Transcript Gender Dermatology - The 2nd World Congress on Gender Specific

Gender Dermatology
ADAM and EVE
Where is the apple ?
1
Why mainstream the
gender perspective ?
• Gender influences health and well being
throughout the life of an individual.
• Everyone has a gender.
• Understanding the implications of gender
differences is vital for:
•
•
•
•
good clinical practice
targeted options for treatment
relevant medical education
unbiased medical research
2
Medical Evidence
• A lack of sex disaggregated data does not
mean “there is no evidence of difference.”
• It means a lack of evidence –
not a lack of difference.
3
Gender Differences - Epidemiology
4
Gender Differences - Epidemiology
5
The Impact of gender
Lifestyle
Occupation
Immunology
Hormonal
Genetics
Age
Psychology
6
OCCUPATION
Housewife's eczema
7
OCCUPATION
Sailor’s skin
8
OCCUPATION
Mycosis fungoides
9
LIFESTYLE
Contact dermatitis fragrance
10
LIFESTYLE
HIV
11
LIFESTYLE
Sexually transmitted diseases
12
LIFESTYLE
Cosmetic acne
13
LIFESTYLE
Sex hormones
14
IMMUNOLOGY
Collagen vascular diseases - SLE
15
Sex hormones are immunomodulators
Associations in humans
More than 75% of autoimmune patients are women.
Exacerbation of lupus with pregnancy, postpartum,
exogenous estrogen.
Males with Kleinfelter’s syndrome develop SLE.
Hypoandrogenism is found in some males with SLE.
Associations in animal models (NZB mice)
Female mice fare worse than male mice.
Administration of estrogen to mice results in the
production of inflammatory cytokines - IL6, IL10.
Molecular observations
Estrogen increases the secretion of Ig in vitro.
Estradiol acts on the genome as a transcriptor factor.
16
Sex hormones and autoimmunity
The genetic link
Human MHC encodes for class I proteins, class II proteins,
complement proteins, TNF alpha, heat shock proteins – all
part of the immune system.
MHC alleles combinations are present in half of
autoimmune patients.
Specific MHC background in multiple sclerosis mice model
(EAE) is associated with specific steroid/ hormonal and
complement loci.
Source: Sex, MHC and C4 in autoimmune disease, Trends in Immunology, 2004
17
The dimorphic immunomodulator paradigm
Androgens
depress cellular and humoral immunity
Estrogens
enhance humoral immunity
cellular immunity
Enhancement of TH2
Amelioration of TH1
Sources: Science 1995 ● Immunopharmacol 2001 ● Ann N Y Acad Sci 2002 ●
J Immunol 2002 ● Immunol Letters 2005
18
Hyperestrogenic settings
• Pregnancy
• Exogenous intake – HRT, OCs
• Environmental exposure
•
•
•
•
•
plastics (bisphenol A, phthalates)
detergents (octylphenol)
pesticides (methoxychlor, DDT, dieldrin)
phytoestrogens
mycoestrogens – Fusarium sp.
19
Immune system in pregnancy
• “The baby is an allogeneic allograft”
• The fetus can survive and thrive by the
following mechanisms
• Anatomic separation of fetus from
its mother
• The antigenic immaturity of the fetus
• The immunologic inertness of the mother
Source: Sir Peter Medawar – Symp Soc Exp Biol, 1953
20
Immune system in pregnancy
The prevailing concept
• Activation of innate immunity resulting in
• increased phagocytosis
• increased conscription of effector cells granulocytes, monocytes, eosinophiles
• increased secretion of inflammatory
mediators
• A shift in adaptive immunity arms:
TH1 and TH2
21
Dermatoses in pregnancy
Aggravated
Ameliorated
•
•
•
•
• Psoriasis
• Sarcoidosis
• Rheumatoid arthritis
Collagen diseases
Immunoblistering
Atopic dermatitis
Neutrophilic disorders –
EN, AGEP
• Gestational special
variants: Herpes
(pemphigoid)
gestationis, impetigo
herpetiformis
22
The estrogen receptor
23
The nuclear receptor family
• Thyroid receptor (TR)
• Steroid receptors
(glucocorticoid, mineralocorticoid)
• Retinoids receptors (RARs and RXRs)
• Vitamin D receptors (VDR)
• Estrogen receptors
(ERa and ERb), androgens
• Prostaglandins
• Orphan receptors for which no ligand
has been identified
24
The nuclear receptor family
(cont.)
• Belongs to the family of nuclear receptors
/ transcription factors responsible for
biologic processes in reproduction,
cardiovascular, skeletal, immune and
neurocognitive functions
• In the skin, responsible for modulation of
keratinocyte growth and differentiation,
production of GF and ground substance
25
Identifying medical issues
through the gender lens
• Does the disease affect both men
and women?
• Were both men and women included in
the study? If not, why not?
• Is the data presented in a sex
disaggregated way?
• Do the implications of the study for
treatment differ for men and women?
26
Thank
you
27