpful.
We did an ultrasound and hence there was no constrast used. We do not know why more nodes are appearing - But I hope what you said is true - that the problem is resolving
We have so far not given any medication for the abdominal pain but she gets the pain almost every day. Could you please advise if we need to look at any medicines or look from a different angle.
As always we are grateful and thankful for your help
Thank you again for your response. How do we find out if the inflammation is from the intestine and not from the nodes. Any advise would be helpful.
We did an ultrasound and hence there was no constrast used. We do not know why more nodes are appearing - But I hope what you said is true - that the problem is resolving
We have so far not given any medication for the abdominal pain but she gets the pain almost every day. Could you please advise if we need to look at any medicines or look from a different angle.
As always we are grateful and thankful for your help
Hi TonyBob
Thank you again for your response. How do we find out if the inflammation is from the intestine and not from the nodes. Any advise would be helpful.
We did an ultrasound and hence there was no constrast used. We do not know why more nodes are appearing - But I hope what you said is true - that the problem is resolving
We have so far not given any medication for the abdominal pain but she gets the pain almost every day. Could you please advise if we need to look at any medicines or look from a different angle.
As always we are grateful and thankful for your help
Thank you again for your response. How do we find out if the inflammation is from the intestine and not from the nodes. Any advise would be helpful.
We did an ultrasound and hence there was no constrast used. We do not know why more nodes are appearing - But I hope what you said is true - that the problem is resolving
We have so far not given any medication for the abdominal pain but she gets the pain almost every day. Could you please advise if we need to look at any medicines or look from a different angle.
As always we are grateful and thankful for your help
COMMUNITY LEADER
Matt, do you think the abdominal pain might arise from inflammation in the intestine itself, and not from the swollen nodes?
I don't know what that might mean, except it can be a hopeful sign that the problem is diffuse and decreasing in magnitude... like waves getting smaller and smaller at each cycle until they might be gone.
Then again, assuming that contrast is used for the scan, maybe the increase in number of detected nodes is due to some change in the uptake of the contrast?
Did you try diphenhydramine again for the pain? Or maybe even something like cimetidine? You'll recall that mast cells are especially plentiful in the intestinal wall, and they degranulate histamine. Just a thought.
I don't know what that might mean, except it can be a hopeful sign that the problem is diffuse and decreasing in magnitude... like waves getting smaller and smaller at each cycle until they might be gone.
Then again, assuming that contrast is used for the scan, maybe the increase in number of detected nodes is due to some change in the uptake of the contrast?
Did you try diphenhydramine again for the pain? Or maybe even something like cimetidine? You'll recall that mast cells are especially plentiful in the intestinal wall, and they degranulate histamine. Just a thought.
Hi TonyBob,
Thank you for your reply. Thanking god that the fever has not returned so far(knock on wood). But she had severe abdominal pain for four to five times a day. We did an ultrasound that showed that the mesenteric nodes size has decreased in size from 20mm to 12mm but then the number has increased from three/four to six in the same place. The doctor has asked us to ignore the pain which is very hard for us to just watch. Thank you for your help and advise
Thank you for your reply. Thanking god that the fever has not returned so far(knock on wood). But she had severe abdominal pain for four to five times a day. We did an ultrasound that showed that the mesenteric nodes size has decreased in size from 20mm to 12mm but then the number has increased from three/four to six in the same place. The doctor has asked us to ignore the pain which is very hard for us to just watch. Thank you for your help and advise
COMMUNITY LEADER
Hi, Matt. I guess they're following the idea of suspecting the unlikely, since there's nothing else to do at this point. Maybe they'll even want to try the colchicine, and if she responds then that tends towards the HIDS.
I hope you get some progress soon, but then again the condition is not getting worse and so that's good in and of itself.
Did she experience the fever that was due to arrive soon?
I hope you get some progress soon, but then again the condition is not getting worse and so that's good in and of itself.
Did she experience the fever that was due to arrive soon?
Sorry did not respond for long to your post. I was just going through the articles you had mentioned and basically in a stand still mode. Just an update - one rhemutoloist recommended testing the IdG immunoglobulin level which is what we are doing now. Please do share your valuable thoughts and if you think of anything please do add to the post.
