Day #343 - Interstitial Lung Disease

This is likely to be my final blog of the academic term. It has been a great 'year in medicine'. I hope those of you who read this have gotten something out of it. It will be likely be resumed by the incoming chief resident(s) @ Mount Sinai and/or TGH in July. I will be continuing to blog about other cases as I progress through my Infectious Diseases fellowship. For anyone who cares to read, you will find that blog starting here in July.

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Today we presented a challenging case -- where Occam's Razor again met head to head with Hickam's dictum.

The discussant began by talking about the various rheumatoid manifestations in the lung.

We then honed in on interstitial lung disease (previous blog on IPF here), and discussed the phenomenon of acute exacerbation of ILD (other review on non-IPF related AE-ILD here) -- a relatively new concept in respirology.

We also talked about the possibility -- and confirmation -- of pulmonary embolism. Noting of course that PE would not explain the diffuse ground glass opacities.

We discussed the possibility of a superimposed community acquired pneumonia, or TNF-alpha associated granulomatous infection and the need for treatment of same.

Day #341 - Likely TB Pleural Effusion

I missed it today -- but seems eeerily similar to this post....

Day #340 - Occular Myasthenia

Today we discussed a patient who presented with bilateral ptosis. EMG revealed evidence of myasthenia gravis and the patient responded to treatment with an acetylcholine esterase inhibitor.




The JAMA rational clinical exam series addresses the physical diagnosis of MG here.



History:

"speech becoming unintelligible during prolonged speaking" LR 4.5

presence of the peek sign increase the likelihood of myasthenia gravis LR 30 (eyes "peek" open within 30 seconds of closure)

Bedside Tests:

• Ice test LR + 24 LR - 0.16
  (apply ice to the eyelids x 2 mins then evaluate response which should be immediate and short-lived)


• Response to an anticholinesterase medication LR+ 15 LR - 0.11
  (give tensilon, look for response within 30 seconds lasting less than 5 mins)


• Sleep test LR+ 53.0; LR - 0.16
  (have patient lie in a dark room resting the eyes for 30 mins, look for improvement of ptosis)

A review of autoimmune NMJ diseases is available here.

A discussion of myasthenia mimics is available here.

Day #337 - Cirrhosis (PBC)

Today we heard a case of a patient with decompensated cirrhosis (new diagnosis). The precipitant was likely a general anesthetic on the background of unrecognized cirrhosis.

Given the markedly elevated ALP with no bony symptoms and normal ducts on the ultrasound, we proposed a diagnosis of Primary Biliary Cirrhosis (see review here).

See the associated review/editorial on cholestatic liver diseases from a prominant Toronto hepatologist here.

I have also provided a link to a review article on Hepatitis C and HIV co-infection, since it was discussed and is relevant. There is some evidence that HAART may actually worsen the liver disease in these patients and that perhaps the HCV needs to be treated.

Day #336 - Terminal Illeitis and Abscess

Today we heard a case of presumed Crohn's disease (new diagnosis) with intrabdominal abscess. A NEJM review is available here. American practice guidelines are available here.

The NEJM article on the radiation risk of CT scan is available here.

Day # 335 - Severe Influenza

Today we discussed a case that I have talked about before of severe influenza. This case highlights several key issues -- the most important is pointing out just how sick young patients can get with influenza.

We have previously talked about influenza here and pneumonia here.

Day #333 - Hyponatremia

I've previously blogged and referenced hyponatremia here

Day #330 - HSP

Today we heard about a patient with a diagnosis of Henock Schonlein Purpura (Henock left, Schonlein, right). A similar case is presented in the NEJM here.
They presented with a prodromal URTI (more common in patients younger than 30) and then:

• Lower extremity purpuric rash (picture here)
• Abdominal pain with or without gastrointestinal bleeding (GI manefestations reviewed here)
  
• Symetrical arthritis of the large joints in the lower limbs
• Macroscopic hematuria with the development of renal failure and nephrotic syndrome

While mainly a disease of children, approximately 10% of patients with HSP will be diagnosed as adults. In children severe renal disease is rare; however, in up to 30% of adults renal involvement can be severe and up to 10-15% of adults will develop severe renal disease. Treatment in these cases involve steroids with consideration of other immunosuppressants.

Poor prognostic signs include:

• Creatinine more than 120


• Proteinurea more than 1g/day


• Fibrosis or necrosis on kidney biopsy greater then 10%.

The major differential of purpuric skin rash and macroscopic hematuria includes drug-induced hypersensitivity vasculitis, which usually has a good prognosis and cryoglobulenemic vasculitis, which has a much worse prognosis.

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If you speak german, I think this is schonlein's book from 1832 where he first describes this condition.

I've been on a medical history theme this week -- here is an article from 1914 by Osler on HSP.

Day #329 - Fever of Unknown Origin

Today we discussed a patient with fever of unknown origin (previous blogs here including links to the articles I mentioned)

I erred when I said that abdominal imaging was required prior to making the diagnosis -- however, given the ease at which we can get said imaging I would say that it probably *should* be required before labeling as FUO. Certainly, it should be the first test performed in the "second tier"

On the basis of profound inflammatory markers and microscopic hematuria (in the absence of other causes) I postulated that this case may be a medium-small vessel vasculitis such as microscopic polyangiitis. A classic NEJM review on small vessel vasculitis is available here and the corresponding article on medium vessel vasculitis is available here.

This article reviews the guidelines for the management of medium and small vessel vasculitis.

Day #328 Cushing Syndrome

Today we had a patient present with weight gain, facial changes, abdominal obesity, psychosis and hypertension with hypokalemia.

The most common cause of Cushing Syndrome is Cushing's Disease (ACTH producing pituitary adenoma 68%). Ectopic ACTH production and adrenal ademomas are the second most common causes at approx 10% each.

