Thursday, 1 March 2007

The Tanned Lady

This Case from another hospital has been anonymised.

This 50 year old female was admitted to a hospital with the following Chief Complaints:

  1. Fever
  2. Back pain
  3. Fatigue
  4. Muscle Weakness
The history was relatively short being only 8 days which started with fever up to 38 deg C and associated back pain. She attended a nearby Clinic and the doctor prescribed antibiotic therapy although it is not known what diagnosis was established at that time. She took the antibiotics for 3 days but there was no symptomatic improvement.

After 6 days she developed Fatigue and Loss of Appetite. After a further 2 days, she was becoming increasingly weak and could not get out of bed. Her husband needed to help her get to the toilet, and on one occasion she experienced diarrhoea.

At this point, several important questions were asked to elaborate on the history such as what type of fever was it? Continuous or Oscillating / Spiking Fever. The latter is very suggestive of a bacterial / viral infection / abscess whereas continuous low grade fevers can represent non-infective aetiologies once infection has been ruled out. It was a continuous fever, although the patient said it was 'up and down' suggesting it was a spiking fever.

Moreover, where was the back pain? It was in her central back. Then, what type of pain? Was in continuous? Intermittent? Dull? Sharp? Associated with movement? Tearing? Worse on breathing deeply?

The importance of back pain can represent many different aetiologies here especially with fever such as a discitis, vertebral osteomyelitis, paravertebral abscess, myeloma, inflammatory arthropathies, metastatic disease, dissection, chest infection, pulmonary embolism, UTI, renal pain from rhabdomyloysis??....the list is extensive and by no means complete here, and by asking the right questions can lead the doctor to a more accurate idea of what is going on.

The patient had diarrhoea but it was not asked whether the diarrhoea was painful, the colour, the amount, whether there was any associated blood or mucus. This could possibly fit with inflammatory bowel disease which can cause diarrhoea (bloody), fever, fatigue, and arthropathy or a reactive arthritis / Reiter's Syndrome. The diarrhoea of course could be just due to antibiotic therpay!

Was the back pain due to pancreatic cancer invading the retroperitoneum and causing malabsortion and steatorrhoea?? The importance of asking the most minute details about diarrhoea cannot be taken lightly.

Were there night sweats? Weight loss? These questions needed to be asked and in addition, any history of TB exposure, chronic cough, haemoptysis-- TB can cause fever, and if it spread to the spine it may cause back pain too (Pott's disease).

The patient's past history included some congenital hip problems only and the patient had never smoked, did not drink alcohol and had never had a blood transfusion.

She was taking no medications apart from the antibiotic therapy.

No Family History or Detailed Social History was asked which is unfortunate as these may have given some clues.

Physical Examination: She was sleepy and hardly answered questions which may account for the paucity of history.

Temp: 39.1 Deg C, BP 82/40, SpO2 96% ? with Oxygen or Room Air. No Resp Rate or heart rate were recorded which in this situation was very important as the patient was clearly ill.

There were no meningeal signs-- no neck stiffness, No Kernig's Sign. Babinski was not performed.

The rest of the examination was described as normal.

Clearly, from the above examination, it was not entirely clear what the problem was with this patient.

However, the patient was clearly shocked and with a high fever and low blood pressure one has to consider Septic Shock as the primary problem.

Chest Xray revealed a left sided pneumonia. CT Chest again confirmed the pneumonia seen on chest xray.

Blood tests:

WBC 11,200, Platlets 9.4 , CRP 29.3, INR 1.46, D-Dimer 2.7, [FDP not tested]
CK 615
BUN 76, Creat 4.57, K 4.0, Na 128
Hb 10.3, MCV 84.2

AST 97, ALP 1434, gamma-GT 266, Bil 3.4 (Direct 2.4, Indirect 1.0), LDH 295, Alb 2.5

Urine: WBC 10-19. No bacteria. Myoglobin 1632.

