Category Archives: Infectious Disease

Moffitt Cardiology Pearls 12.5.17 – Sinus Exit Block and Endocarditis

Thank you Nadia (my co-fellow to be next year!!) for presenting an amazing cardiology case with Anne Thorson. She presented the case of a man w/ hx of crack cocaine use and recent strep pneumo meningitis p/w acute SOB found to have a diastolic murmur, PR prolongation, sinus exit block and an perivalvular abscess!! The patient was found to have severe chronic AI and was being evaluated by CT surgery for definitive management while on IV abx. Keep us updated!!

Key Pearls

  1. ECG conduction changes, from first degree AV block to complete heart block, are associated with increased mortality in patients with known endocarditis (Am Heart J 2001;142:280-5.)
  2. See this study in the American Heart Journal for more information about conduction abnormalities and endocarditis (remember that these will occur at the level of AV node).
  3. See Figure below for more information on sinus exit block.

For more information see –



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

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 9.29.17 – Fever in a Returning Traveler – Part 2

Moffitt Pearls 9.29.17 – Fever in a Returning Traveler – Part 2

Thank you to Kenny and Manoj for presenting the interesting case of a young man with tetralogy of fallot returning from Australia and Indonesia with a jaundice, fevers, sore throat and adenopathy initially treated for strep throat then admitted with atypical lymphocytes c/f EBV related mononucleosis. Once again we had to re-frame the patient in real time and prevent anchoring on travel history for diagnosis.

Key Pearls

  1. Thank you to HH for sharing the ddx for a mono-like illness (fevers, adenopathy, sore throat): HIV, CMV, EBV, toxoplasmosis and bartenella.
  2. The differential for peripheral lymphocytes includes acute viral infections such as EBV/CMV, bacterial infections such a pertussis, TB or brucellosis and malignancies such as lymphoma, CLL and ALL.
  3. See the NEJM article below for approach to fevers in a returning traveler from Feb 2017.

Intern Report Peals from yesterday (thank you Rabih for diagram!!)





Moffitt Pearls 7.10.17 – PD-1 Inhibitors & PCP Pneumonia

Pulmonary Report 7.10.17

Thank you to Ugo for presenting the case of an elderly male with widely metastatic melanoma refractory to PD1 inhibitors presenting with 1-2 weeks of fatigue, FTT, DOE found to have PCP pneumonia!

Top Pearls:

  • PD1 inhibitors are considered first-line therapy for metastatic melanoma.
  • Common toxicities of immune check point inhibitors include immune-mediated inflammation of virtually any organ system. See below for more details on PD1 inhibitors.
  • The risk for opportunistic infections w/ checkpoint inhibitors is related to the steroids that are generally given to treat the checkpoint inhibitor toxicities. A case report & paper ( illustrating this risk.
  • Remember! For patients on steroids if > 20 mg/day of prednisone for > 2 weeks –> give PCP prophylaxis. (per expert opinion -> the rule of Dr. Jen B!)

Which patient that are immunocompromised get PCP?

  • HIV-positive patients (CD4 < 200)
  • Cancer, solid organ transplant, BMT – related to type & chemo intensity
  • Rheumatologic (GPA has intrinsic risk)
  • Chronic steroids (see Jen rule above)

Steroids for Rx of PCP in HIV-Negative patients??

  • Not well studied in HIV-negative patients, only a few retrospective studies
  • No mortality benefit, but may expidite recovery
  • Steroids are recommended in the AJT guidelines
  • 40-60 mg Prednisone BID x 5-7 days with 7-14 day taper


Table Comparing PCP in HIV Positive and Negative Patients (thanks Jen!)

table PCP


PD-1 Inhibitors (blast from the past)


Emerging data show that 20% of patients with melanoma treated with ipilimumab achieve long-term survival! See this associated review.

PD-1 (programmed cell death 1) and its association with the ligand (PD-L1) is a necessary step in stimulating apoptosis of T-cells, serving as an immune checkpoint. PD-L1 is generally expressed by native cells, signaling to the T-cell “I’m one of you! Don’t hurt me”.  Some tumors have been found to also express PD-L1, enabling them to evade destruction by T-cells.  In order to treat these malignancies, PD-1 inhibitors (pembrolizumab, nivolumab) serve to block the interaction between PD-1 and PD-L1, enabling T-cells to stay “programmed on”, and thus enable immune-mediated destruction of tumor.

Because of this mechanism of action, a common consequence is the upregulation of cell-mediated immunity and, unfortunately, inhibition of native tissues to turn off T-cells. As a result, we commonly see autoimmune-mediated inflammation manifested as new rash, diabetes, thyroid disease, pneumonitis, hepatitis, colitis, etc.

Common Immune-Mediated Toxicities Seen with Check-point Inhibition:

Organ System Manifestation Management
Skin & Mucosa Pruritic rash (most common!)




Topical corticosteroids

Oral antipruritics

Consider oral steroids

GI Tract Diarrhea/colitis – presents ~6wks into treatment R/O infxn

Anti-motility agents

Steroids if severe

Liver Hepatitis (rate <5%, severe toxicity very rare) Stop therapy if moderate-severe.

Steroids + mycophenolate given rarely.

Lung Pneumonitis – (rate <5%, but occasionally fatal) Steroids common. Infliximab, cyclophosphamide also used, though patients requiring therapy beyond steroids have nearly 100% mortality.
Endocrine Hypophysitis

Autoimmune thyroid disease

Adrenal Insufficiency T1 DM

Hormonal replacement


Less commonly reported immune-mediated adverse events include the following: acute renal injury, pancreatitis, neurotoxicity (GBS, myasthenia gravis, PRES, aseptic meningitis, autoimmune encephalitis), cardiotoxicity (myocarditis), hematologic (cytopenias), and ocular inflammation.

