Clostridium difficile Infection

The following table summarizes the current Infectious Diseases Society of America (IDSA) Guidelines on the management of Clostridium difficile infections (Hint: click on the table to make it bigger):

It is borrowed from the recent succinct article by some of our own colleagues in Internal Medicine in Toronto, which you can find at this link!

For the full set of guidelines, click on this link.

If you are concerned about toxic megacolon, always remember to order a flat plate of abdomen. Even though a maximum colonic diameter greater than 6 cm is consistent with the diagnosis of megacolon, the overall clinical condition of the patient is more important than the absolute width of the dilated segment. Early surgical consultation is of utmost importance.

Cryptogenic Organizing Pneumonia

Cryptogenic organizing pneumonia (COP), previously known as Bronchilitis Obliterans Organizing Pneumonia (BOOP), is a distinct clinical entity with predominant features of pneumonia.

To summarize:

- It usually occurs in fifth or sixth decades of life.
- Men and women are affected equally.
- Most patients are symptomatic for less than two months, with a clinical presentation that mimics community-acquired pneumonia.
- Multiple ground-glass opacities and/or consolidations (with air bronchograms) are commonly noted on imaging.
- An open or thoracoscopic lung biopsy is suggested to confirm the diagnosis.
- Histopathology typically demonstrates excessive proliferation of granulation tissue within small airways (proliferative bronchiolitis) and alveolar ducts, associated with chronic inflammation in the surrounding alveoli.
- The diagnosis of COP requires positive histopathology AND the exclusion of any other possible cause of pneumonia (in particular, infectious causes).
 - Glucocorticoid therapy typically induces rapid clinical improvement and clearing of the opacities on chest imaging, usually without significant sequelae.
- Relapses are common upon tapering or discontinuation of glucocorticoids.
- It can be idiopathic, but also associated with connective tissue diseases, a variety of drugs, malignancy, and other interstitial pneumonias.

Please click on this link to read an excellent 2011 review from Chest on this topic.

Respirology Pearls

Here are a few respirology (and non-respirology) pearls for you to mull over today:

1) Correlation between arterial and venous blood gases

Much of the literature surrounding this concept is found in the Emergency Medicine literature. A prospective study involving 95 patients in Emergency Medicine Journal  from 2007 comparing ABG and VBG samples drawn as close in time as possible concluded that VBG analysis for pH, bicarbonate, and pCO2 (but not paO2, not surprisingly) may be a reliable substitute for ABG analysis in the initial evaluation of an adult patient population presenting to the ED. Click on this link to read the full article.

2) Hypertrophic pulmonary osteoarthropathy

Hypertrophic pulmonary osteoarthropathy, also known as Bamberger-Marie disease, is periostitis of the long bones of the upper and lower extremities. It is thought to be a paraneoplastic manifestation of lung carcinoma. These patients often get clubbing and increased bone deposition on long bones. Their presenting symptoms are sometimes only clubbing and painful ankles. Check out this link for an interesting "Images in Clinical Medicine" in NEJM illustrating the paraneoplastic phenomena of hypertrophic pulmonary osteoarthropathy and tripe palms (or acanthosis palmaris).

3) Batson venous plexus

The Batson venous plexus is a network of valveless veins that connect the deep pelvic and thoracic veins draining the inferior end of the bladder, breast, and prostate to the internal vertebral venous plexuses. They are thought to to provide a hematogenous route for metastatic spread of rectal and prostate cancer to the vertebral column or brain. The plexus is named after anatomist Oscar Vivian Batson, who first described it in 1940.

Right Heart Failure

Yesterday's Rapid Fire Morning Report was a testament to the breadth of clinical presentations that Internal Medicine has to offer.

We heard about the smörgåsbord of cases that were seen the evening prior, including cases of:

- transient hypoxia of unclear etiology
- paraspinal absess
- management of cancer-related pain
- right-heart failure

I thought I was take a moment to review the diagnosis and management of right heart failure, which are gleaned from guidelines published by the Canadian Cardiovascular Society in 2009. You can find the full set of guidelines by clicking on this link.

Right heart failure (RHF) can be due to systolic and/or diastolic dysfunction, and can be an isolated occurrence, though it is more commonly associated with left heart failure.

