Horses and Zebras

Decompensated cirrhosis

2011-11-17T15:00:00.001-05:00

Today in morning report was a case of decompensated liver failure. For more on this topic, see a prior post here.

We also discussed about the management of spontaneous bacterial peritonitis. See a nice review of cirrhosis and ascites in NEJM here.

Hemolytic anemia

2011-11-14T08:59:00.001-05:00

Today's morning report was an interesting case of hemolytic anemia: check out a prior post on the topic here, with a few links at the bottom to review articles.

Non-resolving pneumonia

2011-09-19T11:50:00.001-04:00

Today in morning report was a great case of non-resolving pneumonia. For more, see a prior post here.

See the IDSA guidelines here, and skip to recommendation #38 to read about the work-up of a pneumonia that fails to respond to therapy.

Levamisole toxicity

2011-09-16T14:44:00.001-04:00

Today's amuse-bouche was a case of a levamisole-related cutaneous vasculitis syndrome. A few quick points:

Recent trend in cocaine being adulterated by levamisole,

An anti-helminth agent in the 1960s first identified as a cocaine adulterant in the USA in 2003
Now found in majority of cocaine seized at US borders, common in Canada also
Proposed that levamisole potentiates the psychotropic effects of cocaine, and that producers intentionally add it during the cocaine manufacturing process

Associated with a cutaneous vasculitic syndrome

Purpuric lesions and/or cutaneous necrosis
Involves the ears in ~50% of reported cases
Lab associations:neutropenia + pANCA and + cANCA

Hyponatremia

2011-09-16T14:19:00.002-04:00

Today in MR we had a case of hyponatremia. See a prior post here with links to a few good review papers.

Neurologic presentations of HIV infection

2011-09-16T13:47:00.004-04:00

Last week in morning report was an excellent case of ptosis and diplopia in a patient with HIV infection. This is a big topic, but a few points about neurologic involvement in HIV:

1) Acute seroconversion reactions:

-Although rare, acute neurologic presentations at the time of HIV infection do occur, including aseptic meningitis, Bell's palsy, and inflammatory neuropathies. CSF testing for HIV may be positive in these patients.

2) Opportunistic infections: A variety of OI can manifest with neurologic presentations:

- Progressive Multifocal Leukoencephalopathy (PML): a demylenating CNS disease caused by JC virus, mostly in patients with CD4 counts less than 100. Usual presentation is a subacute deterioration in mental status with possible focal neurologic signs/symptoms, with fever and headache not usually present.

- Cytomegalovirus (CMV): although 60% of the population have evidence of exposure to CMV, patients with HIV and CD4 counts less than 50 and other immunocompromised states are at risk of clinical disease from reactivation. CMV can infect and reactivate throughout almost the entire spectrum of the CNS and PNS- from the brain to peripheral nerves. For this reason, the neurologic presentation can be any combination of encephalitis, ventriculitis, myelitis, gangionitis and peripheral polyneuropathy.

- Cryptococcus neoformans: an encapsulated yeast found throughout the world. It usually is cleared by the immune system, but in immunocompromised patients, including HIV patients with CD4 counts less than 100, it can remain in a latent state that can disseminate to organs, with the CNS being particularly common. The usual presentation is that of a subacute menigoencephalitis, with fever, headache and malaise. It can also present with complications of increased ICP, including seizure.

- Toxoplasma gondii: intracellular protazoan with high seroprevalence in the population, with most primary infections being asymptomatic or flu-like. Reactivation can occur in immuno compromised hosts, usually in patients with HIV and CD4 counts less than 200. Usually casues an encephalitis and presents with fever, headache, and focal neurologic signs or seizures.

3) Neoplasms: primary CNS lymphoma is usually a high grade B-cell lymphoma and almost always related to Epsetin -Barr Virus (EBV). It usually presents in HIV patients with CD4 counts less than 100 with headache, changed mental status, focal neurologic signs or seizures.

4) Immune reconstitution inflammatory syndromes (IRIS): a group of syndromes casued by the inflammation generated by a reconstituted immune system in the first 4-8 weeks after starting on combined antiretroviral therapy. Usually seen in HIV patients with CD4 counts less than 50 being started on therapy for the first time in the setting of an opportunistic infection. Typically presents as a paradoxical worsening of course in patients with HIV encephalitis, cryptococcal meningitis toxoplamsamosis encephalitis and PML.

5) HIV associated peripheral neuropathies: many peripheral neuropathic syndromes have been reported in the context of HIV infection, with the most common being a distal peripheral sensory neuropathy. Modifiable risk factors include use of neurotoxic medications, diabetes and alcohol abuse.

6) HIV-associated vacuolar myelopathy: an entity of unclear pathophysiology affecting the spinal cord neurons, more often the dorsal column. It presents with often initial errectile dysfunction and hyper-refexia, but progresses to asymmetric spastic leg weakness, dorsal column vibration/position sensory loss, and ataxic gait.

7) HIV Associated neurocognitive disorders (HAND): this is a group of neurocognitive changes thought to be a spectrum of a subcortical process that primarily affects attention/concentration, psychomotor speed, memory/learning, information processing, and executive function, while language and visuospatial abilities are often relatively unaffected.

More on diagnosis of these conditions from a review article here.

Elevated liver enzymes

2011-09-13T13:47:00.000-04:00

Today in MR was a case of elevated liver enzymes. See here for a previous post on the topic.

Weekly Amuse-Bouche Links

2011-09-09T09:56:00.000-04:00

For more on this week's amuse-bouche topics see the following links:

- Pendred's syndrome here
- Dermatologic findings in dermatomyositis here
- Familial Adenomatous Polyposis here
- Limb lead reversal here

Hyperkalemia and Renal Tubular Acidosis

2011-09-08T13:43:00.002-04:00

We had a great case of hyperkalemia in MR, likely due to an underlying type IV renal tubular acidosis in the setting of diabetes.

A prior post on hyperkalemia here, with a link at the bottom to a recent CMAJ article on management.

A prior post on renal tubular acidosis here, with a good review from the Archives here.

Hypercalcemia

2011-09-01T09:32:00.001-04:00

Morning report today was a case of hypercalcemia. More from a prior post here.

Medullary Thyroid Cancer

2011-09-01T09:02:00.003-04:00

Yesterday in morning report we had a really interesting case of medullary thyroid cancer presenting with chronic diarrhea and complicated by heart failure, likely secondary to amyloidosis.

A little more about medullary thyroid cancer (MTC):

- MTC can be either sporadic or inherited. Inherited forms involve mutations to the RET proto-oncogene and can be either be alone or as part of one of the Multiple Endocrine Neoplasia syndromes- MEN 2A or MEN 2B.

- MEN 2A is characterized by MTC with hyperparathyroidism and/or pheochromocytoma

- MEN 2B is characterized by MTC with typical phenotyic features such as marfanoid body habitus or mucosal neuromas with or without pheochromocytoma.

- Most patients present with a thyroid mass, but some present with symptoms of local spread such as dysphagia, dyspnea, or hoarseness. Roughly 10% will present with systemic symptoms related to the production of neuroendocrine mediators such as calcitonin, resulting in bone pain, flushing, and/or diarrhea.

- Those that present with systemic symptoms usually have metastatic disease.

- More in a review from Cancer here

We also found out through our group searching excercise that MTC is associated with secondary amyloidosis casued by calcitonin.

-A good related article sent out by Dr. Abrams here.

- More on amyloidosis from a prior post here.

Takotsubo cardiomyopathy

2011-08-10T15:45:00.002-04:00

The amuse-bouche today was a case of Takotsubo cardiomyopathy. A few points:
•It is also known as :Stress-induced cardiomyopathy, apical ballooning syndrome, or broken heart syndrome
•Characterize d by transient systolic dysfunction of the apical and/or mid segments of the left ventricle
–mimics myocardial infarction with ST segment changes
–absence of obstructive coronary artery disease
•Typically presets w. RSCP, but occassionaly with new onset dyspnea
–Women >> Men
–Often at time of intense physical or emiotional stress
•Pathogenesis not well understood
–? Catecholamine surge
–? Vasospasm

See a nice brief article in CMAJ here.

Acute Cardiac Tamponade

2011-08-10T11:14:00.004-04:00

Today's morning report case was of a patient with cancer presenting with sudden onset dyspnea and a new pericardial effusion. We had a great discussion about cardiac tamponade. A few points:
Cardiac tamponade is a clinical syndrome with a few defining characteristics:
-hemodynamic instability (hypotension, tachycardia)
-dyspnea
-pulsus paradoxus >10 mmHg
-jugular venous distention
- reduced heart sounds

The primary physiologic abnormality is compression of all cardiac chambers as a result of increasing intrapericardial pressure, which is mostly determined by the rapidity of fluid accumulation, rather than the absolute size of an effusion.

The diagnostic modality of choice is doppler echocardiography. In the presence of an effusion, some echocardiographic signs of tamponade:
- Early diastolic collapse of the right ventricle
- Late diastolic collapse of the right atrial free wall

Less specific than RV collapse unless lasting for >30% of cardiac cycle

-Left atrial collapse

Only in 25% of cases, but is highly specific

-Accentuated respiratory variation in peak mitral and tricuspid inflow velocities

-Reduction/absence of the normal decrease in inferior vena cava diameter during inspiration

See here for a good NEJM review
See here for the JAMA acticle "Does This Patient With a Pericardial Effusion Have Cardiac Tamponade?"

Auricular cartilage calcification

2011-08-09T11:32:00.001-04:00

The amuse-bouche today was auricular cartilage calcification in adrenal insufficiency taken from the NEJM images in medicine series.

Auricular cartilage calcification and even true ossification of the auricular cartilages have been described in association with:
–mechanical tissue injury
–exposure to cold
–inflammatory conditions
–endocrinopathies including adrenal isufficiency

See more from NEJM here.

Hemoptysis

2011-08-09T11:26:00.001-04:00

Morning report today was a great case of hemoptysis. See here for a prior post with links to a few good review articles.

Digitalis Effect

2011-08-08T09:43:00.004-04:00

Today our amuse-bouche was an ECG with typical changes from digoxin.
The classic digitalis effect has 4 typical findings on ECG:
1.T-wave changes

Virtually any: flattening, inversion, other abnormal waveforms such as peaking of the terminal portion (seen in about 10% of patients)

2.QT-interval shortening

3.Sagging or “scooped” ST-segment with concomitant ST-segment depression

More pronounced in leads with tall R waves (e.g. lateral leads)

4.Increase in the U-wave amplitude

It is important to remember that these do not correlate with toxicity as they can be seen at levels well within normal therapeutic range.

For a good review on this and the other important arrythmias assiociated with digoxin toxixicy, see here.

Systolic heart failure

2011-08-08T09:35:00.002-04:00

Today in morning report we had a case of new grade 4 systolic heart failure. See here for a prior post on diagnosis. We talked briefly at the end about device therapies, see here for a prior post on the topic, with links to some of the major trials.

von Recklinghausen disease

2011-08-04T14:33:00.002-04:00

Today the amuse-bouche was a case of von Recklinghausen disease, better known as neurofibromatosis type 1.

A few points about NF-1:

•It is a neurocutaneous syndrome resulting from a mutation in NF1 gene
–Autosomal dominant inheritance

–1/2 are familial; 1/2 new mutations
–New mutations primarily in paternal chromosomes
–Complete penetrance but variable expression

•At least 2 of the following features needed to make the diagnosis:
–6 or more café-au-lait macules
–2 or more neurofibromas of any type or one plexiform neurofibroma
–Freckling in the axillary or inguinal regions
–Optic glioma
–2 or more Lisch nodules (iris hamartomas)
–A distinctive bony lesion such as sphenoid dysplasia or thinning of the long bone cortex

–A first-degree relative (parent, sibling, or offspring) with NF1 based upon the above criteria

See here for a good review paper in the Lancet

Palliative feeding

2011-08-04T14:25:00.001-04:00

Today in morning report we talked about a few palliative issues, but the issue of feeding at the end of life came up. See here for a prior post on that contains a link to a good review article on the topic of nutrition and hydration at the end of life.

Vertigo

2011-08-03T12:46:00.002-04:00

Morning Report today was a case of vertigo, likely Benign Paroxysmal Positional Vertigo.

A prior post on differentiating the central and peripheral casues of vertigo here. See the bootom for more info on the Eply manuvers.

Infective endocarditis

2011-07-19T09:54:00.001-04:00

Morning report today was a case of presumed endocarditis in a VERY susceptible host. See a prior post here with a link at the bottom to the AHA 2008 update.

ECG limb-lead reversal

2011-07-19T09:15:00.005-04:00

Amuse-bouche yesterday was an ECG with limb-lead reversal. These are important to pick-up as some can mimic clinical scenarios.
Findings and clinical mimics of common limb-lead changes:
Right arm-Left arm:

Q wave I, aVL

Inverted p-wave I, II, II, aVF

Mimics: old lateral infarct, non-sinus atrial activity, dextrocardia (limb lead reversal will still have normal R-wave progression, dextrocardia will not)

Right arm- Left leg:

Q wave II, III, aVF

Inverted p-wave II, III, aVF

Mimics: old inferior infarct, non-sinus atrial activity

Right arm- Right leg:

Diffuse low voltage in limb leads (esp. lead II)

Mimics: any condition causing low voltage (limb-lead reversal will have normal precordial voltages)

Other limb lead reversals causing only minor changes with no real clinical mimics include Left arm- Left leg, Left arm- Right leg and leg-leg reversals. Precordial lead changes will interfere mostly with R-wave progression.

More from an old but concise review here.

Thrombotic thrombocytopenic purpura

2011-07-18T11:49:00.001-04:00

Morning report today was a great case of Thrombotic thrombocytopenic purpura (TTP). Please see here for a prior post on TTP, with links at the bottom to two good NEJM articles.

Mesothelioma

2011-07-15T14:47:00.004-04:00

AB today was on mesothelioma.

A few points on mesothelioma, with more in NEJM here:
–Malignancy of pleura (<90%) or peritoneum (>10%)
–~90% of patients will have a history of exposure to asbestos, with mean time from exposure to diagnosis ~35y (wide range)

-Usually presents with local pain, cough or dyspnea, and often assocaited with weight loss/fatigue

- Pleural biopsy (VATS or open) is usually definitive, but special stains are required to differentiate from adenocarcinoma

- Despite some advances, including agressive multi-modal therapy (chemo/radical surgery/radiation) and new active agents (pemetrexed), survival is poor with <10% surviving past 2 years.

- Although Canadian and US incidence is dropping (likely due to asbestos regulation), the overall worldwide incidence is increasing- for which Canada is playing no small part (see here).

Hyponatremia

2011-07-15T14:45:00.001-04:00

Morning Report today was on hyponatremia. See an old post here for a good overview. There are two good papers linked at the bottom of the post.

Familial Adenomatous Polyposis

2011-07-14T10:07:00.008-04:00

Amuse-bouche today was Familial Adenomatous Polyposis (FAP). This results from a mutation of the tumor suppressor gene APC on chromosome 5. A quick review of the features:

Develop hundreds of adenomatous colon polyps during adolescence

Have a 100% risk of developing colorectal cancer (mean age ~40y)

Associated with:

Upper-GI tumors: Fundic gland polyps, duodenal adenomas

Adenocarcinoma of the ampula of Vater

Extra-intestinal features: osteomas, desmoid/soft-tissue tumors, retinal pigment hypertrophy

Here is a link to a basic BMJ review on hereditary colorectal cancer.

Renal failure in multiple myeloma

2011-07-14T10:03:00.001-04:00

Today in morning report, a good case of renal failure in multiple myeloma. A good prior post on all of the causes here with a link at the bottom to a review article.

Dermatomyositis

2011-07-13T16:07:00.003-04:00

Amuse-bouche today was Gottron's papules and dermatomyositis. A prior post on dermatomyositis here.

A quick review of the associated dermatologic findings:

Gottron’s papules-80% of patients

Hyperkeratotic, erythematous, flat papules

Dorsum MCP and IP joints, less commonly wrists/elbows/knees

Heliotrope rash- <50% of patients

Periorbital violaceous/erythematous rash

One or both eyelids

May be accompanied by edema

Shawl sign

Macular erythema in V shape at nape of neck

Mechanic's hands

Rough and scaly with fissuring

Lateral and palmar areas of fingers

Nail changes

Periungal erythmea

Telangiectasias on the proximal nail fold

Renal failure and hyperkalemia

2011-07-13T09:07:00.002-04:00

In morning report today was a case of acute renal failure. A good prior post with a link at the bottom to a good NEJM article here.

We didn't get in to the management of hyperkalemia, but as Dr. Bunce said- you should know it by tomorrow, so here is a prior post with a good link to a review at the bottom.

Pendred's syndrome

2011-07-12T09:43:00.002-04:00

The amuse-bouche today was Pendred's syndrome. A link to a good article here.

Pendred's syndrome is an autosomal-recessive disorder of iodine organification caused by mutations in iodine transport protein pendrin.
It is characterized by the combination of congenital sensorineural hearing and goiter, and accounts for up to 10% of cases of hereditary deafness.
Patients have a positive perchlorate discharge test because they cannot provide substrate for the organification step in thyroid hormone synthesis.

Decompensated cirrhosis

2011-07-12T09:28:00.003-04:00

Morning report today was a case of fever and decompensated cirrhosis. A prior post on cirrhosis with a link to a good lancet article on management here.

A reminder of the Child-Pugh score above, with total points giving grades A (5-6 ) B (7-9) and C (10-15) and higher mortality with inreasing points/grade.

Seizures and alcohol withdrawl

2011-07-11T17:28:00.002-04:00

Morning report today was a case of seizure, more on seizure related topics here.

We also discussed alcohol withdrawl, which has a good blog post previously here.

Plasmacytoma and multiple myeloma

2011-07-11T09:26:00.002-04:00

Today's amuse-bouche was a plasmacytoma of the skull. More from NEJM here.

Related is a prior post on multiple myeloma here.

CLL and stem cell transplants

2011-07-07T11:04:00.014-04:00

Today in morning report, and interesting case of fever in CLL. Here is a link to a prior post on CLL and immunodeficiency; see the bottom of the post for a link to the role of IVIG: http://morningreporttgh.blogspot.com/2010/04/cll-and-its-complications.html
The other discussion was on stem cell transplants and graft versus host disease (GVHD). A few points:

1) Types of stem cell transplant:
Autologous: Patient's own mononuclear cells are harvested from bone marrow or (now more commonly) from peripheral blood prior to high-dose myeloablative chemotherapy/radiotherapy. The cells are then reinfused during the period of prolonged bone marrow failure that occurs after these treatments in order to help restore hematopoiesis. Classically this type of transplant was used in lymphoma, but there is an ever-expanding list of trials for other indications including solid tumors and plasma-cell dyscrasias.

Allogeneic: Stem cells are harvested from the bone marrow of healthy donors or newborn umbilical cord/placenta. The cells are infused to reconstitute the patient's hematopoeitic system, but also can have direct anti-leukemia activity, termed graft-versus-leukemia (GVL). Given that the cells are from a donor, there are a greater number of risks than in autologous transplant due to immune suppression and graft-versus-host-disease (below).

2) Graft versus host disease:
Lymphocytes from the donor may target normal host tissues and cause inflammation, with particular predilection for skin, gut, liver, and lungs. The acute form usually occurs before 100 days post-transplant and can present with a maculopapular or bullous rash, cholestasis potentially leading to hepatic failure, or secretory diarrhea. The chronic form more resembles other autoimmune disorders, presenting with arthritis, scleroderma-like skin changes, sicca syndrome, chronic hepatitis, and GI malabsorbtion.

