Controversies In Women`s Health

Transcription

Controversies in
Women’s Health:
Hot Topics: Dermatology 2008
Jack Resneck, Jr, MD
Assoc Prof, UCSF Dept of Dermatology
Assoc Prof, UCSF Institute for Health Policy Studies
Dermatology Residency Director & Faculty Practice Director
Disclosures

No Financial Conflicts of Interest
Many off-label uses

Will note them verbally as we go

Almost everything we do in derm is off-label
Outline
Controversies in Women’s Health: Dermatology 2008

Hair Loss in Women
The Older Woman with the Red Leg
Treatment-Resistant Acne in Adult Women
Isotretinoin Safety and the FDA
Genital Wart Treatments
Topical Treatment of Skin Cancer and
Photodamage
Sunscreens, Cancer Prevention, and Vitamin D
Hair Loss (Alopecia) in Women

Common (30% Lifetime Incidence)
Distressing
Difficult to work up, diagnose, and treat
Hair Biology, A Quick Review

Scalp has 100,000 Hairs
90% Anagen (3 years (range 2-6), growing)
1% Catagen (2 weeks, apoptosis outer root
sheath)
9% Telogen (3 months, resting)

Normal loss: 100-150 per day
1cm growth / month
Hair Loss
The First Fork in the Road

Scarring (cicatricial)

Non-Scarring
Scarring Alopecias

Discoid Lupus

Folliculitis Decalvans

Lichen Planopilaris

Dissecting Cellulitis
Scarring Alopecias

Traction Alopecia

Many other scarring alopecias

Trichotillomania
Scarring Alopecias

High Stakes
Difficult to diagnose and manage
Referral encouraged
Approach to Non-Scarring
Alopecias

Use history/physical to identify cases
where diagnosis is clear
Consider labs/biopsy in remaining cases
Anagen/Telogen
Pull Test
Tug Test
Case 1

Evolved rapidly
+ Pull Test at
Periphery
Non-scarring
Alopecia Areata

Auto-immune etiology, active T-cells target follicular
melanocytes
Anagen effluvium, hairs taper and break
Assoc with higher incidence SLE, autoimmune thyroid dz,
diabetes, vitiligo
DDx: Syphillis, tinea, early scarring, …

May consider RPR, KOH, bx (but usually not required)
Treatment:

Mainstay: Intralesional Kenalog, 10mg/cc (scalp).

Limit of 30mg/tx. Treat once/month. Checkerboard pattern,
careful to inject into dermis (not epidermis or s-q).
Other options
Prognosis
Case 2

Began heavy
shedding 3 mos
post-partum
Evolved rapidly
Non-scarring
+ Pull Test (>25)
Telogen hairs
Telogen Effluvium

Abrupt shift to telogen (often 30% of hairs)
Triggers:

Pregnancy, major illness, major surgery
Nutritional deficiency (abrupt low-protein diet)
Drugs (oral retinoids, heparin, interferon alpha,
lithium, terbinafine, valproate, warfarin, betablockers, ACE-inhibitors)
Hypothyroidism?
Iron deficiency?
Most regrow over period of months
Case 3

“Help me – I used to have such thick hair, but now it’s all
coming out – I see way more hair in the shower than I
used to – look at this photo of how thick my hair was.”
Evolved slowly
Often + fam hx
Non-scarring
- Pull Test (<5)
- Tug Test
Mostly vertex/frontal
No change in hairline
No bald spots
Not hirsuit, menses nl.
Female Pattern Hair Loss
Androgenetic Alopecia
Androgenetic Alopecia?

38% prevalence by age 70
Usually central frontal or vertex, sparing
frontal hairline
Approach

Eliminate scarring alopecia, external causes
(traction from hair care practices,
trichotillomania)
If male pattern, hirsuit, or irregular menses,
check androgens
Consider recent telogen effluvium unmasking
existing female pattern (can take up to 50% loss
to be evident)
Consider nutrition, ferritin, thyroid, KOH, RPR
Treatment

Reassurance
Topical minoxidil (2% vs 5%*)
Sprironolactone and OCPs?
Finasteride not effective
Surgery
•2% minoxidil is only rx FDA approved for hair loss in women
Pt referred for persistent cellulitis

One year chronic sore red legs
(relapsing/remitting) despite multiple
courses of:
Cephalexin
Dicloxacillin
Clarithromycin
Azithromycin
Clindamycin

What would you do?