To make the diagnosis, at least two features should be present:

1) Signs and symptoms consistent with RHF. These typically fall into three categories:

- Fluid retention (eg, ascites, peripheral edema, anasarca)
- Exercise intolerance and fatigue (eg, low cardiac output, diastolic and systolic dysfunction)
- Hypotension (especially with atrial and ventricular arrhythmias, and low cardiac output)

2) Objective evidence of abnormal right-sided cardiac structure or function or elevated intracardiac pressures

The etiology of RHF can often be broken down into the following categories:


- Increased afterload, including left-sided heart failure and pulmonary arterial hypertension
- Right ventricular (RV) myopathic process, RV infarction and restrictive heart disease
- Right-sided valvular heart disease (triscuspid and pulmonary)
- Congenital heart disease
- Pericardial disease (a mimic of RHF)

On physical examination, one may find one or more of the following:

- Elevated JVP (with CV waves possibly present with tricuspid regurgitation)
- Hepatomegaly (from passive hepatic regurgitation)
- Ascites
- Peripheral edema
- RV heave
- Palpable P2
- Systolic murmur at left lower sternal border consistent with tricuspid regurgiation
- Right-sided S3

The diagnosis is typically made using:
- Echocardiography
- Consider cardiac MRI and MUGA scan, as indicated
- If the diagnosis of pulmonary arterial hypertension is felt to be the cause, then right-heart catheterization should be considered, as it is the gold standard for the diagnosis of pulmonary hypertension.

In regards to management, generally, diuretics are the mainstay of therapy. However, diuretics should be given judiciously, as patient's LV filling pressures are often low, and overdiuresis may lead to intravascular volume contraction, precipitating hypotension, pre-renal acute kidney injury, etc.

Always be mindful of the patient's electrolyte status (in particular, their potassium and magnesium), as diuretics can lead to hypokalemia and hypomagnesemia - a recipe for arrythmias (and thus, further exacerbation of their heart failure).

Acute Tubular Necrosis

Yesterday, in Nephrology Morning Report, we reviewed the tried and true approach to acute kidney injury (AKI). All together now: pre-renal, intra-renal, and post-renal.

Moreover, we learned about the spectrum of injury caused by intravascular volume depletion (which can be either due to true hypovolemia or low effective circulating volume), namely:

- pre-renal AKI (the cardiac equivalent would be "stable angina")
- all the way to intra-renal AKI, in the form of ischemic acute tubular necrosis (ATN) (the cardiac equivalent would be "myocardial infarction")

ATN is largely caused by two broad categories of injury:

1) ischemic ATN (as described above)
2) nephrotoxic ATN (classic causes include aminoglycosides, CT contrast, and hemepigments, such as in rhabdomyolysis)

In order to distinguish pre-renal AKI from ischemic ATN, one can look at the urine sediment looking for heme granular casts, which are often described as "muddy brown" in appearance.

If a patient has sustained AKI in the form of ATN, then it is prudent to monitor for acute indications of dialysis. These include:

1) Hyperkalemia (refractory to medical management)
2) Volume overload (refractory to medical management)
3) Uremia, typically resulting in pericarditis (refractory to medical management)
4) Acidosis (refractory to medical management)
5) Removal of toxins, such as lithium or salicylates (refractory to medical management)

Let's end off today's post by paying homage to one of the greatest puppeteers of all time, Jim Henson, who we learned died from a Group A Streptococcus infection. Thank goodness for the Muppets.

Autoimmune Polyendocrine Syndrome

Although Final Jeopardy! was a stumper this morning, that doesn't mean you still do not have an opportunity to learn more about Autoimmune Polyendocrine Syndrome, which is a heterogeneous diagnosis classified into three distinct types based upon the putative genetic mechanism, and nicely summarized in the table below (hint: click on the table to enlarge it). It is borrowed from a nice review article from NEJM in 2004, which you can find by clicking on this link.

Interesting historical fact: John F. Kennedy was thought to have Autoimmune Polyendocrine Syndrome type II. 

Click on this link for an absolutely fascinating article from the Annals of Internal Medicine that builds the case for this hypothesis based upon historical events and conversations with his personal physicians.

N.B. Alex Trebek sends his apologies and regards for not being able to attend Jeopardy! Morning Report today.

