Upload
others
View
2
Download
0
Embed Size (px)
Citation preview
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 ([email protected])"