ABG: pH 7.5, Low pCO2, HCO3 19.6, PO2 54.4 and BE -0.9

The above results signify severe problems for this patient including:

  • Acute [probably Bacterial] Pneumonia with Hypoxaemia and Respiratory Alkalosis
  • Disseminated Intravascular Coagulation
  • Rhabdomylosis
  • Acute Renal Failure [probably from combination of Shock, Sepsis and Rhabdomyolysis]
  • Severely abnormal liver function [? Shock Liver -- unlikely here as usually ALT and AST are very high in shock liver; this picture looks more obstructive]
The patient was treated with a 3rd generation cephalosporin and this was changed to meropenem by the 13th day.

No organism was identified by blood culture which may be due to previous antibiotic therapy.

She also received gamma-globulin, Anti-Thrombin III for the DIC and under went plasmaphoresis for endotoxin related shock and renal failure on several occasions.

The HDF was stopped when the plasma creatinine reached 0.94 although the bilirubin was now 5.7

Antibiotics were stopped 14 days after admission.

However, she was complaining of itching. She was otherwise saying that she felt well.

The most striking thing that was noticed was her tanned skin which was not the yellow one sees with Jaundice, but a tan from being in the Sun.

However, she said she never went out in the sun and she did not come from a Southern area of Japan. She said her skin had become increasingly tanned since last year BEFORE she was unwell with this acute problem. She otherwise was feeling well.

She had never had Hepatitis B or C infection and as mentioned, she did not drink alcohol.

This suggested, before examination, that the liver problem pre-dated the infection and was chronic in nature.

On examination, she looked well. There was no asterixis [liver flap], slight palmar erythema [red palms], and mild excoriations [scratch marks] on her arms.

She had deep tanning in exposed and non-exposed area of her skin.

JVP was not raised. No lymphadenopathy. Eyes were jaundiced. No liver breath [fetor hepaticus].

Pulse 80/minute, No heaves / Thrills. Heart sounds were normal. Mild peripheral pitting oedema.

Respiratory rate was 18/minute. Chest revealed some mild left basal crepitations [crackles] which did not clear on coughing consistent with resolving pneumonia.

Abdominaal Examination was abnormal: The patient had one spider naevus [vascular spider] on the left supraclavicular area. The liver was enlarged about 3 fingers below the costal margin and was mildly tender but smooth to the touch. Splenomegally could not be identified from palpation, but Traub's Space was Dull on percussion consistent with mild splenomegally.

Bowel sounds were normal.

Clinical Impression

The acute problem had clearly resolved.

However, she had obvious Hepatosplenomegally, Deeply Tanned Skin, Signs of Chronic Liver Disease and Liver Biochemistry consistent with an Obstructive Picture and particularly a High Alkaline Phosphatase.

The CT abdomen confirmed the physical findings and ultrasounds showed no dilatation of the Common Bile Duct.

Obviously, the above findings are consistent with Primary Biliary Cirrhosis. A differential diagnosis, if this were a Caucasian patient, would be Haemochromatosis especially because of the Deep Tanning of the skin.

Autoantibodies were performed and ANA was positive 160 (+), Anti-Mitochondrial M2 Antibody 49.4 (+)

Hence, the diagnosis here was likely to be PBC. It would fit the clinical features of this patient in that it is common in females aged between 30-60 years and approx 50% have no symptoms prior to diagnosis. Particular features include pruritis [itchy skin], tanning of the skin[due to increased Melanin deposition NOT BILIRUBIN], and smooth Hepatomegally in advanced stages. Most other causes of chronic liver disease produce a small liver. However, acute hepatitis can produce an enlarged liver.

PBC is associated with other autoimmune phenomena such as Sjogrens syndrome, autoimmune thyroiditis, CREST syndrome and autoimmune arthritides.

Most patients thesedays are identified by picking up blood abnormalities when asymptomatic with a raised ALP being one of the first signs.

Obviously, this patient had advanced disease and it is a surprise that it was not identified sooner than this when it could have been more amenable to therapeutic intervention.

Most patients are commenced on ursodeoxycholic acid as this is the only drug known to alter the natural history of PBC although it does not prevent chronic liver failure or the need for transplantation. Other drugs that have been used in the past include: colchicine and methotrexate although in randomisd trials they have shown no statistical benefit. [please see UpToDate 15.1 for further details]

It suggested that other causes of liver disease should also be ruled out including Haemochromatosis [ferritin level], Wilson's Disease [caeruloplasmin], and alpha-1-antitrypsin deficiency. Note that copper metabolism is abnormal in PBC and Keyser-Fleischer Rings can occur in these subjects.

