Paraneoplastic Demyelination

First, wow and thank you to Dr. Panisko for flexing his muscles and walking through the differential diagnosis of yesterday's case! We discussed, among other things, an approach to weakness with a focus on demyelinating disease. A paraneoplastic syndrome was the likely conclusion.

You can find an overview on paraneoplastic neurologic disorders here.

Here is a case report of GBS associated with an adenocarcinoma of the gallbladder (only one that I could find).

Finally, here is a review of chronic demyelinating disorders.

Venous Thrombosis

Today we briefly discussed DVTs in morning report. Clinically, these can be a diagnostic challenge but clinical prediction tools are available. Check out an article in JAMA's Rational Clinical Exam series here.

We often separate severity of venous thrombosis on the basis of location (deep vs superficial). Earlier this year, a French study looked into this and found some interesting associations. Here is the link.

Finally, in our patients with COPD exacerbations of unknown cause, this article in CHEST suggests that pulmonary embolism may be the cause.

Thrombocytopenia

Today we discussed an approach to thrombocytopenia. Here is a brief overview.:

Pseudothrombocytopenia:
This is a consequence of platelet clumping as a consequence of the EDTA (lavender top) tube. The presence of this leads to the platelet clumps being miscounted on the automated system. If this is an issue, order the CBC to be drawn in citrate.

Decreased Production:
The bone marrow is unable to produce platelets in sufficient quantity as a consequence of toxicity (meds, chemotherapy, alcohol), infection (viral, TB, histoplasma), replacement (cancer, fibrosis, amyloid, sarcoid), or nutrition (folate and B12 deficiency).

Sequestration:
Think of the spleen as a giant sponge and its easy to see how as hypersplenism can reduce counts. We usually see this as a consequence of portal hypertension but primary hypersplenism is also possible. Typically, counts do not drop below 1/3 of the lower limit of normal (50k) if this is the only problem.

Destruction/Consumption:
This can be broken down into mechanical (high flow over prosthetic valves, malignant HTN), immune (HIT, ITP) or consumptive (TTP, DIC) causes. TTP is a medical emergency and this is why the blood film is so important. You need to ensure that there are no schistocytes (RBC helmets) present. I will blog on TTP as a separate post in the near future. Also, remember that ITP is a diagnosis of exclusion.

Our patient was ultimately diagnosed with ITP. A great overview on diagnosis and treatment can be found here, in the recent consensus guidelines.

Legionnaire's Disease

Today we discussed a case of a pneumonia that did not initially respond to empiric therapy. Supplemental investigations were notable for a positive Legionella urinary antigen.

Legionnaire's Disease was first described after an outbreak in Philadelphia in 1976. It is now being recognized as a more common cause of respiratory infections. It is a difficult to culture organism requiring special growth media (talk to the micro lab if you are thinking about it). Testing can also be done by the rapid urinary antigen assay (only detects L. pneumophilia serotype 1). Interestingly, one study demonstrated persistent urinary antigen positivity months after exposure (in an immunocompromised host).

Overall, empiric therapy for CAP (respiratory fluoroquinolones or a macrolide) should cover Legionella species and there are no RCTs that show one class to be superior to the other.

Here is a recent review.

Hydatid Cysts

Today we discussed a patient with abdominal pain who had a surprising finding on his abdominal imaging.

The differential diagnosis included a hydatid cyst (Echinococcus granulosus).

Information regarding the lifecycle and pathogenesis can be found in this review.

Interestingly, in a hepatic abscess caused by Klebsiella, there is an association with DM and septic endopthalmitis.

Other causes of liver cysts are discussed here.

Systemic Lupus Erythematosus

Today we discussed an unfortunate patient with multisystem disease, a positive ANA (as depicted here) and a new diagnosis of SLE.

SLE appears on the differential in many medical conditions due to the multiple organs it can involve (and the multiple manifestations required for diagnosis).

The diagnositic criteria for SLE can be found at this site.

A pathophysiologic review, with a table of the classic rhematologic antibody assays is published in NEJM here.

Have a great weekend!

Congestive Heart Failure

Today, in addition to piloting another format to morning report, we discussed congestive heart failure. Management issues surrounding associated acute renal failure and atrial fibrillation were also reviewed. Here is a brief summary:

ARF

This can make management difficult. When the renal failure is secondary to poor perfusion pressure, this sometimes improves with diuresis. ACE/ARBs are vital to the management of CHF and should be continued whenever possible.

Atrial Fibrillation

This is a classic "chicken or the egg" scenario in that did the AFib push the patient into failure, or did the "atrial stretch" from fluid overload cause the patient to go into Afib? In any case, diuresis is paramount. If needed, rate controlling agents (Digoxin, Amiodarone, intravenous magnesium) can all be used to slow the patient down, but all will be ineffective without diuresis.

In both scenarios above, a trial of BiPaP can go a long way in stabilizing the patient (decreases afterload, increases preload and increases CO) while you are awaiting the effects of diuresis.

Here is a recent review on CHF from NEJM. Also, here is an interesting article on using intravenous iron therapy for iron deficient patients in heart failure.

The Adrenal Incidentaloma

Today we had a great discussion on the approach to an incidentally discovered adrenal mass.