The clinical symptoms and physical signs are wonderfully illustrated in the figure below (with thanks to the TWH CMR who drew it)

The diagnostic algorithm (review here) is as follows:

1. Confirm cortisol excess. 24h urine cortisol or the 1mg overnight dexamethasone supression test are the best in terms of sensitivity and specificity.


2. Is the ACTH high? If yes proceed to evaluate for adrenal adenoma or ectopic ACTH. Is ACTH low? Look at the adrenals.

ACTH High (see original publication by Hurst -- former faculty @ Toronto (memorial tribute here) from 1928 lancet)

From the diagnostic algorithm article: "A woman with mild to moderate hypercortisolism, a normal or slightly elevated plasma ACTH, and normokalemia has at least a 95% likelihood of having Cushing’s disease. In contrast, a patient with prodigious hypercortisolism, hypokalemia, and marked elevations of plasma ACTH may be more likely to have an occult ectopic ACTH-secreting tumor. "

Pituitary MRI is the next step:

Adenoma -- likely not ectopic ACTH (above) = resect

No adenoma, or likely ectopic ACTH = more evaluation

The 8mg dexamethasone suppression test is not sensitive or specific.

Petrosal sinus sampling with CRH stimulation is the best diagnostic test, but is invasive.

If ectopic ACTH confirmed:

bronchial, thymic carcinoids or other neuroendocrine tumors (e.g. islet cell, medullary carcinoma of the thyroid, or pheochromocytoma)

CT thorax and abdomen may find the tumor. If negative consider octreotide scan. Sometimes you won't find it.

Day #327 Anuric Renal Failure

Today we heard a case of a patient post ETOH binging who presented with acute anuric renal failure. We briefly discussed hepatorenal syndrome and then abandoned this diagnosis.

We discussed an approach to renal failure.

We then discussed the possibility of interstitial nephritis, and the role (or lack therof) of testing for urine eosinophils which I have blogged about here.

Some speculations included undiagnosed/untreated pancreatitis or rhabdomyolysis leading to pre-renal azotemia and subsequent acute tubular necrosis (review here).

A nature review of the value of the competant microscopy urinalysis is available here.

Ultimately this patient will have a renal biopsy to make a more definitive diagnosis.

Day #326 Renal Failure and Hemolysis

Today we presented a case of a patient with hepatitis C presenting with a presumed non-antibody mediated hemolytic anemia with renal failure and hematuria.

We have discussed the vascular and renal complications of Hepatitis C, including cryoglobulinemia and membranoproliferative glomerulonephritis previously. Another good review of crytoglobulinemia and hepatitis C is available here.

Note that hemolysis is not a common feature of this syndrome. It is possible that the anemia is related to GI bleeding, particularly small bleeding caused by mesenteric ischemia from vasculitis. Perhaps this isn't hemolysis, particulary because the bilirubin is not elevated (see approach to hemolysis) even though the haptoglobin is low and the LDH is mildly elevated.

This article reviews 'cold hemolytic anemia' or hemolytic anemia related to IgM mediated antibodies and can be seen occasionaly in cryoglobulinemia.

Day #323 - Autoimmune Hepatitis

See approach to massive transaminitis here.

There is a nice NEJM review on autoimmune hepatitis here. The table below is linked from there.

Labs:

• In general, ANA is positive more than 1:80, anti-smooth muscle antibody 1:80, there is an elevated IgG, pANCA may be positive

Treatment:

• Prednisone 20-60mg per day with AZATHIOPRINE 50-100mg per day
• Maintentance with AZATHIOPRINE (or other)
• Goal is normalization of liver enzymes and IgG.

Day #322 - Enterococcal Endocarditis

This patient presented with stroke. This article reviews stroke in IE. This related article reviews the neurologic manifestations of IE.




An original article by Osler on IE!



Some key points:
Mitral Valve IE ~ 10% stroke rate
Mortality is high -- 35% in hospital 52% at one year
Early antibiotic therapy reduces neurologic complications


I have previously blogged about infective endocarditis (see here) including enterococcal endocarditis. The first post goes over the Duke Criteria.



Indications for Surgical Treatment of IE (Native Valve):

• Development of heart failure
• MR/AR with dilating LV, or development of pulmonary hypertension
• Fungal IE or that caused by highly resistant organisms (think of it in MRSA)
• Patients with heart block, cardiac abscess, abnormal chamber-chamber connections
• Recurrant emboli despite ABX
• Class IIb -- large vegetations

Day #321 - Polyarticular Gout

Today we discussed a patient with polyarticular gout presenting with fever and multiple swollen joints.

Precipitants:

Drugs: HCTZ, other diuretics, ASA, pyrazinamine, allopurinol, cyclosporin, other
Foods: Alcohol (red wine), Red Meat, Cheeses
Diseases: Myeloproliferative disorders, hematologic malignancies, renal failure

Diagnosis (how to do an arthrocentesis):

Synovial fluid cell count usually in the 10,000-20,000 range but can be as high as 100,000.

Crystals should be seen -- negatively birefringent needle shaped crystals which are intracellular

Acute Treatment (usually one of):


NSAIDS: I.e. Naproxen 500mg PO BID
Steroids: Intrarticular (i.e. depomedrol 20-40mg) or systemic prednisone (i.e. 40mg x 3 days then taper by 10mg every three days)
Colchicine: colchicine 0.6mg po q1h x3 (diarrhea, nausea) then 0.6 OD-BID (renal dosed)

Long term Treatment:
Weight loss, avoidance of foods and drugs that precipitate

Initiate low dose colchicine if you are going to start anti-hyperuric medications to avoid precipitating an attack

Generally initiate therapy if one/more of: (i) urate nephropathy or recurrent stones (ii) destructive tophi (iii) greater than three attacks per year (iv) greater than 1100mg urinary urate per day

Some advocate for use of 24h urine urate -- if >800 then uricosuric therapy is contra-indicated. Titrate to uric acid less than 360umol/L

Uricosuric therapy:

Probenecid start 250mg BID titrate to 500-1000 BID

Consider vitamin C 500mg PO OD

Consider losartan as an antihypertensive if needed (has uricosuric effect)

Consider fenofibrate

Xanthine Oxidase Inhibition:

Allopurinol 100mg PO OD titrate to effect (usual dose ~ 300mg/day)

I have previously blogged about the approach to the mono/oligo arthritis (and septic arthritis) here.

