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

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 disease. � Kanade Shinkai, MD PhD 
 Associate Professor of Clinical Dermatology 
 University of California, San Francisco � A preview � • Fictional patient � � Acne � • 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 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 � How do OCPs work? � • Estrogen provides the most benefit � � • Actions: � � 1. Stimulates SHBG synthesis (liver): � � � - decrease free testosterone, DHEA-S � � 2. Inhibit 5 α -reductase � � 3. Decrease production of ovarian, adrenal androgens � • 226 publications, 32 RCT � � • Antibiotics superior @ 3 months � • Lesion count reduction: 40-70% � • Equivalent to systemic antibiotics @ 6 months � � � � � � 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 � Effective: non-FDA approved, no placebo-controlled trials � � -Ortho Tri-Cyclen: norgestimate + ethinyl estradiol/ EE � � � • spironolactone alone or with OCP (50-200mg/day) � � -EstroStep: norethindrone acetate + EE �� � � • 33-85% reduction in acne � � -Yaz: drospirenone + EE � � � - dosing 50-100mg/day: 33% improvement � � • High estrogen, low androgenic (progesterone) activity � � � - 100mg + drospirenone: 85% improvement � � � -norgestimate, desogestrel (3 rd gen progestins) � � � � -drosperinone (4 th gen progestin) � � � -nomegestrel acetate (NOMAC) � Brown J et al (2009) Cochrane 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 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) � 425 mg � 366 mg � 600 mg � 30 mg � 235 mg � • blood pressure 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 � young acne patients � 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 � 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? � • Hirsutism, acanthosis nigricans � Vaginal ring: minimal data on efficacy with acne � � � • etonorgestrel (derivative of 3 rd gen progestin) � • Oligomenorrhea (<8 per year) or amenorrhea � � • Cochrane review (2010): Nuva-users have less acne � � � • adverse effects: intermediate clotting risk � • Virilization: � Deepening voice � � � � � Clitoromegaly � Intrauterine devices: caution � � � � � Increased muscle mass � � • levonorgestrel (2 nd gen progestin) � � � � Decreased breast size � � • hormone-eluting IUDs may worsen acne (Cutis 2008) � � � � � � �� � • plasma concentration @ 1 month: 50% of Norplant � Virilization = sign of androgen-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, C D003552 � Escobar-Morreale H et al (2012) Hum Reprod Update, 18:146-170 � JC Harper (2008) J Drugs Derm 7: 527-530 � Chi IC (1991) Contraception, 44: 573--588 � � 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 hyperandrogenism � � • 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 � � • 17-hydroxyprogesterone � • Blood pressure � preserved � • trans-vaginal ultrasound � • Fasting lipid panel � • total baldness is rare in � • Fasting insulin, glucose � women � � � • 2 hour glucose challenge � � • DHEA-S � � • TSH � • HgbA1c � • topical minoxidil 5% daily � • prolactin � • ALT � • 6-12 months � • androstenedione � � • 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 doxycycline, your patient develops an itchy generalized maculopapular rash � 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 � �

Drug eruptions: 
 When do the symptoms subside? � when to worry � Up to 1 week � Minimal systemic symptoms � Systemic involvement � Morbilliform drug eruption � DRESS � � AGEP � � Stevens-Johnson (SJS) � � Toxic epidermal necrolysis � � (TEN) � Simple � Complex � Potentially life threatening � Require systemic immunosuppression � Drug eruptions: 
 Signs of a serious drug eruption: � timing of onset can be helpful � • Mucosal involvement (ie, oral ulcerations) � • Erythroderma � Minimal systemic symptoms � Systemic involvement � • 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, kidney > 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 