The risk of GVHD is directly related to age and inversely related to the the degree of major histocompatibility antigen matching between donor and recipient. It remains the major complication of allogeneic transplant, affecting upwards of 40% of patients.

Brugada syndrome

2011-07-06T16:21:00.001-04:00

The answer to this morning's amuse-bouche was Brugada syndrome. More from an old blog post here: http://morningreporttgh.blogspot.com/2010/03/brugada-syndrome-and-arrhythmogenic-rv.html

Pericardial effusion

2011-07-06T14:00:00.000-04:00

Morning report today was on pericardial effusions.

Here is a prior post on the causes of pericarditis
http://morningreporttgh.blogspot.com/2009/04/shot-through-heart-and-your-to-blameyou.html.
When thinking of pericardial effusions, the causes are all the same, as well as the addition of hypothyroidism.

We talked only briefly about cardiac tamponade, but here is a link to the JAMA rational clinical exam paper 'Does this patient have cardiac tamponade'
http://jama.ama-assn.org/content/297/16/1810.abstract

Blogging is so 2010

2011-07-06T11:38:00.017-04:00

It's early July: the season of bad tan lines and new chief medical residents (in this case maybe both in one package...just you wait!)
I will be using the blog quite a bit this year, but I plan to use it a little differently than before in a few ways:

(1) I will try to post daily:

I want to spare your email inboxes, so I will post daily on this site, and you can check things out as you see fit for your own learning goals.

(2) I will not really be blogging:

The posts will usually be shorter, less like a true blog and more similar to twitter-style tweets, with links to papers or other resources (including prior blog posts from TGH, TWH, and MSH morning report blogs).

However, I will write longer posts on topics that haven't been covered before and can be reasonably covered in without too much text .

(3) I will also tweet:

For those of you who already have twitter or are interested in using it, I will tweet the same links as I blog @tghcmr (http://twitter.com/#!/search/tghcmr)

I am here to help you learn internal medicine this year, so if you find none of this works well for you, let me know, and I can always make changes.

Cheers,

Chris

Renal Tubular Acidosis and Fanconi Syndrome

2010-11-24T16:05:00.006-05:00

Today is my last post here on Horses and Zebras. Thanks for the good times. The banner will be picked up again by the next CMR come January.

This morning we discussed Fanconi Syndrome and touched briefly on Renal Tubular Acidosis (RTA).

Here are two links to review articles, one from the Journal of the American Society of Nephrology and one from the Archives of Internal Medicine.

Some points about RTA:

1) In the setting of an acidosis, the kidneys maintain acid/base homeostasis by increasing resorption of HCO3 and increasing H+ excretion. HCO3 resorption occurs predominantly in the proximal convoluted tubule (85-95%) with the remainder occurring in the distal convoluted tubule (10%). The secretion of H+ typically occurs in the DCT as ammonium.

2) In RTA, the kidney loses the ability to perform one of these functions and a non-anion gap (hyperchloremic) metabolic acidosis develops.

3) There are 3 types of RTA:
a) Type 1 (distal)
b) Type 2 (proximal)
c) Type 4 (hypoaldosteronism)

(Type 3 RTA is a mix between types 1 and 2 and is seen in a rare genetic disorder)

4) Type 1 (distal) RTA:
a) Results in decreased ammonium secretion in the DCT causing systemic acidosis (HCO3 less than 10).
b) Most common adult causes include: autoimmune diseases (Sjogren's, RA, SLE), hyperglobulinemia, meds (lithium, amphotericin B), hypercalciuria, liver disease and sickle cell disease.
c) Often presents with NAG metabolic acidosis, hypokalemia, hypercalciuria and an elevated urine pH (greater than 5.5).

5) Type 2 (proximal) RTA:
a) Can occur in isolation, but is most commonly seen in the setting of diffuse proximal tubular dysfunction (Fanconi syndrome - as discussed today).
b) The typical findings in Fanconi syndrome include: bicarbonaturia, glucosuria, phosphaturia, uricosuria, aminoaciduria and tubular range proteinuria.
c) Isolated Type 2 RTA presents with bicarbonaturia due to impairment in bicarbonate resorption in the PCT.
d) While the bulk of HCO3 resorption occurs in the proximal tubule, some occurs in the DCT. In Type II RTA, there is a threshold level of serum HCO3 above which filtered the HCO3 overwhelms the resorptive capacity of the DCT and HCO3 loss in the urine occurs. The borderline is generally around 16mmol/L.
e) The most common cause of Fanconi syndrome in adults is multiple myeloma (due to light chains), acetazolamide use and some chemotherapeutic agents.

6) Type 4 (hypoaldosteronism) RTA:
a) Characterized by a deficiency in, or tubular resistance to, the action of aldosterone.
b) Typically presents with hyperkalemia and a mild acidosis.
c) Most common causes include: diabetic nephropathy, CKD, primary adrenal pathologies and medications that inhibit the RAAS.

7) Differentiating Type I from Type II:
a) Consider calculating the urine anion gap (Na + K - Cl) on a random sample. The Cl- is an indirect marker for NH4+ secretion and thus a positive value supports a dx of Type I RTA (reduced H+ secretion) whereas a negative value may suggest Type II.
b) An increased urine osmole gap can also suggest Type I RTA.
c) The metabolic effects of Fanconi syndrome are only found in Type II RTA.
d) Urine pH will always be elevated in Type I RTA but will be variable and increase in Type II RTA if the serum HCO3 is raised beyond the reabsorbing threshold of the DCT (since the PCT is dysfunctional).

8) Management of Type I and II RTA typically involves reversing any causative conditions and providing oral alkali either as sodium bicarbonate or citrate. Type IV RTA is managed again by addressing the underlying etiology and providing aldosterone replacement in the form of fludrocortisone.

Streptococcus Anginosus Empyema

2010-11-23T09:45:00.003-05:00

Today we discussed a patient with a chronic empyema ultimately proven to be secondary to streptococcus anginosus.

Please follow the link to a recent review on parapneumonic effusions and empyema.

Some take-home points about S.anginosus and empyema:

1) The Streptococcus milleri group of organisms is made up of S. intermedius, S. anginosus and S. constellatus which are considered a sub-group of Viridans streptococci. These gram positive cocci are normal flora in the respiratory and GI tract and are known to cause abscesses in the brain, liver, lungs and oropharynx.

2) S.milleri are generally susceptible to beta-lactam antibiotics.

3) In general, lung abscesses related to S. milleri are thought to occur from aspiration of oropharyngeal contents.

4) Don't forget to look for the caramel of butterscotch smell associated with S. anginosus infections! Actually no, please don't.

5) The management includes prompt drainage of any collections and IV antibiotic therapy, usually with a beta-lactam. Duration of treatment is dependent on symptoms, but often a minimum 4 week duration of IV antibiotics is required. Specific antibiotic selection should be based on sensitivity testing.

6) Regarding complicated parapneumonic effusions and empyema:

a) These effusions typically occur in the context of pneumonia and represent a spectrum from an uncomplicated parapneumonic (UPPE) effusion to a complicated parapneumonic effusion (CPPE)to an empyema.

b) The signs and symptoms of an empyema are often indistinguishable from a typical pneumonia. All patients with pneumonia should be assessed for a pleural effusion.

c) In the setting of pneumonia with a pleural effusion, the phrase "never let the sun set on a parapneumonic effusion" is used to emphasize the importance of prompt investigation and drainage if necessary. Effusions greater than 10mm on the lateral decubitus CXR should be sampled.

d) More chronic presentations of an empyema can occur with less virulent organisms such as S.anginosus (as in our patient).

e) In general, a PPE should be drained if the pH of the fluid is less than 7.2, there is a positive gram stain/culture, a glucose less than 40-60 (U.S. units), an LDH greater than 1000 (U.S. units) or the effusion is greater than 50% of the volume of the hemi-thorax.

f) Drainage of a CPPE or empyema typically involves a large bore chest tube +/- adjunctive therapies such as fibrinolytics, VATS or decortication.

Antibiotics and Pneumonia

2010-11-22T11:31:00.005-05:00

Today we talked today about a patient with community acquired pneumonia (CAP) and the appropriate antibiotics and investigations for CAP.

Here's a link to the 2007 IDSA/ATS CAP Guidelines (scroll down to CAP). The BTS also released guidelines in 2009.

In brief:

1) While it seems obvious, an infiltrate on CXR (in the right clinical context) is required for the diagnosis of pneumonia.

2) Generally, all patients with pneumonia admitted to hospital should have blood and sputum cultures drawn.

3) In patients with severe pneumonia, urinary antigens for Legionella pneumophila and Streptococcus pneumoniae should be sent.

4) Options for outpatient treatment:
a) If previously healthy, can use a macrolide or doxycyline.
b) In patients with comorbidities or recent Abx use, give a respiratory FQ or a (beta- lactam + a macrolide).
c) Remember, if the presence of macrolide resistant S.pneumo is greater than 25% in your practice area, macrolides should be avoided.

5) Inpatient, non-ICU treatment:
a) (Respiratory FQ) or a (beta-lactam + a macrolide).

6) Inpatient, ICU treatment:
a) A beta-lactam plus either a macrolide or a FQ (better evidence for FQ over macrolide).
b) If concerned re: pseudomonas, give an anti-pseudomonal beta-lactam that has anti-pneumococcal activity (PipTazo, Cefepime, Imipenem or Meropenem) plus either (Cipro of Levo) or (an aminoglycoside + azithromycin) or (an aminoglycoside + an anti-pseudomonal FQ).
c) Add Vano or Linezolid if MRSA risk factors present.

7) The beta-lactam in the outpatient and in-patient not ICU treatment arms can be high dose amoxicillin/ampicillin.

Fever of Unknown Origin

2010-11-22T10:15:00.002-05:00

Last week Friday at Rheumatology Morning Report we discussed a patient with a fever of unknown origin (FUO).

This is a challenging Internal Medicine presentation with limited high quality evidence and a wide differential diagnosis.

A number of reviews have been published in recent years offering varied approaches to making a diagnosis. Take a look at our own Toronto approach published by Drs. Mourad, Detsky and Palda in the Archives of Internal Medicine. Two other reviews include one from AFP and another from Postgraduate Medicine.

A few points about FUO:

1) The classical definition of FUO is a temperature greater than 38.3C on multiple occasions over a period of 3 weeks with no diagnosis found after 1 week of inpatient investigations.

While this definition is likely outdated in the era of expanded outpatient management, the bottom line is that there must be a documented fever for a prolonged period of time. This is done in an attempt to exclude any transient viral infections. One modern definition suggests that the fever should persist for more than 3 weeks despite 3 outpatient visits and/or 3 days of in-hospital investigations to be considered an FUO.

The classic definition and approach to FUO typically excludes patients with HIV, immunosuppression or neutropenia.

2) The incidence of FUO has been estimated in one series to be less than 3% of admitted medical patients. The frequency of FUO continues to decline with the advent of increasingly sophisticated investigative modalities (cultures, serology, radiology).

3) The etiologies of FUO can be grouped into 5 categories: infection (16%), inflammation (22%), malignancy (7%), miscellaneous (4%) and undetermined (51%).

4) As always, the investigation should start with a focused history and physical examination. Remember to pay special attention to recent travel, medication use (including anti-pyretics), possible immunosuppression, the pattern of fever and any localizing symptoms.

5) A number of initial investigations have been suggested. One approach is to ensure the patient has a minimum set of investigations before proceeding down a FUO algorithm.

These might include:
i) CBC and differential
ii) Blood film
iii) 3 set of blood cultures (separated in space and time)
iv) Lytes, Cr, HCO3, LDH, liver enzymes and function tests
v) Urinalysis and culture
vi) CXR

From here if a source of fever has not be elucidated, further minimum investigations might include:

i) ANA and RF
ii) HIV testing
iii) CMV IgM or heterophile testing (if suggested clinically)
iv) Hepatitis serologies (if liver enzymes elevated)
v) ESR or CRP
vi) One article suggests Q-fever serology (if suspected clinically)
vii) One article suggests an SPEP (if MM suspected clinically)
viii) CK
ix) A TB skin test has been suggested in some articles

If this second set of investigations fails to yield of a diagnosis, all non-essential medications should be discontinued had imaging should be pursued:

i) CT chest/abdomen - assess for lymphadenopathy or collections
ii) One article suggests a technetium scan in addition to the above CTs.

Following these investigations, if no etiology is apparent, then further testing should increasingly be focused towards the most likely diagnosis. This may include:

i) Echocardiography - assess for valvular vegetations
ii) Leg dopplers - assess for a silent DVT
iii) Temporal artery biopsy - in patients greater than 50 years old to assess for TA
iv) Liver biopsy - if clinically deteriorating
v) Bone marrow biopsy - if abnormalities are seen in the CBC and blood film

6) Therapeutic Trials
In general, therapeutic trials of antibiotics or corticosteroids are discouraged unless a thorough hunt for an etiology has been completed. This is out of concern of exacerbating an undiagnosed infection (steroids), sterilizing cultures (antibiotics) or suppressing a fever while the etiology remains.

7) Prognosis
If no diagnosis is found after an extensive evaluation, the prognosis of these patients is generally good.

Pulmonary Embolism and IVC Filters

2010-11-17T22:00:00.006-05:00

Today we discussed the diagnosis and management of a pulmonary embolism (PE) and the role of Inferior Vena Cava (IVC) filters.

The role of IVC filters in PE remains controversial and there is significant variability in clinical practice. Guidelines from the ACCP exist, however recent evidence suggests that up 25% of IVC filter insertions are done for indications that do not follow the guidelines.

As mentioned today, IVC filters can be associated with catastrophic consequences in the event of filter fracture and embolism as discussed in this 2010 study.

Here's an excellent recent review on acute PE from the NEJM this year and a link to the PIOPED II Trial we discussed today.

A few points on the diagnosis and management of a PE with a focus on IVC filters:

1) The diagnosis or exclusion of a PE is heavily influenced by the pre-test probability before objective testing begins. The Well's criteria is a well validated scoring system to estimate the pre-test probability of a PE:

i) Clinical symptoms of a DVT - (3 points)
ii) Other dx less likely than PE - (3 points)
iii) HR greater than 100 - (1.5 points)
iv) Immobilization for more than 3 days or
surgery within the past 4 weeks - (1.5 points)
v) Previous DVT/PE - (1.5 points)
vi) Hemoptysis - (1 point)
vii) Malignancy - (1 point)

A score of greater than 4 is considered "PE likely" whereas a score of 4 or less is considered "PE unlikely". A reasonable approach is to pursue CTA in the "PE likely" group and consider d-dimer (ELISA) testing in the "PE unlikely" group. One caveat is that most of these studies were done in outpatients and the approach of using d-dimer testing may not be generalizable to admitted GIM patients. Often this means going directly to CTA.

Remember, PIOPED II demonstrated that if the results of CTA are discordant with your clinical assessment (i.e. CTA negative in a high pre-test probability patient or positive in a low risk patient), this should promote additional testing.

2) After the diagnosis is made, anticoagulation should be initiated with heparin first (preferably LMWH over IV heparin) or Fondaparinux. The patient can then be bridged onto warfarin for a minimum of 3-6 months of anticoagulation. The exception to this is in patients with an active malignancy or receiving chemo where the CLOT Trial showed that anticoagulation with LMWH is superior to warfarin in preventing recurrent VTE and may reduce mortality in patients with solid tumors (sub-group analysis).

3) Consider thrombolysis in patients with hemodynamic instability from an acute PE.

4) The only indication for IVC filter insertion recommended in the 2008 ACCP Guidelines is for patients with a PE and a contraindication to anticoagulation. Furthermore, if an IVC filter is inserted, anticoagulation should be re-instituted as soon as is deemed safe.

5) Some authorities suggest inserting an IVC filter in the context of a recurrent pulmonary embolism while on anti-coagulation.

6) Controversy exists regarding the role of IVC filter placement in patients with poor cardiopulmonary reserve or a large clot burden.

7) "Prophylactic" IVC filters should be avoided.

8) The largest trials to date have shown that in hemodynamically stable patients, IVC filters reduce the incidence of recurrent symptomatic PEs, but do not change mortality and cause an increased rate of DVTs (when left in). The benefits may be greater in hemodynamically unstable patients.

9) Most IVC filters are retrievable! Talk to Interventional Radiology and arrange to have them removed. Do not leave your patient with a long term IVC filter unless they still need it!

Portal Vein Thrombosis

2010-11-16T09:22:00.004-05:00

Today we discussed a patient with a portal vein thrombosis (PVT) in the setting of acute cholecystitis. Following the management of acute cholecystitis, the discussion turned to the management of a PVT.

Here's an excellent review article on an approach to managing a PVT.

A few things to keep in mind:

1) The causes of a PVT include inflammatory, malignant, infectious and hypercoaguable states, however the most common cause is cirrhosis (25%).

2) An incidentally found PVT should trigger a search for cirrhosis, a hypercoaguable state or occult malignancy (including a myeloproliferative disorder).

3) An acute PVT is usually asymptomatic.

4) The rationale for treating a PVT is to prevent clot extension and compromise of intestinal perfusion and to prevent portal HTN.

5) It's estimated that 85-90% of patients with a chronic PVT thrombosis have esophageal varices.

6) There is very limited evidence to inform the decision to anticoagulate or not. Management is often extrapolated from the lower extremity DVT literature.

7) In the context of cirrhosis, anticoagulation is generally NOT recommended due to the increased risk of bleeding.

8) In a chronic PVT with portal HTN and NO cirrhosis, it may be reasonable to anticoagulate if there is a history of a hypercoaguable state or previous thrombosis. Otherwise, the risk of bleeding in the context of portal HTN (varices) may outweigh the benefits.

10) In an acute PVT and NO cirrhosis, it is reasonable to investigate for and treat any underlying etiology (including a hypercoaguable state) and consider anticoagulating for a minimum of 3-6 months or longer if there is a persistent risk factor.

11) If anticoagulating, the same medications (warfarin, LMWH, IV heparin) and targets (i.e. INR 2-3) can be used as for lower extremity DVTs.

12) The management of a PVT is highly variable, clinician dependent and must be tailored to the individual patient and clinical scenario.

ASA Overdose

2010-11-15T09:19:00.005-05:00

This morning we talked about the approach to an aspirin (ASA) overdose. This is an important topic to review since we don't see it very frequently on GIM yet its management requires time sensitive interventions to prevent morbidity and mortality.

Here's a flow chart from the BMJ. If you have access, here's a review article from Postgraduate Medicine. The Merck Manual also has a short review as does Harrison's. The Uptodate article on "Aspirin Poisoning in Adults" is also a nice summary.

We talked about urine alkalinization quite a bit today. Here's a link to a position paper published in the Journal of Toxicology that supports urinary alkalinization.

Some key points:

1) Salicylates are found not only in aspirin (acetylsalicylic acid), but also in a number of OTC/herbal products including Bismuth subsalicylate (Pepto Bismol), salicylic acid and Oil of Wintergreen.

2) In general (watch your units):
i) Therapeutic Range: 0.7-2.2mmol/L
ii) Toxic Range: >greater than 2.9mmol/L
iii) Consider dialysis when level is greater than 7.2mmol/L

3) In usual doses, aspirin is rapidly absorbed and reaches a peak concentration in 1 hour. However, in the setting of an overdose, this can be significantly delayed (5-6 hours from ingestion) due to slowed gastric emptying or enteric coated/slow-release preparations.