Day #320 - Hypercalcemia from Presumed Sarcoid

A great case today -- and some good topics were covered by the discussant.

1) Hypercalcemia (previously blogged here)

2) Hepatitis C and its complications including:
* Mixed cryoglobulinemia (image) which can cause a vasculitis
* Membranoproliferative glomerulonephritis (review here)
* Porphyria Cutanea Tarda
* HCV Associated Lymphoma

3) Sarcoidosis (from review)

"sarcoidosis is established on the basis of compatible clinical and radiologic findings, supported by histologic evidence [review] in one or more organs of noncaseating epithelioid-cell granulomas in the absence of organisms or particles"
"as a diagnostic tool, measurement of serum ACE levels lacks sensitivity and specificity"

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Fascinating --> Evidence exists that sarcoidosis can be caused/exacerbated by HCV treatment with interferon.

Day #319 - Temporal Arteritis

From the JAMA series:

History:

• Jaw Claudication LR + 4.2 LR - 0.72
• Diplopia LR + 3.9 LR - 1

Other historical features not helpful to rule in or out. Most sensitive sign is headache (~70%) other signs and symptoms have sensitivity less that 50%

Physical:

• Beaded temporal artery LR + 4.6 LR - 0.9
• Prominant Temporal Artery LR + 4.3 LR - 0.7
• Tender Temporal Artery LR+ 2.6 LR - 0.8

Other physical exam findings are not helpful to rule in or rule out. Most sensitive is combination of ANY temporal artery abnormality (~75%)

Laboratory:

• Normal ESR LR - 0.2 (96% sensitive)

An review on the diagnosis and treatment of GCA/TA is available here. We discussed the relative merits of TA biopsy when the diagnosis is highly likely. The authors suggest that it is important to confirm the diagnosis because if negative, while it could still be TA, this should prompt a re-evaluation of the diagnosis as up to 50% will have an alternative diagnosis.

We then discussed the relative merits of TMP/SMX prophylaxis for PCP in patients on high dose steroids (Table below) from this meta-analysis. In general, though there is no consensus, PCP prophylaxis should be considered in patients on greater than 30mg of prednisone for greater than three months or those who are on moderate-high dose steroids with another immunosuppressive agent (i.e. patients with Wegner's)

Day #316 - Swine Flu

Today we heard a case of a patient with undelying Wegner's Granulomatosis who presented with several days of fever and cough. Her chest xray showed no infiltrate. The majority of patients with influenza will present with cough (90%) and fever (~70%). Headache, myalgias, arthralgias, fatigue are also common but seen in only 50-60%. There is a rational clinical exam on influenza here.

The nasopharyngeal swab revealed influenza, which was PCR confirmed to be "swine flu"

Influenza evolves by two processes. Antigenic drift, where small mutations occur over time in the surface molecules which gradualy cause waning immunity. This is the basis of seasonal influenza.

Antigenic shift invoves abrupt changes in the surface molecules, often as a conseuqnce of recombination with swine or avian lineages, into a strain to which few in the population are likely to have immunity. This leads to epidemic (and pandemic) influenza.

Treatment of Influenza:

• Supportive care
• In patients admitted to hospital/ICU or those with severe disease or severe undelying co-morbidities should receive antiviral therapy (also give to healthy people with less than 72h of symptoms)
• Oseltamavir (neuraminadase inhibitor -- blocks entry of virus into cell) --> available orally, circulating H1N1 are resistant, circulating H3N2 are likely resistant.
• Zanamavir (neuraminadase inhibitor) --> inhalational only, all are currently succeptible
• Amandadine (M channel inhibitor) --> blocks release of viral RNA into the cytoplasm from the lysosome. Available orally, most H3N2 resistant, many H1N1 succeptible.

I have previously blogged about influenza here, here, and here.

Day #315 - Sepsis with DIC

Today we discussed a great case of SEPSIS (focus of infection unclear) with associated DIC.

SIRS Criteria:
Fever or hypothermia
WBC >12,000 or less than 4,000
HR >90
RR >20


Sepsis = 2 or more SIRS criteria of presumed infective etiology
Severe sepsis includes sepsis with end organ dysfunction or lactate >4

Septic shock includes severe sepsis with refractory hypotension requiring inopressors
I have blogged about Early Goal Directed therapy here. Source control is as essential as broad spectrum antibiotics in the treatment of sepsis.

These are recent guidelines on the diagnosis and management of DIC here. Transfusion of plateletes and factors is limited to patients who are bleeding or at high risk of bleeding (i.e. post-op), therapeutic heparins are limited to patients who have thrombosis, DVT prophylaxis is required.

Day #314 - Pulmonary Eosinophilia

Very complex case facilitated by an expert discussant. The key focus, other than on the case at hand was a demonstration of clinical reasoning and Bayes theorem.

We highlighted the importance of Occam's Razor -- but stressed the importance of recognizing Hickam's dictum.

I have previously blogged about pulmonary eosinophilia here (with references). In my mind, an important consideration in this patient (given travel to China) is to exclude disseminated strongyloidiasis because like infliximab related interstitial lung disease (NEJM article here) 'strongy' can appear to improve on steroids.

This is a recent review from the Lancet on TNF-alpha blockade and the interaction with tuberculosis.

NB: Review of radiographic manifestations of pulmonary TB.

Day #313 - Pancytopenia

Today we heard a case of a patient presenting with symptomatic anemia and thrombocytopenia (with co-incidental leukopenia).

