Today we welcome Dr. Aparna Sridhar, an associate clinical professor of obstetrics and gynecology at UCLA Health. Dr. Sridhar walks us so nicely through the combined hormonal contraceptives, and picking the right one for our patients.
Admittedly we are not dermatologists… but hydradenitis suppuritiva (HS) affects a substantial number of our patients and because of the locations it affects, OB/GYNs are often the first to see it.
What is HS?
Chronic, recurrent inflammatory disease of apocrine sweat glands
Also known as acne inversa
Located usually in axillae, groin, genitals, perineal, buttocks, and inframammary areas
Women tend to be more affected than men
Prevalence
1%-4%, onset usually between puberty - 40 years of age, usually in second or third decade of life
Why do we care?
Can cause significant pain, issues with scarring
May have huge impact on self-esteem and quality of life can be severe, thus importance of early diagnosis and treatment
Very rarely, squamous cell carcinomas develop within sites of HS
How do we recognize it and diagnose it?
Pathogenesis
Follicular occlusion is most likely the even that is responsible for the initial development of HS lesions; may be due to ductal keratinocyte proliferation → hyperkeratosis and plugging
There is then follicular rupture → formation of sinus tracts
Associated factors
Genetics
Mechanical stress (ie. pressure, friction, etc.),
Obesity (maybe...but it’s also present in those without obesity),
Smoking (strong correlation; majority of affected patients are smokers),
Hormones (some people may experience perimenstrual flares)
History and Physical exam
Typical lesions, typical locations, relapses and chronicity
Inflammatory nodules - first lesion is single, painful, deep-seated inflamed nodule in the intertriginous area; diagnosis is usually missed at his stage; can be diagnosed as a “boil” or furunculosis
After some time, the nodule can progress to form an abscess → may open to skin surface spontaneously
Pain usually improves after drainage
Sinus tracts - skin tunnels; can happen if HS is persistent for months or years; can release blood-stained, seropurulent, malodorous discharge periodically
Comedones - can appear with longstanding HS
Scarring - healed areas can have individual, pitted, acneiform scars; may be atrophic or keloidal
Lab studies - usually not needed, but if you’re uncertain, can do skin biopsy → r/o squamous cell carcinoma
Differential Diagnosis
Folliculitis, acne vulgaris, pilonidal disease, Crohn disease
Stage II disease — image courtesy of Wikimedia commons.
Stage III disease with active infection ongoing -- image courtesy of Wikimedia Commons.
What is the Hurley Staging System? - divides patients with HS into three disease severity groups:
Stage I: Abscess formation (single or multiple) without sinus tracts and cicatrization/scarring
Stage II: Recurrent abscesses with sinuses tracts and scarring, single or multiple widely separated lesions
Stage III: Diffuse or almost diffuse involvement, or multiple interconnected sinus tracts and abscesses across the entire area.
How do we manage HS, and when should we refer out?
Goals
Reduce formation of new areas, sinus tracts, and scarring
Treat existing lesions and reduce symptoms
Minimize psychological morbidity
For all patients
Education, psychological support if needed - it’s a chronic disease, not due to poor hygiene. Course can vary from person to person
Wound and skin care techniques
Pain management - NSAIDS usually, but discuss opioid analgesia if needed
Treat associated symptoms and conditions
Encourage smoking cessation if they smoke
Stage I - Aim is to reduce burden of disease
Topical clindamycin - can reduce inflammatory lesions; usually applied 2x/day
If fail topical therapy → oral therapy
Oral tetracyclines: 100 mg doxycycline daily or BID
If oral antibiotic therapy achieves good disease control, patients can stop and continue with topical clindamycin for maintenance
Antiandrogenic agents - spironolactone and finasteride; can be used, but they should NOT be given if there is possibility patient is pregnant
Oral contraceptives - very small study that showed some improvement
Metformin - can help promote weight loss, which can help HS
For acute symptomatic lesions - warm compress
May want to refer out for this: possibility of intralesional corticosteroid injections
Unroofing the area over the nodule
I&D - not advised for routine treatment. It can lead to immediate relief, but can promote lesion recurrence and scarring
Stage II and III - Can try everything above, but if not working, usually this is when we would say you should refer out for other treatments
If they don’t achieve good control with antibiotics, metformin or antiandrogenic therapy, may require oral retinoids, dapsone and biologics
We’ll mention some, but we won’t go into detail, since we don’t really do this stuff as Ob/Gyns
Oral retinoids - may only have limited benefit
Oral dapsone - sulfone drug with immunomodulatory and antibacterial properties
Adalimumab - FDA approved treatment for moderate to severe HS
Acute symptomatic lesions: oral glucocorticoids may also be used
For severe, refractory disease
Wide excision - extensive surgical intervention can get to greatest likelihood for resolution of active inflammation, but can be disfiguring and involve a prolonged recovery time.
