Category Archives: General Internal Medicine

Moffitt Pearls – 11/15/17 – VZV Encephalitis

Thank you to Andrew for presenting the case of an elderly man with recent CVA presenting with progressive encephalopathy 2/2 to VZV encephalitis.

Key Pearls

  • Acute toxic-metabolic encephalopathy (TME) is an acute condition of global cerebral dysfunction in the absence of primary structural brain disease
  • Acyclovir neurotoxicity should be considered with new neurological symptoms or encephalopathy 24 hours initiation of treatment, particularly in the presence of renal impairment.
  • Herpes zoster encephalitis (HZE) is an uncommon complication of herpes zoster with immunosuppression (HIV, immunosuppressive medications, increasing age) being the principal risk factor for the development of HZE.
  • Localized zoster can cause CSF pleocytosis and positive VZV PCR despite lack of active CNS infection -> this is b/c neurons are the primary site of latent virus
  • In suspected cases of zoster encephalitis send BOTH VZV PCR and Viral anti-body. The presence of one or both is evidence of small-vessel encephalitis due to VZV.
  • VZV encephalitis is rare and life-threatening-> Empirical treatment with IV Acyclovir 10-30 mg/kg per day for 10 days is currently recommended, however no RTCs have been performed.

The figure below outlines the disease pathology of VZV infection from primary infection to reactivation. See Dr. Gilden’s (a leader in the study of VZV) for an excellent review of VZV in the NEJM – “Neurologic Complications of the Reactivation of Varicella-Zoster Virus.”

VZV Encephalitis


Moffitt Pearls 11/7/17 – Cards Report – Vasopressors and PA Catheters

Thank you Matt H for your help with these PEARLS!!!

Thanks to Chloe for presenting a fascinating case of a 65 year old man with history of HOCM (w/o obstruction) who presented with acute onset shortness of breath, ultimately thought secondary to flash pulmonary edema from paroxysmal hypertension. We had a great discussion on vasopressors to use in different types of shock. Below is a summary of some of the more common vasopressors, as well as brief information on key considerations in their use. Finally, there is a bit of info on the ESCAPE trial that led to reductions in use of PA catheters in management of cardiogenic shock.

For more information, refer to the UCSF Hospitalist Handbook and the MGH CCU handbook.

Key Pearls

  • Dobutamine is considered a first line pressor in cardiogenic shock b/c it improves contractility and drops SVR (watch out for dropping BPs).
  • HOWEVER, never write for a MAP goal and titration parameters when using dobutamine as patients MAPs will sometimes drop with up titration (this is why we sometimes start this with norepinephrine).
  • The ESCAPE (2005) showed no improved 6 month mortality in patient with decompensated heart failure randomized to management with PA catheter monitoring vs. usual care. See indications for when to us a PA catheter below.

Vasoactive/Inotrope medications

Class Drug Dose Mechanism
Vasopressor Phenylephrine 0-200 mcg/min α-1 agonist
Vasopressin 0.04 units/min V-receptor agonist
Mixed Norepinephrine 1-20 mcg/min α-1, β-1 agonist
Epinephrine 1-20 mcg/min α-1, β-1, β-2 agonist
Dopamine 1-3 mcg/kg/min

2-10 mcg/kg/min

10-20 mcg/kg/min

D agonist

β-1, β-2 agonist

α-1 agonist

Inodilator Dobutamine 2-5 mcg/kg/min β-1 > β-2 agonist
Milrinone 0.375-0.75 mcg/kg/min PDE III inhibitor


Receptor Action
α-1 Vasoconstriction
β-1 Inotropy
β-2 Vasodilation, bronchodilation
D Splancnic vasodilation – increases renal blood flow
V Vasoconstriction

Quick info on selected vasoactive agents:

Norepinephrine: 1st line pressor for sepsis, cardiogenic shock, undifferentiated shock.

