3/14 Presby report: polyarthritis

Thanks to Alex for presenting a great case of a middle aged woman with oligo/polyarthritis, ultimately diagnosed with disseminated gonococcus!

Polyarthritis can be a challenging complaint to parse through.

Important questions to ask

  • Timing (acute = <6 weeks)
  • Inflammatory or not (swelling suggests inflammatory)
  • Symmetry
    • This is not necessarily an exact science; a patient with mostly inflamed MCPs and a single DIP on one side and the converse on the other hand would still be considered symmetric
  • Large vs small joints
    • Ex: Lyme often presents with an acute monoarthritis, commonly in the knee; small joints are uncommon
  • History of crystal arthritis
  • Age
    • Older patients are more likely to p/w CPPD/pseudogout
  • Things that predispose to high uric acid
    • CKD
    • EtOH use
  • NSAID responsiveness

On exam, make sure to look for:

  • Joint exam
  • Nodules
  • Tophi (found particularly in the olecranon bursa and in fingertips- they can be very subtle!)
    • Gout tophi tend to be right in the olecranon, whereas rheumatoid nodules tend to be a little distal to the olecranon

Check out this calculator which may help you think about how likely gout is in your patient.

We talked briefly about the ANA.

The ANA is not a standardized test from lab to lab.

  • One lab might be different than another
  • So positivity depends on where it’s being tested, so 1:80 might be considered positive in one place and negative somewhere else
  • In one study, up to 20% of patients have a low level positive ANA
  • Some labs will use an ELISA for the ANA, for which the result will just be a number (not a titer)

The patient was ultimately diagnosed with disseminated gonococcus, with a synovial WBC count of 96000- this is unusual because gonorrhea usually causes a WBC count <50000!

  • Tx: ceftriaxone x 2 weeks + azithromycin
  • Also consider doing a surgical washout of the affected joint, particularly if it’s weight bearing; this may allow the patient to return to weight-bearing status more quickly!

3/12 Presby report: vertigo, MS/NMO

Thanks to Rebecca Wang for presenting a cool case of a middle aged man who presented with dizziness/vertigo and was found to have demyelinating brain lesions, felt to be MS vs NMO.

Differentiating between dizziness and true ‘room spinning’ or vertigo is important. You can categorize the complaint of dizziness into pre-syncope, disequilibrium, lightheadedness and true vertigo (which should be accompanied by the ‘room spinning’ sensation).

Questions to ask when investigating vertigo

  • How long the vertigo has been going on (longer = more concerning for central)
  • Things that provoke the symptoms (changes in head position, head trauma, loud noises)
  • Tinnitus/hearing loss
  • Recent URIs
  • Focal neuro deficits
  • Once vertigo is established, try to differentiate peripheral and central causes.  Central causes are often the more acutely concerning because they include mass lesion, stroke, as well as demyelinating conditions, etc
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Here’s an excellent table that helps distinguish central vs peripheral vertigo. Note that no one test or feature reliably distinguishes the two. Initial Evaluation of Vertigo, AAFP.

In one study, the presence of vertigo upon waking up in the morning was predictive of a peripheral cause.

Provoking factors may also be helpful in identifying a diagnosis.

  • Symptoms provoked by…
    • positional changes: BPPV
    • recent URI: vestibular neuronitis or labrynthitis
    • migraine triggers: vestibular migraine
    • straining, recent head trauma, loud noises: perilymphatic fistula
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The Dix-Hallpike maneuver for positional vertigo is performed by the examiner, who stands at the head of the bed. As the patient is supported and lowered into a position whereby his or her rotated and extended head hangs off the end of the examining table, the examiner observes for nystagmus. In this view, the patient’s head has been rotated to the left and expresses nystagmus with a slow response to the right and a rapid response the left. Repeating the maneuver with the head rotated in the opposite direction would reverse the direction of the nystagmus. A maneuver (with positive indication) will reproduce the patient’s symptoms.

Remember that the Romberg test is generally not a test for cerebellar function but for peripheral neuropathy.

Finally, the HINTS (Head Impuse, Nystagmus, Test of Skew) exam! This test is useful for distinguishing brainstem and cerebellar ischemia from vestibular neuritis or other peripheral causes of vertigo and is most helpful in patients who have had continuous feelings of vertigo or dizziness. It is not useful in patients with momentary position-related transient vertigo (often benign positional vertigo) or those with TIAs who are not dizzy when examined

HINTS was found to have a sensitivity of 96.5% and specificity of 84.4% in identifying central causes of vertigo, which was much better than ABCD2. This is even better than MRI

To summarize: a REASSURING HINTS exam is ALL of the following 1) unidirectional nystagmus 2) no vertical skew 3) abnormal head impulse test (abnormal = nerve problem, not brain problem).