Today we welcome Dr. Vivienne Meljen, senior resident at Duke OB/GYN, to talk to us about one of her favorite topics — bHCG, the “pregnancy hormone.” There’s a lot to unpack — so these notes are broken down as our Q&A conversation!
What is hCG?
Human chorionic gonadotropin or hCG is part of a family of glycoprotein hormones including TSH, FSH, and LH.
These are hormones produced by the pituitary gland. hCG included!
They are each heterodimers and have an alpha and a beta subunit. The alpha subunits are identical and beta subunits are all a bit different
In fact, luteinizing hormone (LH) and hCG are super similar and come from shared genes, so when LH is being made in large amounts, hCG is also made and may be elevated.
HCG is metabolized by the liver and kidneys.
Where does hCG come from?
Traditionally we think of hCG as being produced by “a pregnancy”. The part of a pregnancy that makes hCG is the trophoblast - what will eventually become the placenta.
It also comes from the pituitary gland as we mentioned earlier. And some cancers can make hCG
What does hCG do?
To understand what hCG does, we need to back track a bit and remember how a pregnancy starts.
To get to hCG production, there must be fertilization and then implantation of the pregnancy. This process of reaching implantation takes about 7 – 10 days as the embryo floats through the tube to its final implantation site.
Once it has implanted, the trophoblast makes hCG which then stimulates the corpus luteum to keep making progesterone, which helps continue to support gestation. At about 10-12 weeks, hCG levels usually peak and thereafter, the placenta takes over hCG production.
This is apparent in patients’ thyroid testing. In normal pregnancy with an asymptomatic patient, TFTs could be slightly abnormal at this point due to the cross-reactivity and homology between TSH and hCG.
So someone can be pregnant, but not necessarily have hCG? Is that right?
Yes, while that blastocyst is making its way to implantation, the corpus luteum is making its own progesterone and there is no hCG yet so a pregnancy test will be negative. In order to minimize variation in ability to detect a pregnancy, we should time pregnancy testing to be done at 15 days after LH surge, instead of testing at the time of expected menses.
This is why in contraception management if we cannot reasonably exclude pregnancy, we recheck in ~ 2 weeks because we would “capture” most pregnancies at that point.
I know there is hCG, but I always hear about “betas” or “checking a beta”. What’s that about?
Like I mentioned, hCG is a heterodimer with an alpha and a beta subunit. Most people say “check a beta” meaning “check a quant”. The reference to betas is actually due to a misunderstanding back when the hCG immunoassays were first being created, and a bottle of antibodies was labeled as “beta subunit” and it was interpreted as the test only testing for beta subunits. In fact, most hCG tests are detecting all different types of hCG when you get a quant.
What can we use hCG testing for?
Detecting pregnancy
Tumor marker monitoring in molar pregnancy and GTN
Screening for trisomies in pregnancy with quad screen for example
What can we use hCG itself for?
One of the evidence-based and legitimate ways to use it is in the REI world for ovarian hyperstimulation for ART. HCG is the “trigger shot” to help mature eggs because it simulates an LH surge due to its homology.
Note- by the time you’d want to test for pregnancy in a woman undergoing ART, this should have cleared so it shouldn’t affect testing.
What’s the normal rate of rise for hCG in a normal pregnancy?
We use serial hCG concentration measurements as a tool to help us differentiate normal from abnormal pregnancies
Back in the day, the rule of thumb was that hCG would rise ~51% every 48 hours.
