A Great Expert and a Great Guy Too

Dear Bloggers

This week, Dr Makoto Aoki visited our institution to do a Problem Based Learning case conference on a patient with a Fever of Unknown Origin.

Dr Aoki went through and dissected the elements of the chief complaint meticulously leaving no stone unturned and reeling off lists of causes for each abnormal component of the history, physical exam or lab data.

Not only that, when doing his teaching in spoken Japanese language, he admixes this with fluent English so that non-fluent Japanese speakers such as myself can understand. Moreover, he writes everything in English which is a really unique way to teach the residents written medical English corresponding to the Japanese vocabulary.

Dr Aoki's stories of previous cases are enlightening and his jokes a joy to listen to.

It is always a great pleasure to have Dr Aoki come to vist and teach on Infectious Disease medicine.

I just wish he would translate his new Infectious Diseases book into English ! :-)

Keep up the great work Makoto!!!

November Case - Answers

Dear Bloggers

I am sorry for setting you such a difficult case but all of the information to work out the case lies in the history, examination, radiology and microbiological results.

Firstly, in order to work out the case, the hidden clues lie in the fact that although the patient is only slightly confused and her mini-mental state examination reveals a pretty good cognitive state, she is most likely able to answer further questions to derive more history.

So, let's go through each question and answer in turn:

Questions:

1) What does the Skull Xray show?

The skull Xray shows a vertical, linear metallic object in a vertical plane on the lateral view of the patient. There is also evidence of previous dental work because of the metallic fillings present and absence of teeth!


2) How will you try to work out the cause of the abnormality?

In dealing with the main abnormality, which is the vertical metallic object, the history and physical examination are there to guide you. There is no evidence of any head trauma and no history of any cranial surgery. Hence, is the metallic object actually inside this lady's skull or on the surface of her skull? Remember, an X-ray in one plain does not always give you the location of an abnormality. An anteroposterior film would also be needed to locate the abnormality.

However, there is an even easier way to establish the cause of the abnormality in this patient. First of all, if the patient had severe confusion and could not answer questions then a simple physical examination of the scalp for a metaliic object would be in order.

However, this patient can answer questions. All that was done was to ask the patient "Do you wear hairpins?" -- the patient replied "yes, all the time". Examination revealed no hairpin as it had been removed by the thorough nursing staff before her head CT scan!

Hence, the hairpin is a 'Red Herring' put in to divert your attention away from the real problem that follows next! Sorry!! :-o
Hence, history, history and history again wins the day. Ask the patient! This avoids expensive scans and radiation exposure..... :-)

3) What could be the cause of the positive blood cultures?

This patient has a history of aortic stenosis and atrial fibrillation. Both these conditions can predispose to collapse and even more so in combination. Moreover, she is using Ramipril which is contraindicated in severe aortic stenosis because it can result in hypotension. The warfarin is also another potential concern in respect of unrecognised haemorrhage which could be gastrointestinal or intracerebral as likely foci to result in sudden collapse.

The history of a peptic ulcer compounds the suspicion of a possible GI bleed on warfarin. However, there was no complaint of abdominal pain or malena although not all elderly patients experience painful GI haemorrhage nor do they develop malaena in the early stages.

The fact that the patient has no neurological signs makes a massive stroke less likely although a small subarachnoid bleed is still possible but there was no 'thunder clap' headache making this diagnosis somewhat tenuous. The CT head scan revealed no infarct, bleed or SAH. There was no intra-cranial metallic foreign body either! :-)

The real clue lies in the fact that the patient has a fever and positive blood cultures formed of chains of streptococci and she has a cardiac murmur. One must always consider infective endocarditis as a hidden source of infection and vegetations can embolise during anticoagulation therapy (although as mentioned, in this patient there were no localising signs in the neurological examination).

The Xray of the skull comes back to tell us that this lady has dental disease -- she has had multiple tooth extractions! Streptococci in chains might suggest oral streptococci. Of course, other sources of strepococci can come from the pharynx, middle ears, skin (cellulitis) etc but the patient complained of no such symptoms in any of those areas and the physical examination revealed no evidence of these possibilities.

The fact the patient might have a superimposed infection (i.e. sepsis) on a background of aortic stenosis, atrial fibrillation and on an ACE-inhibitor would be sufficient reason to predispose this patient to a collapsing episode. However, a small stroke and subsequent seizure e.g. from a septic emboli, might just as well cause a collapse. As in all elderly patients, silent acute coronary syndrome (ACS) should always be ruled out (please see my previous blog entries).

4) How will you determine the predisposing cause?

Again, ask the patient !!! This patient admitted that she had a tooth extraction 2 weeks before her collapse for dental disease and for fitting a new set of dentures. She was not given prophylactic antibiotics.

The fact that the patient had an aortic murmur could be due to a Bicuspid Aortic valve which is a risk factor for endocarditis. Without a dentist knowing about a cardiac murmur they cannot be expected to give prophylactic antibiotics.

It is very important to inform all patients if they have a murmur so that they can inform their dentist such that antibiotics can be given prophylactically during dental procedures.

In this case, the lady underwent a transthoracic cardiac echo which did not reveal a vegetation. The aortic valve area was and gradient were consistent with only mild aortic stenosis.

However, during her admission, she complained of several episodes of central chest pain at rest that were gripping in nature with subsequent ECG changes and a mild tropinin T rise (0.15). It is entirely feasible that an additional potential cause of collapse was indeed a silent acute coronary syndrome although this is not supported by her admission ECG nor is it supported by a previosuly normal troponin T test. Another potential cause of coronary ischaemia is coronary artery emboli from a vegetation.

This patient also unwent cranial MRI imaging which revealed 3 fresh small infarctions that were not visible by CT, consistent with septic emboli.


The above Diffusion MRI picture shows a 'bright' area consistent with a new infarction.


In the above MRI picture, a midline bright dot is consistent with a new infarction.

In the above MRI picture, an asymmetric frontal lobe lesion is again consistent with a new infarction.

In view that the eventual culture results grew Streptococcus Lancefield Group G this would be very consistent with a picture of infective endocarditis as was suspected at the bedside on the morning of the admission.

This lady meets the criteria for definite I.E. with one major criteria (positive blood cultures with an organism known to cause I.E), and three minor criteria (Temp >38 degrees C during her admission, embolic phenomena and a predisposing heart condition i.e. abnormal cardiac valve).

This is the second case I have come across in the last few years whereby I.E. has been diagnosed using the modified Duke's criteria with an absence of obvious vegetation. For the other case, please visit this link.

This was followed up by a transoesophageal echo which showed aortic stenosis and mild mitral regurgitation but no vegetation was seen. This however, does not rule out infective endocarditis.

In view of the history, examination, lab tests, microbiology and MRI result, it is most likely that the vegetation embolised to the patient's brain resulting in there being no visible evidence on the heart valve.

The patient was commenced on penicillin G and gentamicin for this fully sensitive organism.

This patient chose not to undergo coronary artery investigations.

Group G Streptococcal Endocarditis

The usual cause of a streptococcal I.E. has classically been by Group A Strep (GAS) although in recent years Group C and G have also been found to cause I.E. In fact, both Group C and G strep produce disease in a very similar way to the GAS and can be considered en bloc.