Matt
Matt
COMMUNITY LEADER
hi, Matt. one quick thing for now: how about this doctor from India, who is giving online free advice:
http://drpeds.blogspot.com/
he seems to be currently active on his site.
Btw, he also has an article on managing fever generally:
http://drpeds.blogspot.com/2005_06_05_drpeds_archive.html
in which he mentions that letting a fever run its course can indeed sometimes cure the condition, but not to let it get above 101F in children. So that threshold is new to me, but I didn't know much about pediatric medicine anyway.
Also, I have to say that I think that you are an absolutely wonderful and capable parent, and she is lucky to have you. Her best chance with this mystery condition is that she has you helping her. From what I can see, you are doing everything that is possible to do.
Related to that, allow me to suggest this CME:
http://cme.medscape.com/viewarticle/495298
and pay attention throughout to the statements that periodic fever can be very difficult to diagnose. So this can perhaps assure you that there is not something that you are missing, something which could solve everything.
But on the plus side, notice also that there is not talk in that article of this being a very serious condition, instead that the main bad result is discomfort, and that it may resolve on its own - without anyone ever knowing why it happened.
We also see that it is not progressing. You have all along been doing what is recommended: keeping careful records on onset and offset etc.
Consider this: "However, in the majority of patients, fever will eventually resolve without any specific cause ever being delineated. When this occurs, parents just need to be reassured of the unlikely presence of any long-term sequelae. In cases of periodic fever, if all of the 4 syndromes described above are ruled out, the chance of establishing a diagnosis is small". Notice it does not mention cancer, or any very serious outcome. That should set you somewhat at ease.
Back to detective work :) Here is a chart already made for use in the differential diagnosis:
http://www.clinimmsoc.org/teaching/tips/periodic_fever_comparisons.pdf
note they are using cytokines as markers. Did your daughter have those tests?
And back to the CME (Continuing Medical Education for doctors) that I cited above, note this regarding PFAPA: "Aphthous stomatitis, cervical adenitis, and pharyngitis are present in 70% to 88% of cases". So maybe your daughter is in that other 30-12%
My guess is that I don't think we should rule out PFAPA, especially since we don't seem to have a genetic cause. The response to prednisone might tell a lot.
Also, I mentioned the needle biopsy as a less-invasive possibility for the future.
As regards the biopsy that was done, maybe I was being paranoid. Yes, it is a very good idea to ask for another pathologist to look at the sample. If another pathologist is able to successfully read the slide, then that solves that.
Keep me up to date - and as always, best wishes to you and your little daughter :)
http://drpeds.blogspot.com/
he seems to be currently active on his site.
Btw, he also has an article on managing fever generally:
http://drpeds.blogspot.com/2005_06_05_drpeds_archive.html
in which he mentions that letting a fever run its course can indeed sometimes cure the condition, but not to let it get above 101F in children. So that threshold is new to me, but I didn't know much about pediatric medicine anyway.
Also, I have to say that I think that you are an absolutely wonderful and capable parent, and she is lucky to have you. Her best chance with this mystery condition is that she has you helping her. From what I can see, you are doing everything that is possible to do.
Related to that, allow me to suggest this CME:
http://cme.medscape.com/viewarticle/495298
and pay attention throughout to the statements that periodic fever can be very difficult to diagnose. So this can perhaps assure you that there is not something that you are missing, something which could solve everything.
But on the plus side, notice also that there is not talk in that article of this being a very serious condition, instead that the main bad result is discomfort, and that it may resolve on its own - without anyone ever knowing why it happened.
We also see that it is not progressing. You have all along been doing what is recommended: keeping careful records on onset and offset etc.
Consider this: "However, in the majority of patients, fever will eventually resolve without any specific cause ever being delineated. When this occurs, parents just need to be reassured of the unlikely presence of any long-term sequelae. In cases of periodic fever, if all of the 4 syndromes described above are ruled out, the chance of establishing a diagnosis is small". Notice it does not mention cancer, or any very serious outcome. That should set you somewhat at ease.
Back to detective work :) Here is a chart already made for use in the differential diagnosis:
http://www.clinimmsoc.org/teaching/tips/periodic_fever_comparisons.pdf
note they are using cytokines as markers. Did your daughter have those tests?