Now we know that hCG rate of rise depends on the initial value with the % rise being greater at lower values. For an initial hCG level of < 1,500 the expected rate of rise is > 49% versus starting over 3,000 the expected rate of rise is in the ~33% range. Most normal pregnancies will rise faster than this.
What about hCG levels going down?
While we have some clear guidelines about a 15+% decrease in hcg levels between days 4 and 7 following mtx administration for suspected ectopic pregnancy, it is less clear in other situations.
There is no specific rule, but per ACOG, following an SAB hCG levels should normalize within 2-6 weeks. This likely depends on the initial value.
What can cause a positive pregnancy test?
Pregnancy (normal, abnormal, ectopic)
HCG doping (people use it for weight loss and for sports)
A slew of possible causes of false positives we will get into later
What’s the deal with urine and serum testing for hCG?
Urine tests are QUALITATIVE – positive or negative
Most Serum tests are QUANTITATIVE – give you a number amount usually in IU/L
Urine tests will typically turn positive at the same point at which a serum test is > 20-25. However, you can have a false negative urine study if the urine is very dilute and a woman’s hCG level is low.
Most of these test employs antibodies that sandwich hCG when present and then are converted into a test result.
Because they use antibodies though, some other things can cause antibodies to link and create a false positive or negative result that you need to be aware of.
On a typical urine test or a “UPT” seeing 1 line is a sign that the control and test works, 2 lines means hCG is present.
You can get a false negative test with a rare situation called the “hook effect” when you have SUCH a high level of hCG (think GTN levels) that the sandwich antibodies are saturated on both ends and can’t link together to give a signal.
False positive tests seem to be fairly common and weird. Can you take us through those?
Heterophile antibodies are often referred to as “phantom hCG”. These are nonspecific, low affinity antibodies that can crosslink the antibodies in the test and make it seem positive.
Where do these antibodies come from? - Some people at greater risk of these heterophile antibodies are people who have worked on a farm or in a veterinary facility, women with rheumatologic conditions, patients who have rec’d recombinant antibodies for medical treatment, some who have received plasma exchange from an unknowingly pregnant donor. You can filter out for these by cross checking with urine that should be negative, trying a different assay, or having your lab perform serial dilutions or use a heterophile-blocking agent.
Pituitary hCG is often seen in perimenopause or post-chemotherapy. This makes sense because of the homology to LH. So when LH is high, hCG rises with it. You can suppress this by giving OCPs to see if it normalizes in a few weeks.
“Chemical pregnancy” is another potential “false” but not really false positive. This is an implanted conception that produces hCG but results in a SAB by the time of expected menses.
Familial hCG is a bizarre and rare cause where there is a hereditary cause of hCG production that can be present throughout ones entire life at low levels.
Kidney disease is one of the more common causes I’ve been called for and this is a tricky one. The exact mechanism for why patients with ESRD have false positive hCG is not known but we think its related to impaired renal clearance and increased gonadotropin levels. The tough part is that these patients often do NOT produce urine so they get serum testing which if positive, we can’t cross check with urine to see easily if it is a heterophile. Often, these patients are tested in the setting of prepping for transplant and sometimes, in the final stretch before going to the OR for a new kidney; so a positive test can really complicate things. To make matters worse, they often have complicated menstrual histories so it is very hard to cross check timing of a possible pregnancy. It’s estimated that approximately 1.5% of dialysis receiving reproductive-aged women conceive over ~2 years so it’s possible. Usually, using a good history one can work this out and often these patients have a series of low positive quants over the course of years to help support that it is a false positive test. Some authors suggest using a good old fashioned progesterone level to help clarify the situation, though it isn’t fool proof.
Infrequently in the general gynecologist’s office, you may be asked to evaluate a child for concern of vulvovaginitis. Today’s episode will review some common questions regarding approach in pediatric gynecology, and be specific to a pre-pubertal population.
Many times this is the first time that the young patient has seen a gynecologist! It’s going to be a scary and unfamiliar environment, as the only context for physicians for many children at this point are their pediatrician or family physician. You’ll likely have to lean in to the parent/close relative/guardian for history and more information regarding chronicity, anxieties, and specific complaints.
