Wednesday, April 28, 2010


Today we discussed syphilis. Some points about this infection that has made a resurgence:

Treponema pallidum (spirochete), is spread through contact with infectious lesions or fluids. 50-75% of exposed sex partners get infected.

Clinical manifestations (NB- syphilis is the "great imitator"; these are the more common presentation, but keep a high index of suspicion in the right epidemiological setting)

-skin lesion (chancre) at site of innoculaion ~21d after exposure. Often goes unnoticed. Classically non-tender, indurated, non-purulent. Heals spontaneously.

-4-10 weeks after chancre appearance. Rash in 90%; pink, red, or purpule macules on flanks, shoulders, arms, chest, back. May become maculosquamous/papular and affect hands/soles in 50-80%.
-other signs/symptoms include sore throat, malaise, h/a, lymphadenopathy. Can cause neurologic, renal, ophthalmologic, GI, hepatic disease. Resolves without treatment, may recur.

Years later- aortitis, gumma (mass), iritis.

A word about neurosyphilis:
Neurosyphillis can occur early or late. May coexist with primary, secondary, or tertiary. May see meningitis, cranial nerve involvement, eye involvement, meningoencephalitis, meningovascular (presents as stroke). Late findings are rare; occur decades later: paresis, dementia with psychosis (rapidly progressive), tabes dorsalis (posterior column involvement, bowel, bladder dysfunction).

LP indicated in any of 1) neuro/ocular/otic symptoms/signs. 2) biochemical evidence of late latent syphilis (or unknown duration) in HIV pt. 3) active tertiary- gumma, aortitis, iritis. 4) treatment failure for non-neurosyphilis

Lab testing
The lab testing for syphilis is very complex and confusing. Here are some general comments; click
here for detailed interpretation from the Ontario Public Health Lab website

NB- RPR is essentially synonymous with VDRL
1) EIA (enzyme immunoassay), TPPA, FTA-Abs. All of these are durable antibody tests that are very sensitive, and remain positive for life. If negative, syphilis is usually ruled out. If positive, need confirmatory testing (there are false positives)
2) RPR- This is also an antibody test, but more suggestive of active infection. If postive, this confirms diagnosis. If negative, it can mean 1 of several things: a) very early primary- retest in 2 weeks. b) successful treatment. c) late latent d) biologic false positive

NB- latent =seroreactivity without clinical manifestations. Early is infected within previous year by documented conversion. Late is over 1 year from primary infection

Primary, secondary, early latent: Pen G 2.4M U IM single dose
Late latent, unknown, tertiary: Pen G 2.4M U IM qweekly x 3.
Neurosyphilis, ocular, otic: Pen G IV 18-24M units/d divided q4h for 10-14d.

NB- need repeat serology to confirm/document treatment success- see paper below for details

Primary should have RPR negative at 1 year. Secondary at 2 years. Tertiary at 5 years.


Click here for a JAMA review of syphilis that most of this post is based on
Click here for the Ontario Public Health Lab algorithm for interpreting the MANY permutations and combinations of lab results

Wednesday, April 21, 2010

Myelopathy causes

Today we discussed myelopathy (i.e. spinal cord pathology)

Features to suggest myelopathy:
-bilateral motor and sensory signs or symptoms not involving the head
-weakness, spasticity, hyperreflexia (although may see hyporeflexia acutely)
-sensory findings with a descrete level
-bowel and bladder involvement

Causes of myelopathy:

1) Compression- herniated disc, tumor (extramedullary or intra-medullary) most common. Epidural abscess (often st. aureus). Also consider in conditions with c-spine instability like Down's and rheumatoid arthrititis

2) Inflammatory- MS; typically incomplete. SLE- usually incomplete, within a vascular territory (i.e. transverse myelitis), CNS vasculitis

3) Metabolic- subacute combined degeneration (i.e. dorsal column and corticospinal tract)- ddx is B12 deficiency and tabes dorsalis (syphilis)

4) Infectious- cord itself: syphilis, HIV, HTLV (esp in Caribbean), VZV. Surrounding structures causing compression: epidural abscess, vertebral osteomyelitis (bacterial, mycobacterial or fungal)

5) Vascular- cord infarction- rare (can be seen in aortic dissection or hypercoagulable state), AVM- very rare.

