8/17 PPMC Report: AL-Amyloidosis

Today we discussed the case of a patient who presented with macroglossia and was found to have AL amyloid and multiple myeloma.

We reviewed physical exam findings to confirm macroglossia — including scalloped tongue and a thorough differential for macroglossia including amyloid, hypothyroidism, acromegaly, space occupying lesions (abscess v. hemangioma v. lymphangioma v. cyst etc.) and exceedingly rarely GCA (1).

Types of Amyloidosis:

Type of Amyloid Description
AL Deposits monoclonal light chains – associated with plasma cell dyscrasias but can occur alone!
AA Deposits amyloid A – associated with chronic inflammation (ie RA, IBD, spondyloarthropaties), frequently presents with nephrotic syndrome
Dialysis Related Deposits beta 2 microglobulin, has an osteoarticular prediliction
Hereditary/Familial Deposits transthyretin, alpha cahin of fibrinogen A, apolipoprotein
Age Related (Senile) Deposits transthyretin – clasicially cardiac presentation
Organ Specific 2/2 locally produced proteins rather than circulating

The PPMC Report Team did a thorough screen for other end-organ involvement including renal (nephrotic range proteinuria), hepatosplenomegaly, CHF/restrictive cardiomypoathy, peripheral neuropathy, and carpal tunnel syndrome. We also discussed the increased risk for bleeding diathesis in AL amyloid patients due to both liver involvement AND direct factor X deficiency due to factor X binding to amyloid fibrils.

PPMC Team identified the disease specific signs/symptoms of multiple myeloma…the CRAB!

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(hyperCalcemia >11, Renal dysfunction with Cr >2 , Anemia hgb <10, Bone disease >=1 lytic lesion)

We reviewed the different diagnostic criteria for plasma and lymphoplasmacytic cell dyscrasias (2):

PCD

We also reviewed the criteria for a patient with amyloidosis to qualify as having MM (3).  I may have misspoken during conference, so I just want to clarify here in this post: Patients with AL-amyloidosis who have >10% plasma cells on BMBx should be considered as having MM — Essentially pretend that smoldering myeloma doesn’t exist for AL-amyloid patients.

Our conference wrapped up with a discussion on cardiac amyloid and the medications in our arsenal to treat this disease: loop diuretics +/- spironolactone. Beta-blockers and CCB are contraindicated due to their negative inotropy and ACE-I are associated with significant hypotension (possibly unmasking some subclinical autonomic neuropathy). These patients should ALSO be considered for anticoagulation (with the help of a cardiologist) based on both rhythm and low atrial flow velocities.

 

References:

  1. Helfrich DJ, et al. Giant cell arteritis of the tongue presenting as macroglossia. J Rheumatol. 1988 Jun;15(6): 1026-8.
  2. American College of Physicians. MKSAP 17: Medical Knowledge Self-Assessment Program. Philadelphia: American College of Physicians,  2016.
  3. Kourelis TV et al. Coexcitent multiple myeloma or increased bone marrow plasma cells define equally high risk populations in patients with immunoglobulin light chain amyloidosis. J Clin Oncol. 2013 Dec;31(34):4319-24.

8/10 PPMC Report: Secondary Amenorrhea

Today we discussed the case of a 31 yo F with PMH of ?PCOS presenting with difficulty conceiving after attempting for 3 years.

First of all — the PPMC report team agreed that three years was too long! She should be referred for work up after 1 year (or 6 months if >35yo) of attempting to conceive (sex ~2x weekly) without resultant pregnancy.

We discussed the Rotterdam criteria to diagnose PCOS (2003).

Two out of three of the below:

  1. Oligo/anovulation
  2. Clinical/biochemical signs of hyperandrogenism
  3. Polycystic ovaries on US (>12 follicles)

WITHOUT other causes of hyperandrogenism present.

We reviewed the other causes of hyperandrogenism (…and when to go looking for them) including tumor (ovarian/adrenal), congenital adrenal hyperplasia, Cushing’s disease and acromegaly.