Common complaints can include:
Itching or discharge.
Pain or irritation.
Issues with going to the bathroom (ie. some children may have issues of leaking urine, seemingly losing the developmental milestone of urinary continence).
The approach in pediatrics is somewhat different:
Getting the trust of the patient - this may be harder for us as Ob/Gyns, since we are not always used to dealing with a pediatric population.
Stickers, coloring books, asking about school and friends etc.
If they are old enough to speak for themselves, always ask them what’s going on!
Then ask/tell them that you are going to talk to their parent/guardian who is with them that you’d like to ask them as well what is going on — this is respectful of the child and keeps them involved.
For adolescent patients, usually have the parents/guardian step out of the room for some time for sensitive questions
Assess risk: safety at school, home, people they don’t get along with or who may be hurting them
Drug/alcohol/tobacco use - kids may feel guilty about using. Ask if friends/family use, then can broach the subject with them.
Sexual activity (usually approached with “Do you have anyone at school that you might like? Have you held hands or kissed them?).
Specific questions related to the complaint:
Assessment of vulvar hygiene
Showering/bathing habits - bubble baths? What types of soaps?
Toileting - how do they wipe? Have them demonstrate
Choice of clothing/clothing due to hobbies/activities - leotards, tights, swimsuits, etc - how long are they wearing them during the day? What kind of underwear? What about pajamas?
The exam
Most children will not have had a pelvic exam, and most (read: almost all) do not require a speculum exam!
Check for abnormal breast development (ie. early breast development) in younger children.
Check for abdominal masses.
Pelvic exam:
Child can be laid back on the table in frog leg position, can also have parent sitting on exam table and holding child on lap in this position.
Careful external examination, also can spread labia from lower legs/bottom and look at urethra/hymenal ring.
Look for skin changes on the labia - red? White? Thin?
Also, see if there is labial adhesions.
Purulent discharge/other types of discharge can be seen on underwear as well
Q-tip test to evaluate for vaginal potency.
Foreign objects that cannot be easily removed should not be done in the office with smaller children, may require vaginoscopy
Now let’s review some differential diagnoses that may present in young children.
Infectious
Candida
Possible to have yeast infection in children who have had recent antibiotic treatment or if they wear diapers.
Usually uncommon in normal prepubertal girls, unlike in women.
If mostly on the outside, or diaper dermatitis, can use topical antifungal agents like nystatin, clotrimazole, miconazole, etc.
Gardnerella - also possible, but it is not common. Treat like BV.
STI - suspect if purulent discharge with evidence of sexual abuse on interview/exam
Evidence includes anal or genital tears, evidence of ejaculation.
Laceration to lower half of the hymenal ring, usually 3-9 o’clock is consistent with penetrating injury.
Suspicion of child abuse is something that requires mandatory reporting to authorities.
Things to test for include gonorrhea, chlamydia, trichomonas.
Genital warts: can be diagnosed clinically and usually with biopsy.
Noninfectious
Foreign body
Can cause acute and chronic vulvovaginitis with purulent discharge, foul smell, and even bleeding.
Most common things are toilet paper, small toys, etc → can usually be removed with warm vaginal lavage (ie. obtaining thin catheter and attach to 60cc syringe). Place the tip of catheter into the vaginal canal, and can lavage several times
Can treat introitus with small amount of Xylocaine jelly if needed for pain / local anesthetic.
If large object or not easily removed, may need sedation/anesthesia for extraction.
If there is suspicion for battery within the vagina, this is a reason for anesthesia, vaginoscopy for possible burns
Trauma
Vulvar trauma can cause significant bleeding - area is highly vascular
Interview is important - was there recent straddle injuring/skating injury?
History should correlate with physical finding - otherwise suspect abuse.
Straddle injury: injury usually anterior area of the vulva, including mons, clitoral hood, and anterior aspect of the labial
Should not have injury to the posterior fourchette and hymenal areas - this would suggest sexual abuse.
Assess ability to urinate and presence of hematoma; if unable to urinate,, need to drain bladder, ice, and give pain medication if large hematoma.