An ERCP was recommended to rule out Primary Sclerosing Cholangitis.

Moreover, the patient would have needed a liver biopsy to confirm the diagnosis and stage of liver involvement.

Ultimately, the patient would require a liver transplant.

Other things to consider include checking levels of fat-soluble vitamins including A, D, K [ and E, but not clinically relevant]. Vitamin A deficiency can lead to night blindness in severe disease especially in those with raised bilirubin levels. A prolonged clotting time can be indicative of vitamin K deficiency and vitamin D deficiency can lead to osteomalacia. If levels are low, they need to be replaced.

Malabsorption can lead to steatorrhoea and reduced nutritional absorption. In such cases, either fatty acid intake is reduced and / or pancreatic enzyme substitutes are given.

The patient should have also been considered for a diagnostic-therapeutic upper GI endoscopy as the patient has a high risk for oesophageal varices even in the absence of obvious cirrhosis. Treatment consists of banding varices and reducing portal pressure with non-selective beta-blockers and calcium antagonists.

This case, once again, underlines the importance of obtaining a thorough history and physical examination.

Finally, causes of Hepatosplenomegally should be reviewed here and include:

  • Liver disease and Elevated Portal Pressure including PBC
  • Infections: Malaria, Schistosomiasis, Toxoplasmosis [cats: social history!], CMV, EBV, Acute Hep B, C infection, Weil's Disease [Rat's urine -- Social History!], Brucellosis [food history part of social history!]
  • Haematological-Neoplasia: CML, CLL, Lymphoma, Extramedullary haematopoiesis of myeloporliferatice disease e.g. polycythema rubra vera
  • Granulomatous: TB, Sarcoidosis
  • Inflammatory: Amyloidosis
  • Vascular: Budd-Chiari Syndrome
Causes of Hyperpigmentation should also be reviewed and include:

  • Racial
  • Sun Related
  • Dermatological: severe chronic eczema, freckles, acanthosis nigricans, chloasma [pregnancy related]
  • SunTan Supplements e.g. Tanning Creams (がんがろ!!)
  • Tattooing, arsenic exposure, gold, argyria.
  • Drugs: chloroquine, chlorpromazine, minocycline, amiodarone.
  • Topical Agents: benzoyl peroxide, tretinoin, flurouracil
  • Berloque hyperpigmentation: phototoxicity from citrus or celery
  • Drug Eruptions: Septrin, NSAIDs, Tetracyclines
  • Oral Supplements: Beta-carotenaemia
  • ACTH related: Primary Hypoadrenalism, ACTH secreting Pituitary adenoma, ACTH secreting tumours e.g. Ca Lung
  • GI related: Haemochromatosis, Primary Biliary Cirrhosis, Wilson's Disease, Whipple's Disease, Hyperbilirubinaemia from any cause.
  • Infection: Visceral Leishmaniasis

Wednesday, 28 February 2007

Collapsing Patients and Drugs

This case has been anonymised for patient safety but provides good examples of investigating collapses in elderly patients.

This elderly female patient was recently admitted to another institution due to 1) symptoms of a chest infection and 2) Collapse.

The patient was demented and was unable to provide any history of what happened. The brief history was provided by the care home.

The patient had recently developed a cough, sputum and fever and had been seen by a local community physician who had diagnosed a chest infection for which levofloxacin had been prescribed.

The patient had been getting better and the sputum had stopped although the patient had developed rhinorrhoea and general upper respiratory symptoms for which a further course of levofloxacin had been prescribed.

The patient had been eating her dinner when she suddenly collapsed at the table with her head falling forwards on to the table. Within a few minutes, the patient had regained consciousness. The patient could not remember anything of the event. There was no description of seizure activity. It was not clear whether the patient had bitten her tongue or developed urinary incontinence during the episode.