6) Genetic- Devic's (optic neuritis, myelopathy only- probably variant of MS)

Click here for a NEJM review paper by UHN physicians on cervical radiculopathy and myelopathy

Thursday, April 15, 2010

Dyspnea in a patient with cancer

The general approach to the patient with a malignancy who presents with dyspnea is similar to that in a patient without a malignancy, but some considerations are more prominent in this situation. Some issues to think about:

-post-obstructive pneumonia
-opportunistics: PCP, especially if on prednisone 20mg for over 2 months (or equivalent).
-nosocomial pneumonia
-fungal esp. if neutropenia.
-TB reactivation
-tachypnea as compensation for lactic acidosis in sepsis

-pulmonary embolism
-lymphangitic carcinomatosis
-tumor emboli syndrome (seen in lung, prostate, breast- micromets plugging pulmonary capillaries. PFTs may show diffusion abn).
-secondary pulmonary HTN

-endobronchial lesion
-COPD- esp smoker with lung ca,

-phrenic nerve involvement
-steroid myopathy

Parenchymal/interstitial (in addition to infectious items above):
-drug effect
-radiation effect

-pleural effusion
-pleural involvement of malignancy itself

-pumonary edema seconary to cardiomyopathy- chemotherapy toxicity (esp. anthracyclines) -pericardial effusion


Wednesday, April 14, 2010

CLL and its complications

Today we discussed CLL and some issues related to hyperleukocytosis

Chronic lymphocytic leukemia:
Briefly, the most common leukemia; commonly an indolent condition for up to decades, but a subset transform to another lymphoproleferative disorder (e.g. lymphoma) or AML.

Most commonly picked up as incidental finding of lymphocytosis >5000, splenomegaly, lymphadenopathy, smudge cells on blood film (shown above). Sometimes B symptoms. Is diagnosed by flow cytometry showing monoclonal B markers (bone marrow bx not always needed).

Complications of CLL:
1) Immunodeficiency as outlined below
2) Autoimmune hemolytic anemia

3) Red cell aplasia
4) Transformation as above

Immunodeficiency in CLL:
This is B-cell disorder, so humoral immunodeficiency.
This type of immunocompromise is seen in congenital hypogammaglobulinemia (common variable immunodeficiency), B cell disorders (inc. myeloma, Waldenstrom's, CLL). Causes susceptibility to encapsulated (s. pneumo, H. flu, meningococcus), as well as Giardia, and C. Diff.
IVIG may be indicated in severe infection or immunoglobulin level <0.5 lower limit of normal (see link below). These pts get recurrent sinopulmonary infections because they do not produce secretory IgA.

In patients with CLL who are treated, there can be severe immunodeficiency of other types:
1) Neutropenia from myelotoxic chemotherapy (e.g. chlorambucil)
2) Cell-mediated- from fludarabine (t-cell inhibitor sometimes used); susceptible to PCP, listeriosis, fungal, etc.

This makes a severe, combined immunodeficiency state (like congenital SCID)

More important if cells are sticky (esp blasts). Causes leaky endothelium. May cause noncardiogenic pulm edema, retinal hemorrhage, encephalopathy, stroke, renal failure, MI, heart failure.
Not all leukocytosis is the same; risk of hyperviscosity/leukostasis depends on how 'sticky' the involved cell is:
Highest risk is blasts in AML.
If AML, very high risk is WBC over 100
CML- WBC in 200's or blast conversion
CLL-very rare to have leukostasis complications regardless of level.

If acute complications of leukostasis, hematologists/oncologists will sometimes use hydroxyurea, cyclophosphamide, or even leukopheresis


here for the abstract of the RCT showing benefit of IVIG in pts with CLL with hypogammaglobulinemia and recurrent infections

Tuesday, April 13, 2010


Today we discussed amyloidosis. A few points about this rare, but serious and often multi-systemic condition

Amyloidosis refers to deposition of an altered conformation of a protein into amyloid fibrils that deposit systemically, giving various clinical manifestations depending on which system(s) are involved. One way of classifying amyloidosis is by which protein is forming the amyloid:

AL: amyloid is formed by immunoglobulin light chains or fragment produced by clone of plasma cells. Plasma cell burden is usually low (~5-10%). 10% have multiple myeloma.

AA: amyloid is formed by 'amyloid A protein', an acute phase reactant. This form of amyloid is associated with longstanding inflammatory conditions. Classic ones are RA, IBD, FMF

Familial amyloidosis: proteins forming amyloid are transthyreitin, apolipoproteins, lysozyme, etc.

"Senile systemic": transthyreitin amyloid, predominantly in heart.

