10/5 Presby report: possible PID

Thanks to Jake Martin and Malcolm Kearns for presenting a perplexing case of a young woman with several days of high fevers and abdominal pain, which later progressed to include transaminases in the 400s, a CK >1000, and RUQ pain–> all of which was ultimately thought to be due to pelvic inflammatory disease (although that’s not completely confirmed)!

What is pelvic inflammatory disease?

  • PID is an ascending infection that goes up from the cervix up to the uterus, fallopian tubes, ovaries and can even spread intraperitoneally, leading to liver capsule inflammation (Fitz-Hugh-Curtis syndrome)
    • PID can lead to high rates of infertility despite treatment: in one study, ~20% of women with treated PID reported infertility or ectopic pregnancy, suggesting that inflammation itself could lead to long-term damage despite adequate antimicrobial treatment

Clinical manifestations/microbiology

  • PID encompasses a broad spectrum of clinical manifestations (see table below)
    • Acute symptomatic PID: acute lower abdominal/pelvic pain, pelvic organ tenderness, possibly abnormal uterine bleeding or dyspareunia, RUQ pain if perihepatitis. Fever may not be present.
    • Subclinical PID: more indolent, with more atypical manifestations
    • Chronic PID: low grade fever, abdominal pain and weight loss over a long period, particularly associated with TB and Actinomyces (?association w/ IUDs)
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NEJM 2015

Diagnosis

PID is a clinical diagnosis, requiring:

  • Pelvic organ tenderness (CMT, uterine compression tenderness on bimanual exam, adnexal pain) PLUS
  • Lower GU tract inflammation (endocervical exudate or as yellow/green mucus on swab placed gently into the cervical os (positive “swab test”); cervical friability or increased WBCs on wet mount of vaginal secretions

The presence of fever or leukocytosis can help, but are not necessary. Imaging (TVUS, CT, MRI) can also be helpful: thickened, fluid-filled tubes/oviducts with or without free pelvic fluid could represent salpingitis, or tubo-ovarian abscess.

Unfortunately this clinical diagnosis only about 60-70% sensitive, which highlights the importance of empiric treatment given the high risk of withholding antibiotics.

All patients w/ suspected PID should undergo: vaginal exam w/ wet mount of secretions (to evaluate for increased WBCs), GC testing, HIV, RPR, pregnancy test, +/- ESR/CRP

We touched on the testing characteristics of GC testing. You can test for GC using NAAT (= gold standard), culture or gram stain.

  • For women, NAAT screening obtained by vaginal swab is best; endocervical swab is fine if you’re doing a pelvic exam anyway, but not necessary to do one just for NAAT
  • NAAT is >99% sensitive and specific for urogenital gonorrhea from cervical specimens (urine is about 10% less sensitive)

Lastly, treatment options

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Treatment duration is usually 14 days. Interestingly, removal of an indwelling IUD does not hasten resolution (and may even worsen it)

References

  1. Recommendations for the Laboratory-Based Detection of Chlamydia trachomatis and Neisseria gonorrhoeae — 2014

  2. Pelvic Inflammatory Disease. NEJM 2015.
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8/31 (HUP): fever in a returning traveler, typhoid fever

Ben Larson most excellently presented a cause today of a young man from Mali who presented with an acute febrile illness and was found to have GNRs in his blood, which were ultimately proven to be Salmonella, leading to typhoid fever!

Characteristic clinical features of typhoid fever

  • Fever and flulike symptoms after a 1-2 week incubation period
  • Patients may have a relative bradycardia, but this is not always present
    • NB: HR should increase by 10 for every degree (F) increase in temp (don’t forget to check if they’re on beta blockers); but you can really only try to discern the pulse-temp relationship at a temp >102F
    • This phenomenon is most commonly seen with some but not all intracellular bugs, often GNs: Salmonella, Legionella, Chlamydia psittaci; also leptospira and yellow fever
  • Patients may have a characteristic “apathetic” affect
  • Feared but rare complication: erosion of necrotic Peyer’s patches into intestinal mucosa (commonly the ileum), leading to perforation or GI bleed

Up to 4% of convalescing patients may become chronic carriers, excreting the organism in feces for >1 year. There is some concern that chronic Salmonella carriage (in the gallbladder) may be a risk factor for GB cancer.

Two other quick Salmonella pearls from TB:

  • Salmonella loves to settle into long bones (particularly in abnormal bones, like in sicklers)
  • It also can seed atherosclerotic plaques (and cause mycotic aneurysms, aortitis, etc), so in an older bacteremic person with a large known/suspected atheromatous burden, you might consider treating for longer

On the subject of fever in a returning traveler, there are key questions to ask that can help narrow the differential:

  1. Pre-travel vaccines
  2. Disease prophylaxis (ex: antimalarials)
  3. Sexual contacts while abroad
  4. Exposure to animals (particularly bites), including birds and insect bites
  5. Piercings/tattoos or medical procedures while abroad
  6. Other drugs taken while or since traveling (as they may partially treat the underlying infection and delay/alter presentation)
  7. Exposure to fresh water or ‘bad food’ (TB thinks this might be a less useful question since most people that go somewhere will say yes to this question)

Remember that the duration of time they spent abroad can be tremendously important; if they were there for just a day or two and come back with a febrile illness, infections acquired in the US can be just as likely as something acquired abroad.

References

  1. Typhoid fever, NEJM.
  2. Fever in a returning traveler, NEJM.
  3. Soravia-Dunand et al. Aortitis Due to Salmonella: Report of 10 Cases and Comprehensive Review of the Literature. Clinical Infectious Diseases 1999.

8/24 PPMC Report: Vertigo

Today’s case was a 47 yo F with congenital lymphangiectasia presenting with vertigo.

Obviously — the first thing we discussed was a quick review of congenital lymphangiectasia. It’s an exceedingly rare disease in which there are dilatation of intestinal lacteals resulting in lymph leakage into the small bowel. This disease is responsible for a protein-losing enteropathy leading to lymphopenia (CD4 count 36), hypoalbuminemia, and hypogammaglobulinemia.

Next we did a review of central vs. peripheral vertigo and how to differentiate between the two based on history and exam. While it’s not COMPLETELY black and white, the table below gives general guidelines to differentiate between the two.vertigo

 

Based on our patient’s presentation with vertical and horizontal nystagmus and positive skew deviation she was referred for MRI with c/f a central lesion.

Her MRI demonstrated multiple rim-enhancing brain lesions and we discussed the broad differential for an immunocompromised patient — including bacteria (abscess v. TB v. syphilis/gummas), fungal (crypto v. aspergillosis, v. histo v. coccidio v. actino v. mucor), Parasitic (toxo), Inflammatory (sarcoid v. whipple’s v. MS v. lupus v. PML v. Behcet’s) and Neoplastic (metastases vs. primary CNS lymphoma vs. GBM vs astrocytoma).

She had a biopsy that demonstrated primary CNS lymphoma.

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).