Answer to August 2009 Case

Dear Bloggers

Thanks for waiting for the answers to this exciting case.

I would like to apologise for the typing error with the PNS exam which should have been like this

RUL LUL RLL LLL

Supin +/- ++ n/a n/a
Bicep +/- ++ n/a n/a
Tricp +/- ++ n/a n/a
Knee n/a n/a +/- +/-
Ankle n/a n/a +/- +/-

RUL = Right Upper Limb
LUL = Left Upper Limb
RLL = Right Lower Limb
LLL = Left Lower Limb

This month Prof Alan Lefor (Surgeon, USA) and Professor Gerald Stein (Rheumatologist, USA) have kindly answered the case. Their comments follow on below:

Professor Lefor

Question 1: From the history and examination, please make an appropriate problem list. Problem List:

1. History of LOC with urinary incontinence 2. Changes in bowel habits (loose stool, black stool) 3. Neurology symptoms (double vision, dizzy, tingling, reflexes asymmetric) 4. Hx of adrenal tumor 5. PAF 6. Hx of previous Htn 7. Abnormal physical exam with axillary nodes, hypotension and tachycardia

Question 2: Please provide a differential diagnosis (es).

It would be nice to tie all of this together in one package, which may be possible, but there are other possibilities with multiple diagnoses. 1. GI tumor with brain mets, anemia 2. Other primary tumor (e.g. melanoma) with GI, brain involvement 3. GI bleeding from a non-malignancy and significant anemia 4. New onset seizures from tumor or from metabolic disturbance 5. Metastatic adrenal tumor (someone should get the details of this tumor from old records, it is essential).

Question 3: What would you immediately do for this patient?

Immediate actions: 1. Complete the physical exam with a stool guaiac test 2. IV fluid resuscitation with catheter placement to follow urine output 3. If her anemia is significant, given her LOC, tachycardia and hypotension, then transfusion is indicated.


Question 4: What tests would you perform and why?

1. I think the stool guaiac will probably be positive. She needs a colonoscopy. If that is negative then upper endoscopy especially if an NG tube shows bloody drainage 2. She has enough neurological symptoms to mandate a CT of the head for ischemic damage or mets as a cause 3. I would check a CBC (?anemia) and electrolytes (?cause of seizures, etc) 4. If all of this is uninformative, especially the endoscopy, then the axillary lymph nodes should be biopsied in the search for a primary tumor.


Question 5: What other bedside physical examination test(s) could provide additional information to aid your diagnosis?

1. Stool guaiac 2. Fundoscopy looking for signs of increased intracerebral pressure 3. Pass NG tube to R/O upper GI bleeding

Professor Stein Question 1: From the history and examination, please make an appropriate problem list.

1. Transient Loss of Consciousness with urinary incontenence need duration
2. Loose BLACK stools
3. Parathesias LUE, diplopia (Cr N 6), proptosis L eye, LUE & LLE ??? DTR
4.Adrenal tumor>-ectomy
5. HTN
6. PAF
7. 2 anti plat Rx + NSAID
8. Anemia
9. Lymphadenopathy
10. Hypotension
11. Tachycardia

Question 2: Please provide a differential diagnosis (es).

1. R/O GI bleed/hypovolemia/hypotension 2. R/O Subdural hematoma 3. R/O Midbrain or Brain stem infarct 4. R/O Brain emboli [PAF] 5. R/O arrythmia 6. R/O AMI & PE 7. R/O DM/Addison???s 8. R/O causes of hyperuricemia: renal, lymphoma 9. R/O seizure

Question 3: What would you immediately do for this patient?

1. Fluid resuscitation-hourly urine output 2. Capillary Glucose 3. STOP anti plat & NSAID Rx

Question 4: What tests would you perform and why?

Stool & NG fluid occult blood; if + EGD/colonoscopy, ECG for PAT/hidden flutter CBC, electrolytes, Blood glucose, BUN/creat, cardiac markers, D-dimer, cortisol, Chest xp, Brain CT Cardiac, ECHO, EEG-later if needed

Question 5: What other bedside physical examination test(s) could provide additional information to aid your diagnosis?

Stool occult blood, Fundoscopy, Ausculate neck for carotid bruits and Bilat upper limb BP???s/pulses

Thank you to Professors Lefor and Stein for such excellent answers. I will now reveal the case answer below!

Question 1: From the history and examination, please make an appropriate problem list.

Problem List

1. Loss of Consciousness
2. Dizziness on standing
3. Urinary incontinence
4. Loose stools
5. Pins and Needles of the left arm
6. Double vision
7. Right adrenalectomy
8. Paroxysmal AF
9. Hyperuricaemia
10. Disopyramide / Aspirin / Voltarol / Allopurinol / Ranitidine/ Lactulose / Senna
11. Large, rubbery, smooth, multifocal lymphadenopathy
12. Tachycardia
13. Hypotension
14. Rectal Examination - Black stool
15. Proptosis of Left Eye
16. Abduction Palsy of Left Eye
17. Left arm relative Hyper-reflexia

Question 2: Please provide a differential diagnosis (es).

In the under 50s it is often desirable to try and use Okham's Razor to bring all elements of the problem list together to try and make one unifying diagnosis. However, in the over 50s although Okham's Razor can still be used, Hickham's Dictum is perhaps more relevant. This means that patients are allowed to have as many diagnoses as '...they well please' ! :-) This was described by Hickham in the 1950's when it was said that patients are statistically more likely to have several distinct illnesses / diseases then one rare disease (re Okham), which logically becomes more likely as the patient ages.

Hence, when looking at this case, it should be considered that there are multiple diseases rather than one. Let's first consider why the patient collapsed.

The fact that the patient experienced dizziness on standing, has vital signs consistent with shock (when the patient is usually hypertensive) and has a rectal examination consistent with malaena (despite the patient saying no to this) makes an upper GI bleed the most likely cause of the collapse. The cause of such bleeding is the combination of Aspirin and NSAID despite the use of Ranitidine (H2-blocker). H2-blockers are not as effective as PPI medication and even the latter cannot always prevent GI bleeding. However, one should also consider other causes:

• Infection - sepsis can result in collapse from shock. Remember that sepsis can cause DIC with low platelets and a coagulopathy. This can result in GI bleeding too. The fact that the patient was unconscious should alert us to intracerebral infection such as acute bacterial meningitis. Of course, other bacterial infections can cause septic shock e.g. gram negative UTI, GI infection
• Endocrine - remember that this patient has had a previous adrenalectomy and may therefore be relatively hypoadrenal. Hence, under a period of stress of any cause, hypoadrenalism can result with collapse (from hypotension), loss of consciousness / confusion (hypoglycaemia) etc. One might also observe a rise in the K+ and a low Na+ level. One should also consider thyroid disease e.g. thyrotoxicosis, which is a precipitator of AF.
• Trauma - no evidence to support this but the patient is taking anti-platelet agents so minimal head trauma could conceivably cause intracranial bleeding.
  