Further questions I would have liked to ask include: pre-syncopal dizziness, palpitations, chest pain, sudden onset of headache and visual aura before the collapse. Also, was the patient coughing prior to the syncope (cough syncope), any history of collapse / dizziness on turning of her head (hypersensitivity of baroreceptor response). Any cardiac history such as dysrhythmias, valvular disease, ischaemic heart disease?

Previous history included hypertension and dementia plus borderline diabetes.

Drugs included amlodipine, topical GTN patch, oral cough medication (opiate based I think), and levofloxacin.

The care home did not mention about angina but the patient was clearly taking medication that would be used for her heart!

No known drug allergies.

From the history alone it was convincing that this was a Cardiac Syncope possibly induced by drugs (combination of calcium blocker, nitrate, opiate derivative) plus there is the possibility of Torsade de Pointes from a Long QT interval induced by Levofloxacin especially on a back ground of probable ischaemic heart disease.

Vitals revealed a BP of 151/57 (large pulse pressure), pulse 70 regular, Resp Rate 20/min, Sats 97% on RA. Patient was afebrile.

Pulse examination revealed a Bounding and Collapsing pulse suggesting possible Aortic Regurgitation. JVP was not raised. There was an obvious Carotid Murmur originating from the heart and a Soft systolic mumur at the Aortic area.

Chest examination was normal with no crackles.

Leg examination revealed mild oedema probably as a result of the Amlodipine, which is a known side effect.

Chest Xray revealed calcification of the rib ends which is a normal sign of aging. There was some mild shadowing behind the heart which was consistent with consolidation with current or recently treated infection.

ECG revealed sinus rhythm but with first degree heart block and a corrected QT of 416ms. There were no acute changes.

Urine revealed 4+ bacteria and 2+ white cells.

Bloods showed a raised CRP and white cell count was normal. CK and CK-MB were normal. There was some mild chronic renal failure consistent with the patient's advanced age.

Clinical Impression:

1) Syncope due to drop in cardiac output possibly from combination of hypotensive drugs and opiate-derivative (which causes venodilatation).

2) Possible Torsade de Pointes from Levofloxacin ( a rare but well described phenomenon)

3) Post-pneumonic changes on chest Xray

4) Current Urinary Tract Infection


It was suggested that the Levofloxacin be stopped and continue with the already started Ceftriaxone. The patient coming from a Care Home might have a multi-drug resistant bacterium and hence, urine culturing and sensitivity would be of prime importance here plus blood cultures. Levofloxacin is an excellent drug for treating UTI, but with the urine being positive suggests to me that the infection was not being effectively treated.

It was also suggested obtaining a cardiac echo to ascertain if there was underlying aortic regurgitation because if moderate-severe, it can be dangerous using nitrate drugs as these can cause sudden drops in cardiac output and collapse.

It would also be of advantage to obtain continuous cardiac monitoring or at the very least a 24 hour Holter monitoring to see if a dysrhythmia can be identified.

It was also suggested that if the above tests proved negative the Carotid Sinus Massage (CSM) could be performed to see if there was any underlying hypersensitivity of the carotids to cause sudden heart block and collapse.

This is done with the patient in a recumbent position wired up to a monitor. The patient must not have any carotid stenosis (otherwise stroke might occur!) and hence, it should be done on the side with
no murmur. If a patient has bilateral murmurs, then a Carotid Doppler would need to establish if the carotids have any disease and hence, whether it would be safe to perform CSM. If safe to do so, the carotid on ONE SIDE of the neck is massaged with light pressure for 30 seconds to one minute to see if there is any cardiac slowing. If the patient feels unwell during the procedure such as dizziness, then the procedure should be terminated.

If the patient's heart rate slows, then it should be recorded and printed out if possible.

If this test is normal, then a Dix-Hall-Pike test can be performed which involves cardiac monitoring and manouvers angulating the patient. This can reveal underlying problems causing collapse.

Tuesday, 27 February 2007

Every Breath You Take- Every Move You Make

Professor Lonny Ashworth, MEd, RRT.

Today we had the pleasure of having Professor Lonny Ashworth from Boise State University in the USA attend the hospital to lecture on how to use ventilators.