And back to the CME (Continuing Medical Education for doctors) that I cited above, note this regarding PFAPA: "Aphthous stomatitis, cervical adenitis, and pharyngitis are present in 70% to 88% of cases". So maybe your daughter is in that other 30-12%
My guess is that I don't think we should rule out PFAPA, especially since we don't seem to have a genetic cause. The response to prednisone might tell a lot.
Also, I mentioned the needle biopsy as a less-invasive possibility for the future.
As regards the biopsy that was done, maybe I was being paranoid. Yes, it is a very good idea to ask for another pathologist to look at the sample. If another pathologist is able to successfully read the slide, then that solves that.
Keep me up to date - and as always, best wishes to you and your little daughter :)
Hi TonyBob,
Thanks for your reply. I'll take to your advice on prednisone and ask the doctor about trying it. On the LDH we will try another test(this is the 20th blood test in as many months) and hope that the LDH has gone down.
I'm really scared when you mention that the biopsy was covered up. Why would that be - I hope they did not do such a thing. I'm getting really worried. Is it possible to have another opinion on the same slide. I will try that.
I do not think that the nodes shrunk, because before and after the surgery, the ultrasound still shows enlarged lymph nodes.
They did not do a Fine Needle biopsy. They did a laproscopy.
With respect to the fever pattern - I think that it is more periodic than is caused by external factors. When they is not fever, my daughter can play anywhere(even in the rain) and nothing happens, and then when the time comes, however careful we are(diet, not going out, anything), the fever just comes.
Thanks for all you thoughts, but now I'm at a stage that I just do not have real answers and just do not know what to do. I feel that I'm not doing enough and if it were someone else, my daughter would have been cured. I just do not know what to do. Please help.
Thanks for your reply. I'll take to your advice on prednisone and ask the doctor about trying it. On the LDH we will try another test(this is the 20th blood test in as many months) and hope that the LDH has gone down.
I'm really scared when you mention that the biopsy was covered up. Why would that be - I hope they did not do such a thing. I'm getting really worried. Is it possible to have another opinion on the same slide. I will try that.
I do not think that the nodes shrunk, because before and after the surgery, the ultrasound still shows enlarged lymph nodes.
They did not do a Fine Needle biopsy. They did a laproscopy.
With respect to the fever pattern - I think that it is more periodic than is caused by external factors. When they is not fever, my daughter can play anywhere(even in the rain) and nothing happens, and then when the time comes, however careful we are(diet, not going out, anything), the fever just comes.
Thanks for all you thoughts, but now I'm at a stage that I just do not have real answers and just do not know what to do. I feel that I'm not doing enough and if it were someone else, my daughter would have been cured. I just do not know what to do. Please help.
COMMUNITY LEADER
Hello, Matt. I'd guess that the doc abandoned the pred idea when he saw that th e inflammation markers did not decline when the fever went down. Therefore, reducing the inflammation maybe wouldn't reduce the fever, since they are not tied... You probably were thinking the same thing already. Even so, it can be helpful when a person is researching on their own to have a sounding board - so I'll continue with the rest of the points.
The urine protein being normal seems to be a good sign that there is no current danger of amyloidosis, so you must be relieved about that.
But if it were me I'd still try the prednisone, because there is not much harm.
Yes, I was trying to refer to that 'surprise' factor earlier, in that when things are a mystery then the only thing to do is try to pick up on some surprising aspect, which might give some clue. So if her LDH is now normal, with no apparent cause, then who knows? Maybe the syndrome is even over - she should be due for another episode soon, right?
Has something environmental change that can account for the lowered LDH? Weather, food, anything?
But of course, once again you show your aptitude for this by wondering if the LDH test was accurate.
Which leads to the other point: that maybe the first biopsy was botched. Maybe someone said 'non-specific' to cover up.
Maybe they didn't find the largest node because it had shrunk by then? I'd think the aim to get the largest is because 1) you get more overall tissue to test and 2) being larger means there is more of the 'extra' tissue present there, and 3). in neoplasia the largest node would likely be the most aggressive, so you want those cells [more than one type of lymphoma can be found in one person].
