Back to Basics - PUO- Case Scenarios - Dr Bala subramahnian

Added: 2026-05-26

[00:00:00]A warm welcome to all of you to the sixth episode of back to basics where we are concentrating on uh basic topics uh in pediatrics for practicing pediatricians.

[00:00:15]We are not uh uh concentrating on any um newer uh innovations and newer research topics only the basics we are taking in each episode and this is our sixth episode and this is a initiative from AP Kerala and it is uh being appreciated uh nationwide by all our uh members and central IP members as well. And I would like to welcome our speaker for the day who has kindly consented uh to take this uh all important topic on fever of uh more uh longer duration with uh case scenarios today and he has uh um the first call itself he has consented to take the topic and he has been ready since two or 3 months but we couldn't u manage the dates with him. So welcome you sir. I also welcome uh senior uh professors and uh also the senior uh pediatricians from central AP and uh IP Kerala as well as from other states who have joined us today and welcome all the delegates who have joined us on this platform. Thank you Jind [ __ ] >> Thank you sir. We are honored by the presence of state president of IP Kla.

[00:01:36]May I invite Dr. Dr. Nandukumar sir to address the gathering.

[00:01:40]>> Good evening all respected chairperson back to basics Dr. Johnny and today's speaker and most respected Dr. Balumar and senior professors Dr. Singasa Dr. Sugan and other dignitaries on this platform. My dear colleagues and friends, as you all know, pyrexy of unknown origin syndicating clinical scenarios in pediatric practice. While fever is among the commonest symptoms encountered by pediatrics, long fever without obvious sources often demands careful balance of clinical equipment, systemic evaluation and judicious investigations.

[00:02:26]in present day with the emerging infections challenging disease pan approach to PI has become more even more dynamic and evidence-based to discuss today we have lucky to have as Dr. John mentioned Dr. Balu Sudan is an outstanding academician, inspiring teacher, gifted orator and one of the most respected in pediatric experts in pediatric inferial disease in this country. His immense contribution to pediatric academics, clinical practice and continuing medically based educator has enlightened generations of pediatrics.

[00:02:59]With this few words over to Dr. Sua for further proceedings. I wish all the very best for this program and happy learning. Thank you.

[00:03:09]Thank you sir. As we give more importance to the academics, we are planning to keep the inaugural session short. May I in now invite Dr. Gopi Moan sir for the fellow stations.

[00:03:22]>> Uh respected Nanduma sir the dignit senior dignitaries my colleagues uh we have a very uh renowned speaker who wellknown and needs no introduction and Johnny and the topic is also very relevant. I will not uh u extend this inauguration uh by speaking much. I wish you all the best and wish you all a happy learning. Thank you for bringing Subraman in sir. It will be a very good experience for us also to learn from you. Thank you.

[00:03:57]>> Thank you sir. Now to propose a formal vote of thanks. May I thank all may I thank all respected uh dignitaries who have gathered here especially our president Dr. Nandum Kumar sa who has always been supportive of our academic activities our respected the teacher of teachers the renowned academician renowned pediatrician Dr. Balisramanin sir who has gracefully uh arrived here for this academic feast. Thank you so much sir from the bottom of all our hearts. May I also thank all the senior pediatricians everyone who have joined here for this academic feast. Without further ado, let us move on to the academic fiesta. May I invite Dr. Jou Joseph the central zones coordinator of back to basics presidential action plan to in uh introduce our respected speaker.

[00:04:49]>> Thank you Shwa. Gooding sir. It is a pleasure to have you with us. It is an honor to be introducing you. You are a teacher of teachers and all of us all still learn from you. Very happy to hear that you are continuing strongly with academics. Sir is a visiting consultant in g in kanchi kamakot chennai.

[00:05:08]>> He's a trustee of he's a trustee of child's trust medical research foundation. The head of academics at raila women and children hospital former director of the ker. He's been chairperson of the pediatric infectious diseases. His talks is something which all of us look forward to. He is someone who's as rightly told renowned across the country for his very practical evidence-based case and we are very sure we are very sure we are soon going to listen to sir for a very very practical case-based topic. Over to you sir.

[00:05:47]Um, thank you very much. Let me share my screen in a moment. Yeah.

[00:05:57]Yeah. Is my screen visible?

[00:06:00]>> Yes, sir.

[00:06:00]>> Yes, sir.

[00:06:01]>> Yeah. Audio is okay?

[00:06:03]>> Yeah.

[00:06:04]>> Yes, sir.

[00:06:05]>> Thank you. Uh, at the outset, uh, I thank Dr. Sebastian and my good friend Dr. Nandanda Kumar for uh the invite to address uh the Kerala IAP pediatricians and uh I'm indeed very happy that I'm going to address uh an audience which is which I always consider as an elite audience in Kerala because the the the fundamentals of clinical pediatrics are always have seen that they are very strong in the state of Kerala probably stronger than many other states in India including Tamil Nodu so I'm very very happy about it uh before uh I start session I would take around 45 to 50 minutes uh I have a I have a caveat here uh I'm not going to talk about recent advances in PU that's not that reason advances they they are all there in literature that's not a problem I'm going to only talk about the fundamental principles of clinical approach to PU with some case scenarios which I have seen where I have struggled to get the diagnosis and to reach the final destination The focus in this uh session would be like this.

[00:07:57]First I'll discuss the definition of uh a pu mute all of you please mute yourself.

[00:08:11]Yeah, muted. Muted.

[00:08:13]>> I would take you through some case scenarios where there were dilemas. I'm not going to take many case. I'm going to take only five cases with dilemas in investigations and treatment where we had difficulties in the diagnosis.

[00:08:28]And in the end I thought I would share what I personally feel is a reasonable protocol for management of PO and necessarily all these sessions ultimately uh should end with some good take-home messages for young practitioners in pediatrics.

[00:08:54]Now if a PG student is asked what is P or F of your of unknown origin each one will have a definition.

[00:09:15]is four five days fever and we have started something on day one or two for practical purposes but if you want to go by the textbook definition I'm afraid there is no consensus there's no consensus there is no definite definition for PO in fact usually when I ask postgraduates questions on PO first question I asked what is the most accepted definition of PU? That's how I asked. I don't know what's the definition of PU because there's no consensus definition and there is no consensus definition on very common things like recurrent respiratory tract infection. That's medicine.