His visit was brief, just for 4 hours only, with him previously having been visiting a hospital in Chiba.

Today, he hosted two identical practical sessions whereby junior doctors could try Ventilators for themselves to see how CPAP feels, in additon to Square Wave Forms, Assisted ventilation and SIMV to mention but a few topics discussed and tried.

Each doctor got to be a 'patient' on a ventilator with the other doctors changing the controls.

The ventilators used were very hi-tech, the ones that I am used to seeing in the UK.

The junior doctors appeared to enjoy themselves very much and with the help of a translator, were able to understand well.

Here some junior doctors pretending to look studious but really being comedians!

Looks like SCUBA diving but a great lesson in ventilator control !!

No sleeping or time to be intubated and ventilated ! !

During his lecture, Lonny made a joke and said 'Every breath you take....' and I said 'Every move you make....' and he said --- ah no that's a song!!! Yes, from Sting and the Police ! A great respiratory song.

Some panoramic views of the study session....

Lonny, we really enjoyed your session and you are welcome back anytime!

Monday, 26 February 2007

History and Physical Revisited: a neurological quandry

This case has been anonymised for patient confidentiality.

A male patient of advanced age who presented with a sudden history of collapse. The patient apparently did not lose consciousness and returned to his home. Following this, the patient's conscious level began to decrease, and his breathing became laboured and his family admitted him to hospital.

It was not clear exactly what was described when the patient's breathing became abnormal. For example, did respiratory rate increased or decrease? Did the patient develop asthma-like symptoms, was there any pulmonary oedema, cough, sputum, haemoptysis?

Also, there is no history about what happened before the collapse. Where was the patient? What was he doing? Was there a sudden onset of headache? Were there any other features? Was there seizure activity and if so, was it sustained?

With the paramedics attending his home, his GCS was described as 3/15 but on admission to hospital, the GCS had apparently increased to 14/15 and the patient was able to speak and follow commands during examination.

However, following this, his breathing became further laboured with there being identification of hypoxaemia on blood gas analysis and the patient was intubated and ventilated.

The patient had not apparently sustained any head injury but other details of history such as sudden onset headache / chest pain / neck stiff were not elicited.

The previous medical history was that of hypertension only for which he took medication, although on admission, it was not known what medication he was taking.

Vitals signs were slightly abnormal, with the patient being normotensive, afebrile but with a of pulse 100/min and regular.

From what was relayed to me, the CNS examination was relatively unremarkable and the only positive finding on the rest of the physical examination were bilateral crackles at both bases on chest exam.

The patient had had the usual tests including chest Xray and Chest CT which showed old changes which looked like fibrosis, but there was no obvious pneumonia.

CT head showed a very small area of fibrosis near the thalamus on the right side, but this looked old. There was no blood or space occupying lesion (SOL). The MRI scan showed no abnormality apart from some artifact over the left frontal area. The diffusion MRI was otherwise normal.
The vascular scan showed no obvious abnormality.

Bloods revealed a slightly raised BUN of 27 but a normal creatinine. White cell count was slightly raised and CRP was increased to 2.1. CK, CK-MB, Troponin T were all normal. All other usual bloods were normal.

ABG- revealed a normal pH but CO2 and HCO3 were decreased and the SpO2 was approx. 50mmHg consistent with a compensated respiratory alkalosis and hypoxaemia.

The team were concerned that a pneumonia may be causing the chest symptoms but were unable to ascertain the cause for the collapse and coma, especially as the examination and tests had been normal.

My Opinion.......

On hearing this rather brief history, the differentials that come to mind include:

  • Subarachnoid haemorrhage -- initial collapse from bleed and then as vascular constriction ensues, and intracranial pressure increases, the patient can become comatosed from ischaemia. Some SAH cannot be picked up on CT and only a Lumbar puncture performed, usually after 18 hours will pick up Xanthochromia.
  • Stroke: a sudden onset phenomenon with sudden loss of neurological function either from infarction or bleeding. When considering thrombotic stroke, one should remember that thrombo-emboli can originate from the heart chambers, the valves, myxoma, platelet rich emboli from the carotids and primary thrombosis from atherosclerotic plaques. Paradoxical embolus and stroke can occur from a patent foramen ovale giving a right to left shunt through the atria. Emboli can pass from right to left cardiac circulations and cause stroke! This however is very rare. Patients may regain some level of consciousness but this may deteriorate with cerebral oedema.
  • Sudden Cardiovascular Collapse: Loss of cardiac output for any reason such as a dysrhythmia, can lead to collapse and patients may suffer cerebral hypoxia and brain damage or head injury. With the latter, injuries to the temporal area can cause laceration of the middle meningeal artery and tense extradural bleeds and reduced consciousness.
  • Dissection: Dissection can lead to acute collapse from sudden loss of valvular competency and / or tamponade, and if there is a proximal dissection, it can occlude the arteries supplying the head and neck leading to stroke.
  • Pulmonary Embolism: Large PEs can cause sudden collapse and unconsciousness due to sudden cardiovascular compromise. PE can be chronic in nature and cause fibrotic change. Hypoxaemia from a massive PE can lead to hypoxaemia and reduced conscious level.
From the scans and data, there was neither an obvious large stroke nor an SAH. There was no evidence of a dissection or head injury either. The CT chest, which showed contrast imaging of the pulmonary vessels, did not reveal any PE.

Further results revealed a normal CSF examination with a slightly raised protein level only.

Urine results revealed no sugar but two plus of ketones (probably explained by fasting state)

Blood sugar approx 210. Could have this been an undiagnosed DKA with respiratory compensation??? I think unlikely in view of the absence of glucose in the urine.


Examination of the patient was difficult due sedation from propofol. However, at the end of the bed, the patient was making some unusual movements of adducting his shoulders and turning his wrists slightly inwards. He also had twitches which I thought might be sub-clinical seizure activity.

On examining him, his pupils were approx 4mm bilaterally and responded rapidly to light and were hence intact. Response to pressure on the nailbeds on both hands revealed Extension to Pain. Babinski responses were bilaterally positive as was Achille's Tendon Pinch which also causes plantar extension. Just to ensure that this was not just a withdrawal response, the patient was tested with a noxious stimulus, which in the case was a blunted pin. A normal response should be to plantar flex away from the pin tip when applied to the dorsal aspect of the toe. A positive response is dorsiflexion towards the pin tip. This patient showed bilateral Positive Signs confirming bilateral Upper Motor Neurone impairment.

Chest examination revealed bilateral crackles with them being of higher intensity of the right side.

Clinical Impression

Following this most revealing examination, it showed that the patient actually had developed severe neurological signs. With the signs being Bilateral this suggested that both cerebral hemispheres had probably become involved.

With the patient Extending to pain, this is a decerebrate condition. However, his pupillary responses were spared and when examined by a very astute neurologist, the Doll's Eyes reflex was also normal suggesting a normal midbrain.

Hence, a definite abnormality was identified which could now account for some of the features of the history.

The basic neurological examination helped reveal the problem that no scan could identify.

This underlines the importance of a good history (where possible from the patient / family /friend /bystander) and detailed physical examination.

Please remember that detailed physical examination should be able to reveal gross physical abnormalities. When performing a neurological examination on a conscious or unconscious patient, the Babinski Response can be of paramount importance. There are many other tests for finding upper motor neurone signs such as Hoffman's Sign in the fingers and many other in the feet which can be found in any good neurology textbook.

Don't forget to check for Clonus as more than three beats is signifcant og UMN signs.

Don't forget the Reflexes. It does not take long to do but can reveal the possible level of the problem and determine absent, decreased, normal or increased reflexes, which are all significant of either normal or abnormal neurological states.

Don't forget to do sensory testing in the conscious patient as this again can determine the level of a lesion.

This patient had a repeat scan but again this was normal.

After discussion with the neurologist, it was suggested that the clinical features and a normal set of scans with 24 hours of admission could be accounted for by:

  • Diffuse bilateral hypoxic-ischaemic damage of the cerebral hemispheres
  • Multiple embolic phenomena
Hence, the history of sudden collapse and waxing-waining consciousness might be accountable from a cardiovascular cause leading to cerebral ischaemia or multiple infarction.