Disclosures Controversies in womens health 2016: Recognition and - - PDF document

Controversies in women’s health 2016:
 Recognition and treatment of common disorders

• f the skin

Kanade Shinkai, MD PhD
 Associate Professor of Clinical Dermatology
 University of California, San Francisco

Disclosures

I have no conflicts of interest to disclose.

• I may discuss off-label use of treatments for cutaneous

disease.

A preview

• Fictional patient
• Series of dermatology visits
• Numerous concerns
• Acne
• Drug eruptions
• Skin cancer

Acne

Acne “emergency” Acne pearls for adult female patients

• Many adult females fail standard acne therapy
• 82% fail multiple systemic antibiotics
• 1/3 fail systemic isotretinoin
• Systemic antibiotics (short-term use only)
• indicated for nodulocystic acne, truncal acne
• may require 3 months for truncal lesions
• works faster than hormonal therapy (2-3 weeks)

Hormonal treatment can be highly-effective for acne in this population

Hormonal therapy versus antibiotics

• 226 publications, 32 RCT
• Antibiotics superior @ 3 months
• Equivalent to systemic antibiotics @ 6 months
• Koo EB et al (2014) JAAD 71:450-459

How do OCPs work?

• Estrogen provides the most benefit
• Actions:
• 1. Stimulates SHBG synthesis (liver):
• decrease free testosterone, DHEA-S
• 2. Inhibit 5α-reductase
• 3. Decrease production of ovarian, adrenal androgens
• Lesion count reduction: 40-70%
• Koo EB et al (2014) JAAD 71:450-459

Haider A and JC Shaw (2004) JAMA 292:726-735

Which OCP is best?

• FDA-approved for acne: no superiority data
• Ortho Tri-Cyclen: norgestimate + ethinyl estradiol/ EE
• EstroStep: norethindrone acetate + EE
• Yaz: drospirenone + EE
• Arowojolu AO et al (2012) Cochrane Database Syst Rev, 6:CD004425

Haider A and JC Shaw (2004) JAMA 292:726-735

• High estrogen, low androgenic (progesterone) activity
• norgestimate, desogestrel (3rd gen progestins)
• drosperinone (4th gen progestin)
• nomegestrel acetate (NOMAC)

My acne patient didn’t respond to OCP. 
 Will adding spironolactone help?

Effective: non-FDA approved, no placebo-controlled trials

• spironolactone alone or with OCP (50-200mg/day)
• 33-85% reduction in acne
• dosing 50-100mg/day: 33% improvement
• 100mg + drospirenone: 85% improvement
• Brown J et al (2009) Cochrane Database of Sys Rev 2:CD000194

Haider A and JC Shaw (2004) JAMA 292:726-735 Shaw JC (2000) JAAD 43:498-502 Krunic A et al (2008) JAAD 58:60-2

Spironolactone: safe, has side effects

• 8 year safety study in acne: no serious complications
• Main side effects: menstrual irregularities (22%)
• breast tenderness (17%)
• fatigue (15%)
• headache (13%)
• monotherapy only at low doses, select patients
• hyperkalemia (minimal rise in K+ in 13%, no sequelae)
• blood pressure reduction: mean 5mmHg SBP, 2.6mmHg DBP
• TERATOGEN: Category C/D
• Black box warning: benign tumors in animal studies
• Haider A and JC Shaw (2004) JAMA 292:726-735
• Shaw JC (2000) JAAD 43:498-502

Shaw JC, White LE (2002) J Cut Med Surg 6:541-545

• George R et al (2008) Sem Cut Med Surg 28:188-196
• Spironolactone: the scare over potassium

Plovanich M et al (2015) JAMA Derm, 151:941-944

RDA K+: 4700 mg Low usefulness of screening in healthy young acne patients

• 425 mg
• 235 mg
• 366 mg
• 30 mg
• 600 mg

Do other forms of contraception help acne?