Group G strep can be found in the oral cavity and there have been several case reports of it causing I.E. especially on abnormal cardiac valves.

Moreover, Group G Strep I.E. has been documented to have a higher risk of embolisation than other forms of I.E. as has been found in this case.

Diagnosis

1) Infective Endocarditis with Embolic Stroke ? cause of collapse and confusion

2) Acute Coronary Syndrome (? atherosclerotic ? embolic from endocarditis)

3) Atrial Fibrillation

4) Mild Aortic Stenosis and mitral regurgitation

Professor Gerald H Stein, University of Florida, kindly answered this case and got the 'nail' on the head! Well done. Here are his comments:

1. Skull xp shows a metal object which could be an artifact- an object outside of the skull such as a woman's hair pin. Upper dentures are also seen. C 3 has an anterior osteophyte. No skull Fx in the single view provided.

2. To prove my idea of the metallic object, I would examine her scalp to search for the object, and if not found, ask her about a prior reason for any such intra-cranial object. It is bad form to have only 1 skull view; multi-projections are required in every case of skull xp's.

3. Strep in 4 BC's= a septic source. The axillary fever would be about 38 *C if taken orally. Her mild confusion/delirium is likely from the sepsis. Most likely source is infectious endocarditis. However, more than 1 source is possible. In this case with mild confusion and fever an LP is indicated to rule out co-existing bacterial meningitis. Septic brain emboli are a real possibility. Best to perform brain CT to r/o skull Fx and brain abscess before LP

4. TTE for vegetation on aortic or less likely mitral valve+ assess degrees of aortic stenosis. Warfarin may exacerbate the septic emboli shower. Urinalysis for RBC and RBC casts + rheumatoid factor are indicated. These are sometimes + in IE.

An anonymous comment was received which is below. Thank you to this person who contributed their answers to this difficult case.

1) What does the Xray show?

I would say that there is something metallic in the skull and that seems going through the base of the cranium into inside. In addition, there appears to be a part where the continuity of the bone is lost.
However, any evidence of trauma was not found on physical examination and history, therefore there is probably no fracture.

2) How to work out the cause of the abnormality

At first, I would like to see the nasopharynx. If something penetrated the cranium, I might be able to observe some abnormality at its entrance. Fiber scopes would be useful.
With or without any information I could get from it, I will order head CT to get more information. This patient possibly have brain abscesses or hemorrhages.
In addition, cardiac echo is required to find the clue of IE or clot .

3) What could be the cause of the positive blood cultures

IE (infectious endocarditis) or
infection through foreign bodies

4) How to determine the predisposing cause

To be honest, I have no idea, but I am worried about her multiple medications and renal failure. If her confused status is thought to derive from digitalis intoxication, ECG, electrolytes, drug concentration would be helpful.
Regarding IE, the predisposing cause may be cardiac valve diseases or poor oral hygiene.

The Moral of This Case

What you initially see is not always what it is. Once all usual causes of an abnormality have been ruled out, no matter how unusual or obscure it may seem, what is left may indeed be the problem.

Go back to basics. Find out by asking the patient and looking, and if necessary, take that extra AP plain view of the skull to be certain. More advanced radiology should only be ordered if there is a reason to do so, for example, in this case there was a real suspicion of septic emboli. The fact that an MRI of the brain was performed means by definition that there was no intracranial metallic object!

Risk factors for new disease can sometimes be inferred by the presence of existing diseases e.g. aortic stenosis, and physical examination findings, but at the end of the day, it is the history from the patient that gives you the real information. If you don't have the data for a patient then go back to the bedside and take more history.

Medicine is not an exact science. You need to be a medical Sherlock Holmes and find the clues that lead you to the answer. It may not happen all in one go but gradually, gradually the answer may come from the patient to make everything more clear.

Dental Prophylaxis

Although the AHA guidelines for prophylaxis for endocarditis changed in 2007, the recommendations for high risk procedures causing bacteraemia are still firmly in place.

Dental treatment is a high risk procedure whereby manipulation of the gum tissue, penetration of the tooth substance or oral mucosal breach can result in entry into the systemic circulation of oral commensal bacteria resulting in infective endocarditis, usually on an abnormal valve.

Hence, prophylactic antibiotic options include:

• Amoxicillin, 2 g orally 30 to 60 minutes before the procedure; a second dose is currently not longer recommended.

Alternative regimens are still given 30 - 60 mins before the procedure and include:

• Cephalexin (2 g) PO or
• Azithromycin (500mg) PO or
• Clarithromycin (500 mg) PO or
• Clindamycin (600 mg) PO or
• Cefazolin or ceftriaxone (1 g intravenously) or
• Clindamycin 600 mg intravenously or intramuscularly

Please consider.....

A New Case For November

Dear Bloggers

I thought I would try and test your diagnostic skills with the following anonymised case.

A 75 year old lady was admitted from her home having fallen and being found in a collapsed state.

She was unable to remember what had happened although when found, she was confused and febrile.

She denied tongue biting, urinary incontinence, headache, neck stiffness, photophobia, visual disturbance, dizziness, chest pain, palpitations, dyspnoea, cough sputum, haemoptysis, urinary symptoms, musculoskeletal pains or skin problems.

Previous medical history included atrial fibrillation, gastric ulceration, hypertension, aortic stenosis and mild renal failure.

She was taking digoxin 125mcg/day, warfarin 3mg/day, lansoprazole 15mg/day and ramipril 5mg/day.

There was no family history of note and she was a non-smoker and non-drinker. She had a relatively active life and lived alone and independently.

On Examination

She was febrile 37.4 degrees C
Conscious level - mildly confused: date - wrong, time of day - wrong, person - correct. GCS 15/15

Generally - looked mildly unwell. No JACCOL.

HEENT - no obvious abnormalities or trauma

CVS: Pulse 80/min irregularly irregular, BP 124/78mmHg, JVP not raised. No heaves or thrills. Levine 2/6 aortic ejection systolic murmur heard best over the right parasternal border in the 2nd intercostal space with radiation to the carotid arteries and best heard with the patient sitting forwards and breathing in expiration.
There were normal peripheral pulses and no differences in quality of pulses on either side. Blood pressures of her arms and legs were approximately equal in respect of systolic and diastolic pressures.
No splinter haemorrhages, no Janeway Lesions, no Osler Nodes or conjuctival haemorrhage were notes.

RESP: Respiratory Rate 14/min, SpO2 95% breathing ambient room air, trachea central, expansion equal bilaterally, percussion note resonant and breath sounds vesicular with no wheeze or crackles.

ABDO: Soft, non-tender, no masses, no hepatosplenomegaly, no renal angle tenderness, no ascites, no distension of the bladder. Bowel sounds were normal and no bruits were identified. Rectal examination showed no evidence of bleeding.

CNS:
II- pupils equal and reactive to light, consensual response + and normal accommodation. Visual fields grossly normal.
III / IV / VI -Extra-ocular movements normal.
V - Motor and Sensory normal.
VII - Normal
VIII - Normal for her age
IX / X / XI/ XII - No focal abnormality

PNS:
Tone: Normal throughout
Power: Normal power MMT 5/5 in all 4 limbs
Reflexes: All present and normal in all 4 limbs
Coordination: Normal
Sensation: Normal throughout
Gait: Not tested.