• Inflammatory (connective tissue disease) - no evidence to support this
• Neoplastic - see later. Gastric Ca with bleeding (possibly metastatic to brain), metastatic adrenal tumour -> cerebral mets ->seizure
  
• Haematovascular - SAH, intracerebral bleeding/infarction, subdural, extra-dural bleeding (less likely due to the PNS exam)
• Metabolic - Hyponatraemia, Hypoglycaemia, Hypercalcaemia
• Cardiovascular - cardiac dysrhythmia e.g. underlying worsening of PAF, other dysrhythmia induced by the disopyramide (!!!Remember that Class I drugs are also arrythmogenic!!!), Pulmonary embolism (always on the differential diagnosis list for collapse!) Vascular: Hypovolaemia / Sepsis / bleeding
• CNS - Seizure (as a result of metastatic tumour / metabolic / electrolyte / structural / vascular abnormalities)

The second set of problems we must assess are the cause of the tingling left arm with hyper-reflexia, diplpopia and proptosis with a impairment of abduction of the left eye. The lymphadenopathy may also be relevant here along with the hyperuricaemia. Although the CNS manifestations are physically presenting on the same side of the body, the fact that there is proptosis of the left eye strongly suggests a space occupying lesion in the left orbit. The hyper-reflexia of the left arm with tingling suggests a right sided cerebral lesions possibly affecting the sensory (post-central) cortex. Hence, the intracranial lesions are on different sides suggesting a multifocal pattern!

The fact that there are lymph nodes makes one consider the possibilities of:

• Infection e.g. Tb
  
• Neoplasia e.g. Ca stomach, lymphoma
  
• Connective tissue disease
• Granulomatous disease e.g. sarcoid

The raised uric acid might simply be 'idiopathic' perhaps related to her diet or alcohol consumption (which we are not told about). On the other hand, high turnover of cells might suggest the presence of a tumour e.g. lymphoma (as suggested by Professor Stein)

However, the description of 'smooth and rubbery' usually points towards the idea of a lymphoma as the cause. If there are indeed multifocal intracranial space occupying lesions, common things should be considered first e.g. malignancy (metastatic disease), intracerebral lymphoma, tuberculosis, etc. Hence, the differential diagnoses on admission have been separated into the causes of collapses and the causes these odd neurological symptoms and signs with some of the causes certainly over-lapping.


Question 3: What would you immediately do for this patient ? & Question 4: What tests would you perform and why?

• This patient has shock vital signs and she requires volume resuscitation and glucocorticoid therapy until such time that hypoadrenalism has been ruled out.
• In view of the malaena, it is advisable to cross match 6 units of blood for possible transfusion immediately or to use later if the patient bleeds more extensively. Large bore venous lines should be placed in each antebranchial fossa of the upper limbs for the purpose of rapid fluid transfusion.
  
• In order to guide fluid status, it is often advisable to place a central venous line to maintain the CVP at 8-12cmH2o and place a urinary Foley catheter to ensure adequate urinary output e.g. >30ml urine/hour. In Japan, CV pressure is estimated using echo measurements of IVC compliance that can estimate whether the CV pressure is raised or decreased. Remember that both methods are fraught with inaccuracy and hence, repeated physical examination is ALSO required to gauge when fluid rehydration is inadequate, adequate or excessive.
  
• Venous glucose should be checked and if in any doubt, 50ml 50% glucose should be given to treat for hypoglycaemia. Remember that peripheral and CNS glucose have a poor correlation. Hence, even if the peripheral glucose is normal, the CNS glucose can be low!
• Blood, sputum and urine culture should be obtained to investigate causes of sepsis. Remember that ranitidine and allopurinol drugs can affect the haemopoietic system causing immune dysfunction. If in doubt about the focus of infection, please treat accordingly with antimicrobial agents until infection has been fully excluded by negative cultures or another definitive diagnosis has been established.
• This patient should have basic laboratory data checked to establish haematological or biochemical abnormalites (as discussed) and a chest Xray which could be a clue for the cause of cerebral lesions e.g. cancer, Tb
• To investigate upper GI bleeding, an NG tube can be passed to aspirate blood. A negative test does not exclude GI bleeding but supports it if it positive. There is not evidence that passing an NG tube makes variceal and non-variceal bleeding any worse and it can be helpful diagnostically to know if there is fresh active bleeding. Once haemodynamically stabilised (and not before!) an EGD (gastroscopy) can be performed to look for a cause of possible upper GI bleeding. Intravenous PPI should be given e.g. omeprazole 80mg stat, followed by continuous infusion for 72 hours. Consider tranexamic acid which also reduces GI bleeding. Assess patient's Rockall score for potential of rebleeding AFTER the gastroscopy. This will help to know if the patient requires a 'bleeder bed' -- high input care on a GI ward.
• STOP ANTI-PLATELET AGENTS and CORRECT ANY COAGULOPATHY
  
• Remember, never do procedures on an unstable patient. Moving the patient to the GI room could prove catastrophic with a 'bleed out' on the way. Better if you can take the gastroscopy machinery to the patient!
• Once stabilised, this patient will need a CT head scan to look for SOLs, edema, bleeding, etc. If normal, a lumbar puncture would be very reasonable to exclude meningitis / bleeding. Remember, you have already given the antibiotic to cover infection. CSF can remain positive for up to 4 hours after injection of intravenous antibiotic. Even if the CSF is visibly negative for organisms, PCR can be performed.
• Lymph node biopsy should be performed as soon as possible to look for the underlying cause e.g. lymphoma.
• Remember to check the ECG and if there is still concern, a 24 hour Holter ECG can be performed. The disopyramide might need to be stopped until the cause of the collapse can be fully elucidated.
• Checking of cardiac enzymes (e.g. CK-MB, Troponin I/T) and D-Dimer should be performed. The fact that there may be underlying sepsis or malignancy can give a false + D-Dimer result and hence, as part of the work-up, a cardiac echo may be required. If the pressures are normal, then a life threatening pulmonary embolism (PE) can be ruled out whereas if they are elevated, proceeding to Spiral CT would be necessary. An Echo would also be useful to exclude large intra-cardiac clot that could give rise to cerebral emboli resulting in stroke and collapse.
  