4) Pathophysiology of Toxicity:
i) Uncoupling of oxidative phosphorylation at the cellular level
ii) Stimulation of the respiratory centre in the medulla
iii) Metabolic acidosis (primary from salicyltes, secondary from mitochondrial poisoning)
iv) Central hypoglycemia despite normal peripheral blood glucose levels

5) Signs and Symptoms of overdose: nausea, vomiting, tinnitus, hyperventilation. More severe symptoms include: fever, decreased LOC, non-cardiogenic pulmonary edema, rhabdomyolysis, hypotension, seizures and AKI.

6) When suspecting any overdose, always check a Tylenol and ASA level.

7) Important investigations: ASA level (check q2h until two values show decreasing levels), ABG (or venous blood gas), CBC, lytes, creatinine, liver enzymes, INR, plasma glucose, extended electrolytes, urinalysis, urine pH and CXR. The blood work and urine tests should be repeated frequently during the initial period of management.

8) ASA intoxication is one of the prototypical causes of a mixed repiratory alkalosis with an anion gap metabolic acidosis (although an isolated anion gap metabolic acidosis can be seen).

9) Remember the common causes of an anion gap metabolic acidosis: methanol, uremia, diabetic/starvation/alcoholic ketoacidosis, lactic acidosis, ethylene glycol, salicylates.

10) Management:

i) Stabilize ABCs.

ii) If tolerated, activated charcoal should be given (1g/Kg up to 50g) and can be repeated q4h x 2 after the first dose. This works best if given within 1 hour of toxic ingestion. Contraindicated if level of consciousness is depressed unless the patient is intubated.

iii) Supplemental glucose should be given in patients with altered LOC due to the risk of neuroglycopenia despite normal peripheral blood glucose.

iv) Potassium must be aggressively replaced. Hypokalemia can impair urine alkalinization, and any initial hypokalemia will be exacerabted by alkalinization.

v) Urine alkalinization: This is a critical step. Here's a position paper published in the Journal of Toxicology on the topic.

Salicylic acid is a weak acid. The non-ionic form can diffuse across membranes, while the ionic form cannot. Increasing the serum pH will result in diffucion of the non-ionic form out of cells and trap it in the blood/urine in the ionic form.

Pre-existing alkalosis is not a contraindication to urinary alkalinization.

A rise in the urine pH of 1 unit can theoretically increase salicylate excretion by a factor of 10.

Start with a bolus of 1-2mEq/Kg of NaHCO3 followed by an infusion of 3amps of NaHCO3 mixed in 850cc D5W (NOT normal saline) run at 1.5-2 times maintenance. Urine pH should be checked frequently with a target of > 7.5 - 8. Failure to achieve this within 1-2 hours may be an indication for dialysis.

11) Avoid acetazolamide and any medication that depresses respiratory drive.

12) Indications for dialysis:
i) Renal failure impairing salicylate clearance
ii) Inability to alkalinize the urine
iii) Fluid overload limiting sodium bicarbonate treatment
iv) Plasma salicylate level greater than 7.2 mmol/L
v) Coma
vi) Failure of medical management

13) Always call your local poison centre for advice when managing an overdose.

Hemorrhage

2010-11-12T15:01:00.004-05:00

Yesterday we talked about a patient presenting with a Hg of 42 and an MCV of 50 with no signs of bleeding. During our discussion, a number of topics related to anemia, hemorrhage and transfusions came up.

We talked briefly about the TRICC trial published in the NEJM. This study looked at 838 ICU patients with a Hg of less than 90 and randomized them to a liberal (transfuse if Hg less than 100) vs. a conservative (transfuse if Hg less than 70) transfusion strategy.

The study showed that at 30 days there was no between arm difference in mortality but there was reduced in-hospital mortality in the restrictive transfusion arm. In sub-group analysis, this arm also demonstrated reduced mortality in younger patients (less than 55 years old) and less acutely ill patients (APACHE-II score less than 20). No difference in outcome was seen between the arms in patients with an ACS.

TRICC Bottom Line:

1) These were ICU patients so be cautious with generalizing to GIM patients, but we generally follow the results from TRICC.

2) Consider a RBC transfusion in patients with a Hg of less than 70, especially if symptomatic. This is not a hard and fast rule - you may not transfuse a patient with a Hg of 65 who is well and asymptomatic, especially if it is chronic.

3) Consider not transfusing RBCs in a patient with a Hg greater than 100. However, it may be reasonable to aim for a higher Hg (i.e. greater than 100) in patients with an acute coronary syndrome.

4) A significant gray zone exists inbetween 70 and 100.

Sources of Blood Loss:

1) When presented with a very low Hg, you need to rule out immediate life theatening causes right away - bleeding and hemolysis.

2) A reasonable initial screen for hemolysis includes an LDH, haptolgobin, blood film and bilirubin. The combination of an elevated LDH and low haptoglobin are 90% specific and 92% sensitive for hemolysis.

3) Looks for obvious sources of bleeding: GI tract (BRBPR, melena, hematemesis), GU tract, trauma (laceration, hemo-thorax/peritoneum, etc.) or Gyne.

4) If no obvious source, consider hemolysis and/or a retroperitoneal bleed.

5) Large hemodynamically significant blood loss will not occur from an intracranial hemorrhage due to the limited space in which there is to bleed. Additionally, in a pulmonary hemorrhage, hypoxia will be a greater threat to life before anemia is.

A few points on microcytic anemias:

1) We talked briefly about differentiating iron deficiency anemia from thalassemia. Thank you to Lauren for pointing out that the RDW may be useful in this case. In thalassemia, the RDW is generally low or normal whereas in iron deficiency anemia it may be elevated as the bone marrow pushes out RBC precursors.

2) In a patient over the age of 50 with iron deficiency anemia, remember to look for occult bleeding from a GI malignancy.

3) A ferritin of less than 10-15 is virtually diagnostic of iron deficiency anemia (99% specific, 59% sensitive). Using a value of 41 increases the sensitivity to 98% and the specificity to 99%. The challenge is that ferritin is an acute phase reactant and is increased in inflammation. One possible approach is to divide the ferritin value by three in these patients, if it's less than 20, this is highly suggestive of co-existing iron deficiency anemia.

4) Don't forget celiac disease as a not uncommon cause of iron deficiency anemia.

5) Many other tests including iron saturation, TIBC, Hg electrophoresis, reticulocyte count, soluble transferrin receptor and blood film examination can help in the assessment of a microcytic anemia.

Atrial Fibrillation

2010-11-10T09:12:00.007-05:00

Today we talked about atrial fibrillation in a patient with a history of rheumatic fever. On GIM, atrial fibrillation is a diagnosis we see very commonly.

One of the best atrial fibrillation resources is the 2006 ACC/AHA Guidelines which you can find here. As a side note, the ACC/AHA have guidelines on a huge variety of cardiovascular topics that provide an evidence base for cardiac decision making on the wards. Here's the list.

Briefly about atrial fibrillation:

1. Afib is a very common arrhythmia. Seen in ~10% of patients greater than 85 years old.

2. While afib can cause distressing symptoms (palpitations, SOB, etc.), the biggest concern is thromboembolism and the impact of afib on cardiac function.

3. Generally we classify afib as:

a) paroxysmal (less than 7 days duration)

b) persistent (lasting greater than 7 days and terminating spontaneously or with cardioversion)

c) permanent (afib lasting greater than 1year and failed cardioversion/not attempted).

Regardless of the classification,

they all portend the same yearly risk of stroke.

A fourth classification is "lone atrial fibrillation" which applies to atrial fibrillation in a patient with no structural heart disease (and often less than 60 years old). These patients are generally felt to be at a low risk of stroke.

4. Most common causes of afib: HTN, valvular disease, hyperthyroidism, heart failure and alcohol.

Usually afib is not associated with stable coronary artery disease unless it results in an MI or heart failure. Afib can also be seen in the context of surgery or a pulmonary embolism.

5. Minimum set of investigations for new onset atrial fibrillation: ECG (confirm diagnosis, assess for other complicating disease), CBC, lytes, TSH and 2D Echo (to assess for structural heart disease).

6. Management consists of rate vs. rhythm control and thromboembolism risk reduction.

a) Rate vs. rhythm control:

Often a trial of cardioversion is given for the first episode of atrial fibrillation. In the long term, most patients with recurrent atrial fibrillation are managed with rate control rather than rhythm control (unless they have significant symptoms or cardiovascular compromise when in afib).

The AFFIRM Trial demonstrated that there was no survival or stroke risk advantage to a rhythm control strategy and that rhythm control more frequently resulted in medication side effects and hospitalization.

Rate control is usually accomplished with B-blockers, non-dihydropyridine calcium channel blockers (Dilt, Verapamil) or Digoxin. The guidelines suggest a HR target of less than 80bpm at rest and less than 110bpm with exercise. However, the recently published RACE-II Trial suggests that strict rate control may confer no additional benefit over lenient rate control.

b) Thromboembolism risk reduction:

The yearly risk of stroke depends on a variety of factors. Several risk scores exist, but one of the easiest to use is the CHADS2 Score. This only applies for patients with non-valvular atrial fibrillation:

Chronic Heart Failure - 1 point

HTN - 1 point

Age greater than 75 - 1 point

Diabetes - 1 point

Stroke/TIA - 2 points

If the CHADS2 score is 0 then no therapy or ASA is reasonable. With a CHADS2 score of 1 then ASA or Warfarin (INR 2-3) is acceptable and with a CHADS2 score greater than 1 warfarin is recommended.

The reason for this is that the benefit you obtain from ASA or warfarin is determined by your yearly risk of stroke. ASA provides a RRR of ~25% while warfarin gives a RRR of ~66%. The risk of a significant bleeding complication from ASA is small, while with warfarin is ~1%/year (depending on the patient).

Remember, for patients with valvular atrial fibrillation, their stroke risk is much higher (as in our patient this morning) so they should be managed with warfarin.

Interestingly, the recently published RE-LY trial showed that Dabigatran, a direct thrombin inhibitor that does not require monitoring may be superior to warfarin in terms of stroke prevention or bleeding risk (depending on the dose). This could revolutionize the way atrial fibrillation in managed.

Acute Hepatitis

2010-11-09T09:36:00.005-05:00

Today we discussed a case of acute hepatitis NYD with moderate-severe liver enzyme elevation. This is not an uncommon referral to Internal Medicine.

Here's a very useful review from CMAJ in 2005 on elevated liver enzymes.

Some points about marked liver enzyme elevation (>5x the upper limit of normal):

1. Remember that the "liver function tests" are bilirubin, INR, albumin +/- glucose and can reflect the synthetic function of the liver. Conversely, the "liver enzymes" - AST, ALT, ALP and GGT are NOT liver function tests as they offer no information on the liver's synthetic function but merely are a marker of hepatocyte integrity and/or cholestasis.

2. The differential diagnosis of moderate to severe transaminitis includes: viral hepatitis, toxic hepatitis, ischemic hepatitis, severe obstruction, autoimmune and alcoholic hepatitis.

3. Decide what the predominant pattern is to help you guide investigations:
a) Hepatic (increased AST, ALT > ALP)
b) Cholestatic (increased ALP > AST, ALT)

4. How elevated are the enzymes? 5x vs. 5-10x vs. >10x of normal? What is the trend? Is there synthetic dysfunction (increased INR, bilirubin, decreased albumin)? Typically liver enzyme values at this level represent acute liver injury.

5. In acute viral hepatitis, the liver enzymes often peak before the bilirubin and the patient may have non-specific symptoms such as fatigue, arthralgias and a low grade fever (as in our patient) .

6. Consider ischemic hepatitis in the right clinical context and an ALT/LDH ratio of less than 1.

7. Hepatitis screen: Hep A IgM Ab, Hep B core Ab (IgM), Hep B surface Ag and Ab, Hep C Ab.

8. Always ask about Tylenol use, herbal and over the counter medications, periods of illness (hypotension), autoimmune symptoms and alcohol.

9. Some form of abdominal imaging (usually ultrasound) is often appropriate to assess for evidence of hepatitis and/or obstruction.

10. Once the common causes of moderate to severe transaminitis have been ruled out, consider testing for auto-immune hepatitis and other viral causes such as EBV and CMV.

Knee Pain

2010-11-08T14:20:00.008-05:00

Yesterday we talked about the diagnostic dilemma of a painful knee that ultimately was presumed to be secondary to osteoarthritis.

This a good opportunity to review the approach to an acute monoarthritis and to osteoarthritis.

Let's start with some Canadian content. Here's a recent review published in the CMAJ looking at the management of a patient with an acute monoarthritis.

The NEJM published a very thorough review article on OA of the knee in 2006.

There are many causes of knee pain outside of a monoarthritis or osteoarthritis, many of which we do not see very often as internists (i.e. orthopedic problems in younger patients).

To summarize, here are some key points on evaluating a patient with acute knee pain:

1. Determine if there is a recent history of trauma. This raises the pre-test probability of a fracture, hemarthrosis, meniscal tear or ligamentous injury.

2. Decide whether this is an intra-articular, peri-articular or referred process (there is significant overlap in some of these signs/symptoms):

a) Intra-articular: pain localized to the knee without radiation, knee effusion, mechanical symptoms (clicking, locking, giving way), abnormal structural physical exam, reduced range of motion.

b) Peri-articular: focal area of pain or abnormalities on exam, pain only during parts of the range of motion, +/- mechanical symptoms.

c) Referred pain: vague location of pain, back or hip pain, pain not exacerbated by knee movement, lack of an effusion, normal knee exam.

3. If the pain is articular, you need to decide if it is inflammatory (i.e. arthritis - pain, redness, swelling, warmth) or non-inflammatory (structural). Any acute effusion should be drained and analyzed.

4. Remember if an effusion is present -> rule out INFECTION. Missing a septic joint can have catastrophic consequences for the joint, and very quickly.

5. Arthrocentesis fluid should be sent for cell count and differential, gram stain, C&S, microscopy for crystals at a minimum.

6. Imaging: Start with x-rays. If there is any history of trauma, lack of localizing symptoms to the knee or a question of pain origin, image the ipsilateral joints above and below the knee.

7. Consider MRI as the next imaging test of choice after x-ray if no diagnosis can be found or if a soft tissue etiology is being considered.

8. An effusion can be present in an acute exacerbation of osteoarthritis.

Renal Cell Carcinoma

2010-11-05T09:17:00.006-04:00

Today we talked about renal cell carcinoma presenting with anorexia, abdominal distension, hematuria, ascites and renal failure.

Here are links to two review articles, the first is from the Lancet in 2009 and the second is from NEJM in 2005.

Some key points about RCC:

1) RCC is the 7th most common cancer in men and the 9th most common in women. The peak incidence is in the 6th and 7th decades of life (mean age of 60). Men are affected twice as frequently as women.

2) Risk factors include: HTN, obesity, smoking, acquired cystic diseases of the kidney, ESRD and certain inherited conditions (e.g. von Hippel-Lindau). Regardless, most patients with RCC do not have an identifiable risk factor. Fruit and vegetable consumption may be protective!

3) This tumor was classically known as "The Internist's Tumor" due to its varied presentation, however with the widespread use of abdominal imaging and incidental diagnosis, some argue that RCC is now "The Radiologist's Tumor".

4) Signs and Symptoms at Presentation:
a) Local: The classic triad of abdominal pain, a palpable mass and hematuria is uncommonly seen today.
b) Systemic: Anorexia, fatigue, wasting and a variety of paraneoplastic phenomena including hypercalcemia (PTHrp), HTN (renin) and erythrocytosis (EPO).

5) Any patient over the age of 40 with hematuria should be assessed for RCC since prognosis is determined by stage.

6) Imaging: CT abdomen is the investigation of choice. However, abdominal U/S while less sensitive can help differentiate a simple cyst from a more complex structure. MRI can be useful if the U/S is non-diagnostic or contrast dye is contraindicated.

7) If a solid renal mass is identified with radiologic features consistent with RCC, biopsy is usually not performed due to low specificty and concern with seeding the peritoneum. Good surgical candidates often go directly for a partial or radical nephrectomy.

8) Surgical resection is the cornerstone of therapy as chemotherapy is minimally effective. Surgery can be curative in the majority of patients with Stage I, II and III disease. Resection of the primary tumor is recommended even in the setting of metastatic disease (in patients with good functional status).

9) Significant interest is currently focused on biologic agents including VEGF and mTOR inhibitors given the limited benefit and significant toxicity of Interleukin-2 immunotherapy.

The Art of Pimping

2010-11-04T13:10:00.003-04:00

Hi folks,

Usually we keep things pretty formal and academic here on Horses and Zebras, but today we're going to talk about something different - the art of pimping.

For those unfamiliar with the term as it applies to Medicine, this is when a staff "poses a series of very difficult questions to an intern or student." Often this is done to further learning or highlight gaps in knowledge, but at times it can make the learner feel self-conscious or even uncomfortable.

We've all experienced this and part of going through your training is knowing how to handle it.

Check out the very humorous, but all too true article that started it all. Some excellent defensive tips are offered.

Our own Dr. Detsky furthered the discussion on this topic with his article from JAMA in 2009.

In all seriousness, "pimping" will continue to be a part of medical education for the foreseeable future. Here are some things (from one trainee to another) that have helped get me though the 10,000 times I've been put on the spot:

1) Remember that your staff is trying to help you learn, not hurt your feelings. You will never forget something you got wrong when pimped (i.e. the Toronto clinical prediction rule for aortic stenosis).

2) It's OK to stop, take a deep breath and think about the answer rather than blurting out the first thing that comes to mind.

3) If you don't know the answer or are never going to remember it, just be honest and say, "I don't know." This is better than squirming for 5 minutes during which time it'll be obvious you didn't know the answer.

4) If you think you know the answer, then answer with confidence. Not arrogance, but confidence. If you're right, you'll get credit for being right! If you're wrong - you were going to be wrong anyway, so you've lost nothing. However, if you're right but you answered in a sheepish, high pitched and uncertain voice, you'll only get credit for guessing.

Finally, when it's your turn to be the teacher, remember what it felt like to get "pimped".

Chronic Diarrhea

2010-10-27T11:26:00.011-04:00

Today we talked about a patient with chronic diarrhea.

Here is a useful review article from Gastroenterology in 2004.

Guidelines from the American Gastroenterology Association were published in 1999.

Working up chronic diarrhea can be challening as the differential diagnosis is quite broad, clinical trials are lacking and expert opinion is varied.

Some key points:

1) Chronic diarrhea is not well defined. A reasonable definition might be:

Decrease in stool consistency ("stool that takes the shape of the vessel it is in")
>3 stools and/or >200g of stool per day
>4 weeks duration

2) Have an organized approach to the types of chronic diarrhea (which leads to the differential). The guidelines suggest watery vs. inflammatory vs. fatty. Another classification scheme includes secretory vs. malabsorption/osmotic vs. inflammatory.

3) Use the history and physical exam to direct your initial set of investigations. Make sure to take a good medication and travel history!

