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

of the skin"

Kanade Shinkai, MD PhDAssociate 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 foracne 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"

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 """"

Virilization = sign of androgen-secreting tumor""""

Hyperandrogenism workup: results"

Escobar-Morreale H et al (2012) Human Repro Update, 18:146-170"

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"

Schmidt T et al (2015) JAMA Derm, Dec 23:1-8!

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"

Schmidt TH, Shinkai K (2015) JAAD 73:672-690"""

Androgenic alopecia: poor skin sign of hyperandrogenism"

Pearls:"• frontal hairline ispreserved"• total baldness is rare inwomen""• topical minoxidil 5% daily"• 6-12 months"

Schmidt TH, Shinkai K (2015) JAAD 73:672-690"""

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?

Dizon M, Schmidt TH, Shinkai K (2016) Cutis, 98:11-13""

"• 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 DRESSAlso: 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 oflesion (Breslow’s depth)"– < 1mm thickness is low risk"– > 1mm consider sentinel lymph node

biopsy"

•  If melanoma is on the differential, completeexcision or full thickness incisional biopsy isindicated"

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 erythematousplaque 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 knownhistory 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 agreat option"""

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

Q&A"