Vasopressin: Often 2nd line pressor in sepsis. Use caution in patients with coronary or peripheral vascular ischemia. Not affected by acidosis (many other pressors are less effective in this situation)

Phenylephrine: Useful for pure vasodilatory hypotension (e.g. sedation-related hypotension). Generally avoid in cardiac patients as can cause reflex bradycardia with decreased cardiac output. HOWEVER, can be useful in unstable arrhythmias when beta agonism may be undesirable. Also useful in HOCM with dynamic outflow obstruction (‘stents’ open the obstruction) or fixed obstruction in AS as it increases SVR without changing afterload felt by the heart.

Epinephrine: Primary use is in ACLS, though can also be used as 3rd pressor in refractory hypotension. Adverse effects include tachycardia/tacchyarrythmias, peripheral vasoconstriction and end-organ damage

Dobutamine: Increases contractility while reducing SVR. Often decreases blood pressure, therefore should not be thought of as a vasopressor, should also not be titrated to MAP goals. Risk of arrhythmia with higher doses, also risk of myocardial ischemia from increased oxygen demand.

Milrinone: PDE-3 inhibitor, inhibits cAMP breakdown. Similar to dobutamine, results in both inotropy and decreased SVR (perhaps more reduction in afterload, but also more risk of hypotension, than dobutamine). Requires dose-reduction in renal impairment.

Indications for PA Catheters

ESCAPE trial (2005) – randomized patients with acute decompensated heart failure to therapy guided by PA catheter vs no PA catheter. No difference in 6 month mortality or days out of the hospital. Based on this trial and meta-analysis, PA catheters are no longer used routinely. They still have a role in shock of uncertain etiology or when initial management is unsuccessful.

AHA guidelines on PA catheters (2013):

  • Recommended in patients with respiratory distress or evidence of impaired perfusion when intracardiac filling pressures can’t be determined by clinical assessment (class I, level C)
  • Can be useful in heart failure with persistent symptoms despite standard therapy if any of the following are present: (class IIa, level C):
    • Uncertain volume status, perfusion, SVR, PVR
    • Persistent hypotension
    • Worsening renal function despite initial therapy
    • Need for vasoactive agents
    • Anticipated need for mechanical cardiac support
  • Routine use not recommended in normotensive patients with acute decompensated heart failure responding to diuresis and afterload reduction (class III, level B)

Double Moffitt Pearls 11/3 & 11/6 – ALF, Toxic ingestions and Mesenteric Lymphadenopathy

Moffitt Pearls 11.3.17 – Saipan Case

Thank you to Amy for presenting a case from Saipan!! We learned about a middle-aged man presenting with encephalopathy and jaundice found to have acute liver injury and renal failure of unclear etiology. The leading thoughts were possibly leptospirosis vs biliary colic that self resolved. The patient was managed with IV abx and IVFs and improved over 2 weeks. We discussed the limitations of practicing in this setting and inability to transfer this patient to a center for transplant evaluation.

Key Pearls

  • EtoH Hepatitis: jaundice, anorexia, fever, and tender hepatomegaly. Labs: transaminases (typically less than 300 int. unit/mL), AST/ALT ratio > 2. Patients may also present with right upper-quadrant/epigastric pain, hepatic encephalopathy, and signs of malnutrition.
  • Acute liver failure is defined as the presence of coagulopathy (INR > 1.5), encephalopathy and no pre-existing liver disease. See more details below.
  • Leptospirosis has a broad range of manifestations, from subclinical illness or mild self-limited disease (approximately 90% of infections) to Weil’s syndrome (Weil’s disease), which is characterized by renal failure, jaundice, and hemorrhage and has a 5 to 15% mortality rate (1).
  • See this NEJM article where HH crushes the diagnosis in the first couple of sentences (it is related to this case)

Overview of Acute Liver Failure 

ALF = coaguapathy INR > 1.5, encephalopathy, and no signs of chronic liver disease

