3/14 Presby report: polyarthritis

Thanks to Alex for presenting a great case of a middle aged woman with oligo/polyarthritis, ultimately diagnosed with disseminated gonococcus!

Polyarthritis can be a challenging complaint to parse through.

Important questions to ask

  • Timing (acute = <6 weeks)
  • Inflammatory or not (swelling suggests inflammatory)
  • Symmetry
    • This is not necessarily an exact science; a patient with mostly inflamed MCPs and a single DIP on one side and the converse on the other hand would still be considered symmetric
  • Large vs small joints
    • Ex: Lyme often presents with an acute monoarthritis, commonly in the knee; small joints are uncommon
  • History of crystal arthritis
  • Age
    • Older patients are more likely to p/w CPPD/pseudogout
  • Things that predispose to high uric acid
    • CKD
    • EtOH use
  • NSAID responsiveness

On exam, make sure to look for:

  • Joint exam
  • Nodules
  • Tophi (found particularly in the olecranon bursa and in fingertips- they can be very subtle!)
    • Gout tophi tend to be right in the olecranon, whereas rheumatoid nodules tend to be a little distal to the olecranon

Check out this calculator which may help you think about how likely gout is in your patient.

We talked briefly about the ANA.

The ANA is not a standardized test from lab to lab.

  • One lab might be different than another
  • So positivity depends on where it’s being tested, so 1:80 might be considered positive in one place and negative somewhere else
  • In one study, up to 20% of patients have a low level positive ANA
  • Some labs will use an ELISA for the ANA, for which the result will just be a number (not a titer)

The patient was ultimately diagnosed with disseminated gonococcus, with a synovial WBC count of 96000- this is unusual because gonorrhea usually causes a WBC count <50000!

  • Tx: ceftriaxone x 2 weeks + azithromycin
  • Also consider doing a surgical washout of the affected joint, particularly if it’s weight bearing; this may allow the patient to return to weight-bearing status more quickly!

1/31 PPMC Report: Aspiration and PJP Pneumonia

Thank you to Dr. Palevsky and Dr. Gluckman for helping us discuss a really interesting case of an 82 year old gentleman with persistent hypoxia who was ultimately found to have a new diagnosis of HIV presenting with PJP pneumonia.

We discussed techniques for performing a thorough pulmonary exam: (images: https://meded.ucsd.edu/clinicalmed/lung.htm)pcp1

Many of these exam maneuvers use principles of physics to help us determine if the lung tissue is aerated normally, or if there is a process compromising aeration and anatomy. Since sound waves are vibrations, they are transmitted differently through air and solid/liquid media. Thus processes causing consolidation of lung tissue, alveolar filling, or other anatomic/functional pathology will transmit sound waves differently Рleading to different findings on egophony, whispered pectoriloquy, tactile fremitus, and percussion.

Our patient experienced respiratory distress and decompensation following an upper endoscopy procedure. We discussed that his clinical circumstances were concerning for aspiration Рwhich can cause either a pneumonitis (transient inflammation without leading to infection) or a pneumonia (infection). Dr. Palevsky taught us that due to anatomy of the airways branching, aspiration does not always go to the lung bases, and it is important to listen in the central lung fields too.

After a course of treatment for aspiration pneumonia, our patient continued to be hypoxic and tachypneic, so additional workup was pursued and ultimately he was diagnosed with HIV/AIDS and PJP pneumonia. We learned from Dr. Gluckman that 6% of new HIV diagnoses are made in patients older than 80 years, so always think about sending an HIV test on all of your patients, regardless of their age!

PJP is currently classified as a fungus, which is normally cleared by host macrophages and CD4 cells coordinating an immune response – which is why patients with CD 4 < 200 (and other immunocompromised states) are at risk of this infection. Typical symptoms include progressive shortness of breath especially with exertion, fever, and tachypnea, although patients can be asymptomatic. Classic imaging shows bilateral diffuse patchy pulmonary infiltrates. A very elevated beta-D-glucan is supportive of this diagnosis, but the definitive diagnosis requires confirming the presence of PJP in the respiratory secretions or sputum. PJP does not grow in cultures, and obtaining samples can sometimes be difficult and require invasive techniques.