• The fact that the collapse was unwitnessed and the patient has multi-focal neurological signs warrants an EEG to look for a focus of seizure. The patient might require intravenous medication -- remember though, disopyramide and pheytoin (the usually IV drug for seizures) are both Class I drugs. Phenytoin induces liver enzyme induction and can reduce the effective levels of disopyramide.
  

Question 5: What other bedside physical examination test(s) could provide additional information to aid your diagnosis?

• If the patient has an intra-orbital SOL, performing fundoscopy might reveal raised pressure which may be visualised as papilloedema.
• Comfirming the black stool as malaena with the Guaiac test would be supportive of GI haemorrhage.
• As mentioned above, an NG tube could be passed to look for upper GI bleeding.
  

Comments on the Case

Below are the CT pictures that confirm the physical examination findings. Please note the multiple SOLs were considered BEFORE the CT head scan was done. Proptosis and gaze palsy with axillary lymphadenopathy should suggest the possibility of an intra-orbital tumour, as was suspected in this case. Cerebral edema from an SOL was additionally suspected as part of the differential diagnosis. There needed to be careful consideration of using high dose dexamethasone given the possibility of it affecting the GI bleeding by impairing ulcer healing.

The scan shows two mass lesions - one in the left lateral orbit (as suspected) and one in the right cerebrum with edema.

Admission laboratory data was as follows:

Hb 11.o, WCC 8.2, HCT 32.6, MCV 80.1, Plts 135, INR 1.3 Na 132, K 5.3, BUN 60.2, Creat 1.3, Ca 8.7, Glu 160, LDH 290. Normal liver function tests. Albumin 2.8, Total protein 5.9

As can be seen above, the BUN/Creat ratio is 46.3 (hence, more than 20) suggesting an upper GI source of the bleeding. Note the Na 132 and K 5.3 which might signify hypoadrenalism (remember the loss of aldosterone leads to accumulation of K and failure to absorb Na in the kidney). Even though the Hb is 11.0, a normal female Hb level is from 11.5 to 16.o and hence, this patient does have an anaemia. Moreover, the MCV is more than 80 but for the local laboratory measurement it is low! Remember to ALWAYS refer to your own lab's normal range otherwise the microcytic anemia can easily be missed !

The stool examination was +/+ for blood.

As a consequence, the patient underwent a gastroscopy and a large acute gastric ulcer was present (see below) and treated accordingly.

Despite the other mentioned possibilities of sepsis and hypo-adrenalism, unfortunately, these were not followed up by the attending team. The chest x-ray below reveals bulky perihilar areas, which given this case, is suspicious of hilar lymphadenopathy.

Lymph node biopsy revealed Diffuse Large B Cell Lymphoma. Diagnoses in this case:

1. Acute Upper GI Bleed (iatrogenic) from Aspirin and NSAIDs causing collapse and shock
2. Diffuse Large B Cell Lymphoma (multifocal e.g. intracranial, axillary) ? possible seizure due to intracerebral SOL with edema.
3. Possible hypoadrenalism

Take Home Message

• When patients are admitted with loss of conscious, unless there is a reliable witness to the events, search for more than just one cause especially in the elderly.
  
• In loss of consciousness, perform a rectal examination to look for bleeding. Failure to do so may miss GI bleeding!
• In loss of consciousness, perform a full neurological examination if the patient recovers consciousness. Even if unconscious, the GCS/JCS can be performed in addition to pupillary size, corneal reflex, fundoscopy, caloric test, tendon reflexes and Babinski reflex as common examples. In this case, only after asking specific questions did the patient offer up the neurological symptoms and only after a repeat examination did the abnormal neurology come to light. It had been otherwise missed. Hence, you need to have a high suspicion of neurological disease and actively ask additional questions rather than passively relying just on what the patient wants to tell you! Remember, patients don't write the textbooks and they don't know what you want to know (unless they are medical professional themselves!)
  
• Remember that resuscitation of the patient must be done first before considering moving them to have a gastroscopy, a CT or going for surgery etc.
  
• Correct all that can be corrected. This patient's INR was 1.3. That is abnormal. Giving vitamin K will not work to resolve the coagulopathy acutely. It takes several hours to have an effect by which time your patient could have bled out. The quickest treatment is giving factor replacement e.g. factor concentrate (II, VII, IX, X) if warfarin has been used, or Fresh Frozen Plasma (FFP). Even if it is justly slightly abnormal means that it is NOT normal and should be corrected. Don't take risks with your patients. Treat them how you would like to be treated given you being in the same situation.
• If hypoadrenalism is suspected, perform a rapid ACTH test and start appropriate dose steroids e.g. hydrocortisone 100mg iv every 6 hours. Do Not Wait for the results as it can take several days to the detriment of the patient!

Thank you for your consideration.

Many thanks to Prof Lefor and Prof Stein for providing their expert opinions on this month's case.

Thanks to Dr MM, Drs Y, A, Y & U.

History Revisited With Examination ! It CAN be better than a CT scan!

Dear Bloggers

A 70 year old patient was recently admitted with fever of 'unknown' origin to a rural hospital.

The patient had developed the fever suddenly with associated shivering sensation and had presented to the same hospital. Other symptoms included some rhinorrhoea and a mild cough. The on-call physician took blood cultures and prescribed an antibiotic for an URT infection and the patient went home at her own request.

However, after several days the blood cultures grew Group G Streptococcus in both sets of culture bottles. The patient was contacted and admission was arranged for inpatient investigation and treatment.

The patient had a background history of suspected infective endocarditis 6 months previously with the same type of organism, which was treated accordingly. However, at that time the transthoracic and transesophageal echocardiograms were normal. Colonoscopy revealed several polyps but no source of bacterial translocation was identifiable.

The patient was treated for suspected I.E and made a good recovery at that time.

Otherwise, there was no other apparent medical history.

The patient was taking no regular medications.

Alcohol consumption was moderate with several cups of Japanese sake per day and the patient smoked several cigarettes per day for the last 30 years.

Of note, she had recently bought a puppy.

Physical Examination had failed to establish the focus of the fever.

The laboratory data revealed a raised white cell count, raised inflammatory markers, and mild elevations in the liver function tests only.

The chest radiograph was within normal limits.

Transthoracic echo revealed previously noted mild valvular insufficiencies but there was no worsening and no vegetation to be seen.

A CT scan was performed to look for an abscess but only some mild splenomegaly was identified. The CT was hence, quite unhelpful.

At this point, the suspected diagnosis was vegetation negative endocarditis. However, if one reviews the Modified Duke's Criteria, this patient does not meet the criteria for definite I.E. with only one major criteria (typical bacteria) and two minor criteria (Fever>38 degrees and underlying valvular heart disease).