Vaginal ring: minimal data on efficacy with acne

• etonorgestrel (derivative of 3rd gen progestin)
• Cochrane review (2010): Nuva-users have less acne
• adverse effects: intermediate clotting risk
• Ilse JR et al (2008) Cutis, 82: 158

Lopez LM et al (2010) Cochrane Review, CD003552 Chi IC (1991) Contraception, 44: 573--588

Intrauterine devices: caution

• levonorgestrel (2nd gen progestin)
• hormone-eluting IUDs may worsen acne (Cutis 2008)
• plasma concentration @ 1 month: 50% of Norplant

When should I worry about a hormonal disorder?

• Hirsutism, acanthosis nigricans
• Oligomenorrhea (<8 per year) or amenorrhea
• Virilization: Deepening voice
• Clitoromegaly
• Increased muscle mass
• Decreased breast size
• Azziz R et al (2004) J Clin Endo Metab, 89:453-462

• Virilization = sign of androgen-secreting tumor
• Hyperandrogenism workup: results

PCOS is #1 cause of androgen excess Tumors, hormonal disorders are very rare

• PCOS

Idiopathic HA Idiopathic Hirsutism NCCAH Tumors Misc

71% 15% 10% 3% 0.3% 0.7%

Polycystic Ovary Syndrome (PCOS)

• Prevalence: 5-10%
• Heterogeneous presentation
• Stein & Leventhal (1935) Am J Obstet Gynecol, 29:181-191
• Rotterdam ESHRE/ASRM-sponsored PCOS Consensus Workshop Group (2004) Human Reproduc. 19:41-47
• oligomenorrhea (< 8 per year)
• serum or clinical hyperandrogenism
• ultrasound (+) polycystic ovaries

Rotterdam criteria (2003): 2 of 3

Cutaneous signs of PCOS

Cross-sectional UCSF study 401 women suspected of having PCOS Comprehensive skin exam by dermatologist 92% of patients with PCOS had skin finding

• Hirsutism: best skin sign of hyperandrogenism

Pearls:

• look beyond the face

(trunk, proximal extremities)

• spironolactone 100 qD-

BID has best efficacy

• Androgenic alopecia: poor skin sign of

hyperandrogenism

Pearls:

• frontal hairline is

preserved

• total baldness is rare in

women

• topical minoxidil 5% daily
• 6-12 months

• Diagnostic workup for PCOS
• Testosterone (free, total)
• 17-hydroxyprogesterone
• trans-vaginal ultrasound
• Step 1:

Endocrine

• Step 2:

Metabolic

• BMI
• Blood pressure
• Fasting lipid panel
• Fasting insulin, glucose
• 2 hour glucose challenge
• HgbA1c
• ALT
• When?

• DHEA-S
• TSH
• prolactin
• androstenedione
• LH: FSH (>3 in 95% PCOS)

Back to our acne patient:
 10 days after starting doxycycline, your patient develops an itchy generalized maculopapular rash Drug eruptions

• Morbilliform drug eruption
• common
• erythematous macules, papules

(can be confluent)

• pruritus
• no systemic symptoms
• begins in 1st or 2nd week
• treatment:
• D/C med if severe
• symptomatic treatment:

hydroxyzine, topical steroids

When do the symptoms subside? Up to 1 week Drug eruptions: 
 when to worry

Potentially life threatening Require systemic immunosuppression

Morbilliform drug eruption

• Simple

DRESS AGEP Stevens-Johnson (SJS) Toxic epidermal necrolysis (TEN) Complex Minimal systemic symptoms Systemic involvement

Drug eruptions: 
 timing of onset can be helpful

Potentially life threatening Require systemic immunosuppression

Morbilliform drug eruption

• Simple

DRESS AGEP Stevens-Johnson (SJS) Toxic epidermal necrolysis (TEN) Complex Minimal systemic symptoms Systemic involvement

5-14 days 2-6 weeks 1-4 days 5-20 days

Signs of a serious drug eruption:

• Mucosal involvement (ie, oral ulcerations)
• Erythroderma
• Skin pain
• Target lesions
• Bullous lesions
• Denudation (skin falling off in sheets)
• Pustules
• Facial swelling, anasarca
• Fever
• Internal organ involvement: liver, kidney > lung, cardiac