4) Reasonable initial tests beyond the routine:

Stool osmotic gap [290 - 2(stool Na + stool K)] and pH
FOBT
TSH
anti-TTG and IgA level (if risk factors for celiac)
Stool C&S, O&P (repeat over several days) and C.diff
Fecal WBCs
Response to fasting
+/- 72 hour fecal fat testing (difficult to get done)
+/- Colonoscopy or Sigmoidoscopy
+/- Abdominal imaging

5) Stool osmotic gap (see above):

a value less than 50 suggests secretory diarrhea (i.e. lots of secreted electrolytes in the lumen)
a value greater than 125 suggests osmotic diarrhea (i.e. lots of unmeasured osmoles in lumen)
values in between are indeterminate

6) Testing for pancreatic insufficiency, bacterial overgrowth, hormone levels (gastrin, calcitonin, VIP, carcinoid), mucosal abnormalities, etc. can be pursued as appropriate following the initial set of investigations.

7) Some authors suggest that more than 80% of chronic diarrhea cases have a treatable etiology.

Hemoptysis

2010-10-26T11:25:00.010-04:00

Hey folks,

Horses and Zebras is back after a brief absence!

Today we talked about a patient with new onset hemoptysis and an otherwise normal physical exam, screening blood work and CXR.

Here's a short and focussed review article from AFP on hemoptysis. It includes a very easy to follow algorithm and a good differential diagnosis.

A couple of key take-home points:

1) Always start with the ABCs. While we worry about dropping hemoglobin and hypotension, remember that one of the biggest risks in patients with hemoptysis is airway compromise and hypoxia.

2) Decide if this is actually hemoptysis! Blood from the GI tract or above the vocal cords (pseudohemoptysis) can mimic hemoptysis.

3) Infection and cancer are the most common diagnoses.

4) Evaluate for massive hemoptysis (>200-600cc/24 hours). This may suggest a diagnosis but also implies a much higher risk of airway compromise and need for aggressive airway management.

5) Reverse the reversible - correct coagulopathies, thrombocytpenia, etc.

6) After routine bloodwork - get a CXR. Go on to bronchoscopy or a high resolution CT scan of the chest in patients with massive hemoptysis, persistent bleeding, CXR findings or risk factors for lung cancer.

7) Call for help sooner rather than later - ICU, respirology, thoracic surgery - if the bleeding is not resolving or is getting worse. Specialized airway skills may be needed.

Multiple Myeloma

2010-09-17T11:33:00.008-04:00

Today we discussed a classic case of Multiple Myeloma with hypercalcemia, renal failure, anemia, and bone pain secondary to lytic bone lesions... these features make up the mnemonic CRAB: hyperCalcemia, Renal failure, Anemia, Bone pain.

Here is a link to a previous Horses & Zebras blog summarizing the Clinical Features of Multiple Myeloma, as well as some links to articles reviewing investigation and management of hypercalcemia and current management options for multiple myeloma.

Management of hypercalcemia +/- acute renal failure is often the primary problem that needs to be managed on admission to hospital. Hypercalcemia can be considered to be mild (2.6 - 2.9 mmol/L), moderate (3.0 - 3.4 mmol/L), and severe (greater than 3.5 mmol/L); however, there are no official cut-off points for hypercalcemia. As we discussed this morning, ~40% of calcium is bound to albumin and thus low albumin states will lower the measured calcium. This can be corrected roughly by adding 0.2 mmol/L to a calcium measurement for every drop in albumin of ~10.

Treatment of Hypercalcemia

1. First line treatment for hypercalcemia is fluid resuscitation, as the majority of patients will be volume contracted. Rapid, aggressive resuscitation is the goal, monitoring for any potential volume overload/heart failure in susceptible patients.

2. Administration of an IV bisphosphonate is also considered appropriate in severe hypercalcemia. Pamidronate (60 - 90 mg) is the usual choice, given once over 2-4 hours, and most often normalizing calcium within 5-7 days.

3. For more immediate calcium-lowering calcitonin can be considered; however, it is not uncommon for patients to develop tachyphylaxis and thus its use is limited.

4. Alternatively, and often more effective in the setting of lymphoma or multiple myeloma induced hypercalcemia, glucocorticoids such as prednisone (1 mg/kg daily) can be considered.

5. Management of hypercalcemia always includes investigation into the underlying cause, and treatment of such problem otherwise the hypercalcemia will recur.

Guillain-Barre Syndrome

2010-09-10T14:55:00.005-04:00

This week we explored 2 different (potential) cases of Guillain-Barre Syndrome, or GBS. First during Physical Examination Rounds and then again in Morning Report.

The most common form of GBS is an idiopathic acute inflammatory demyelinating polyneuropathy (AIDP), and in fact GBS is often synonymous for AIDP. It is an autoimmune process directed against Schwann cell membranes. There are 5 other variants of GBS, including the Miller Fisher Variant which often presents with the triad of ophthalmoplegia, ataxia, and areflexia.

GBS occurs anywhere from 1 - 2 per 100,000 per year. It is often (~2/3 of cases) preceded by either a respiratory or GI infection, most commonly Campylobacter. GBS has also been reported after vaccinations and to be associated with systemic illnesses, such as SLE, Hodgkin's Lymphoma, Sarcoidosis, etc.

Patients with GBS often present with parasthesias in their limbs, followed soon after by ascending weakness. This progresses over days to weeks. GBS can also be associated with autonomic dsyfunction such as orthostasis, urinary retention, constipation, and tachycardia.

Physical examination most often reveals symmetrical motor weakness in an ascending pattern, with absent reflexes, flaccid tone, and a normal sensory exam.

Patients with GBS need to be monitored closely for respiratory failure due to involvement of the diaphragm. A good rule of thumb for consideration of intubation is the 20/30/40 rule:

20: Vital Capacity less than 20 cc/kg
30: Maximum Inspiratory Pressure less than 30 cm H2O
40: Maximum Expiratory Pressure less than 40 cm H2O

Treatment for GBS is most often supportive, and may require an ICU setting for ventilatory support, hemodynamic support, nutritional support, and pain control. If diagnosed within the first 4 weeks then IVIG or plasmapheresis can be considered. A recent Cochrane review suggests that IVIG treatment has similar outcomes to plasmapheresis in the setting of early (ie: within 2 weeks) diagnosed GBS.

Outcomes for patients with GBS are quite good with ~80% achieving full recovery within a few months to a year; however, minor deficits often persist. 5-10% will have permament disabling deficits, and another 2-3% will die as a result of their GBS. Approximately 5-10% of patients may develop one or more relapses of their GBS, leading to a diagnosis of Chronic Inflammatory Demyelinating Polyneuropathy (CIPD).

Here is a very thorough review of GBS from 2005, in The Lancet.

Pulmonary Hypertension

2010-09-03T10:36:00.004-04:00

Today we discussed a case of newly diagnosed Pulmonary Hypertension in a young woman.

Pulmonary Hypertension (PH) is defined as a Pulmonary Arterial Pressure over 25 mmHg at rest (normal 12-16 mmHg).

Patients often present with months or years of gradually progressive symptoms, such as shortness of breath, fatigue, cough, angina, peripheral edema, and rarely hemoptysis.

Cardiovascular examination often reveals a loud, palpable P2, a split S2, and an RV heave.

There are multiple causes of PH, but all result in increased pressures within the pulmonary vasculature, either due to vasoconstriction of the blood vessels, obstruction by way of a mass or pulmonary emboli, or fibrosis within the lung parenchyma related to systemic illnesses. In order to overcome this increased pulmonary pressure, the heart then is required to create elevated right-sided pressures in the heart. In turn, this leads to RV hypertrophy and potentially RV failure.

PH is classified according to the WHO into 5 major categories:
Class I: Pulmonary Arterial Hypertension

Idiopathic

Familial

Connective Tissue Disorders, HIV, Drugs, Toxins, Congenital Left-to-Right Shunts, etc.
Class II: PH with Left Heart Disease

Left Atrial or Ventricular Heart Disease

Left-sided Valvular Heart Disease
Class III: PH Associated with Lung Diseases or Chronic Hypoxia

COPD, Interstitial Lung Disease, Sleep Disordered Breathing, etc.
Class IV: PH Due to Chronic Thrombotic and/or Embolic Disease

Thromboembolic obstruction of the proximal or distal pulmonary arteries

Nonthrombotic obstruction of the pulmonary arteries (ie: tumor, foreign body, etc.)
Class V: Miscellaneous causes

Sarcoidosis, Lymphangiomatosis, etc.

Given the numerous potential causes for PH, any patient with suspected PH requires significant investigations to diagnose PH and then to determine the etiology of their PH. This includes basic blood work (looking for evidence of polycythemia), an ECG (evidence of RAE or RVH), a CXR, and echocardiogram, a CT Chest, a V/Q scan (to detect chronic thromboembolic disease), a 6-minute walk test, and a Right-Heart Catheterization to name a few!

These patients are managed by the multidisciplinary PH team where the goals of treatment include symptom management, improving quality of life, and prolonging survival, which often requires a lung or heart-lung transplant.

Here is a review article on the mechanisms of PH, and here are the 2009 American College of Cardiology Consensus Guidelines for PH.

TIA Management

2010-07-29T10:40:00.015-04:00

Today we reviewed the approach to a patient presenting with symptoms suggestive of a Transient Ischemic Attack (TIA).

A TIA is defined as an abrupt focal loss of neurologic function caused by reduction in blood flow that persists less than 24 hours and clears without residual disability.

Diagnosis is made with a thorough history and physical examination, where the latter can be normal in many patients.

The patient's risk for progression to stroke can be assessed by the ABCD score, which helps to guide the clinician on the need for admission:

A: Age - 1-pt if over 60 years old; 0-pt if less than 60

B: Blood Pressure - 1-pt if SBP greater than 140 OR 1-pt if DBP greater than 90

C: Clinical symptoms - 2-pts if unilateral weakness; 1-pt if language disturbance but no weakness; 0-pt for other symptoms

D: Diabetes - 1-pt if patient has diabetes; 0-pt if not

D: Duration - 2-pts if more than 60 min; 1-pt if 10-59 min; 0-pt if less than 10 min

Score 0-3: low risk, 2-day stroke risk 1%

Score 4-5: moderate risk, 2-day stroke risk 4%

Score 6-7: high risk, 2-day stroke risk 8%

Low risk patients don't need to be admitted for stroke work-up; however, they do require expedited investigations which sometimes warrant an admission. Moderate risk patients and High risk patients generally warrant an admission and investigations and monitoring for stroke.

Current Canadian Stroke Guidelines recommend rapid turn around times for investigations in a patient presenting with a TIA. Patients are categorized into Emergent, Urgent, and Semi-urgent; and based on these 3 categories, their stroke work-up is recommended to be performed within the given timeline.

Emergent: investigations within 24-hrs

• Symptoms within the previous 24-hrs with 2 or more high-risk clinical features (ABCD criteria)
• Acute persistent or fluctuating stroke symptoms
• One positive investigation (evidence of acute infarct on CT/MRI; evidence of carotid artery stenosis > 50%)
• Other factors based on individual presentation and clinical judgment

Urgent: investigations within 72-hrs

• TIA within the previous 72-hrs

Semi-urgent: investigations within 30-days

• Does not meet urgent or emergent criteria

Investigations include standard screening blood work, an assessment by a neurologist or stroke specialist, brain CT or MRI, carotid imaging (doppler, CT angio, or MR angio), and ECG.

Management should include initiation of an anti-platelet agent, once confirmation that there is no intracranial hemorrhage. If not already on ASA, start with 160-mg followed by 81-mg daily. If failing ASA treatment, then change to either Clopidogrel (load with 300-mg followed by 75-mg daily) or Aggrenox (1-tab BID).

Those with 70 - 99% blockages in their carotid arteries (matching their TIA symptom pattern)should undergo endarterectomy within 2-weeks.

If Atrial Fibrillation is discovered the patient should be initiated on anti-coagulation therapy immediately after their event, once an intracranial hemorrhage has been ruled out.

All modifiable risk factors should be addressed by way of smoking cessation, blood glucose control (HbA1C less than 7%), lipid management (LDL less than 2), and blood pressure reduction (less than 140/90).

The complete Current Canadian Stroke and TIA guidelines can be found here.

Pulmonary-Renal Syndromes

2010-07-23T10:20:00.006-04:00

Yesterday we discussed a case of hemoptysis NYD and today we reviewed an elderly gentleman with acute renal failure who was diagnosed with Goodpasture's syndrome.

Yesterday's differential diagnosis for hemopytsis included vasculitis. In particular one always needs to consider pulmonary-renal syndromes in the differential for hemoptysis, including Wegener's Granulomatosis (WG) and Goodpasture's syndrome.

WG's can present in many ways, but often involves a history or sinusitis or rhinitis, along with constitutional symptoms, hemoptysis, renal failure, and occassionally polyarthralgias. Patients can develop a "saddle nose" due to collapse of their nasal support.

The pathological triad of WG includes:
1) systemic necrotizing angiitis
2) necrotizing granulomatous inflammation of the respiratory tract
3) necrotizing glomerulonephritis

Diagnosing Wegener's requires a detailed history and physical exam as well as blood work, looking for evidence of c-ANCA or anti-PR3, a urinalysis looking for RBC casts, chest imaging, and often a biopsy of either the kidney or lung. Lung biopsies frequently reveal evidence of vasculitis and granulomatous inflammation. Renal biopsies demonstrate a Pauci Immune picture (i.e.: no deposition of immunoglobulin or complement) with segmental crescentic necrotizing glomerulonephritis.

Treatment includes pulsed steroids and often cyclophosphamide urgently as this is a rapidly progressive disease. Involvement of a rheumatologist and nephrologist for management and follow-up is usually warranted.

Goodpasture's disease is a triad of pulmonary hemorrhage, glomerulonephritis (GN), and circulating anti-glomerular basement membrane (anti-GBM) antibodies in the blood. However, not all patients present with the triad, but anti-GBM antibodies is a distinguishing feature of Goodpasture's. Most patients (~60 - 80%) present with both pulmonary and renal disease, 20 -40% have only renal disease, and less than 10% have only pulmonary disease.

Diagnosis, like WG, involves a thorough history and physical exam as well as blood work looking for anti-GBM antibodies, chest imaging, and usually a renal or lung biopsy. Direct immunofluorescence of the renal biopsy will light up and stain along the basement membrane, reflecting the deposition of IgG.

Treatment again, requires rapid aggressive management; however, in the setting of Goodpasture's there is a role for plasmapheresis to remove any circulating anti-GBM antibodies. This occurs in conjunction with immunosuppression with pulsed steroids and often cyclophosphamide. Again, consultation with a nephrologist is often warranted!

Here is a review on the differential diagnosis of hemoptysis and here is a brief case report and review of Goodpasture's from The Lancet.

Lymphadenopathy

2010-07-20T09:46:00.008-04:00

Today we discussed the unfortunate case of a 25 year old young man presenting with a multitude of complaints, including 4-weeks of right shoulder pain, 8-months of lower back pain, head ache, RUQ pain, dyspnea, non-productive cough, night sweats, and an "intentional" weight loss of ~30 pounds over 2 months. He had recently returned from South America, where he had spent the past few months.

We generated a broad differential diagnosis for this diffuse constellation of complaints. The 3 main categories we reviewed were:

1) Neoplasm - hematologic vs. solid organ (ie: testicular, given his gender and age)

2) Infectious - TB, liver abscess, amoebic infection, liver fluke, malaria, infectious endocarditis

3) Inflammatory - inflammatory bowel disease, SLE, sarcoidosis

A CT scan revealed multiple lesions within the liver as well as porta hepatis and para-aortic lymphadenopathy. Large volume lymphadenopathy was also seen in the chest, along with some lytic bone lesions. The clinical picture, along with these imaging findings, raise the most likely diagnosis to lymphoma.

Lymphomas are a heterogeneous group of cancers arising from the reticuloendothelial and lymphatic systems, which often present as solid tumors of lymphoid cells. Historically lymphomas have been categorized as Hodgkins Lymphoma (HL) or Non-Hodgkin Lymphoma (NHL), but as we learn more and more about these cancers the classifications are constantly being upgraded. Currently lymphomas are still broadly categorized as HL and NHL, with the latter group being further subclassified based on the type of cell from which they originate: B-cell, T-cell, or Natural Killer cell.

HL results from clonal transformation of cells of B-cell origin, giving rise to the pathognomic Reed-Sternberg cells. The cause is unknown, but genetic susceptibility and environmental associations are thought to play a role. HL is slightly more common in patients with immunosuppression secondary to post-transplant drugs, congenital immunodeficiency, HIV, and autoimmune diseases (SLE, RA, Sjogren's, etc.). Patients often present with painless lymphadenopathy, that can become painful after consumption of alcohol... for no clear reason! Usually the lymphadenopathy arises in one area and spreads in a contiguous manner. The classic "B symptoms" are often described: fever, night sweats, and unintentional weight loss. Diagnosis requires a lymph node core biopsy +/- a fine needle biopsy. Depending on the specific type of HL identify on pathology, and the stage at diagnosis, treatment usually involves chemotherapy +/- radiation therapy, surgery, or stem cell transplant.

NHL is also a disease of clonal transformation, most often of B-cells, but different subtypes of NHL can develop as a result of clonal transformation of T-cells or Natural Killer cells; classification depends on immunophenotyping, genotyping, and cytogenetics. NHL is much more common than HL. Immunosuppressed patients are also at risk for NHL. The exact etiology of NHL is yet to be discovered, but it is hypothesized that a viral cause may be at play. Patients often present again with painless lymphadenopathy; however, in NHL they can often have multiple areas of involvement. Occasionally patients can present with SVC syndrome secondary to compression of the SVC from nodal enlargement, or acute renal failure secondary to obstruction of the ureters from retroperitoneal or pelvic lymph nodes.

Diagnosis requires a lymph node core biopsy for nodal architecture as well as immunophenotyping and cytogenetics for subclassification of the lymphoma. Full imaging with CT of the chest/abdo/pelvis and a BM biopsy is required for staging +/- a PET scan (this image shows lymphoma with increased uptake of 18-FDG in the brain, chest, and spleen). Although not fully validated in clinical settings, PET scans can be used in the proper setting, as determined by the oncologist and the radiologist.

Staging of NHL follows the Cotswold Modified Ann Arbour Staging. Prognosis is generally better for those with B-cell NHL compared to T-cell NHL. The International Prognostic Index (IPI) is used to help guide clinicians and patients with aggressive lymphomas. There are 5 risk factors with the IPI, and outcomes deteriorate as the number of risk factors increases.

1) Age over 60

2) Poor performance status measured by the ECOG (Eastern Cooperative Oncology Group)

3) Elevated LDH

4) More than 1 extranodal site

5) Stage III or IV disease

Patients in the highest IPI risk group (4-5 risk factors) have a 50% survival rate at 5-years, whereas those in the lowest IPI risk group (no risk factors) have a very high cure rate. Modifications to the IPI have been made to account for diffferent NHL, including the FLIPI (follicular lymphoma) and the R-IPI (diffuse large B-cell lymphoma).

Treatment for NHL is again specific to the subtype of lymphoma and the stage at diagnosis; however, it generally incorporates chemotherapy "R-CHOP" (rituximab (anti-CD20 monoclonal antibodies), cyclophosphamide, doxorubicin, vincristine, prednisone), radiation therapy, or both +/- stem cell transplantation.

Here is a great review article on the approach to a patient with lymphadenopathy.

Welcome to the Horses & Zebras of TGH

2010-07-09T15:40:00.021-04:00

Welcome to GIM at TGH and this, the official blog of the TGH CMR!

This is my first posting and I will try to update the blog every few days with summaries from morning report, noon rounds, physical exam rounds, etc. as well as links to articles and web sites that provide excellent reviews of the topics at hand. Today's post will be a brief summary of the past week's salient teaching points!