On reviewing the patient, several additional questions were asked:

• The patient had previous tooth problems and the bottom left incisor was loose but no dental treatment had been performed recently
  
• The patient had experienced several flea bites recently from her dog
  
• There was no history of sinusitis or headaches
• The patient had been diagnosed with a type of eczema for which ointment had been prescribed but the patient could not remember the name of the therapy
  
• There was no foreign travel
• No history of consumption of raw or under cooked food stuffs
  

On re-examination, new information came to light as follows:

HEENT- eczematous changes of the upper eyelids and eyebrows consistent with seborrheic dermatitis. Scalp examination also revealed seborrheic dermatitis (fungal origin). No sinus pain. Loose front, lower incisor (when pushed with a chopstick at the bedside) but no acute gingivitis seen.

CVS: pulse 80 regular, BP 120/80mmHg, JVP not elevated. Heart sounds I + II. No III/IV sounds. Pansystolic murmur at the apex radiating to the left axilla - Levine II/VI. Murmur loudest on expiration. No carotid bruits. No peripheral stigmata of I.E.

RESP: RR 14/min, Sats 98% on room air, trachea central and no tug. Percussion resonant and no crackles or wheeze.

ABDO: Soft, non-tender, no masses, no clinical hepatosplenomegaly on palpation but dullness in Traub's space. Small, non-tender, lymph nodes in the groin areas.

Skin: Several healing flea bites on the abdomen. Redness and increased temperature of the left hand after failed insertion of a venous line on the admission day. As noted above, eczematous changes over the face. Her left leg revealed a well circumscribed area 3 x 3 cm with peripheral redness with central clearing consistent with fungal infection. Foot examination revealed extensive tinea pedis (fungal infection).

The extremities had not been mentioned during the original presentation of the history. It therefore came as a surprise to see a 30cm vertical anterior scar running down the right tibia with extensive erythema of the skin with soft tissue swelling. The patient admitted to a previous fracture of the tibia.

On noting the leg changes, further questioning revealed that the redness and swelling had got worse over the last 10 days but it was not painful and so the patient did not mention it especially as it was a chronic problem for which she thought her current fever was unconnected. The patient admitted that several months earlier there had been a flare-up which required antibiotic therapy. Examination of the leg revealed increased temperature of the lower limb and tapping the bone was non-painful. These changes were clearly acute on chronic but raised the possibilities of cellulitis +/- chronic osteomyelitis.

Group G streoptococcus is an uncommon cause of cellulitis but this patient had the risk factor of previous injury and extensive fungal skin infection which can allow entry of skin associated bacteria. Moreover, Group G strep is also an uncommon cause of osteomyelitis (please see Medline).

The fact that the same organism was identified 6 months previously when the diagnosis was 'endocarditis' and that several echocardiograms showed no vegetation, makes I.E. unlikely and recurrent cellulitis / chronic osteomyelitis of the right leg far more likely a cause.

The patient was commenced on benzylpenicillin for which the bacteria was sensitive and an MRI was considered to look for osteomyelitis.

Take Home Message

• Patients do not always tell you the history you want to hear to make a diagnosis. You have to ask the right questions! Then the history comes forth from the patient bit by bit.

• If you see a skin abnormality or a bony abnormality, ASK about it. 'What happened here?' In this case, the patient had chronic problems with the leg dating back 40 years and the patient did not think that it was relevant. But it is the physician's duty to recognise the problem to decide if it is relevant. Hence, using history and physical examination to establish the facts.

• If the history, physical, lab data and echocardiograms do fit the picture for I.E. then don't diagnose I.E. Use the Modified Duke's criteria, but if the criteria are not met, then I.E cannot be made as the diagnosis. Consider other causes of chronic infection e.g. sinusitis, osteomyelitis, abscess....

• Examine your patients from HANDS to HEAD to TOE and look actively for problems that might otherwise account for the fever and bacteraemia despite the 'lack of symptoms'. Do not just accept that because the patient 'did not say , that they therefore do not have'. ASK and you will KNOW.

• This is the importance of using the Review of Systems (ROS) questions to probe each system for problems. More focused questions can then be asked if clear abnormalities come to light. Without using the ROS you will miss important problems that could lead you to the diagnosis. ROS is like a verbal CT scan -- it is used to 'scan' each system with trigger questions that make the doctor consider various diagnoses if the patient says 'yes' to such questions. Indeed, it takes longer than a CT scan to perform but is more localising and without radiation. **Always remember that by subjecting your patient to a CT scan you increase their risk of malignancy and so CT should be avoided if at all possible**
  

• In this case, a good old fashioned history and physical examination made the diagnosis at the bedside rather than a barrage of blood tests, echocardiograms and a 'pan-man' CT. If the diagnosis does not seem right then it probably is not right, and as such, please go back to the patient and re-interview and re-examine to get more relevant information. The answer is sometimes staring you in the face!
  

Have a great weekend.

August 2009 Case

Dear Bloggers

Here is August's case. It is a great one for sure! Please have a go and see if you can get the diagnosis!

A 65 year old lady was admitted to the hospital with loss of consciousness.

She had been found by her husband having collapsed in the toilet at 3am. The loss of consciousness had been unwitnessed but the patient was found to have urinary incontinence. Her husband called for an ambulance and she was transferred to the ER department. There was no obvious head trauma and no tongue biting.

The patient later became rousable in hospital and admitted to feeling dizzy when standing over the last few days. The patient also had some loose stools over the preceding days prior to admission but she described the colour as normal. There had been no associated abdominal pains. She denied straining whilst defecating.

She also admitted to recent ‘pins and needles’ in her left arm and some double vision over the preceding days prior to admission. She had no perioral paraesthesia.The symptoms had come on gradually and nothing had made them better or worse.


She denied the following symptoms

• CVS: No chest pains, no palpitations, no leg swelling
• RESP: No cough, bo sputum, no breathlessness
• ABDO: No nausea, novomiting, no haematemesis, no malaena, no swelling, no jaundice.
• Musc: No muscle pains, no weakness, no joint problems.
• URO: No frequency, no nocturia, no haematuria.
• CNS/PNS : No headaches, no visual loss, no speech disturbance, no hearing loss. No weakness of arms or legs. No unsteadiness.
• Endo: No excessive thirst, no tremor, no sweats, no weight loss
• Skin: no skin problems

Previous Medical History

• Right adrenal tumour – diagnosed 5 years ago. The patient had undergone unilateral adrenalectomy but she was uncertain of the final diagnosis.
• Hypertension
• Constipation
• Paroxysmal Atrial Fibrillation (PAF)
• Hyperuricaemia


Medications

• Disopyramide 40mg 4x/day
• Aspirin 81mg/day 1x/day
• Allopurinol 100mg/day 1x/day
• Voltarol 50mg 3x/day
• Ranitidine 150mg 2x/day
• Lactulose 10ml 2x/day
• Senna two tablets 1x/day

No Known Drug Allergies

Family & Social histories: these were uncertain on the admission day

On Examination

General: Patient was alert. GCS 15/15 and was oriented in time, place and person. Afebrile.