Rapid Fire Morning Report

And now, a smörgåsbord of learning points from today's wonderful Rapid Fire Morning Report:

1) Does This Adult Patient With Suspected Bacteremia Require Blood Cultures?

A recent addition to the JAMA Rational Clinical Examination Series by several members of the Department of Medicine here at Mount Sinai has helped us to better answer the aforementioned age old question.

- The pretest probability of bacteremia varies considerably and is determined largely by the clinical context (including the presence or absence of an identifiable focus of infection).

- Blood cultures should not be ordered simply because isolated fever or leukocytosis is present in patients for whom the pretest probability of bacteremia is low.

- The SIRS criteria and Shapiro decision rule show promise in further defining low-risk patients but require prospective validation.

- The existing data do not allow generalization of these conclusions to immunocompromised patients or those under consideration for endocarditis.

2) HIV-associated Diarrhea

Today's discussion regarding HIV-associated diarrhea reminded me of a previous Rapid Fire Morning Report in which this exact diagnosis and its differential diagnosis was discussed. Clicking on this link will lead you to a previous post discussing this exact entity.

3) Heyde's Syndrome

Bleeding from angiodysplasia in the GI tract in patients with aortic stenosis has been called Heyde's syndrome. This is a well-known association, first reported by Dr. Edward Heyde in the NEJM in 1958, although the hypothesis of causality remains controversial.

The purported mechanism by which aortic stenosis may lead to the development of angiodysplasia is through the development of an acquired form of von Willebrand disease from mechanical disruption of von Willebrand multimers as they pass through a tight aortic valve, as well as from a vWF interaction with platelets that triggers platelet clearance.

Fever of Unknown Origin

Today in Morning Report, we discussed the workup of a Fever of Unknown Origin (FUO).

To review, FUO is defined as a temperature higher than 38.3°C on several occasions and lasting longer than 3 weeks, with a diagnosis that remains uncertain after 1 week of investigation, that commonly include:


- a full history and physical
- CBC, electrolytes, creatinine, glucose, liver enzymes, LDH, bilirubin
- blood cultures and blood film
- hepatitis serology (if liver enzymes abnormal)
- urinalysis, urine microscopy, and urine culture
- CXR


The three broad categories in which to frame one's differential diagnosis of FUO commonly include:

- infections
- malignancies
- connective tissue diseases

A systematic review published right here in Toronto in the Archives of Internal Medicine in 2003 detailing a Comprehensive Evidence-Based Approach to Fever of Unknown Origin recommend the following workup for FUO (in addition to the above):

- ANA, RF
- HIV, CMV, EBV, Q-fever

The following diagram outlines a suggested evidence-based approach for the further workup of FUO after the above investigations are complete:

The aim is to find the cause, in order to temper the Disco Inferno.

Viral Meningitis

Today, in Morning Report, we discussed the diagnosis of viral meningitis.

How opportune a  moment to firstly review a previous post last month on Bacterial Meningitis.

We discussed the importance of not delaying administration of parenteral medications (antimicrobial therapy +/- dexamethasone) upon suspicion of bacterial meningitis following collection of blood cultures in order to perform a lumbar puncture.

In fact, administration of antibiotics does not change the composition of the CSF cell count, differential, or biochemistry for at least 24 hours. Please click on this link for the abstract to a paper published in 1983 detailing this finding.

However, if one is able to obtain CSF in a safe and timely manner that does not delay patient care, it is certainly preferable, as we recognize from studies, such as this one, that CSF sterilization may occur more rapidly after initiation of parenteral antibiotics than previously suggested, with complete sterilization of meningococcus within 2 hours and the beginning of sterilization of pneumococcus by 4 hours into therapy.

The classic CSF cell count, differential, and biochemistry compositions of different diagnosis can be reviewed here.

Lastly, the most common causes of viral meningitis include enteroviruses, West Nile Virus, and Herpes Simplex Virus (more often type 2).

Pulmonary Function Tests

Today in Morning Report, we reviewed an approach to pulmonary disease, with a focus on the utility of pulmonary function tests.

I thought this would be an opportune time to review the definitions of the different "capacities" and "volumes" in pulmonary physiology.

Here is a review of some of the classic flow- volume loop morphologies for pulmonary function tests.

And, lastly, here's a link to the ATS/ERS Task Force: Standardization of Lung Function Testing guide for Interpretative strategies for Lung Function Tests published in Eur Respir J in 2005.

