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.

History Taking is a Continuous Process

Dear Bloggers

Today I would like to revisit history taking. In fact, one of the main purposes of this blog is to discuss various elements of the history taking process.

Once the patient has been admitted to the hospital it is often necessary to obtain further history in order to understand the current patient problems plus existing co-morbidity to thereby construction a diagnosis which can then be tested.

Taking a thorough history on admission and doing it quickly is an art and something that experienced doctors are adept at doing. However, junior doctors through a lack of experience and perhaps a lack of sufficient training, take time to develop such skills that are the essential elements of any physician.

Hence, a patient who is admitted to the hospital will often not have a thorough enough history taken and therefore, it is up to the senior doctors to identify the areas that the junior doctor has failed to recognise and to then go back to the bedside and speak to the patient to obtain the salient information through appropriate questioning.

This is the best opportunity for the junior doctor to learn i.e. by seeing the senior doctor's style, methodology and purpose of questioning. This is part of the bedside teaching process.

By obtaining more detailed information can lead to the uncovering of information that guides the physician in a different direction or it may merely confirm what the junior doctor already thought. Taking further history is essential to fill in the gaps.

I often say, and even more so in these times of world financial collapse, 'if you were buying a house, you would read all the details and fine print before signing your savings over to the bank and obtaining a mortgage, which is only money. But, if you were a patient admitted into hospital wouldn't you want to be asked the finite details to help the doctors understand your symptoms on which your life might depend?'

In the days of CT, MRI, SPECT, PET etc, aren't we becoming complacent in our own confidence of being able to make a diagnosis with these tools at the neglect of history taking plus physical examination?

For example, in another hospital some time ago, a patient with COPD was admitted with a chest infection for which he was not getting better despite the use of a 3rd generation cephalosporin antibiotic. The junior doctor was concerned because of the continued fever and dyspnoea. A senior doctor went to the bedside and took more history whilst the patient was eating his food. It soon became clear that the patient was coughing when trying to swallow his food. The senior doctor obtained a classic history consistent with aspiration i.e. coughing when eating and when lying flat.

These symptoms had not been posed to the patient on admission, but as easily as asking an open question of how he was, he offered up the information of potential aspiration. Such important information was able to redirect the focus of investigation and treatment with obvious benefit to the patient.

However, junior doctors should not simply rely on the admitting history and stick rigidly to it and bypass asking any further questions. History taking is an ongoing process throughout the inpatient stay and beyond into the post-discharge outpatient follow-up.

By not asking questions to our patients, we are doing them a disservice.

Please consider.

Pulmonary Embolism - A New Way To Look At An Old Problem

Dear Bloggers

The European Society of Cardiology has recently updated the guidelines for the diagnosis and treatment of pulmonary embolism (PE).

There has been much research in this field and there are now new ways to look at the severity of PE and with more defined criteria for therapeutics derived from studies on prognostic factors.

One area that has developed is with the use of cardiac biomarkers of severity which now include measuring the BNP and Troponin ( I or T ) in addition to measuring the D-Dimer. The BNP and especially Troponin levels give prognostic information and may help to guide treatment.

The guidelines make it more clear with regards to those patients who ultimately require thrombolysis / surgery based on their risk of early death in PE rather than by pure CT criteria. This is a major advance in the field of PE -- the guidance advises that even if PEs do not look 'massive', they can nevertheless still cause significant haemodynamic compromise and hence, such PEs should be regarded as potentially causing a high early mortality rate if they result in hypotension or shock.

Hence, the terms 'massive', 'submassive', 'catastrophic', 'minor' should probably no longer be used. It does not matter so much with regards to the anatomical shape, distribution or burden of the PEs on a scan, but more from the haemodynamic consequences of this disorder. The newer terminology of High Risk for early death and Non-High Risk are being adopted instead to replace the above misleading terms that are heavily dependent on imaging interpretation rather than how the PE actually affects the patient's cardiovascular system.

The European Society of Cardiology guidelines on PE are some 32 pages in length (including 400 references!!) and they are very detailed and complete. Moreover, they provide a template on how to effectively stratify patients at presentation and how to workup the patients according to specific algorithms.

If you wish to read the current guidelines, they can be downloaded from the European Society of Cardiology website here.

The major concern for me is in those patients who have a high risk PE score either via the Well's Score or Modified Geneva Score and have a negative scan for PE, but are nevertheless at high risk. The guidelines intonate that further investigations can be performed but do not go further to elucidate what these tests should be.

