Monday, October 24, 2016

Acute Chest Syndrome in Sickle Cell Disease

During Grand Morning Report, we briefly discussed a patient with sickle cell disease and a history of acute chest syndrome.  This is a common complication of sickle cell disease and is a frequent cause of death in this patient population, making early diagnosis and treatment critical. 

What is acute chest syndrome?

What causes acute chest syndrome?

A number of different causes for acute chest syndrome have been identified.  These include the following:
  • Pulmonary infarction due to vaso-occlusion from sickled cells
  • Fat embolism due to release of fat into the bloodstream from bone marrow infarction during a vaso-occlusive crisis
  • Infection
  • Hypoventilation
It is also important to recognize that patients can present with what appears to be a straightforward pain crisis and still go on to develop acute chest syndrome during their hospitalization.

What else should be on the differential?

Given that many of the features of acute chest syndrome are vague or non-specific, other etiologies for the patient’s presentation should be considered and/or ruled out.  The following are alternate diagnoses not to miss:
  • Acute coronary syndrome
  • Pulmonary embolism
  •  Exacerbation of asthma or COPD
  • Pneumonia (although this is often indistinguishable from acute chest syndrome)

How is acute chest syndrome treated?

The mainstays of treatment for a vaso-occlusive crisis still apply:
  • Early and aggressive pain control
  • IV fluids to maintain normovolemia
  • Oxygen 
  • Incentive spirometry
  • DVT prophylaxis 
However, the following therapies should also be considered, along with Hematology consultation:

  • Since it is often impossible to distinguish pneumonia from acute chest syndrome, patients should be started on antibiotic therapy early.  This should also include coverage for atypical organisms as mycoplasma pneumoniae and chlamydia spp. are thought to be frequent culprit organisms.   
·         Simple vs. Exchange Transfusion:
  • Simple transfusion should be considered for mild acute chest syndrome while patients with moderate to severe disease typically require exchange transfusion.  The goal of both therapies is to lower the overall proportion of hemoglobin S and improve oxygenation. 

References and more reading...

Paul RN, et al.  “Acute chest syndrome: sickle cell disease”. Eur J Haematol. 2011 Sep;87(3):191-207.

Vichinsky EP, et al.  “Causes and outcomes of the acute chest syndrome in sickle cell disease.  National Acute Chest Syndrome Group”.  NEJM; 2000 Jun 22;342(25):1855-65.

Sunday, July 31, 2016

Initiation of Therapy for Active TB

We have discussed the initiation of TB therapy on a few occasions already this year, including a case where a patient developed toxicity to the medications.  Downtown Toronto we are very fortunate to have fast access to input from our infectious disease colleagues as well as specialized TB clinics, but in other locations starting a patient on TB therapy may fall into the scope of practice of a general internist.  This week's blog post will outline a basic approach to treating a patient for TB based on the Canadian guidelines.   

What do I need to do before starting therapy?

·         Counseling:
o   Importance of adherence to therapy
§  Many patients participate in Directly Observed Therapy (DOT) through the Department of Public Health.
o   Avoidance of alcohol and hepatotoxic medications (ie. acetaminophen, herbal remedies)
o   Need to seek immediate medical attention if the following develop:
§  Symptoms of acute hepatitis such as nausea, vomiting, right upper quadrant pain, jaundice
§  Changes in vision
§  Rash

·         Baseline Testing
o   CBC, lytes, creatinine
o   Liver panel
o   Hepatitis A/B/C and HIV
o   Uric acid
o   Visual acuity, red-green color discrimination

What regimen should I start empirically in most patients?

Daily Dose
Side Effects
Rifampin (RMP)
Max 600mg
Drug interactions, hepatitis, rash, cytopenias
6 months
Isoniazid (INH)
Max 300mg
Hepatitis, rash, neuropathy, CNS toxicity, anemia
6 months
Pyrazinamide (PZA)
Max 2000mg
Hepatitis, arthralgias, rash, gout
2 months
Ethambutol (EMB)
Ocular toxicity, rash
2 months*

Prevention of peripheral neuropathy from INH
While on INH
* Can be stopped as soon as sensitivities back if pan-sensitive

How do I monitor patients once they have been started on therapy?

·         Monitoring Disease Activity:
o   Patients who are AFB smear positive require weekly smears until negative
o   Once smears are negative, cultures should be done at 2 months, and 6 months prior to completion of therapy

·         Monitoring for Complications:
o   Patients on active therapy should be seen at least monthly and should be assessed at each visit for adverse reactions
o   There are no clear guidelines regarding how frequently to repeat liver enzymes
§  This is currently based on clinical judgment and baseline risk for toxicity

What happens if my patient develops drug-induced hepatitis?