Posterior Reversible Encephalopathy Syndrome

Today in Morning Report, we talked about Posterior Reversible Encephalopathy Syndrome (PRES), which is also known under the moniker, Reversible Posterior Leukoencephalopathy Syndrome (RPLS).

PRES is a neurologic syndrome diagnosed by clinical AND radiologic findings:

Clinical Presentation

Classically characterized by the following:

- headaches

- altered level of consciousness

- visual changes

- seizures

Radiologic Findings

The classic findings upon neuroimaging of PRES is symmetrical white matter edema in the posterior cerebral hemispheres, particularly the parieto-occipital regions, although this not always the case. PRES can often been seen on CT imaging of the head, although MRI brain is best.

Here's a CT head non-contrast revealing bilateral hypodensities involving the occipo-parietal region.

Here's a  T2-weighted MRI brain demonstrating multiple cortico-subcortical areas hyperintense lesions involving the occipital and parietal lobes, as well as the pons.

   

Causes of PRES

The most common causes of PRES include:

- hypertensive encephalopathy

- eclampsia

- immunosupprseive medications, including calcineurin inhibitors (cyclosporine, tacrolimus)

- TTP/HUS

- vasculitis (e.g. SLE, PAN)

- renal failure (acute and/or chronic)

Management of PRES

- The most important aspect of management is to treat the underlying cause (whether this means blood pressure lowering, delivery of baby, discontinuation of offending medication, plasmapheresis, etc.)! 

- Seizures can be treated with antiepileptic agents, most commonly phenytoin. 

Most patients demonstrate the "R" of PRES, meaning their symptoms are reversed by treating the underlying cause, often with two weeks of management, although a small minority do not make a full neurologic recovery.

Diabetic Emergencies

Today at Noon Rounds, we talked about the management of Diabetic Ketoacidosis (DKA) and Hyperglycemic Hyperosmolar State (HHS).

Please click on the link below to read an oldie-but-goodie post regarding this topic:
http://morningreportmsh.blogspot.ca/2012/07/diabetic-ketoacidosis.html

The following is a nice schematic diagram outlining the initial management of patients with DKA and HHS from the American Diabetes Association Consensus Statement on Hyperglycemic Crises in Adult Patients With Diabetes. (Hint: click on the picture to make it bigger). Reference: Kitabchi AE et al., Diabetes Care. 2009;32(7):1335-1343.

Lastly, what's a post on diabetes and glycemic control without reference to the two landmark trials that changed the landscape of glycemic control for patients with type 1 (DCCT and it's follow-up trial, EDIC) and type 2 (UKPDS) diabetes. For your reference, please click on the links to read these important trials.

1) Diabetes Control and Complications Trial, NEJM (1993)
2) Epidemiology of Diabetes Interventions and Complications Trial, NEJM (2005)
3) United Kingdom Prospective Diabetes Study, Lancet (1998)

Severe Sepsis

Today at Noon Rounds, we learned about the management of severe sepsis.

Remember, the enigmatic "sepsis" fits within a spectrum of disease:
1) SIRS (systematic inflammatory response syndrome) = at least 2 of a) temperature >38.3ºC or <36ºC, b) pulse >90 bpm, c) RR>20 breaths/min or PaCO2<32 mmHg, and d) WBC>12 or <4
2) Sepsis = SIRS + source of infection
3) Severe sepsis = Sepsis + end-organ dysfunction (including CNS, renal, cardiac, respiratory, hematologic)
4) Septic shock = Severe sepsis + inability to respond to adequate fluid resuscitation


The "Surviving Sepsis Campaign" is an international campaign designed to raise awareness and streamline the management of this important syndrome, which still carries with it a 30-day mortality rate of approximately 30%.

Click on this link for the full set of guidelines published in Critical Care Medicine in 2008, and on this link for the handy-dandy pocket guide.

These Guidelines are based, in part, upon the "Rivers Protocol" or Early-Goal Directed Therapy, published in NEJM in 2001. Click here to read this seminal paper.

In addition to these important hemodynamic parameters, we must not forget about treating the source of sepsis. This typically means identification of the source of infection and early and appropriate broad-spectrum antibiotics (within one-hour of identification of severe sepsis, and ideally after cultures have been drawn) +/- source control.