Neuromyelitis optica (NMO)

NMO is a demyelinating disease that primarily targets the optic nerves and spinal cord. 55-85% of brain imaging is normal, although patients can have nonspecific optic nerve enhancement and C/T spine enhancement. Almost all lesions are spinal cord or in cranial nerves.

Hallmark features

  • bilateral or rapidly sequential optic neuritis
  • transverse myelitis (leading to limb weakness, sensory loss, bladder dysfunction)
  • Trunk/leg pain
NMO vs. MS
  • NMO was originally classified as part of MS
  • NMO is now recognized as a separate disease because they do worse than MS patients.  NMO is also associated with IgG antibodies to Aquaporin 4, although this is neither necessary nor sufficient for diagnosis
  • NMO shares many features with MS, such as the development of lesions over time and space
  • More acute than MS; progressive decline over several years w/ a higher mortality than MS
  • NMO lesions are almost exclusively brain stem and cranial nerves, and may include transverse myelitis

Differentiating NMO from MS is based on differences with respect to clinical course, pathophys, and response to MS drugs. Some radiographic features that are more suggestive of MS than NMO:

• Lesions adjacent to lateral ventricle
• Inferior temporal lobe white matter lesions
• Ovoid (ie, “Dawson finger”) periventricular lesions
• U-fiber juxtacortical lesions


Labuguen R. Initial Evaluation of Vertigo. AAFP 2006.


2/26 VA report: pancytopenia, B12 deficiency

Thanks to Ling Wu for presenting an excellent firm report today: a 51 year old Sudanese man with subacute fatigue and weight loss, found to have pancytopenia and Coombs-negative hemolysis and ultimately found to have severe B12 deficiency.

Broadly speaking, pancytopenia results from:

  1. Bone marrow infiltration/replacement: malignancies, infection (TB, fungi), myelofibrosis
  2. Bone marrow aplasia: nutritional deficiencies, infection (HIV, Parvo B19), immune destruction, medications
  3. Cell destruction or sequestration: DIC, TTP, MDS, hypersplenism

Pancytopenia has a huge differential which can be looked up on UpToDate, so I won’t put it here.

How to work up new pancytopenia? Things to consider:

  • CBC w/ differential, BMP, LFTs (look for hemolysis/jaundice)
  • Peripheral blood smear
  • PT/PTT/INR, fibrinogen
  • B12/folate/iron studies
  • Infectious w/u: HIV, HBV/HCV, EBV or CMV as the history dictates, Parvo B19
  • Thorough medical review, consider autoimmune workup

Things like flow cytometry and bone marrow biopsy may need to be considered if the initial workup is unrevealing.

This patient was ultimately diagnosed with B12 deficiency.

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Normal mechanisms and defects of B12 absorption. The vitamin B12 (Cbl) released from food protein by peptic action is bound to haptocorrin (HC) in the stomach and travels to the duodenum, where pancreatic proteases digest the HC, releasing Cbl to bind to intrinsic factor (IF). The IF-Cbl complex binds to a specific receptor in the distal ileum (the cubam receptor) and is internalized, eventually released from lysosomes, and transported into the blood. NEJM 2013.


See the NEJM article below for more comprehensive information on causes of B12 deficiency.

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Clinical manifestations of B12 deficiency. NEJM 2013.


  • The B12 assay is imperfect: although an extremely low level (<100) is usually associated with clinical deficiency, such low levels are rare
  • Up to 50% of tests have either false positive or false negative values
  • Moral of the story: don’t use the lab’s lower limit of normal to reassure yourself that there’s no B12 deficiency. If they have compatible signs/sx despite a value above the LLN, they may still require supplementation.


  • The body’s daily requirement of B12 is 2.4 μg
  • Severe deficiency may require injected B12, sometimes lifelong if it is for treatment of pernicious anemia
  • Neither injection nor oral therapy are very efficiently absorbed
  • An increase in the reticulocyte count should be seen in 1 week and correction of megaloblastic anemia in 6-8 weeks


  1. Stabler S. Vitamin B12 deficiency. NEJM 2013.

2/22 VA report: hypocalcemia (mechanisms and management)

Thanks to MK Hannan for giving an outstanding intake report yesterday on a 61 year old alcoholic with a h/o RCC s/p nephrectomy who presented with hypocalcemia.