A. Admit for IV Antibiotics
B. Prescribe one pound of Triamcinolone
C. Biopsy for histopath and tissue culture
D. Begin vasculitis workup
E. Refer for patch testing
What would you do?

A. Admit for IV Antibiotics
B. Prescribe one pound of Triamcinolone
C. Biopsy for histopath and tissue culture
D. Begin vasculitis workup
E. Refer for patch testing
Stasis Dermatitis

Often bilateral
Itchy and/or painful
Eczema may be weepy or dry,
scaling, lichenified.
Red, hot, swollen legs may mimic
cellulitis
No fever, elevated WBC, LAD, or
streaking
Look for: edema, hemosiderin
deposition, hyperpigmentation
Superimposed contact dermatitis
common
Treatment: Compression,
emollients, liberal use of topical
steroids
Watch out for venous ulcers
DDx: Cellulitis

Infection of the
dermis/subcutis
Strep pyogenes and
Staph aureus
Rapidly spreading
Erythematous, tender
plaque, swollen but not
fluctuant
Preceded by fever
Occ. LAD, streaking
WBC often nl
Blood Cx often neg
Rarely bilateral
Treat tinea pedis (portal
of entry)
Ddx: Leukocytoclastic Vasculitis

Small post-capillary
venules
Immune Complex
Mediated
Palpable purpura is
hallmark
May also be
vesicular, pustular,
ulcerated.
Early fevers and
erythema may mimic
cellulitis
LCV Etiologies

Infectious:

Staph aureus
Group A Strep
Hepatitis B
M. Tuberculosis
M. Leprae
Hepatitis A & C
HSV
Influenza
Many parasitic
infections
HIV-associated
Neisseria Meningitidis
RMSF
DGC
Bacterial Endocarditis
Salmonella, Yersinia

Drug-Induced:

Penicillins
Sulfas
Thiazides
Allopurinol
NSAIDs
Montelukast (Often
Churg-Strauss)
Tamoxifen, G-CSF, OCPs,
Influenza Vaccine, Alpha
Interferon, Minocycline, COX-2
Inhibitors, Methotrexate,
Furosemide, B-Blockers, AntiSeizure (Hydantoins),
Phenothiazines
Co-exisiting d/z

SLE, Sjogren’s
Rheumatoid Arth
Behcet’s
Mixed cryos (CTD,
Lymphoproliferative,
Hepatitis)
Ulcerative Colitis
Lymphoproliferative
Lung, Colon, Ovarian,
Renal, Prostate, or
Breast Cancer
Genital Warts / Condylomata

HPV Point Prevalence Rates
>60% in Sexually Active
Young Women (PCR)
Lifetime Risk exceeds 80%
Latent Infection common.
Mean duration uncertain

1990-1997 Original Study of UW Female Undergrads
Those with +HPV followed up
147 Patients, 1 or 2 visits only
Median 10 Years Later
Cervical and vulvovaginal swabs obtained

50% HPV Positive
33% of them had same genotype as before
Human Papilloma Virus

Correlation between HPV type and clinical
lesions produced
Low risk types (6,11) = Condyloma
High risk types (16,18,31,45) = Dysplasia

Virtually all exophytic external genital
warts are caused by low risk types
So HPV typing is not indicated for external
genital warts
Quadrivalent vaccine: 6/11/16/18
Genital Warts
Treatment

Goal of treatment: Get rid of the warts

That’s why the patient is in the office
Counsel patient appropriately
Don’t confuse relationships
Support through patient education

Detect early cervical dysplasia
Treat other STDs
Genital Warts
Transmission

Risk of transmission after clearance with
treatment unknown
Bottom line: Transmission is still possible,
but probably already occurred
Monogamous couples, barrier protection
when warts are present; they decide what
to do when warts are gone
Genital Warts
Overzealous Treatment

Patients’ immunity will eventually control
the infection (why the immunosuppressed
are so hard to treat)
Treatment should not be worse than the
disease: Don’t produce long-term sequelae
(physical or psychological)
Genital Warts
Destructive Therapies

No Proven Reduction in Transmission or
Progression to Neoplasm
25% Podophyllin Applied in Office (40%)
0.5% Podophyllotoxin at Home (60%)
Cryotherapy (80%)
Electrofulguration (95%)
Laser (90 - 95%)
Clin Infect Dis. 1999 Jan;28 Suppl 1:S37-56.