·         Risk of hepatitis:
o   Pyrazinamide > Isoniazid > Rifampin
·         Immediate action is required if the transaminases are > 5x ULN or the patient becomes jaundiced
o   Stop all three of the above drugs
o   Start alternative regimen with a fluoroquinolone + one other agent
·         Once transaminases normalize, reintroduce rifampin, followed by isoniazid, followed by pyrazinamide

Special Circumstances:

·         Treatment considerations are different in the following scenarios, and expert consultation should be sought:
o   HIV-associated TB
o   Extrapulmonary TB
o   Multi-drug resistant TB

The information in this blog post was adapted from the Canadian Tuberculosis Standards, 7th Edition, Chapter 5: Treatment of Tuberculosis Disease.  It can be accessed at 

For additional reading check out:
Horsburgh CR, Barry CE, Lange C. Treatment of tuberculosis. NEJM. 2015; 373:2149-2160.

Sunday, July 17, 2016

Approach to Dyspnea in a Patient with an Underlying Malignancy

--> In morning report this week, we discussed the case of a woman with a known history of breast cancer presenting with shortness of breath.  This case highlighted that although the most common etiologies for dyspnea seen on GIM are still very much applicable in this setting, we have to broaden our differential to consider additional causes, some of which are life threatening.   Dr. Abdullah provided a very helpful framework for approaching the differential diagnosis as outlined below:

 A few additional points to consider when working through this differential based on our discussion in Morning Report:

1.    A thorough treatment history is very helpful!      
·      What chemotherapy did they receive and when?
·      When was their last dose of radiation?
·      Was their left ventricular ejection fraction measured before and after treatment (typically with a MUGA)?
·      When was their last staging/surveillance imaging?  What did it show?

2.    VTE is not only more common in patients with cancer, it is also associated with poor prognosis1.  Unless there is a clear alternate cause, many of these patients will need a CT PA.
·      This will also provide a lot of additional useful information, such as evidence of infection or pericardial effusion, which may not be evident on CXR.

3.    If a pericardial effusion causing tamponade crosses your mind, you need to rule it out.
·      In addition to dyspnea, most patients with tamponade will also have tachycardia, elevated JVP, enlargement of the cardiac silhouette on chest x-ray and pulsus paradoxus.  On the contrary, less than half of patients will exhibit hypotension, muffled heart sounds or characteristic ECG changes.2 
·      It can be a challenging diagnosis to make based on physical exam alone so  have a low threshold to order a TTE.  If the patient had a CT chest, it is also helpful to check the report for presence of a pericardial effusion with the caveat that the size tends to be overestimated on CT.

4.    Radiation pneumonitis typically occurs four to twelve weeks post-radiation whereas fibrotic disease takes six months to 2 years to manifest.
·      Certain types of chemotherapy can increase the risk of radiation-induced lung injury.  These agents include bleomycin, doxorubicin and cyclophosphamide, among others.3 

5.    For respiratory infections in this patient population, consider your choice of antibiotic therapy carefully.
·      Many of these patients will have had extensive health care exposures, previous infections and will be immunosuppressed. 
·      Check previous cultures, if available.  However, broader initial therapy and more extensive investigations including CT chest +/- bronchoscopy may be required depending on the degree of immunosuppression.

1.         Timp JF, Braekkan SK, Versteeg HH, Cannegieter SC. Epidemiology of cancer-associated venous thrombosis. Blood. Sep 5 2013;122(10):1712-1723.
2.         Roy CL, Minor MA, Brookhart MA, Choudhry NK. Does this patient with a pericardial effusion have cardiac tamponade? Jama. Apr 25 2007;297(16):1810-1818.
3.         Graves PR, Siddiqui F, Anscher MS, Movsas B. Radiation pulmonary toxicity: from mechanisms to management. Semin Radiat Oncol. Jul 2010;20(3):201-207.

The Canadian Cancer Society has helpful information about chemotherapy and its side effects (including organ-specific side effects) for both patients and healthcare providers on their website at


Friday, April 8, 2016

Tumor Lysis Syndrome

Today in morning report we discussed a case of newly diagnosed lymphoma and tumor lysis syndrome. Here are a few key points based on our discussion this morning.