Amenorrhea

Following the above workup algorithm, our patient had hypogonadotropic hypogonadism and an MRI which demonstrated a pituitary mass. Given her presentation with hyperandrogenism, the PPMC report team went back and ordered a Cushing’s and Acromegaly work up which demonstrated elevated IGF-1 which did not suppress with a glucose load — diagnosing this patient with acromegaly 2/2 a hyperfunctioning pituitary adenoma!

8/8 PPMC Report: Ticks!

Today we discussed a patient diagnosed with early localized Lyme with persistent fevers >72 hours after initiating doxy found to have babesia co-infection.

We reviewed the various stages of Lyme disease and how this affects treatment duration and PO vs. IV antibiotics as well as treatment for babesia (Atovaquone + Azithro vs. Clinda + Quinidine — depending on severity).

Lyme

In different areas of the country (especially in New England) the rates of co-infection with babesia can be as high as 39% (1) and, in these areas, patients diagnosed with Lyme disease should probably be screened for babesia as well. We discussed approaching co-infection by identifying the regional tick species, in this case, Ixodes. Co-infections based off of the Ixodes tick include, Anaplasma, Babesia, Lyme and Powassan.

We also reviewed Lyme mimickers including STARI (carried by the Lone Star tick — which also carries Ehrlichiosis), but that geographically this was ruled out in our case.

As Dr. Gluckman pointed out, early localized Lyme is a CLINICAL diagnosis and no lab testing was necessary to MAKE the diagnosis — but that serologies later can be used to confirm the diagnosis.

Lastly we reviewed the 2016 NEJM article which discussed screening the US blood supply for Babesia microti (2) — it hasn’t been rolled out to the Red Cross yet, but keep your eyes peeled!

Just as a quick reminder and plug for the Philadelphia Department of Public Health — they track Lyme disease every year (among a million other things) — and we see a LOT of it in areas you might not expect.

Below is the 2016 info-graphic for number of cases of Lyme by Zip Code (3).Lyme in philly

References:

  1. Vannier et al. Human Babesiosis. NEJM 2012; 366:2397-406.
  2. Moritz ED et al. Screening for Babesia microti in the U.S. Blood Supply. NEJM 2016; 375:2236-45.
  3. https://hip.phila.gov/DataReports/TickborneDiseases

8/3 PPMC Report: Bacterial Meningitis

Today we covered the often thought of (but less frequently diagnosed) bacterial meningitis and a case diagnosed and treated by our own Dr. Ferrante!

We discussed pattern recognition (“thinking fast”) and the benefits in this case. We reviewed the data on the signs and symptoms at presentation for meningitis including that having fever, neck stiffness and AMS is only 46% specific; however >95% of patients who were eventually diagnosed with bacterial meningitis had 2+ of these clinical findings (1).

We chatted about who needs a HCT prior to LP (2):

  1. Immunocompromized patients
  2. History of CNS disease (masses, stroke, focal infection)
  3. New onset seizure (within the last week)
  4. Papilledema
  5. Abnormal level of consciousness (inability to answer 2 consecutive questions or follow 2 commands)
  6. Focal neuro defect

We also reviewed the data for dexamethasone (10mg Q6H x 4 days) started prior to antibiotics in adults. The 2002 NEJM article (3) demonstrated decreased unfavorable outcomes in the dexamethasone group as compared to the placebo (15% vs. 25% with RR 0.59). This was especially pronounced in those with S. pneumo meningitis (26% unfavorable outcome vs. 52% in placebo group). While the data for steroids improving outcomes with Neissieria is lacking, until you have the bug back, it’s worth the steroids!

Finally, we reviewed the CDC guidelines for pneumococcal vaccines and the data that demonstrated that PCV vaccination DECREASES S. Pneumo meningitis (54% reduction in incidence in those >65 during) (4).

  1. Attia J et al. Does This Adult Patient have Acute Meningitis? JAMA 1999;281(2): 175-181.
  2. Tunkel AR et al. Practice Guidelines for the management of bacterial meningitis. CID 2004;39:1267-84.
  3. De Gans J et al. Dexamethasone in Adults with Bacterial Meningitis. NEJM 2002;347:1549-1556.
  4. Hsu, HE et al. Effect of pneumococcal conjugate vaccine on pneumococcal meningitis. NEJM 2009;360:244-56.