Mini-Mental Test Score: 8/10

The Admitting Resident took this skull Xray in view of the confusion and fall to look for fractures.



Blood cultures revealed chains of streptococci in 4 bottles.

Questions:

1) What does the Skull Xray show?

2) How will you try to work out the cause of the abnormality?

3) What could be the cause of the positive blood cultures?

4) How will you determine the predisposing cause?

Advice: Some of these questions are tricky and the answer may not be exactly what you think it is...... Have fun ! Please send me your answers!!

Electronics and Medicine -- The iPhone 3g

Dear Bloggers

I have spoken about the use of PDAs (Personal Digital Assistants) many times before on this blog and I thought that it was about time to update things.

I want to discuss about the iPhone 3G which has come to many countries throughout the world.

Although it is a phone, it is so much more. With the advent of the AppStore from Apple, there are now many applications which are being tailored for the use of health care professionals.

For example, epocrates (www.epocrates.com) has now been ported to the iPhone with it being most famously used on the Palm and Windows Mobile platforms. This application allows checking of drugs doses, side effect profiles and drug-drug interactions. This is a must get application for any resident and is of great use to senior doctors alike.

For those interested in working out those difficult blood gases in the early hours of the morning when 'on-call' with tiredness overtaking and the ability to think has long since disappeared into the night, the use of the application 'ABG' can help you work out your acidosis from your alkalosis and can even tell you what the predicted values should be and whether there is a mixed acid-base disturbance. It is well worth getting hold of. It is free!

Skyscape has released a trio combination of applications in one download package which includes a drug reference book, Archimedes medical calculator and Outlines in Clinical Medicine (OCM) quick reference book. This again is a must have application. Whereas other applications for the iPhone available at www.skyscape.com are available for a 1-year license, this trio combination package is currently free and resides in the memory of your iPhone not in the clouds of the internet somewhere making it accessible all the time !

There are several medical calculators available that can help you work about many of the medical equations that we all once had to learn and have long since forgot. Hence, having such a calculator at hand is very convenient especially when you are on to your 30th patient on the long arduous ward round and are just beginning to lose the will to live and you are faced with needing to work out the estimated GFR (MDRD equation) or predicting the risk of PE with the long list of variables on the Well's Score. One free application is called simply 'Medical Calc' and it is very similar to the MedCalc of the Palm and Windows Mobile platforms. This is well worth the free tariff!

Other applications that I would also recommend include:

• Isilo - again originally developed on the Palm platform, this app can read Pilot Data Base (pdb) files and hence, those large 80 megabyte books can be once again read on the iPhone. Whoopppeee!
• PubSearch - this is an inexpensive app that allows direct access to Medline via the wifi / 3G function of the iPhone and hence, now evidence based medicine is available at your finger tips when your consultant asks if there is 'any evidence'. You can now com back with a list of 20 papers and teach the consultant a thing or two :-)
• Netter's Flash Cards for Anatomy e.g. musculoskeletal, neuroanatomy etc are perhaps the most priciest apps on the AppStore for doctors and most recently, there are a series of Surgical books available. For those that need quick access to the famous Netter pictures, these are the ones for you on the iPhone.

In case you thought you might have more than enough medical apps for the iPhone, hang on a moment. UpToDate have a dedicated version of the great evidence based online reference on the iPhone. Of course, this is wholly dependent on an internet connection to search for information. I sincerely hope that the UpToDate team can produce a version that can be uploaded onto the iPhone unit meaning that access to this reference can be anytime and in any place.

Lastly, StyleTap.com are currently developing the Palm OS 5.0 platform to run on the iPhone. Several months their statement about the app said it would be initially available via a 'jailbroken' iPhone unit. One would hope that Apple will allow the StyleTap app to run on the iPhone so that the great Palm apps can be ported over to the iPhone negating many Palm users having to buy all of their Skyscape books again --- annually! Moreover, the Palm OS is a very quick and stable OS albeit somewhat dated.

All in all, the iPhone is a great unit and I think that it will take over as the new PDA / Smartphone for medics around the globe. My overriding concern is the poor 3G coverage / signal and the lack of battery life. I hope these matters will be fully addressed in the next OS update for the iPhone which will be version 2.2

Prof Tierney - heart murmurs

Dear Bloggers

Prof Tierney was back in Japan from this week.

I was fortuitous to attend and contribute to several of his lectures ( from within the audience ) throughout the week, and following that, he very kindly attended an exciting annual case conference where he demonstrated his famous portrayal of left-sided cardiac murmurs. This was indeed a rare treat for the residents and I was lucky to catch the whole thing on film.





I hope you enjoy this autumn gem as much as I did.

Have a great week!

Another PE in Japan !!!

Dear Bloggers

The following case has been anonymised but has been published for means of teaching about problem based learning.

This 79 year old male patient was normally fit and well. He was admitted to a distant hospital following a loss of consciousness whilst taking a bath. His wife found him mouth-deep in the water and he was unresponsive. The paramedics were called and he regained semi-consciousness en route to the hospital.

In the ER department he was in respiratory distress with profound hypoxaemia on 15L mask rebreather with PaO2 of 50mmHg and respiratory rate of 40 breathes per minute. BP was stable at 120/80mmHg, pulse 100 beats per minute and regular. He was afebrile.

No history could be taken from the patient although his wife said that he had been unstable on his feet for a week and he had fallen several days before and fractured his right arm which was managed with a back-slab.

He had apparently not complained of any chest pain, dyspnoea, cough sputum, abdominal pain, muscle or joint problems, headaches, visual disturbance etc...

He had no previous medical history of relevance, no family history of disease and he was a non-smoker and a non-drinker.

On examination

HEENT: Nothing abnormal detected (NAD)

CVS: pulse 100/min, regular, good volume. JVP not raised. Heart sounds 1 & 2 present. No added heart sounds or murmurs.

Respiratory: RR 40/min, trachea central, expansion normal, percussion not performed. Auscaltation: bilateral crackles throughout and worse at the lung bases.

Abdomen: Soft, non-tender, no masses, no hepatosplenomegaly, no renal angle tenderness, bowel sounds normal.

Extremeties: Right thigh warmer than the left and slightly red. No venous distension. Upper limbs - no venous distension. Right forearm mildly swollen (back-slab in place).

CNS: Pupils equal and reactive to light. No obvious gross cranial nerve abnormality. Fundoscopy was not performed. No neck stiffness.

PNS

• Tone - decreased throughout
• Power - patient was able to move all 4 limbs but formal assessment not possible
• Reflexes - slightly reduced throughout
• Coordination - not possible
• Plantars - flexor bilaterally (Babinski negative)

Skin- no rash.

Impression

1. Collapse of uncertain cause
2. Aspiration of bath water
3. Respiratory distress

Plan

The patient was intubated soon after admission and commenced on ventilatory support. Antibiotic therapy was started.

ECG revealed mild T wave abnormalities in the left sided limb and chest leads that were non-specific.

Chest X-ray revealed bilateral shadowing consistent with some early pneumonitis which was confirmed by CT of the chest.