Tumor lysis syndrome is an emergency. There are a few oncologic emergencies that every internist should be able to identify and manage. This is one of them. The major concerns with tumor lysis syndrome (TLS) include the complications associated with electrolyte abnormalities and renal failure. There are two ways to describe tumor lysis syndrome: Laboratory TLS involves the typical biochemical abnormalities in the right clinical context. Clinical TLS is laboratory TLS plus one of (1) increased creatinine, (2)  cardiac arrhythmia, or (3) seizure.

Think of the pathophysiology to remember the biochemical abnormalities. Think about what is actually happening to the cells in tumor lysis syndrome. The cells are rapidly being destroyed with the intracellular contents being spilled into the systemic circulation. Since cells are full of potassium, phosphate and nucleic acid; you get hyperkalemia, hyperphosphatemia and hyperuricemia. Hypocalcemia also occurs because the calcium precipitates with phosphate. The deposition of uric acid and calcium phosphate in the renal tubules causes AKI.

An ounce of prevention is worth a pound of cure. It is important to identify patients at high risk of tumor lysis syndrome so that they can receive appropriate prophylaxis in order to reduce the risk that they develop full blown TLS.  Patients at increased risk of TLS include those with rapidly growing malignancy, hematologic malignancies and those with high tumor burden. Tumor lysis syndrome can occur spontaneously (like in our patient) but is commonly triggered by chemotherapy.  Prophylaxis for TLS includes IV hydration and uric acid lowering agents – allopurinol or rasburicase – depending on the risk.

Treatment of TLS involves close monitoring, fluids and uric acid lowering agents. If your patient is diagnosed with TLS, the first thing to do is place the patient on a cardiac monitor and check electrolytes frequently. Acutely treat any dangerous electrolyte abnormalities and start IV hydration to wash out the uric acid and calcium phosphate crystals. Rasburicase is also used to reduce uric acid levels. Consider dialysis if the symptoms/AKI are severe or if the electrolyte abnormalities are persistent. 

Check out this great review from the NEJM: The Tumor Lysis Syndrome. Scott C. Howard, M.D., Deborah P. Jones, M.D., and Ching-Hon Pui, M.D.N Engl J Med 2011; 364:1844-1854. 

Wednesday, March 9, 2016

Staph Aureus Bacteremia

We discussed a case of non-specific abdominal pain and the diagnosis was found to be a staphylococcus aureus epidural abscess!

Just to recap, here are a few key points about staphylococcus aureus bacteremia:
  • Always take a finding of staph aureus in the blood seriously. This infection is associated with high mortality and morbidity. Staph aureus can spread rapidly and lead to abscesses. Remember that staph loves the spine (among other organs) and is a common cause of endocarditis.  Treatment consists of antibiotics and source control (just like every infectious disease). Vancomycin a good choice for empiric treatment to cover MRSA until the culture sensitivity can guide further management. If you find out that the organism is MSSA then a 4-6 week course of cloxacillin is generally sufficient. Also – ID consultation has been shown to reduce mortality in staph aureus bacteremia so make sure to involve your ID colleague early!
  • Look for a source. Keep in mind that the chances of finding a source are quite good if the patient acquires the bacteremia in hospital; however, we only identify a source in about 50% of patients who present from the community. Make sure to do a detailed history, physical and appropriate investigations to assess for sources like prosthetic material, septic joint, skin and soft tissue infections, endocarditis, endovascular lines and spinal/epidural abscesses. This includes a TTE to rule out endocarditis. However, keep in mind that TTE is not perfect at picking up endocarditis so you need to do a TEE if you are concerned.
  • Assess for complications. If and when you find a source of the infection, take some time to assess for complications associated with staph aureus bacteremia. Remember that staph aureus has the ability to metastasize to almost anywhere in the body so once you find a source, look carefully to rule out any other foci of infection. Pay attention to findings like new back pain (even if very mild), joint pain,  or even subtle physical findings of endocarditis. Renal and pulmonary sites of spread should also be considered.
  • Staph in the urine can be a marker for staph in the blood. Staph aureus in the urine is weird! It is not a typical organism we think about when considering UTI. So, this finding should prompt you to send blood cultures which may reveal staph aureus bacteremia.

Tuesday, November 10, 2015


Today in morning report we discussed the case of a patient who presented with hypothermia. We don't come across this every day in GIM so it is good to review the causes. Hypothermia is defined as a temperature less than 35 degrees Celsius. It is important to consider getting a second reading from a different body site to confirm that this is a true reading.