[00:10:01]But by and large the number of days of fever has come down with regard to fear of unknown origin. That only tells us that doctors are under pressure to diagnose chronic problems quite early.

[00:10:15]All right. So that's one of the reasons why the most accepted definition is a fever of 8 days duration. Eight or more days duration where the there is definite documented temperature at least once per day 101 or more.

[00:10:35]Very important. At the end of 8 days suppose everything has been done whatever that is that is that is required for the case 8 days I'm sure no parent will wait no pediatrician will wait you will definitely do a good history taking do a good physical examination and by by 7 days almost all the basic investigations including cultures and others x-ray everything would be normally over. See we have done all this and if there is fever for eight or more days this is an accepted definition of PO. But another question postgraduates might be asked in Va what is pseudo PO? I said pseudo fuo or pseudo puo is a term where sequential fibral illnesses as we see sometime in deni sometime in in viral infection you get a bifphasic illness 3 to 4 days fever one day or two days gap another four days that is not pu it's actually a pseudo Po A very common sopo if you ask me is deni deni sometimes ebv infection also may present like this it can happen with measles also see initial viral exanthem fever tends to come down and then secondary complications occur fear comes back that's not pu that that's a pseudo pu with vague symptoms and there are some dilemas in giving the labels.

[00:12:23]The most important dilemma sometimes postgraduates young doctors for 10 days fever they will write a label fever without focus that's not the correct terminology for 8 10 days fever and all it's only a few there will be some focus clinical focus focus is very rare to see a p with the 8 days not having any clinical finding I would say less than 5% would be a dry PU all the other POS will be a will be wet they will give you clues and PO has to be differentiated from fever without source or fever without focus where the fever usually is less than for one week and definitely you will get clues on examination or investigations quite well like bacteria, viral infection etc. But then the management of PO differs from the management of fever without focus.

[00:13:28]Why am I saying this?

[00:13:32]PO by and large is not a medical emergency.

[00:13:37]Okay? Most POS that I see are all fevers in stable children. I'm sure senior practitioners like Dr. Nandakumar would agree.

[00:13:50]No 10 days fever. Sebastian might have seen 10 days fever, 12 days fever. They don't present you straight away with the presentation of shock or respiratory failure. POS don't present like that.

[00:14:03]Most POS are stable patients. Whereas your fever without focus can be deadly. It can present with septic shock, meningoitis, osteo osteomiitis, pylonritis, renal failure etc. So that's the difference between po and fever without focus.

[00:14:26]Having come to consensus between us that any fever for 8 days with adequate history, physical examination and basic laboratory test you don't have a diagnosis that you call it as PO. Let us go through some case scenarios of PO what I have seen in the last few years.

[00:14:55]This was a very interesting uh case where this is a 12-year-old adolescent.

[00:15:03]She had fever for 18 days, high grade. She had occasional disura absolutely no organal.

[00:15:14]She was toxic as I said very stable but not in shock. She was ill. She was ill.

[00:15:22]Clinical examination nothing other than fever. Nothing not even plengali lymphnopathy nothing was there and outside she had been treated with uh the first uh 3 days nothing was given. Fourth day sepoxine because she had disoria culture was done and somebody added nitroferentine.

[00:15:47]Child was admit the girl was admitted given septraone as entry fever hospitalized given pipas and amicosine in a government institution and they took the girl against medical advice and landed with us.

[00:16:10]Now the question is I went through the records complete blood counts are remarkably normal h 6,000 counts polymer of neutral lymphocy ratio is fine plate okay peripheral smear is normal and of course the only once a CRP was done on four four days of fever which is around 30 not very high and blood culture in a Norman hospital was reported to grow klepsial on day 12 a fever.

[00:16:44]Now at this point this was a girl with po 18 days toxic absolutely no clues and no symptoms related to GI drug except some disoria related to renal system.

[00:17:01]No manial signs, cardiac normal, blood pressure normal, fundus also we examine, everything was normal.

[00:17:08]We checked the forlim BP everything was fine.

[00:17:13]Now if I were to give this case to four different pediatricians and ask them how you will investigate, I'm sure I will get four different protocols.

[00:17:27]But then the first thing is I'm sure nobody will have the guts to treat this girl as OP OP. I'm sure you would admit.

[00:17:36]So the first question we must answer is answer is whether to admit a child with PO or not. If you ask me, not all POS need to be admitted, right? You can >> monitor the temperature at home, do investigations OP also if the child is stable. Of course, in this child who at 16 days, she has come from 16 days. She has come from outstation. She was toxic.

[00:18:04]No diagnosis obviously we would admit. So if you want to know the indications of hospitalization, the most important indication is toxmia or ill appearance and any symptom which is progressive for example respiratory distress, cough, joint pain or any clinical deteration is an indication for hospitalization.

[00:18:31]And of course one peculiar indication if you ask me how many cases you have seen manasan syndrome a proxy I've seen at least four including a doctor mother's child this can happen so to rule that out whether it is pseudo puo we'll have to admit and monitor the child sometimes abuse okay can result in pseudo pu and of course there is a definite need for observation of the child in a control setting with in somebody who is having fever for more than 8 days and of course investigations always are done in a most disciplined manner in an inatient setting. This is what is the consensus with regard to hospitalization.

[00:19:22]Then if you ask me the first thing in fact when when I when I see a case like this I pick up a junior most PG I ask him to take history I also sit down ask more points in the history ask him to write down then do a physical examination then check his findings I do everything then I discuss preferably with a senior PG because they will know more DD and more syndrome than what I and try to find out where it fits into.

[00:19:54]It's almost like a jigsaw puzzle.

[00:19:57]And most cases, history and physical examination will definitely at least in 90% of cases it'll give you a good clue to the diagnosis. Most often incomplete history only leads to problem. Overlook physical findings also lead to problem.

[00:20:18]And there might have been many laboratory clues on simple lab test like CBC, CBC which which might have been ignored. So these three things have to be looked at.