However, a collaboration of senior doctors considered why the patient had collapsed twice in a week in an otherwise normally fit individual.

Normally when there is a loss of consciousness of sudden onset, the causes are usually cardiovascular or cerebrovascular in origin.

Cerebrovascular: The fact that the patient had no focal neurology made a stroke less likely although a seizure could have occurred leaving the patient post-ictal. Subarachnoid haemorrhage would be an additional consideration here, but again, there was no focal neurology and no neck stiffness.

Cardiovascular: It is entirely feasible that the patient could have had a dysrrhythmia (fast or slow) causing the loss of consciousness. Moreover, with the slight abnormalities present, an acute coronary syndrome should also be entertained. However, with the recent fracture, marrow embolus or fat embolus could have occurred. The slightly red and warm right thigh could be a deep vein thrombosis. DVT could predispose to pulmonary embolism leading to the collapse, previous unsteadiness and profound hypoxaemia. Vasovagal episodes could cause the recurrent collapses and could have been precipitated by the hot bath water.

It was suggested to do the following:

• Check the D-Dimer, Troponin T and BNP
• Arrange urgent spiral CT to rule out PE
• Ultrasound scan the lower and upper limbs for thrombosis
• Echocardiography
• Continuous cardiac monitoring
  
• Electroencephalogram
• Cranial CT

Results

1. Cranial CT showed no abnormality and atrophy was consistent with the age of the patient.
2. Continous cardiac monitoring showed no rhythm disturbance.
3. TropT and BNP were normal.
4. Cardiac Echo showed
5. D-Dimer was 20
6. Limb ultrasonography revealed a right thigh DVT
7. Chest spiral CT revealed multiple pulmonary emboli.

Diagnosis:

1. Deep Venous Thrombosis
   
2. Multiple Pulmonary Emboli due to #1
   
3. Collapse due to #2
4. Aspiration pneumonitis (and near drowning) due to #3
   

The patient was commenced on heparin prior to all the above tests. Also remember that a patient such as this should be investigated for the underlying cause of the thrombosis.

In 30% of PE patients investigated for the underlying cause, no cause can be found. However, in the remaining 70%, causes might include drugs e.g. oestrogens, infection, trauma (venous), connective tissue disease (e.g. Behcet), neoplasia, thrombophilia (ATIII def, Protein S / C def, APL syndrome, Prothrombin mutation and Factor V Leiden) etc... Malignancy e.g. prostate and some other tumours, can result in an hypercoagulable state (Trousseau's Syndrome) resulting in thrombosis.

Please see a more detailed textbook description for a complete list and explanation.

Moral of the Story

It would be nice and convenient to fit the patient problems into one neat box and just accept the diagnosis without wanting to accept that another problem may be going on. However, in this case, the patient had collapsed twice in a week and he had previously been well. The fact that the loss of consciousness in the bath led to aspiration should not take your focus off from the underlying cause of the collapses.

Most acutely collapsing patients have either a cerebral or cardiac cause and hence, a thorough workup of the possible causes is essential. The physical examination provided subtle clues as to the diagnosis. Do not ignore what you might consider trivial. It might be related to the cause. All the problems from the history and physical examination should have an assessment and followed up with a plan to investigate and treat.

Remember, if you consider the diagnosis of PE you MUST start heparin immediately, as to delay can result in increased mortality. The benefit of anticoagulation outweighs the risk of a significant bleed and hence, there should be no delay in starting treatment before ruling in or ruling out PE. Start the treatment (unless there are absolute contraindications e.g. GI bleeding) and if PE is ruled out by the tests, the heparin can be stopped.

Please consider....

A New Case For October - The final answer

Dear Bloggers

Here are the answers to the latest blog case for October. Thanks for waiting!!

Questions

1) Please make a problem list from the above history and physical examination.

• Abdominal swelling
• Dyspnoea on exertion and orthopnoea
• 3 year history RA under control on drug therapy
• On methotrexate, bucillamine and COX-2 inhibitor
• History of elevated liver function for 10 years of unknown aetiology
• JVP elevated
• Tachypnoea
• Shifting dullness consistent with ascites
• Peripheral oedema
  
• Percussion dull at both lung bases with decreased tactile vocal fremitus and reduced air entry
  
• Fluid containing 77 mmol Na in 500ml with daily rate at 80ml/hour
  

2) Please list several differential diagnosis and please identify one of the likely contributory causes from the history.

With a history of undiagnosed liver dysfunction, rheumatoid arthritis with use of long-term methotrexate makes me immediately consider drug-induced (MTX) chronic liver disease. However, what goes against this to some extent is the almost complete lack of physical signs of liver disease!

Causes of Liver Cirrhosis (resulting in ascites from portal hypertension) in this patient might include:

• Drugs e.g. Methotrexate
• Infective: HBV, HCV
• Autoimmune: Primary Sclerosing Cholangitis
• Primary Biliary Cirrhosis
• Autoimmune Hepatitis
• Undisclosed alcoholism!

Other GI causes of Ascites might also include:

• Budd-Chiari Syndrome (associated with autoimmune disease and malignancy e.g. HCC)
• Portal Vein thrombosis
• Protein Losing Enteropathy.

Non-GI causes of Ascites include

• Cardiac: constrictive pericarditis, any cause of right sided heart failure with tricuspid regurgitation e.g COPD, primary pulmonary hypertension, pulmonic stenosis, chronic PE and cardiomyopathy.
• Renal: Nephrotic syndrome -> drug induced (bucillamine), infective e.g. post-streptococcal, endocarditis, autoimmune -> related to RA (less likely as good control on medication), amyloidosis (chronic inflammation).
• Ovarian: Ovarian tumour can cause Meig's syndrome producing a transudate!
  

3) What tests would you do to confirm your hypothesis?

Simple tests first!!

• Liver function tests and coagulation studies
• Renal function tests
• Urinalysis (including protein)
• Analysis of ascites e.g. serum to ascites albumin gradient, WBC count (ascites portends a high risk for spontaneous bacterial peritonitis), microscopy / culture.
• Autoantibody studies: Anti-nuclear Abs, Anti-DS DNA Abs, AMA, Anti-SMA, IgA (increased in alcoholics!)
  
• Alpha-1 antitrypsin, Caeruloplasmin, Ferritin, alpha foeto protein (AFP)
  
• Ultrasound of the liver, kidneys, portal vein, pelvis and heart.
• Gastroscopy (screening for asymptomatic varices)

4) What would be your evidence based treatment strategy for such a patient?

In this patient, the ultrasound revealed a contracted liver consistent with cirrhosis. However, remember that liver cirrhosis cannot be definitely diagnosed on ultrasound. A liver biopsy is the gold standard method. There was also evidence of portal vein thrombosis.

Cardiac echo showed a normal ejection fraction and no evidence of raised right sided heart pressure.

Renal ultrasound revealed no abnormality.

Lung scintigram was performed to investigate pulmonary fibrosis which was positive with the addition of a mildly raised marker of fibrosis (used in Japan).

Lab studies showed normal AST, ALT, gamma GT and ALP. Bilirubin was 1.8 and PT-INR was 1.34

Urinanalysis was NAD with no protein present.

Autoimmune studies were consistent with rheumatoid arthritis but other immune studies were unrevealing.