Last week we discussed an interesting case of seizure in a patient with a recent history of malaria, travel, and fever. We reviewed the general breakdown of the most common causes of seizure by age category:

Children:
-febrile seizure, seizure disorder
Adults (~20 - 50):
-trauma, toxic, alcohol withdrawal, metabolic, seizure disorder/idiopathic
-less likely stroke or tumour
Older Adults (>50):
-more likely stroke or tumour
-could still be one of the other causes

Last Friday we discussed a great case of HCV cirrhosis and SBP, spontaneous bacterial peritonitis. Here is a NEJM review article on the management of cirrhosis and ascites. There is also a very helpful video on NEJM demonstrating how to perform a paracentesis found here. And this all links in well with Physical Exam Rounds yesterday, where we examined a patient with ascites. You should all have received the JAMA Rational Clinical Exam paper entitled "Does this patient have ascites?" in your inbox (it is not possible to link to the website!). Key points to remember for physical examination of ascites:
1) Most sensitive findings are ANKLE EDEMA and INCREASED GIRTH
2) Most specific finding is FLUID WAVE

During our Emergency Lecture Series we have had a variety of excellent topics covered, including a review of atrial and ventricular arrhythmias. Here you will find the 2006 ACC/AHA guidelines for patients with Atrial Fibrillation as well as the 2003 guidelines for patients with SVT. Here you will find the ACC Pocket Guide for ventricular arrhythmias. And on that note, here is a link to drugs that can induce Torsades de Pointes.

Today's Morning Report discussed a fascinating case of SOB, muscle weakness, swollen joints, and weight loss. The patient was found to have an elevated CK and a small pericardial efffusion on 2D Echo, but normal inflammatory markers (ESR and CRP). There were no sensory findings and only mild objective muscle weakness on exam.

During our discussion the topic of Constrictive Pericarditis came up and how to make the diagnosis; which requires a right and left heart catheterization to compare pressures across the septum. Constrictive pericarditis is a relatively rare diagnosis that is often caused by tuberculosis or other infections agents such as fungi and parasites. Here is a great article, as mentioned in Morning Report, describing a case of constrictive pericarditis!

For our case, there is no diagnosis as of yet - hopefully Team 5 will keep us all posted! However, as we discussed, our differential for this case includes (but is not limited to):

1. Malignancy with associated Polymyositis/Dermatomyositis
2. Rheumatoid arthritis
3. Inclusion body polymyositis
4. Mixed connective tissue disorder

Dermatomyositis (DM) is less likely given that the patient has no skin manifestations. The classic skin features of DM include:

Gottron's papules: lacy, pink/violaceous, raised or macular lesions, symmetric over the dorsal interphalangeal joints, elbows, and knees
Heliotrope rash: a violaceous discolouration of the eyelids with periorbital edema
Shawl sign/V-sign: erythematous rash over the shoulders/neck (in the pattern of a shawl) OR neck/chest (V-sign)
Periungual telangiectasias: nail changes (cuticular hypertrophy) with or without Raynaud's
Mechanic's hands: coarse, fissured, scaly, hyperkeratotic hands

Thanks to former CMR David Frost for the DM links! For a complete review of DM please see this great review article in American Family Physician and a previous Blog by David Frost.

Signing off...

2010-06-28T13:03:00.002-04:00

This is the last blog post of the year for me...

I've enjoyed managing the TWH Tangents and TGH Horses and Zebras Blogs for 2009-2010. I hope you found them helpful

Your CMR 2009-2010

Pancytopenia

2010-06-14T11:11:00.003-04:00

Today we discussed an approach to the patient with pancytopenia

This is an indication for a bone marrow aspirate and biopsy, which usually shows increased or decreased marrow cells:

Hypocellular marrow
-Marrow toxins: May be dose-dependent, predictable as with chemotherapeutic agents, immunomodulators (methotrexate, cyclophosphamide, etc) or idiosyncratic (chloramphenicol, sulfa drugs, phenytoin, many others); radiation, EtOH
-Infection: Parvovirus B12, EBV, HIV, HHV-6, viral hepatitis; severe sepsis
-Immune: SLE, RA (rare), graft-versus-host
-PNH
-Idiopathic stem cell failure

Hypercellular marrow
-MDS, leukemias, lymphomas, myeloma
-Nutritional- severe megaloblastic anemia (B12, folate)
-Marrow replacement/infiltration: myelophthisic anemia , myelofibrosis, granulomatous disease (TB, sarcoid, fungal), solid tumor metastases (prostate and breast are most common)

The topic of the MGUS and multiple myeloma 'spectrum' came up. Here are some helpful criteria based on the NEJM review paper cited below:

MGUS
Marrow plasma cells less than 10% and M-protein (in blood) less than 30g/L
No clinical manifestations

Smouldering MM
Marrow plasma cells at least 10% and/or M-protein at least 30g/L
No clinical manifestations

Multiple myeloma
Marrow plasma cells over 10% and/or M-protein at least 30g/L
Clinical features of hypercalcemia, renal failure, anemia, bone lesions, infections, plasmacytomas

Waldenstrom's macroglobulinemia
Marrow plasma cells over 10% and M-protein over 30 (IgM)
Clinical features of anemia, bleeding, organomegaly, IgM immunoglobulin

Primary amyloidosis (AL)
Marrow plasma cells less than 10% and M-protein less than 30
Clinical fearures of fatigue, wt loss, purpura, nephrotic syndrome, CHF, neuropathy, orthostatic hypotension, massive hepatomegaly

Links:
Click here for a "medical mystery" from NEJM on panyctopenia
Click here for an excellent review paper on MGUS/myeloma differentiation

Eating disorders- medical complications

2010-06-12T13:27:00.003-04:00

Today we discussed the medical complications of eating disorders, which can be devastating and affect any system, with mortality as high as 10% in anorexia and 2% in bulemia. A few points:

Electrolyte/renal abnormalities
-Hypokalemia (may be from vomiting, diuretic abuse, laxative abuse)
-Metabolic alkalosis (volume depletion, diuretics)
-Hyponatremia (diuretics, polydipsia prior to weighings)
-Hypophosphatemia
-Hypomagnesemia
-Chronic kidney disease (may be contributed to by nephrocalcinosis, tubular dysfunction)

Cardiovascular
-Bradycardia (may or may not be secondary to electrolyte abnormalities)
-Cardiomyopathy (potentially reversible)
-Long QT
-Mitral valve prolapse

GI
-Parotic hypertrophy
-Decreased contractility
-Mallory-Weiss teats
-SMA syndrome
-Gallstones

Endocrine
-Amenorrhea
-'Sick euthyroid' syndrome
-Growth retardation
-Hypoglycemia

Skeletal
-Osteopenia/osteoporosis

Hematologic
-Marrow suppression

Neurologic
-Seizures
-Peripheral neuropathy

Dermatologic
-Lanugo hair
-Hair loss
-Yellow/orange skin- hypercarotenema
-Russell sign (callus over knuckles)
-Edema

Refeeding syndrome: When pts become rapidly "anabolic" after prolonged periods of starvation, severe electolyte abnormalities can develop and must be aggressively replaced.
-Hypophosphatemia
-Hypokalemia
-Hypoglycemia
-Edema

Link:

Click here for a NEJM review of anorexia

Click here for a case report of reversible severe cardiomyopathy from anorexia

Status Epilepticus

2010-06-08T10:46:00.003-04:00

Today we discussed an approach to status epilepticus and seizures in general.

Defined as continuous or repeated seizures without return to baseline for 20-30min (brain activity; may not have convulsions).
NB- there is a movement to make the time part of this definition much shorter (to 5 minutes)

Most seizures last 1-2 min. You need to intervene if beyond this point. At 20 min, the seizure per se damages the brain (scarring, self-perpetuating as sz focus). Also treat if series of short sz with incomplete recovery in between.

Approach is to treat the seizure AND look for the underlying cause

Acute causes: bleed, stroke, trauma, metabolic (e.g. hypoglycemia, hyponatremia, hypocalcemia, others), infections (esp. CNS), hypoxia, intoxication/drugs (or withdrawal), major organ faiure (uremia, hepatic failure)
Chronic: mass, non-compliance with meds

Complications of sz: aspiration, orthopedic complications, lactic acidosis, rhabdomyolysis

Practical approach:

ABC- clear the airway (do NOT put anything in the pt's mouth to prevent 'tongue biting, etc), roll on side, ensure breathing (apply O2)
Get monitors- Vitals, O2 sat,
IV access
CHECK THE GLUCOSE!, If low, amp of D50, glucagon 1mg IM if no IV
Thiamine 100mg IV (esp. if EtOH, pregnant, cancer pts)
Blood: CBC, lytes, renal, Ca profile, glucose, transaminases, drug levels, tox screen

If no immediately reversible cause (e.g. hypoglycemia), drugs to use acutely:

Benzos- lorazepam IV 12-24h anti-sz effect. Loraz 0.1mg/kg at 1-2mg/min (usually 1-2mg aIV at a time, repeated to max) This will stop 80% of sz.
May give diazepam PR if no IV access. 0.2mg/kg PR x 1 or midazolam 5mg IM x1

Phenytoin (Dilantin) 20mg/kg IV load at 50mg/min (e.g. 1400mg over 30 min in 70kg)
If needed, give further 5-10mg/kg.
A couple of points about phenytoin for status:
Do not mix phenytoin and D5; it crystallizes, which is not very helpful in status epilepticus.
Never give dilantin and dopamine together; can cause profound hypotension for unclear reason

Phenobarbital: Strongly consider intubation here
20mg/kg IV @50-75mg/min. This pt should be in ICU

Others: Propofol infusion, midazolam infusion

Look for underlying- bloodwork, CT, LP if fever.
Mimics of status: myoclonus, rigors, movement disorders, herniation (early)

Link:

Click here for an excellent review of status epilepticus from Chest (yes, a weird place for it to be)

Endocarditis

2010-06-03T10:14:00.003-04:00

Today we discussed endocarditis. This is a very important topic to have knowledge of regardless of what area one practices in, both in terms of suspecting and confirming the diagnosis, and proper management. The natural history of untreated endocarditis is 100% mortality. A few points:

Traditional breakdown is by time course; perhaps less relevant today than previously.

Subacute classically presents as a chronic, wasting illness, with fever, wt loss and progressive heart failure and complications as the heart is progressively damaged over weeks to months. Typical organisms are (in order) viridans group streptococci, enterococcus, st. aureus

Acute presents with rapidly progressive valvular destruction over days, often with catastrophic hemodynamic and other complications. Typical organisms are st. aureus, enterococci, viridans group streptococci, HACEK organisms.

Other useful classifications that help with predicting microbiology and complications are native vs. prosthetic valve and R-sided vs. L-sided.

Some physical findings (not exhaustive!)

Signs of valvular involvement or local complications:
-murmurs (esp. AI, MR, TR)
-signs of L or R-sided heart failure
-bradycardia (heart block can occur from paravalvular abscess)

Signs of embolic complications/phenomena and vasculitis
-any focal neurological deficit-peripheral cutaneous signs: Splinter hemorrhages, Osler nodes, Janeway lesions, Roth spots, clubbing, subconjuntival and other mucosal petechiae. Remember to look for these on the feet too
-splenomegaly

Signs of underlying causes
-track marks for IDU
-oral exam for dental hygiene

Diagnosis:
-multiple blood cultures from different sites off antibiotics are KEY to the diagnosis and management

Modified Duke's criteria can be helpful (see link for full details):

Major

-multiple blood cultures consistent or Q-fever serology +ve
-echo consistent (oscillating mass, abscess, dehiscence of prosthesis)
-new murmur

Minor
-predisposing heart condition or IVDU
-fever
-vascular phenomena (emboli, etc as above)
-immunologic phenomena (as above)
-blood cultures not meeting criteria for "major"

Definite: (2 major) or (1 major+3 minor) or (5 minor)
Possible: (1 major and 1 minor) or (3 minor)

ECG- check for new blocks (esp. 1st degree AVB; suggests abscess)

Therapy
General principles- need cidal antibiotic. Generally need minimum 4-6 wks of IV therapy

Indications for valve replacement (NB- surgery is probably under-utilized)
-CHF as a direct consequence
-Severe valvular insufficiency
-Paravalvular abscess
-Embolic phenomena post-initiation of therapy
-Persistently positive cultures or fever despite adequate medical therapy
-Size of vegetation (relative)

Links:

Click here for the complete modified Duke's criteria

Click here for a review article from NEJM

Paroxysmal Nocturnal Hemoglobinuria

2010-05-31T11:46:00.003-04:00

Today we discussed a very rare cause of anemia and thrombosis, PNH.

This disease results from an acquired mutation in DNA encoding components of complement system, which leads to several clinical manifestations:

1) Hemolysis, which is episodic ("paroxysmal"). The degree of hemolysis depends on how many RBCs are abnormal. Unclear why it is sometimes nocturnal, as shown above. Chronic hemolysis can cause severe anemia, and renal failure from myoglobin-induced tubular damage

2) Thrombosis. It is unclear why patients with PNH are hypercoagulable; it may have to do with platelet abnormalities in PNH (all hematopoietic stem cells can be involved). Thrombosis is usually venous, but can be arterial. The hallmark is thromboses in relatively unusual places, most commonly portal vein or other intra-abdominal veins and cerebral venous sinus thrombosis.

3) Diminished hematopoiesis. Because marrow stem cells are involved, pancytopenia can be ther presenting manifestation.

Diagnosis: "PNH assay", which is flow cytometry for the clone of cells with abnormal complement-related proteins.

Therapy:

1) For hemolysis:
-supportive measures include transfusion, iron supplementation, folic acid supplementation.
-specific therapy is Eculizumab, a monoclonal antibody that inhibits complement activation, and significantly reduces hemolysis. Limiting factor is cost, estimated at $400,000 / year

2) For thrombosis:
-anticoagulation with heparin then warfarin as secondary prevention
-there may be lower risks of thrombosis on Eculizumab
-there is retrospective evidence supporting prophylactic anticoagulation with warfarin in selected patients

Stem cell transplant is also an option reserved as a last resort

Links:

Click here for the paper showing the effect of Eculizumab in PNH

Cocaine- medical complications

2010-05-20T11:54:00.003-04:00

Today we discussed cocaine intoxication. Some points:

Acute intoxication:
Cocaine is a sympathomimetic, and acute intoxication presents with this toxidrome:
Hypertension, tachycardia, fever, flushing, diaphoresis, mydriasis, altered mental status, possibly seizures

The anticholinergic toxidrome presents very similarly. The 2 can be distinguished by:
-diaphoresis in sympathomimetic (vs. 'dry as a bone' in anticholinergic)
-more prominent hypertension in sympathomimetic

Management:
Besides the specific organ issues discussed below, general managment consists of
-benzodiazepines (mainstay!)
-if BP control is required, DO NOT USE PURE BETA BLOCKERS; this causes unopposed alpha agonism and makes hypertension/vascular effects worse; labetalol is safe in this situation (because it is both alpha and beta-blocker), and phentolamine or phenoxybenzamine are alpha-blockers that can be used.

Common specific organ effects (besides acute intoxication):
CNS- cerebral vasoconstriction, including stroke; movement disorders
CV- coronary vasospasm, which may cause MI; tachyarrhythmias, hypertensive urgency/emergency
Resp- perforated septum, smoking cocaine causes SOB, wheezing, chest pain hemoptysis in a large proportion of users. Acute fever, dyspnea, hypoxia, infiltrates soon after smoking has been called "crack lung"; is from alveolar damage. Interstitial lung disease is possible.

Recently recognized complication:
In the past year or so, there have been many recognized cases (including at this hospital) of patients presenting with agranulocytosis from cocaine "contaminated" with levamisole, an anti-helminth drug used in animals.

Click here for a summary of this complication

Click here for a paper from the Annals of Internal Medicine describing this. CMAJ has a similar report.

Dilated cardiomyopathy

2010-05-19T15:50:00.004-04:00

Today we discussed causes of dilated cardiomyopathy,

Some etiologies of DCM:

1) Ischemia
This is the most common cause of cardiomyopathy in the developed world. Within the category of "initially unexplained" DCM, ischemia is less common, since this is usually the first etiology excluded.

2) Valvular heart disease
Some valvular lesions are compensated chronically by LV dilation- mitral regurgitation and aortic insufficiency are the most common (although NB- MR can follow DCM from dilation itself; this is often termed "functional MR"). End-stage aortic stenosis can also cause DCM

3) Infections
-Viral infections can cause myocarditis, which can lead to DCM. Coxsackie, adeno, echo are the most common. HIV is a recognized as a cause of DCM
-Chagas' disease (a protozoan infection) is most common cause of DCM in Central and South America.
-Lyme disease is associated with cardiac muscle dysfunction, although heart blocks are more common.

4) Toxins
-Alcohol; amount and duration correlate with risk
-Cocaine; may be independent of ischemia
-Anthracycline-based chemotherapy (usually takes a dose of 450mg/M2; each cycle has about 50)

-Trace elements. Rare cause; cobalt, arsenic, mercury... Click here for an interesting "outbreak" of cobalt-induced DCM in Quebec

5) Genetic

6) Peripartum CM- unclear cause; occurs in late pregnancy and early post-partum. Carries relatively good prognosis, but high risk of recurrence in subsequent pregnancies

7) Infiltrative CM's- hemochromatosis, sarcoidosis, amyloidosis

8) Tachycardia-induced cardiomyopathy. Prolonged tachycardia can cause reversible, sometimes severe, LV dysfunction

9) "Stress cardiomyopathy" AKA "Takotsubo" cardiomyopathy:
Rare, but increasingly recognized cause of LV dysfunction, with characteristic apical ballooning on 2D echo. May be associated with ECG changes including ST elevation. Sometimes associated with a stressful event (physiological or psychological); self-resolving. Click here for the origin of this term, the Japanese octopus trap...

In a significant proportion of cases, the cause remains idiopathic.

Links:

Click here for a recent NEJM review of DCM that goes over the evidence base for various pharmacologic and device therapies

Click here for a study looking at underlying causes and prognosis for initially idiopathic dilated cardiomyopathy.

Hyperthyroidism- physical exam

2010-05-14T09:52:00.004-04:00

Today we discussed some of the physical exam findings of hyperthyroidism and how to diagnose a goiter

Hyperthyroidism
A general approach to the examination for hyperthyroidsm with some possible findings
General appearance: restless, anxious, thin
Vitals- tachycardia, atrial fibrillation, wide pulse pressure, fever
Eyes-
lid lag (superior sclera visible as patient looks down),
lid retraction, widened palpebral fissure
Graves' orbitopathy (see below)
CNS- fine tremor with hands outstretched, increased reflexes, proximal muscle weakness
CV- flow murmur
Abdo- increased bowel sounds
Extremities- warm, moist skin, velvety skin, pretibial myxedema (in Graves)
Associations: other autoimmune- e.g. vitiligo, adrenal insufficiency

A word about eye findings in hyperthyroidism
Some eye findings are general to all causes of hyperthyroidism (from increased sympathetic activity), and some are specific to Graves' disease.

