Download Sebaceous-disorders-I

SEBACEOUS GLANDS
DISORDERS(PART I)
Prof
IHAB YOUNIS
SEBACEOUS GLANDS
• Found on all areas of the skin
except for the palms & soles
• Holocrine glands, i.e. secretion is
formed by cell destruction
• Ducts open in
hair follicles
(pilosebaceous
apparatus)
• Free sebaceous glands (not
associated with hair follicles) open
directly to the surface of the skin,
e.g., Meibomian glands of the
eyelids and Fordyce spots on the
lips and areola & penis
Sebum composition and function
• Composed of triglycerides and
free fatty acids, wax esters,
squalene, and cholesterol
• It controls moisture loss from
the epidermis
• Protects against fungal and
bacterial infections
• They secrete Vit E
Hormonal control
• Sebaceous gl.development is an
early event in puberty
• The prime hormonal stimulus is
androgen
• sebaceous gl.are large at
birth, probably as a result
of androgen stimulation
in utero
• Sebum production is low in
children
• Testicular androgen maintains
sebum production at a higher
level in men than women where
androgens are produced by the
adrenals and ovaries
• In women sebum production
decreases significantly after the
age of 50
ACNE VULGARIS
Etymology
• The word acne
comes from the Greek
word "akme“ which
means “Point”
• Common English: Pimples
• ‫العد الشائع‬
Etiology
Sex prevalence
• It starts earlier in girls than boys
due to earlier onset of puberty
• It is more common in males than
in females during adolescence
but more common in women than
in men during adulthood
Age prevalence
• It may be present in the first few
weeks of life when a newborn is still
under effect of maternal androgens
• Some degree of
acne affects 95%
of 16-years old
boys and girls but
only 20% of
sufferers need medicalhelp
• Adolescent acne usually begins prior to the
onset of puberty, when the adrenal gland
begins to produce and release more
androgen hormone
• Acne resolves between the age of 20-25
• As many as 80% of patients
have some degree of acne by
the age of 40 but only 1% of
males and 5% of females have
significant lesions
Genetic factors
• Acne was present in 45% of
boys with a history of affection
of one or both parents
compared to 8% of boys
without affected parents
• Acne is more common in
whites than in blacks
Pathogenesis
• Four key factors are responsible
for the development of acne:
1. Excess sebum(seborrhea)
2. Comedone formation
(comedogenesis)
3. Presence & activity of
Propionibacterium acnes
4. Inflammation
1. Excess sebum(seborrhea)
• Excess sebum may dilute the
normal epidermal lipids resulting
in diminished concentrations of
linoleic acid
• Relative decrease in linoleic acid
may be what initiates comedone
formation
2. Comedone formation
(comedogenesis)
The exact underlying cause is not
known, 3 theories exist:
i.Androgen hormones
• Comedones begin to appear around
adrenarche
• The degree of comedonal acne in
prepubertal girls correlates with
circulating levels of DHEA
• Most patients have normal levels of
androgens, thus an end-organ
hyperresponsiveness may be present
• Sebaceous activity is predominantly
dependent on androgens, thus,
abnormally high levels of sebum
secretion could result from high
overall androgen production, or
increased availability of free
androgen
ii- Changes in lipid composition(see
later)
iii- Inflammation(see later)
3.P. acnes
• P. acnes is a microaerophilic
organism
• It has not been shown to be present
in microcomedo, but its presence in
later lesions is almost certain
• The role of P. acnes in inflammation
of acne is not infective but
immunologic by binding to the toll-
like receptor (receptors that
recognize abnormal organisms)
on monocytes leading to the
production of multiple
proinflammatory cytokines,
including IL-12, IL-8, and tumor
necrosis factor
• Hypersensitivity to P. acnes
may also explain why some
individuals develop
inflammatory acne vulgaris
while others do not
4. Inflammation
• Interleukin–1–alpha has been
shown to induce follicular
epidermal hyperpro-liferation and
comedone formation
• Prior to duct rupture mediators of
inflammation diffuse though the
follicular duct into the dermis
causing a type IV (cellular)
immune response
• Later, the duct ruptures causing a
macrophage giant cell foreignbody reaction
• P.acnes is the source of antigen
to which the reaction is produced
Clinically
• Lesions are distributed over the
areas rich in sebaceous glands
• The face may be the only
involved skin surface, but the
chest, the back, and the upper
arms are often involved
Types of lesions
1. Comedonal acne
-Blackheads(open comedones):result
when a pore is partially blocked
leading to partial trapping of sebum,
bacteria & dead keratinocytes The
black color is due to
the presence of
melanin
- Whiteheads(closed
comedones):result when a pore is
completely blocked.
