8/17 (HUP): diffuse GGOs and PCP

Thanks to Tom Franzon and Ben Manning for presenting two (different) patients who presented with subacute shortness of breath and were found to have diffuse groundglass opacities (GGOs) on chest CT and were ultimately diagnosed with HIV for the first time.

Along the way, we went through a diagnostic approach for diffuse ground glass opacities. Developing a differential for just ‘GGOs’ is a Herculean task, but creating a differential for diffuse GGOs (as opposed to scattered GGOs, particularly in association with some other consolidation) is actually much easier to do.

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Diffuse GGOs in a patient with methotrexate pneumonitis. AJR 2005.

Here’s a table from a paper by Penn radiologist/wizard Wally Miller:

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Miller and Shah, AJR 2005

This man was ultimately diagnosed with PCP pneumonia.

A few key points about diagnostic testing related to HIV and opportunistic infections:

  • Beta-D-glucan has excellent sensitivity (~95%) and specificity (~70-80%) for the diagnosis of PCP; in a patient who truly has PCP, BDG levels will likely be >400-500
  • CD4 counts can decrease with periods of acute/critical illness, so the CD4% may be a more stable marker to follow in someone with HIV, as it shouldn’t change all that much
    • An absolute CD4 count >500 corresponds to a CD4% of >30%

    • An absolute CD4 count between 200-500 corresponds to a CD4% of 15 to 30%

    • An absolute CD4 count <200 cells/microL corresponds to a CD4% of <15%

  • Most of the time, non-HIV related low CD4 counts don’t predispose to opportunistic infections, with the exception of idiopathic CD4+ lymphopenia— patients with this condition behave similarly to HIV+ patients with low CD4 counts in terms of OI susceptibility, except that they don’t have HIV!
  • Legionella urine antigen tests only for Legionella pneumophila serovar 1, so as a whole it has about a 70% sensitivity
  • The histoplasma urine antigen is best in HIV+ patients with disseminated disease (95% sens); sensitivity is probably similar in non-HIV patients
    • It’s really not a great test for less severe pulmonary histo or chronic cavitary histo, especially in non-AIDS patients
    • It can be false positive with other endemic fungi (Blasto, coccidio, etc)
  • A brief note on IRIS
    • It represents ‘unmasking’ of an underlying, unrecognized infection as the immune system ‘reconstitutes’ itself while on ART
    • Many pathogens (TB, NTBMB, PCP, HBV, crypto) have been associated with IRIS, while others (ex: toxo) are rarely associated with it
    • Generally develops when pre-ART CD4 nadir <100, and generally develop within one week to a few months after initiation of ART (depending on the kind of infection, host characteristics, etc)

References

  1. Miller, Wally Jr and Shah, Rosita. Isolated Diffuse Ground-Glass Opacity in Thoracic CT: Causes and Clinical Presentations. AJR 2005.
  2. Kauffman, C. Histoplasmosis: a clinical and laboratory update. 2007.
  3. Murdoch et al. Immune Reconstitution Inflammatory Syndrome (IRIS): review of common infectious manifestations and treatment options. 2007.

8/8 PPMC Report: Ticks!

Today we discussed a patient diagnosed with early localized Lyme with persistent fevers >72 hours after initiating doxy found to have babesia co-infection.

We reviewed the various stages of Lyme disease and how this affects treatment duration and PO vs. IV antibiotics as well as treatment for babesia (Atovaquone + Azithro vs. Clinda + Quinidine — depending on severity).

Lyme

In different areas of the country (especially in New England) the rates of co-infection with babesia can be as high as 39% (1) and, in these areas, patients diagnosed with Lyme disease should probably be screened for babesia as well. We discussed approaching co-infection by identifying the regional tick species, in this case, Ixodes. Co-infections based off of the Ixodes tick include, Anaplasma, Babesia, Lyme and Powassan.

We also reviewed Lyme mimickers including STARI (carried by the Lone Star tick — which also carries Ehrlichiosis), but that geographically this was ruled out in our case.

As Dr. Gluckman pointed out, early localized Lyme is a CLINICAL diagnosis and no lab testing was necessary to MAKE the diagnosis — but that serologies later can be used to confirm the diagnosis.