Sympathetic
-lid lag
-lid retraction
-stare
-conjunctival injection

Graves orbitopathy
-EOM involvement
-lid edema
-exophthalmos
-loss of visual acuity

Evidence for how to diagnose a goiter:
Inspect and palpate
-look for lateral prominence = distance from imaginary line between cricoid and suprasternal notch to surface of thyroid gland
-Categorize as normal or goiter
-Subcategorize as small (1-2x) or large (over 2x) goiter

Ruling out a goiter:
Normal size by palpation (negative R 0.15)
No lateral prominence (NLR 0.41)
“Goiter ruled out” = normal thyroid size or gland not visible with neck fully extended

Ruling in a goiter:
Estimated size by inspection;/palpation
1-2x normal (positive LR 1.9)
over 2x normal (PLR 25)
Lateral prominence 0-2mm (PLR 3.4)
Lateral prominence > 2mm (PLR infinity)
“Goiter ruled in” = large goiter or lateral prominence over 2mm

Link:

Click here for link to JAMA Rational Clinical Examination for goiter (unfortunately, a special JAMA subscription is required)

Scleroderma

2010-05-12T09:20:00.003-04:00

Today we discussed scleroderma (AKA systemic sclerosis)

This is a multisystem disesase of small vessels and skin/organ fibrosis

Epidemiology: Age 35-65, Female more common than male (7-12:1).

There are 2 types of systemic sclerosis- limited and diffuse

Limited SSc: sclerosis, thickening of distal limbs without truncal involvement. CREST fits into this category. Associated with anti-centromere AB. Calcinosis refers to localized hand masses on fingers/forearms. Telangiectasias are seen in face/mucosa/hands. Most serious manifestations of limited are pulm HTN, digital ischemia.

Diffuse SSc: thickening over distal and proximal limbs and trunk with significant organ involvement. Criteria are thickening of extremities proximal to MCPs or digital ischemia, pulmonary fibrosis. Edematous skin, painful joints, tendon friction rub, rapidly progressive skin fibrosis. Associated with SCL70 antibody.

Clinical:
Initially nonspecific; Raynaud's, fatigue, MSK complaints followed in variable time period by further sx (soon in diffuse, later in limited).
First specific manifestations are skin thickening, starting as swelling/puffiness over fingers/hands.
Subsequently variable; skin, pulmonary, cardiac, renal, GI involvement.

90% of SSc pts have Raynaud's and fibrosis of fingers, with loss of digital pads (sclerodactyly) and digital ulceration.

Skin: edema, tightness, decreased flexibility, contractures, then fibrosis.

MSK: arthralgias, arthritis, calcinosis, tendon involvement. Late: weakness/atrophy, possible overlap myosits

Pulm: Pulmonary fibrosis, PFTs show decreased volumes, diffusion impairment.

GI: small mouth, dysphagia, GERD/esophagitis. Loss of peristalsis

Cardiac: Myocardial fibrosis, myocarditis, diastolic dysfunction

Renal: Pathological change in most (small vessel vasculopathy); extreme is scleroderma renal crisis (acute kidney injury, with microangiopathic hemolytic anemia)

Therapy: No proven disease modifying agents; treatment is by organ system involved. In severe cases, immunosuppression may be used (e.g. steroids, methotrexate, cyclophosphamide)

Skin- key is moisturize, treat pruritus
Raynaud's- CCB, prazosin in severe
GI- treat GERD, prokinetics for paresis
Renal- ACE-I
Pulmonary- measures for pulm HTN

Links:
Click here for a recent NEJM review of scleroderma
Click here for a review from Rheumatology on scleroderma

Alcoholic hepatitis

2010-05-10T13:44:00.005-04:00

Today we discussed alcoholic hepatitis.

This is distinct from chronic alcohol-induced liver disease, which causes steatosis and predisposes to fibrosis, then cirrhosis.

Alcoholic hepatitis is a clinical syndrome of jaundice and liver failure (usually after decades of over 100g/d intake). Patients have often stopped drinking for several weeks before onset. Female sex is a risk factor for this specific condition (with equal intake to men), but more men have the typical intake required.

Rapid onset of jaundice is the cardinal sign. Others include fever and ascites. Liver is typically enlarged and tender. Signs of chronic liver disease are often present.

Alcoholic hepatitis is a poor prognostic indicator; 40% of patients with severe alcoholic hepatitis die within 6 months

Diagnosis:
Lab: AST usually above 2x ULN, but rarely over 1000. ALT is lower. WBC count (esp. neutrophils), and INR are usually high. Renal failure (if it is hepatorenal syndrome) carries a poor prognosis.
Biopsy shows swollen hepatocytes with Mallory bodies. Cholestasis may be present.

Ddx includes NASH, viral hepatitis, drug-induced, fulminant Wilson's, autoimmune liver disaese, alpha-1, pyogenic abscess, cholangitis, HCC.

Severity indices:
Maddrey's discriminant function: [4.6 x (pt's PTT - control PTT)] + bili (mg/dL)
Value over 32 indicates severe alcoholic hepatitis; this is threshold for starting steroids.
MELD over 21- severe

Therapy:
General
salt restriction, diuretics, lactulose, thiamine, withdrawal tx as indicated. Tap for SBP
EtOH abstinence
Specific
Steroids: prednisolone 40mg/d x 4 weeks, then taper (or equivalent)
Pentoxyfylline- 400mg PO TID increases in-hospital survival; little head-to head data comparing to steroids; should be considered where there are contraindications to steroids.

Link:
Click here for a 2009 review from NEJM on alcoholic hepatitis that goes over the evidence for various therapies.

Syphilis

2010-04-28T08:58:00.004-04:00

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)

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

Secondary:
-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.

Tertiary:
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

Treatment:
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.

Links:
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

Myelopathy causes

2010-04-21T09:27:00.004-04:00

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)

Link:

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

Dyspnea in a patient with cancer

2010-04-15T18:41:00.003-04:00

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:

Infections:
-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

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

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

Neuromuscular:
-Lambert-Eaton
-phrenic nerve involvement
-steroid myopathy

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

Pleural:
-pleural effusion
-pneumothorax
-pleural involvement of malignancy itself

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

Other:
-anemia

CLL and its complications

2010-04-14T10:11:00.005-04:00

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)

Leukostasis:
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

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

Amyloidosis

2010-04-13T11:00:00.004-04:00

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.

Link:

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

Hypercalcemia

2010-04-09T09:18:00.003-04:00

Today we had some discussion about hypercalcemia. Some points:

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

Etiology:
Useful first division is by PTH level
1) High PTH- expect high Ca, low PO4.
-primary/secondary/teriary hyperparathydoidism, parathyroid hyperplasia
-lithium
-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.)
-Myeloma
-Medications- HCTZ, Ca, vit. D
-Milk alkali syndrome
-Hyperthyroidism

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

Tx:
Fluids!
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

Atrial fibrillation- acute management

2010-04-06T09:32:00.006-04:00

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.

Lymphadenopathy

2010-04-05T11:06:00.003-04:00

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.

Local-

Cervical:
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)

Supraclavicular:
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)

Axillary:
Infection- cat scratch, trauma
Malig- BrCa, mets

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

Inguinal:
Infection- lower ext/gu inf
malig- lymphoma

Generalized:

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

Approach:

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.

Link:

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

Diplopia and dysconjugate gaze, ptosis

2010-03-31T10:55:00.007-04:00

Today we discussed an approach to ptosis, diplopia and dysconjugate gaze. A few points:

An approach to diplopia: A useful first step is to break down between monocular (i.e. present with 1 eye closed) and binocular (far more common). If binocular, run through the potential causes anatomically from the central to peripheral.

Monocular: Consider ophthalmological causes

Binocular:
If changes through the day, consider myasthenia gravis
If thyroid disease present, consider Graves ophthalmopathy
If facial trauma, consider orbital fracture (most likey to cause inferior oblique palsy because of orbital floor fracture) other orbital diseases (e.g. tumor, infiltration, etc)

Once neurological:
1) Cerebral hemisphheres- gaze palsy/preference from frontal lesion (e.g. stroke), progressive supranuclear palsy (vertical then horizontal palsy with dementia, parkinsonism)
2) Brainstem- III, IV, or VI nuclei, internuclear ophthalmoplegia (can't adduct eye)- ipsilateral median longitudinal fasciculus (MLF)- leaves convergence intact. Brainstem causes include ischemic stroke, tumor, bleed, infection, demyelination
3) Nerves exiting the brainstem- compression (tumor, aneurysm), infarction or inflammation(e.g. DM2, vasculitis). REMEMBER WERNICKE'S! (thiamine deficiency), Miller-Fisher variant of Guillan-Barre (would have areflexia, ataxia),
4) Meninges- meningitis, neurosarcoid, leptomeningeal spread of cancer
5) Cavernous sinus thrombosis- III, IV, V1, V2, VI pass through; often associated with facial infections
6) NMJ- myasthenia as above

In someone with diplopia, how do you figure out which eye is the problem (if it's not obvious)?
A couple of pearls:
1) If someone complains of diplopia on looking in one diagonal direction, it is either the same-sided and oriented rectus muscle or the other-sided oppositely-oriented oblique muscle (e.g. diplopia on looking up and right, it is either R superior rectus or L inferior oblique. Diplopia on looking down and L is either L inferior rectus or R superior oblique)
2) If you cover up an eye when the patient is having diplopia, the eye that, when covered, takes away the most peripheral image is the problem

Ptosis:
Some considerations:
CN III palsy- should have ocular movement abnormalities, may have pupillary involvement (would be mydriasis from loss of parasympathetics)
Horner's syndrome- miosis (from loss of sympathetics), anhydrosis
Neuromuscular junction disorders- myasthenia gravis, botulism

Links:

Click here for a review from Neurology on evaluation of diplopia (need subscription to get)

Click here for a review of the link between migraine and stroke (a controversial, hot topic)

Pleural effusions

2010-03-29T10:41:00.009-04:00

Today we discussed pleural effusions

Most common causes of effusion in North America are CHF, pneumonia and cancer.

Indication for thoracentesis: Clinically significant effusion (i.e. over 10mm thick on u/s or lateral decubitus) with no clearly known cause.
If CHF with bilateral effusions, trial of diuresis first. 80% of CHF effusions are bilateral. If unilateral, should be tapped. 75% of CHF effusions resolve within 48h of diuresis.
If over 3d, thoracentesis is indicated.
If pt has SOB at rest, therapeutic in addition to diagnostic tap should be done (i.e. up to 1-1.5L).

No need to do routine CXR post except if air is obtained, c/p, cough, dyspnea.

Bloody effusion narrows Ddx somewhat to cancer, PE, trauma, infection (inc. pneumonia, TB)

Transudative: leading causes are CHF, cirrhosis, PE.
Exudative: leading causes are pneumonia, cancer, PE.

Light's criteria for exudative effusion:
Any of
protein level pleural:serum over 0.5
LDH pleural:serum of over 0.6
pleural LDH over 2/3 upper limit of normal for serum

Light's criteria are sensitive for exudate; may have transudates falsely called exudates. If clinical appearance suggests transudate but Light's criteria says exudate, measure albumin in serum vs. pleural fluid. If serum albumin is over 12 greater than pleural fluid almost all have transudative. This criterion is more specific for transudate, because it calls some exudates transudates.

If transudative effusion, determine which of CHF, cirrhosis, PE exists.
If exudative, further workup is needed, including cell counts, culture, glucose, cytology, TB studies.

Cell count:
Predominence of PMNs (over 50%) suggests acute process (parapneumonic, PE, pancreatitis). Only ~15% of malignant, and almost no tuberculous effusions have PMN over 50%.
Mononuclear predominance (lymphocytic) suggests chronic process; cancer, tuberculous, post-CABG.
Eosinophils (over 10%) is usually blood or air in pleural space. Unusual causes are Churg-Strauss, drugs (dantrolene, bromocripine, nitrofurantoin), asbestosis, parasitic infections.
Basophils: leukemic infiltration

Culture: yield is higher if also blood C+S.

Glucose: low glucose suggests empyema or malignant. Less commonly, hemothorax, TB, parasitic (e.g. paragonimiasis), primary inflammatory (e.g. RA, SLE, Churg-Strauss)

Cancer: cytology yield is highest for adenoca. Less useful for mesothelioma, squamous, lymphoma, sarcoma. VATS is choice if suspected ca but negative cytology. If lymphoma suspected, flow cytometry can show pleural fluid clonal population.

TB: tuberculous pleuritis effusions resolve, but pulmonary or extrapulm TB develop in >50%. Investigate for TB if lymphocytosis. Less than 40% have positive pleural cultures.

pH: indicated if parapneumonic or malignant suspected.

PE: Suspect if dyspnea out of keeping with size of effusion, pleuritic c/p, hemoptysis.

"Complicated pleural effusion"- i.e. an indication for drainage (pigtail or surgical chest tube) Any of
1) cloudy fluid
2) pH less than 7.2
3) Glucose less than 2.2
4) Pleural to serum glucose ratio less than 0.5
5) LDH over 1000
6) Neutrophils over 25000
7) effusion occupying 50% of hemithorax (relative indication)

Links
Click here for NEJM review of pleural effusions by Dr. Light himself
Click here for an excellent review from Clinical Infectious Diseases on empyema and parapneumonic effusions

Ileitis

2010-03-23T17:11:00.006-04:00

Ruptured terminal ileum from intestinal TB

Today we discussed ileal inflammation (AKA 'terminal ileitis') and some related issues. A few points:

In any patient presenting with RLQ pain, always exclude life-threatening conditions:
-Appendicitis, diverticulitis with or without abscess
-Strangulated hernia
-Ectopic pregnancy
-Pelvic inflammatory disease
-Others presenting atypically (e.g. ruptured AAA, bowel obstruction, etc)

Specific causes of ileitis:
Infectious:
Bacterial: yersinia, campylobacter, typhoid (from Peyer's patch enlargement), actinomyces Mycobacterial: TB, or non-tuberculous mycobacteria
Parasitic: amebiasis- can present exactly like Crohn's
Viral: CMV
Typhlitis (aka neutropenic enterocolitis or ileocecal syndrome)- seen in immunocompromised pts

Inflammatory:
Crohn's disease
Microscopic colitis

Neoplastic:
Small bowel lymphoma

Vasculitic:
Henoch-Schonlein purpura (rarely!)

Intestinal TB
Difficult to diagnose; need high index of suspicion;
non-specific chronic abdominal pain is the most common symptom, with constitutional symptoms. Palpable mass in 25-50% of patients. May see ascites, which helps to distinguish from some of the above causes of ileitis. Treatment is similar to pulmomary TB, and usually responds well

Links:
Click here for a CMAJ review of extrapulmonary TB
Click here for a NEJM clinical pathological conference where the differential of ileitis is discussed

Mitral stenosis

2010-03-17T11:27:00.006-04:00

Today we discussed mitral stenosis. A few issues that came up about this big topic:

Predominant cause is rheumatic. Many pts with rheumatic heart disease have multiple valve lesions (25% have isolated MS; 40% have MS+MR; ~35% have aortic valve involvement)

Primary problem in MS is insufficient flow across the MV that leads to LA enlargement and high LA pressures to compensate. Remember that the pressure gradient for given valve area varies with square of flow (i.e. doubling flow requires 4x higher pressure gradient- this is also important in aortic stenosis).

Therefore, situations that increase flow (usually from tachycardia) cause dyspnea -
A-fib, infection, pregnancy, exercise are common ones

Tachycardia also decreases diastolic filling time, decreasing forward flow.

The high LA pressures needed to compensate for decreased diastolic filling time in tachycardia can lead to flash pulmonary edema. Atrial fibrillation is even worse because the atrial kick is relatively more important.

LA enlargement from elevated pressures predisposes to AF

Important complications of MS: pulmonary edema, atrial fibrillation, cardio-embolic stroke (from stasis and A-fib- very high risk of stroke in this setting), pulmonary HTN, endocarditis

Symptoms:
1) Dyspnea: most common, esp with exertion. Any situation causing increased flow across valve brings on (esp. tachycardia).
2) Hemoptysis: May occur from rupture of dilated bronchial veins
3) Chest pain: uncommon; often from secondary pulmonary HTN
4) Palpitations: A-fib
5) Other: Hoarseness (Ortner's sign for medical jeopardy fans), edema

Physical:
General- May see obvious resp distress, mitral facies (i.e. pink-purple patches from vasoconstriction on face)
Pulse: May see A-Fib. Usually normal, but may see low volume.
JVP: May see signs of pulmonary HTN as consequence of MS
Palpation: may have tapping S1 (pliable anterior leaflet). In LLD, may palpate diastolic thrill. May have RV heave and palpable P2 from pulm HTN.

Heart sounds:
Major findings are
1) loud S1 early, soft late in course
2) opening snap- early diastolic sound of MV opening; moves closer to S2 with more severe
3) diastolic rumble (murmur) post- opening snap
4) late diastolic murmur with presystolic accentuation from atrial kick

Others:
1) ECG- L atrial enlargement- 'p-mitrale'
2) CXR- splayed carina, double R heart border, flat or everted L heart border from LA enlargement

Link:

Click here for a nice website from the Cleveland Clinic summarizing MS

Thrombocytopenia and ITP

2010-03-15T10:45:00.006-04:00

Today we discussed an approach to a bleeding diathesis, and issues related to thrombocytopenia and ITP. A few key points:

General approach to bleeding history:
Try to differentiate primary hemostasis problem (vascular response and platelet plug) vs. secondary hemostasis problem (fibrin clot, or resolution phases)

Clues:
Primary- excessive immediate post-traumatic bleeding usually. Petechiae, purpura, mucosal bleeds: nose, mouth, gums, GI, uterine
Secondary- delayed, subcutaneous, deep tissues, joints, GI/GU, post-op.
Acquired vs. inherited: new-onset vs. lifelong, new medical problem or drug, FHx.