No JCCO; conjunctival pallor (+), rubbery, mobile, smooth lymph nodes (+) in the left and right axillae. Maximum diameter of the LNs approx. 15mm.

HEENT: No evidence of fracture or soft tissue injury. Tongue was atraumatic. Mouth did not demonstrate any blood. Ears - no blood or fluid. Nose - no blood or fluid.

CVS: Pulse 110 / min, regular. BP 86/70mmHg. JVP not elevated. No heaves or thrills. Apex in normal position. Heart sounds 1 + 2 normal. No S3 or S4. No murmurs. No leg edema or signs of calf swelling / pain / redness.

RESP: RR 16/min, SpO2 95% on room air. Trachea was central. Percussion note was resonant. Auscaltation revealed normal vesicular breath sounds.

ABDO: Soft, non-tender, no masses, no hepatosplenomegaly, no inguinal lymphadenopathy. No bladder distension, and no renal angle tenderness. Rectal exam – black stool.

Musculoskeletal: No focal abnormalities

CNS

II: grossly normal visual fields. Pupils equal and reactive to light and accommodation + consensual response. Proptosis of the left eye.

III/IV/VI: impaired abduction of the left eye with associated double vision when looking to the left lateral side. Other eye movements were all normal.

V: Normal motor and sensory components

VII / VIII /IX / X / XI / XII: all grossly normal.

PNS

Tone – normal throughout the upper and lower limbs

Power – Upper and lower limb power 5/5 throughout

Reflexes

RUL LUL RLL LLL
Supin +/- ++ +/- +/-
Biceps +/- ++ +/- +/-
Tricep +/- ++ +/- +/-
Knee +/- +/- +/- +/-
Ankle +/- +/- +/- +/-

Sensory: Gross sensation , nociception and joint position senses appeared intact.

Coordination: No cerebellar signs

Fundoscopy was not performed.

Endocrine: no tremor, no thyroid enlargement, no evidence of bitemporal hemianopia.

Skin: no focal abnormality

Question 1: From the history and examination, please make an appropriate problem list.

Question 2: Please provide a differential diagnosis (es).

Question 3: What would you immediately do for this patient?

Question 4: What tests would you perform and why?

Question 5: What other bedside physical examination test(s) could provide additional information to aid your diagnosis?

July's Case 2009- The Answers

Dear Bloggers

I hope that you found this case thought provoking.

Professor Masami Matsumura has kindly considered this month's case despite his busy schedule. I thank him for his time and input.

His answers to the blog case are as follows:

Thank you for showing difficult case again. I would try to solve.

The patient was a 64-year-old lady.

Problem list on admission

#1Benzodiazepine overdose

Diazepam 1,000mg and Lorazepam 200 mg

Altered mental status, GCS 3/15

Tone decreased throughout

Reflexes generally depressed

No response to pain

#2Aspiration pneumonia

Fever

Tachycardia

High RR [respiratory rate]

Hypoxia

#3History of anxiety and insomnia

Problem list on second episode

#1 Unresponsive

#2 Shock

#3 Hypoxia

#4 Acidemia, respiratory acidosis

#5 Tachycardia

#6 After flumazenil administration

Question 1: Why did the patient lapse into unconscious despite initial improvement on the evening of admission to the hospital?

Benzodiazepine overdose will last for several days and flumazenil is a short-acting drug. I think second episode was caused by benzodiazepine overdose again.

Question 2: Why did the patient deteriorate so quickly during resuscitation, with profound hypotension and sinus tachycardia >200/min and why did it resolve?

PSVT with high rate can cause hypotension. Additional flumazenil administration and intubation can alleviate patient condition better.

Question 3: What acid-base disturbance is demonstrated by the blood gas?

Hypoxia and respiratory acidosis with hypercapnea caused by benzodiazepine overdose.

Question 4: What additional therapies may have helped this patient when admitted to the hospital that could have been commenced in the ER department?

Activated carbon administration can absorb overdose of benzodiazepine in GI tract.

What had happened in this case? (Question 1-3 are covered in the following text)

Firstly, we must look at the drugs. This patient has both long and short acting benzodiazepines. Remember that benzodiazepines get metabolised into other active benzodiazepines that can have longer half-lives. Hence, these drugs can have sedative effects for a prolonged period of time. The effects are more marked in the elderly who have reduced ability to excrete these drugs. For example, diazepam has a half-life of 20-40 hours but its active metabolite is Nordazepam which has a half-life of 60 hours!! The overall duration of action is about 24-48 hours !

Nordazepam is converted to Oxazepam (the same compound produced from Temazepam) which is then combined with glucuronic acid and excreted renaly. On the other hand, Lorazepam is a shorter acting benzodiazepine although is half life is 8-12 hours. However, it has no active metabolite so its overall half is the same.

The action of Flumazenil is rapid and hence it is no surprise that the admitting resident considered the patient 'stable' after injecting the 'antidote'. However, Flumazenil only acts for a short period of time (maximum of 2 hours) and the actions of the long acting benzodiazepines can return. This is indeed what happened here.

The benzodiazepines caused unconsciousness and respiratory compromise despite the respiratory rate of 24 per minute. The patient had decreased air entry on examination and hypopnea despite tachypnoea. This resulted in CO2 retention and acute respiratory acidosis.

However, if one looks at the ABG result, the HCO3 level is minimally elevated and base excess is -5. These suggest an added metabolic acidosis. This is unsurprising in the presence of severe hypoxaemia. Her calculated bicarbonate should have been 36.2 if a pure respiratory acidosis were present.

The history, physical exam and vital signs suggested that she had SIRS (systemic inflammatory response syndrome) as part of a septic syndrome. The fact that her blood pressure dropped on minimal incline suggested hypovolaemia and / or septic shock.

The patient having vomited and aspirated was evidence enough of an unsafe airway and the patient should have been intubated on admission prior to administration of Flumazenil. Moreover, such patients need to have activated charcoal. Most texts suggest that the activated charcoal be given within 1 hour of an overdose. This is not entirely accurate because some drugs have a slower absorption e.g. Lorazepam, and the use of charcoal can have benefits even after 1 hour. Moreover, in view of the unconscious state, the charcoal could only have been administered with the patient being intubated to protect the airway.