It is indeed worthwhile checking the D-Dimer, Troponin and BNP in such high risk patients and performing ultrasonography of the pelvic and lower limb veins. Remember that PE can occur from the deep veins of the upper limbs (Paget-Shroetter Syndrome) so a hunt for thrombosis of the upper limbs can sometimes be fruitful. Ventilation Perfusion (V/Q) scanning is less sensitive than that of multi-detector CT but in terms of those patients who have multiple subsegmental PEs which the CT scanner may not be able to pick up, this test might still be useful in the 5% of cases of CT negative - PE positive patients. Ultimately, despite extensive testing, the patient may still have PE and hence, it may be considered of greater benefit to treat than to withold therapy. Remember the risk of death from PE can be as high as 30-45% whereas the risk of a major bleed on warfarin is about 3%, at least a 10 times difference.

The other area of concern is in those patients who have a confirmed single subsegmental PE with a negative ultrasound scan of the deep veins. These patients are apparently at low risk of subsequent death. Do we anticoagulate such patients??

I think the answer to the above questions will only come with future studies.

I hope you enjoy the above guidelines as much as I did.

Have a great weekend!

Answer To September Case

Dear Bloggers

I have been fortuitous to have received several most excellent workups of the recent case, all with the correct diagnosis! I have included the replies below.

One reply was from a 6th year medical student, Hirotaka Kato of Kumamoto University. This is the first time a medical student has answered a blog case and I hope this sets a precedent whereby other medical students and junior doctors feel they can contribute to future case answers. Medical students are always most welcome to reply.

Q1.
# cough and severe dyspnea
# SpO2 88%
# wheezes on bilateral sides
# bilateral pleural effusions on CXR
# rash on left arm and chest
# right eyelid and facial swelling
# finger numbness, (decreased sensation)
# dull/ right upper abdominal pain
# past history of asthma, nasal polyp, chronic sinusitis
etc.

Q2.
I suspected vasculitis first from the positive findings,
but I had no confidence because of no fever, no elevated
leukocytes.
Second, I thought of allergic diseases.
Allergy can explain no fever, but I wonder if Allergy
could cause finger numbness.
Though it was hard for me to decide the priority of
suspected diseases, my differential diagnosis became the
following,

# Churg-Strauss syndrome
# ABPA (allergic bronchopulmonary Aspergillosis)
# severe asthma attack such as aspirin-induced asthma
# dermatomyositis
# drug allergy

Q3.
The diagnostic test is measuring MPO-ANCA.
Besides, eosinophil count, aspergillus antigen and so on.

Q4.
steroid pulse therapy could relieve his symptoms.

The next response is from Dr Gerald Stein, University of Florida.

Question 1: From the history, physical examination, radiology and laboratory data, please make a list of the positive findings.

1 Cough and dyspnoea,wheezing

2 Facial swelling
3 Arm and chest rash with pruritis

4 Dull abdominal pain
5 Finger numbness

6 Chronic Sinusitis (30 years)

7 Asthma (life long)
8 Nasal polyp operation (8 years ago)
9 Recurrent Urticarial-like skin rashes (from 5 years before)

10 Recurrent Eyelid and Facial swelling (from 5 years before)
11 Autoimmune Haemolytic Anaemia (AIHA) treated with steroid pulse therapy 3
years before.
12 Urinary stones (5 years before)

13 Mother had tuberculosis

14 Resp Rate 18/min, SpO2 88% breathing ambient room air.
15 percussion decreased at both bases. Wheeze throughout both lungs R>>>L. Few crackles at both bases.

16 Abdomen: tender right hypochondrium and epigastrium.

17 Sensation decreased in the finger tips of both hands
18 Chest Radiograph: Bilateral pleural effusions

Question 2: Please give a likely list of differential diagnoses based on your list generated in question 1.

Churg-Strauss Syndrome with resp, GI, neuro & skin involvement

DDx ASA sensitivity syndrome-nasal polyps, asthma,
vasculitis: micro polyangiitis [no renal]
Wegeners {does not occur in Japanese}
SLE
HIV
Tuberculosis
HCV
CA with paraneoplastic syndrome

Question 3: What tests would you perform to ascertain the diagnosis?

Immune markers: RF, anti-CCP, ANA, ss, sd ANA, ANCA(P&C). Eosinophil count absolute and %, skin Bx, possible sural nerve Bx, HIV Ab, Tb skin test, sputum smear & CULTURE for Tb, HCV Ab, stool occult blood, FiberColon with Bx; later consider thoracocentesis if no Dx from earlier tests, spirometry with DL CO, sinus CT, Chest CT, haptoglobin, nerve conduction study

Questions 4: With the likeliest diagnosis in mind, what is the treatment of the disorder?