Treatment

All rheumatic drugs were stopped based on the proposition that there was drug induced liver disease on a background of idiopathic hepatic dysfunction plus drug induced pulmonary fibrosis.

Portal Vein Thrombosis: The fact that this patient developed a portal vein thrombosis likely reflects the portal hypertension and venous stasis or reversed venous flow in the portal system. However, infection, malignancy (HCC) or prothrombotic diatheses e.g. Protein C deficiency can promote such this problem. The treatment depends on whether it is considered that such a thrombosis is acute or chronic. Acutely, such thromboses are treated with finbrinolytic therapy and chronically, either with beta-blockers to reduce the formation of varices, surgery, TIPS or anticogulation. Most of you will winge when considering using warfarin in such patients who are at high risk of varix formation and bleeding. However, Condat et al ( Gastroenterology 2001 Feb;120(2):490-7. ) found that anticoagulation in such patients with portal vein thrombosis does not increase the severity of bleeding, with the Authors conclusions being that the risk to benefit of using such treatment in patients with portal vein thrombosis lie in favour of its use.

In decompensated liver disease the intravascular volume is low resulting in the patient having high renin-angiotensin-aldosterone levels. This translates into a situation whereby there is avid salt and water reabsorption such that it is easy to develop ascites. The methodology for reducing ascites should include:

• High dose spironolactone: 100mg starting dose (UpToDate recommendations) up to 400-600mg /day as a once daily dose.
• Oral Furoesmide: 40mg once daily. Remember that in Liver disease the absorption of furosemide is unimpaired unlike in chronic heart failure. The reason for this is in heart failure there is generalised oedema of the internal organs from the back pressure of the heart leading to poor absorption. In liver disease the ascites forms from high portal pressure. The reasoning for not initially using furosemide intravenously is due to rapid fluid movement from the intravascular space that can result in worsening renal function. Oral furosemide produces a more gradual reduction in intravascular fluid which can be replaced by the reabsorption of the ascites.
• Salt restriction: Salt restriction should ideally be no more than 2g/day; this is almost impossible in Japan where the intake of salt can be anywhere up to 12g/day. In order for patients to be losing weight in liver disease, they need to lose >88mmol Na/day. 10mmol is lost via non-renal routes whereas >78mmol needs to lost via the kidneys to produce a net loss. Hence, if a patient is not losing weight it may mean that they are not taking their diuretics and/or they are not salt restricting sufficiently. A simple test is to check a spot Na level to check for compliance.
  
• Fluid restriction: Some experts recommend fluid restriction although this must be considered together with parameters such as blood pressure and renal function. There is no one specific maximum amount that can be given to a patient at the outset. It is a trial approach with the aim to work out how much fluid is required to maintain hydration without resulting in formation of ascites or conversely causing renal impairment. However, large volumes of water should be avoided. A general amount of 1-1.5L H20 per day may be acceptable.
• Daily Weights: The patient should be weighed daily to assess weight loss. In patient with peripheral oedema plus ascites, up to 1.5L per day can safely be lost because fluid is more easily reabsorbed from the peripheral tissues. However, if the patient just has ascites, 0.5L is the generally agreed amount that can safely be lost to avoid hypotension and worsening renal function.
• OGD: The patient should undergo screening for oesophageal varices and if found, they should be treated accordingly. There are several strategies for reducing portal pressure to reduce rupture of varices and they include the use of beta-blockers and calcium peripheral calcium channel blockers. Remember though, if beta blockers are used in such patients, if they do eventually bleed, you cannot rely on the usual tachycardia to judge about severity of cardiovascular compromise because patients will have a slow pulse (if well beta blocked and compliant !)
• Avoid Constipation: The patient needs to avoid constipation because this is a precipitant of hepatic encephalopathy and the usual treatment is with lactulose to produce 3 soft stools per day. Remember that lactulose has a significant quanitity of potassium and therefore, K levels need to be checked especially if the patient is using aldosterone antagonists, ACE-Is or ARBs. Conversely, a low K level in liver disease is a precipitant of encephalopathy. In this situation, the kidney produces NH3 resulting in hyperammonaemia. Hence, maintaining a balance of the K level is essential. However, checking the ammonia level is not always clinically helpful. The clinical signs of hepatic encepalopathy e.g. asterixis (liver flap) is a sensitive albeit not entirely specific physical sign of encepahlopathy and is a good guide for improvement in the patient's condition as it will disappear as the encephalopathy dissipates.
  
• Biopsy: In patient on methotrexate therapy with abnormal liver function from the onset, a liver biopsy should be performed before starting such treatment. There are several recommendations from various medical societies suggesting at what interval repeat liver biopsy needs to be performed. Essentially, if the patient has abnormal liver function and is started on methotrexate, a liver biopsy needs to be performed before intiating the drug to assess the cause of the liver dysfunction and if deemed permissible to commence such treatment, for every 1g of accumulated dose of the drug, a liver biopsy needs to be repeated. In those patient without liver dysfucntion, a biopsy is recommended after 2g of accumulated methotrexate dose. In such patients, liver dysfunction is more likely to occur after 3-4g of accumulated dose. In patients with existing liver dysfunction the accumulated dose may well be lower.
  
• If the patient has ascites, it is not possible to perform a transabdominal biopsy because of the risk of bleeding. However, some centres can perform a liver biopsy internally via the inferior vena cava. The advantage of this is that any bleeding will enter the venous circulation! The disadvantage is that it requires expertise with the inherent risk of pneumothorax, carotid artery puncture, bleeding and infection. However, with the appropriate use of ultrasound guidance to find the internal jugular vein, such risks can be reduced.

As an addition, one other thing to remember in such patient is that they do not need to have a fever to have an infection, they do not need a raised WBC count to have an infection and the CRP should never be relied on especially in liver disease patients (CRP is derived from the liver!!), nor should it in any patient!!!
Patients should be evaluated for infection and a low threshold for treating if such a risk exists. Hence, ruling out infective endocarditis might be worthy in a liver patient with new onset renal failure and a new murmur (this patient did not have a murmur though).

For the purposes of not prolonging the discussion, I will not be discussing the various causes of pulmonary fibrosis. However, in a patient such as this the likely causes are drug-induced and the primary rheumatoid arthritis, although the latter is considered less likely in view of the quiescent nature of the patient's connective tissue symptoms.

Professor Matsumura has kindly answered the case from the history and physical examination.

Thank your for showing me an interesting case again. In this case, the patient has rheumatoid arthritis. It is important to evaluate whether new symptom is related to rheumatoid arthritis or not. I would be careful all patient history, including medications. Dr. Stein had taught me that the importance of evaluation all information.

Questions

1) Please make a problem list from the above history and physical examination.

#1 Abdominal swelling and shifting dullness with ascites.
#2 Dyspnoea on mobilizing and no paroxysmal nocturnal dyspnoea (PND)
#3 JVP slight elevation
#4 RR = 30/min
#5 Percussion dull at both lung bases with decreased tactile vocal fremitus
#6 Reduced air entry at both bases.
#7 Pitting oedema of both lower limbs and arms
#8 Swollen hands
#9 Three-year history of rheumatoid arthritis under good control
#10 Taking methotrexate
#11 Taking Bucillamine
#12 Taking COX-2 inhibitor
#13 Containing 77 mmol Na in 500ml with daily rate at 80ml/hour
#14 Elevated liver enzymes over 10 years ago

2) Please list several differential diagnosis and please identify one of the likely contributory causes from the history.