Why did this patient drop her blood pressure and develop a rapid tachycardia?

The side effects of Flumazenil include hypotension and dysrrhythmia aside from the other serious side effect of seizures in patients taking benzodiazepines chronically. In essence, too much Flumazenil had been administered.

Typical guidance suggests starting with 0.2mg then waiting 30 seconds for a response. Following that give 0.3mg and wait another 30 seconds for a response. Following that, 0.5mg can be administered.

Patients may sometimes require Flumazenil every 20 minutes in view of the short half life of the drug especially when long acting benzodiazepines have been taken in overdose. However, this depends entirely on how the patient responds to treatment. Hence, in view of the short lived hypotension and tachycardia, it is likely that Flumazenil being given at too high a dose was to blame here.

Question 4: What additional therapies may have helped this patient when admitted to the hospital that could have been commenced in the ER department?

• Patients should receive activated charcoal even after 1 hour post-overdose and further doses can be administered several hours later if considered appropriate.
• If the patient has a GCS of less than 8/15, intubation should be initiated to protect the airway and also to allow for activated charcoal to be administered. Remember though, an ET tube is not completely 100% protective against aspiration. Also remember the saying -- 'if the GCS is less than 8 then intubate'
• Flumazenil should be used with extreme caution because of its adverse side effects and should be given in low dose and titrated up. Despite the ability to reverse the effects of the benzodiazepines, its actions are short lived and repeated doses may be necessary. Remember though, benzodiazepines do not usually cause significant respiratory depression making them relatively safe in overdose. Most patients just sleep off the effects of this class of drug. It is when respiratory depression occurs then the antidote should be considered and especially when taken in combination with other CNS depressants.
  
• Remember that Flumazenil is CONTRAINDICATED in mixed overdoses with Tricyclic Antidepressants as the effects of the latter drug can be increased.
• Patients with sepsis often require large amounts of fluid. It is appropriate to administer adequate amounts of fluid and for BP and Pulse to be checked regularly in addition to urine output to assess volume status. In reality, in patient with sepsis, it is better to place a central venous line to assess volume requirements rather than guessing. A CVP of 8-12 cmH20 would be considered an appropriate goal to achieve in sepsis.
  

Take Home Message

The moral of the story here is that we should not be complacent that this is just 'another overdose patient'. If we do not take precautions and manage such patients appropriately, then problems can and do occur to the detriment of the patient.

In cases of overdose, the patient should be managed as a minimum in a high-intensity emergency medicine admissions unit with experienced staff or on an HCU or ITU . Full monitoring equipment should be utilised. Patients should not been placed on a general ward in a side room.

Physicians need to take more care to find out the mental state of the patient before prescribing medications that can be used in overdose and they should not be given out like candy. A thorough drug history is required to be taken by the doctor and drug-drug interactions need to be considered before adding in another medication.

Drug-drug interactions can be easily checked with PDA software e.g. ePocrates

Many thanks to Prof Matsumura.

July's Case: A Patient with Benzodiazepine Overdose

Dear Bloggers

Here is an anonymised case of a female patient admitted to a hospital with an overdose of prescription tablets.

She was a 64 year old lady who had a history of anxiety and insomnia who was normally treated with benzodiazepine therapy on a long term basis. She had otherwise been well. Several days before admission, the patient had been informed of the sudden death of her mother, the news of which she took badly. She lived alone and her main contact was her brother who visited daily.

On the morning of admission, the patient was found by her brother lying on the floor in an unrousable state with vomit dripping from her mouth. Mixed with the vomit were semi-digested tablets. The brother noticed that several blister packs of tablets were empty despite the prescription for the tablets having been given just a few days before.

The brother phoned for the emergency services. On arrival, the emergency personnel checked the Airway, Breathing and Circulation and transferred the patient to the ER department for further assessment and treatment.

The patient had no other significant history.

There was no significant family history and the patient was a non-smoker and non-drinker.

Medications taken in overdose included:

• Diazepam 20mg x 50
• Lorazepam 5mg x 40

ER Vital Signs

GCS 3/15, T 38.6 deg C, Pulse 120 bpm regular, BP125/80mmHg, RR= 24/min, SpO2 92% on 5 L oxygen

Airway - Slight vomit but no obstruction. Cleared with suction.

Breathing - Chest movement equal and normal expansion. Air entry decreased and bilateral coarse crackles with bronchial breath sounds. Oxygen given via face mask.

Circulation - Pulses present, warm peripheries. No evidence of haemorrhage. IV lines inserted and fluid commenced.

Secondary Examination

HEENT - No focal abnormality

CVS - Peripheries warm, pulse 120/min regular and normal pulse volume. JVP not visible. Heart sounds I + II. No III or IV heart sounds. No murmurs. No leg swelling.

RESP - Trachea central and no deviation. No tracheal tug. Percussion anteriorly resonant. Posterior, dullness at both bases. Auscultation revealed coarse crackles and bronchial breath sounds.

ABDO - Soft and non-tender. No rebound or guarding. No masses or organomegaly. Bowel sounds present. Rectal examination revealed no blood and no masses.

CNS - Pupils small but equal and reactive to light. Corneal reflexes positive bilaterally. No facial palsy.

PNS - Tone decreased throughout. Unable to assess power. Reflexes generally depressed. Babinski's unresponsive. No response to pain.

Tests

• The patient underwent an emergency drug screen which revealed only benzodiazepines. No alcohol was present.
• CXR revealed infiltration of the lung in the right lower zone. There was a small pleural effusion present on the left lower zone.
• ECG showed a sinus tachycardia of 125 bpm and no acute changes.
• Other blood tests were otherwise unremarkable except for a neutrophilia.
• Gram stain of tracheal aspirates revealed mixed organisms.

The patient was considered to have a benzodiazepine overdose and aspiration pneumonia.

Treatment - The patient was given emergency treatment with Flumazenil which improved her conscious level whereby she was able to converse with the medical staff. She was commenced on Augmentin intravenously after blood cultures having been taken.

The patient was moved to a private room to await the morning round by the Attending Physician.

In the morning, despite the history of improvement noted by the resident the night before, on arriving in the patients room, she was unresponsive and oxygen saturation had dropped to 75% on oxygen 5L.