An adrenal incidentaloma is defined as an adrenal mass (>1cm) that is discovered serindipitously on abdominal imaging designed to look for something else. These are common with an estimated frequency of 6% of the general population.

Imaging characteristics
Many radiographic findings can help determine the malignant potential of a lesion. These include size (>4cm), contrast washout time, density, and border contour of the lesion.

Biochemical Workup
The basic principle is to determine whether the lesion(s) is functional or impairing the function of the gland. See Table 2 in the linked article for some guidelines on workup.

Role of Biopsy
The role of fine needle aspiration in an adrenal mass is primarily useful in determining adrenal from non-adrenal tissue (r/o mets or infection). Actual tissue architecture is required to determine if the lesion is a primary adrenocortial carcinoma. Always remember to r/o a pheochromocytoma (24h urine metanephrines) before asking someone to put a needle into these lesions (hypertensive crisis)

There is an excellent NEJM review here.

Aortic Stenosis

This afternoon, physical exam rounds focused on Aortic Stenosis.

This topic was blogged about by Dr. Dave Frost (Last year's CMR) in a previous post. Here is the link.

Enjoy your weekends!

Renal Failure

Today we had a fantastic discussion regarding causes of renal failure secondary to multiple myeloma.

To summarize:
Hypercalcemia
Hypercalcemia (as a consequence of bone destruction) can predispose a patient to renal failure in 3 ways. First, high calcium levels lead to a diuretic effect, reducing the effective circulating volume. Second, calcium can deposit into the kidney itself (nephrocalcinosis). Finally, the high calcium levels can precipitate in the collecting system leading to stone disease.

Stones
In addition to calcium based stones, the high cell turnover also predisposes the patient to form uric acid stone (gouty nephropathy). This can also be nephrotoxic.

Cast Nephropathy
Filtration of toxic light chains leads to both tubular injury and intratubular cast formation (and obstruction). The light chains bind avidly to the normal tubule mucoprotein (Tamm-Horsfall) and lead to obstruction. As the tubule becomes damaged, adult onset Fanconi Syndrome, a proximal type 2 RTA, can develop (loss of amino acids, glucose and ability to acidify the urine).

Light Chain Deposition Disease
Excess monoclonal light chains deposit in the kidney (without forming fibrils) and can lead to a nephrotic type syndrome.

Amyloid
Circulating light chains are taken up by macrophages where they are partially processed, then excreted as Congo-red positive, beta-pleated fibrils. These are nephrotoxic.

Recurrent Infections
Both systemic overwhelming infections (sepsis) and recurrent urologic infections are more common in myeloma patients which put them at risk for renal failure.

NSAIDS
Bone pain hurts. Patients often turn to NSAIDS to help manage the pain and this can lead to renal failure in a number of ways (will be discussed in a future blog).

Renal Vein Thrombosis
MM is a hypercoagulable state (loss of anti-thrombin 3 in the urine). The renal vein is susceptible to thrombosis and subsequent renal failure.

The "anti-kidney" antibody
Multiple antibodies against various "kidney-ness" have been described (evil-humors?) and associated with renal failure.

Cord Compression
Plasmacytoma love the spinal cord and as a consequence, cord compression can develop. A real emergency!

Pretty impressive list. If I missed something, add it to the comment section. Also, check out this article from JASN.

Listeriosis

Today we discussed the interesting case of Listeriosis.

L. monocytogenes is a facultatively anaerobic, nonsporulating, gram-positive rod that grows over a broad temperature range, including refrigeration temperatures. (making small lapses in sanitation at food processing centres an even more dangerous event).

Here is a brief overview of some of the clinical manifestations.

Gastroenteritis
Usually develops within 48 hours of ingestion of a large inoculum of bacteria in contaminated foods (milk, deli meats, soft cheeses and salads). Manifestations include fever, diarrhea, headache, and constitutional symptoms. Unless in a high risk group (see below) no treatment is usually required.

Meningitis/Encephalitis
L. monocytogenes causes ~5–10% of all cases of community-acquired bacterial meningitis in adults in the United States. Case-fatality rates are reported to be 15–26%. This is usually a more sub-acute presentation with a predominance in chronically ill patients or at the extremes of age.
L. monocytogenes can directly invade the brain parenchyma, producing either cerebritis or focal abscess.

Infection in Pregnancy (Nothing makes an internist more uncomfortable than a pregnant patient - except maybe kids).
The usual presentation in pregnancy is a nonspecific acute or subacute febrile illness with myalgias, arthralgias, backache, and headache. Preterm delivery is a common complication. Prepartum treatment of bacteremic women enhances the chances of delivery of a healthy infant. Women usually do well after delivery: maternal deaths are very rare, even when the diagnosis is made late in pregnancy or postpartum. Overall mortality rates for fetuses infected in utero approach 50% in some series; among live-born neonates treated with antibiotics, mortality rates are much lower (~20%). Granulomatosis infantiseptica is an overwhelming listerial fetal infection a feared complication.

Treatment
High dose Ampicillin (2g q4h) or Pen G (4MU q4h) is the recommended therapy for serious Listeria infections. In penacillin allergic patients, desensitization is always an option, although good results have been demonstrated with Septra.

For more information, check out this review.