A tale of 2 cases - July 23, 2012

Thank you to team 8 for bringing 2 cases, and to Dr. Wayne Gold for hosting today’s morning report.  We discussed 2 interesting cases.

The first case involved a patient with a stroke.  We discussed that in patients already receiving ASA, neither Plavix (clopidogrel) nor Aggrenox (ASA + extended release dipyridamole) is superior to the other agent for preventing recurrent stroke, as demonstrated in the PRoFESS trial (Prevention Regimen for Effectively Avoiding Secondary Strokes) published in 2008 (Sacco RL, et al; PRoFESS Study Group. Aspirin and extended-release dipyridamole versus clopidogrel forrecurrent stroke.  N Engl J Med. 2008 Sep18;359(12):1238-51.).  They randomized 20322 patients and followed them for a mean of 2.5 years for the primary outcome of first recurrence of ischemic stroke.  No difference was found in the primary outcome (9% in the ASA + extended release dipyridamole group and 8.8% in the clopidogrel group; hazard ratio 1.01; 95% CI 0.92 to 1.11).  However, some patients may benefit from anticoagulation if there is known cardioembolic stroke risk such as atrial fibrillation, or apical thrombus.  In reality, the benefit of antiplatelet or anticoagulant therapy must be balanced against the individual bleeding risk of the patient.

We then discussed the differential diagnosis of episodic decreased level of consciousness post stroke.  The most prominent being post-stroke seizure (+/- accompanying post-ictal phenomenon).  Hemorrhagic conversions are less likely to present as transient decreased level of consciousness.  It is important to obtain imaging to rule out structural causes, EEG to assess for seizure, and to complete a metabolic work-up to rule out non-CNS causes.  Syncope is also in the differential diagnosis of episodic loss of consciousness and cardiac investigations (including the ruling out of dysrhythmias) may be warranted.

In the discussion of our second case, we discussed the principles of management of febrile neutropenia.  We discussed the importance of starting empiric broad-spectrum antibiotics first without waiting for results of cultures.  Minimum of blood and urine cultures, and chest x-ray should be obtained.  Other investigations should be directed based on patient’s presenting symptoms and physical exam findings.  Empiric therapy should cover gram positive organisms (including Staph aureus) +/- CNST (coagulase negative staph), AND gram negative organisms (including Pseudomonas).  Many institutions have empiric therapy guidelines based on local resistance pattern.  The Infectious Diseases Society of America (IDSA) Guideline on antibiotics used in febrile neutropenic patients can be found here.  (Freifeld AG. Clinical practice guideline for the use of antimicrobial agents inneutropenic patients with cancer: 2010 Update by the Infectious DiseasesSociety of America.  Clin Infect Dis. 2011 Feb 15;52(4):427-31.)

We then discussed a rash in the setting of febrile neutropenia.  In general, the rash can represent a primary skin/soft tissue infection, or a secondary manifestation of a systemic infection.  The latter can be from hematogenous seeding (as in the case of Janeway lesions in infective endocarditis), immune mediated (e.g. disseminated gonococcal infection), activation of coagulation cascade (purpura fulminans), or toxin-mediated (as in staphylococcal toxic shock syndrome).  In our patient, we suspect the skin lesion is ecthyma gangrenosum.  In febrile neutropenic patients, this may represent a gram negative infection (commonly Pseudomonas).  Other infections (e.g. fungi [Candida, Aspergillus]) are also possible.  See this article by Yas Moayedi which summarizes mechanism of skin manifestation of systemic infection, other organisms that can cause ecthyma gangrenosum, and principles of management.  (Moayedi Y,Bunce PE, Sade S, Ghazarian D, Gold WL.  Fromthe outside looking in.  Am J Med. 2012May;125(5):457-60.).

Note that in most patients with skin infection, we do not routinely obtain aspirate and biopsy of the skin.  However, in a patient with febrile neutropenia, this is worthwhile as it has a higher yield of recovering the organism(s) responsible.  We chose to treat this patient with two anti-pseudomonal agents to ensure that there is at least one agent that is active against the organism should it later turn out that this patient had a resistant organism.  Once sensitivity known, antibiotics can then be tailored.


Your chief resident (Lauren) will return tomorrow.  Thank you for a week of interesting cases.  Terence