General approach to thrombocytopenia

3 major categories
1. Decreased platelet production
2. Increased platelet destruction or platelet consumption
3. Sequestration

Decreased PLT production: Bone marrow problem; marrow shows decreased megakaryocytes
Aplastic anemias (congenital or acquired)
Myelophthisic anemia - i.e. marrow replacement (malignancy, granulomatous, etc)
Megaloblastic anemias (B12, folate deficiency)
Marrow suppression from drugs, toxins, infection, etc)

Peripheral destruction or consumption
Immune-mediated: ITP- Primary (idiopathic) or secondary (SLE, HIV, EBV B-cell disorders), drug-induced, post-transfusion
Non-immune: Thrombotic thrombocytopenia purpura- TTP, disseminated intravascular clotting

Sequestration:
Usually portal hypertension, hypersplenism

ITP specifics

Most cases are idiopathic.
In adults, it is generally chronic, the onset is often insidious. Approximately
twice as many women as men are affected

If all these conditions are met, bone marrow bx (gold standard) is not required
-age less than 60
-isolated TCP
-no splenomegaly
-no lymphadenopathy

To exclude before calling "idiopathic ITP":
-non-immune causes of TCP (primary marrow problem, TTP, HIT, DIC, etc)
-infection- HIV especially, EBV
-inflammatory disorders, esp. SLE
-malignancy, esp. B-cell disorders (CLL, myeloma, etc)
-drug induced (for immune-mediated, B-lactams, quinine, vancomycin, others)

Therapy:
In serious bleeding
1) hemodynamic and RBC transfusion support
2) platelet transfusion
3) steroid
4) IVIG
5) some evidence for factor VII in life-threatening bleeding

Most pts require therapy; those who do not are those with mild (over around 50), asymptomatic, incidentally discovered thrombocytopenia. Otherwise, options are:
-Steroids (prednisone 1mg/kg, tapered over 4-6 weeks depending on response or dexamethasone 40mg PO x 4d). 50% have relapse. RCT underway comparing these regimens
-IVIG; indicated for severe bleeding, pre-operatively or pre-delivery, and in steroid-refractory cases
-Splenectomy (need appropriate vaccinations first)
-Rituximab (controversial whether should be tried before splenectomy)

In chronic refractory cases, there may be a role for vincristine, azathioprine and cyclophosphamide, and thrombopoeitin agonists

Links:
Click here for a NEJM review of ITP

Click here for a series demonstrating effect of short course of dexamethasone described above

Hypocalcemia

2010-03-11T10:39:00.002-05:00

Today we discussed hypocalcemia. A few points:

Clinical manifestations:
-Paresthesias
-Lethargy
-Seizures
-possibly arrhythmias (lengthens QT)

-Chvostek's sign:
Tap cheek 2cm anterior to tragus, look for ipsilateral upper lip twitch

www.youtube.com/watch?v=CVpWhiQNwGc

NB- this video is freely available on YouTube, and is not a patient cared for in this hospital

-Trousseau's sign:
Inflate BP cuff above systolic pressure for 3 minutes, look for painful carpal spasm (shown above)

An approach to causes of hypocalcemia (which drives appropriate history, physical, and investigations):

Think of major determinants of calcium handling, and what can affect each:

Low PTH:
-iatrogenic (most common cause); e.g. post-thyroidectomy
-autoimmune (can be part of autoimmune polyendocrine syndrome with vitiligo and candidiasis)
-infiltration of the parathyroids (sarcoid, hemochromatosis)
-hypomagnesemia (alters PTH receptor sensitivity)

Low Vitamin D:
-malabsorption of fat-soluble vitamins (ADEK)
-liver disease
-kidney disease
-inadequate sun exposure

GI tract:
-malabsorption of calcium (proximal small bowel): celiac, Crohn's, others in addition to vit D malabsorption

Kidneys:
-Loop diuretics
-Calcium wasting: Fanconi's syndrome (proximal tubular reabsorption problem; causes hypocalcemia, hypophosphatemia, non-anion gap metabolic acidosis, hypoglycemia, hypoalbuminemia)

Bone:
-"Hungry bone syndrome"- post parathyroidectomy after hyperparathyroidism, increased bone uptake of calcium after prolonged calcium "leaching"
-osteoblastic metastases (esp. prostate, breast)

Intravascular Ca binding:
-citrate (e.g. in dialysis or massive transfusion)- binds ca
-hyperphosphatemia

Calcium deposition sites:
-severe pancreatitis
-rhabdomyolysis

Others:
-secondary hyperparathyroidism; often have normal or low Ca in renal failure for many reasons
-DiGeorge syndrome- affects PTH receptor
-Bartter's syndrome- acts like a loop diuretic causing calciuresis
-"pseudohypoparathyroidism"- looks like hypoparathyrodism, except PTH is high; receptor mutation

Tip: The phosphate level can be quite helpful in sorting out causes; PTH increases calcium and decreases phosphate. Vitamin D increases both calcium and phosphate.

Link:

Click here for a NEJM review of hypoparathyroidism that discusses much of above

Peripheral neuropathy

2010-03-10T12:51:00.004-05:00

Today we discussed peripheral neuropathy. A few points on this very broad topic:

Important differential: 'THIN'
1) Toxic, Metabolic- medications, DM2, EtOH, metals, B12
2) Hereditary- Charcot-Marie-Tooth and variants
3) Inflammatory and infectious- Guillain-Barre, CIDP (chronic inflammatory demyelinating polyneuropathy), vasculitis, and HIV, HTLV, leprosy
4) Neoplastic/paraneoplastic: multiple myeloma

Important points on history:
1) Temporal course- acute (days to weeks), subacute (4-8 weeks), chronic (>8 weeks); relapsing? progressive?
2) Proximal vs. distal motor and sensory symptoms (trouble reaching overhead, climbing stairs vs. opening jars, picking things up)
3) What are the sensory symptoms? negative- e.g. numbness or positive- e.g. paresthesias, burning, throbbing, etc.
4) Questions around above differential

Important physical exam:
Atrophy, fasiculations for LMN lesion
Distribution of weakness- nerve vs. plexus vs. root
Reflexes
Sensory- pin prick, vibration (named nerve vs. nerve root vs. length-dependent)

Important investigations:
FBG, HbA1C
CBC, Cr, Vitamin B12, TSH, serum and urine electrophoresis, HIV

Multiple named nerve palsies = mononeuritis multiplex
Essentially diabetes-related vs. vasculitis.
Common nerves involved in DM2: CN III, IV, VI, median nerve, peroneal nerve.
Vasculitides that commonly cause mononeuritis multiplex: Churg-Strauss, polyarteritis nodosa, rheumatoid arthritis with vasculitic component

Link:
Click here for an excellent review of peripheral neuropathy from Lancet

Pancreatitis

2010-03-09T09:48:00.003-05:00

Indeed...

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

Acute = no pre-existing pancreatic pathology; usually resolves without permanent damage.
Chronic = pre-existing fibrosis/scarring/calcification. EtOH-induced is often acute on chronic.

Pancreatitis is essentially autodigestion, release of zymogens, and in severe cases, a retroperitoneal chemical burn injury.

Etiologies:
-EtOH
-Gallstone
-Drugs (commonly reported include some HIV medications, HRT, azathioprine, tetracycline, 5'ASA, sulfasalazine)
-Metabolic- hypertriglyceridemia, hypercalcemia
-Iatrogenic (esp. post-ERCP)
-Autoimmune
-Others- anatomic (pancreas divisum), scorpion bites (everyone's favourite), cystic fibrosis, infection

Symptoms: Epigastric abdo pain, better leaning forward (Ingelfinger's sign for medical jeopardy fans), radiating to back, N+V

Things to look for on exam:
Vitals: Tachypnea, tachycardia, fever
-jaundice
-abdominal distension, absent bowel sounds (ileus)
-cullen/grey turner signs
-dull lung bases from pleural effusion
-abdominal tenderness.

Lab: Lipase/amylase (NB- macroamylasemia, salivary gland pathology, and tubo-ovarian pathology give high amylase but normal lipase). Lipase and amylase support the dx, not make it. The levels fall off in days.

Imaging:

AXR: may show colon-cutoff sign or ileus

CT may show pseudocyst or necrosis in addition to stranding, inflammation

Prognostic factors: Development of organ failure, SIRS (look for ARF-most common, ARDS), necrosis, abscess, pseudocyst. Others: Ranson criteria, APACHE score, etc.

Therapy:

Largely supportive; monitor closely for complications.

Principles of managment:
1) Fluid resuscitate aggressively as needed
2) Watch respiratory status, and intervene if necessary (ABG's, etc)
3) Watch for other organ involvement (AKI, DIC, etc)
4) Nutrition: Do not rest the pancreas; start enteral nutrition (increased metabolic requirements, decreased bacterial translocation) - evidence for early PO feeding.
5) Pain managment
6) Antibiotics- very controversial; only convincing evidence is in pancreatitis with necrosis (there are scoring systems based on CT), in which case meropenem has proven benefit. In some cases, a fine needle aspirate of a collection is done to determine whether infected and only treated if positive.
7) If gallstone-related, ERCP and cholecystectomy (during current admission if mild or delayed if severe) reduces recurrence risk from 25% to 8%.

If severe deterioration, consider surgery for debridement, but this is high-risk.

Links:

Click here for an interesting paper highlighting common problems and pitfalls in pancreatitis management

Click here for a Cochrane review of antibiotics in pancreatitis

Click here for a trial comparing symtom-drive vs. standing benzos for alcohol withdrawal

Brugada syndrome and Arrhythmogenic RV cardiomyopathy

2010-03-08T10:07:00.005-05:00

V1 leads in Brugada syndrome (left) and ARVC (right)

Today we discussed syncope. For a discussion of an approach to syncope with a link to an excellent review from Circulation, click here

The topics of the Brugada syndrome and arrhythmogenic right ventricular cardiomyopathy -ARVC (aka ARVD, d for 'dysplasia') came up. A few points on these rare, but important causes of syncope:

Brugada syndrome:

Characterized by "pseudo-RBBB", with ST elevation in R precordial leads and high incidence of sudden death in patients with structurally normal hearts (up to 4% of all sudden deaths, 20% of cases with structurally normal heart). Typically presents in adulthood.

Prevalence is unknown; estimated to be 5/10,000 but may be as high as 50/10000 in Asian populations.

May be associated with either atrial or ventricular arrhythmias.

Diagnosis:
Classic ("type 1") ECG is "coved" ST eleation over 2mm in one or more of V1-V3 with T-inversion (shown above).

There are less classic ECG changes in Brugada syndrome, including "saddlebacked" ST elevation in same leads.
Many other conditions can mimic the R-sided ST changes seen in Brugada syndrome, including RBBB, LVH, early repolarization, MI, PE, hyperkalemia, ARVD, hypothermia, and Duchenne's muscular dystrophy.

The use of a sodium channel blocker like procainamide can bring out the ECG changes, and this type of "challenge" can be helpful diagnostically (obviously needs to be done in appropriate setting...)

Therapy may consist of antiarrhythmic therapy (quinidine) or implantation of a defibrillator (ICD). General indications for an ICD include aborted arrest, inducible VT on EP study, and suggestive ECG with otherwise unexplained syncope or family history.

ARVC:

This is a genetic condition (autosomal dominant with variable penetrance) characterized by progressive replacement of RV myocardium with fibro-fatty infiltration, which predisposes to ventricular arrhythmia.

Prevalance is estimated to be 1-5 per 1000; highest prevalence in southern European populations (especially Italian). Typically presents from teens to 30s, and affects more males than females.

Diagnosis should be considered in adolescents or young adults presenting with palpitations, syncope, or aborted sudden death. ECG may show T-inversion in R precordial leads (shown above), possibly with "epsilon wave"- small "saddle" in ST segment in V1-V3.

Imaging modalities sigh as 2D echo (most commonly used) and cardiac MRI (becoming more common) may show RV structural changes, and are part of the diagnostic criteria. Family members should be screened.

Therapy:
ICD is indicated for similar indications to above for Brugada syndrome (aborted sudden death, inducible VT).
There is a role for pharmacologic therapy (B-blocker like sotalol antiarrhythmic like amiodarone) in supprssing arrhythmias.
Participation in sports increases the risk of sudden death 5-fold; 24 years of a screening programs in Italy has led to a significant decline in sudden death in athletes.

There is no well-validated risk stratification tool to assess which patients are most likely to benefit from which therapies.

Links:

Click here for a 2005 review from Circulation on Brugada syndrome

Click here for a 2009 review from Lancet on ARVC

Click here for a JAMA paper showing the mortality reduction in Italy from screening for ARVC in competitive athletes

Pericarditis

2010-03-03T09:27:00.005-05:00

Today we discussed pericarditis. A few key points:

Causes of pericarditis:
Vast majority are viral/idiopathic (90%).
Long list of other causes includes
-other infections (purulent pericarditis- H.Flu, pneumococcal, many others), TB
-aortic dissection, trauma
-uremia
-malignancy (although more commonly effusion than pericarditis)- breast, lung, esophageal, hematologic malignancies
-primary autoimmune of inflammatory disorders (esp. SLE, RA, mixed CTD, many others)
-post radiation
-drugs

Pain in pericarditis is usually retrosternal, acute onset, and pleuritic. Often worse supine, improves leaning forward

Physical exam may show pleural rub (mono, bi, or tri-phasic)- each phase corresponds to movement of pericardium. Triphasic rub has 2 diastolic components (early and late diastolic filling) and 1 systolic component. Differentiate pleural vs. pericardial rub by having pt stop breathing. Also look for signs of effusion and tamponade or constrictive pericarditis- JVP findings, pulsus paradoxus, etc.

ECG in pericarditis: 4 stages described
1) diffuse ST elevation (concave up; not dome-shaped) and PR depression
2) normalization of ST and PR changes
3) diffuse T-wave inversions
4) normalization of T changes
ECG in pericarditis vs. MI: In MI, uncommon to have diffuse STE, concave up ST segments, PR depression. T-inversions in MI usually happen before ST segments return to baseline (as opposed to above sequence).

Poor prognostic factors- consider 2D echo +/- admission:
-fever
-subacute onset
-immunosuppression
-trauma-associated
-anticoagulation
-elevated troponin (implies myocardial involvement)
-tamponade suspected (no kidding...)

Every pt should have CBC, troponin., Other tests are guided by evaluation.

Treatment:
If no specific cause found (majority of cases), options include
-high dose ASA (2-4g/day)
-ibuprofen (1600-3200mg/day) or other high dose NSAID

In recurrent pericarditis, colchicine or prednisone are often effective.

Complications of pericarditis:
-cardiac tamponade
-constrictive pericarditis

Link:

Click here for a NEJM review of pericarditis

Click here for JAMA Does this patient have cardiac tamponade?

Parkinsonism

2010-02-24T13:58:00.004-05:00

At physical exam rounds, we went over the examination for Parkinsonism. One approach:

Vital signs: Postural drop (autonomic dysfunction)

Face/head and neck:
-lack of facial expression "mask"
-lack of blinking
-drooling (autonomic dysfunction)
-brow for seborrhea (autonomic dysfunction)
-speech (soft, monotonous)
-cognitive dysfunction, depression

Extraocular movements for progressive supranuclear palsy (upward, then downward gaze palsy)- a "Parkinson's plus" syndrome

Special test: Glabellar tap- tell pt to look straight ahead, tap firmly on mid-forehead outside of the patient's visual field. Expect blinking with each tap x 5-10, then blinking should stop

Standing, gait:
-difficulty initiating movement (akinesis, bradykinesia)
-shuffling gait
-difficulty walking heel to toe
-freezing
-festination (small steps, seeming to "hurry")
-retropulsion (tendency to fall back)
-'en bloc' turning

Upper extremities
-resting tremor with arms relaxed (4-7 hz)
-tremor diminishes on finger to nose (vs. essential tremor, which increases with movement)
-wrist tone for cogwheeling; may look for activated rigidity (movement of opposite hand brings out cogwheeling)
-tests for bradykinesia: finger pinching (progressively smaller), rotation of hands, opposing thumb sequentially with each finger (may add while rotating other hand)
-micrographia

Lower extremities
-foot tapping: low amplitude, progressively smaller (bradykinesia)

Evidence: From JAMA- Does this Patient Have Parkinson Disease?

Most sensitive tests:
Glabellar tap- negative likelihood ratio of 0.13
Difficulty with heel-toe walking: NLR 0.3

Most specific tests:
Tremor, rigidity and bradykinesia: PLR 2.2
Difficulty with heel-toe walking: PLR 2.9
Glabellar tap: PLR 4.5

Findings making Parkinson's disease very unlikely:
Cerebellar signs
Pyramidal signs
Cranial nerve palsies

Link:

Click here for abstract of JAMA paper quoted above

Ischemic limb

2010-02-24T10:24:00.004-05:00

Today we discussed an approach to a patient with an ischemic limb. This may be subdivided into acute vs. chronic ischemia, as these present and are managed differently.

Chronic peripheral arterial disease

Occurs in patients with vascular risk factors; almost always accompanied by CAD and cerebrovascular disease

Usually affects 3 distinct areas:
Aortoiliac-weak/absent femoral pulse (and popliteal, DP)
Femoropopliteal- weak/absent popliteal pulse (and DP)
Peroneotibial - weak/absent dorsalis pedis

Symptoms: Claudication, arterial ulcers and their complications (usually on toes, heel)
Signs:
-Skin, hair, nail changes- definitely should look, but not very helpful when looked at from EBM standpoint
Wounds/sores/ulcers- very specific; classically punched-out ulcer without surrounding venous stasis changes
-Temperature: asymmetrically cool foot is not sensitive, but is quite specific for PAD
-Pulses: absent femoral pulse is highly specific, not sensitive. Any absence of femoral, popliteal, DP is sensitive (i.e. if there is no pulse abnormality at all, negative LR is 0.3). Presence of any pulse abnormality is reasonably specific (positive LR is 15)
-Bruits: Presence is specific, absence is not helpful (i.e. not very sensitive)
-Special tests:
Cap refill: should do, but not very helpful from EBM standpoint
Pallor on elevation, dependent rubor: Sensitive for femoropopliteal disease, not very specific.
Venous refill time (find a prominent foot vein, elevate the leg to at least 45 degrees for one minute then sit patient up and measure the time it takes for the vein to rise above the skin surface again)- over 20s is very specific, but not sensitive.

Investigations: Ankle-brachial index
1.3: non-compressible, calcified arteries
1.0-1.3: normal
0.4-0.9: moderate obstruction, often with claudication
less than 0.4: advanced ischemia
Others: Arterial dopplers, angiogram (CTA, conventional angiogram)

Therapy:
Non-pharmacologic: exercise, smoking cessationPharmacologic: evidence for clopidogrel from CAPRIE trial; soft evidence for pentoxifylline

Surgical: Stenting, revascularization

Acute limb ischemia:

Acute onset of P's: pain (esp. resting), pallor, pulselessness, parasthesia, paralysis.
Etiology- thrombotic vs. embolic.
If thrombotic, usually progression of atherosclerotic disease to critical point. Other possibilites include primary arterial disease (i.e. large vessel vasculitis), spontaneous arterial clot event (e.g. antiphospholipid antibody syndrome, myeloproliferative disorders, Bechet's, possibly hyperhomocysteinemia, others)
If embolic, cardioembolic is common- A-fib, akinetic LV

Therapy: Anticoagulation and urgent surgical intervention- open or endovascular.

Links:

Click here for JAMA: Does the Clinical Examination Predict Lower Extremity Peripheral Arterial Disease?

Click here for Archives of Internal Medicine: Physical examination and chronic lower-extremity ischemia: a critical review

Cellulitis and "Cellulitis"

2010-02-23T09:33:00.004-05:00

Today we discussed an approach to cellulitis, and its mimickers. Some key points:

Cellulitis: acute, spreading pyogenic inflammation of dermis and subcutaneous tissue, sometimes complicating a wound, ulcer, or dermatosis. Lacks demarcation from uninvolved skin.

Erysipelas: superficial cellulitis with prominent lymphatic involvement, making peau d'orange appearance with raised border demarcated from uninvolved skin. Patients are often sicker.

Predisposing factors: saphenous vein harvesting, edema, mastectomy with lymph node dissection, liposuction, "skin popping" in IVDU

Source: portal of entry in skin (e.g. tinea pedis, ulcer)- by far most common; other possibilities include osteomyelitis, bacteremia.
Unusual sources: seawater (vibrio vulnificus), fresh water (aeromonas hydrophilia), fish (strep iniae)

Cellulitis in unusual areas:
Periorbital cellulitis: eyelid and periocular tissues anterior to orbital septum
Orbital: Involves extraocular muscles; predisposes to cavernous sinus thrombosis, decreased visual acuity.

Micro:
80% gram +ve (staph, strep), 20% gram -ve. Aspirates/swabs are not indicated (unless ulcer)
Broader coverage may be indicated in pts with DM2.
Blood cultures are indicated in lymphedema, buccal, periorbital, water exposure, chills or fever. Otherwise, bacteremia is rare (less than 4%).