[00:20:30]Revisit the history, revisit the physical exam, revisit the labs done outside and revisit the therapy given outside.

[00:20:40]So we did all that. The only thing of course I had a chart of the antibiotics given to her but I thought it's so bad that I didn't want to show to anybody you know four antibiotics uh not really correct for example giving nitrurentine for UTI in a child who having fever is irrational it is not going to work unless it is cyitis this is pyphritis if it is eye fever UTI it won't work at all right So klepsiala blood culture after so much of antibiotic older child mostly it is a contaminants unless there is a urinary focus very rare for klepsial bacteria in a 12-year-old stable child. So we thought that this could be still one of those common causes of infectious causes of PO rather than autoimmune disease or malignancy or miscellaneous group.

[00:21:42]So what we did we did a CBC again smear both a normal again 6,000 total count urine routine and culture of course we did X-ray chest which is mandatory for some PO like this. Yes. Echo mandated to root Kawasaki myocarditis infectarditis.

[00:22:02]Ultrasonogram to look for any hidden absess. The radiologist said there is mild spomegali. What we couldn't make out CRPS 80 and ESRs 60.

[00:22:14]Blood culture.

[00:22:16]First we do a blood culture right at the OP. When she got admitted it was negative.

[00:22:23]Fever is spiking. Urine culture was negative. At this point of time, you're wondering what to do. Of course, we have not picked up the organism looks like infection. So, we did a bone marrow.

[00:22:38]And mind you, of course, if you ask me what we started, I'll tell you we started only on septraone and doxycyc. Doxycycline.

[00:22:50]So any fever more than 8 days or 7 days PO today in Chennai I don't know about Kerala in Chennai most patients we start on a combination of septraone to cover entry fever and we always add doxycyc in most patients because in child stress where I have been attached to for the last two and a half decades uh many patients come from Andra. The incidence of scrub tyers in POS coming from Andra is very very high and in there was there were times we always used to take history of going to a jungle lodge tour something like Shimoga something like K visit etc and then started thinking of we started thinking of scrub ters and nowadays even in ananagar in Chennai Basanagar in Chennai mount road in Chennai there are cases of scrub ters We see SRS in Mville. In fact, we are going to the jungles and building houses and all the animals are coming to our houses including your scrub type as a transmitter. So these these diseases are not uncommon even in an urban setting. I don't know about Kerala. I'm sure you will all have more experience than me. So the bone marrow culture while she was on cetraxone 2 3 days later 72 hours the microbiologist said it is gram negative baseli and it was salmonella paria she responded very well to septra because we discharged with acithroyin but they wanted to go back home she's well on follow this is the temperature chart see we started subtraction right on day one after doing a bone marrow biopsy and then she became aware in 4 days when the right antibiotic was given she became completely all right we discharged oraliz in terms of protocols if you ask me what are the learning points from this case number one history physical examination see look at this girl when we went back I didn't put it in the slides When we went back actually she had abdominal pain. She had a few loose stools indicating that this is disease is probably localized to the gastroenteral system. Dysphoria was only for one day. It was not persistent disoria. So in an older child absence of persistent disoria with so much of toxmia we knew that it is in our pilotis.

[00:25:40]He knew this is likely to be a gastrointestinal infection and empirical antibiotics should be chosen only after a learned and educated guess.

[00:25:51]See we must know what we are dealing with before we start start any antibiotic and again Klepsial blood culture seen 12 days later one must really find out whether it is a contaminant or not. In fact, one of the standard practices we follow at our institution in POS or difficult fever cases is to take two blood cultures. I'll tell you it is not great. People may think it may increase the cost. I'm afraid it's not. It doesn't. is worth doing two blood cultures in such difficult cases for the simple reason. See if you grow from both cultures different sides you know it's not a contaminant if it is cons only one culture the other culture is negative you know it's a contaminant right so doing two blood cultures should become standard practice for PO in fact two decades back for infectious three to five cultures are recommended at the height of fever it should be done so with the regulations are put. Now all that is gone. You take two simultaneous blood cultures.

[00:27:10]Maybe in infective endocarditis if you suspect you can take two in one day otherwise two simultaneous blood cultures from two different sides with good volume of blood should be able to pick it up. But in this girl probably she was she was an antibiotic only bone marrow culture picked up. The reason why I put this case is because bone marrow culture will be positive in entry fever.

[00:27:35]Even if the number of basili is very few even five per cubic mm it'll pick up.

[00:27:41]You don't have to have a large bacterial load. Nowadays with our automated systems it doesn't fail at all. The yield is nearly 90 to 95% in entry fear but it's never 100%.

[00:27:55]Without history and physical examination, you should not arrive at a provisional diagnosis.

[00:28:04]Of course, I will admit in this case after the culture, we went and examine the spleen properly. It is actually palpable.

[00:28:13]Okay.

[00:28:14]So, detail examination also will sometimes confirm your diagnosis and bone marrow culture helped us pick up the diagnosis.

[00:28:26]At this point of time there's one question people might ask.

[00:28:31]Okay, you are admitting a PO.

[00:28:34]Should you start antibiotic for every PO? That's one question number one.

[00:28:40]And how do you decide the empirical antibiotic therapy for PO? What is the choice? The answer is very simple.

[00:28:48]If the child is very stable, there are no red flags on examination. Nothing suggesting any organ compromise renal metabolic cardiac respiratory CNS.

[00:29:03]The best policy is to give a antibiotic holiday for a day or two. I know it requires courage to do that but you can always and parents may tell you sir 14 days fever you're not giving anything.

[00:29:16]You can always explain to them.

[00:29:19]Okay. In developed countries the rates of infectious ethologies is decreasing.

[00:29:24]In fact even in India infections are definitely coming down. More we see are viral infections and non-infectious illness. Of course, you should not wait for proof when you have a diagnosis clinical like osteomiitis, septic arthritis or endocarditis or absess anywhere you are going to start after starting after doing cultures and sometimes entry fever is is is a problem. See even if you take cultures before starting antibiotic the e is only around 70%. Even with back tech maybe 80%.

[00:30:03]Bone marrow culture also 90 to 95%.

[00:30:07]So you adult I mean mature physicians can make a diagnosis clinical entry fear based on findings and start antibiotic.

