ZSFG AM Report Pearls 3/28/2018: B-b-b-b-b-bad, Bad to the Bone Marrow: ET, PV, and MDS Mutations and Work-Up

On this day, we discussed an elderly patient who presented with leukocytosis and severely elevated platelets. We discussed the DDx for these findings as well as some of the common genetic tests. Shout out to Corynn Kasap for dropping some serious knowledge on all of us!

=============================================================

See the NEJM article referenced in the sources for more information, but this is super interesting!

Myeloproliferative Neoplasms:

These are three hematopoietic stem-cell disorders that share mutations that activate the physiologic signal-transduction pathways responsible for hematopoiesis.

  • Polycythemia vera
  • Essential thrombocytosis
  • Primary myelofibrosis

The mutations that are most commonly involved in these diseases include:

  • JAK2
  • MPL
  • CALR
  • Cases are often from sporadic mutation, but about 7% of cases involve familial predisposition
  • Pathogenic mutations have been identified in more than 90% of patient with myeloproliferative neoplasms
    • 50-60% of patient have only a driver mutation: JAK2, CALR, MPL or in rare cases LNK
    • These mutations are not mutually exclusive, nor are they exclusive to a particular myeloproliferative neoplasm and their absence does not preclude any of these neoplasms!
  • These myeloproliferative neoplasms can evolve into others and can develop into AML
Source:
  • Spivak JL. (2017). Myeloproliferative neoplasms. NEJM. 376:2168-2181.

Evernote:

 

ZSFG AM Report Pearls 3/27/18: 2 Steps Forward, 2 Steps Back: Paradoxical Reactions & IRIS in TB Tx in HIV+ Pts

Hey Team! Playing a little catch up on these awesome pearls from late March. We discussed an interesting case of an HIV+ pt who was diagnosed with TB. After starting TB tx, they ended up looking more sick and had to pause treatment. This brought up discussion about paradoxical reactions in treating TB as well as a few other pearls:
++++++++++++++++++++++++++++++++++++++++++++++++=
Epidemiology of TB in the US:
In the US, only 3.2% of the population is estimated to have latent TB
There are only 11,000 cases annually of active TB (remember though what your base population is – San Francisco, CA is not Dayton, OH)
>50% of cases are are in individuals born outside of the US
In the US, only 10% of cases in the US are coinfected with HIV
Extrapulmonary TB:
Prevalence = 10-42% worldwide depending on the race or ethnic background, age, presence/absence of underlying disease, genotype of the M. tuberculosis strain, and immune status (note that this is probably lower given US population)
Can affect any part of the body with a wide range of clinical presentations
TB Treatment and Paradoxical Reactions:
Paradoxical reactions to TB treatment – defined as the worsening of existing lesions or presentation of new lesions during anti-TB therapy nad typically associated with exaggerated inflammatory symptoms like fever, lymphadenitis and pulmonary manifestations
Epidemiology: Frequency somewhere between 2% and 23%
  • HIV infection is also associated with a syndrome in which paradoxical inflammatory consequences occur during therapy: the immune reconstitution inflammatory syndrome (IRIS).
    • Here, the commencement of HAART leads to an exacerbation of an existing opportunistic disease, or unmasking of a previously subclinical infection.
  • IRIS is most frequently observed in mycobacterial infections
    • Several forms have been described in HIV/TB co-infected individuals
      • The commonest of these is paradoxical TB-IRIS, in which inflammatory exacerbations of TB symptoms occur after commencement of HAART in HIV-seropositive patients being treated for active TB,15 the frequency of which was estimated to be 15.7% in a meta-analysis of 3459 individuals.
      • A second form, unmasking TB-IRIS, is when a new presentation of active TB arises after commencing HAART. The occurrence of unmasking TB-IRIS is thought to be lower than paradoxical TB-IRIS, with estimates varying between 1.4% and 23%.14,17–19 I
      • It is also suggested that HIV-seropositive individuals with active TB may have an increased incidence of PR when commencing antimycobacterial therapy, compared to HIV-seronegative individuals.
Diagnostic criteria do not yet have consensus guidelines but include worsening of clinical or radiologic findings after the initiation of appropriate antimycobaterial therapy.
The physiology behind this is not well understood and the hypotheses are based on clinical observations but are somewhat summarized in the graphic below:
  • Prior to treatment, there is a building mycobacterial load/infection, while the inflammatory system is calmed down (and likely suppressed from HIV)
  • Once you start treatment (typically for both TB and HAART for HIV) the immune system ramps up
  • In people who don’t get paradoxical reactions and IRIS, the immune system and mycobacterial load is more in sync
Evernote:

Source:

  • Gordin FM & Masur H. (2012). Current approaches to Tuberculosis in the United State. JAMA. 308(3):283-289.
  • Zumla A et al. (2013). Tuberculosis. NEJM. 368:745-755.
  • Bell LCK et al. (2014). Paradoxical reactions and immune reconstitution inflammatory syndrome in tuberculosis. International Journal of Infectious Disease. 32:39-45.