I personally don't see any reason to be concerned about that. Can you elaborate?
Btw, you might be aware that there is also the 'fine needle biopsy', which they can do while guided by sono or other scanning like MRI. They'd probably use sonogram unless the target is very tiny. However, this method results in many false negatives, because you might just miss the bad part of the node. Still, it's much easier on the patient.
As far as FMF: low urine protein might mean that untreated disease is leading to amyloidosis; however, it is not necessarily present in early stage or milder disease (that's my take on it, anyway)
However, I brought up FMF for this reason: when usual investigation by signs and symptoms leads to a dead end, one might try to analyze according to mechanism. IOW, what process could cause the observed results in FMF and can that same mechanism be responsible in your daughter? Notice that even Armenians are testing positive for the gene. Also that some are diagnosed with FMF despite not having the gene. Is FMF periodic (according to calendar) or episodic (triggered by some outside event)? Is your daughter's pattern really according to time, or perhaps some outside event occurs semi-regularly and is the real trigger?
Who knows, maybe those lines of thought might lead to somewhere. The docs have the advantage in knowledge over you and me - but you have one big advantage in that you have only one patient to concentrate exclusively on :)
The urine protein being normal seems to be a good sign that there is no current danger of amyloidosis, so you must be relieved about that.
But if it were me I'd still try the prednisone, because there is not much harm.
Yes, I was trying to refer to that 'surprise' factor earlier, in that when things are a mystery then the only thing to do is try to pick up on some surprising aspect, which might give some clue. So if her LDH is now normal, with no apparent cause, then who knows? Maybe the syndrome is even over - she should be due for another episode soon, right?
Has something environmental change that can account for the lowered LDH? Weather, food, anything?
But of course, once again you show your aptitude for this by wondering if the LDH test was accurate.
Which leads to the other point: that maybe the first biopsy was botched. Maybe someone said 'non-specific' to cover up.
Maybe they didn't find the largest node because it had shrunk by then? I'd think the aim to get the largest is because 1) you get more overall tissue to test and 2) being larger means there is more of the 'extra' tissue present there, and 3). in neoplasia the largest node would likely be the most aggressive, so you want those cells [more than one type of lymphoma can be found in one person].
I personally don't see any reason to be concerned about that. Can you elaborate?
Btw, you might be aware that there is also the 'fine needle biopsy', which they can do while guided by sono or other scanning like MRI. They'd probably use sonogram unless the target is very tiny. However, this method results in many false negatives, because you might just miss the bad part of the node. Still, it's much easier on the patient.
As far as FMF: low urine protein might mean that untreated disease is leading to amyloidosis; however, it is not necessarily present in early stage or milder disease (that's my take on it, anyway)
However, I brought up FMF for this reason: when usual investigation by signs and symptoms leads to a dead end, one might try to analyze according to mechanism. IOW, what process could cause the observed results in FMF and can that same mechanism be responsible in your daughter? Notice that even Armenians are testing positive for the gene. Also that some are diagnosed with FMF despite not having the gene. Is FMF periodic (according to calendar) or episodic (triggered by some outside event)? Is your daughter's pattern really according to time, or perhaps some outside event occurs semi-regularly and is the real trigger?
Who knows, maybe those lines of thought might lead to somewhere. The docs have the advantage in knowledge over you and me - but you have one big advantage in that you have only one patient to concentrate exclusively on :)
Thank you for suggesting using Prednisone. The infectious doctor we consulted initially did mention giving a small dose but when we gave the blood test results during and after the fever - he backtracked and asked us to wait or three months before doing anything. Is there any reason for this? The bloodtest were normal(WBC was high at 14 during fever and returned to normal at 10 after the fever - but the ESR and CRP rates were high - 37 and 29 respectively during and after the fever. The ESR and CRP rates have been high during the last 10 months). The urine protien test was done two to three times and the results were normal.
We tried to have a second opinion of the lymph node biopsy, but the second opinion could not be made as the pathologist said that the slides were too thick. The inital pathologist is from a reputed hospital.
We did an LDH test last week and it had dropped to a normal range of 290 which suprised even the doctors. The LDH was around 637 for about 4 months and just dropped on the fifth month. I just hope that the lab results are right.