I have blogged about my approach to isolated anemia and thrombocytopenia. The combination of the two suggests a number of processes:

Decreased Production:

• Bone Marrow Problem: Leukemia, Lymphoma, Myeloma, Myelodysplastic Syndromes, Myelofibrosis, Myelopthysis, Aplastic Anemia


• Substrate Deficiency: B12/Folate, copper
• Toxin: ETOH, Methotrexate, Chemotherapy, Phenytoin, Heavy Metal Poisoning, etc.
• Infection: Miliary TB, disseminated fungal infection, HIV, Parvovirus B19 (usually just anemia!)

Increased Destruction:

• Microangiopathic haemolytic anemia
• Hypersplenism
• Evan's Syndrome (AIHA and ITP) or associated with collagen vascular disease

The key in distinguishing is looking at the reticulocyte count and then, if low or abnormally normal, performing a bone marrow biopsy. In this case there was a "dry tap" -- which can occasionally be due to inadequate technique -- but often is a sign of a "packed marrow" with leukemic/lyphoma, metastatic cancer, or granulomas (TB).

Day #309 - Unexplained Anemia

Today we heard a case of a patient with alcoholic cirrhosis who developed a significant anemia in hospital without overt blood loss. In this case, it turned out to be a large buttock/thigh hematoma which was not detected because the patient was quadraplegic. It mimicked haemolytic anemia because of the massive resorption.

I have previously blogged about anemia here (including hemolytic anemias here, and here)

The consultant mentioned Zieve's syndrome, the constellation of haemolytic anemia, jaundice, hepatitis and lipemia developing after cessation of alcohol consumption -- which Zieve talks about here.

Day #308 - Pontine Infarct

Today we heard the case of a patient who presented with diplopia, ataxia and vertigo in association with severe hypertension. The CT Scan was normal.

We discussed the differential diagnosis including hypertensive encephalopathy, PRES (posterior reversible encephalopathy syndrome, first described in NEJM here with two good reviews here and here), and a pontine infarction.

We highlighted the difference in management depending on the etiology and decided (as the presenting team did) that an urgent MRI was required.

We went on to discuss acute ischemic stroke:

• antiplatelet therapy in stroke
• the role of ACEi/thiazide combination in stroke
• the role of statins in stroke

Day #307 - Decompensated Cirrhosis

Today we discussed a case of a patient with jaundice from decompensated cirrhosis with encephalopathy, hepatorenal syndrome, and likely spontaneous bacterial peritonitis, who had a decreased level of consciousness.

The presumed etiology was ETOH cirrhosis with possible co-morbid hemochromotosis (NEJM review and recent study). Hemochromotosis is suggested when the transferrin saturation is above 45% (NB: in liver failure the transferrin levels may be low, artificially increasing the iron saturation) and/or the ferritin is above 200 in women and 300 in men.

There is a complex interplay between ETOH and iron overload with the two compounding to cause liver dysfunction as suggested in this article.

We also briefly noted the association between increased IgA and alcoholic liver disease.

He also had a traumatic subdural hematoma which needed to be urgently decompressed.

Day #306 - TB Pleuritis

We discussed a great case of tuberculosis causing pleural effusion today. I have previously blogged about this before.

Previous blogs on pleural effusion here and here (including discussion of Light's Criteria and parapneumonic effusions/empyema).

Modified Light's Criteria (see review here):

• Change LDH pleural fluid 0.45 ULN (increases sensitivity but reduces specificity)

Alternative tests:

• LDH (0.45ULN), cholesterol (45mg/dl) and protein (29g/L) of pleural fluid, done in combination have similar performance characteristics to Light's criteria and don't require paired serum samples.

Day #305 - HIV Lymphoma

Today we discussed a case of a patient with known HIV disease (CD4 300-500, not on therapy) who presented with fever, diffuse adenopathy, and splenomegaly. The presumed cause is lymphoma.









The differential diagnosis would include:

Infections:

• • HIV with high level viremia
  • Mononucleosis syndromes (EBV, CMV, acute toxoplasmosis)
  • Syphilis
  • Disseminated TB
  • In the more immunosuppressed host:
    
    • Mycobacterium Avium Complex
    • Bartonella Henselae
    • Disseminated fungal infection (i.e. histoplasmosis)
• Non-infectious
  
  • Lymphoma
    
  • Multicentric Castleman's Disease
  • Sarcoidosis
    

I have previously blogged about HIV here, here (with cryptococcal meningitis), and here (with PCP pneumonia).

I have blogged about lymphoma including staging here.

A review of the pathology of HIV associate lymphomas is here. An article reviewing the treatment of HIV associated lymphoma is here.

Scenario Rounds - Wolff Parkinson White Syndrome

What to do with symptomatic patients? (ACC Guidelines on ablation, ACC Guidelines on the management of supraventricular tachycardia)

AVRT is the most common arrythmia seen in WPW.

• If you've had sudden death -- you need an ablation.
• If your refractory period is short (less than 240ms) you should consider an ablation to prevent sudden death.
• Risk of cardiac death is about 0.25% per year or 3-4% over lifetime, with the majority of the risk in patients with refractory periods of the accessory pathway that are less than 220ms.

• Success of ablatation approaches 95% with ~ 5% recurrance rate.
  
  • Risk of major complications is ~ 2% including:
    
    • complete heart block 0.2-1%
    • tamponade 0.3-1%
    • stroke 0.2-0.5%
      
    • death 1-2 per 1000.

What to do with asymptomatic patients with WPW on ECG?

Low risk for sudden death is seen in patients who lose the conduction via the accessory pathway during exercise (or stress), patients with intermittant pre-excitation (comes and goes), and patients who stop conducting down the accessory pathway when given a dose of procainamide. Low risk patients should receive a copy of their ECG with diagnosis and should be managed expectantly.