Problem #1 shows ascites.
Problem #2 - #6 disclose massive pleural fluid and possible cardiac failure.
Problem #7 and #8 shows oedema of extremities. Daily sodium administration is 296 mmol, too high from #13. Differential diagnoses are as follows.

Vascular: Less likely Infection:
Liver cirrhosis, non HepB and HepC Neoplastic: HCC, Peritonitis cartinomatosa
Autoimmune: Secondary amyloydosis caused by rheumatoid arthritis, less likely Toxic/Metabolic: Less likely
Trauma/Degenerative: Less likely Iatrogenic:
Nephrotic syndrome caused by Bucillamine
Idiopathic: Less likely
Congenital: Less likely Cardiac failure, liver cirrhosis, nephrotic syndrome, malignancy, or other cause of low serum albumin, for example protein loosing enteropathy can cause ascites.

Possibility of cardiac failure is not high. Because heart sounds is normal, no S3 or S4, no PND, and no crackles in lung sounds. Possibility of liver cirrhosis is low, because no hepatic flap, palmar erythema, spider naevae, and jaundice. I think patient’s serum albumin is low.

In this case, nephrotic syndrome is highly suspected. Because this patient is taking Bucillamine. Most likely diagnosis is nephritic syndrome caused by Bucillamine. Bucillamine use for rheumatoid arthritis is common in Japan. Several cases with nephrotic syndrome caused by Bucillamine were reported in the past. Membranous glomerulonephritis is suspected.

3) What tests would you do to confirm your hypothesis?

I would perform pit recovery time in leg oedema first. If patient’s serum albumin is low, pit recovery time will be more than 40 seconds. This patient’s pit recovery time can be under 40 seconds, if period of leg oedema is short. Urinalysis should be performed immidiately. This is very easy test.

4) What would be your evidence based treatment strategy for such a patient?

Dose of sodium administration must be reduced first. If massive proteinuria is confirmed, Bucillamine should be stopped. In the past prednisolone was prescribed for treatment of this adverse effect in several cases.
Following recent reports suggest that discontinuation of Bucillamine is enough. 1) Obayashi M, et al. Clinical course of bucillamine-induced nephropathy in patients with rheumatoid arthritis. Clin Exp Nephrol 8: 288-290, 2004. 2) Hishino J, et al. Outcome and treatment of bucillamine-induced nephropathy. Nephron Clin Pract 104: c15-19,.2006.

Thank you for such an enlightening opinion and especially about nephritic syndrome associated with Bucillamine in RA patients.

Hello, Dr.B. It's Hirotaka Kato, U of Kumamoto. I email my answer. Please forgive my simple words/email. It is difficult for me this time...I'm looking forward to the answer.

Q1. Problem List
#1. ↑abdominal swelling started 3 m. ago
#2. Dyspnea only on mobilising or lying flat
#3. RA under good control (for 3 years)
#4. Medications (MTX, Bucillamine, folic acid, COX-2 inhibitor)
#5. Elevated liver enzymes pointed out over 10 y. ago
#6. RR 30/min
#7. Percussion stony dull at both lung bases with decreased tactile vocal fremitus
#8. Reduced air entry at both bases
#9. Grossly distended abdomen
#10. Shifting dullness with approximately moderate ascites
#11. Evidence of a previous puncture site on the left lateral abdominal wall
#12. JVP slight elevation
#13. Pitting Edema of both lower limbs
#14. Swollen hands

Q2. Differential diagnosis

I would say the patient's symptoms are caused by congestive heart failure because CHF can unify them. However, lots of negative findings confused me. I was unable to decide the most likely cause. I listed differential diagnosis with no confidence below.
#1. Congestive heart failure due to constrictive pericarditis (?)
# Cor pulmonale due to pulmonary HTN (←RA, MTX)
# Liver cirrhosis
# Nephrosis
# collagen disease (SLE, MCTD, SSc)
# latent malignancy
# Filariasis
# Beriberi

Q3. tests

Chest CT, Cardiac echo Abdominal echo, Abdominal puncture Blood test : CBC(Hb, WBC, Plt) liver enzymes, TP, Aib, BUN, Cr If #1 is suspected, catheter could also be indicated.

Q4. treatment

Firstly, diuretics can be considered for controlling CHF. When CHF cannot be controlled by medications, operation should be performed.

Thank you Kato-san for such a good attempt at answering this difficult case.

In this case, because the physical findings are so non-specific and that it could potentially include three major systems such as cardiac, renal or hepatic, one is somewhat reliant on history to try and elucidate causes. In the end, the laboratory data allows us to check our hypothesis.

The importance of a problem list allows us to list all of the problems and assess each problem individually and then together as a group disorder. It allows us to generate differential diagnoses and plan our investigations logically. Without a differential diagnosis and logical testing, if our only diagnosis is refuted by tests then we have no ability to investigate further. However, by generating the differential diagnosis, when one diagnosis is refuted then the next can be investigated and so on until the real diagnosis (hopefully) is confirmed. That does not mean to say that treatment is witheld until the diagnosis is made. Far from it. All of these conditions are treated in a similar way by reducing fluid and Na. However, many of the above tests can soon be obtained and a streamlined treatment plan can be tailored for the patient.

I hope you emjoyed the challenge of this October case.....another case is coming in November :-)

An Interesting Chest Radiograph

Dear Bloggers

Here is an interesting chest radiograph of an elderly patient with an acute onset of central chest and back pain which subsequently propogated to the abdomen. On admission, the patient had hypotension and distant heart sounds. The chest radiograph (with the history and physical findings) provided the diagnosis within seconds-- a proximal to distal aortic dissection (Stanford A type / DeBakey Type I).
Echocardiography revealed pericardial blood causing tamponade and an emergency thoracic contrast CT scan revealed a large Stanford type A dissection -- as suspected!

The ECG showed no signs of myocardial infarction which would be the differential diagnosis in such a case.

Remember that in patients with acute aortic dissection, the central chest pain can be severe. It may become a tearing pain in between the scapulae (interscapular pain). Such pain may further propogate down the back and into the abdomen as the aorta further dissects. Although this CXR is a classic example of a dissection, a chest radiograph can be normal in a proximal dissection. Even though it is often quoted that the blood pressure between the arms can be unequal it is not sensitive or specific for dissection and cannot be relied upon.

Good tests for investigating dissection include the quick bedside cardiac echo to look for haemopericardium and one may sometimes see the tear of the artery near to the aortic valve. However, the gold standard examination is the emergency CT.

If you have a high suspicion of dissection, please first stabilise your patient before moving them to the CT scanner -- remember the basics of Airway, Breathing and Circulation.

Please remember to give the patient adequate pain relief e.g. diamorphine, although bear in mind the potential hypotensive effects of the drug . It is not humane to leave patients in pain.

Ensure that the patient can be transported (if feasible) to a specialist cardiothoracic centre and if already there, ensure that the surgeons are told early rather than delaying for other reasons because 'time is artery'.