[00:30:18]Leptospiryosis and brucyosis you can consider empirical treatment. For example, leptospiryosis exposure to rain water brillosis exposure to unboiled milk even with because it takes about 7 to 10 days for the brusela culture to be positive and IGM is not recommended. PCR is not always available.

[00:30:39]So you can empirically consider starting treatment if you suspect it is brusalis based on history.

[00:30:48]Of course leptospirros will respond to any betalactum or antibiotic or doxycycline and you should choose your antibiotics with a learned guess.

[00:30:59]Case number two, this is a very difficult case which I handled about 25 years back maybe maybe 27 years back.

[00:31:08]It was an adolescent girl 11 years old who came with fever, rash and lympodopathy and hemeaggali high fever. High fever. Okay. Rashes like this maculopular typical viral exam thing like rash. 10 year old girl. She had generalized lympadinopathy epitroclear axillary cervical popial name any any gland. She was sick.

[00:31:47]The story was that this girl had some GTC seizure was given an anticon convulsion for 10 days. The grandmother promptly stopped the medicine after 10 days because she thought it is mata measles. The drugs are stopped. When she presented to us she was very toxic.

[00:32:04]Total count hyperlucosytosis 54,000 poly 64 lymphosy 25 is 11. Hemoglobin 11 platelets four lakhs and she was hypoxic.

[00:32:19]We she required oxygen and we did a bone marrow bone marrow culture hystopathology is reactive and viral markers EBV CMV HIV two cultures everything were negative and this was the this is the clinical picture of the girl. Can anybody put the correct diagnosis in this in the chat box?

[00:32:51]Okay, I'm sure many would make out the difficulty we had. What is the likely diagnosis?

[00:32:58]Is it a drug fever? That there is m as you see here in the counts milderia but the counts are very high. Can this be drug fever? Because we had root out malignancy including TB, gastric juice everything we have done. Tuboclo is ruled out. Viral infections are ruled out. Fungal infections are ruled out.

[00:33:19]Bone marrow cultures are negative. CT thorax showed interial pneumonitis and all infections of malignancy and negative. at this stage what what to do now at that point this is two 26 years back as I told you there was a nice case record of the Massachusetts General Hospital in New England Journal which had come to our library and we saw an article where an Indian boy in US develops carbomasipin hyper sensitivity syndrome following administration of anticon conversion for epilepsy. Look at the story. This girl received carbomicipin but even after stopping it went on and on and on.

[00:34:09]Finally we gave her steroids and she recovered. So the bottom line in this drug fevers are difficult to diagnose unless you take proper unless you start thinking of it.

[00:34:23]You'll be all be surprised to know that sephilosporins are the most common groups of drugs which cause drug fever in the United States. There's no Indian data on it. We use sephilosporins left and right. So any eostilia, any rash, any dress syndrome, please do not miss the possibility of drug fever. By and large, most drug fevers have eestilia.

[00:34:48]But the important caveat is that drug fevers you may think that once you stop the drug the fever may come down like in this case the mother has stopped even 20 days back but the fever went on. So in situation like dress even after stopping the inflammatory reaction may take two to four weeks to subside and you may have difficulty and of course steroids are lifesaving and by and large most drug fever should stop when you stop the drug in 72 hours rarely it may take two to 6 weeks this is the first case of carbomispin hyper sensitivity which we published in Indian pediatrics now we don't use carbon at all. We don't see these cases. The the lesson that we learned from that case is that any patient who started on carbomisipin or the newer molecule related to oxarbasin should always counel the parents that any cervical fever or rash coming within one to two weeks please come back. In fact in this patient we didn't advise because we did not know about this.

[00:36:01]The next is how do you obtain history in PO?

[00:36:06]First is document the fever pattern may give you a diagnosis. For example, you know the the cotian fever of soja is so characteristic right pattern may give you diagnosis of malaria.

[00:36:21]When there is recurrent infection, you should always think of a primary immuno deficiency, a secondary immuno deficiency, rash, autoimmune disorder in the family will give a clue that there may be an autoimmunity. For example, SLE, dermatomyasitis, any neutropenia in the recent past, ethnicity, race, where do they come from, family history, genetic background, TB contact, sick contact, geographical location. If they're coming from asam, you have to start thinking of malaria. They're coming from BR, you have to start thinking of leashmanasis.

[00:37:01]Travel history is very very important.

[00:37:02]Nowadays we have to start thinking even antivirus and Ebola virus animal and raw milk exposure associated symptoms drug exposure. Finally I like this term historic alternance. What is historic alternance? Go back to the history once more. Take the history once more. That is called it's not pulses alternance. It is historic alternance.

[00:37:26]Let us move to the case number three.

[00:37:31]This again were a true was a true story.

[00:37:34]This is a 3 months old who presented with fever of 9 days.

[00:37:41]Birth weight is 3 kg. No weighing 5 kg reasonably okay.

[00:37:47]Highgrade intermittent fever male child and was absolutely was absolutely well in between episodes of fever. So we thought this could be viral that the infant is pale hepatitis spomegal mild was there cuz we did a work up we took a blood culture started on antibiotics total count 16,000 polymer of 74 platelets were one lakh only CRP 120 urine routine and culture negative blood culture negative septone outside the gonoxy claw we started on septraxone and day eight while in our hospital day eight of fever day day eight of hospitalization fever is persisting and we are just planning for the next set of investigations I told the PG we'll start do a bone marrow tomorrow this again happened 15 years back uh the infant developed seizures was intubated went into the ICU.

[00:38:57]In the ICU, of course, we had just started adding doxycyc to all fever cases. We escalated the antibiotic to mirror banko. That's what we do when there is aptic shock.

[00:39:10]And mind you in the evening my junior most PG called me and told me sir there is an SR in the subra region. Okay. which we missed which we missed scrub tus IGM and PCR from the scrub tus leion SR was also positive blood PCR was also positive and with doxygen fortunately the infant recovered I'm admitting the mistake I made by missing the SR and not thinking of scrub ters today in PO where you start suspecting infection It's probably reasonable to cover doxycycline even in young infants to cover ricketetts infection and we all know in acute febrial link inopathy we always use septra doxycyc and dy initially empirically coming to the physical examination some dos and don'ts are required but examine methodically please strip the child and see every corner of course taking permission if it's an older child from the parents or from the Right? Don't miss findings in various parts of the body and you should examine more than once.