Lastly we reviewed the 2016 NEJM article which discussed screening the US blood supply for Babesia microti (2) — it hasn’t been rolled out to the Red Cross yet, but keep your eyes peeled!

Just as a quick reminder and plug for the Philadelphia Department of Public Health — they track Lyme disease every year (among a million other things) — and we see a LOT of it in areas you might not expect.

Below is the 2016 info-graphic for number of cases of Lyme by Zip Code (3).Lyme in philly

References:

  1. Vannier et al. Human Babesiosis. NEJM 2012; 366:2397-406.
  2. Moritz ED et al. Screening for Babesia microti in the U.S. Blood Supply. NEJM 2016; 375:2236-45.
  3. https://hip.phila.gov/DataReports/TickborneDiseases

8/3 PPMC Report: Bacterial Meningitis

Today we covered the often thought of (but less frequently diagnosed) bacterial meningitis and a case diagnosed and treated by our own Dr. Ferrante!

We discussed pattern recognition (“thinking fast”) and the benefits in this case. We reviewed the data on the signs and symptoms at presentation for meningitis including that having fever, neck stiffness and AMS is only 46% specific; however >95% of patients who were eventually diagnosed with bacterial meningitis had 2+ of these clinical findings (1).

We chatted about who needs a HCT prior to LP (2):

  1. Immunocompromized patients
  2. History of CNS disease (masses, stroke, focal infection)
  3. New onset seizure (within the last week)
  4. Papilledema
  5. Abnormal level of consciousness (inability to answer 2 consecutive questions or follow 2 commands)
  6. Focal neuro defect

We also reviewed the data for dexamethasone (10mg Q6H x 4 days) started prior to antibiotics in adults. The 2002 NEJM article (3) demonstrated decreased unfavorable outcomes in the dexamethasone group as compared to the placebo (15% vs. 25% with RR 0.59). This was especially pronounced in those with S. pneumo meningitis (26% unfavorable outcome vs. 52% in placebo group). While the data for steroids improving outcomes with Neissieria is lacking, until you have the bug back, it’s worth the steroids!

Finally, we reviewed the CDC guidelines for pneumococcal vaccines and the data that demonstrated that PCV vaccination DECREASES S. Pneumo meningitis (54% reduction in incidence in those >65 during) (4).

  1. Attia J et al. Does This Adult Patient have Acute Meningitis? JAMA 1999;281(2): 175-181.
  2. Tunkel AR et al. Practice Guidelines for the management of bacterial meningitis. CID 2004;39:1267-84.
  3. De Gans J et al. Dexamethasone in Adults with Bacterial Meningitis. NEJM 2002;347:1549-1556.
  4. Hsu, HE et al. Effect of pneumococcal conjugate vaccine on pneumococcal meningitis. NEJM 2009;360:244-56.

7/31 PPMC Report: Acute Diarrhea!

Acute Diarrhea

Today’s resident intake report from the effervescent Nancy Aitcheson was a 31 yo M p/w 4 days of nausea, vomiting and diarrhea.

As discussed — the differential is in the HISTORY! Most acute diarrhea can be lumped into inflammatory or non-inflammatory based on history alone and occasionally a quick peek at the stool.

We reviewed that extensive testing, including stool cultures, CDiff, fecal leukocytes and O+P are for the most part unnecessary, but discussed the few times when those tests SHOULD be run.

We also highlighted the treatment options:

  1. Rehydrate the patient! — oral is better than IV. If they can’t keep fluids down (like the case presented) then they are likely to need an admission.
  2. Early re-feeding — don’t keep your patient on a clear liquid diet. It turns out letting them eat what they can ASAP helps reduce bowel permeability and decreases illness duration
  3. Loperamide — we’ve all been nervous about giving this to patients, but if the diarrhea ISN’T bloody and they aren’t at risk for CDiff then go ahead!
  4. Pepto Bismol — it’s a tried and true medicine cabinet staple for a reason. Almost ALL patients can take this medication (even if they have fevers and inflammatory diarrhea)!
  5. Probiotics and Zinc — the data backing this up primarily comes from the pediatric population, but if your patient is at home and needs to feel empowered, go ahead and recommend these two treatments. There’s very little downside and potentially some benefit (studies pending).