If not obstructive, can ice and give pain medication. Most hematomas will resolve spontaneously
Surgery is rarely needed and can result in introduction of skin → infection
Skin issues
Lichen sclerosus
We talked about lichen sclerosus in postmenopausal women previously!
It can cause itching, discomfort, even discharge.
Usually appears white, thin skin (onion skin, cigarette-paper), and usually around the vulva and perianal regions.
Can usually diagnose with visual inspection, and biopsy is rarely needed, though in adults you should biopsy (can be associated with malignancies in adulthood).
Treatment: superpotent topical steroids → first start with more frequent treatment, then maintenance therapy.
Labial adhesions
Most frequently in infants and young children, peak incidence up to 3% in second year of life in girls.
Usually due to inflammation + low estrogen.
Can lead to discomfort and possible issues with urination, recurrent urinary tract infection.
If asymptomatic, no treatment is necessary especially if it only involves a small portion of the labia.
If symptomatic - initial treatment with topical estrogen/estradiol cream twice a day with fingertip or Q-tip, sometimes with a little pressure, but do not try to manually separate the adhesion as this can cause tearing/pain/bleeding.
Usually can see a thin, translucent raphe in the middle (location of placing estrogen)
Another option is topical betamethasone as alternative or adjunctive topical treatment
Surgical separation - rarely indicated. Usually only for those with severe obstruction to urinary flow or who have urinary retention.
Vulvar ulcers
Can be non-sexually transmitted ulcers and can present with systemic symptoms like fatigue, malaise, fever, etc.
Etiology may not always be determined, but viruses can sometimes cause them (ie. flu A, EBV, mycoplasma, CMV).
Take a careful sexual history to rule out other STDs, HSV - but perform these tests as well just in case.
Can also test with CBC and monospot test.
If continues to be painful, unable to urinate, some girls may need to be admitted for pain control and foley placement.
Other things to rule out: Behcet’s syndrome (if chronic ulcers), Crohn’s disease.
Nonvaginal issues
Urethral prolapse
Distal end of the urethra can prolapse either partially or in a complete circumferential fashion (“donut-like”).
Tissue can be friable and can become infected.
Usually will have pain with urination, bleeding, etc.
May need to differentiate from other things like sarcoma botryoides or prolapsed ureterocele (may need a urologist!).
If symptomatic, can be treated with topical estrogen 2x/day for two weeks, and then reassess.
Pinworm
Can cause vulvar symptoms as well, like itching, but usually is perianal itching.
Caused by the worm enterobiasis.
Can be diagnosed with visual inspection or “paddle test” where there is a plastic paddle sometimes with adhesion pressed to perianal area → then place on glass slide to see worms.
Treatment is with albendazole or mebendazole, and should think about treating the entire household.
Wash all bedding and clothes!
Epidemiology of Abortion
In 2017:
60% of abortions occured prior to 10 weeks gestation;
Medication abortion comprised 39% of all abortions.
Medication abortion may be more attractive than procedural abortion because it can be done safely, effectively, and discretely, at the patient’s preference.
Who is eligible for medication abortion?
Most patients at 70 days gestation or less are eligible for medical abortions. Patients with distorting fibroids, uterine anomalies, or scarring of the introitus due to FGM may benefit (versus aspiration). Multiple gestation is not a contraindication, and can use the same regimen as singleton gestations.
Gestational age should be confirmed prior to initiating a medication abortion, by certain LMP within the past 56 days in patients with regular cycles and no symptoms or signs of ectopic pregnancy. Clinical or sonographic exam are not required before medication abortion.
Rh status should be verified, with RhoGam administered if indicated for Rh negative patients. Research here is continuing, but RhoGam is recommended by ACOG for all Rh negative patients. Some situations may call for shared decision-making on this front, and some institutions and professional groups do not recommend RhoGam prior to 10 weeks gestation.
Additional laboratories, counseling, or evaluation may be required by local or state laws prior to proceeding with medication abortion.