Patients without low risk features should be considered for EP study, and if high risk features on EP study are found should be considered for ablation, depending on age, gender, occupation, athletic lifestyle.

NB: One of the earlier publications, by Wolff, is available here.

Day #301 - Pheochromocytoma

Today we discussed the case of a patient with the classic presentation of paroxysms of hypertension, headache (80%), palpitations (60%), and diophoresis (70%).

This is a rare diagnosis occuring in approximately 1-2 per 100,000. Approximately 10% will be extra-adrenal. About 10% of sporatic pheo will be malignant. Approximately 10% will have metastasis.

25% of patients may have a genetic predisposition to pheochromocytoma. Syndromes which include a propensity to pheochromocytoma include neurofibromatosis type 1, von hippel lindau, Multiple endocrine neoplasia types 1 and 2

A review of the condition and the diagnostic algorithm is available here.

Initially control of the BP should be achieved with alpha blockade, with agents like phenoxybenzamine (10 mg PO BID titrated every 2-3 days by 10-20mg until achieving effect), prazosin or terazosin. For long term use, prazosin or terazosin are theoretically preferred to phenoxybenzamine b/c of shorter half lives and fewer side-effects. They should be started 7-10 days pre-resection.

Beta-blockers are then added to control tachycardia and arrythmias -- but only after alpha blockade has been achieved.

Calcium channel blockers may safely be used as an adjunct for hypertension.

The goal SBP is 120 lying or sitting.

Pre-op patients should receive intravenous crystalloid to achieve a good ECF volume. This will help avoid post operative hypotension. The preferred operative route is to perform a laparascopic resection of the adrenal mass.

Catecholamine levels should return to normal by 10 days post op. Failure to decrease suggests a residual PHEO.

Post resection patients should be followed periodically for recurrence.

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FYI - Management of hypertensive emergency

Day #299 - Enterococcal Prosthetic Valve Endocarditis

Great case. I have previously blogged about the diagnosis of endocarditis here and here.

Patient with multiple prosthetic valves develops sepsis in the context of an enterococcal bacteremia. Highly suspicious though non diagnostic echo for PVIE. Treated with VANCOMYCIN ("penicillin allergy" is a pet peeve of mine) and GENTAMICIN (for synergy). The evidence for synergy is not totally supported by clinical experience. Nephrotoxiciy is common but similarly has not been shown to impact mortality. The combination of VANCOMYCIN with an aminoglycoide increases the risk of nephrotoxicity.

We also reviewed aminoglycoside ototoxicity -- presenting either as sensory-neuro hearing loss or vestibulary dysfunction.

This patient developed renal failure presumably related to ATN from the VANCO+GENT; however, one can get a glomerulonephritis in endocarditis.

There is evidence that AMPICILLIN plus CEFTRIAXONE (which usually has no enterococcal coverage) can be used effectively in the treatment of enterococcal endocarditis.

Day #295 - Tuberculosis and Immune Reconstitiution

We discussed a case of pulmonary and extrapulmonary tuberculosis which presented on TNF-alpha antagonist therapy.

Addendum: TB Immune Reconstitution Reviewed Recently here.

We also discussed paradoxical worsening of TB post-discontinuation of immunosuppression. The case report I was talking about is available here.

Day #293 - Advanced ETOH Cirrhosis

Today we discussed

1. ETOH dependency and withdrawl
2. Alcohol and tylenol co-ingestion
3. Cirrhosis, and the management of cirrhotic complication

Day #292 - Meningoencephalitis

Today we discussed a few issues:

1. The developing influenza outbreak (see previous blogs on influenza). A review of the neurologic manifestations of influenza infection is available here.
   
2. A case of meningoencephalitis (see TWH blog), presumably due to mumps (though I have my reservations as the parotid enlargement classically predates the encephalitis and the IgM is still pending!)
3. TB Meningitis was discussed given the epidemiology.
   

Day #289 - Hypernatremia

Today we talked about a patient with decreased level of consciousness from hypernatremia.

This a great review of the topic.

The key in management is to provide free water at a rate that allows the serum sodium to decrease 10mmol/L/24h. This is usually accomplished after treating any severe ECF volume contraction with normal saline.

Day #288 - Fulminant Hepatitis from Hepatitis B

Today we discussed a case of a patient with chronic hepatitis B who presented with massive elevations of his liver enzymes. The cause was felt to be a flare of his underlying hepatitis B.

Day #287 - Massive Splenomegaly

Today we heard about a patient with massive splenomegaly who presented with symptoms anorexia and weight loss.

We discussed the physical diagnosis of splenomegaly. We also talked about differentiating the spleen from an enlarged kidney or stomach based.

Spleen

• Has notch
• Cannot palpate above
• Descends with inspiration
• Cannot ballot
• Splenic rub

Kidney

• No notch
• Can ballot
• May be able to palpate above
• No change with inspiration

Stomach

• No notch
• Cannot ballot
• Can not palpate above
  
• Succession splash
  

We then discussed the differential diagnosis for massive splenomegaly (8cm below costal margin or greater than 1kg) which includes:

• CML, CLL, Hairy Cell Leukemia, and other lymphomas
• Myelofibrosis (less commonly PRV)
• Gaucher's disease (or rarely sarcoidosis)
• Autoimmune Haemolytic Anemia
• Kala-Azar

Remember, the spleen can be enlarged by three mechanisms:

1. Hypertrophy or hyperplasia related to increased splenic function (i.e. thalasemia, infection, autoimmune disease)
2. Congestion due to portal hypertension
3. Infiltration (i.e. lymphomas, leukemias, extramedulary haematopoesis, amyloid)

We finally ended up talking about making the diagnosis in this case, which is likely lymphoma.

Day #280 - Anion Gap Metabolic Acidosis in an Alcoholic

Today was great!

We talked about the approach to acute confusion.