Others: Alzheimer's disease is associated with amyloid fibril deposition in the brain; the protein is a-beta 40 and 42. It is unclear whether amyloid fibrils are causitive.

Possible clinical manifestations:
1) Neurological- CNS- intracranial hemorrhage (amyloid angiopathy), dementia. PNS- peripheral neuropathy (glove-stocking), compressive neuropathy (e.g. carpal tunnel)

2) Cardiac- infiltrative cardiomyopathy- systolic or diastolic dysfunction, arrhyhtmia (heart blocks or ventricular arrhythmias). Cardiac involvement carries the worst prognosis. Rare in AA amyloidosis.

3) Renal- may cause nephrotic syndrome or asynptomatic proteinuria

4) GI- hepatomegaly with or without splenomegaly, GI bleeding, dysphagia

5) MSK- macroglossia as shown above, arthritis

6) Dermatologic- ecchymoses from friable vessels,
periorbital purpura, fat infiltration is common but asymptomatic- may allow for diagnosis

7) Hematologic- Factor X deficiency leading to bleeding diathesis, petechiae (F10 binds to amyloid fibrils)

8) Pulmonary- less common; persistent pleural effusions

Diagnosis is made by organ system involved. Abdominal fat pad bx (stained for Congo red) is positive in 80% of AL, 65% of AA.

Treatment depends on type.
In AA, directed at underlying inflammatory disorder
In AL, directed at underlying plasma cell disorder

For cardiac amyloidosis, implanted defibrillator is sometimes indicated. High dose systemic chemotherapy (e.g. melphalan) is sometimes used.

Click here for a NEJM case discussion of amyloidosis- nicely summarizes the issues

Friday, April 9, 2010


Today we had some discussion about hypercalcemia. Some points:

GI- anorexia, n/v, abdo pain, constipation.
Renal: stones, polyuria.
Neuro: weakness.
Cardiac: arrhythmias

Useful first division is by PTH level
1) High PTH- expect high Ca, low PO4.
-primary/secondary/teriary hyperparathydoidism, parathyroid hyperplasia
-familial hypercalcemic hypocalciuria

2) Low PTH
-PTHrP from malignancy (esp. SCC- lung, H+N)
-hypervitaminosis D- expect high Ca and high PO4- from granulomatous disease, lymphoma)C) -OAF = IL6 (local paracrine effect; in breast and hematological cancers)
-Direct effect of mets (e.g. prostate, lung, etc.)
-Medications- HCTZ, Ca, vit. D
-Milk alkali syndrome

As inpatient, #1 cause = malignancy
As outpatient, #1 cause = primary hyperparathyrodisim

Consider bisphosphonate if malignancy-related or v. high (but takes days to work)
Calcitonin by nasal spray or subq.
If hyper D from sarcoid or lymphoma, possible steroids.
Avoid lasix since most patients are profoundly volume depleted.
Last resort is dialysis

Milk-Alkali syndrome
Triad of hypercalcemia, met alk, renal failure assoc with ingestion of large amts calcium, alkali
Once common because of PUD treatement. Making resurgence b/c of calcium for osteoporosis, and prevention of secondary hyperparathyroidism in CKD
Sequence: hypercalcemia, dec GFR, met alkalosis ("contraction"). Hypercalcemia per se stimulates renal bicarb fomation.
Pts on vit D, thiazides, vol contraction, CKD are at higher risk

Some links:
Click here for NEJM clinical problem solving case on hypercalcemia
Click here for a review of calcium disorders in renal disease

Tuesday, April 6, 2010

Atrial fibrillation- acute management

Today we discussed issues related to acute management of atrial fibrillation. A few points:

After establishing that the patient's airway and breathing are stable, the first decision point is
whether the patient needs emergent synched cardioversion.
Indications as per ACLS algorithm:
1) Hemodynamic instability, 2) Shock (i.e. hypoperfusion), 3) Pulmonary edema, 4) Ischemia
HOWEVER, remember that clinical judgement is absolutely required; this is not risk-free, and many patients have mild pulmonary edema and borderline hypotension with rapid A-fib and do not all need to be cardioverted.