Many of the adverse events described above can be managed with continued use of PD-1 inhibitors if mild. However, for severe adverse reactions, PD-1 inhibitors are withheld and potential discontinued permanently.

Moffitt Pearls 6.27.2017 – Cardiology Report – Chagas Cardiomyopathy


Thank you to Satvik for presenting a case of a young man with newly diagnosed bi-ventricular HF thought 2/2 meth use, c/b LV thrombus presenting with SOB + CP presenting with afib with RVR. We discussed the nuanced management of a patient with hemodynamically significant RVR with a known LV thrombus, later found to have positive Chagas antibodies!



  1. Acute management of supraventricular tachycardia generally depends on an assessment of hemodynamic stability. In the unstable patient, you should consider early cardioversion.
  2. Triggers for atrial fibrillation with RVR: volume overload (w/ decompensated heart failure), medication non-adherence, coronary ischemia, drug use, PE, infection.
  3. Bedside IVC ultrasound can help provide additional information for assessment of CVP and fluid responsiveness (see attached)
  4. Differential for biventricular heart failure: ischemia, long-standing LV failure, substance abuse (meth, EtOH), infiltrative disease (amyloid, hemochromatosis, sarcoid), tachycardia-mediated, infectious (Chagas).


Differential Diagnosis of Dilated Cardiomyopathy


Disease Conduction Disease TTE Features Treatment
Cardiac Sarcoid


+++ + Perfusion defects, inflammation Corticosteroids, methotrexate, antimalarial agents
Giant cell myocarditis


+ Nonspecific Corticosteroids, cyclosporine
LV noncompaction


+ WPW ↑ Trabeculation, LV thrombi NA
AVRC (arrhythmogenic RV)


+++RBBB RV>>LV diltion/dysfunction, RV aneurysm of free wall NA
Chagas Disease


Early: +++ RBBB+ LAFB

Late: CBH + RBBB

Apical aneurysm or thrombus and infarct pattern Benznidazole early, Transplant late


More Details on Chagas Cardiomyopathy

  • Etiology: Protozoal parasite Trypanosoma cruziI spread by insect vector triatomine bug
  • Endemic regions: Central and South America
  • Epidemiology: Most common cause of non-ischemic cardiomyopathy in Latin America
  • Pathophysiology: Mechanism of cardiac injury is not well known, but is hypothesized to be a robust immune response to a small population of remaining protozoa.
  • Extracardiac involvement: Gastrointestinal dysmotility often a clue
  • Cardiac involvement: Acute infection is usually not recognized and is rarely life-threatening. ~ 20% of patients develop chronic Chagas disease within 10-20 years after an acute infection. Of these patients between 1/3 and 1/2 develop chronic cardiomyopathy characterized by conduction abnl RBBB, LV thrombi and regional wall motion abnormalities without obstructive CAD.
  • Diagnosis: Serological IgG and IgM and demonstration of cardiac or GU involvement
  • Treatment: Acute and indeterminate phase – guidelines recommend benznidazole; Chronic disease – paucity of data, however per guidelines treatment as per above (some evidence that tx may alter cardiac course – see article below), in addition to supportive care for heart failure, arrhythmias (ICD and medical therapies) and tx for thromboembolism. Ultimately, definitive therapy for those with global BiV heart failure is with heart transplantation.

IVC*We use both the maximum IVC diameter as well as IVC collapsibility


More reading for those interested below:

  • Review of dilated cardiomyopathy with conduction disease and arrhythmias.
  • Long-term cardiac outcomes of treating chronic Chagas disease with benznidazole versus no treatment: a nonrandomized trial.Viotti R, Vigliano C, Lococo B, Bertocchi G, Petti M, Alvarez MG, Postan M, Armenti Ann Intern Med. 2006 May 16; 144(10):724-34.
  • Another excellent article complements of HH on disease reactivation after transplant:

Moffitt Intern Report Pearls 6.8.17

CONGRATS INTERNS ON YOUR LAST INTERN REPORT!!! And HUGE thank you to Lev for presenting a fascination case of middle aged man s/p prolonged treatment with steroids for EtoH hepatitis who presented with fevers and abdominal pain found to be in decompensated cirrhosis and later found to have semi-invasive pulmonary aspergillosis – wow!

Key Pearls

  1. If the direct bilirubin makes up greater than 20% of total bilirubin this is defined as direct predominance.
  2. Patients likely have impaired cellular immunity when steroid dosing reaches 20 mg for at least 14 days. At this dosing level you should consider starting PCP prophylaxis. More details below…
  3. Classical risk factors for semi-invasive Aspergilosis pulmonary infection:
    • severe or prolonged neutropenia
    • receipt of high dose corticosteroids per above
    • Other drugs or conditions that lead to chronically impaired cellular immune responses (e.g. AIDs, immunosuppressive regimen)

Thank you, Brad Monash, for sharing some more info on PCP prophylaxis in the setting of steroid use:

  1. The evidence for when to start PCP prophylaxis is weak. Some say that PCP ppx should be considered for patients on > 20 mg prednisone for > 2-3 weeks.
  2. Most evidence pertains to patients on steroids + underlying immunosuppressed state. Many experts will not use PCP ppx for steroids alone in the absence of other immunodeficiency.
  3. Here’s a fantastic review of PCP ppx from 2004, and one of the most cited papers on the topic (
  4. The article below cites the lowest dose of steroids on which patients developed PCP as 16 mg daily. (
  5. Interestingly, PCP has been described in Cushing syndrome!
  6. Check out this outstanding review of glucocorticoids and infection from 2008. (