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Disclosures

Controversies in women’s health 2016: Recognition and treatment of common disorders I have no conflicts of interest to disclose. of the skin I may discuss off-label use of treatments for cutaneous .

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

A preview

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

Acne “emergency” Acne pearls for adult female patients

• Many adult females fail standard acne therapy - 82% fail multiple systemic - 1/3 fail systemic • 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 How do OCPs work? • provides the most benefit • Actions: 1. Stimulates SHBG synthesis (): - decrease free , DHEA-S 2. Inhibit 5α-reductase • 226 publications, 32 RCT 3. Decrease production of ovarian, adrenal • Antibiotics superior @ 3 months • Equivalent to systemic antibiotics @ 6 months • Lesion count reduction: 40-70% Koo EB et al (2014) JAAD 71:450-459 Koo EB et al (2014) JAAD 71:450-459 Haider A and JC Shaw (2004) JAMA 292:726-735

My acne patient didn’t respond to OCP. Which OCP is best? Will adding spironolactone help? • FDA-approved for acne: no superiority data -Ortho Tri-Cyclen: + ethinyl / EE Effective: non-FDA approved, no -controlled trials -EstroStep: norethindrone acetate + EE • spironolactone alone or with OCP (50-200mg/day) -Yaz: + EE • 33-85% reduction in acne - dosing 50-100mg/day: 33% improvement • High estrogen, low androgenic () activity - 100mg + drospirenone: 85% improvement -norgestimate, (3rd gen progestins) -drosperinone (4th gen progestin) -nomegestrel acetate (NOMAC)

Brown J et al (2009) Database of Sys Rev 2:CD000194 Haider A and JC Shaw (2004) JAMA 292:726-735 Arowojolu AO et al (2012) Cochrane Database Syst Rev, 6:CD004425 Shaw JC (2000) JAAD 43:498-502 Haider A and JC Shaw (2004) JAMA 292:726-735 Krunic A et al (2008) JAAD 58:60-2

Spironolactone: safe, has side effects Spironolactone: the scare over

• 8 year safety study in acne: no serious complications • Main side effects: menstrual irregularities (22%) tenderness (17%) (15%) (13%) • monotherapy only at low doses, select patients • (minimal rise in K+ in 13%, no sequelae) 425 mg 366 mg 600 mg 30 mg 235 mg • reduction: mean 5mmHg SBP, 2.6mmHg DBP • TERATOGEN: Category C/D RDA K+: 4700 mg • Black box warning: benign tumors in animal studies Low usefulness of screening in healthy

Haider A and JC Shaw (2004) JAMA 292:726-735 young acne patients 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 Plovanich M et al (2015) JAMA Derm, 151:941-944

Do other forms of contraception help acne? When should I worry about a hormonal disorder?

Vaginal ring: minimal data on efficacy with acne • , acanthosis nigricans • etonorgestrel (derivative of 3rd gen progestin) • Cochrane review (2010): Nuva-users have less acne • Oligomenorrhea (<8 per year) or amenorrhea • adverse effects: intermediate clotting risk • : Deepening voice Intrauterine devices: caution Clitoromegaly • (2nd gen progestin) Increased muscle mass • -eluting IUDs may worsen acne (Cutis 2008) Decreased breast size • plasma concentration @ 1 month: 50% of Norplant Virilization = sign of -secreting tumor Ilse JR et al (2008) Cutis, 82: 158 Azziz R et al (2004) J Clin Endo Metab, 89:453-462 Lopez LM et al (2010) Cochrane Review, CD003552 Escobar-Morreale H et al (2012) Hum Reprod Update, 18:146-170 Chi IC (1991) Contraception, 44: 573--588 JC Harper (2008) J Drugs Derm 7: 527-530 Lolis MS et al (2009) Med Clin N Am 93:1161-1181

Hyperandrogenism workup: results Polycystic Ovary Syndrome (PCOS)

Rotterdam criteria (2003): 2 of 3 PCOS Idiopathic Idiopathic NCCAH Tumors Misc • oligomenorrhea (< 8 per year) HA Hirsutism • serum or clinical • ultrasound (+) polycystic ovaries