Environmental exposure is a common cause of hypothermia which can usually be elicited from the history. However, sometimes there is no history of cold exposure. In these cases you should think about the other causes of hypothermia. You can divide these into broad categories [that relate to the reasons your house might be too cold]:

Increased heat loss [the doors/windows are open]
  • Drugs that cause vasodilatation (drugs, alcohol)
  • Iatrogenic causes (cold infusions, CRRT, bypass)
  • Burns or severe skin conditions (psoriasis)

Reduced heat production [the furnace is not working properly]
  • Endocrine causes (hypothyroidism, adrenal insufficiency, hypopituitarism)
  • Hypoglycemia
  • Malnutrition
  • Reduced muscle activity (extreme elderly, inactivity)
Impaired regulation [the thermostat is incorrectly set]
  • Central CNS pathology (Stroke, intracranial hemorrhage, hypothalamic dysfunction, parkinsonism, MS, CNS drugs
  • Peripheral CNS pathology (spinal cord transection)

Miscellaneous causes [your house has an infection? ok, this one doesn’t apply to the house analogy]
  • Sepsis
  • Pancreatitis

Check out the following article for a nice review of hypothermia:  

Sunday, November 1, 2015

Evaluating a patient with headache

We discussed an interesting case of a young man presenting with a headache. This is such a common complaint that it is worth having a solid organized approach. Here are a few key points we discussed in morning report.

Think of the common and serious causes when evaluating a patient with a headache

Headache is a common, non-specific complaint that can be benign or life-threatening. For this reason it is important to have a good approach to headache. One approach is to come up with a differential for the causes that you don’t want to miss and also a list of the most common causes. You can use these lists to direct your history, physical exam and investigations.

Always consider epidemiology when creating your differential. For example, patients who are immunocompromised or those with previous intracranial pathology/surgery may invoke other diagnoses. Here is the differential diagnosis that we came up with at morning report (and one which I generally start with). Keep in mind that there are many other causes of headache that you may have to consider based on the specific clinical situation.

Common causes: Migraine, Tension-type, Cluster, Medication withdrawal, Headache associated with volume depletion or other systemic illness.

Serious causes: Meningitis, Subarachnoid hemorrhage, Temporal arteritis, CNS lesion, Sinus venous thrombosis, artery dissection, hypertensive emergency.

Use a history and neurological exam to rule in (or out) ‘serious’ causes of headache and guide your subsequent workup

The ‘POUNDing’ criteria was described in JAMA as a method of deciding whether a patient with a headache has a migraine or should undergo neuroimaging (JAMA Article Link). The 5 criteria are: Pulsatile, lasts 4-72 hOurs, Unilateral, Nausea/Vomiting and disabling. If a patient has 4/5 of the POUNDing criteria, the positive likelihood ratio for this being a migraine is 24.

It is also important to ask about red flags associated with the ‘serious causes’ listed above. Your history and physical exam will then direct your investigations. For example, you may order neuroimaging (ie. suspecting subarachnoid hemorrhage or CNS lesion), get a lumbar puncture and give antibiotics (ie. suspecting bacterial meningitis), start steroids (ie. suspecting GCA), and so on.

Bacterial meningitis should always be on your differential for headache

Check out this phenomenal one page CMAJ article on bacterial meningitis that gives a really great overview of 5 things you should know about bacterial meningitis (CMAJ Link). If there is one teaching point that I can highlight it is the following: Do not delay antibiotics (and steroids) in patients who you suspect have bacterial meningitis. This means that if you need neuroimaging or think that the LP will be delayed – give the antibiotics right away. Antibiotics might lower your chances of obtaining a positive diagnostic CSF culture but early antibiotics will improve the outcome for your patient.  Plus, you can still use other CSF indicators, like the WBC count/differential, to help support your diagnosis of bacterial meningitis.

If you are unsure about whether the patient has aseptic meningitis or bacterial meningitis you should consider treating empirically with antibiotics

The patient we discussed in morning report had aseptic meningitis. There is a long list of viral causes of aseptic meningitis.  The major families of viruses to think about include herpesviruses (ie. HSV-II), arboviruses (ie. West Nile virus), enteroviruses (ie. coxsackie) and don’t forget about HIV. Other causes to consider in the appropriate patient includes tuberculous meningitis or fungal meningitis. Choose specific CSF testing based on the clinical picture. 