If emergent cardioversion is indicated, important steps include
1) Consider pre-treatment with antiarrhythmic (e.g. amiodarone); increases the likelihood of success
2) Analgesia and sedation, requiring the capability to deal with the airway; usually requires the help of anesthesia unless in the ICU
3) Application of the pads- "sandwich"- front and back is more successful than sternal and lateral
4) Synchronized cardioversion with 50-100J
5) Anticoagulation for at least 4 weeks post-cardioversion

Watch for
-bradycardia (pts usually have some AV nodal agent "on board" prior that was dosed to their a-fib; if now in sinus, may be bradycardic
-embolic complications

If elective cardioversion (i.e. not emergent), considerations include
1) Embolic risk
If a-fib is present more than 48h (usually difficult to determine) or the patient was not therapeutically anticoagulated for 2 weeks or more prior, there is a significant (but difficult to quantify) risk of systemic embolization with restoration of sinus rhythm. A trans-esophageal echo that shows no evidence of a thrombus makes the risk very low, and is done in situations where emergent cardioversion is not necessary, and the above criteria are not met.
NB- the risk of embolization exists for pharmacologic cardioversion as well, although may be lower than electrical (think about this when using antiarrhythmics like amiodarone)

2) Procedural risk (sedation, analgesia, arrhythmia, etc)

If cardioversion is not indicated, rate control is the next management choice. Options include:
1) Beta-blockers (e.g. metoprolol 2.5-5mg IV over 5-10min)
2) Non-DHP calcium channel blockers (e.g. diltiazem 15-20mg IV over 5-10 min)
3) Digoxin (e.g. 0.25mg IV load)
4) Amiodarone (but note cardioversion risk as outlined above)

There is little evidence to guide us in the acute setting (but lots of evidence in the chronic setting- e.g. AFFIRM)
Reasons to use beta blockers or CCB: Little toxicity, easy to titrate, often the patient has another indication (for B-blocker), rate control is more reliable than digoxin (see below)
Reasons to think twice before using a beta blocker or CCB: LV dysfunction (esp. CCB), pulmonary edema (both), reactive airways (B-blocker), conduction system disease (both)

Reasons to consider digoxin: Is an inotrope, and carries lower risk of hypotension or worsening pulmonary edema. Works particularly well in decompensated aortic stenosis since allows more filling time without affecting contractility
Reasons to think twice before using digoxin: Patient can override it with sympathetic stimulation (that is usually present) since it does not block this, risk of toxicity if levels supratherapeutic, more difficult to use, debatable long-term benefit (definitely no mortality benefit from DIG trial)

Anticoagulation may be initiated in the ED if clearly indicated, but may also wait until the patient is more stable, and risks/benefits (which usually favour anticoagulation) have been discussed.

Monday, April 5, 2010


Today we discussed an approach to lymphadenopathy. A few points:

Normally, nodes are smaller than 1cm, mobile, soft, nontender. May be larger in young pts. Palpable inguinal nodes or submandibular can be normal.

Generally subdivide into local (1 grp) vs. general.

Infection- EBV, CMV, toxo, TB (lymphadenitis if intact, "scrofula" if burst), cat scratch (bartonella), staph, strep infections
Malignancy- lymphoma, metastatic squamous ca (esp. posterior)
Other- Kikuchi's disease (cervical LA and fever in young female)

Malignancy- 24-50% of pts over 40 with supraclavicular adenopathy. R-sided is associated with thoracic (lung, mediastinum, esophagus). L-sided is assocaited with abdominal (virchow's node; especially gastric ca)

Infection- cat scratch, trauma
Malig- BrCa, mets

Infection- local trauma, secondary syphilis, tularemia
Malig- lymphoma
Other- sarcoid

Infection- lower ext/gu inf
malig- lymphoma


Malignancy- lymphoproliferative, leukemia, mets
Infection- HIV (acute seroconv), EBV (fever, lymphad, pharyngitis; post>ant), typhoid, CMV, histoplasmosis, mycobacterial infection (TB, MAI), others...
Serum sickness (=tetrad of fever, arthralgias, rash, LA). Drugs often cause: allopurinol, phenytoin, penicillin, hydralazine, carbamazepine, gold, etc)
Others: Sarcoidosis, Castleman's disease


H: infection/malig, time course, pain, etc, exposures (bites, uncooked meat, sexual hx, drugs)
P: location, size, tenderness, consistency, mobility, spleen, look for primary

Inv: in generalized, CBC, lytes, ca, LDH, uric acid, PBF, CXR, HIV, ANA, VDRL. Localized: if no suggestion of malig, may observe for 3-4 wks. If persistent, biopsy.


Click here for an excellent article on lymphadenopathy from American Family Physician