[00:40:30]Sometimes the initial clues may be missed which may become more apparent later.

[00:40:38]Important clues that are missed are SR, BCG ariththma for Kawasaki, epidlear lympodmopathy for EB virus infection, tonsular exate for EBV infection, weight loss for TB, murmur for infected endocarditis, rash for vasculitis or ricketettil infection, bone tenderness for leukemia. These are common findings which are often missed by us.

[00:41:04]We should always look first for disguised horses rather than zebras.

[00:41:08]Right. So you should look for mis missed findings.

[00:41:14]Case four.

[00:41:16]This is a 3 years 7 months old girl child previously well thriving and developmentally normal.

[00:41:24]Her main complaint was fever along with pain. The pain had started even before the fever. But the fever is the major complaint from the parents.

[00:41:34]There is a history of active TB in the paternal grandfather and he is on ADD and outside a pediatrician had admitted a child and given muropenum and bankcomin thinking it will be osteomiitis the child was not getting better and of course the letters are very small what happened we did we took the counts counts are all essentially okay around 5,000 to 6,000 to 8,000 So initially 8,000 later became 5,000 lymphosy predominant rather than neutrfil.

[00:42:13]Hemoglobin had dropped from 10.8 to 8 and platelets were marginally low initially around two lakhs. It had come to 1.6 lakhs. Now peripheral smear outside reported was absolutely normal and this was an X-ray taken outside outside. They came with the X-ray like this and can anybody identify the abnormality in the X-ray?

[00:42:46]Anybody can put in the chat box.

[00:42:52]Okay. We I also missed initially the wet film when I saw then I went and saw once more there is a beautiful perostial elevation as you see here in this when compared to the other right and with this story of two weeks we knew that this is not infection this is not infection hemoglobin drop dropping down so PO It can belong to only four groups.

[00:43:24]Infection, malignancy, autoimmune, miscellaneous.

[00:43:29]This doesn't seem to be infection.

[00:43:32]This could be either autoimmune disease or a malignancy. And with this finding, we knew that this could well be a malignancy.

[00:43:41]And what investigation you do particularly when there is falling hemoglobin straight away bone marrow and bone marrow culture it was the bone marrow was full of lymphoblast.

[00:43:55]Why am I putting this?

[00:43:57]You must know the role of bone marrow in PU. Many people might think doing a bone marrow is an invasive procedure. Even yesterday in our midterm conference in PETA they presented a case where they said parents refuse bone marrow. You have to convince them. Okay. Unless there is superior media, you cannot give anesthesia.

[00:44:17]Bone marrow is a very simple procedure you can do properly. You can get yield of cultures, rare organisms, common organisms.

[00:44:27]And in non-infectious P malignancies, HLH you can't diagnose that bone marrow.

[00:44:33]And in an autoimmune disease like soja slee if you have bone marrow if you have some hematological abnormalities before starting steroids you should do a bone marrow to rule out malignancy you should not start >> steroids with the diagnosis of soja without doing bone marrow and in fact you should also do LDH and uric acid in such cases the moral of the story from this case.

[00:45:04]My last case, this is again adolescent female who had fever and cervical adinopathy for 20 days.

[00:45:15]Again, Andra case given antibiotics.

[00:45:18]The cervical adinopathy tended to disappear after a week. Again the adinopathy came back with the bang. The ultrasound the radiologist felt it could be reactive.

[00:45:30]He couldn't pick up any lesions suggestive of an absess or tuberculosis.

[00:45:35]Treated a tamox outside not resolved.

[00:45:39]Posterior cervical lymphopathy mattered lymph nodes otherwise nothing on examination nothing no anemia no thrombocetapinia bone no bone tenderness nogali and of course we did start parental antibiotic we did start subtraction and clinamy symptomatic relief was there and at this point of time the consistency of the lymph node was worrying So actually don't ask don't tell me that why did you do PT spec pet I didn't do it they had their family physician came and said sir we have to do pet CT they got it done they took the child out and got it done and the PET CD was reported to show metabolically active cervical and upper abdominal lymph nodes and they said it could be Cox to most probably and the doctor relative wanted me to start empirical at I said nothing doing we'll do a biopsy and uh of course they had done a FNAC which didn't reveal anything and we did the biopsy and mind you a report that came showed features of cukuchi's lymphodinitis looking back this again was an old is why did we miss it? The one clue that was there I didn't put it in the bontly put it in the investigations was very very significant. What was the clue?

[00:47:20]In spite of fever and lymphenopathy in this girl the ESR was 100 but the CRP was negative negative.

[00:47:33]That's very very unusual. This discordance of high CRP with low C sorry high ESR with low CRP or negative CRP is seen only in three conditions.

[00:47:49]One is SLE SLE actually they are all SLE patients are deficient in CRP. They don't produce CRP.

[00:47:59]But in SLE CRP can go up and there is infection or polycositis or arthritis.

[00:48:06]Two is kikuchi which is the cin of sle which can present as lympodopathy and p is small bubble cronhn's disease.

[00:48:18]Cronhn's disease not please remove the impression that cronhn's disease always will produce high and high CRP. not necessary in small bubble crowns. ESR will be high, CRP will be very low. This clue we missed in this girl the ESR was 100, CRP was negative.

[00:48:41]In fact, we could have made as clinical diagnosis. Nowadays, we pick up this early. This lesson made us diagnose more and more cases of SLE right on arrival when there is a high CRP with negative high ESR with negative CRP.

[00:48:57]Now as I said earlier PO has only four groups.

[00:49:04]One is your infection, second is autoimmune disease, third is malignancy, fourth is miscellaneous. You should start suspect suspecting infection mimics when there is a multi- systemm disease in older children and children in spite of high fear for long time they are not toxic high platelet count should make you suspect autoimmune disease Kawasaki like or SJA and inflammation everywhere total count will be high urine will show pyora no bug will be there and of course discordance between ESR, CRP and the new uh uh agent new agent of inflammation proalciteton.

