HIV, Splenomegaly & Lymphoma

Today we discussed the case of an HIV positive man presenting with "L flank pain" found to have anemia, splenomegaly, and a left renal vein thrombosis.

There are many learning points from this case:

The differential diagnosis for splenomegaly:

• Reticuloendothelial hyperplasia (chronic hemolysis, sickle cell, thal major)
• Infection-related hyperplasia (including HIV, EBC, CMR, TB, malaria, MAI)
• Autoimmune hyperplasia (SLE, RA - known as Felty's syndrome when neutropenia present)
• Malignancies (myeloproliferative, leukemia, lymphoma, myeloma, amyloid)
• Granulatomous disease (Sarcoid, TB)
• Congestion (Cirrhosis, CHF, portal or splenic vein thrombosis, schistosomiasis)
• Infiltration (storage diseases)

The rational clinical exam for splenomegaly (see here) that suggests that palpation and percussion are most helpful if your pretest probability is >10%

The clear association between HIV and lymphoma, most commonly high-grade B-cell non-Hodgkin's lymphoma. However, increasingly we are seeing more and more Hodgkin's lymphomas in HIV+ patients as well. See here for more details.

Hyponatremia and psoas abscess

Last week we discussed a patient with chronic liver disease secondary to alcohol presenting with gram-negative bacteremia, hyponatremia, and a psoas abscess. We focused mostly on the diagnosis and management of hyponatremia.

Hyponatremia: there are a few questions you must ask yourself:

1. Is it real?

• Think of other osmoles - glucose, mannitol, paraproteins

2. Is the urine reponse appropriate - ie what is the Urine Osmolality?

• If low, the urine is appropriately dilute
• If > 100, it is inappropriately concentrated - there must be ADH on board

3. What is the patients volume status?

• Determine if hypo-, iso-, or hypervolemic
• Physical exam is helpful in the extremes, but interobserver reliability is low.
• In the absence of diuretics, Urine Na can be helful - less than 20 suggests the kidneys are avidly reabsorbing Na, so the patient is either hypovolemic or has low effective circulating volume but hypervolemic. The physical exam is helpful in differentiating these states.
• If the patient is on a diuretic, the fractional excretion of urea can be used (value >35% is euvolemic). Defined as Fractional Excretion of Urea (FEUrea) = (Serum_Cr * U_Urea ) / (Serum_Urea x U_Cr) %.

Once you have answered these three questions, you can accurately classify their hyponatremia as hypovolemic (renal or extra-renal losses, the urine Na can help determine), euvolemic (SIADH based on your urine Osm, adrenal insufficiency, hypothyroidism, or primary polydipsia/low solute diet if the urine is appropriately dilute), or hypervolemic (ie liver, cardiac, or renal failure).

In managing hyponatremia, it is essential to avoid overly rapid correction which can cause osmotic demyelination syndrome. Treatment modality will depend on the patients volume status. There are very few indications for hypertonic saline - essentially only if the patient is seizing and you think it's related to their sodium. Remember to monitor the sodium level frequently as well as the urine output - once you have volume repleted the patient, the stimulus for ADH gets 'shut off', resulting in sudden outpouring of dilute urine which can cause a sudden (too quick!) rise in your serum sodium.

Here is a brief review of hyponatremia.

If you are interested in learning more about psoas absecesses, take a look at this review.

Fever of Unknown Origin

After a month of junior attending, the blog is back! On Tuesday we discussed an interesting case of fever of unknown origin (FUO). FUO is a clinical entity that is defined as a T > 38.3 on several occasions for >3 weeks, the etiology of which remains unclear after 1 week of diagnosis.

A home-grown review article (see here) highlights the importance of approaching these patients methodically. Of note, this algorithm does not apply to patients who are HIV+ or have a known malignancy, or to children. Up to 20% of patients with FUO remain undiagnosed. Among those in whom a diagnosis is found, 25-30% are found to have infectious causes, 20-30% are found to have inflammatory causes, and 15-20% have malignant causes. The remainder belong to the "other" category - see below.

Infectious Causes of FUO

Bacterial

Endocarditis (apply Duke criteria, think of HACEK organisms and Q fever)

Abscesses (especially intra-abdominal - consider CT)

Dental abscesses, sinusitis

Osteomyelitis

Mycobacteria (TB)

Spirochetes (Syphilis - get VDRL, Lyme disease)

Viral

HIV, HBV, HCV, EBV, CMV

Fungal

Aspergillus, histoplasmosis, coccidiodomycosis, blastomycosis, disseminated candida

Parasites

Malaria, schistosomiasis, Chagas

Inflammatory Causes of FUO

SLE, RA, PMR, Sjogren's

Vasculitis (GCA, WG, PAN)

Behcet's Disease

Sarcoid, IBD, Still's Disease

Malignant Causes of FUO

Leukemia, Lymphoma

Renal Cell CA

Hepatocellular CA

Colorectal CA

Other Causes of FUO

Drug fever

DVT/PE

Subacute thyroiditis

Familial mediterranean fever

Factitious

Disorder of hemostasis

Key principles and approach (see article link above for a great algorithm):

1. Take a thorough Hx and P/E to point you to a focus: thorough ROS, travel/medication/sexual/occupational history, infectious risk factors

2. Stop all non-essential medications and fight the urge to treat empirically

3. Basic investigations: CBC + diff + film, Cr, LFTs, anti-HCV, HBsAg, anti-HBs, Blood cultures x3, UA and urine culture, HIV, CMV/EBV serology may be helpful, ANA, RF, LDH, CXR

4. Abdo CT to rule out abscess and look for tumour, nodes +/- Technitium-based nuclear scan to identify a focus

5. Apply duke criteria and obtain echo, blood cultures

6. Leg dopplers to rule out DVT

7. If older than 50, get temporal artery biopsy to rule out GCA

8. Liver bx can be helpful if LFTs abnormal