DIV Steroids & Entoxin, nasal O2, cover for Tb if skin test+

The last expert opinion is from Dr Masami Matsumura, Kanazawa University Medical School.

Thank you very much for showing me a challenging case again! This patient has history of several disorders, especially autoimmune diseases. The fact that this patient has history of asthma alludes the key of the diagnosis. His first symptom is a one-month history of productive cough with following symptoms of heart failure with or without worsening of asthma. Interestingly, he has finger numbness again! His history doesn’t indicate possibility of diabetes. Mononeuritis multiplex or polyneuropathy is highly suspected in this case. Probably he has mononeuritis multiplex. A rare vascullitis is suspected.

Question 1: From the history, physical examination, radiology and laboratory data, please make a list of the positive findings.

#1 Cough
#2 Dyspnea
#3 Hypoxia
#4 Wheezing
#5 Crackles at both bases
#6 Cardiomegaly
#7 Right abdominal pain
#8 Facial swelling
#9 Skin rash with pruritis
#10 Sensation decreased in the finger tips of both hands
#11 Anemia
#12 Increased platelets
#13 Pleural effusions
#14 Asthma
#15 Paranasal sinus abnormality
#16 Recurrent Urticarial-like skin rashes
#17 Recurrent Facial swelling
#18 Autoimmune Haemolytic Anaemia
#19 Family history of tuberculosis

Positive findings from #1 to #6 and #13 showed cardiac failure with or without an asthmatic component. Positive finding of #10 indicates of possibility of a mononeuritis multiplex. Polyneuropathy is less likely because he doesn’t have symptom in the feet. Positive findings #11 and #12 means a chronic inflammatory process.

Question 2: Please give a likely list of differential diagnoses based on your list generated in question 1.

Differential diagnoses are as follows.
Vascular: Less likely
Infection: HIV, TB
Neoplastic: Lymphoma, Paraneoplastic syndrome
Autoimmune: Churg-Strauss syndrome, Wegener’s glanulomatosis, Microscopic polyangiitis, Polyarteritis nodosa, Goodpasture’s syndrome, SLE, Sarcoidosis, Waldenström’s macroglobulinemia, Cryogloblinemia
Toxic/Metabolic: Less likely
Trauma/Degenerative: Less likely
Iatrogenic: Less likely
Idiopathic: Amyloidosis
Congenital: Less likely

My most likely diagnosis is Churg-Strauss syndrome (CSS).

Second candidate is Wegener’s granulomatosis.

Both disorders are very uncommon in Japan!! CSS is very rare disease. Estimated annual occurrence is 1 –3 per million.

The American College of Rheumatology 1990 criteria for the classification of Churg-Strauss syndrome are as follows:

1: Asthma
2: Eosinophilia >10%
3: Neuropathy, mono or poly
4: Pulmonary infiltrates, non-fixed
5: Paranasal sinus abnormality
6: Extravascular eosinophils
* For classification purposes, a patient shall be said to have Churg-Strauss syndrome if at least 4 of these 6 criteria are positive. The presence of any 4 or more of the 6 criteria yields a sensitivity of 85% and a specificity of 99.7%.

Masi AT, et al. The American College of Rheumatology 1990 criteria for the classification of Churg-Strauss syndrome (allergic granulomatosis and angiitis). Arthritis Rheum 1990; 33:1094-100.

This patient has three criteria, asthma, mononeuritis multiplex, and paranasal abnormality. I would confirm white cell differentials first.

CSS can cause multi-system disorders, paranasal sinus, lung, cardiac, skin, GI-tract, or neurologic. Cardiac involvement is suspected in this patient because he has cardiac failure. Eosinophils can infiltrate cardiac muscle. This phenomenon should be removed as soon as possible.

I would introduce one clinical pearl.
“Leukotriene inhibitors such as montelukast, given for asthma, have been implicated as causing some cases of Churg‐Strauss syndrome”
This patient doesn’t take leukotriene inhibitors.

Question 3: What tests would you perform to ascertain the diagnosis?

I would order white cells differentials, ESR, Urinalysis, ANA, C3, CH50, P-ANCA, C-ANCA, EKG, and cardiac echo.
Skin biopsy should be performed, if patient agrees. I would confirm of infiltration of eosinophils and/or vasculitis.

Questions 4: With the likeliest diagnosis in mind, what is the treatment of the disorder?

If diagnosis is correct, oral prednisolone is indicated. This treatment will be successful. I would add one point. He has family history of TB. Patient’s symptoms and chest radiograph should be carefully monitored for reactive TB.

