Is the answer always syphilis? (Le, 2021)

Thanks to Dr. Jimmy Le for an excellent Grand Rounds presentation this week on Syphilis. Rates of syphilis have been on the rise in the US and in Sonoma County for the last decade.

A recording of his excellent presentation is available HERE.

For those of you who want the notes, here are my notes:

Epidemiology:

• Before 2013, cases of syphilis in the US were generally concentrated in men who have sex with men (MSM) 
• From 2013-2018, there has been increase of 170% primary and secondary syphilis diagnosis in women AND rising rates in black/Latinx populations
• There is a high rate of co-infection w/HIV (42% MSM with syphilis also have HIV)
• In 2019, 129K cases of syphilis in the US (MSM and MSMW), 1870 cases reported of congenital syphilis (unfortunately more common in BIPOC mothers)
• In SoCo, as well, rates have been increasing, similarly transitioning from primarily a disease in MSM to a wider category of folks, including more women, homeless, persons who inject drugs

What is syphilis?

• A spirochete infection caused by treponema pallidum
• Multiple stages of syphilis can be confusing (see graphic below from Emory)
• The incubation period 9 days-3 months (can be asymptomatic)
• Neurosyphilis, ocular syphilis and otic syphilis can happen at ANY time during infection (should have low threshold to test for these)

Primary syphilis: 3-90 days after exposure, painless chancre, round and firm, can appear anywhere, generally 3 weeks after infection, heal on own in days/weeks, place where chancre appears is where exposure occurred (e.g. anus, vagina, penis). Gets missed, people don't notice because it doesn't hurt!

Secondary syphilis: 3-6 months after initial infection: "bigger rashes", more widespread (hands, feet, trunk, tongue, hair loss)

Tertiary syphilis: years to decades after exposure, "the great imitator", can show up in any tissues: cardiovascular, skin, bone, etc

Early latent: asymptomatic, <12 months of exposure

Late latent: asymptomatic  infection >12 months of exposure, "syphilis of unknown duration"

Neurosyphilis: CNS infection (meningitis), general paresis, tabes dorsalis

Ocular syphilis: vision loss, blurry vision, eye pain, redness

Otic syphilis: sensorineural hearing loss, tinnitus, vertigo

Transmission:

• Primary syphilis is VERY transmittable (lots of treponemes in primary chancres-- any surface is vulnerable), likelihood of transmission is ~30%
• As you move through stages, you become less and less infectious, can definitely still transmit but less than primary
• Syphilis is also one of TORCHES infections, the spirochete crosses the placenta very readily

Diagnosis:

• Two types of tests:
• Non-treponemal test: tests for cardiolipin cholesterol-lecithin antigen (RPR, VDRL), always presented as titers
• Treponemal test: detection of Ab against Ag. once positive, will always test positive (FTA-ABS, TPPA)
• Two methods for testing, decision which algorithm to use is based on prevalence. Generally thought higher prevalence area should use reverse testing algorithm 
• Traditional (see image) starts with RPR, reflex to TPPA confirmation
• Reverse (see image), do the opposite (start with TPPA), if that tests positive, reflexes to RPR)
• Once a patient is positive, Treponemal tests will ALWAYS be positive, so you always need RPR and titers
• Do note, you can have false negative RPR in latent period and upon appearance of chancre 1-3 weeks (e.g. if you are testing "too early", if you see a chancre, treat treat treat)
• Dx of neurosyphilis requires high clinical suspicion and low threshold for doing LP and getting CSF: test for protein, WBC, CSF-VDRL (which has poor sensitivity, 70% can test negative)

Treatment

Penicillin is ALWAYS the treatment (see chart above for details)

• Don't forget to get an RPR on the day of treatment (to get baseline)
• If a patient reports contact with anyone with syphilis in the last 90 days, treat empirically! 
• including partner treatment!
• www.dontspreadit.com (anonymous texting about exposure)
• Primary, secondary, early latent (<12 months): PCN 2.4 million units IMx 1
• Late latent (>12 months), unknown duration of tertiary with normal CSF: need to be treated with IM injections x 3 (one week apart)
• Neuro/ocular/otic syphilis: treatment is IV PCN 10-14 days (usually initial hospitalization)
• If a patient has PCN allergy, desensitization and treatment with PCN is still recommended (JAMA article on PCN desensitization available HERE)
• Follow-up testing is KEY: 
• for primary/secondary, early latent, retest with RPR at 6, 12 month (looking for 4x decrease in titer)
• for late latent, unknown, you should retest at 6, 12, and 24 months
• RPR baseline will be your guideline to determine if someone has been reinfected (4x increase demonstrates reinfection)

Questions about staging/treatment, can always call: Team Vida 707-583-8823 or SoCo Health Department 707-565-4566

Congenital Syphilis:

• complex diagnosis and treatment algorithms (see diagram from California DPH below)
• steady rise of congenital syphilis since 2012, 400% increase since 2012
• syphilis readily crosses placenta or via contact with chancre during delivery
• can affect ALL organs of the body, can lead to infant death and miscarriage
• wide clinical presentation: < 2 year old, usually presents by 5w-3 months of age, 60-90% will be symptomatic
• sx include hepatomegaly, jaundice, rhinitis ("snuffles"=white discharge, more severe than common cold, mucous discharge VERY infectious because lots of treponemes in them), rash, generalized LAD, skeletal abnormalities
• Treatment: IV PCN 50K units/kg q8 hours x 1 week, then q12 hours OR PCM IM x daily x 10 days
• Evaluation: neurodevelopmental, hearing, eye, serologic testing with RPR until negative or 4x decrease (usually non-reactive by 6 months)

https://californiaptc.com/in-the-news/new-tool-for-clinicians-unveiled-to-ensure-appropriate-treatment-of-congenital-syphilis/

Screen for STIs!