These products
contain propane or
dimethyl ether
LN2 is -196
degrees Celsius
Imiquimod (Aldara)

Local Interferon Inducer
Application Schedule (3x/week)
72% Total Clearance in Women
33% Total Clearance in Men

70% Partial Response in Men
? Lower Recurrence Rates
$700 for 3 month supply
Patient-Administered Therapies
Imiquimod vs. Podofilox
IMIQUIMOD
8-12 weeks to clear
Burn: 26% (F) 9%(M)
Erosion: 30%
Complete Clearance
Females: 72%
Males: 33%
Recurrence: 20%
Pregnancy: Cat B
Cost: $230/month
PODOFILOX 0.5%
2-6 weeks to clear
Burn: 37%
Erosion: 27%
Complete Clearance
Females: 50%
Males: 45% - 63%
Recurrence: 30%
Pregnancy: Cat X
Cost: $190/month
A very expensive placebo
Imiquimod has poor efficacy
away from mucosal sites
What about Imiquimod Here?
Imiquimod Treatment of
Basal Cell Carcinoma

Success Rates:

80-90% in Superficial BCC (FDA approved)
60-80% in Nodular BCC (not FDA approved)
Very Low in Micronodular, Invasive, & Morpheaform
Patient selection is the key
Long courses (months) may be required
Biopsy to confirm diagnosis before Tx
Biopsy to confirm cure after Tx
Imiquimod for BCCs

Not ideal for most patients
Inflammation may be severe and lengthy
Cure rates suboptimal

May be useful for
Patients who are surgery-averse
Patients with relative contraindication to surg.
Pre-surgical reduction in tumor burden in
cosmetically sensitive areas

Photodamage / Dermatoheliosis
The Treatment of Sun-Damaged Skin

I am not an expert on cosmetic use of lasers, intense
pulsed light, chemical peels, abrasive physical
techniques, or OTC cosmeceuticals for sun damaged skin
Medical treatments to treat photodamage and
precancerous lesions:

OTC Alpha Hydroxy, Glycolic, and Lactic Acids and Retinols (minimal
effect)
Top. Retinoids (Effective for photodamage, mild improvement)
5-Fluorouracil (Effective for AKs, tolerability an issue)
Imiquimod (Effective for AKs, tolerability an issue)
Oral Retinoids (Useful in transplant and high risk populations)
Photodynamic Therapy (Jury is still out)
Topical Tretinoin

Tretinoin 0.02% or higher qhs effective for mild
improvement of hyperpigmentation and fine
wrinkles in photodamaged skin.
Histologic evidence of new dermal collagen,
keratinocyte damage repair
Reasonable expectations:

4-6 months time course for initial benefit
Erythema, irritation, scaling can be significant
Both benefit and side effects are dosedependent
Interventions for photodamaged skin. Cochrane
Database Syst Rev. 2005 Jan 25;(1):CD001782.
Topical Treatment of Actinic Keratoses

5-Fluorouracil 5% cream

5-Fluorouracil 0.5% microsponge cream

twice daily x 2-4 weeks
daily x 2-4 weeks
Imiquimod 5% cream
2x / week x 16 weeks
Off Label:

3x / week x 12 weeks
3x / week, 4 wks on, 4 wks off, 4 weeks on

Must counsel patients about significant side effects
and select only those who are eager and willing
Efficacy Comparison?
Clearance Rates 1-2 months after
end of therapy
Sustained field clearance rates 12
months after end of therapy
A randomised study of topical 5% imiquimod vs. topical 5-fluorouracil vs. cryosurgery in
immunocompetent patients with actinic keratoses: a comparison of clinical and histological
outcomes including 1-year follow-up. Br J Dermatol. 2007 Dec;157 Suppl 2:34-40.
Sunscreens & Skin Cancer
Sunscreens can block
vitamin D
At least some sunlight is necessary to stay healthy
By Robert Bazell
Correspondent
NBC News
Rickets Makes A Comeback
WASHINGTON
I BEG TO DIFFER
A Dermatologist Who's Not Afraid
to Sit on the Beach
Scientists:
Sunshine May
Prevent Cancer
Debate over the
Benefits of Sun
Exposure