[00:49:50]Having discussed all this what is the correct way to investigate PO? What is the appropriate protocol?

[00:49:56]Before we go into it, we must know infections are responsible for most POS in pediatrics much more common than in adults.

[00:50:07]Bacterial is number one including TB, bristle losses, rickets here, viral EBV, CME, HIV even adinoirus others fungal right non-infectious oncologic or autoimmune orgic and miscellaneous miscellaneous like I said you know manasan syndrome by proxy kay disease is you know autoimmune disorder periodic fever syndromes etc. Having said that if fever is above 8 days no identifiable source child is well initial workup can be done towards ruling out infection stop non-essential medications including antibiotic if the patient is well CBC urine analysis blood culture basic metabolic panel X-ray LFT observation and serial examination is good enough you can take an antibiotic holiday but the child is not well you should admit in addition to the basic workup do cultures without cultures you can't treat a PU if necessary do a CSF do imaging like CT MRI empirical antibiotics may be started serial physical exam if you identify the source for example you have picked up a liver absess picked up an appendicular absess picked up a so absess The source resolution should be carried out by treating the source. For example, when there is localization of infection, antibiotics will not work. You will have to call the surgeon.

[00:51:51]And if there is no source identified, categorical workup. What do you mean by categorical workup?

[00:51:59]This is very important. If it is infection, everything has to be done including all the TB test, molecular test nowadays, NGS, PCR, etc. oncology bone marrow PET CT and don't give steroids biopsy uric acid LDH autoimmune rheumatological ANA all those antibodies feritin for HLH C3C4 CH50 immuno deficiency workup if necessary for PO imunoglobins plustmetry NBT and all exom sequencing etc and the categorical workup still you not identify the source please refer to a tertiary care center and consider repeat cultures pet CT MR new cerologies NGS bone marrow etc nowadays most POS require a PET CT if you ask me what is the role unlike Take adult POS PET CT is not so helpful in pediatrics but what is important for you to remember is that it involves lot of radiation two cost third it may not give you the diagnosis it give you only the localization of the lesion for example you have generalized lymphopathy you don't know the cause if you do a PET CT you may pick up a lesion from a bone or some soft tissue area which may be amorable to biopsy or heptically is there you can't do a spleen biopsy liver biopsy they're all invasive if you get some other soft tissue lesion picked up by the PCD it may localize the lesion it may help you make a proper diagnosis of course there is concern of cost and radiation and the other problem is do you give an approxim for P as a trial for autoimmune disease. The answer is no. On the other hand, consider doxycyc in most P. If you think of infection and last is the summary for you.

[00:54:24]In fact, fever is a response to infection. It can be a friend to the child, but PO is not a friend to the child. Right? Infections are the most common. And I like this cartoon. We must remember fever is not a sign of subtraction deficiency.

[00:54:41]In the next few years, we may also change the slide to fever is not a sign of muropenum deficiency because there's more and more use of muropenum these days. Most POS are only uncommon manifestations of common infection like entry fever, TB, ricketet cell etc. I already said there are only four groups.

[00:55:00]General appearance should determine the rapidity of test and initial antibiotic therapy. Malignancy as a cause of P is much less common in children when compared to adults.

[00:55:11]Having said all this, even if the best of center is onethird of POS, no diagnosis is finally made. The child may become better also. Again go back to history and physical examination.

[00:55:23]Physical findings may change. You have to be careful not to miss them.

[00:55:27]Stepwise tired approach should be implemented to decrease cost and time to diagnosis.

[00:55:33]Persistent toxmia is unusual in autoimmune disease. Multi-system involvement in older children is not common in bact infection.

[00:55:42]Any bicyina with high platelet count think of vasculitis. High CRP sorry high PSR with negative CRP SLA or kikuchi or chron should be thought of. High feritin and LDH may give clues to HLS. Always check the forlim BP. Hypertension fever is not likely to be infection. And always call an opthalmologist. Always do an echo. Always start an antibiotics or steroids only after doing bone marrow. And don't hesitate to take help with your lab experts like pathologists, microbiologists, biochemists and also ID experts.

[00:56:28]When in trouble take history like a first year UG examine like an exam going PG. Look for clues like Sherlock Holmes.

[00:56:34]Remember most of children we see have not read Nelson and present often atypically.

[00:56:41]It is important to maintain faith and clinical skills and judgment. I am afraid the scene of PO is changing. How is it changing? We are moving away from infection to more and more cases autoimmunity, allergy, malignancy and lifestyle diseases in terms of PO. Thank you very much. There are any questions?

[00:57:02]I'll be happy to answer.

[00:57:07]Thank you so much sir for that excellent and crisp and very lucid talk. As as sir has rightly pointed out many many a times the PU is actually uncommon uh manifestations of uh common infections.

[00:57:22]Usually we come across a lot of uncommon manifestations of common infections. So there is a couple of questions in the chat box. any role of MRI in place of PET scan?

[00:57:36]>> Absolutely. That's a very valid question. In fact, if uh uh the child is older, if no anesthesia is required, whole body MRI is preferable to reduce radiation.

[00:57:54]But when it comes to picking up a malignant lesions, certainly PET CT is superior to MRI. In recognizing lesions in the brain, MRA may be superior. But when it comes to recognizing lesions in the lung, heart, PET CT is superior.

[00:58:17]That's what they say. And uh in in most western centers they would prefer MRI particularly if it is an adolescent girl rather than PET CT.

[00:58:32]>> So the next question is how common is borderia sepacesia infection?

[00:58:38]If you get a burad area growth either from the sputum or from the blood, you should start thinking of cystic fibrosis or chronic granitus disease or a contaminant from the lab. That's why I said if it is burket area definitely both the cultures from different sides should grow otherwise it can come from tap water right it may be a contaminant it's a frequent contaminant so it's better to have two cultures but if you have pneumonia and growth of burkaderia from sputum or from b you should start thinking of cystic fibrosis blood culture positivity of burkad area sputum culture positive make start making you think of chronic granome disease and more importantly your burket area will not respond to septra you may have to use either mopinum or septic which is the specific drug and prolonged courses may be required that is regarding burk it's not common it may be newborn outbreak but in older children in older infants if you get burkadia as I CF CGD have to be ruled out and immuno deficiency.