Finally, medication abortion may not be an appropriate choice for patients:
with suspected or confirmed ectopic pregnancies,
patients with an IUD that remains in situ,
patients with chronic medical conditions:
long-term steroid use,
coagulopathy or anticoagulation use,
adrenal insufficiency.
Anemia or hemoglobinopathy:
Transfusion rates are higher with medication abortion versus aspiration (0.1 to 0.01%); patients in this category may benefit from aspiration or closer monitoring but are likely reasonable candidates.
Finally, patients should be willing to follow up completely and have good contact information, understand that medication abortion may take some time for completion, and be able to understand instructions to ensure success.
Counseling:
Clear instructions on what to expect should be provided to patients who undergo medication abortion:
Bleeding and cramping, with bleeding much heavier than menses.
Bleeding heavier than two maxi pads per hour for 2 hours should prompt patients to contact their clinician.
Patients should be counselled that additional intervention may be needed in the event of excess bleeding or suspected failure; however this is rare (less than 1%, and transfusion rates less than 0.1%).
Rate of ongoing pregnancy is low, and the risk increases at later gestational ages.
The risk of ongoing pregnancy at 64-70 days gestation is around 3%.
Teratogenicity is associated with the use of both mifepristone and misoprostol, so patients should be counseled about this in the event of medication failure, or if patients attempt to use high-dose progestins for unsanctioned “abortion reversal.”
There is no regimen that has been demonstrated to reverse abortion after administration of medications, and this has been shown in small studies to increase risk of complications.
Side effects of misoprostol use are commonly GI upset, hot flushes, fever or chills. Mifepristone is generally well tolerated with few side effects.
Risk of infection is overall very low, so there is no indication for antibiotic prophylaxis.
What medications are used for medication abortion?
There are a number of approved regimens, but the most successful and preferred is a combination of mifepristone and misoprostol.
Mifepristone is a selective progesterone receptor modulator.
Binds progesterone receptor with greater affinity than progesterone, but does not activate it, thus acting as an antiprogestin.
The provision of mifepristone in the USA is dependent on a “risk evaluation and mitigation strategy,” or REMS program, facilitated by the FDA. ACOG and other professional organizations oppose the ongoing use of the REMS program as it does not make care safer and creates a barrier to the most effective form of medication abortion.
Misoprostol is a prostaglandin E1 analog.
Causes cervical softening and uterine contractions.
The FDA approved combination is mifepristone 200mg orally, followed 24-48hrs later by 800 mcg of buccal misoprostol.
The WHO suggests misoprostol can be administered vaginally, buccally, or sublingually at the same dose and interval.
Success rates range from 93% to 98% (lower success rate at more advanced gestational age). The rate of ongoing pregnancy in the highest gestational age range (64-70 days) was small at 3.1%.
Misoprostol alone may also be used at 800 mcg vaginally, sublingually, or buccally, every 3 hours for up to 3 doses. However, mife-miso is a much more effective method and should be used if available.
What clinical follow up is recommended after medication abortion?
Follow up can be performed clinically or remotely via telemedicine. Clinicians are able to successfully determine if pregnancy expulsion has occurred with 96-99% accuracy based on symptomatology alone. The use of pregnancy tests can also be a helpful adjunct to confirm expulsion, but are not absolutely necessary.
Sonography can be used as well, but may also predispose patients to additional unnecessary procedures. The measurement of endometrial thickness does not predict need for subsequent aspiration or complications.
If abortion is suspected to be incomplete, the patient can be counseled about aspiration versus a repeat dose of misoprostol or expectant management. Surprisingly, studies have shown that even with a gestational sac is retained at 2 weeks after initial medication use, expulsion will usually occur spontaneously in the coming weeks! Ongoing symptoms such as irregular bleeding can persist in this case though, so many patients opt for intervention.
What about contraception after medication abortion?
Most contraceptive methods are safe to start immediately or soon after abortion. Complete abortion should be ensured before placement of an IUD; usually a week after medication administration.
Progestin-based contraceptives have a theoretical risk of interfering with mifepristone efficacy; this has been demonstrated with DMPA use on day 1 of the medication abortion, and thus patients should be counseled that risk of ongoing pregnancy may be greater in this scenario. This has not been observed with etonogestrel implants.
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