Disclosures Controversies in women s health 2018: 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 Professor of Clinical Dermatology University of California, San Francisco A preview Fictional patient Series of dermatology visits Acne 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 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) What are alternative, effective treatments for treating acne in this population?
Systemic antibiotics and combined OCPs are equally effective in the treatment of acne in adult women: Systemic antibiotics and combined OCPs are equally effective in the treatment of acne in adult women: 1 True 1 True 2 False 2 False Hormonal therapy = antibiotics How do OCPs work? Estrogen provides the most benefit 226 publications, 32 RCT Antibiotics superior @ 3 months Equivalent to systemic antibiotics @ 6 months Actions: 1. Stimulates SHBG synthesis (liver): - decrease free testosterone, DHEA-S 2. Inhibit 5a-reductase 3. Decrease production of ovarian, adrenal androgens 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 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 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 blood pressure reduction: mean 5mmHg SBP, 2.6mmHg DBP TERATOGEN: Category C/D Black box warning: benign tumors in animal studies In healthy young patients taking spironolactone, screening for hyperkalemia is: 1 Never needed 2 Sometimes needed dose-dependent 3 Sometimes needed depends on individual 4 Always needed 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 In healthy young patients taking spironolactone, screening for hyperkalemia is: Spironolactone: the scare over potassium 1 Never needed 2 Sometimes needed dose-dependent 3 Sometimes needed depends on individual 4 Always needed 425 mg 366 mg 600 mg 30 mg 235 mg RDA K+: 4700 mg Low usefulness of screening in healthy young acne patients Plovanich M et al (2015) JAMA Derm, 151:941-944 When should I worry about a hormonal disorder? Hyperandrogenism workup: results Hirsutism, acanthosis nigricans Oligomenorrhea (<8 per year) or amenorrhea PCOS Idiopathic HA Idiopathic Hirsutism NCCAH Tumors Misc Virilization: Deepening voice Clitoromegaly Increased muscle mass Decreased breast size Virilization = sign of androgen-secreting tumor 71% 15% 10% 3% 0.3% 0.7% PCOS is #1 cause of androgen excess Tumors, hormonal disorders are very rare 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 Escobar-Morreale H et al (2012) Human Repro Update, 18:146-170
Polycystic Ovary Syndrome (PCOS) Hirsutism: best skin sign of hyperandrogenism Rotterdam criteria (2003): 2 of 3 oligomenorrhea (< 8 per year) serum or clinical hyperandrogenism ultrasound (+) polycystic ovaries Prevalence: 5-10% Heterogeneous presentation Best cutaneous signs: hirsutism, acanthosis nigricans - not: acne, hair loss Stein & Leventhal (1935) Am J Obstet Gynecol, 29:181-191 Rotterdam ESHRE/ASRM-sponsored PCOS Consensus Workshop Group (2004) Human Reproduc. 19:41-47 Schmidt T et al (2015) JAMA Derm, Dec 23:1-8 look beyond the face (trunk, proximal extremities) spironolactone 100 qd-bid has best efficacy Schmidt TH, Shinkai K (2015) JAAD 73:672-690 Androgenetic alopecia: poor skin sign of hyperandrogenism frontal hairline preserved, total baldness rare (females) topical minoxidil 5% qd-bid (6-12 months) Schmidt TH, Shinkai K (2015) JAAD 73:672-690 Diagnostic workup for PCOS Step 1: Endocrine Testosterone (free, total) 17-hydroxyprogesterone trans-vaginal ultrasound DHEA-S TSH prolactin androstenedione LH: FSH (>3 in 95% PCOS) When? BMI 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 a medication is stopped following a simple drug eruption, new skin lesions may appear for up to: 1 1 day When a medication is stopped following a simple drug eruption, new skin lesions may appear for up to: 1 1 day 2 3 days 2 3 days 3 7 days 4 10 days 3 7 days 4 10 days 5 14 days 5 14 days 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 Clinical features of melanoma include: Clinical features of melanoma include: 1 Asymmetry 1 Asymmetry 2 Irregular border 2 Irregular border 3 Color variegation 4 Diameter > 6mm 3 Color variegation 4 Diameter > 6mm 5 All of the above 5 All of the above
Melanoma Melanoma: initial evaluation A = asymmetry B = irregular border C = color D = diameter >6mm E = evolution 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 complete biopsy D/dx of a pigmented lesion? Seborrheic keratoses benign keratinocytic papules trunk, extremities > face do not progress to malignancy stuck-on tan, ovoid papule/ plaque sometimes symptomatic Solar lentigo/lentigines Pigmented, flat, even color Irregular borders Sun exposed areas 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 Squamous cell carcinoma scaly erythematous plaque to nodule sun exposed area potential to metastasize Rx: surgical excision IL 5-FU, MTX in situ -> topical What is the recommended frequency of skin cancer screening in asymptomatic adults? USPTF: 2016 update - insufficient evidence to assess benefits, harms of visual skin exam by a clinician Prevention? Let s talk about photoprotection - Primary care sensitivity 42-100% melanoma - Primary care specificity 70-98% melanoma JAMA 2016; 316(4):429-435 Ann Int Med 2009; 150(3):188-193 Ultraviolet radiation Sunscreen and the UV spectrum UVA: 320-400nm UVB: 290-320nm Photoaging, melanomasunburn, skin cancer, melanoma Not blocked by glass, clouds, Blocked ozone by clouds, ozone Sunscreen ban 2018: Hawaii bans oxybenzone, octinoxate
Sunscreen versus sunblock Photoprotection 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 Pearls for approach to the skin Acne management in adult women: hormonal therapy is a safe, effective option Important differential of drug eruption: when to worry Q&A Changing skin lesions: when to worry Kanade Shinkai (kanade.shinkai@ucsf.edu)