[00:59:56]>> So Kawasaki disease now emerging as an important cause of PO IVIG can be used as a therapeutic test or not.

[01:00:05]>> No, the answer is no. Now IVIG is see I'll tell you therapeutic tests very rarely confirm any diagnosis.

[01:00:18]Uh in fact it is the other way. If you suspect ricketettsial infection or scrub typhus, if you start doxycyc, if the fever does not regress in 7 48 to 72 hours, it is not ricochetial infection.

[01:00:36]Okay. Even in ricketettial miningo enaphilitis if you give even oral doxycycline the fever subsides in like I told you the case infant which presented with seizures and all doxycycline 48 hours child came out of the ICU if it doesn't it is not infection that is one but therapeutic trial of IV I'm afraid is not rational is not rational you must have some working diagnosis But IVIG can you know suppress so many infections also infections even severe bacterial infections maybe suppressed temporarily because you are giving lots of antibodies IGG I don't think it is rational to give IVIG without a diagnose one second important point if you want to give IVIG on a doubtful diagnosis sometimes yeah we do give IVIG without all the essential features of Kosaki based on our clinical journal. I'm not saying I don't give yes we consider but one caution is if you want to give IVIG please take 5 ml of serum and preserve one sample before taking out IVag.

[01:02:03]The reason is if IVIG doesn't work and the fever continues you are thinking of some rare disorder like moard antibbody enkaphilitis autoimmune diseases like SLE your massive IVIG may change the test reports in a significant manner.

[01:02:26]So please take one sample preserve and then give I a empirically if you think there is justification for it for PO per se without a diagnosis prob at least a probable diagnosis I don't think it is rational to give IVIG >> so what level of increased LDH or uric acid suggestive of malignancy >> what level uh uh I'm afraid my I I don't know the correct level but you see you must remember LDH will go up in malignancy will go up in eskeemic hepatitis or any hepatitis or any eskeeia to any organ even if a person suffers from myioardial infection LDS can go up pulmonary infection LDS can go Hemolytic anemia LDH will go up.

[01:03:28]Hepatitis whether it is viral hepatitis or typhoid hepatitis LH will go up.

[01:03:36]Uric acid I don't know the levels. I I'll have to refer I'll refer what level but you know you don't expect uric acid to go up in a PO unless there is malignancy. If both are high, I think the possibility of leukemia or lymphoma is extremely high extreme. Of course, both being normal does not rule out leukemia or lymphoma early stages.

[01:03:59]That's my answer. But I can I I don't know what level should be considered significant. I'll have to refer and tell you. I don't know honestly.

[01:04:08]>> Thank you, sir.

[01:04:10]>> Any more?

[01:04:12]Sir there is there are a few more questions in the chat box.

[01:04:16]>> Uh one is when to do CSF in PO.

[01:04:20]>> If you suspect meningo ankaphilitis that's that's a straightforward answer.

[01:04:25]Clinical diagnosis of meningoitis you do a lumbar puncture otherwise you don't do.

[01:04:33]>> Okay sir. Thank you. Uh there were a few more questions regarding the first case sir.

[01:04:37]>> Yes just one minute regarding the regarding the CSF.

[01:04:41]uh you know now uh of course I had some more cases for I mean I didn't want to spend too much of time presenting all sorts of cases one other case actually I wanted to present was a child who presented with fever alone 10 days fever first five six days not there is there are no clinical clues except irritability of the child older fellow four years 5 year old fellow and slowly became more lethargic. Initially he was irritable, later he became lethargic. No manial signs and uh we thought this is this was behaving funnally. We got an MRI which is suggestive of Adam and we did a serum antibody it was positive. We gave pulse he walked home in 2 days. So nowadays admod antibbody enkaphilitis they are notorious for presenting as p and in the early phases they may not have many cns manifestation they may just behave like any other fever without organomegali without lymphodenobi and even the blood counts all will be normal we have been b I've seen at least two cases of Modard antibbody encaplitis presenting SP1 and at least two cases of ADM first five six days nothing happening the CSF later increasing lethargy initially no menial signs MRA picking up ADM and then we do a CSF that's very rare >> so usually indication if you suspect mogard or anti autoimmune enkaphilitis or ADM of course CSF is required so be Other point you must know tuberculus minisitis can cheat all of us. First one week it may not show any features of CNS infection at all. Child may only lose sleep and vomit that's all. So child will be usually Adam and this not necessary sir. Whatever I have seen both were not follow changes. I agree with you but we must >> we have we have an Adam with us now that is referred as UK because child had this urinary retention >> and urine examine show 12 >> so they treated as missing then they started antibiotic then referred as UK not responding to antibiot >> in fact I often joke in sessions you know 20 years back we didn't have all these autoimmuneis antibiotics ADM you would have treated all this empirically as TBM with steroids and they would have record also ironically now we don't do that we don't start at just like that because we have definitely better uh battery of test for diagnosis and we don't do uh the so-called we don't give the empirical therapy in CNS tuberculosis anymore Thank you sir. There were two more questions sir regarding the first case.

[01:08:11]Uh one was uh what about the role of panel of PCR test available in case one?

[01:08:21]>> That's a that's a good question.

[01:08:24]you know uh is it I'll tell you whatever said and done today cultures are the most reliable available diagnostic test for common infections like entry fear in in typhard I'll tell you the problems we have as clinicians The first problem we I don't know about Kerala we continue to unnecessarily rely on vidol which is a useless test.

[01:09:08]In fact there is actually an article which which which calls for banning of vidol test by the government of India.

[01:09:15]Even today I saw a patient in my clinic two days of fever from Msel town in Tamil Nadu older girl somebody does a widall slight test one in 320 positive their parents have been frightened they have been asked to admit the girl they came she's playing I gave parasol and sent I didn't do any investigation wol should be banned if you ask me it has no role today in 2026 Six, right? It is like keeping a BSNL telephone in the house. Nobody has today, including me. Useless. We should abandon Wol one.