Bacterial Meningitis

During Noon Rounds on Friday, we discussed the importance of recognizing and treating bacterial meninigits, a diagnosis that still carries with it a case-fatality rate of 16.4%! (Please visit this link to connect you to the 2007 NEJM article detailing surveillance data on culture-confirmed cases of bacterial meningitis in the United States from 1998-2007).

To review, the classic triad consists of: fever, nuchal rigidity, and altered mental status. Remember, many patients do not present with all three features, but most will present with at least one.


Jolt accentuation of headache is the most sensitive maneuver for detecting meningitis.

The common culprit bugs include Streptococcus pneumoniae, Neisseria meningitidis, and, primarily in patients over age 50 or those who have deficiencies in cell-mediated immunity, Listeria monocytogenes.


Knowing this, first-line empiric antimicrobial therapy consists of:
1) ceftriaxone 2 g iv q12h
2) vancomycin 1 g iv q8h
3) ampicillin 2 g iv q4h (in those patients where Listeria monocytogenes is a consideration)

In those patient's where Streptococcus pneumoniae meningitis is a consideration, give dexamethasone 0.15 mg/kg iv q6h for four days, with the first dose given 15-20 minutes prior to or at the time of antibiotic administration.

Please visit the following link to view the Infectious Diseases Society of America Clinical Practice Guidelines on the Management of Bacterial Meningitis.

Decompensated Heart Failure

Today in Morning Report, we walked through a case of decompensated heart failure.

We learned that it is not only important to treat decompensated heart failure by decreasing preload and afterload, but it is equally important to look for the precipitant of decompensation.

Common precipitants of decompensated heart failure include:


Medications (either changes in doses, additions, or discontinuations, top culprits include NSAIDS, ACE inhibitors/ARBs, beta-blockers, CCBs) 
Dietary indiscretion
Iatrogenic volume overload (read: the "unnecessary" continuous intravenous fluid infusion)
Cardiac
- Valvular disease (e.g. aortic stenosis or acute or progressive mitral regurgitation)
- Myocardial infarction and myocardial ischemia
- Progression of underlying cardiac dysfunction
- Cardiomyopathy (inherited, such as HOCM, vs acquired, such as Takotsubo cardiomyopathy and cardiotoxic agents such as alcohol, cocaine, and some chemotherapeutic agents, like anthracyclines)
- Arrythmias (e.g. atrial fibrillation, and less commonly, atrial flutter, sinus tachycardia, other supraventricular tachycardias, and ventricular tachycardia)
Severe hypertension (increasing afterload)
Renal failure
Infections (e.g. UTIs, pneumonia)
Anemia
Metabolic (e.g. hypo- or hyperthyroidism)
Pulmonary embolism


Click here for a link to the 2009 Canadian Cardiovascular Society consensus guidelines on the diagnosis and management of right-sided heart failure.

A Tale of Three Cases

Today in Rapid Fire Morning Report, we discussed three interesting and different cases that showcase the wonderful depth and breadth that Internal Medicine has to offer. And, now, a Tale of Three Cases:

1) Proton Pump Inhibitors and Upper GI Bleeding
- There is a lot of evidence supporting acid suppression in the setting of bleeding peptic ulcers.
- However, oral dosing of PPIs has not been directly compared with high-dose intravenous therapy.
- A meta-analysis of five trials evaluating oral PPIs found a significant reduction in the risk of recurrent bleeding and surgery compared with treatment with placebo or an H2-receptor antagonist.
- High-dose PPIs given orally achieve adequate acid suppression more rapidly than standard doses. And, high-dose intravenous PPIs achieve adequate acid suppression more rapidly than high-dose oral PPIs. Whether this leads to any appreciable difference on hard clinical outcomes, such as morbidity and mortality is still up in the air. 

2) Acute Exacerbation of Bronchiectasis
- Antibiotics are used to treat acute exacerbations of bronchiectasis and prevent recurrent infections by minimizing or erradicating the existing bugs that colonize bronchiectatic airways.
- These problematic bugs include Pseudomonas aeruginosa, Hemophilus influenzae, Streptococcus pneumoniae, Mycobacterium avium complex (MAC), and Aspergillus species (see the "Diagnosis Aspergillosis" post for more information).
- Diagnosed clinically: increased sputum production, change in sputum colour, dyspnea. Fever and CXR findings are not always found.
- A good first-line option for treatment of an uncomplicated exacerbation in the outpatient setting is a fluoroquinolone (e.g. ciprofloxicin).
- Consideration can be made to include dual anti-Pseudomonal coverage for treatment of exacerbations in the inpatient setting.
- Always consider and tailor antimicrobial therapy to previous cultures and sensitivities if they are available.