Then we talked about alcohol withdrawl and the treatment thereof. An approach that seems "easy" to remember is to use CIWA-A hourly giving 15mg for CIWA-A 8 to 15 and 30mg for scores above 15. Diazepam or lorazepam can be substituted. Disorientation and hallucinosis can be treated with small doses of haloperidol (i.e. 2.5-5mg)

Then we talked about the differential diagnosis of anion gap metabolic acidosis and the fact that the osmolar gap can sometimes be normal in toxic alcohol poisoning.

Then we talked about the management of HONK/DKA.

Day #279 - Cirrhosis and Possible Myxedema Coma

The patient (not the man in the picture!!) today had alcohol induced cirrhosis -- cirrhosis, its complications, and treatment thereof previously blogged (here, here, and here) with hepatic encephalopathy, massive ascites, and jaundice and possible hepatorenal syndrome.

We also later learned that the patient initially underreported their alcohol consumption. I couldn't find any literature on this in patients with cirrhosis; however, in my experience this is common.

The red-herring in this case was the anorexia and hoarse voice with cough which was supicious for malignancy -- however, we later found out that the patient was also severly hypothyroid which may have explained the hoarse voice -- and the anorexia could be explained by the severe liver disease.

The mental status may have also been depressed due to superimposed myxedema coma and it was important to recognize this.

Day #278 - Cavitary Lung Lesion

Today we heard the case of a young man with a history of constitutional symptoms (sweats, weight loss) in association with a non-productive cough and a cavitary right upper lobe infiltrate.

I have previously blogged about the differential of cavitary lung lesions

Based on the presentation I favor an infectious etiology, most likely tuberculosis. The absence of AFB on the bronchoscopy does *not* mean this isn't tuberculosis.

This study of 230 cases of culture positive pulmonary tuberculosis showed that the BAL AFB stain was only positive in 48/95 patients without spontaneous sputum production. In this study, the sensitivity of BAL AFB stain was better, but still only 70%.

The take home message is that a negative smear does not exclude TB in a compatible case. Repeat samples are sometimes indicated and awaiting the final culture is also required. In this case I would add induced sputum daily in the AM for three days to maximize my chances of making the diagnosis.

This article reviews the various radiographic manifestations of pulmonary tuberculosis.

Treatment of Pulmonary TB (see Canadian Tuberculosis Standards):
Initial:

• Isoniazid (INH) +/- Vitamin B6
  
• Rifampin (RIF)
  
• Pyrazinamide (PZA)
  
• Ethambutol (ETH)
  

If demonstrated susceptible to INH/RIF/PZA:

• Can stop ETH immediately
  
• Continue INH/RIF/PZA until 2 months then stop PZA
• Continue INF/RIF 4 months to complete 6 total months
  

Day #273 - Autoimmune Haemolytic Anemia (AIHA)

Great case of haemolytic anemia presenting as shortness of breath. I have previously blogged about AIHA and linked to good articles here. The approach to anemia is discussed in this blog, and the approach to microangiopathic haemolytic anemia (and TTP).

We also discussed the approach to dyspnea as a presenting illness which is easily remembered by the pneumonic FIT-RCMP


Fitness (i.e. out of shape)
R - Respiratory causes
C - Cardiac Causes
M - Metabolic (anemia and hyperthyroidism)
P - Psychological

... And I stand corrected -- a pulsus pardoxus of 10mmHg is felt to be signficant. Less than 10mmhg is highly sensitive for ruling out (LR -ve of 0.03) , more than 12 is more specific for ruling in (LR +ve 5.9)

Scenario Rounds - Severe Asthma and Severe Hypothermia

A good review of severe asthma is available here. The ACLS guidelines are available here.

The ACLS guidelines for the hypothermic patient.

Day #267 - Seizure

Today we heard a very complicated case of a man with an extensive cardiac and vascular history who presented with decreased level of consciouness and paresis which was felt to be due to a seizure (Todd's paresis)

The underlying cause for the seizure was presumed to be multiple old and subacute infarcts, the etiology of which was unclear -- but suspicious for embolism given his recent large territory myocardial infarction.

There is a good NEJM review of the initial treatment of epilepsy here. Another good review on the use of anti-seizure medication in adults and the elderly is available here. Choice of therapy depends on a number of issues:

1. Efficacy of medication for clinical scenario (i.e. partial complex vs. generalized)
2. Side effect profile and patient history
3. Drug-Drug Interactions
4. Cost or availability
5. Familiarity of prescriber

Most patients I see have been started on phenytoin, which is an old drug with poor pharmacokinetics and many drug-drug interactions. This drug is chosen because of low cost, familiarity, availability of IV formula. It can be effective. The article cited above would suggest that we have alternative options.

Though not discussed today, I have previously blogged about status epilepticus here.

One astute participant mentioned driving. The CMA has guidelines on medical fitness to drive which you can access for free here. The medical condition report form is available here.

Day #266 - Febrile Neutropenia

Today we discussed a case of a patient with multiple immunological deficiencies (a review of primary immunodeficiencies is available here)

Multiple myeloma with dysgammaglobulinemia predisposing to infections with encapsulated organisms like streptococcus pneumoniae and other bacterial infections like staphylococci.

High dose prednisone leading to relative deficiencies with cell mediated immunity predisposing to intracellular organisms (i.e. salmonella, listeria), mycobacterial, and fungal infections.

TNF alpha antagonist leading to further risk of fungal and mycobacterial infections

And drug induced febrile neutropenia predisposing to infection with bacteria including pseudomonas as well as fungi such as candida species, aspergillus, and other moulds.

The 2002 (under revision) IDSA guidelines for the management of febrile neutropenia are available here.

When initially seeing the febrile neutropenic patient, the goals (in general) are to:

1. Stablize and rescucitate as appropriate
2. Identify any specific focus of infection on history and physical exam
   
   • Pay attention in particular to sinuses and dental sources, mucositis, new murmurs, skin foci including central line sites and tunnels, evidence of pneumonia, evidence of intrabdominal focus, peri-rectal exam (no DRE)
   • CXR for all cases. Sinus, CT thorax, abdominal, other imaging as clinically indicated.
     