Resuscitation was commenced as follows:

• High flow oxygen 15L via reservoir mask
• Blood pressure - 90/60 at 30 degrees incline, 125/75 mmHg lying supine
• IV fluid - high flow, stat
• Flumazenil 0.5mg IV push
  
• ABG - pH 7.02, pCO2 145mmHg, pO2 60mmHg, HCO3 26.4, BE -5
  
• The patient was moved from a side room to the HCU within minutes
• Patient was intubated and commenced on a mechanical ventilation

However, the patient developed profound hypotension of 60/40mmHg and a sinus tachycardia of 200 bpm, the latter as confirmed by 12 Lead ECG prior to tracheal intubation, and both which were initially refractory to high volume fluid administration.

The ECG showed no acute ST changes or T wave abnormalities.

After several litres of fluid the blood pressure increased to 80/50mmHg. Her circulation required minimal support with dopamine to increase the systolic pressure to over 100mmHg. Her pulse dropped back to 125 bpm within 30 minutes of this profound deterioration. The patient was miraculously alert with spontaneous eye opening and nodding in response to verbal commands. The dopamine was later discontinued.

She went on to make an excellent recovery!

Question 1: Why did the patient lapse into unconscious despite initial improvement on the evening of admission to the hospital?

Question 2: Why did the patient deteriorate so quickly during resuscitation, with profound hypotension and sinus tachycardia >200/min and why did it resolve?

Question 3: What acid-base disturbance is demonstrated by the blood gas?

Question 4: What additional therapies may have helped this patient when admitted to the hospital that could have been commenced in the ER department?

Answer To June 2009 Case

Dear Bloggers

Welcome back. Today I will discuss the answer to the recent case. This was one of the most difficult cases I have ever experienced and I thought it would be nice to share this with you all. I was reminded by a colleague also involved with the case, that the rash was in fact painful rather than painless and hence, the initial description of her symptoms was inaccurate for which I apologise :-o

Professor Matsumura has kindly provided his opinion on the case (see below) in respect of the revised history of the patient. His ideas were very much in keeping with the team looking after the patient on initial presentation.

The patient was a 43-year-old woman. I would describe problem list first.

Problem list

#1 Skin rash

The lesions were circular, purplish, discrete, raised with an umbilicated central area. The lesions began as smaller discrete nodules that rapidly expanded. After several days, existing lesions developed a necrotic centre with circumferential erythema. The lesions eventually crusted over leaving large areas of eschar.

#2 Fever

#3 Tachycardia

#4 History of right breast cancer

#5 Acyclovir and ciprofloxacin administration

The main problem of this patient is fever and rash. Differential diagnosis is broad in fever and rash. However, I would think three main category, infection, neoplastic, and autoimmune. Characteristics of skin rash are likely infectious disease. Neoplastic or autoimmune is less likely. But neoplastic disease should be considered for background of this patient

Questions:

1) From the history and physical examination what would be your likely differential diagnosis?

Vascular: Less likely

Infection: Varicella, HIV, molluscum contagiosum, disseminated cryptococcosis, eosinophilic folliculitis, cutaneous anthrax

Neoplastic: (Recurrence of breast cancer)

Autoimmune: Sarcoidosis

Toxic: Less likely

Metabolic: Less likely

Trauma: Less likely

Degenerative: Less likely

Iatrogenic: Less likely

Idiopathic: Less likely

Congenital: Less likely

I would think varicella is the most likely based on the character of skin rash. The problem is this patient was a 43-year-old woman. Varicella is common in children. Moreover, this patient had history of breast cancer and acyclovir administration.

2) What are the two most important tests to confirm the diagnosis?

Tzanck smear for detecting multinucleated giant calls.

Direct immunofluorescent antibody (DFA) staining.

3) What is your chosen treatment?

Depend on following assessment, question 4.

4) What addition problem should you consider screening for in this patient?

Interstitial pneumonia as complication of adult varicella should be carefully monitored. Cancer screening including recurrence of breast cancer should be evaluated. Moreover, I would confirm pregnancy test.

The Answer

The team caring for this patient were very concerned about an infectious disease such as varicella and even cutaneous anthrax, despite no history of there being any exposure to the latter infectious disease. Therfore, she was nursed with full barrier protection as a precautionary measure.

Her laboratory studies were normal except for a neutrophilia. Varicella IgG was present and IgM was absent suggesting previous infection. Autoimmune serology including ANCA was negative.

Blood cultures were negative.

The patient had the lesions tested for varicella zoster with viral cultures, which were negative.

Chest radiograph was normal.

CRP was 13.6 and ESR was 17mm/hr.

She developed secondary staphylococcal infection as evidenced by impetigo and positive skin cultures. She was commenced on ceftriaxone.

She was reviewed by the hospital infectious disease specialist and dermatologist respectively, who both considered infectious, autoimmune and primary dermatologic disease.

The dermatologist also considered Acute Febrile Neutrophilic Dermatosis (Sweet's Syndrome) in view of the presentation, background history, fever and neutrophilia.

The patient therefore underwent a skin biopsy which confirmed the histopathology consistent with Sweet's Syndrome. She also met the proposed criteria for Sweet's Syndrome (see below).

She was commenced on corticosteroids orally (Prednisolone 60mg per day) with resolution of her symptoms and the lesions over several days. She was discharged home with outpatient follow up.

In view of her history of metastatic breast cancer, a search for secondary causes of Sweet's Syndrome such as a recurrent malignancy, would have been considered appropriate.

Sweet's Syndrome

Described by Robert Sweet 1964: A reactive process characterised by the abrupt onset of tender red-to-purple circinate plaques.

Usually occur on the

• extremities
• head
• neck

and typically are accompanied by fever and peripheral neutrophilia.

Pathophysiology

Neutrophil mediated hypersensitivity reaction to systemic factors, which may include, haematologic disease, infection, or drug exposure.

Evidence suggests that Sweet’s Syndrome is a cytokine T-cell-mediated disease with secondary and only temporary activation and participation of neutrophils.

Primarily skin affected but lung and kidney can be involved.

Frequency

Uncommon condition; several hundred reported cases in literature ~2.7 cases/million (Scotland) Kemmett et al 1990

~10-15% cases in setting of malignancy (which includes recurrent breast cancer) but most cases are idiopathic and benign.

Females predominantly affected (F:M 2-3:1) esp. non-malignancy associated Sweet syndrome.

Age at onset

• Females 30-50
• Males 60-90

Causes

• Idiopathic (~70% cases)
• Haematologic Malignancy: CML, AML, MDS. Hodgkin disease, cutaneous T-cell lymphoma, NHL, multiple myeloma, and hairy cell leukemia.
• Non-Haematological Malignancy: Slight increase in genitourinary cancers, rectal cancer, oral / tonsilar cancer, breast cancer and osteosarcoma.
• Infection: Streptococcal pneumonia, Yersinia infection. Atypical mycobacteria.