3) HIV-associated Diarrhea
- The differential diagnosis of diarrhea in a patient with HIV is long(!)
- But, don't be overwhelmed. Always remember your ABCs first. Resuscitate the patient. Then, you will have time to think through your workup and management plan.
- Always take into account their immunologic status (what is the CD4 count?)
- Broadly speaking, the diagnosis typically fits into one of the following categories:
Infectious (the regular stuff, such as E. coli, Salmonella, Campylobacter, Clostridium, etc., as well as the opportunistic bugs, such as CMV, cryptosporidia, microsporidia...and HIV itself)
Malignancy (e.g. Kaposi sarcoma, lymphoma)
Drugs (e.g. ritonavir)
- Send the stool for culture and sensitivity, ova and parasites, and C. difficile toxin. Consider blood cultures, blood for AFB and CMV antigenemia, and abdominal imaging.
- Consider asking for expert advice from our colleagues in Gastroenterology and/or Infectious Diseases.

That's right. All in a night's work.

Lymphadenopathy

Today in Morning Report, we discussed the differential diagnosis of lymphadenopathy. Broadly, one should consider the following etiologies:

- Infectious (bacterial, viral, mycobacterial, fungal, protozoal, spirochete)
- Malignancy (primary vs. metastatic; hematologic vs. solid)
- Lymphoproliferative (hemophagocytic lymphohistiosis)
- Immunologic (serum sickness, drug reactions)
- Endocrine (hypothyroid, Addison's)
- Other (sarcoidosis, SLE, rheumatoid arthritis)

When you first approach such a presentation, it is important to differentiate between localized and generalized lymphadenopathy.

Localized lymphadenopathy involves typically only one of the following lymph node regions:

Cervical: systemic infection (EBV, CMV, toxoplasmosis,TB), lymphoma, head and neck malignancy.
Supraclavicular: right-sided (associated with thoracic malignancies), left-sided/"Virchow' node" (associated with intraabdominal malignancies).
Axillary: local infection (cat scratch disease), malignancy (breast).
Epitrochlear: palpable epitrochlear lymph nodes are always pathologic, differential diagnosis includes infection, lymphoma, sarcoidosis, secondary syphillis.
Inguinal: lower extremity infection, STIs, malignancy.

Generalized lymphadenopathy is commonly a feature of a systemic disease, including:

HIV: in acute, primary infection, typically non-tender.
Mycobacterial infection (tuberculous and non-tuberculous): called "scrofula" when it involves lymph nodes alone, typically the neck.
Infectious mononucleosis: classic triad of fever, lymphadenopathy, and pharyngitis.
SLE: more frequently noted in acute presentation or exacerbation of disease.
Medications: often associated with "serum sickness" (fever, arthralgias, rash, generalized lymphadenopathy), e.g. allopurinol, atenolol, antiepileptics, hydralazine.

Uncommon causes include: Castleman's disease, Kikuchi's disease, Kawasaki disease, amyloidosis.

A lymph node biopsy: 
- can be considered if an abnormal node has not resolved after four weeks.
- should be performed immediately in patients with other findings suggesting malignancy (fever, chills, night sweats, unintentional weight loss).
- open lymph node biopsy is preferred, if feasible.

Check out this NEJM Images in Clinical Medicine for a less than subtle presentation of axillary lymphadenopathy: http://www.nejm.org/doi/full/10.1056/NEJMicm071065.

Overdose!

I thought I'd take the opportunity to review one of the most common toxidromes we encounter in the world of Internal Medicine, the anticholinergic toxidrome.