Key History: 

  • IVDU, travel, sexual, ingestions, Fmhx Wilson’s, (note: Hemochromatosis – no acute liver failure)

Physical Exam:  

  • Vitals, stigmata of liver disease, neuro exam, optho exam

Etiology of Acute Liver Failure

  • Ischemia*
  • Toxins* – Tylenol (most common cause in USA), Amanita
  • Acute viral hepatitis*
    • Professional: HAV, HBV, sometimes HCV, HEV
    • “Moonlighters”: HSV, CMV, VZV, parvovirus
  • Autoimmune Hepatitis
  • Acute Budd Chiari – esp if concomitant portal vein thrombosis
  • Reactivation of HBV or HDV on chronic HBV
  • Wilsonian crisis – often with concomitant hemolytic anemia
  • Malignant infiltration – breast, small cell lung, lymphoma, melanoma, myeloma
  • HLH
  • Heat stroke 
  • Remember -> NOT causes of acute liver failure – ETOH, NAFLD, iron overload, alpha-1 def, PSC, PBC
  • * denotes are most likely to cause AST/ALT in the 1000s


Moffitt Pearls 11/6 – Toxic Ingestions

Thank you to Tim for presenting a fascinating case of a young woman 9 weeks post-partum presenting with a profound gap acidosis and osm gap initially c/f ethylene glycol vs methanol ingestion found to have severe starvation ketosis. We discussed the evaluation of possible ingestions and treatment for suspected Ethylenel Glycol ingestion with fomepizole (below).

Thank you HH for presenting a mini-case of a young engineer returning from India p/w abdominal pain, n/v and mild hepatocellular transaminitis (300s) found to have mesenteric lymphadenopathy 2/2 hepatitis E!!

Key Pearls

  • Per EM guidelines send Serum Osm, Salicylates, APAP and EtoH levels in any suspected ingestion.
  • Fomepizole is used in ethylene glycol and methanol toxic ingestion. It is a competitive inhibitor of alcohol dehydrogenase and prevents formation of glycolic acid which is responsible for both the acidosis and oxalate crystal formation. See this NEJM article for more info.
  • We learned the ddx for mesenteric lymphadenopathy include hepatitis E in addition to those listed below!!

Effect of Fomepizole on Metabolism of Eythlene Glycol and Methanol (Brent J. N Engl J Med 2009;360:2216-2223)Picture1

Differential Diagnosis for Mesenteric Lymphadenopathy

  1. Malignancy – almost any intraabdominal malignancy and metastatic process can cause mesenteric lymphadenopathy, however the following are more common:
    1. Lymphoma
    2. Carcionid Tumors
    3. Kaposi Sarcoma
    4. Carcinoma of pancreas, colon or small bowel
  2. Infection
    1. TB or MAC
    2. Salmonella and Yersinia
    3. T. Whippelii
    4. Viral Infections –EBV and Hepatitis E
  3. Inflammatory

Moffitt Pearls 10.2.17 – Upper GI Bleed

Key Pearls for Upper GI Bleed Evaluation and Management

  • JAMA Rational Clinical Exam series: Does this patient have a severe upper GI bleed? A great resource for evaluation of a patient with suspected upper GI bleed attached below!
  • Bleeding sources proximal to the ligament of Treitz are considered Upper GI bleeds by definition

-> Top 3 causes include peptic ulcer bleed, gastritis and variceal bleed.

  • NG lavage with blood or coffee grounds has a positive LR of 9.6 for UGIB, but sensitivity is only 44%! If it’s there, you’re likely dealing with UGIB, but if it’s not, you still might be!
  • The other features that have solid likelihood ratios for UGIB are melena on exam (LR, 25) and BUN/Cr ratio >30 (LR, 7.5).
  • Blood clots in the stool make UGIB much less likely (LR 0.05).
  • The Blatchford prediction score efficiently identifies patients who do NOT need urgent scope. Score components are HR, BP, hgb, BUN, melena, syncope (as in our patient today), liver disease, and heart failure.
  • Remember: We usually use a transfusion threshold of hgb 7.0, but if someone is unstable and actively bleeding, transfuse regardless of hgb level!