Treatment recommendations depend on severity of disease. Our patient progressed to respiratory failure requiring mechanical ventilation, so he definitely had severe disease! The recommended regimen in that case is high dose trimethoprim-sulfamethoxazole (weight-based) for 21 days, given IV until patient stabilizes. Patients with severe disease should also be treated with steroids. Finally, studies support early initiation of ART in patients presenting with PJP pneumonia.


PPMC Report 1/4: Refugee Health Cases

Hi PPMC team!

Thanks for allowing me to pinch hit for Amy on a very snowy day! We were able to cover a LOT of ground — from the global refugee crisis and how the changes to the US policies regarding refugees impacts those attempting to come to this country to some interesting cases and common diseases seen among our refugee population.

Displaced people

As discussed, currently we have a record high share of individuals who are displaced from their homes. This is thought secondary to the number of conflicts, the extended duration of conflicts, and the fact that there are few long term solutions which means more people are in limbo.


We reviewed that while the number of refugees that have entered the US have waxed and waned over the years, until this year, we admitted individuals in proportion to the number displaced internationally. In fact, 2017 is the first year in which the United States decreased the number of refugees accepted into the country while the numbers of displaced individuals continued to climb. The Pew Research group notes that as of Oct 2017 only 28,000 refugees had been resettled in the U.S. which is far less than in 2016 where approximately 98,000 had been resettled. This is on track to accept just 0.2% of the world’s refugee population — which is much less than the historic average of 0.6% and even lower than the share admitted in 2001 and 2002 following the September 11th attacks (2). Even looking ahead to 2018, the Trump administration has proposed decreasing the refugee resettlement cap to 45,000 — down from 50,000 (2).


Additionally we covered several cases from our Refugee Clinic at Penn Center for Primary Care. We discussed the routine screening and testing performed in the clinic which is specific to the individual’s country of origin and then areas in which the lived in refugee camps.

We discussed the extremely common diagnosis of schistosomiasis and the international push to screen and treat everyone, especially young women — in an attempt to preserve fertility (4).

We also discussed Polio and the sequelae of prior infection. In addition to recognizing common complications of prior Polio infection, we discussed who needs boosters of their polio vaccine prior to travel — it’s approximately 25 countries — Not just the three with endemic Polio (Afghanistan, Pakistan, Nigeria)!


Lastly we discussed some complications of long term malnutrition including rickets. We discussed both Calcipenic Rickets and Phosphopenic Rickets and their respective lab abnormalities. Our patient likely had phosphopenic rickets based on lab findings, which in the US is most commonly secondary to renal wasting diseases or other genetic abnormality. However, in our Bhutanese refugee, her story lined up well for nutritional deficit which corrected with appropriate diet/supplementation.


  1. http://www.pewresearch.org/fact-tank/2017/11/02/how-u-s-refugee-resettlement-shifted-in-states-since-2002/
  2. http://www.pewresearch.org/fact-tank/2017/01/30/key-facts-about-refugees-to-the-u-s/
  3. http://www.unhcr.org
  4. WHO Department of control of neglected tropical diseases. Female Genital Schisosomiasis. http://www.who.int/schistosomiasis/en/

1/2 PPMC Report: CMV Retinitis and Ocular Neurosyphilis

Thank you to Dr. Gluckman for your expert insight as we discussed a really interesting case of a 52 year old male who was diagnosed with ocular neurosyphilis. Our patient has a history of AIDS diagnosed when he presented with CMV retinitis 7 years ago, after which he was adherent with ARTs until several months ago Рthen six weeks prior to presentation he restarted ARTs. He reported approximately one week of increased floaters and decreased visual acuity in his left eye. He was evaluated in ophthalmology clinic and found to have decreased left visual acuity as well as optic nerve edema and inflammation, and was admitted for further workup.

A few words about CMV retinitis — we do not see it very much now that there is effective combination ART, but before that was available this was pretty common in AIDS patients. It is usually seen with very low CD4 counts (<50), and can be unilateral initially. It is thought to represent hematogenous spread of CMV, and then causes full-thickness retinal edema and necrosis, which spreads centrifugally and causes visual symptoms that depend on the involved areas. When the inflammatory phase is resolved, it leaves behind thin atrophic retinal scars, which are prone to retinal¬†detachment and tears.