You are right in saying that it is the enlargement of the lymph nodes that is worrying us and was raised as a concern by the doctors. I'm aware that there are around 600 lymphnodes in the body - but the enlarged lymph nodes with the high LDH was what prompted that doctors to do a biopsy. Why couldn't they not find that largest node. Is it okay to biopsy any node and not just the largest node. The surgeon said that it was okay. I hope and wish that they are right. They did a laproscopy and not an exploratory laprotomy.
On whether the fever could be FMF. The ESR and CRP are high as mentioned above and the urine protien is normal. No one in my family or extended relatives have had any periodic fevers. One doctor we consulted has asked us to take the Iimmunoglobulin levels (overall antibody levels) evaluated, as a low level (of the type called IgG) can cause periodic fever.
We will do that test also next time.
I really appretiate your suggestions and analysis.
We tried to have a second opinion of the lymph node biopsy, but the second opinion could not be made as the pathologist said that the slides were too thick. The inital pathologist is from a reputed hospital.
We did an LDH test last week and it had dropped to a normal range of 290 which suprised even the doctors. The LDH was around 637 for about 4 months and just dropped on the fifth month. I just hope that the lab results are right.
You are right in saying that it is the enlargement of the lymph nodes that is worrying us and was raised as a concern by the doctors. I'm aware that there are around 600 lymphnodes in the body - but the enlarged lymph nodes with the high LDH was what prompted that doctors to do a biopsy. Why couldn't they not find that largest node. Is it okay to biopsy any node and not just the largest node. The surgeon said that it was okay. I hope and wish that they are right. They did a laproscopy and not an exploratory laprotomy.
On whether the fever could be FMF. The ESR and CRP are high as mentioned above and the urine protien is normal. No one in my family or extended relatives have had any periodic fevers. One doctor we consulted has asked us to take the Iimmunoglobulin levels (overall antibody levels) evaluated, as a low level (of the type called IgG) can cause periodic fever.
We will do that test also next time.
I really appretiate your suggestions and analysis.
COMMUNITY LEADER
so, unfortunately Matt, the mystery deepens. The following are just some thoughts/guesses that might spark some idea:
It no longer seems to be PFAPA, since it does not have the hallmark of the throat/neck connection. That was a good observation on your part. However, if it was me, I'd still try giving the dose of prednisone at the onset of the next attack - just because this is such a mystery and doctors are stumped and the low dose pred wouldn't harm anything. The chance of success seems small, that is true. But it could still be PFAPA that has an atypical presentation, or it could be something similar that responds to pred. You would get some clue from the response of lack thereof, and it seems to me better than merely waiting.
The lack of neck involvement similarly seems to rule out HIDS.
Nothing on the list of periodic fevers here:
http://my.clevelandclinic.org/disorders/periodic_fever_syndrome/rheumatology_overview.aspx
seems to fit.
I'd also keep in mind at this point that the chances of the enlarged nodes being a lymphoma, without also evidence of any lymphoma in neck, armpit, groin or marrow, seems very unlikely. Also, I'd think that the non-specific hyperplasia argues against cancer, since cancer cells even look highly unusual under a microscope to a trained eye. No one has used the word 'neoplasia', from what you've written here, so the structure of the nodes is also normal.
I assume you are aware that LDH can be elevated from many, many causes. You can bang your leg and get elevated LDH.
Just to be sure: you are aware that the lymph nodes are there normally within the mesentery, they are just enlarged now and that's why the docs are remarking on them, right? Lymph node are throughout the body in many locations.
We still aren't sure if there is an infection, or just an immune response without actual active infection, or something else. (For example, predisone itself would increase the WBC count, even as it reduces the activity of leukocytes. The immune system is very complex.)
What do you think about the possibility of Familial Mediterranean Fever? True, the ethnicity connection is not there. But you might get a baseline test for SED rate, and repeat during the next episode. For urine protein, too, according to that Cleveland Clinic web page cited above.
This could be some similar mechanism with a gene defect that governs some immune protein. But I assume you have asked every relative you can find about periodic fevers in the family tree.