Empiric treatment: Cefazolin or cephalexin. Other possibilities: cloxacillin, clindamycin, penicillin, amoxicillin-clavulin. May want broader coverage (e.g. gram -ve coverage) in diabetics

Ancillary measures: Elevation, immobilization. Interdigital dermatophytic infections should be treated (e.g. clotrimazole and miconazole), terbinafine, etc

Some cellulitis mimickers to consider (see link to paper below for more)
-stasis dermatitis (especially if bilateral)
-superficial thrombophlebitis (often with IV/catheter site)
-DVT
-contact dermatitis
-drug reaction (can be 'fixed'- i.e. single area)
-Sweet syndrome (neutrophilic dematosis- see previous post)
-gout (can cause erythema overlying joint- i.e. 'periarthritis')

Links:
Click here for excellent NEJM review of cellulitis that most of this post is based on
Click here for Annals of Internal Medicine review of cellulitis mimickers (common and uncommon)

Monoarthritis

2010-02-22T11:16:00.004-05:00

Today we discussed acute monoarthritis. Some points about the general approach and specific causes:

First question: Is this really arthritis (i.e. is it articular)? Important because non-articular causes are completely different (edema, ligamentous, tendon injury, etc)

Articular: Pain with any range of motion, effusion, morning stiffness, jt line tenderness. If multiple areas involved, more likely articular
Non-articular: Pain with specific ranges of motion, none of above.

Common causes of acute mono or pauciarthritis:
Septic arthritis- S. aureus, N. gonorrhea, S. pneumo
Crystal- gout/CPPD
Seronegative arthritis- esp. reactive, IBD-associated
RA (mono-articular)
Sarcoidosis (often bilateral ankle)
Trauma (fracture, hemarthrosis)

Common causes of acute polyarticular arthritis:
Endocarditis
Viral (HBV, HIV, parvo)
Serum sickness (drug rxn)
RA
SLE
Lyme (may also be monoarticular)

Some general features of specific causes:

Septic arthritis:
Risk factors: age, diabetes mellitus, rheumatoid arthritis, joint surgery, hip or knee prosthesis, skin infection, HIV, IV drug use
Clinical features: Joint pain in ~85%, joint welling in ~80%, and fever in ~60%
There are no physical exam findings that reliably rule in or out septic arthritis according JAMA Rational Clinical Exam paper linked below
Joint aspirate:
WBC over 100,000- Positive LR 28
WBC over 25,000- Positive LR 2.9
WBC less than 25,000- Negative LR 0.32
PMN over 90%- Positive LR 3.4; Negative LR 0.34
Also send for Gram stain, C+S, crystals
Common organisms:
St. aureus, St. pneumo, N. gonorrheae, Gram neg bacilli
Empiric tx: vancomycin and ceftriaxone

Crystal arthritis:
NB- finding crystals does not rule out septic joint! Can present the same way with fever, high WBC.
Gout vs pseudogout:
Gout: needle-like crystals, negatively birefringent, 1st MTP/ankle/knee. Risk factors are hyperuricemia, obesity, culprit meds (HCTZ, low dose ASA, others)
CPPD: rhomboid crystals inside macrophages, often hemorrhagic synovial fluid, positively birefringent. Knee, wrist, other. Risk factors: hypercalcemia, hemochromatosis, CKD.

Gout therapy
Acutely: Options are NSAID/colchicine/intra-articular steroid/systemic steroid
NSAID: Not in CHF or renal failure
Colchicine: Works, but often limited by GI side effects
Steroid:
Intra-articular highly effective with 1-2 jts. Confirm the diagnosis first.
Systemic- Prednisone 30-50mg PO x 3-5d then stop. Works well, but side effects.

Chronically: if 3 or more attacks per years, consider allopurinol

Links:
Click here for CMAJ review of monoarthritis
Click here for JAMA: Does this Patient have Septic Arthritis?

IgA nephropathy

2010-02-19T11:46:00.004-05:00

Today we discussed IgA nephropathy. A few key points:

For a general approach to renal failure, click here.

Some important parts of assessment
1. Previous creatinine
2. Hx: drugs, volume, systemic disease (lung, joint, skin, fever...)
3. Volume status assessment, assesment for dialysis indications
4. Urinalysis: blood, protein, casts, cells, eosinophils
5. Urine lytes, osmolality
6. U/S of abdo to r/o obstruction
7. Serology: ANA, anti-GBM, ANCA, C3, C4 (if appropriate)

IgA nephropathy is the most common form of primary glomerulonephritis in the world.
Henoch-Schonlein purpura is a vasculitis associated with IgA deposition and may be a "systemic" form of IgA nephropathy (often with purpura, abdominal pain, arthralgias). Other associated conditions are celiac disease, IBD, and many other autoimmune conditions, and HIV.

Most commonly presents in 20's or 30's, more common in men than women (~5:1)

Many pts with IgA nepphropathy are asymptomatic. Most common ways of coming to clinical attention are

1) microscopic hematuria or proteinuria, which may be intermittent or

2) episodes of macroscopic hematuria or cola-coloured urine, which are classically associated with upper respiratory tract infection (but not commonly).

Firm diagnosis can only be made with biopsy, but which patients need biopsy is controversial.

Course is highly variable, from totally benign to rapidly progressive renal failure.

Worse prognostic indicators are:
1) degree of proteinuria
2) HTN
3) males

Conservative tx is BP management, ACE-I or ARB, fish oil (some evidence).

Specific tx is for crescentic/rapidly decreasing GFR. Cyclophosphamide, chlorambucil, steroids.

Link:
Click here for a NEJM review of IgA nephropathy

Diarrhea and HIV

2010-02-12T10:08:00.005-05:00

Today we discussed diarrhea in the setting of HIV.

As a general rule, whenever faced with a new (or worsened) problem in the setting of a pre-existing disease, a useful dichotomy is whether this new problem is related or unrelated to the underlying disease. Pts with underlying HIV are still "entitled" to have the more common causes of diarrhea (or any other presentation)

Diarrhea, weight loss, malnutrition, and wasting was interestingly one of the first described syndromes of what came to be known as AIDS in 1985; it was initially called "slim disease" by African populations, as this Lancet article describes

Clinically significant diarrhea occurs in about 50% of HIV-infected patients in North America. The majority of these patients have an identifyable enteric pathogen if extensive enough workup is done. There is a small subset of HIV patients with "HIV enteropathy", in whom there is no identifyable pathogen. This is likely due to the effect of HIV itself and inflammation involving the GI lymphatic tissue.

Diarrhea may be more characteristic of small bowel pathology (post-prandial, voluminous, associated with weight loss and malnutrition) or large bowel pathology (frequent, small volume, with possible blood and mucous, tenesmus).

One way to approach the MANY opportunistic and other causes of diarrhea is by CD4 count:

Any CD4 count:
Bacterial: C. Diff, salmonella, shigella, campylobacter
Mycobacterial: M. TB
Parasitic: strongyloides, cyclospora, isospora, entamoeba histolytica, giardia lamblia

CD4 below 200: all of above and
Histoplasma capsulatum
Coccidioides

CD4 below 100: all of above and
Cryptosporidium (shown above)
Microsporum
Leishmaniasis

CD4 below 50: all of above and
MAI
Cryptococcus
CMV

Treatment is generally targeted at the identified pathogen. See Table 3 in below paper for details on specific agents for each of above.
Non-specific treatments include anti-diarrheals, low fat diet, nutritional support, and avoidance of lactose

Link:
Click here for a 2009 review from Gastroenterology on HIV and diarrhea (need journal access)

Fever and rash, Sweet's syndrome

2010-02-10T10:31:00.005-05:00

Today we discused an approach to the patient presenting with fever and rash, some of the causes of a diffuse erythematous rash (i.e. erythroderma), and the more specific entity of "Sweet's syndrome"

Fever and rash- a broad differential needs to be considered, some of which are life-threatening and require immediate attention.

One possible way to approach this is by the type of rash involved, then subdivide by etiology (not intended to be complete):

Petechiae/purpura
Infections: Bacteremias (esp. meningoccemia, endocarditis), viral, rickettsial diseases.
Drug reactions (esp. septra, NSAIDs, b-lactam antibiotics)
Inflammatory: Vasculitis, autoimmune conditions (SLE, cryoglobulinemia, sjogren's, RA, many others)

Vescicular/bullous
Infections: Disseminated herpes zoster, disseminated herpes simplex
Drug reactions (Stevens Johnson, toxic epidermal necrolysis)

Macules/papules
Viral exanthem (think of parvo, HIV, HCV, EBV, others)
Syphillis (secondary); esp. hands and feet
Drug reaction (erythema multiforme, others)
Neoplastic: if fever-associated, hematologic malignancy more likely

Erythroderma- defined as 90% of body surface involved with erythema, swelling, scale. This narrows the differential somewhat; major causes include
Psoriasis
Cutaneous T-cell lymphoma
Sweet's syndrome
Drugs (esp. anticonvulsants, allopurinol, hydralazine)
Toxic shock syndrome

Sweet syndrome (shown above)- acute neutrophilic dermatosis
Papules coalescing into plaques. Erythematous, tender, on face, back, arms. May see fever, arthritis, conjunctivitis. 10% of these pts have malignancy, often AML. Other associations include infections (esp viral), autoimmune conditions, drugs.

Treatment usually includes steroids.

Wallenberg's syndrome

2010-02-09T09:44:00.005-05:00

Today we discussed stroke in general, central vs. peripheral vertigo, and specifically the lateral medullary syndrome (i.e. Wallenberg's)

Vertigo- Central (brainstem, cerebellum) vs. Peripheral (inner ear)

Central:

Nystagmus is often bidirectional, sometimes vertical

Visual fixation makes no difference in symptoms

Vertigo may be chronic and often not severe

Cranial nerve deficits are common

Ear symptoms are absent

Peripheral:
Nystagmus is horizontal, often unidirectional

Visual fixation may improve symptoms

Vertigo is often severe

Head position often clearly exacerbates

No associated cranial nerve deficits

Often assoicated ear symptoms (deafness, tinnitus, otalgia)

Differential diagnosis of stroke -i.e. acute onset focal neurological deficit(s)
Seizure, dissection (esp young pt), migraine, demyelination, vasculitis. Any underlying brain abnormality with something that can cause delirium can cause focal findings (inc. infection, metabolic disturbances)

Lateral medullary stroke:
Results from occlusion of the ipsilateral vertebral artery (thrombotic, embolic, dissection), or a branch, the posterior inferior cerebellar artery.

Possible findings ipsilateral to lesion:
Pain, numbness of half of face (V1-V3)- 5th nerve nucleus
Ataxia, falling towards side of lesion- spinocerebellar tract, cerebellar peduncle
Nystagmus, diplopia, vertigo, nausea and vomiting- ipsilateral vestibular (8th nerve) nucleus
Horner's syndrome- ptosis, miosis, anhydrosis- sympathetic chain
Dysphagia, hoarseness- 9th and 10th nerve nuclei
Facial weakness (usually lower motor neuron type if 7th nerve nucleus involved)

Possible findings contralateral to lesion
Impaired sensation over half of body- spinothalamic tract
Limb power usually not involved because is more medial medullary (pyramidal tract)

Others: Intractable hiccups

Link:

Click here for a NEJM review of vertebrobasilar disease that includes a discussion of the lateral medullary syndrome

Falls in the elderly

2010-02-08T12:38:00.003-05:00

Today we discussed the common problem of falls in the elderly. A few points:

May broadly approach causes for falls as "intrinsic" or "internal" vs "extrinsic" problem:

1) Exernal- overwhelming external hazards. Applies to anyone- surface (e.g. ice), tripping over surfaces, stairs, inadequate lighting, etc. Of course, the elderly may be less able to compensate for external hazards.

2) Internal- May be thought of like a computer (analogy courtesy of Dr. Ed Etchells)
Subdivided into: inputs, processing, and outputs, and power for the system

Inputs: vision, proprioception, vestibular apparatus
Therefore, problems with acuity, peripheral neuropathy, dorsal column pathology, inner ear pathology

Processing: cognition, basal ganglia, cerebellum
Therefore, primary CNS problems including dementia, Parkinson's, any cerebellar pathology

Output: Spinal cord, peripheral nerves, neuromuscular junction, muscle power.

Need adequate power to above system:
Cerebral blood flow, therefore arrhythmias, hypotension (inc postural), seizures.
Drugs: esp benzos (odds ratio of falling=30), but anything that causes postural hypotension (or hypotension in general), or any CNS depressant
Postural hypotension (need to check for it)

It may also be useful to divide falls into
1) isolated vs. chronic (look for acute medical issue in isolated)
2) with vs. without syncope (syncope involves a whole other differential)

Link:

Click here for a review paper on falls in the elderly, with references to evidence-based interventions to prevent falls and minimize morbidity from them

Dermatomyositis

2010-02-03T09:41:00.003-05:00

Diagnostic criteria:
1) Proximal muscle weakness (shoulders, pelvic girdle muscles)
2) Increased CK
3) Myopathic changes on EMG
4) Muscle biopsy showing inflammation
5) Dermatologic involvement as outlined below

#5 + 3 others: Definite
#5 + 2 others: Probable
#5 + 1 other: Possible

Presentation:
Usually insidious onset of proximal weakness affecting shoulders, pelvic girdle. Neck flexor weakness also prominent. Dysphagia/dysphonia may occur. Synovitis is rare.
Pulmonary involvement with fibrosis/pneumonitis may occur. Cardiac involvement (myocarditis) occurs, but is relatively uncommon

Dermatologic findings:
Gottron's papules are lacy, pink/violaceous, raised or macular, and symmetric over dorsal IP jts, elbows, knees.
Heliotrope rash is violaceous discolouration of lids with periorbital edema.
Erythema of shoulders/neck (Shawl sign) or neck/chest (V-sign)- shown above
Periungal telangiectasias, nail changes (cuticular hypertrophy)
Raynaud's may be present
Mechanic's hands- coarse, fissured, scaly, hyperkeratotic hands

Investigations:
CK is increased during disease course, but not necessarily early. ASL/ALT/LDH may all be increased. ESR is >50 in 20%, normal in 50%.
EMG shows characteristic (but not pathognemonic) changes. Bx shows focal infiltration, CD8 T cells

Therapy usually consists of steroids, and possible addition of steroid-sparing agents such as methotrexate or azathioprine.

Malignancy association:
20-30% of patients have an underlying malignancy; dermatomyositis may pre-date the malignancy as in other paraneoplastic syndromes
It is controversial how aggressively to search for malignancy, and there is little high quality evidence to guide.
At the very least, everyone should get age-appropriate screening. Many experts would also measure tumor marker levels, and consider additional screening such as thoracic or abdominal imaging.

Link:
Click here for a good online review of dermatomyositis from American Family Physician

Churg-Strauss syndrome

2010-02-02T11:25:00.008-05:00

Today we discussed Churg-Strauss syndrome, and some "tangents" related to it. A few concepts that came up:

Anatomic approach to weakness and associated features

Motor cortex: Upper motor neuron, involvement follows vascular territory. May see associated cortical findings (e.g. aphasia, apraxia, neglect, field defect). Usually unilateral

Internal capsule: Usually pure motor, with arm, leg, and possibly facial involvement. Unilateral. No cortical findings.

Brainstem: Crossed motor and sensory findings (i.e. lateralization of face and body may be different). Associated cranial nerve findings, level of consciousness may be affected

Spinal cord: Usually bilateral, often with a motor or sensory level.

Nerve root: Radiculopathy, usu at 1 level, often painful. Unilateral if physical compression If demyelinating (e.g. Guillain-Barre), bilateral leg weakness with areflexia

Peripheral nerve: Sensory findings associated, in dermatomal distribution. If general peripheral neuropathy, often length-dependent ("glove-stocking"), bilateral. If single nerves, this is "mononeuritis multiplex" or compression neuropathy.

Neuromuscular junction: No sensory findings, sometimes respiratory muscle involvement, with ptosis. Fatiguable if myesthenia gravis.

Myopathy: Bilateral, symmetrical, proximal. Sometimes CK elevation

Generalized: Think about metabolic abnormalities in addition to above (esp. PO4, K, Ca)

Mononeuritis multiplex differential diagnosis:
Essentially diabetes-related vs. vasculitis.
Common nerves involved in DM2: CN III, IV, VI, median nerve, peroneal nerve
Vasculitides that commonly cause mononeuritis multiplex: Churg-Strauss, polyarteritis nodosa, rheumatoid arthritis with vasculitic component

Eosinophilia Ddx
-parasitic infections
-allergic (asthma, allergy, eczema, AIN)
-vasculitic (Churg-Strauss, PAN)
-adrenal insufficiency
-hypereosinophilic syndrome (subset of hematologic malignancy; cardiac, CNS involvement)
-neoplastic (Hodgkin's lymphoma, CML, others)
-idiosyncratic drug reaction (common culprits are phenytoin, hydralazine, TMP/SMX, many others)
-cholesterol emboli

Churg-Strauss vasculitis

Click here for the American College of Rheumatology criteria for diagnosis

Asthma that is difficult to control is essentially an invariable feature of Churg-Strauss, and is one of the main differences between this and other similar vasculitides such as PAN and Wegener's granulomatosis.

Churg-Strauss should be suspected in patients with asthma (esp. adult onset) AND other organ involvement neurologic (esp. mononeuritis multiplex), gastrointestinal, pulmonary infiltrates, cardiac involvement (which would portend a poor prognosis), with eosinophilia.

Renal failure and glomerulonephritis is reported but less common than in other similar vasculitides (Wegner's, PAN)

Diagnosis is made by biopsy of affected organ or enough clinical criteria. 50% of patients have positive p-ANCA.

Treatment consists of high dose steroids and cytotoxic agents in high risk patients.

Link:

Click here for an excellent review of Churg-Strauss syndrome from Lancet

Nephrotic syndrome

2010-02-01T17:27:00.005-05:00

Triad of hypoalbuminemia, edema, nephrotic-range proteinuria (over 3.5g/24h)
Other components of the syndrome: hyperlipidemia, hypercoagulability, lipiduria (causing oval fat bodies seen above)

The primary problem in the nephrotic syndrome is urinary protein loss due to altered permeability of the glomerulus. Other manifestations are all secondary to protein loss.

Loss of albumin and consequent loss of oncotic pressure lead to the clinical manifestation of edema, which may be profound. Periorbital edema is sometimes more prominent in the nephrotic syndrome than other causes of edema.

Hyperlipidemia results from urinary loss of regulatory lipoproteins, and low oncotic pressure may increase hepatic lipogenesis

Hypercoagulability may be arterial or venous, and often involves the kidneys themselves (i.e. renal vein thrombosis). May result from urinary loss of proteins c and s, and possibly antithrombin III

Causes in adults:

Primary renal diseases:
Minimal change
Focal segmental glomerulosclerosis (FSGS)
Collapsing glomerulopathy
Membranous nephropathy
Membranoproliferative GN (MPGN)
IgA nephropathy

Systemic diseases:
Infectious: HBV, HCV, HIV, syphillis, schistosomiaisis, malaria
Inflammatory/rheumatologic: SLE, amyloidosis, cryoglobulinemia
Malignancy: solid tumors, primary hematologic malignancies (e.g. Hodgkin's lymphoma)
Others: Sickle cell disease, heroin, drugs (e.g. gold, penicillamine)

Therapy:
1) treat the underlying cause
2) measures to limit proteinuria- largely ACE-inhibitors and/or ARBs
3) measures to deal with complications- salt restriction, careful diuretic use (as may become easily intravascularly depleted), statins, vitamin D supplementation if deficient

Links:

Click here for a NEJM clinical case on nephrotic syndrome