$150,000 Grant from
Indoor Tanning
Association (Tobacco???)
Dr. Holick’s Work

growing mountain of scientific evidence that proves
regular and moderate exposure to ultraviolet (UV) light
has a profound positive effect on health
Insufficient levels of the vitamin lead to medical
maladies, including heart disease, stroke, multiple
sclerosis, Type 1 diabetes mellitus, rheumatoid arthritis,
and cancers of the breast, colon, and prostate; children
are also more prone to rickets.
validated research has established that more cancer
deaths are due to insufficient UV exposure (30,000) than
to too much UV exposure.
Evidence supporting Holick’s work

High
latitude
higher incidence some cancers,
cardiac disease, Type 1 DM, MS
Lower vitamin D levels
Retrospective association between vitamin D intake or
levels and: colon cancer & breast cancer (both incidence
and survival rates).

No impact on prostate ca risk, increased risk for pancreatic ca?
Retrospective association between vitamin D intake and
mortality in meta-analysis Æ not reproduced in large
prospective study in JNCI Nov 2007
Outdoor workers get prostate cancer later
Vitamin D receptor polymorphisms associated with skin
cancer risk, breast cancer risk
Are We All Vitamin D Deficient?

Traditional definition of deficiency (IOM):

Evolving definition of deficiency:

25-hydroxyvitamin D < 11 ng/mL
Less than 5% deficient (US Non-Hispanic white adults)
About 30% deficient
Proposed definition of deficiency:

About 80% deficient
From Hyperbole to Evidence:
Vitamin D

Six Cases of Rickets in USA reported in
1990s

Associated with prolonged breastfeeding
in dark-skinned babies
Studies of Children with
Xeroderma Pigmentosum
Vitamin D and Prospective Trials
JNCI 2007
RCT : 36,000 p-m women
400u vs placebo 7 yrs
Designed for hip fracture
No difference in breast ca.
High D = Low BMI
NEJM 2006
Same cohort
No difference in colorectal
cancer incidence or tumor
characteristics
Hypertension 2008
Same cohort
No difference in HTN
NEJM 2006, RCT
36,000 p-m women in WHI
CA + 400u D3 vs placebo
No difference in hip fractures
Increased kidney stones
Osteoporosis 2007
RCT : 3,440 elderly
100,000u q4mo vs
placebo x 3 yrs
No difference in fractures
Arch Intern Med 2005, RCT
208 black postmenopausal women
800u qd x2 yrs, then 2000u qd x 1yr
No difference in BMD or bone loss vs
placebo
Circulation 2007, RCT
36,000 postmenopausal women
400u qd x 7 years
No difference in stroke or MI
Non-Melanoma Skin Cancers

Basal Cell Carcinoma

Incidence: >1,000,000 per year in US
Squamous Cell Carcinoma
Incidence: 200,000 per year in US
Mortality: 2,500 per year in US

Most Sun-Inducted
Cumulative exposure
Less controversial

Melanoma

Incidence: 120,000 / Year

Mortality: 7,800 / Year

60,000 Invasive / Year (1/55 lifetime risk)
2,000% Increase since 1930
Leading cause of cancer death in young women age 25-29
Second most prevalent cancer in young adults age 15-29
Cause Less Well Understood

Histologic subtypes have unique molecular genetics

Acral-Lentiginous and Mucosal Melanomas: Not UV-related
Head/Neck of elderly: Chronic Sun Exposure
Trunk and extrems of young adults with many moles:

Intermittent sun exposed skin / history of some burns
BRAF mutations (MAP kinase gene)
Sunscreen & Melanoma
The Existing Evidence

Case-Control Studies

Mixed results
Meta-analyses showed no association

Retrospective Recall Bias
Limited choices “never” “sometimes” “always”
Poorly Controlled Confounders

Sun sensitivity, Skin type (fair skinned are both more likely to use
sunscreen and more likely to get melanoma)
Use of sunscreen to prolong time in sun in era when sunscreens had
little UVA protection -> more UVA exposure
Need better data…
EWG Claims:
1.
2.
3.
4.
Many sunscreens lack adequate UVA protection ;
Misleading claims (water resistance) ;
Products break down in sun :
Products (especially oxybenzone) absorbed in
bloodstream and are toxic ??
My current recommendations

Use sunscreen!