Whiteheads are normally quicker
in life cycle than blackheads
Sandpaper white comedones
•
•
•
•
Numerous(as many as 500)
Very small
Most often found on the forehead
Feel rough to the touch
Macrocomedones
• Greater than 1mm in diameter
• Black or white
2- Mild inflammatory acne is characterized
by painful inflammatory papules and
comedones
3- Moderate inflammatory acne
has comedones,inflammatory
papules, and pustules &
greater numbers of lesions
4. Nodular acne is characterized
by comedones, inflammatory
lesions, and large nodules.
Scarring is often evident
(the term nodulocystic acne is
incorrect as acne cysts
are not true cysts as they
are NOT lined by epithelium)
Scarring in acne
• Scarring occurs in up to 90% but socially
noticed scars occur in only 22% of cases
• Common scars are the ‘Ice picks’ scars
found on the cheeks
• Hypertrophic scars and keloids can occur
less commonly
Classification of acne
Type
Comedones
Inflamm.
lesions
Total
lesions
Cysts
Mild
<20
OR<15
OR<30
-
Moderate
20-100
Severe
>100
OR15-50 OR30-125
OR>50
OR>125
OR>5
Factors affecting acne
1-Diet
• A wealth of folklore has blamed
acne on certain foods, in particular
chocolate and pork fat, but
scientific proof is lacking
2-Premenstrual flaring
• Flare occurs in up to70% of
women 2-7 days before menses,
may be due to change of hydration
of pilosebaceous epithelium
3-Sweating
• Excerbation occurs in up to 15% of
cases living in hot humid climate,
hydration may be responsible
4-UV
• There is no scientific evidence that
sunlight improves acne
• UV radiation may enhance the
comedogenicity of sebum
5-Other factors
• Studies show conflicting results
concerning the effect of stress
and smoking on acne
Histopathology
Closed comedo has a
narrow distended orifice
&keratinous material is
not compact
Open comedo has a
patulous orifice
&keratinous material
arranged in a lamellar
compact fashion
Pustule following rupture of a sebaceous
follicle. New strands of epithelial cells
are migrating from the epidermis to
encapsulate the inflammatory mass,
making the inflammatory material appear
to be within the follicle
Nodule from a ruptured closed
comedo. In the upper portion of the
lesion there is lamellar keratinous
material from the comedo. Below
this, necrotic material is being
encapsulated by new epithelial
cells.
Treatment
• Treatment should be directed
toward the known pathogenic
factors involved in acne i.e.
follicular hyperproliferation, excess
sebum, P. acnes, and inflammation
• The grade and the severity of the
acne help in determining which of
the following treatments, alone or in
combination, is most appropriate
A-Topical treatments
1-Topical retinoids
• Comedolytic
• Aanti-inflammatory
• Normalize follicular hyperproliferation
and hyperkeratinization
• They may be used alone or in
combination with other acne
medications
• Because irritation, redness & peeling
are common, it is used once daily by
night and exposure time is increased
gradually
4 generations of topical retinoids:
-1st generation:Tretinoin (Retin-A)
0.025%, 0.05%, and 0.1%creams.
Also available as 0.01% and
0.025% gels )
-2nd generation:Isotretinoin (Isotrex
0.05% gel )
-3rd generation:Adapalene gel, 0.1%
-4th generation:Tazarotene(Zarotex
0.05% and 0.1% cream and gel )
• The use of mild, nondrying
cleansers and noncomedogenic
moisturizers may help reduce
irritation
• Alternate-day dosing may be used
if irritation persists
• Topical retinoids have been
associated with sun sensitivity.