Moffitt Pearls – Rheumatology Report – 8.21.2017 – Evan’s Syndrome and SLE

Thank you to Leah for presenting a very interesting case of a young man with history of lupus c/b APS and DVT presenting with thrombocytopenia+ hemolysis found to have Evan’s Syndrome (ITP + AIHA)!


Key Pearls

  1. Although the term is falling out of favor Evan’s syndrome describes the combo of ITP & AIHA.
  2. For unclear reasons, lupus flares are often accompanied by a dissociation between ESR (high) and CRP (nl or minimal elevation). Other findings of flare (vs. infection) include drop in complement, recued leukocyte count and + RBC casts and/or proteinuria.
  3. Direct oral anticoagulants have not been studied nor are they recommended as anticoagulants in patients with lupus and known DVT. Treat with warfarin or LMWH only!


More on Evan’s Syndrome

  • Combination of Coombs-positive warm AIHA and immune thrombocytopenia (ITP).
  • Antibodies that cause platelet destruction are unique from those that cause AIHA.
  • Differential Diagnosis:
    • Infectious (eg, HCV, HIV)
    • SLE
    • Lymphoproliferative disorders
    • Common Variable immunodeficiency
  • Treatment (similar to ITP, however azathioprine and cyclophosphamide are used)
    • First line therapy: Glucocorticoid @ 1-2 mg/kg +/- IVIG
    • Second line: Azathioprine or rituximab
    • Third line: Splenectomy
    • Under investigation: Eltrombopag –> a TPO receptor agonist stimulating platelet formation

American College of Rheumatology Classification of SLE

[Always verify all prior diagnoses of rheumatological conditions]

  • SLE Criteria > 3 of 11 ( Se & Sp > 95% and all DO NOT have to be at the same time)
    • Cutaneous Manifestations
      • Malar Rash
      • Photosensitivity
      • Discoid Rash
      • Oral ulcer
    • MSK
      • Nonerosive arthritis – oligioarticualr; symmetrical, migratory
    • Cardiopulmonary
      • Serositis – pleuritic or pericarditis
    • Renal
      • Proteinuria or cellular Casts – > 500 mg/dL on UA or 3+ on dip


    • Neurological
      • Seizures OR psychosis


    • Hematological
      • Hemolytic anemia or leukopenia, or lymphopenia or thrombocytopenia
    • Serologies
      • +ANA
      • +anti-dsDNA or antiphopholipid Abs


Review of Hemolytic Anemias based on Smear


Moffitt Pearls 8.15.17 – Anaphylaxis and Drug Reactions

Case Summary:

Thank you to Karen for presenting a mystery case of a young man with hx of asthma, seasonal allergies and eczema p/w perioral edema, itching and profound hypotension concerning for anaphylaxis! We discussed the importance of early therapy for anaphylaxis, drug reaction patterns and the possibility of serum sickness in the setting of Bactrim exposure and the atypical nature of her presentation.


Key Pearls

  1. Anaphylaxis is a Type 1 IgE mediated hypersensitivity reaction that usually occurs within in minutes of an allergen exposure.
    • Volume and IM epinephrine are mainstays of therapy and should NOT be delayed.
  2. Drug reactions are often delayed days to weeks from drug exposure (make sure to review a log) and are mediated by Type IV hypersensitivity.
  3. Angioedema may be manifested by IgE mediated (Type I Hypersensitivity) drug reaction
    • IgE-mediated reactions tend to become more severe & progress toward anaphylaxis (Bactrum as in our case) upon re-exposure to causative agent