[01:10:00]Next is your IGM test. Another useless test. The kits have not been standardized.

[01:10:09]It is early Wall. is equal to idol in the first week but it's useless. I've seen enough number of cases with IGM positivity not being typhard being deni and IGM negative cases culture group positive useless that also please don't do third culture as I said culture has limitations it doesn't pick up all the cases but it need not if a child has got eosapenia lucopenia gastrenal symptoms penomegali and you have done a culture even the culture is negative if the child is going to respond to sephixima I would complete the course I wouldn't stop if I'm convinced clinically that is entry fever that's all again for typhoid PCR tests have not been standardized the ICMR is trying to uh improve the uh testing systems for uh uh PCR Even yesterday I was discussing with the professor bali of CMC that has not been standardized anywhere in India. Typhoid PCR even though private labs are offering it as part of a fever panel. He says the panel the the typhoid PCR is highly unreliable.

[01:11:31]Okay. So we can't use PCR for diagnos typhoid today which is the most common cause of PU if you ask me. But when it comes to infections like brucela, meloidosis, your burket area, yes, PCR is coming up. Now, fever panel tests by the uh your bioire group is coming up.

[01:12:02]Unfortunately, we must remember every good thing has also got a bad thing in it.

[01:12:08]The problem with all these PCR tests is that there is very high sensitivity even it is from the skin or I'm told the microbiology technician who performing the test if she or he coughs even can become positive in the PCR of the blood imagine or for that matter with any specimen. So the high sensitivity is a disadvantage as well as an advantage.

[01:12:37]And technology is evolving in such a big way that in the next five years I'm sure we have next generation sequencing which will give us confirmation whether it is a pathogen or a contaminant but even then ultimately you have to use your clinical judgment. For example, you have done something, child is playing and responded to one dose of amoxicine.

[01:13:09]Next day they give a report of an unusual organism sensitive only to muropenam.

[01:13:14]Who what will you believe? Will you believe your clinical finding or your lab? I would not believe even the most sophisticated PCR.

[01:13:23]However, these molecular tests have revolutionized diagnosis in TB even in numacco myoplasma okay adino virus RSV.

[01:13:38]The other thing which is very very good about these molecular tests is that they help you in antimicrobial stewardship.

[01:13:46]For example, you have a child with viral what looks like viral pneumonia. None of us will have the guts to withhold antibiotics.

[01:13:55]But the X-ray says to viral pneumonia counts are sessed antibiotic. You do a PCR from a bal or aspirate if it is RSP positive you will definitely stop antibiotic that way it will help right in fact I used to joke just because Dr. Balis is found standing near a liquor shop that doesn't mean I drink.

[01:14:21]So your nasoparangial PCR tests are like that just because they are there it doesn't confirm that they are the cause they are the causes for the pathology in the lung that's the problem with all this even CSF specimens can be contaminated but among all the molecular test CNS is very very useful excellent in picking up pneumocus manoccus and also your HSV Respiratory helps in antimicrobial stewardship helps you pick up puses whooping cough and microplasma but also RSV and adino and if you do bal yes colony count of cultures comes in a big way to your help and PCR is very good when it comes to bone and joint infection there's a separate panel excellent which picks up even king which is rare which is not yet reported highly in India.

[01:15:25]But when it comes to gastro gastroenterology specimens, your gip PCR panel is a useless one. Is a useless one. It'll throw up some positivity. It doesn't help. Only in immuno deficiency it helps.

[01:15:42]That's my take on it. But however technology is changing is getting refined. In the next 10 years I predict that all of us will have one machine in our office.

[01:15:57]Patient will give you your assistant your receptionist will do a swab from the throat put it into the machine. 2 minutes the report will come like a coffee vending machine. You'll get a report. The patient will come with a slip with the report. You won't even examine and you will prescribe accordingly. That's what is going to happen in the next 10 years.

[01:16:20]>> Can I ask one question?

[01:16:22]>> Excellent discussion.

[01:16:24]>> How are you? How are you first of all?

[01:16:25]Very nice.

[01:16:25]>> Fine. Fine. Thank you.

[01:16:27]>> Excellent discussion as expected. And in the chat box there was a question that why um after giving septone why don't you you continue with sephixim rather than I don't know whether you have answered it. I know. I know. Uh actually uh in in my unit for the last 10 years madam we have been practicing a different type of switch therapy.

[01:16:55]Of course Dr. Dhan Lakmi is analyzing the data and she has completed we'll publish it madam this year. By the way in our own experience the relapse rates are very well reduced if you use this switch therapy what we do in our unit uh we we will soon publish madam certainly by this year what we do inatient toxic patients we start with septraxone and when we discharge we discharge with acithroyin for 7 days and we have found that the relapse rates are extremely less Whereas when we continue septra with sephixium the relapse rates were around 5%.

[01:17:39]That has been our protocol.

[01:17:42]Of course if you ask me whether there's any reference for me it is it's my own protocol which I have followed uh and uh I've seen only one relapse in this protocol so far in our cases Dr. Dashmi is analyzing will soon be published.

[01:17:56]madam that's our protocol that's our protocol I would advise for everybody this our unit protocol and we have completed the data and we'll be analyzing and publishing it >> okay thank you so much it's nice hearing you >> thank you madam so I still remember you me taking to several places when I visited your institution thank you so much madam okay bye Thank you very much sir. I think so there are no more questions we can wind up very oh okay sir. Uh are there any more questions from the audience? Any more questions or comments from the audience?

[01:18:42]>> Okay.

[01:18:44]Thank you so much Balisman sir for giving us this wonderful opportunity to learn from you. It was indeed an academic feast and wonderful session and I'm sure everyone who have gathered here have benefited by tons after this class.

[01:18:59]So with this closing remarks with the permission of our chairperson and the state president and the speaker and everyone gathered here let us call this a day. Good night to all.

[01:19:09]>> Good night. Thank you sir. Good night.

[01:19:11]>> Good night Dr. >> Good nightumar. Good night Sebastian.

[01:19:14]Good night. Thank you very much.

[01:19:15]>> Thank you sir. Thank you sir. Thank you sir. See, see see you at next 7th meeting.

[01:19:24]>> Yes.