A New Case For October

Dear Bloggers

This case has been anonymised for the safety of patient confidentiality and it is reported here for the teaching of Problem Based Learning.

This 74 year old lady was admitted with a history of increasing abdominal swelling and dyspnoea. The abdominal swelling started 3 months before and was gradually increasing. There was no pain associated with the swelling and the patient denied changes in bowel habit, urine colour, weight loss, appetite change or jaundice.

The dyspnoea occurred only on mobilising or lying flat and there was no report of palpitations, chest pain, cough, sputum, wheeze or haemoptysis. There was no complaint of leg swelling or paroxysmal nocturnal dyspnoea.

She had a 3 year history of rheumatoid arthritis for which she took methotrexate 12.5mg per week, Bucillamine (similar to Penicillamine), folic acid once per week and COX-2 inhibitor when required. Her RA was currently under good control.

She had been informed that she had elevated liver enzymes over 10 years ago and they were observed without intensive investigation. No cause was identified. There was no history of Hep B or Hep C virus infection, no blood transfusions, no IV drug misuse and no tattoos in the past.

She had never drank alcohol and was a non-smoker. There was no family history of note especially no inherited causes of disease. She otherwise lived independently alone and had a good support network of friends. She was unmarried and had never had children. No sexual history was taken. No gynaecological history was taken.

On examination

She patient looked well. Afebrile. No Dupytren's contracture, no hepatic flap, no palmar erythema and no spider naevae. No jaundice, no anaemia, no cyanosis, no clubbing, no lymphadenopathy. GCS 15/15.

CVS: Pulse 90/min regular, BP 110/80 mmHg, JVP slight elevation, Heart Sounds normal. No S3 or S4 and no murmurs.

RESP: RR = 30/min, sats 98% on ambient room air, trachea central and no tug, percussion stony dull at both lung bases with decreased tactile vocal fremitus. Lung sounds normal with no crackles but reduced air entry at both bases.

ABDO: Soft, grossly distended abdomen. Non-tender, no obvious masses, no hepatosplenomegally. No rebound or guarding. Bowel sounds normal. Shifting dullness with approximately moderate ascites. Evidence of a previous puncture site on the left lateral abdominal wall. No rectal exam performed.

Pelvis: No gynaecological exam performed.

Extremeties: Pitting oedema of both lower limbs and arms. IV line in left arm with containing 77 mmol Na in 500ml with daily rate at 80ml/hour.

Hands: Swollen. Finger joints normal - no pain, stiffness or restriction of motion. Normal metocarpophalangeal joints, normal wrist joints. No evidence of RA nodules at the elbows.

Questions

1) Please make a problem list from the above history and physical examination.

2) Please list several differential diagnosis and please identify one of the likely contributory causes from the history.

3) What tests would you do to confirm your hypothesis?

4) What would be your evidence based treatment strategy for such a patient?

As always, please feel free to send in your attempts at answering the case. The actual case answers will be available in approximately a week. Enjoy sleuthing :-)

Keane - Perfect Symmetry

Dear Bloggers

Although this is a medical blog I wanted to digress to tell you about a new album from the British band Keane.

Yes, this is completely unrelated to medicine!

Their 3rd albumn was released on October 13th and it is brilliant.

Keane's musical style could be described as lying somewhere between that of U2, David Bowie and The Police.

If you are interested in British music or like to hear pop/rock with synthesizers, piano and clear lyrics then check out this album.

I would highly recommend it.

As with the title of today's blog, the album is called Perfect Symmetry.

Please enjoy!

p.s. a new blog case is coming soon, so be ready! :-)

Dr Lo -- Infectious Disease Conferences

Dear Bloggers

Dr Lo from the United States is back in Japan partaking in his annual infectious disease conferences. He has started his lecture series at CH which will continue for a week after which he will go to SK.

For his initial conference, he was presented a case of a patient with pneumonia of unknown aetiology.



Dr Lo made some excellent points during his lecturing which included:

• When doing presentations in English, not using abbreviations for antibiotics e.g. PIPC = piperacillin, CTRX = ceftriaxone, as foreign physicians do not understand such abbreviations as they are not used in other countries.
• Sputum examination for acid fast bacilli cannot completely rule out the presence of TB as the load of tuberculous bacilli organisms may be low despite active infection.
  
• Use of single agents to treat TB can lead to negative smears and negative cultures and can complicate trying to make the diagnosis of mycobacterial infection.
• If possible, always look back at the old radiology e.g. chest xrays, to see if there are any changes on current xrays to differentiate between acute and chronic changes
• Legionella antigen testing of the urine will only pick up 75% of Legionella infections (serotype 1); hence, a negative test cannot completely rule out Legionella infection.
  
• PCR for mycobacterium infection can be variable due to a lack of standardisation. There can be false positive results associated with the test. Hence, it is not a perfect test :-(
• It is important to find out how previous TB was treated e.g. lung operation, antibiotic history (types of antibiotics used, dose and for how long); inappropriately used antibiotic regimens can result in under-treatment of TB and it is conceivable that reactivation can occur in the future.
  
• Quantiferon test for TB cannot determine if a patient has active or latent TB. The blood needs to be processed rapidly and a negative test might result from blood not being processed within the obligatory time! Hence, a negative test might be due to inappropriate handling of the sample! Interestingly, the Quantiferon test is specific for TB and it will not detect other mycobacterial infections making it a unique test for TB identification albeit if the history fits the scenario. Lastly, a previous vaccination with BCG will not affect the result of this serum test. In some cases of indeterminate tuberculin skin testing, a Quantiferon test can be helpful to know if the patient has TB or not.
  

Dr Lo also went on to discuss about the aspects of Fever of Unknown Origin.

FUO is a defined as a fever of more or equal to 38.3 degrees Celsius for more than 3 weeks after investigation as an inpatient for 3 days or 3 outpatient visits with investigations; this is the Rule of 3's for remembering the definition of FUO.

After an interlude, Dr Lo talked further on infection control of tuberculosis. The following is a summary of his talk with additional facts from further reading.