Drugs

G-CSF- well established cause

Possibly
Septrin
all-trans retinoic acid
minocycline

Anecdotal - Limited reports of drug associations include
lithium
furosemide
hydralazine
carbamazepine
levonorgestrel/ethinyl estradiol.

Systemic Disorders

15% cases of Sweet’s Syndrome

Most common association
Crohn’s Disease
Ulcerative Colitis

Sjogren’s, Behcet’s, RA, SLE , undifferentiated connective tissue disease all associated with Sweet’s.

Proposed diagnostic criteria include the following:

Both major criteria must be met in addition to two of the four minor criteria.

Major criteria

1 Acute onset of typical skin lesions
2 Histopathological findings consistent with Sweet’s syndrome

Minor criteria

1 Fever > 38°C or general malaise
2 Association with malignancy, inflammatory disorder or pregnancy or antecedent respiratory or gastrointestinal infection
3 Excellent response to systemic corticosteroids or potassium iodide (KI)
4 Abnormal laboratory values at presentation (three of four required: ESR > 20 mm; leukocytes > 8000; neutrophils > 70%; positive C-reactive protein)

(Rook's Textbook of Dermatology, Seventh Edition)

Treatment

Steroids!! Usually Prednisolone 1.0mg/kg/day -> Lesions should resolve <14>

Other treatment modalities

• Colchicine 1.5 mg/day
• Dapsone 100-200 mg/day
• Clofazimine 200 mg/day
• Cyclosporin A 5-10 mg/kg/ body weight/day
• Indomethacin 50-100 mg/day
• Naproxen 750 mg/day
• Doxycycline 200 mg/day

von den Driesch P. 1994

Prognosis

• Outcome depends on the underlying condition
• Recurrence may occur in up to 50% of patients
• Most likely in cases associated with haematological malignancy or drug reaction.

Take Home Message

When you see a patient with an unusual condition such as this, please involve the dermatologist as soon as possible for advice on the likely cause and for a skin biopsy to be taken.

Without a biopsy, despite the best problem list and differential diagnosis it can be difficult to establish the diagnosis even for the best of diagnosticians.

Certainly the history of the acute onset, location and progression of the disorder help to point to Sweet's syndrome as a possible diagnosis but a skin rash with fever has a wide differential. Hence, a biopsy is the very best way to establish the cause -- tissue is the issue!

Much of dermatology is pattern recongition and it can be difficult even for most senior doctors.

I would like to thank Prof Matsumura for his excellent attempt at diagnosis in this rare case. His suggestions were very good and would have led to the diagnosis through a skin biopsy as inferred from the two tests proposed. Moreover, checking for recurrent cancer and pregnancy showed good lateral thinking and were correct. Well done.

A Case For June 2009: Back with a difficult case!

Dear Bloggers

I am so sorry I have not been keeping up the blog. Life has been somewhat busy ! However, I have a great case for you. Have a go at trying to answer it. Answers in the near future.

A 43 year old Caucasian hospital secretary presented to a hospital with the following:

• Skin rash
• Fever

The lady was usually in good health when she developed an acute rash that commenced on her neck, and progressed to her face, trunk and upper + lower extremities over several days.

The rash was not painful or itchy. She described the rash a 'spotty', 'red' and 'knobbly'.

She went to see her local doctor who thought she might have an infection and prescribed her oral aciclovir and ciprofloxacin. However, rather than the rash regressing, it progressed rapidly at the dismay of the patient. Two days after receiving the antimicrobial therapy the patient developed a low grade fever of 37.6 degrees. The patient attended her local doctor again who referred her to the internal medicine team of the general hospital.

Her only previous history had been a mastectomy for carcinoma of the right breast in 1995 with dissection of 1 lymph node. She had been treated post-operatively with radiotherapy and chemotherapy (chemoradiation). She had been deemed disease free at her last outpatient follow-up.

She had one child aged 10 years old born via a normal vaginal delivery. Her periods were regular every 28 days with 5 days bleeding. Her last menstrual period had been one week before (which had been normal) and she denied pregnancy. She used barrier contraceptive with her husband. She and her husband were monogamous.

She had otherwise been well with no recent infection. She had not traveled recently, there were no pets at home and no recent contact with animals. She had no contact with patients in the hospital where she was employed. Other members of her family were unaffected. She had no unusual hobbies.

She denied taking any medications, herbal supplements or over-the-counter (OTC) drugs prior to the onset of her symptoms. Her daily food intake had not changed. She denied using any new jewellery or washing powders.

She had no relevant family history. She was a non-smoker and drank alcohol only occasionally.

On review of systems, she denied any cardiovascular, respiratory, abdominal, musculoskeletal, urogenital, CNS-PNS or endocrine symptoms. She particularly denied weight loss, appetite change or night sweats.


On Examination


VITAL SIGNS: BP 120/80mmHg, Pulse 108 / min & regular, Respiratory Rate 14/min, T 37.4 degrees C, SpO2 98% breathing ambient room air.

GENERAL: Looked well but slightly shaky. No JACCOL

HEENT - Nil focal except for rash (see below). No goitre.

CVS - Pulse volume and quality: normal, JVP not elevated, no carotid bruits, No heaves or thrills, S1 + S2 present, No S3 or S4, gallop or pericardial rub. Peripheral pulses present throughout. No evidence of DVT in the lower limbs.

RESP: No tracheal tug or deviation. Normal chest expansion. Percussion resonant. Normal vesicular breath sounds.

ABDOMINAL: Soft, non-tender, no masses or organomegaly. No hernial orifices and no groin lymphadenopathy. Rectal exam was not performed.

BREAST EXAM: Left breast normal - no masses, no skin abnormality, no abnormal nipple discharge and no axillary lymphadenopathy. Right mastectomy scar present. No evidence of recurrence. No axillary lymphadenopathy.

SKIN: The following pictures show the rash. The lesions were circular, purplish, discrete, raised with an umbilicated central area. The maximum diameter was about 1cm. The lesions began as smaller discrete nodules that rapidly expanded -- please see the yellowish smaller nodules in the lower part of the picture (below)


After several days, existing lesions developed a necrotic centre with circumferential erythema. The lesions eventually crusted over leaving large areas of eschar from involuting coalesced lesions over the shoulders and proximal lower limbs. Fresh lesions continued to develop.


Questions:

1) From the history and physical examination what would be your likely differential diagnosis?

2) What are the two most important tests to confirm the diagnosis?

3) What is your chosen treatment?

4) What addition problem should you consider screening for in this patient?