The diagnosis is made based on characteristic findings on dilated fundoscopic exam. Notable, CMV viremia is detected in less than half of the patients with CMV retinitis, but negative CMV IgG makes this diagnosis much less likely.

Treatment is aimed at stopping spread to unaffected areas of the retina. If there is immediate threat to vision, intravitreous injection of foscarnet or gancyclovir is indicated. If not, oral valgancyclovir can be used, and many providers will treat for two weeks before starting ART to avoid a recovery uveitis phenomenon.

Our patient did not have characteristic CMV retinitis findings on his fundoscopic exam. He was noted to have a maculopapular rash and a history of syphilis, so clinical concern for neurosyphilis was high. His RPR ultimately came back with a very high titer — remember that if clinical suspicion for syphilis is high and RPR comes back negative, you may need to ask the lab to run a prozone assay. This means additional dilutions to ensure that antigen is not so high as to preclude formation of crosslinking antibodies (resulting in a false negative). Of note, CSF VDRL does NOT need to be positive to have a diagnosis of neurosyphilis. This patient was diagnosed with neurosyphilis and started on Penicillin G for treatment, along with steroid eye drops to help with swelling.

12/7 HUP Report: Disseminated Cryptococcus

Thanks to Dr. Barton for being our faculty expert today to discuss a case of disseminated Cryptococcus! The patient we discussed today did not have the usual risk factors for this infection, which we typically think about in patients who have compromised cellular immunity. Particular patient populations at risk include patients with HIV, hematopoietic stem cell transplant recipients, and solid organ transplant recipients.

Cryptococcus is a budding yeast with a capsule, seen here on silver stain:

CR1                                   http://englishdictionary.education/en/cryptococcus

The most common sites of Cryptococcus infection are the lungs and the CNS. It can also cause skin infection, particularly in HIV patients, which can resemble molluscum in appearance. If Cryptococcus is cultured from any other organ, it should be treated as disseminated infection.



Although disseminated Cryptococcus and cryptococcal meningitis should be treated with the same medications, it is still important to perform an LP in someone with cryptococcemia to check opening pressure — it is frequently elevated in patients with CNS involvement of disseminated Cryptococcus, which can have serious consequences and may require treatment with CSF removal.

Below are guidelines for treatment of disseminated Cryptococcus in non-HIV non-transplant hosts, from the Infectious Disease Society of America. Basically, there are three stages of treatment: induction, consolidation, and maintenance. The induction phase should involve a combination of amphotericin and flucytosine, followed by consolidation with high dose fluconazole and maintenance with lower dose fluconazole.


See below for a reference of a case report similar to our own patient!


Okamoto K, Proia LA, Demarais PL. Disseminated Cryptococcal Disease in a Patient with Chronic Lymphocytic Leukemia on Ibrutinib. Case Rep Infect Dis. 2016;2016:4642831. Epub 2016 Sep 14.



12/4 Presby report: relapsing fevers, EBV serologies

A big thanks to Robin for presenting the case of an older man who developed high fevers that disappeared and then relapsed, along with cytopenias and LFT abnormalities, and was ultimately diagnosed with Anaplasma. There was a lot of rich discussion during this case!

What defines a fever?

  • Normal body temperature fluctuates throughout the day, with temps lower in the morning (max 98.9F) and higher in the evening (max 99.9F)
    • so whether you call something a fever or not may depend on the time of day; the cutoff of 100.4F that we’ve come to use is in some ways quite arbitrary

There’s no strict definition of ‘relapsing’ fever; there just has to be some fever-free interval (generally at least 24-48h) before the fevers start again.