Classification of Allergic Reactions

Type Description Mechanism Clinical Features
I Anaphylactic Usually IgE dependent release of vasoactive substances (histamine, prostaglandins and leukotrienes) Anaphylaxis (definition below), Angioedema, urticarial, GI Sx and bronchospasm
II Antibody (AB)-dependent cytotoxicity Antigen/Haptan associated with cell binds AB -> cell/tissue damage Hemolytic anemia, Interstitial nephritis
III Immune Complex Disease Formation of Antigen-Antibody (AB) Complexes Causes damage Serum Sickness
IV Cell-mediated or Delayed Hypersensitivity Antigen sensitizes T cells, then mediates tissue injury Delayed dermatitis or drug reaction

Drug Reaction Patterns Discussed

SJS (< 10 % body surface area)/TEN (>30% body surface area)

  • Mucosal involvement required, occurs usually within 8 weeks of drug exposure


  • Systemic involvement (fever, adenopathy elevated LFTs) driven by eosinophilia; Reaction begins 2-6 weeks after exposure to offending drug


  • Reaction often occurs 48-72 hours after drug exposure

Fixed Drug Eruption

  • Usually without mucosal involvement, occurs anytime – days to weeks after drug exposure


  • >90% of body surface area involved; ddx wide and includes drugs ~ 20% cases and malignancy (Cutaneous T-cell lymphoma)



Moffitt Pearls – 8.11.17 – Saddle Nose Deformity, Upper GI Bleeding &Munchausen Syndrome

Thank you to HH and Neil for both presenting today! HH first presented a mini case of a patient who came in for a gout flare that was found to have a saddle nose deformity.

Neil then presented the interesting case of a young woman with a hx of gastric ulcers presented with epigastric pain and hematemesis who after extensive work-up including CT and EGD was found to have Munchausen syndrome!************************************************************************************

Key Pearls

  1. The differential diagnosis for saddle nose deformity falls into the classic triad of infectious, inflammatory and malignancy per table below.
  2. 80% of upper GU bleeds are due to four causes: peptic ulcer disease (35%), esophagogastric varices (30%), esophagitis (10%) and Mallory-Weiss tears (~5%).
  3. The management strategy for a pt. w/ munchausen syndrome is VERY difficult, but should include a single provider (w/ help from psychiatry) and goal to limit interventions + discuss diagnosis with patient in a supportive manner.


Differential Diagnosis for Saddle Nose Deformities

Infectious Inflammatory Malignancy Other
Syphilis GCA (formerly Wegner’s) NK T-cell Lymphoma Trauma
Leprosy Sarcoidosis Locally invasive tumor (BCC) Cocaine
TB Relapsing polychondritis Lymphomatoid Granulomatosis Surgery
Cutaneous Leishmaniosis      
Septal abscess      

 Differential Diagnosis for Hematemesis AND Fever

  • Mallory-Weiss Tear
  • Peptic ulcer bleeds c/b perforation
  • Hemosuccus pancreaticus (pseudoaneurysm/aneurysm)
  • Upper GI Malignancy – hemobilia, widespread esophageal/gastric malignancy

Munchausen Syndrome or Factitious d/o Imposed on Self

  • Definition: Falsified general medical or psychiatric symptoms
  • Risk Factors: Females, Unmarried, Healthcare professional
  • Diagnostic Criteria (DSM-5):
  1. Falsification of physical or psychological signs or symptoms, or induction of injury or disease, associated with identified deception
  2. The individual presents himself or herself to others as ill, impaired, or injured
  3. The deceptive behavior is evident even in the absence of obvious external rewards
  4. The behavior is not better explained by another mental disorder, such as delusional disorder or another psychotic disorderPrognosis: Very poor even as multiple studies have shown limited benefit even with psychotherapy
  • Management: One provider should oversee pt with help of psychiatry w/ goal to limit interventions. One should be sure to exclude all possible medical conditions and then discuss diagnosis w/ pt in supportive manner