Category Archives: Infectious Disease

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. (




ZSFG AM Report – 6.2.17 – HIV-Associated GI Pathology

Thank you Kenny for presenting a case of a patient with AIDS, abdominal pain, diarrhea, and fevers found to have a partial SBO and inflammation in the terminal ileum.

Top Pearls:

  1. Partial or complete small bowel obstruction in a patient without prior surgery is very unusual and should raise suspicion for tumors, complicated hernias, Crohn’s disease or other inflammatory processes, gallstones, volvulus, or intussusception.
  2. CT Abdomen/Pelvis is better than KUB for identifying the specific site and severity of obstruction (partial vs. complete), as well as potentially determining the etiology.
  3. Infections in HIV can localize to different parts of the bowel with small bowel etiologies including: HIV enteropathy, MAC, protozoan (Giardia and the spordia), and helminths (strongy)


More Information on HIV-Associated GI Pathology by Location in GI Track:
HIV-Associated GI Pathology (By Location):
                -CMV, HSV
                -Kaposi’s Sarcoma
                -Idiopathic ulceration
                -Neoplasia (Kaposi’s sarcoma, lymphoma)
Small Bowel:
                -HIV enteropathy
                -Protozoa (Giardia, Isospora, Cryptosporidia, Microsporidia)
                -Helminths (Stronglyoides)
                -Viral (CMV, HSV)
                -Bacterial (Clostridia, Salmonella, Shigella, Campylobacter)
                -Fungal (Cryptococcus, histoplasmosis)
                -Neoplastic (KS, lymphoma)


For more info on HIV-associated diarrhea, see this Evernote from Rachel Greenblatt:


Bhaijee F, Subramony C, Tang SJ, Pepper DJ. Human immunodeficiency virus-associated gastrointestinal disease: common endoscopic biopsy diagnoses. Patholog Res Int 2011;2011:247923.

Evernote Link:


ZSFG Morning Report: Dactylitis ddx, IGRA’s, and a hint of NTM/TB

Thanks to Lily Kornbluth for presenting the case of a woman from China admitted with a swollen and painful finger which turned out to be mycobacterial dactylitis!

You’re probably asking yourself: Wait, aren’t those swollen digits just in psoriatic arthritis??? Do I have a framework or a DDX FOR DACTYLITIS??? Well, NOW YOU DO! Here’s a short list generated in report today with the help of Lisa Winston, Stephanie Cohen, Lily, and the #fabulous ZSFG resident crew!

dactyl 1

Dactylitis DDX:


  • NTM
  • TB
  • Syphilis
  • Leprosy
  • Fungi like Blasto, Cocci, Aspergillus
  • Bacterial tenosynovitis or septic arthritis or osteo w/ Staph, Strep, Gonorrhea, Nocardia, and Vibrio (this patient noted a history of food preparation…;)


  • Psoriatic arthritis
  • Reactive arthritis
  • Gout
  • Sarcoid
  • SLE
  • RA

Malignant: Leukemia

Heme: Sickle Cell dz

As we narrowed in on the dx, a diagnostic test returned: POSITIVE QUANTIFERON GOLD! Lisa Winston reminded us about the power of the QTF-Gold and that it’s more specific than the PPD! Here’s a quick refresher and an elegant representation of the box/test….
quant gold

QuantiFERON Gold or more technically since it just rolls off the tongue: Interferon-gamma release assays (IGRA’s):

  • What are they?
    • Diagnostic tools for latent TB indicating a cellular immune response to M. tuberculosis.
      • IGRAs can’t distinguish between latent and active TB aka don’t use them to dx active TB
      • IGRA’s available around the world: QuantiFERON-TB Gold In-Tube (QFT-GIT) assay, Quantiferon-TB Gold (QFT-G) assay, and the T-SPOT.TB assay

  • How do they work?
    • By capitalizing on the M. tuberculosis–specific antigens: early secreted antigenic target 6 (ESAT-6) and culture filtrate protein 10 (CFP-10)!
      • QFT-GIT assay is an ELISA-based test that uses peptides from three TB antigens (ESAT-6, CFP-10, and TB7.7). A positive test denotes IFN-gamma response to TB antigens that’s above the test cut-off.
      • Of note, ESAT-6 and CFP-10 are encoded by genes in the region of difference 1 (RD1) segment of the M. tuberculosis genome. These antigens are more specific for M. tuberculosis than the PPD because they are not shared with any BCG vaccine strains or most species of NTM.
        • HOWEVER: Two of the NTM that affect humans, Mycobacterium marinum and Mycobacterium kansasii, contain gene sequences that encode for ESAT-6 or CFP-10. So infxn with either of these NTM’s=positive QTF test 😦

  • What are their test characteristics?
    • IGRA’s have specificity >95% for diagnosis of latent TB, especially great as unaffected by BCG vaccination. The sensitivity for the IGRA’s T-SPOT.TB and QFT-GIT are 90 and 80%, respectively. PPD sensitivity as reference is 80%. Of note, IGRA sensitivity decreases in patients with HIV!

Once the deep skin biopsy came back “swimming in AFB’s,” we discussed how to approach mycobacteria based on rapid or slow growth. Here is a simplified algorithm to consider…
mycobact outline


*Lisa Winston, Stephanie Cohen, and ZSFG resident crew
*Pai M et al. Systematic review: T-cell-based assays for the diagnosis of latent tuberculosis infection: an update. Ann Intern Med. 2008 Aug 5;149(3):177-84. Epub 2008 Jun 30. PMID:18593687




ZSFG can’t be MIF’d by penile lesion ddx & indications for sgy in endocarditis

At the General, we give you a little bit of this and a little bit of that in report. And same thing goes for the chiefs’ blog. This is a quick run-through of a few recent legendary reports!