  • Serum [Ca] is governed by the actions of PTH and Vitamin D on the bones, gut and kidneys
  • Calcium itself regulates its own metabolism via calcium-sensing receptors (CaSR) in the parathyroid gland (inhibits PTH secretion) and kidney (promotes urinary Ca excretion)
  • Serum calcium is transported partly bound to albumin (~45%); small anions such as phosphate and citrate (15%); and partly in the free/ionized state (‘iCal’: 40%)

Acute signs of hypocalcemia

  • Neuromuscular irritability (tetany): paresthesias, muscle twitching, Trousseau/Chvostek’s, bronchospasm, seizures
  • Cardiac: prolonged QT, heart failure (decreased inotropy), hypotension
  • Papilledema

Diagnosis: consider sending off PTH level (most important), BMP, iCal, Vit D level

PTH-related causes of hypocalcemia

  1. PTH absent (ie low PTH): postsurgical, hypo- OR hypermagnesemia (<0.8 or >5), autoimmune parathyroid destruction or Abs to parathyroid CaSR, s/p XRT, infiltrative (very rare)
  2. PTH ‘ineffective’ (ie high PTH): Vit D deficiency or resistance, end-stage CKD (via decreased calcitriol production and hyperphosphatemia), malabsorption (ex: celiac causing Ca malabsorption), pseudohypoparathyroidism
  3. PTH ‘overwhelmed’: osteoblastic metastases (breast, prostate), pancreatitis, sepsis, massive blood transfusions (via citrate), rhabdomyolysis (via increased serum phosphate)

Drugs that can cause hypocalcemia: EDTA, citrate, bisphosphonates, cisplatin, foscarnet (Phos-based Ca chelator)

Management of hypocalcemia

  • Mg repletion (goal >2)
  • Vitamin D repletion (50K units Vit D2 or D3 x 6-8 weeks)
  • Oral calcium w/ goal 1-2g of  elemental calcium daily, goal Ca 8-8.5 (low end of nl)
    • Many oral supplements like Ca carbonate contain only 40% elemental Ca; so a 1250mg pill contains ~500mg elemental Ca. Ca citrate is ~20% elemental Ca.
  • Ca gluconate can be given IV in acute situations

1/29 VA report: clots clots clots clots clots clots

Thanks to Malcolm Kearns (not Lil Jon as the title might suggest) for giving an excellent talk on DVTs, related syndromes, and their management.

First, we talked about medications that can cause edema:

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Courtesy of Malcolm Kearns

The patient in this case was diagnosed with an SVT. But which veins are considered superficial?

Generally, superficial vein thrombi (SVTs) can be managed conservatively (compression stockings, NSAIDs, hot packs). But there is a role for anticoagulation even with SVTs IF:

  1. The SVT is associated with a DVT
  2. It is located near a junction with a deep vein (saphenofemoral or saphenopopliteal junction)
  3. There is a known or strongly suspected hypercoagulable state (cancer, etc), or the SVT is extensive or recurrent

This patient had repeat imaging that now showed DVTs. It’s important to know that treatment of DVTs can vary depending on where they are:

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Other reasons to anticoagulate isolated distal DVTs include:

  • Unprovoked DVT
  • D-dimer >500 ng/ml
  • Inpatient status
  • Immobility
  • Persistent or irreversible risk factors (malignancy etc)
  • Extensive thrombus
  • Symptomatic

We touched on several studies that studied the use of IVC filters for prevention of DVT/PE. Very briefly, the bottom line for some of them:

  • PREPIC (1998)
    • Groups: pts w/ proximal DVT, high risk for PE, placed on UFH vs LMWH w/ or w/o IVC filter
    • All patients were anticoagulated
    • Bottom line: IVC filters significantly reduced PE incidence at 12 days and 8 years BUT they also significantly increased DVT incidence at 2 years and 8 years
  • PREPIC 2 (2015)
    • Group: pts w/ acute PE, high risk for recurrence, placed on A/C alone or A/C + IVC filter
    • Bottom line: IVC filters did not reduce symptomatic PE at 6 months

In general, the take away is that IVC filters are not a panacea and should really be considered in patients in whom a recurrent PE would be catastrophic (likely due to poor cardiopulmonary reserve).