3. Obtain cultures from all sites including two sets of blood cultures and cultures from any indwelling intravenous lines.
   
4. Initiate broad spectrum antibiotic therapy to cover for usual pathogens implicated in febrile neutropenia adjusting/broadening to include identifiable focus
   
   • In general an antipseudomonal beta-lactam combined with an aminoglycoside is a standard regimen with the addition of VANCOMYCIN in patients with indwelling intravenous catheters, risk for MRSA, or who come in pre-treated with quinolone prophylaxis
5. Tailor antibiotics to culture results but remain broad-spectrum while neutropenic
   
   • i.e. if no gram positive identified can consider stopping VANCOMYCIN at 72h
     
   • if no pseudomonas or gram negative identified at 72h can consider stopping aminoglycoside and continuing the beta-lactam
     

Day #265 Hypertensive Emergency

Today we discussed a case of a patient from a marginalized social status with severe hypertension, decreased level of consciousness and seizure.

The issue of possible cocaine intoxication came up. A review of the cardiovascular consequences of cocaine use is presented here.

The management of hypertensive emergencies also was discussed. In general, with the exception of aortic dissection, the goal is to lower the blood pressure by ~25% of the mean arterial pressure in minutes to hours, and then achieve control of the blood pressure over the next days.

Options include intravenous labetolol (caution in catecholamine excess states like cocaine and pheochromocytoma) and nitrates like nitroglycerin (NB tachyphalaxis, not 1st line in aortic dissection) or nitroprusside (NB cyanide accumulation if renal failure or greater than 24h use, not 1st in aortic dissection).

Day #264 Sickle Cell Anemia

Today we discussed a patient with sickle cell anemia (previous blogs) who presented with acute onset chest pain, bilateral chest xray infiltrates and profound hypoxemia.

This patient had a compound heterozygote of sickle and beta-thalassemia. A review of the various compound heterozygotes is available here.

This patient may have had chest crisis. We did not see the initial xray. The definition of acute chest crisis/syndrome:

• New Chest Xray Infiltrate with chest pain
  AND


• One of: cough, fever, hypoxemia, tachypnea, sputum

A review of the ACS is available here. A more detailed review of the pulmonary complications in sickle cell anemia is available here.

We discussed red cell exchange (review here) which should be considered in ACS.

---

The patient also complained of crushing retrosternal chest pain with a new left bundle branch block on the ECG. This turned out *not* to be myocardial ischemia; although this was diagnosed retrospectively. Interpreting STEMI in the context of LBBB is difficult. This article discusses the relationship of bundle branch block to MI and suggests means of diagnosis that are relatively specific but not sensitive.

A further meta-analysis is available here.

Clearly we need to do better at picking up ischemia in the context of LBBB. I suggested that a STAT echo may have been helpful in this case in picking up LV dysfunction which would be expected with an ischemic LBBB. This is in keeping with the recomendations of the American college of cardiology.

Day #263 - Hemoptysis

Today we discussed a patient with previously resected lung cancer who presents with new onset worsening of hemoptysis. We've previously discussed haemoptysis here .

This case subsequently turned out to be a pulmonary hemmorhage syndrome (Churg Strauss) with glomerulonephritis. There is a good case report in the NEJM here. There is another case in NEJM here as well.

The original case description is available here.

A review on pulmonary vasculitis here.

Day #259 - Hepatic Encephalopathy

Today we heard about a case of a man who presented with acute hepatic encephalopathy of multiple possible etiologies including substance withdrawal and probable GI bleeding.

We reviewed the complications of nasogastric tube insertion.

I have blogged extensively on cirrhosis and its complications (and treatment thereof) previously (here, here, here, and here)

Previous blogs on upper GI bleed here and here.

Day #258 - Meningovascular Syphilis

Today we heard a case of a young man with headache and diplopia who rapidly went on to develop ischemic brain lesions and progressive deficits.

I have blogged about diplopia here.

The final diagnosis was meningovascular syphilis. The discussant also described the natural history (or stages) of syphilis as I have covered here.

Day #257 - Viral Encephalitis

Today we heard the story of a young woman with fever, headache, photophobia, and confusion/drowsiness with a normal CT and an LP with a lymphocytic pleocytosis with elevated protein. The presumed diagnosis was viral meningoencephalitis and she was treated with IV acyclovir.

Despite excellent data on bioavailability, there are only case reports of substituting oral valacyclovir for IV acyclovir in the treatment of HSV encephalitis. This would be an interesting option which would decrease the need for IV in patients who recovered after IV "induction". It is biologically plausible because the levels in the plasma achieved by valacyclovir approximate acyclovir without the concomittant nephrotoxicity. Apparently clinical trials are underway.

We have previously blogged about HSV encephalitis here.

Day #256 -Pleural Effusion/Congestive Heart Failure

I have previously blogged about the approach to pleural effusion here.

We reviewed some general causes of:

Exudate:

• Malignancy
• Infection
  
  • Parapneumonic
  • Empyema
  • TB
  • Subdiaphragmatic abscess
    
• Inflammatory
  
  • SLE/RA/FMF
• Pulmonary Embolism
  
• Hemothorax/Chylothorax

Transudates:

• CHF
• Cirrhosis (including sympathetic)
  
• Nephrotic Syndrome
• Malnutrition
• Hypothyroidism

I have previously discussed congestive heart failure here (link to guidelines there as well).