Common anticholinergic medications include:

- antihistamines (e.g. diphenhydramine/Benadryl)
- antiemetics (e.g. dimenhydramine/Gravol)
- tricyclic antidepressants (e.g. amitriptyline, nortriptyline)
- scopolamine
- "contaminated" recreational drugs (e.g. heroin cut with scopolamine)
- atropine
- neuroleptics (e.g. quetiapine/Seroquel, clozapine, olanzapine/Zyprexa)
- antiparkinson medications (e.g. benztropine)

Anticholinergic drugs competitively inhibit binding of acetycholine to muscarinic cholinergic receptors found in smooth muscle (GI, bronchial, cardiac), secretory glands (salivary, sweat), ciliary body of eye, and the CNS.

Knowing this makes for remember this classic description of anticholinergic toxicity easy as pie:

"Red as a beet" - cutaneous vasodilation
"Dry as a bone" - dry skin
"Hot as a hare" - interference with sweat production interupts thermoregulation
"Blind as a bat" (nonreactive mydriasis) - pupillary dilation and ineffective accomodation = blurry vision
"Mad as a hatter" (delirium, hallucinations) - CNS symptoms of muscarinic blockade, which to the extreme, may result in seizure or coma
"Full as a flask" (urinary retention) - relaxation of detrusor muscle and constriction of urethral sphincter

The fundamental principles of management include:
- Call the Poison Control Centre.
- Stabilize the patient's ABCs.
- Supportive care and cardiorespiratory monitoring.
- Sodium bicarbonate in the setting of QT interval prolongation.
- Treatment of seizures and/or aggitation with benzodiazepines (e.g. lorazepam); do NOT use antipsychotic medications, as these may further prolong an already prolonged QT interval.
- Consideration of physostigmine, an antidote that is an acetylcholinesterase inhibitor that binds reversibly to inhibit acetylcholinesterase in both the peripheral and central nervous system. It's usage is controversial, and no studies have demonstrated its efficacy or safety to date.

- Consideration of activated charcoal depending on the timing of the ingestion, and the patient's level of consciousness.

Rapid Fire Morning Report

Since we had the fortune of hearing about three such fascinating cases this morning, I thought I would take the opportunity to briefly review each of these diagnoses in turn:

1) Polymyalgia Rheumatica (PMR)

- It is a disease of adults. Occurs almost exclusively in those over the age of 50. The average age at diagnosis is 70.

- Presents with aching and morning stiffness greater than 30 minutes in the hip and shoulder girdles, neck, and torso.

- Does NOT typically present with muscle weakness.

- Associated with giant cell arteritis (GCA)/temporal arteritis. PMR occurs in about 50 percent of patients with GCA, while approximately 15 to 30 percent of patients with PMR eventually develop GCA. 

- Diagnostic criteria includes an ESR>40 mm/h, although we typically see ESR in excess of 100 mm/h.

- Prompt response of symptoms with 24 hours to low-dose glucocorticoids (e.g. prednisone 15 mg daily) is classically seen.

Follow the link below for a review article on "Polymyalgia Rheumatica and Giant Cell Arteritis" from NEJM (2002):

http://www.nejm.org/doi/pdf/10.1056/NEJMra011913

2) Massive Hemoptysis

- Always remember your ABCs! Stabilize the patient first. Do not hesitate to ask for help.

- The differential diagnosis includes: 

Bronchiectasis

Tuberculosis

Fungal infections (e.g. aspergillosis, histoplasmosis, blastomycosis)

Lung infection/abscess

Malignancy (especially bronchogenic carcinoma)

Autoimmune lung disease (e.g. pauciimmune vasculitidies, including granulomatosis with polyangiitis/Wegener's granulomatosis, microscopic polyangiitis; Goodpasture's syndrome; SLE)

Pulmonary AVM (such as in hereditary hemorrhagic telangiectasia)

Mitral stenosis

PE

3) Optic Neuropathies

- Clinical features include vision loss, eye pain, RAPD in the affected eye, central scotoma. Remember, findings may not be apparent upon fundoscopy if the disease is retrobulbar.

- The differential diagnosis is broad, and includes:

Optic neuritis (inflammatory demyelinating process that can be idiopathic, or also associated with multiple sclerosis or neuromyelitis optica)

Ischemic optic neuropathy (common in older patients with vascular risk factors)

Infections (including neurosyphyllis, Lyme disease, West Nile virus)

Sarcoidosis 

Autoimmune disease (such as SLE, Sjogren's)

Paraneoplasic causes

Malignancy (such as mass effect)

Drugs and toxins (such as ethambutol)

- Prompt investigations (such as imaging, LP) and referral to the appropriate specialties (such as Ophthalmology, Neurology, Neurosurgery) is of utmost importance. 