Other interesting takeaways:

  • There is no evidence to suggest that SCDs can mobilize a clot in someone who already has a DVT or SVT
  • There is also no evidence that exercise in someone with a PE can lead to recurrent PE
  • The Choosing Wisely Campaign strongly recommends against doing a hypercoagulability workup in patients with a known cause of DVT. In general, these should be left to the outpatient setting, ideally when patients are off anticoagulation

Ultimately this patient was diagnosed with phlegmasia cerulea dolens, an uncommon condition characterized by extensive and dramatic ileofemoral DVT. The clot can extend into capillaries and prevent blood from leaving the leg, leading to compartment syndrome, hypovolemic shock, and gangrene!

1/17 VA report: hypercalcemia and the milk-alkali syndrome

Thanks to Dr. Wahba for walking us through his approach to hypercalcemia.

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Images courtesy of Choksi P, UMichigan

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Ddx for hypercalcemia. Source: http://www.wchcmr.org


We also talked about the milk-alkali syndrome (MAS). It was first described in the early 1900s after (Doctor) Sippy (what a great name) came up with a calcium-laden milk and antacid regimen for the treatment of peptic ulcers. The introduction of PPIs and H2 blockers in the 1970s caused a dramatic decline in its incidence, but recent years have seen a resurgence due to the widespread use of Ca carbonate and Vit D supplementation for osteoporosis. It is now thought to be the 3rd most common cause of in-hospital hypercalcemia, after hyperparathyroidism (#1) and malignancy (#2)!

“Old” MAS: middle aged men with GERD taking Tums
“Modern” MAS: older women with osteoporosis, ESRD patients or those on chronic steroids taking Ca/Vit D supplementation. Don’t forget unusual sources of calcium like nicotine gum; also betel nut chewers from East Asia (though obviously a rare population here in Philly)

Pathogenesis of MAS

  • dietary input of calcium exceeds excretory capacity (thought to be >4-5g Ca/day, but varies widely)
  • Alkalosis further decreases Ca excretion
  • Ca leads to natriuresis and diuresis
  • pre-existing renal insufficiency and failure to suppress calcitriol levels play a role
  • Other meds play a role: NSAIDs, ACEIs, thiazides

The hallmarks of milk alkali syndrome are 1) hypercalcemia, 2) metabolic alkalosis and 3) varying degrees of renal failure. Note that these findings really exist on a continuum (acute, subacute, chronic)

Symptoms of MAS

Early signs: N/V, anorexia, distaste for milk, headache, dizziness, vertigo, apathy, and confusion
Chronic signs: myalgias, psychosis, tremor, polyuria, polydipsia, pruritus, and abnormal calcifications (band keratopathy, soft tissue, etc)


  • A careful history identifying heavy calcium and alkali intake is key
  • Lab findings: hypercalcemia (can be severe), AKI, metabolic alkalosis, low/normal phosphate, low 1,25-OH Vit D and PTH


  • Supportive: treat hypercalcemia, stop calcium/alkali containing supplements, stop NSAIDs, thiazides and other offending meds


Medarov B. The Milk-Alkali Syndrome. Mayo Clin Proc 2009.


1/11 VA report: anasarca, protein-losing enteropathy, ascites analysis

Thank you, Brandon Swed, for presenting an excellent and rich case of a older M->F transgender patient who presented with gross anasarca and ascites, and was found to have pulmonary hypertension that’s still being worked up.

We talked about mechanisms of edema formation, shown below:

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1) Increased hydrostatic pressure 2) Decreased plasma oncotic pressure 3) Increased capillary permeability 4) Decreased lymphatic drainage. Source: Symptom to Diagnosis: An Evidence-based Guide.

Edema is generally pitting, but some can be nonpitting:

  • Lymphedema
  • Thyroid myxedema

With thyroid myxedema, it is postulated that fibroblasts secrete water-loving glycosaminoglycans (GAGs) into the skin and soft tissues that then ‘vacuum up’ and retain water.

Why is myxedema usually nonpitting?

  • normally, edema water moves along tissue planes and is thus easily squeezed along the plane
  • but in myxedema, the water is more bound to the GAGs and less moveable, which is why it’s thought to be nonpitting

We also touched on ascites fluid analysis as a way of figuring out its etiology:

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Harrison’s Manual of Medicine, 18e. “Ascites”.

Lastly, for the wisecracks from the peanut gallery during our discussion of protein-losing enteropathy, there’s a dizzying number of causes of PLE, but here are some common culprits:

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Causes of protein losing enteropathy. Copland and DiBaise 2017.


Copland A and Dibaise J. Protein Losing Enteropathy: Diagnosis and Management. Nutritional Issues in Gastroenterology. April 2017.