Disclosures Controversies in women s health 2016: Recognition and treatment of common disorders of the skin I have no conflicts of interest to disclose. I may discuss off-label use of treatments for cutaneous disease. Kanade Shinkai, MD PhD Associate Professor of Clinical Dermatology University of California, San Francisco 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 High estrogen, low androgenic (progesterone) activity -norgestimate, desogestrel (3 rd gen progestins) -drosperinone (4 th gen progestin) -nomegestrel acetate (NOMAC) Arowojolu AO et al (2012) Cochrane Database Syst Rev, 6:CD004425 Haider A and JC Shaw (2004) JAMA 292:726-735 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 Spironolactone: the scare over potassium 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 28:188-196 425 mg 366 mg 600 mg 30 mg RDA K+: 4700 mg Low usefulness of screening in healthy young acne patients Plovanich M et al (2015) JAMA Derm, 151:941-944 235 mg
Do other forms of contraception help acne? Vaginal ring: minimal data on efficacy with acne etonorgestrel (derivative of 3 rd gen progestin) Cochrane review (2010): Nuva-users have less acne adverse effects: intermediate clotting risk Intrauterine devices: caution levonorgestrel (2 nd gen progestin) hormone-eluting IUDs may worsen acne (Cutis 2008) plasma concentration @ 1 month: 50% of Norplant Ilse JR et al (2008) Cutis, 82: 158 Lopez LM et al (2010) Cochrane Review, CD003552 Chi IC (1991) Contraception, 44: 573--588 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 Virilization = sign of androgen-secreting tumor Azziz R et al (2004) J Clin Endo Metab, 89:453-462 Escobar-Morreale H et al (2012) Hum Reprod Update, 18:146-170 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) PCOS Idiopathic HA Idiopathic Hirsutism NCCAH Tumors Misc Rotterdam criteria (2003): 2 of 3 oligomenorrhea (< 8 per year) serum or clinical hyperandrogenism ultrasound (+) polycystic ovaries 71% 15% 10% 3% 0.3% 0.7% 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 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
Cutaneous signs of PCOS Hirsutism: best skin sign of hyperandrogenism 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! Pearls: look beyond the face (trunk, proximal extremities) spironolactone 100 qd- BID has best efficacy Schmidt TH, Shinkai K (2015) JAAD 73:672-690 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 Schmidt TH, Shinkai K (2015) JAAD 73:672-690 Diagnostic workup for PCOS Step 1: When? Endocrine Testosterone (free, total) BMI 17-hydroxyprogesterone trans-vaginal ultrasound DHEA-S TSH prolactin androstenedione! LH: FSH (>3 in 95% PCOS)! Dizon M, Schmidt TH, Shinkai K (2016) Cutis, 98:11-13 Step 2: Metabolic Blood pressure Fasting lipid panel Fasting insulin, glucose 2 hour glucose challenge HgbA1c ALT
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 1 st 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 Minimal systemic symptoms Morbilliform drug eruption Simple Systemic involvement DRESS AGEP Stevens-Johnson (SJS) Toxic epidermal necrolysis (TEN) Complex Potentially life threatening Require systemic immunosuppression Drug eruptions: timing of onset can be helpful Minimal systemic symptoms Morbilliform drug eruption 5-14 days Simple Systemic involvement DRESS 2-6 weeks AGEP 1-4 days Stevens-Johnson (SJS) Toxic epidermal necrolysis (TEN) 5-20 days Complex Potentially life threatening Require systemic immunosuppression 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 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 Prognosis is DEPENDENT on the depth of lesion (Breslow s depth) < 1mm thickness is low risk > 1mm consider sentinel lymph node biopsy D/dx of a pigmented lesion? Mole/ nevus 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 Sun exposed areas 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 SCREEN study (Germany): - 48% reduction in melanoma-related death - NNT: 100,000 screening to prevent 1 death Prevention? Let s talk about photoprotection Breitbart EW et al (2012) JAAD, 66:201-211 Ultraviolet radiation Ultraviolet radiation UVA: 320-400nm Photoaging, melanoma Not blocked by glass, clouds, ozone UVB: 290-320nm Sunburn, skin cancer, melanoma 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 (kanade.shinkai@ucsf.edu)
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