  • Keep in mind that several etiologic organisms cause fevers in a relapsing pattern, and that there is also an entity called ‘relapsing fever’ which is caused specifically by several Borrelia species

Causes of relapsing fever

  1. Tick-borne relapsing fever (TBRF): caused by Borellia spp (parkeri, turicatae, hermsii) and transmitted by SOFT ticks like Ornithodoros (different from hard ticks like Ixodes which transmit Lyme, Babesia, etc). Main risk factor: rodent exposure
  2. Louse-borne relapsing fever (LBRF): caused by Borellia recurrentis and transmitted by human body louse. Mostly limited to Africa.
  3. Borellia miyamotoi: a newly described pathogen, transmitted by hard ticks which can be contracted in the Northeast US
  4. Leptospirosis
  5. Rare: anaplasma, ehrlichia
  6. Malignant fevers, particularly Pel-Ebstein fevers from Hodgkin’s lymphoma


Lastly, we talked about EBV serology interpretation. Remember that most people get EBV in childhood.

EBV testing has three components: viral capsid antigen (VCA) IgG, VCA IgM and Epstein-Barr Nuclear Antigen (EBNA)

  • The EBNA will stay elevated indefinitely after infection, so if it’s elevated, that indicates past infection
  • If the VCA IgM is elevated and EBNA is not, that likely indicates recent infection
  • The VCA IgG is really ‘corroborative’ and remains elevated after past infection


Screen Shot 2017-12-07 at 10.13.32 AM.png

Interpretation of EBV serologies

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Source: Mayo Medical Laboratories. Note: *Results indicate infection with EBV at some time (VCA IgG positive). However, the time of the infection cannot be predicted (ie, recent or past) since antibodies to EBNA usually develop after primary infection (recent) or, alternatively, approximately 5% to 10% of patients with EBV never develop antibodies to EBNA (past).



  1. Barbour A. Harrison’s Principles of Internal Medicine. “Relapsing Fevers”.

11/15 HUP Report: Infectious Endocarditis

Thank you to Dr. Amorosa for teaching us about advanced management of infectious endocarditis! Today we discussed the case of a young male IV drug user who presented with fever, new cardiac murmur, and evidence of embolic phenomena on his skin exam who was found to have MRSA endocarditis.

When dealing with a case of suspected endocarditis, make sure you get cultures!! This is really important – in the majority of cases cultures will identify an organism and allow for targeted treatment. Ideally, at least two sets of cultures separated in space and time (at least thirty minutes) should be collected. While waiting for this data, if empiric treatment is necessary clinically, consider covering strep, staph (MRSA and MSSA), and enterococcus species.

In cases of MSSA endocarditis, a bacteriocidal agent such as nafcillin or oxacillin is usually recommended; addition of aminoglycoside has not shown clinical benefit and confers the downside of lots of potentially permanent and serious side effects, so their synergistic use has fallen out of favor. In cases of MRSA endocarditis, vancomycin is usually a good first line agent. Coagulase negative staph should be treated like MRSA.

We also discussed surgical interventions in patients with endocarditis. There has been a recent trend toward increased discussion of early surgery (performed before the completion of the initial antibiotic course), especially in cases where the infection has been demonstrated to be causing valvular disease and subsequent heart failure (as in our patient), perivalvular abscess or extension, and other difficult-to-treat situations. Here is some data to support early surgery in cases similar to ours:

  1. This study published in JAMA (full reference below) was a prospective, multicenter study of n= 4166 patients with infective endocarditis. The researchers looked to see which factors were associated with mortality among the patients. Of patients with heart failure symptoms (classified into NYHA classes), those who underwent early surgery had improved in-hospital mortality rates. (Of course, there are confounding factors to consider here).


2. This study from the Journal of Thoracic Cardiovascular Surgery (full reference below) retrospectively reviewed n=212 patients with left-sided native valve infective endocarditis. Early surgery was defined as occurring within 2 weeks of initial diagnosis. They found that in patients who received early surgery, there was statistically significant reduction in IE-related death and major adverse cardiac event (again, there are caveats here too!)


Infectious endocarditis can be difficult to treat. Always get infectious disease colleagues involved! And consider early surgical intervention if clinically indicated. Sadly, this disease is one of the many health hazards that accompanies the opioid epidemic.

Kiefer et al. Association between valvular surgery and mortality among patients with infective endocarditis complicated by heart failure. JAMA 2011; 306(20):2239-2247.

Funakoshi et al. Impact of early surgery in the active phase on long-term outcomes in left-sided native valve endocarditis. J Thorac Cardiovasc Surg 2011;142:836-42.