• Firstly, Japan has the highest incidence of TB among the G8 countries!
• TB is an airborn infection (less than 5 micrometers in size) allowing it to circulate in the air for several days after expectoration. Droplets, on the otherhand, are larger than 5 micrometers and if spread from coughing, sneezing, talking or during invasive procedures, then the perimeter of infection is about 1 metre.
• Droplet spread infections: patients should be in a private room. No negative pressure required. Door can be open! Close contact with patient requires wearing a mask. Droplet spread diseases include: neisseria meningitis, Haemophilus influenza, SARS, Burkholderia pseudomallei, Legionella spp, Aspergillus spp.
• Airborne infections e.g. TB, Varicella zoster virus, influenza, measles, infection can occur several metres away from where they are produced. Patients need to be in a negative pressure room e.g TB. High efficiency filtration is necessary. Door MUST be kept closed. Medical staff and relatives need to wear an N95 mask. If patients need to be moved from their room, patients need to wear a mask as well. Any transportation around the hospital should be kept to a minimum.
• Negative pressure rooms to prevent spread of TB are essential. In the absence of a negative pressure room, ideally the patient should be referred to an institution that does have such facilities.
• Patients should be routinely asked if they have had TB exposure or infection, current symptoms and medical conditions that increase the risk for TB e.g. HIV. This comes back to proper history taking!
• In the USA, in view that BCG is not used, if a PPD / tuberculin skin test is positive (>10mm), then asymptomatic healthcare workers need to be treated for latent TB. However, in those who have been vaccinated, it may be positive in the absence of active TB infection. In HIV+ or immunocompromised patients, a PPD skin test of >5mm is considered positive for active TB.
• Interestingly, when the BCG vaccine is given before 5 years of age, the PPD skin as an adult would be expected to be negative whereas after the age of 5, it might be expected to be positive. Hence, when asking about vaccination, it is essential to know what age it was given!!! :-o
• Latent TB is usually treated with a single drug whereas active TB requires 3-4 drugs.
• So, what do we do when we have an asymptomatic patient in Japan or the UK who has previously been vaccinated with BCG but develops a positive PPD (tuberculin) skin test? For health care workers a positive test would equate to more than 10mm and for an asymptomatic member of the general public more than 15mm (the latter because they are at less risk from TB exposure). In the absence of symptoms this would be regarded as Latent TB which needs to be treated whereas if there are the usual symtpoms of cough, sputum, weight loss, night sweats and culture / microscopy / other confirmatory tests are positive then this is active TB which requires Urgent treatment.
• Basically, there are many authorities who regard the BCG as useless to prevent TB and if positive, then this should be taken to indicate TB infection and with treatment commenced accordingly.
• However, the efficacy of the BCG has been equated to about 80% at best and at worst 0% ! A 60 year study in American Indians showed that those who received BCG vaccinated developed less TB compared to those who were unvaccinated with an efficacy of about 50%. Moreover, a study from Africa in children who were vaccinated for TB confirmed that there was less TB in those children with BCG scars than in those without.
• Hence, it is clear that BCG has some protective benefit but it does not prevent one from getting the disease! It is thought that it may reduce the frequency of disseminated (miliary) TB and intracerebral infection particularly in children.

Today was a great day for the residents to learn from an expert on infection.

Not Over Investigating Patients

Dear Bloggers

Today I would like to discuss about not over investigating patients.

When a patient has a problem, we as doctors have a duty to investigate the problem and to seek its source and hopefully we will find the problem and with even greater hope, there will be effective and curative treatment.

It is not always possible to get all the information from one test and it is quite usual for a combination of tests to be required to provide the jigsaw puzzle pieces to make up the full picture.

It is all too easy to order a panel of lab studies that tests for all manner of conditions including the serum rhubarb (a British medical joke!!) and to get CT this, and MRI that, until we have exhausted every known imaging and lab modality.

However, what we must ask ourselves is 'Will the test result make me change the treatment for this patient?'

For example, an elderly bed-bound patient with a previous large left sided cerebral infarct is admitted to your hospital after his second seizure in 6 months that terminates after 2 minutes without treatment. Infection is ruled out by normal lumbar puncture, normal urine exams and chest Xray. CT head performed on admission confirms the previous massive infarction but no new areas of infarction or bleeding. The patient is already taking warfarin for the paroxysmal AF albeit with a subtherapeutic INR at 1.7. On recovery, there is no new neurology (only existing previous neurology).

Does this patient need an MRI scan, an EEG and a cardiac echo?

There would be many physicians who would want to get all 3 modalities. There would be other physicians who might get one or two and some who would obtain none of the above.

Why would you not take all of these tests?

This patient has had a massive stroke and his risk factors for it i.e. the PAF is already being treated with warfarin although with a currently subtherapeutic INR. Will an echocardiogram result showing us left atrial thrombus, change our treatment of IV heparin until the INR is therapeutic for the warfarin to be continued alone? No.
The treatment of this patient would be with standard anticoagulation. An echocardiogram tells us there may be a thrombus but the treatment in this patient is the same. Hence, logically thinking, will this test actually change our management? No.

One word of warning here, infectious endocarditis of the left side of the circulation can lead to vegetation disseminating to the brain. Anticoagulation is a risk factor for this and if IE were to be considered, an echo would be useful and would lead to a change in treatment i.e. antibiotics / surgery / stopping warfarin. However, this is where history and physical examination become necessary tools. They are there to find out the risk factors for IE and to find the peripheral signs and the murmur. Blood cultures and raised ESR would also be helpful in investigating IE.

Do we need the MRI scan? Again, the CT has shown an old massive infarction with there being no new observable lesion and hence, if there is a small infarction, is this going to make us change our treatment? The patient is still at risk of thromboembolic phenomen from the PAF and will still require warfarinisation which we know is sub-optimal. Knowing if there is a new infarct is not going to lead to a change in treatment and so can it be justified to obtain an MRI looking for infarcts you are already treating? I don't think it can be justified unless the patient has IE and there is a worry about mycotic aneurysm formation. Again, it comes back to history and physical examination and whether you regard IE to be a likely cause in this patient.

Do we need an EEG to confirm the presence of epileptic activity in a patient with known structural brain disease who has already manifested two seizures in 6 months? No. If the patient had a normal brain on CT and was having seziures, an EEG might confer the location and type of the activity and might lead us to a more refined diagnosis with perhaps a different anti-convulsant drug. However, in a patient with obvious structural disease and seizures it is highly likely that the epileptic activity is arising from that location and obtaining an EEG to prove what has aleady be proven serves no purpose. Treatment with an anti-convulsant drug is necessary rather than waiting for tests that are only going to tell us what we already know and will not change our management or treatment !

In a society where diagnoses need to be made quickly and treatment started promptly, delaying because of unneccessary tests that will not alter our treatment is to the detriment of the patient.

With many of the world economies now struggling in the light of decreasing working population sizes, increased longevity of the elderly and the recent financial banking crisis to hit many of the wealthy nations, it is in the patient's best interests to reduce the unnecessary tests which will only lead to more expense for the patient or their family but which do not lead to a change in treatment.

I would be very interested to learn what your opinion is on this topic and how you would proceed in such a patient. Please leave a comment on the blog.

Please consider...

Below are the comments received from a medical student in Japan [comments have been moderated]

I totally agree with Dr B, while it might be hard to judge which tests are beneficial for patients, especially for fledglings such like students and interns. I think we need to keep learning and considering that thing from the patients. And if possible, I hope all Japanese medical students would have such education in the future.

I would like to mention about the necessity of explanation to the patients. I feel that Doctors often do not give enough explanation to them.

Japanese people are said to expect excessive tests now and again (maybe in outpatient ). Actually, I might be one of them because I have a experience once. Why do we (I) do that? The fact we are not fully educated might be one reason, but this subject seems to be difficult to be solved at once. The more important thing is that some patients should worry about their illness too much (like I was so). Doctors have to explain why they(doctors) decide to do or not to do tests and treatment (in addition, probable diseases, conceivable clinical courses, and so on.) We need to convince them in a short time!

...I apologize my unfounded thought and my poor English.

In any case, I think we need plenty of knowledge and skill for History Taking and Physical Examination. And I want to practice Medicine, always thinking 'why, why, why?'.

Thank you for such excellent comments.