Instruct patients about sun
protection
2-Topical antibiotics
• Mainly used for their role against
P. acnes
• They may also have antiinflammatory properties
• Topical antibiotics are not
comedolytic
• Bacterial resistance (up to 58%)
developed to many of these
agents. The development of
resistance is lessened if topical
antibiotics are used in
combination with benzoyl
peroxide
•
•
•
•
Commonly prescribed topical
antibiotics include:
Erythromycin(Acnebiotic,Acne
zincomycin)
Clindamycin (Clindasol)
They may be applied once or
twice a day
Gels and solutions may be more
irritating than creams or lotions
3- Benzoyl peroxide
(Panoxyl, Akneroxid cream and gel)
•
•
•
•
Effective against P. acnes
Resistance has not been reported
Used once or twice a day
May cause a true allergic contact
dermatitis. More often, an irritant
contact dermatitis develops
especially if used with tretinoin or
when accompanied by aggressive
washing
4-Azelaic acid(Skinoren,Azaderm
20% cream)
• It is found naturally in wheat, and it is
produced by Malassezia furfur
• It is bactericidal, keratolytic and
antiinflammatory
• The cream is applied to the area
affected once daily, then if tolerated
twice-daily after thoroughly cleansing
the skin
• Some improvement should be
seen after one month of using
azelaic acid cream. Further
improvement should occur with
maximum results after six months'
continuous use
• It helps reduce pigmentation, so
it's useful for darker skinned
patients whose acne spots leave
persistent brown marks
B- SystemicTreatment
I-Systemic Antibiotics
1-Tetracyclines
• They decrease the concentration of
free fatty acids in sebum
• They may act through direct
suppression of the number of P.
acnes, but part of its action may
also be due to its anti-inflammatory
activity
• Interactions
-Bioavailability ↓ with antacids
-Can decrease effects of oral
contraceptives increased risk
of pregnancy
-Can effects of anticoagulants
• Their use during tooth development
(last half of pregnancy through age
8 y) can cause permanent yellowbrown staining of teeth
• Tetracyclines have been reported
to inhibit skeletal growth in the fetus
A-Tetracycline HCl(Tetracid 250
mg cap)
• It is usually given initially in a dose
of 1000 mg/day(divided). The dose
is often decreased as improvement
occurs and may be continued at a
level of 250 mg/day for a minimum
of 6 months
• It should be taken on an empty
stomach to promote absorption
B- Doxymycine 100mg cap
(Vibramycine, doxymycine)
• Aappears to be more effective
than tetracycline, and drug
resistance is less likely to occur
• Dose: 50 to 100 mg twice daily
• The major disadvantage of its use
is that it can produce
photosensitivity
C- Minocycline(minocine 50 mg
tab)
• Minocycline is given in divided
dosages at a level of 100 mg/day to
200 mg/day.
• Patients on minocycline should be
monitored carefully as the drug can
cause blue-black pigmentation,
especially in the acne scars, as well
as the hard palate, alveolar ridge, and
anterior shins
2- Macrolides:
Erythromycine(erythrocine 500
tab), Azithromycin(Zithromax
250 tab,azrolid 500 tab)
• Erythromycine is the only safe
antibiotic to administer to pregnant
women or children
• Dose 1000 mg/day orally (divided)
on empty stomach
• Due to development of
erythromycin-resistance it is
wise to limit its use to those
cases where tetracyclines are
contraindicated
(pregnancy&young children)
• Azithromycin (500 mg 3 times
weekly), can give 80% clearance
in 12 weeks
3-Clindamycine
(Dalacine C,Clindacine,150 mg cap)
• Oral clindamycin has been used
in the past, but because of the
potential of pseudomembranous
colitis, it is now rarely used for
acne
4-Trimethoprimsulfamethoxazole
(Sutrim,Septazole tab)
• The potential for side effects is
great. So, they should be used only
in patients with severe acne who do
not respond to other antibiotics
• The patient must be monitored for
potential hematologic suppression
approximately monthly
II-Hormonal therapy
1-Contraceptive pills
• Two oral contraceptives are currently
FDA approved for the treatment of
acne: Cilest (norgestimate 250 µg +
ethinyl estradiol 35 µg) and
Estrostep (ethinyl estradiol 20 to 35
µg + norethindrone acetate1 mg )
• They increase SHBG, resulting in a
decrease in circulating free
testosterone
• Estrogen supresses sebaceous