In Neuro Report today, we crushed, I mean discussed, hypercarbic respiratory failure and the role of neuromuscular causes for it. We were joined by neurology guru, Andy Romeo, and here are a few of his pearls:

-Whenever you come across someone reporting dysphagia, make sure to ask about other bulbar sx’s
-In a patient with increased work of breathing in whom you’re considering if diaphragmatic weakness is playing a role, check neck flexor strength to assess if a new neuromuscular weakness is present
MIF & VC are the confrontational tests for the diaphragm. To remind ourselves about those two entities:

  • For Vital capacity (VC) and Mean inspiratory force (MIF), there is the 20-30 rule
  • VC: deep breath and exhalation maximally into spirometer; goal is at least 20cc/kg
  • MIF: inhalation against a closed valve with negative force recorded; goal is “more negative” than -30 cmH20. -60cmH20 is expected or what is associated with weak cough in NL person


In a recent ID report, we discussed the well-known penile lesion ddx and added in a lesser known branch point of the *PRURITIC* penile lesion. The following is a non-exhaustive (and likely with much overlap) summary of what we came up with:

PAINFUL penile lesion

  • Chancroid/H. ducreyi
  • SJS/TEN drug lesion
  • SCC
  • Traumatic lesion/entrapment injury
  • Ulcers in s/o foley
  • HSV
  • Paraphimosis

 PAINLESS penile lesion

  • Syphilis
  • LGV (Of note, the lymphadenopathy *IS* painful in Lymphogranuloma venereum; LGV caused by L1, L2, L3 serovars of Chlamydia trachomatis)
  • Granuloma Inguinale (uncommon infection caused by K. granulomatis)
  • HIV
  • HPV
  • Pearly penile papule

*PRURITIC* penile lesion

  • Fixed drug reaction, DRESS/DHR
  • Yeast
  • Infestation-scabies/pubic lice
  • HSV
  • Behcet’s

 So how do we diagnosis LGV? Does our usual urine test work??????
Lisa Winston teaches us:

Turns out the usual Chalmydia culture or the more commonly ordered/sensitive NAAT test will be positive in LGV as the serovars will be picked up—it just won’t specify that it detected the L1-3 serovars. Usually when the sx’s are classic, empiric tx (longer course) is initiated. If you want a definitive dx, you can talk to colleagues at communicable dz and public health to see if need to send serology or special PCR to the SF public health lab (and then potentially to state’s public health lab or CDC).


Lastly, Mike and Carine presented a patient in intern report with MV endocarditis 2/2 MSSA where we discussed the role of early surgical intervention in infective endocarditis.

There is a fantastic 2013 NEJM Infective Endocarditis review article by Hoen and Duval that breaks down the indications for surgery into three big categories: heart failure, uncontrolled infection, and prevention of embolic events. Or in image form:

indications for sgy

For those of you who want more…

Punag, one of the cardiology fellows, passes on the following for the ACC/AHA class indications for surgical intervention:

Early surgery is recommended for patients with complicated infective endocarditis (IE), but data from randomized trials are scarce. The following are points to remember about the timing of surgery among patients with IE:

  1. The main indications for early surgery in IE are heart failure, uncontrolled infection, and prevention of embolization. The reduction in mortality with surgery is greatest among patients with IE and moderate to severe heart failure.
  2. Heart failure. The European Society of Cardiology (ESC) guideline (2009) recommends emergent surgery for heart failure with refractory pulmonary edema or cardiogenic shock (Class I), or urgent surgery for persistent heart failure with signs of poor hemodynamic tolerance (Class IIa). The American Heart Association (AHA)/American College of Cardiology (ACC) guideline (2014) recommends early surgery for valve dysfunction causing heart failure (Class I).
  3. Uncontrolled infection. The ESC guideline recommends urgent surgery (Class I) for evidence of uncontrolled infection defined as either abscess, fistula, or pseudoaneurysm; or for an enlarging vegetation, persistent fever, or positive blood cultures after 7-10 days of appropriate therapy. The AHA/ACC guideline recommends early surgery (Class I) for evidence of persistent infection, heart block or abscess, or a resistant organism ( aureus, fungi).
  4. Prevention of embolization. The ESC guideline recommends urgent surgery for a vegetation >10 mm with previous embolization or other surgical indication (Class I), or for isolated vegetation >15 mm and feasible valve repair (Class IIb). The AHA/ACC guideline recommends early surgery for recurrent emboli and persistent vegetations despite appropriate antibiotic therapy (Class IIa); or a large mobile vegetation on a native valve (Class IIb).
  5. Neurological complications. Patients with a neurological complication may have other indications for early surgery. However, early surgery may pose a significant risk for perioperative neurological deterioration (related to anticoagulation potentiating the risk of intracerebral bleeding, and to hypotension during cardiopulmonary bypass aggravating neurological ischemia and edema).
  6. Prosthetic valve IE. Prosthetic valve endocarditis is the most serious form of IE, and more difficult to treat using antibiotics alone. In general, current guidelines support consideration of a surgical strategy for high-risk subgroups with prosthetic valve IE, including patients with heart failure, abscess, or persistent fever.
  7. Definitions of early surgery. There is no consensus as to the optimal timing of early surgery. The ESC guideline classifies surgical indications in IE as emergent (within 24 hours), urgent (within a few days), and elective (after 1-2 weeks of antibiotic therapy). The AHA/ACC guideline defines early surgery as occurring during the initial hospitalization and before completion of a full therapeutic course of antibiotics.


Evernote link:


Hoen B, Duval X. Infective Endocarditis. N Engl J Med 2013; 368:1425-1433April 11, 2013DOI: 10.1056/NEJMcp1206782