UVB: SPF of 30+
UVA: Contains:

New FDA Proposed Rule on UVA
If worried about toxins, use a physical blocker only
Daily moisturizers with sunscreen

Avobenzone (Parsol 1789), or
Helioplex (Neutrogena), or
Mexoryl (Anthelios), or
Physicial Blockers (Titanium or Zinc)
Often SPF 15
Many now contain UVA blockers above
Consider oral Vitamin D supplementation
JAMA. 2006;296:1735-1741.
Case

32 year old woman
Acne since age 17
Moderate, inflammatory, affecting chin and
jawline
Normal menses, Not hirsuit
Poorly controlled with oral doxy, oral MCN,
topical bp, topical retinoids, topical clinda
Two courses of oral isotretinoin led to clearance,
but followed by relapse 6-12 months after
treatment
What would you do?

A. Chronic low dose isotretinoin
B. Oral SMZ/TMP
C. Oral azithromycin 3x/week
D. Oral spironolactone
E. Oral contraceptives
What would you do?

A. Chronic Low Dose isotretinoin
B. Oral SMZ/TMP
C. Oral Azithromycin 3x/week
D. Oral spironolactone
E. Oral Contraceptives
Acne Vulgaris in Adult Women

Occasionally
related to true
excess
androgen
PCOS
Metabolic
Syndrome
Adrenal Tumor
Ovarian Tumor
Meds

Acne Vulgaris in Adult Women

Occasionally related to excess androgen
In most others, may be excess androgen
sensitivity of hair follicles:
Other features of androgen excess are often
not present—irregular menses, hirsuitism,
glucose intolerance, alopecia, etc.
Serum free testosterone and DHEA-S are
often normal

Acne in Adult Women

OCPs (estrogen-containing, minimally
androgenic progestin)

Ortho Tri-Cyclen & Estrostep FDA-approved
Yasmin & Alesse also shown effective (off-label)
Sprironolactone 50mg-100mg daily with or
without OCPs can be very effective

Especially helpful in subset of women with nodular
acne of the lower face and neck resistant to other
treatments
N Engl J Med. 2005 Apr 7;352(14):1463-72.
(Excellent Review Article on Treatment of Acne)
Acne that Isn’t
Acne that Isn’t
Acne that Isn’t
Question
These patients initially presented with lip pruritus and
were treated with topical steroids. With each effort to
taper the steroids, they presented with this rash. The
best treatment is:
A.
B.
C.
D.
E.
Increase Potency of Topical Steroids
Add topical pimecrolimus
Add oral Doxycycline & Taper Steroids
Add oral Keflex & Taper Steroids
Patch Test for Contact Allergies
Question
These patients initially presented with lip pruritus and
were treated with topical steroids. With each effort to
taper the steroids, they presented with this rash. The
best treatment is:
A.
B.
C.
D.
E.
Increase Potency of Topical Steroids
Add topical pimecrolimus
Add oral Doxycycline & Taper Steroids
Add oral Keflex & Taper Steroids
Patch Test for Contact Allergies
Perioral Dermatitis

Very, very common

Almost exclusively a disease of women
Most prevalent in ages 23-35
Papules and small pustules around the
mouth, with a narrow spared zone around the
lips (can also be peri-orbital).
Asympotmatic or mild burning sensation
Often triggered by topical steroids
Perioral Dermatitis
Treatment

Stop topical steroids
Hold use of cosmetics, sunscreens
Oral TCN, Doxy, or MCN (primary tx)
Sometimes replace topical steroids with:
Topical Antibiotics (limited use)
Topical pimecrolimus or tacrolimus to bridge
off of steroids

Will get worse before it gets better
Isotretinoin and Depression

A series of case reports:

FDA:

Son of member of Congress (Stupak)
Tampa teen pilot
165 Suicides 1982-2002
vs 220 Predicted Suicides
9 Studies Failed to Show Association
Am J Psychiatry. 2005 May;162(5):983.

PET Scan 18 Accutane patients
Decreased metabolism in the orbitofrontal cortex
Funded by Plantiff’s Litigators
Isotretinoin and the FDA

Depression/Suicide Debate
Pressure to more aggressively regulate
Pregnancy & Pregnancy Terminations
Registry (modeled on Thalidomide)

No Rx’s without registering after March 1, 2006
122 Exposed Pregnancies (no change)
of 92,000 patients treated in first year

28%
25%
8%
7%
19%
1%
Birth Control Pills
Contains Drugs/Medicine
Contains Hormones/Vitamins specially for women
Don’t Know
Don’t Take if Pregnant
Don’t Get Pregnant While Taking
Teratology 64:148–153 (2001)