If the diagnosis is not clear and there is still a suspicion for bacterial meningitis, it is often safest to treat empirically with antibiotics and await culture results.  If you suspect HSV as the cause of aseptic meningitis (ie. oral or genital lesions present) consider treating empirically with acyclovir. 

Detsky, Michael E., et al. "Does this patient with headache have a migraine or need neuroimaging?." Jama 296.10 (2006): 1274-1283.
Moayedi, Yasbanoo, and Wayne L. Gold. "Acute bacterial meningitis in adults." Canadian Medical Association Journal 184.9 (2012): 1060-1060.

Wednesday, August 26, 2015

Elevated Troponin and Rheumatic Heart Disease

Today we discussed a case of a woman with chest pain, new atrial fibrillation and an elevated troponin. She likely had rheumatic fever as a child and an echo revealed severe MR with a dilated left atrium. There were some great learning points that came up! Lets discuss.

Troponin is sensitive, not specific! 
When you assess a patient with an elevated troponin do not immediately jump to ACS as the cause! While this will be the most common cause (and certainly one of the more concerning) there are many other etiologies. Always be rigorous in your history and physical exam to decide whether or not ACS is the most likely diagnosis and to rule out others. Some other causes of elevated troponin include:

  • Myocardial Infarction
  • Post-instrumentation (PCI, cardiac surgery)
  • PE
  • End stage renal disease
  • Pericarditis/Myocarditis
  • Aortic Dissection
  • Heart Failure
  • Sepsis
  • Trauma
  • Stroke or intracerebral hemorrhage
Check out this great article on the differential diagnosis of elevated troponin:

Rheumatic fever is less common in developed countries but we still need to know about it.
Acute rheumatic fever occurs a few weeks after group A strep pharyngitis. However, not everyone who gets group A strep pharyngitis will get rheumatic fever! In fact, in developed countries, only about 3% of patients with untreated group A strep pharyngitis develop rheumatic fever. This number is lower than in developing countries - most likely due to improved hygiene (reduced transmission) and higher rates of antibiotic use for 'strep throat'.

Rheumatic fever is an illness characterized by classic signs and symptoms in a patient who had recent group A strep pharyngitis. 
We are all familiar with the 'Duke Criteria' for endocarditis. Well, rheumatic fever has the Jones Criteria to help you diagnose it:
There is a high probability that your patient has acute rheumatic fever if they had a recent group A strep infection and fulfill 2 major criteria or 1 major + 2 minor critera.

Acute rheumatic fever can lead to rheumatic heart disease.
Those who develop acute rheumatic fever are at high risk of having cardiac involvement and developing cardiac complications. Lasting complications of rheumatic heart disease are due to heart valve destruction and include CHF, stroke, endocarditis and death. How does pharyngitis cause heart disease you ask? Well it's not perfectly understood but you can explain it using buzzwords like 'molecular mimicry' (antibodies against strep will attack native cells/tissue, like myocytes). You'll have to check out another source if you want to learn more about that...

So the key is to prevent acute rheumatic fever by promptly diagnosing and treating group A strep pharyngitis in the first place!

Mitral regurgitation is the most common valve pathology of rheumatic heart disease. These patients will frequently develop chronic mitral regurgitation. According to the ACC/AHA guidelines (which I have summarized here), you should consider surgery for severe mitral regurgitation when any of the following indications are met:
  • Acute, symptomatic severe MR
  • Chronic MR which is symptomatic 
  • Chronic MR with LV dysfunction
  • Chronic MR for patients undergoing other cardiac surgery 
  • Atrial fibrillation
  • Pulmonary hypertension
  • Mitral valve prolapse and ventricular arrhythmias
Thanks Team 1 for a great case!

Check out the following resources for more info:
  1. Seckeler MD, Hoke TR. The worldwide epidemiology of acute rheumatic fever and rheumatic heart disease. Clinical Epidemiology. 2011;3:67-84. doi:10.2147/CLEP.S12977.
  2. Korff S, Katus HA, Giannitsis E. Differential diagnosis of elevated troponins.Heart. 2006;92(7):987-993. doi:10.1136/hrt.2005.071282.
  3. Bonow RO, Carabello B, de Leon AC, Jr., et al. ACC/AHA guidelines for the management of patients with valvular heart disease: A report of the American College of Cardiology/American Heart Association Task Force on practice guidelines (Committee on management of patients with valvular heart disease)12. J Am Coll Cardiol. 1998;32(5):1486-1582. doi:10.1016/S0735-1097(98)00454-9.