It no longer seems to be PFAPA, since it does not have the hallmark of the throat/neck connection. That was a good observation on your part. However, if it was me, I'd still try giving the dose of prednisone at the onset of the next attack - just because this is such a mystery and doctors are stumped and the low dose pred wouldn't harm anything. The chance of success seems small, that is true. But it could still be PFAPA that has an atypical presentation, or it could be something similar that responds to pred. You would get some clue from the response of lack thereof, and it seems to me better than merely waiting.
The lack of neck involvement similarly seems to rule out HIDS.
Nothing on the list of periodic fevers here:
http://my.clevelandclinic.org/disorders/periodic_fever_syndrome/rheumatology_overview.aspx
seems to fit.
I'd also keep in mind at this point that the chances of the enlarged nodes being a lymphoma, without also evidence of any lymphoma in neck, armpit, groin or marrow, seems very unlikely. Also, I'd think that the non-specific hyperplasia argues against cancer, since cancer cells even look highly unusual under a microscope to a trained eye. No one has used the word 'neoplasia', from what you've written here, so the structure of the nodes is also normal.
I assume you are aware that LDH can be elevated from many, many causes. You can bang your leg and get elevated LDH.
Just to be sure: you are aware that the lymph nodes are there normally within the mesentery, they are just enlarged now and that's why the docs are remarking on them, right? Lymph node are throughout the body in many locations.
We still aren't sure if there is an infection, or just an immune response without actual active infection, or something else. (For example, predisone itself would increase the WBC count, even as it reduces the activity of leukocytes. The immune system is very complex.)
What do you think about the possibility of Familial Mediterranean Fever? True, the ethnicity connection is not there. But you might get a baseline test for SED rate, and repeat during the next episode. For urine protein, too, according to that Cleveland Clinic web page cited above.
This could be some similar mechanism with a gene defect that governs some immune protein. But I assume you have asked every relative you can find about periodic fevers in the family tree.
Thank you for your comments. I hope that your thoughts are correct and it is PFAPA. The common symptoms of PFAPA are fever with swollen lymph nodes on the neck, but my daughter has mesenteric lymph nodes. I did a lot of search on PFS and mesenteric lymph nodes and did not find any results which is why I'm worried. Only one or two cases of mesenteric lymph nodes associated one type of PFS(not PFAPA).
We are planning to seek a second opinion soon and hope that goes without any major issues.
We are planning to seek a second opinion soon and hope that goes without any major issues.
COMMUNITY LEADER
hi, I think you can see that the experience of those other parents is similar to yours. That includes going to many doctors over a long period until a diagnosis is made. We know that the diagnosis of PFS (or more specifically PFAPA ) is not certain in your daughter's case, but it sure is looking like it. Would you agree? However, it still can be something different.
That's how it usually goes with rare disorders.
I see you are correct that pred is not preventing episodes. Conversely, it is used to suppress immune reaction in other conditions like ITP (thrombocytopenia). So, you never know.
But the pred does seem remarkably effective in treating, as you have seen others report. I'd ask now for a prescription to have on hand for the next episode, to use immediately. Take a little time to note the effects on blood glucose and salt retention - just to know, even though small doses for short period probably means there is no concern in your case.
I see some saying that they've seen evidence that pred reduces severity of attacks, but increases frequency. Others say the opposite, that it reduces frequency. So I guess it is a matter of trial and error for you, but the point is that a lot of things are uncertain. At least you might be feeling that this is not as bad as it looked a few weeks ago.
You also will be seeing the difference between case reports or anecdotal reports, and statistical studies. The latter are more solidly grounded, but the former might give ideas about what to do. E.g., I saw one parent report about using cimetidine. (And that makes me think of researching diphenhydramine.)
But I also see an actual trial, although very small, which is about using tonsillectomy.
"A Randomized, Controlled Trial of Tonsillectomy in Periodic Fever, Aphthous Stomatitis, Pharyngitis, and Adenitis Syndrome"
"The length of follow-up ranged from 6 to 19 months. Eight (88.89%) of 9 patients had complete remission of symptoms immediately after surgery. The histologic and immunohistochemical examination showed features of chronic tonsillar inflammation."
and "(a) No specific findings were observed in the tonsils of PFAPA patients; (b) we could not find any difference in tonsillar histology between PFAPA and chronic tonsillar inflammation"
[Point (b) could possibly relate to your point on mesenteric nodes not shrinking.]