A summary of the class I recommendations:

• Moderate salt restriction in the diet with daily weights
• Exercise testing and exercise programme
• Stop offending medications (i.e. NSAIDS, most calcium channel blockers)

• Diuretics (e.g. furosemide) as required to keep euvolemic
• ACE inhibitor such as lisinopril, enalapril, ramipril, etc. as tolerated. ARB in patients who are intolerant of ACEi due to cough
  
• Beta-blockade with beta-blocker proven to influence outcome in CHF. Start slowly, when euvolemic, with very slow titration in advanced HF (e.g. carvedilol, bisoprolol)
• Consider adding digoxin (see dosing here) to improve symptoms and decrease hospitalization.
• Consider adding spironolactone in patients with NYHA III/IV symptoms and LVEF less than 35% to ACEi or ARB if Cr less than 150 and K+ less than 5 and you can monitor potassium and renal function. Caveat publication here.
  

Assessment of revascularization and modification of the cardiac risk factors is also important.

When he is no longer NYHA IV, and he is on MAXIMAL medical therapy, and he is expected to live more than one year, he can be considered for an ICD (Ischemic Cardiomyopathy with EF less than 35%) for primary prophylaxis of arrythmogenic death.

An article discussing LV thrombi in the context of ischemic cardiomyopathy is available here.

Scenario - Pericarditis

Examples of ECGs of the 4 stages of pericarditis are here.

• Stage 1: Diffuse concave ST elevation with PR depression
• Stage 2: PR depression only with pseudonormalization
• Stage 3: T wave inversion
• Stage 4: Normalization

Good review in NEJM here. A further review on the use of colchicine in the treatment of acute and recurrant pericarditis is available here.

Day #253 - Idiopathic Pulmonary Fibrosis

Idiopathic pulmonary fibrosis:

Older, but still relevant NEJM review.

There are few treatment options aside from lung transplantation, which actually substitutes one chronic disease for another. A review is available here.

We discussed the concept of "acute exacerbation" of IPF -- a review of this condition and the treatment is here. The mortality is approximately 60-70% at 3 months.

Like many diseases, exercise programs can be helpful in improving functional status.

Day #252 - Infective Endocarditis (Staphylococcus Aureus)

Today we heard a case of a patient with a known history of injection drug use who presented with multiple swollen joints, in the context of a persistant staphylococcal bacteremia. The patient also had a history of previous endocarditis and on exam had evidence of moderate-severe tricuspid regurgitation.

I have reviewed the diagnostic criteria for endocarditis here.

I have previously blogged about staphyloccocal bacteremia here. I will re-iterate that for methicillin sensitive staph aureus vancomycin is INFERIOR to beta-lactam therapy.

Some newer evidence suggests that the risk of using adjuvant gentamicin in native valve staphylococcal bacteremia/endocarditis is greater than the benefit.

An interesting concept, which I am now going to endorse because it is inexpensive and relatively simple, is continuous cloxacillin infusion as opposed to intermittant infusion. In this study the 30 day microbiologic cure was 94% in the CI group as opposed to 79% in the II group (ARR 15%, NNT 8).

There have been several studies looking at treatment options in injection drug users. Long term antibiotic therapy requires indwelling lines and this usually mandates extended hospitalization or "confinement" if ongoing drug use is a concern. These two studies (larger study, smaller study) have evaluated quinolone (ciprofloxacin, though today levofloxacin or moxifloxacin would likely be even more effective) combined with rifampin in right sided IE. These are small studies, so they shouldn't influence practice in general -- but in certain cases may be the only option.

Day #251 - DVT (Phlegmasia Cerulea Dolens)

Today we heard a case of a patient who presented with an acute, cold/blue, painful leg. The cause of this was identified as a mixture of a large DVT on a background of peripheral vascular disease.

In phledmasia cerulea dolens (see right, from NEJM) the DVT, usually very large, causes venous outflow obstruction which, in turn, leads to elevated tissue pressures which can significantly reduce arterial flow leading to tissue ischemia.

In today's patient they presented with a lactic acidosis probably related to tissue hypoxemia.

There are a number of interesting articles about interventional and surgical approaches to the treatment of massive DVT causing PCD. The goal of therapy is to salvage the limb before it becomes gangrenous. This article discusses manual clot aspiration. This is a more complete review of the interventional options.

Note: in our case, thrombolysis was contraindicated because of the recent large ischemic stroke.

My colleague at TWH has posted a summary of the "Wells Criteria" for the clinical diagnosis of DVT.

Using this algorithm, a low risk patient with a negative D-dimer does not have a DVT. A high risk patient, or one with a positive D-dimer will require further investigation.

Duplex Compression Doppler Ultrasound is usually the test of choice. Treatment involves anticoagulation with heparin (unfractionated or low molecular weight depending on clinical scenario -- usually LMWH) which is generally followed by coumadin after 2 days of anticoagulation with overlap until INR 2-3 x 2 days and a minimum of 5 days of heparin

Day #250 - Safe Patient Signover

Today was a special session on safe signover practices. Signover/Signout/Handover of care between physicians (particularly at teaching hospitals) is one of the most dangerous times. By paying attention to the process, we can improve the quality of signover and hopefully provide safer and more efficient cross-coverage.

The presenters referenced these articles:

• ANTICipate - A model for generating a sign out list
• SIGNOUT? - A model for verbal signover
• "Consequences of Inadequate signout"
  

Day #249 - ITP

Today we heard the case of a patient with severe thrombocytopenia, presumed ITP (bone marrow biopsy pending)

I have previously blogged about thrombocytopenia here.

Day #245 - (Cryptogenic) Organizing Pneumonia

Today we talked about a case of a patient with organizing pneumonia in the context of advanced rheumatoid arthritis on penicillamine.

The discussant reviewed the respiratory complications from RA:

• Pulmonary nodules
• Pleural effusion
• Pulmonary Fibrosis
• Bronchiolitis Obliterans
  
• Organizing pneumonia
• Cavitary disease -- with pneumoconiaosis (Caplan's syndrome)
• Related to immunosuppression (i.e. methotrexate lung)
  

We then discussed the diagnosis and management of organizing pneumonia in rheumatoid arthritis.