Target lesions: Stevens Johnson Syndrome (SJS) Mucosal involvement: SJS/ TEN Bullous lesions, denudation, pain: TEN Facial swelling: drug-induced hypersensitivity syndrome or DRESS
 Also: eosinophilia, transaminitis, renal failure

Widespread pustules: acute generalized exanthematous pustulosis (AGEP)
 Also: eosinophilia, renal failure Drug eruption pearls

Look for cutaneous signs of a potentially-fatal drug eruption

• Consider ordering labs if you are not sure
• Lab order

What you are looking for Drug eruption CBC with differential Eosinophilia Any drug hypersensitivity (may be slightly increased in simple drug eruption) ALT, AST Transaminitis Drug-induced hypersensitivity syndrome BUN, Cr Acute renal failure Drug-induced hypersensitivity syndrome, AGEP

“Spots,” skin cancers, melanoma

• Patient returns with a changing mole

Melanoma Melanoma

• A = asymmetry
• B =

irregular border

• C = color
• D = diameter >6mm
• E = evolution
• complete biopsy
• Melanoma: initial evaluation
• Prognosis is DEPENDENT on the depth of

lesion (Breslow’s depth) – < 1mm thickness is low risk – > 1mm consider sentinel lymph node biopsy

• If melanoma is on the differential, complete

excision or full thickness incisional biopsy is indicated

D/dx of a pigmented lesion?

• Mole/ nevus

Seborrheic keratoses

• benign keratinocytic papules
• trunk, extremities > face
• do not progress to malignancy
• stuck-on tan, ovoid papule/

plaque

• sometimes symptomatic
• Seborrheic keratoses

Solar lentigo/lentigines

Pigmented, flat, even color

• Irregular borders
• Sun exposed areas
• Cherry angioma (d/dx: Spitz nevus, melanoma)

Multiple, 1-2 mm in size

• Age 30+

Actinic purpura, actinic keratoses Non-melanoma skin cancer

• What about this new skin lesion?
• Basal cell carcinoma
• pearly papule or plaque
• central ulceration
• telangiectasia
• slow growing
• invade locally
• Rx: surgical excision
• curettage
• superficial -> topical

BCC can be pigmented Squamous cell carcinoma

• scaly erythematous

plaque to nodule

• sun exposed area
• potential to metastasize
• Rx: surgical excision
• IL 5-FU, MTX
• in situ -> topical

SCC on sun-damaged skin Keratoacanthoma: self-resolving SCC

Sun-damaged skin = worry

What is the recommended frequency of skin cancer screening?

• USPTF: 2015 update
• recommended only for patients with known

history of melanoma, NMSC

• no routine screening (including self-exams)
• biopsy in 4.4% screened patients
• 1 in 28 biopsies = melanoma

Breitbart EW et al (2012) JAAD, 66:201-211

• SCREEN study (Germany):
• 48% reduction in melanoma-related death
• NNT: 100,000 screening to prevent 1 death

Prevention?
 Let’s talk about photoprotection Ultraviolet radiation

• UVA: 320-400nm

Photoaging, melanoma Not blocked by glass, clouds, ozone

Ultraviolet radiation

• UVB: 290-320nm

Sunburn, skin cancer, melanoma Blocked by clouds, ozone

Sunscreen and the UV spectrum

https://www.aad.org/public/spot-skin-cancer/learn-about-skin-cancer/prevent/is-sunsceen-safe https://www.aad.org/public/spot-skin-cancer/learn-about-skin-cancer/prevent/how-to-select-a-sunscreen

Sunscreen versus sunblock SPF30 is ideal -> frequent application Broad-spectrum Nano-technology: no known health issues Vitamin D: dietary intake preferred over skin sun exposure

Photoprotection Pearls for approach to the skin

• Important differential of drug eruption: when to worry
• Changing skin lesions: when to worry
• Acne management in adult women: hormonal therapy is a

great option

• Kanade Shinkai (kanade.shinkai@ucsf.edu)

Q&A