71% 15% 10% 3% 0.3% 0.7% • Prevalence: 5-10% • Heterogeneous presentation PCOS is #1 cause of androgen excess Tumors, hormonal disorders are very rare

Escobar-Morreale H et al (2012) Human Repro Update, 18:146-170 Stein & Leventhal (1935) Am J Obstet Gynecol, 29:181-191 Rotterdam ESHRE/ASRM-sponsored PCOS Consensus Workshop Group (2004) Human Reproduc. 19:41-47

Cutaneous signs of PCOS Hirsutism: best skin sign of hyperandrogenism

Pearls: • look beyond the face (trunk, proximal extremities) • spironolactone 100 qD- BID has best efficacy Cross-sectional UCSF study 401 women suspected of having PCOS Comprehensive skin exam by dermatologist 92% of patients with PCOS had skin finding

Schmidt T et al (2015) JAMA Derm, Dec 23:1-8! Schmidt TH, Shinkai K (2015) JAAD 73:672-690

Androgenic alopecia: poor skin sign of Diagnostic workup for PCOS hyperandrogenism Step 1: Step 2: When? Endocrine Metabolic Pearls: • Testosterone (free, total) • BMI • frontal hairline is preserved • 17-hydroxyprogesterone • Blood pressure • total baldness is rare in • trans-vaginal ultrasound • Fasting lipid panel women • Fasting insulin, glucose • DHEA-S • 2 hour glucose challenge • topical 5% daily • TSH • HgbA1c • 6-12 months • prolactin • ALT • ! • LH: FSH (>3 in 95% PCOS)! Dizon M, Schmidt TH, Shinkai K (2016) Cutis, 98:11-13 Schmidt TH, Shinkai K (2015) JAAD 73:672-690

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

Morbilliform

• 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

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

Minimal systemic symptoms Systemic involvement

Morbilliform drug eruption DRESS AGEP Stevens-Johnson (SJS) Toxic epidermal necrolysis (TEN) Simple Complex

Potentially life threatening Require systemic

Drug eruptions: Signs of a serious drug eruption: timing of onset can be helpful • Mucosal involvement (ie, oral ulcerations) Minimal systemic symptoms Systemic involvement • Erythroderma • Skin pain Morbilliform drug eruption DRESS 2-6 weeks • Target lesions 5-14 days AGEP 1-4 days • Bullous lesions Stevens-Johnson (SJS) • Denudation (skin falling off in sheets) Toxic epidermal necrolysis • Pustules (TEN) 5-20 days • Facial swelling, anasarca Simple Complex • Fever • Internal organ involvement: liver, > lung, cardiac Potentially life threatening Require systemic immunosuppression

Target lesions: Stevens Johnson Syndrome (SJS) Mucosal involvement: SJS/ TEN

Facial swelling: drug-induced hypersensitivity Bullous lesions, denudation, pain: TEN syndrome or DRESS Also: eosinophilia, transaminitis, renal failure

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

Patient returns with a changing mole

“Spots,” skin cancers, melanoma

Melanoma Melanoma

A = asymmetry B = irregular border C = color D = diameter >6mm E = evolution

complete biopsy

Melanoma: initial evaluation D/dx of a pigmented lesion?

• Prognosis is DEPENDENT on the depth of Mole/ nevus 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

Seborrheic keratoses Seborrheic keratoses

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

Solar lentigo/lentigines Cherry angioma (d/dx: Spitz nevus, melanoma)

Pigmented, flat, even color Irregular borders Multiple, 1-2 mm in size Sun exposed areas 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 Prevention? - no routine screening (including self-exams) Let’s talk about photoprotection - biopsy in 4.4% screened patients - 1 in 28 biopsies = melanoma • SCREEN study (Germany): - 48% reduction in melanoma-related - NNT: 100,000 screening to prevent 1 death

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

Ultraviolet radiation Ultraviolet radiation

UVA: 320-400nm UVB: 290-320nm Photoaging, melanoma Sunburn, skin cancer, melanoma Not blocked by glass, clouds, ozone Blocked by clouds, ozone

Sunscreen and the UV spectrum 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

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

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 ([email protected])

Q&A