Screen all sexually active patients for HIV, RPR, GC/CT (including swabbing every site they use to have sex, including mouth, vagina, rectal)

Other STIs predict HIV risk (see infographic)

Offer partner treatment always

https://californiaptc.com/wp-content/uploads/2017/03/Slide7.jpg

Pediatric Asthma: 2020 Global Initiative for Asthma (Prystowsky, 10/2020)

Many thanks to Sutter Medical Group of the Redwoods Pediatrician, Dr. Brian Prystowsky, for an amazing (and quite unique) Grand Rounds presentation this week on the "New" Global Initiative for Asthma (GINA) 2020 guidelines. 

Dr. Prystowsky took us to The Land of Make Believe and introduced us to:

• The 2020 Global Initiative for Asthma (aka GINA, the elephant in the room)
• Simba (Symbicort=formoterol/budesonide)
• Bert and Ernie (SABA=Albuterol)
• Jose Canseco (inhaled corticosteroids), and
• "The Purple One" (Advair) 

Stick with me here, and the teaching will stick with you. The 46-page GINA Pocket Guide is available for your here for your bedtime reading enjoyment. 

Asthma management has been upended this year by the 2020 GINA Guidelines.  Here's why.

Traditional management of mild asthma, mild/moderate intermittent asthma, persistent asthma, and exercise-induced asthma has been based on a few standard assumptions that may need some re-evaluation

•  First, that bronchoconstriction is the fundamental pathophysiological problem in asthma
• Second, that intermittent symptoms only need intermittent treatment, a short-acting beta agonist (SABA, e.g. albuterol). 
• Third, that inhaled corticosteroids (ICS) work for patients with persistent symptoms if prescribed chronically but are not indicated for intermittent symptoms. 
• Standard management of asthma involved prn SABA for patients with intermittent/exercise-induced asthma and addition of daily maintenance ICS with SABA as rescue for those with persistent symptoms.

ALL this is changing! A batch of studies suggest that asthma is likely more of an inflammatory condition that we might've previously thought-- or at least that inhaled corticosteroids (ICS) used in combination with a Rescue beta agonist is associated with better outcomes. 

The big practice change from GINA is moving away from use of SABA (albuterol) PRN to use of Symbicort PRN for asthmatics over 12. Symbicort, by the way, is a combination inhaler, which includes Budesonide (ICS) and Formoterol (LABA).

Studies in favor of  SYMBICORT PRN for the treatment of asthma: 

NEJM 2018 study (patients >12 with mild asthma x 52 weeks) found that patients treated with Symbicort PRN (compared with SABA prn in one arm and ICS maintenance with SABA prn) had higher percentage of weeks well controlled, LOWEST rate of severe exacerbation and lower median daily steroid dose (57mcg vs. 340mcg in ICS maintenance).

A NEJM 5/2019 study (patients >18 with mild asthma x 52 weeks) had similar findings: lower exacerbation rate, lowest number of severe exacerbations, and lower mean steroid dose.

A study from Thorax 2/2014 study (of patients >12 with exercise induced asthma, x6 weeks) found use of Symbicort PRN had best symptomatic control (compared to SABA prn and ICS maintenance/SABA prn) with much less steroid exposure.

Btw, Steroid exposure in an older study from Lancet 2011 (children 5-18 years old with mild persistent asthma) was associated with 1.1 cm growth restriction. Unclear how clinically significant this is, but as Dr. Brian said, parents don't want their children to be growth restricted..

What about "The Purple One"?

It seems that "the purple one" (aka ADVAIR; fluticasone/salmeterol) is not as effective as Symbicort in the care of asthma. 

Lancet 2011 study (5-18 years, 44 weeks) found that compared to PRN SABA, a QVAR+SABA prn vs. QVAR maintenance + SABA prn did not improve outcomes.

A 1/2020 study from Journal of Allergy and Clinical Immunology (mild asthma, ages 6-17 years) found that the use of QVAR+ SABA prn vs. QVAR maintenance + SABA prn had basically equal outcomes, except children had higher rates of steroid exposure in the maintenance group

And a study from Journal of Allergy and Clinical Immunology 12/2014 (ages 12-64) found Symbicort (vs. ADVAIR) had less exacerbations, lower oral steroid rates,  and less ER visits (though same hospitalization rates).

Can formoterol be an effective rescue?  Yes And is it safe in young children? Yes.

Compared to salmeterol, formoterol has a more rapid onset of action (at 3 minutes) at all doses

A study of 300 children in Pediatric Allergy and Immunology (3/2019) ages 8 months to 4 years found no safety concerns with the use of formoterol in children.

What are Dr. Brian's take home points for GINA?

• For children over age 12, Symbicort should be used both as rescue and maintenance as a PRN. Children will get at least as good control (maybe better) and will get less steroid.
• For children under age 12, the evidence is still not clear enough to change the historical practice. Continue to use albuterol PRN with ICS prn vs. ICS daily.

Thanks neighbors! And thanks Dr. Brian!