Case Diagnosis The answers to the above questions are absolutely correct. The patient did have a diagnosis of the Churg-Strauss Syndrome. However, the ANCA was negative. The patient agreed to have a skin biopsy and indeed, it did reveal vasculitis. The peripheral eosinophil count was raised and the percentage was 15%.
Despite several weeks of Prednisolone at dose of 50mg/day with initial resolution of symptoms and signs, the patient had a recrudescence of cough and skin rash prompting the introduction of cyclophosphamide.


Churg Strauss Syndrome (CSS)

This is a vasculitis of small and medium sized arteries. It classically involves the arteries of the lung and skin (as in this case) but as Dr Matsumura has pointed out it may affected other organs too.

Epidemiologically, CSS shows no difference in gender with mean age of diagnosis around 50 years. Aetiology is unknown although it is regarded as an autoimmune process because of the predominance of allergic features, increased T and B cell activity, presence of ANCA and an association with HLA subtypes.

On reviewing the literature in respect of leutriene antagonists, it is considered that the drugs probably do not directly cause CSS. However, because these drugs are used in asthma with the aim to reduce steroid use, by so reducing the corticosteroid dose probably unmasks true CSS rather than the leukotriene antagonist causing the CSS-like syndrome.

The CSS can take many decades to fully manifest the full spectrum of features and patients generally have a long history of allergic disease e.g. asthma, atopic disease followed by an eosinophilic stage characterised by peripheral eosinophilia and organ infiltration with eosinophils. The final stage is the vasculitic stage.

A history of asthma is the cornerstone to the diagnosis as most patients will have had asthma for up to a decade before the diagnosis of CSS is made.

Most patients require steroid therapy for their asthma and severity and frequency of exacerbations may increase over time. 2/3 of patients develop skin involvement in the vasculitic stage and generally affect the limbs and may manifest as palpable purpura, macular or papular erythematous eruption, haemorrhage, tender cutaneous or subcutaneous nodules (granulomas).

Indeed, the heart can be affected in the CSS with manifestations including pericarditis, heart failure and AMI. 50% of deaths are related to cardiac disease from the CSS, so it is not a trivial finding.

Neurological manifestations are usually as a mononeuritis multiplex which can progress if the CSS is left untreated. Renal disease can also manifest with the commonest problem being focal segmental glomerulonephritis. Gastrointestinal disease may occur as an eosinophilic gastroenteritis.

Most CSS patients (70-75%) have ANCA against myeloperoxidase (P-ANCA). However, this patient was ANCA negative. In a small analysis it was indicated that there may be a difference between ANCA + and ANCA - patients with the former having more renal involvement and more neuropathy whereas the latter having more heart disease and fever associated with their condition.

Note that this patient had bilateral effusuions. 30% of patients with CSS actually have effusions and analysis usually reveals eosinophils and an exudative composition. As Dr Matsumura has correctly pointed out, the American College of Rheumatology guidelines offer a way to make the diagnosis. In fact, in view of the positive biopsy result, this patient had at least four of the six criteria making the diagnosis of CSS extremely likely.

Treatment is indeed with corticosteroids at a dose of 0.5-1.5 mg/kg/day for 6-12 weeks or until the disease manifestations have completely resolved. The higher dose is required especially if there is cardiac, renal or nerve involvement.

Refractory CSS (as in this case) may be helped with the addition of cyclophosphamide, azathioprine, immune globulin or alpha-interferon. However, some authorities recommend an induction treatment of steroid plus cyclophosphamide and for remission to be maintained with methotrexate or azathioprine. Monitoring of disease is via the eosinophil count and ESR --- not ANCA.

Prognosis: With adequate treatment, 5 year survival > 70%. Most deaths result from complications of the vasculitic phase and include heart failure / AMI, cerebral bleeding, azotaemia, GI bleeding and life threatening asthma.

I would again like to thank everyone for their significant contributions to answering this case. For a more detailed review of the CSS, I would refer you to UpToDate 16.2, Current Medical Diagnosis and Treatment 2008 (McPhee, Papadakis and Tierney) and the Oxford Handbook of Rheumatology, 2nd Edition, 2006 (Hakim, Clunie and Haq).

Have a great week !!!

A New Case For September

Dear Bloggers

The following case was provided to me for publication on this Blog. It has been anonymised to maintain patient confidentiality and is used to provide an example of Problem Based Learning of disease. I thank those wise physicians who made the diagnosis and who enlightened me about this case in a distant part of Japan.

This male patient presented to the outpatient clinic with the following symptoms:

• Cough and dyspnoea
• Facial swelling
• Arm and chest rash with pruritis
• Dull abdominal pain
• Finger numbness

History of Presenting Complaint

The cough began 1 month prior to admission and was productive of clear sputum and this symptom was mild.

