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"

---

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.