ZSFG AM Report Pearls 3/14/18: Just Stop Pressuring, Stop Pressuring Me, Make Me Want to Scream: Guidelines for Secondary Hypertension Work Ups

Thank you to our Cardiology team who presented this great case which was recently presented as again about a very young man who presented with severely elevated HTN, end-organ damage, and AKI on CKD who was admitted for HTN emergency and found to have ESRD requiring dialysis. This brought up a great questions about secondary HTN work-ups

**************************************************************

2010 AAFP Guidelines:

When to Suspect:
-Resistant – doesn’t respond to BP meds
-“Very high” BP
-Age <30, or >55 years
-Sudden onset
-No family hx
-Not obese
Common Causes:
Renal: PCKD, DM nephrotpathy, HTN nephrosclerosis, GM disease, renovascular, CKD of any kind
Vascular: Fibro musc dysplasia (younger women), RAS (any age), coarctation of the aorta (teens)
Endocrine: Cushing, Pheo, Hyderaldo, Hyper-TSH, Hyper-PTH, acromegaly
Meds/Supplements: NSAIDs, cocaine, OCPs, steroids, pseudophed. SSRI, Buspar, Lithium, TCA
Other: OSA, pregnancy, obesity, scleroderma, NF1, White coat, post-surgical
Work-Up:
-Med rec
-Age based:
     -Basic: U/A, Cr, TSH, Lytes, plasma adlo:renin, Doppler U/S, Cortisol if Cushinoid
     -19-39: TSH, FMD, renal parenchymal disease
     -40-64: Aldo, thyrdoid, OSA, cushin, pheo
     ->65: Atherosc RAS, CKD, hypo -TSH
Evaluation Based on Age:
19-39:
     -MRI with gad or CT renal artery
     -TSH
     -+/- ECHO
     -+/- 24hr urinary cortisol and urianry meta
 40-64:
     -Renin and also
     -TSH
     -Sleep study
     -+/- 24hr urinary cortisol and urianry meta
>65:
     -Renal U/S with Doppler – CT renal artery
     -TSH
     -U/A
     -+/- 24hr urinary cortisol and urianry meta

2017 AHA Guidelines:

Screening for secondary causes of hypertension is necessary for:

  • new-onset or uncontrolled hypertension in adults including drug-resistant (≥3 drugs)
  • Abrupt onset
  • Age <30 years
  • Excessive target organ damage (cerebral vascular disease, retinopathy, left ventricular hypertrophy, HF with preserved ejection fraction [HFpEF] and HF with reserved EF [HFrEF], coronary artery disease [CAD], chronic kidney disease [CKD], peripheral artery disease, albuminuria)
  • Onset of diastolic hypertension in older adults or in the presence of unprovoked or excessive hypokalemia.

 

  • Screening includes testing for
    • CKD
    • Renovascular disease
    • Primary aldosteronism,
    • Obstructive sleep apnea
    • Drug-induced hypertension (nonsteroidal anti-inflammatory drugs, steroids/androgens, decongestants, caffeine, monoamine oxidase inhibitors)
    • Alcohol-induced hypertension.
    • If more specific clinical characteristics are present, screening for uncommon causes of secondary hypertension is indicated (pheochromocytoma, Cushing’s syndrome, congenital adrenal hyperplasia, hypothyroidism, hyperthyroidism, and aortic coarctation).

 

Sources:

  • 2017 ACC/AHA/AAPA/ABC/ACPM/AGS/APhA/ASH/ASPC/NMA/PCNA Guideline for the Prevention, Detection, Evaluation, and Management of High Blood Pressure in Adults: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines. J Am Coll Cardiol 2017;Nov 13:[Epub ahead of print].
  • Viera AJ & Neutze DM. (2010). Diagnosis of secondary hypertension: An age-based approach. American Family Physician. Dec 15.

Evernote: https://www.evernote.com/shard/s509/sh/39a663b2-c3cc-4876-92dd-e10aa7cd763b/745c60116211172ee76d6b1b4999f5c2