The patient was becoming increasingly short of breath with wheezing and he was using his asthma medications without effect. On admission, his breathlessness was the worst he had ever experienced. He could normally walk most distances but prior to admission he was limited to only a few feet before encountering severe dyspnoea.

His face also began to swell especially around the right eyelid. There was a rash that was described on the left forearm that was red and itchy. The itchy rash spread to involve his upper chest and neck. Despite using an anti-histamine, the symptoms continued to progress.

5 days before admission he felt a dull pain in the right upper abdomen. The pain continued for several days and was 3/10 in severity. There was no radiation of the pain and he was still able to eat and drink. The patient was able to pass faeces and flatus normally and there was no constipation, diarrhoea or vomiting. The patient denied urinary symptoms and there was no back pain. He denied eating raw or poorly cooked food products.

The finger numbness was described like ‘pins and needles’ and affected only the distal aspects of his fingers. He did not have any symptoms in his feet. He denied any symptoms of diabetes mellitus (thirst, polyuria, lethargy) or high alcohol consumption, and he had a normal diet.

Previous History
• Chronic Sinusitis (30 years)
• Asthma (life long)
• Nasal polyp operation (8 years ago)
• Recurrent Urticarial-like skin rashes (from 5 years before)
• Recurrent Eyelid and Facial swelling (from 5 years before)
• Autoimmune Haemolytic Anaemia (AIHA) treated with steroid pulse therapy 3 years before.
• Urinary stones (5 years before)

Medication
• Epinastine HCl 20 mg (anti-histamine)
• Salmeterol 50 micrograms (inhaled)
• Fluticasone 20o micrograms (inhaled)

Family History
Mother had tuberculosis

Social History
Living independently in a house with his wife and 2 children.
Self-employed as an accountant.
Patient was a non-smoker and non-drinker.

Physical Examination
GCS 15/15. Alert. Temp 36.1 deg C, BP 100/60mmHg, HR 72 regular, Resp Rate 18/min, SpO2 88% breathing ambient room air.

General: Swollen face and obvious erythematous skin rash on left arm and chest. No JACCOL.

HEENT:
Eyes – pupils equal and reactive to light and accommodation, normal visual fields and no scotoma. Full range of extra-ocular muscle movements. No jaundice or anaemia.

Ears – Grossly normal externally. No auditory disturbance, Rinne’s and Weber’s test within normal limits. Tymanic membranes showed no redness, swelling and there was a normal cone of light.

Nose – no current maxillary or frontal sinus pain on palpation or percussion. Nasal examination not performed.

Throat – normal dentition, normal gums, normal tongue and mucosa. Pharynx not erythematous and no obvious swelling. Lymph nodes not palpable and thyroid within normal limits.

Cardiac: Apex located in 5 intercostal space in the left mid-axillary line, no heaves or thrills. Heart Sounds 1 & 2 normal with no 3rd or 4th heart sounds and no murmurs.

Respiratory: Trachea central and no ‘tracheal tug’. Expansion within normal limits (>5cm), percussion decreased at both bases. Wheeze throughout both lungs R>>>L. Few crackles at both bases.

Abdomen: Soft, flat, tender right hypochondrium and epigastrium. No rebound or tenderness.
No hepatosplenomegaly or masses. No hernial orifices. Bowel sounds normal. No renal angle tenderness.

CNS - described as grossly normal.

PNS – Tone, Power, Reflexes, Coordination normal throughout. Sensation decreased in the finger tips of both hands. Foot examination was within normal limits.

Laboratory Data ( )= normal range.
WBC 48 (35-91), Hb 12.4, MCV 93, Plts 447 (130-369), Na 141, K 3.7, Cl 106, BUN 5.4 (10-20), Creat 0.5 (0.4-0.8), CK 34 (11-140), Amylase 31 (43-116), AST 10 (8-38), ALT 7 (4-44), LDH 220 (123-251), ALP 307 (104-338), Total Bil 0.4 (0.3-1.1)

Chest Radiograph: Bilateral pleural effusions

Question 1: From the history, physical examination, radiology and laboratory data, please make a list of the positive findings.

Question 2: Please give a likely list of differential diagnoses based on your list generated in question 1.

Question 3: What tests would you perform to ascertain the diagnosis?

Questions 4: With the likeliest diagnosis in mind, what is the treatment of the disorder?

Please endeavour to have a go at answering the case. Submitted answers will be published anonymously (unless you otherwise specify), so if you have time then please have a go.