I do see that the pred dosage seems very small, which is good. But we always keep in mind that children are not merely mini versions of adults, so drug effects on children are always something to be wary of.
I also appreciate your thought that the nodes do not shrink between episodes. You'd need to compare with observations in other children. There might be something specific in this syndrome that keeps nodes from shrinking. But yes, if normally they do shrink on others, than that argues against PFS in your daughter. This point might take longer to research.
I hope you are not feeling so powerless anymore. Knowledge is power, and you will be an expert soon :)
P.S. the quickness that pred is reported to be acting is remarkable. Immune suppression on other conditions might take weeks and weeks. This makes me think that the mechanism is not obvious.
P.P.S. More mail on the way to you.
Good luck :)
That's how it usually goes with rare disorders.
I see you are correct that pred is not preventing episodes. Conversely, it is used to suppress immune reaction in other conditions like ITP (thrombocytopenia). So, you never know.
But the pred does seem remarkably effective in treating, as you have seen others report. I'd ask now for a prescription to have on hand for the next episode, to use immediately. Take a little time to note the effects on blood glucose and salt retention - just to know, even though small doses for short period probably means there is no concern in your case.
I see some saying that they've seen evidence that pred reduces severity of attacks, but increases frequency. Others say the opposite, that it reduces frequency. So I guess it is a matter of trial and error for you, but the point is that a lot of things are uncertain. At least you might be feeling that this is not as bad as it looked a few weeks ago.
You also will be seeing the difference between case reports or anecdotal reports, and statistical studies. The latter are more solidly grounded, but the former might give ideas about what to do. E.g., I saw one parent report about using cimetidine. (And that makes me think of researching diphenhydramine.)
But I also see an actual trial, although very small, which is about using tonsillectomy.
"A Randomized, Controlled Trial of Tonsillectomy in Periodic Fever, Aphthous Stomatitis, Pharyngitis, and Adenitis Syndrome"
"The length of follow-up ranged from 6 to 19 months. Eight (88.89%) of 9 patients had complete remission of symptoms immediately after surgery. The histologic and immunohistochemical examination showed features of chronic tonsillar inflammation."
and "(a) No specific findings were observed in the tonsils of PFAPA patients; (b) we could not find any difference in tonsillar histology between PFAPA and chronic tonsillar inflammation"
[Point (b) could possibly relate to your point on mesenteric nodes not shrinking.]
I do see that the pred dosage seems very small, which is good. But we always keep in mind that children are not merely mini versions of adults, so drug effects on children are always something to be wary of.
I also appreciate your thought that the nodes do not shrink between episodes. You'd need to compare with observations in other children. There might be something specific in this syndrome that keeps nodes from shrinking. But yes, if normally they do shrink on others, than that argues against PFS in your daughter. This point might take longer to research.
I hope you are not feeling so powerless anymore. Knowledge is power, and you will be an expert soon :)
P.S. the quickness that pred is reported to be acting is remarkable. Immune suppression on other conditions might take weeks and weeks. This makes me think that the mechanism is not obvious.
P.P.S. More mail on the way to you.
Good luck :)
Hi TonyBob,
Thank you again for your reply. Just to add we observed that the WBC increased to 14 during the last fever episode and came do 10 after the fever. Our concern is that the lymph nodes are still there at about the same size we checked last time(last month).
We will definitely ask the doctor about giving NSAID. Also, I read that prednisone reduces the duration of the fever but does not prevent the fever from coming. As per your suggestion we will definitely not go for a long term prednisone. Thank you again for sent me the link to the discussion board.
Thank you again for your reply. Just to add we observed that the WBC increased to 14 during the last fever episode and came do 10 after the fever. Our concern is that the lymph nodes are still there at about the same size we checked last time(last month).
We will definitely ask the doctor about giving NSAID. Also, I read that prednisone reduces the duration of the fever but does not prevent the fever from coming. As per your suggestion we will definitely not go for a long term prednisone. Thank you again for sent me the link to the discussion board.
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