Click on the link for review article on "Optic Neuritis" from NEJM (2006):

http://www.nejm.org/doi/pdf/10.1056/NEJMcp053247

Altered Mental Status in the Elderly

We learned in Morning Report today that medications are the top culprit when it comes to altered mental status in the elderly population.

The "Beers List" is a consensus list of potentially inappropriate medications for older persons published by the American Geriatrics Society. It was first published in 1991, and most recently updated in 2012.

Please click on the following link for a copy of the paper:

http://www.americangeriatrics.org/files/documents/beers/2012BeersCriteria_JAGS.pdf

These high risk medications include, but are not limited to drugs in the following broad categories (with examples that follow in brackets):

- Anticholinergics (antihistamines)

- Antiparkinson agents (benztropine)

- Antispasmodics (hyocyamine or Buscopan)

- Antithrombotics

- Antihypertensives (alpha and/or beta blockers)

- Antiarrythmic drugs (amiodarone)

- Antipsychotic drugs

- Barbituates

- Benzodiazepines

- Nonbenzodiazepine hypnotics (zopiclone)

- Insulin

- Hormone therapy (androgen, estrogen)

- Analgesic agents (opioids, NSAIDS)

- Skeletal muscle relaxants (cyclobenzaprine or Flexeril)

There was mention in passing about the purported influence of digitalis toxicity on Van Gogh's works of art later in life, which were characterized by halos and the colour yellow. Click on the link below for a fascinating paper published in JAMA in 1981 entitled, "Van Gogh's Vision: Digitalis Intoxication?":

http://jama.jamanetwork.com/data/Journals/JAMA/9092/jama_245_7_025.pdf

And, last, but certainly not least, in order to make your Morning Report experience greater than it is already (if that's even possible), please click the link below for Dr. Detsky's guide for "Taking the Stress out of Morning Report":

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2686763/pdf/11606_2009_Article_953.pdf

Diagnosis Aspergillosis

Today in Morning Report, we simplified the hocus pocus surrounding the diagnosis of aspergillosis.


The term "aspergillosis" refers to illness due to allergy, airway or lung invasion, cutaneous infection, or extrapulmonary dissemination caused by species of Aspergillus, which is ubiquitous in nature, and commonly transmitted via inhalation of fungal conidia. 


These conidia then face the innate defenses of alveolar phagocytes and the activation of cellular immunity, which are important in the healthy host for preventing fungal invasion in the surrounding tissue, and determining the extent and nature of the immune response. 


There are four common syndromes by which aspergillosis manifests:


1) Aspergilloma (fungal ball)
2) Allergic Bronchopulmonary Aspergillosis (hypersensitivity reaction of the airways that occurs when bronchi become colonized by Aspergillus species commonly seen in patients with a history of asthma)
3) Chronic Pulmonary Aspergillosis
4) Invasive Aspergillosis


To elaborate on the fourth, and most worrisome manifestation of asperillosis:


- Characterized by progression of the infection across tissue planes, eventually leading to vascular invasion with subsequent infarction and tissue necrosis.
- Classic risk factors include neutropenia, exogenous glucocorticoids, and impaired cellular immune function (e.g. AIDS, immunosuppresive medications).
- Signs and symptoms include fever, chest pain, shortness of breath, cough, and/or hemoptysis. 
- Remember, neutropenic patients frequently present with fever in the absence of localizing pulmonary symptoms.
- Pulmonary aspergillosis typically manifests as single or multiple nodules with or without cavitation, patchy or segmental consolidation, or peribronchial infiltrates, with or without tree-in-bud patterns. 
- In the presence of angioinvasive disease, Aspergillus species can hematogenously spread to the skin, brain, eyes, liver, and kidneys. This obviously portends a poor prognosis.
- To diagnosis invasive aspergillosis, consider initially sending serum biomarkers, such as galactomannan, and obtaining sputum for fungal staining and culture. 
- If the diagnosis is not made, more invasive options include bronchoscopy, image-guided needle biopsy, or video-assisted thorascopic surgery. 
- The recommended intial therapy is voriconazole, or lipophilic amphotericin B if there is a contraindication to voriconazole.