gland leading to decreasing
sebum production by 25%
• Used in unresponsive cases in
young women after more
conventional regimens have failed
• Improvement occurs after 2-4
months , but relapses may occur if
treatment is discontinued
• Side effects include nausea,
vomiting, abnormal menses, weight
gain, and breast tenderness
• Rare but more serious
complications include
thrombophlebitis, pulmonary
embolism, and hypertension
2-Spironolactone
(Aldactone,25,100 mg tab)
• Blocks the binding of androgens
to androgen receptors
• Good candidates for this drug are
individuals with a premenstrual
flare-up of their acne, acne onset
after the age of 25, oily skin,
coexistent hirsutism, and acne on
chin and mandible
• Start patients on 50 to 100
mg/day taken with meals. If no
clinical response is seen in 1 to 3
months, adjust the dose up to 200
mg/day if necessary. Once
maintenance has been achieved,
try to lower the dose to the lowest
effective daily dose
• Menstrual irregularities and breast
tenderness are common side
effects
• The drug should not be used
during pregnancy, because it may
block the normal development of
male genitalia
• Serum electrolytes should be
monitored during initial institution
of therapy. Nausea, vomiting, and
anorexia are also common
3- Cyproterone acetate
(Diane:Cyproterone acetate 2mg and
Ethinylestradiol 35mcg tab)
• Blocks the androgen receptors
• Dose: 1tab/day from the first day
of menstruation for 21 days
• Then stop for 7 (a small amount
of menstrual blood is seen)
• Acne usually improves by 40-50%
by the third cycle and by 80-90%
by the ninth cycle
4- Prednisone (Hostacorten
5 mg tab)
• Useful in females with severe
unresponsive acne with adrenal
gland overproduction of androgens
• 2.5 to 7.5 mg, administered at night
• For individuals with an acute acne
flare, Prednisone can also be used
in a dose of 20 mg/day for 1 week
before an important occasion such
as a wedding
III- Isotretinoin
(Roaccutane;Netlook,
10,20,30 mg cap)
• The oral retinoid, isotretinoin, has
revolutionized the management of
severe treatment-resistant acne
• The response rate may be as high
as 90% with one to two courses and
the longevity of the remission, may
last for months to years in the great
majority of patients
Mode of action
• It causes normalization of
epidermal differentiation,
• Depresses sebum excretion by
70%,
• It is anti-inflammatory,
• and even reduces the presence of
P acnes
Six months later
• Indications for treatment with isotretinoin
include:
1-Less than 50% improvement after 6
months of oral and topical therapy
2- scarring
3-Associated psychological distress
4-Acne that relapses quickly once
conventional therapy is discontinued
Indications
1-Less than 50% improvement after
6 months of oral and topical therapy
2- scarring
3-Associated psychological distress
4-Acne that relapses quickly once
conventional therapy is discontinued
• The initial dose is 0.5 to 1.0 mg/kg
of the patient's body weight
• For the first month, a patient may
be started at 20 mg daily. This
allows for monitoring of any adverse
effects
• The daily dose may be increased
each month by an additional 20 mg
to a dose of approx.1 mg/kg
• Because back and chest lesions
respond less, dosages as high as
2 mg/kg per day may be necessary
• Absorption is enhanced by taking it
with meals
• Severe acne will often develop
marked flares when isotretinoin is
started. Therefore, the initial dosing
should be low, even below 0.5
mg/kg per day
• These patients often need pretreatment for 1 to 2 weeks with
prednisone (40 to 60 mg per day),
which may have to be continued
for the first 2 weeks of therapy
• Clinical results can be obtained with
dosages as low as 0.1 mg/kg per
day. However, with such dosages,
the incidence of relapses after
therapy is greater
• Isotretinoin is usually given for 20
weeks, but the length of the course
of treatment is not absolute; in
patients who have not shown an
adequate response, therapy can be
extended, if necessary
• Some improvement is usually seen
for 1 to 2 months after isotretinoin
is discontinued, so that total
clearing is not a necessary
endpoint for determining when to
discontinue therapy
• At least a 2-month waiting period
and preferably a 6-month period is
advised before one commits a
patient to a second course of
therapy
• In a 10-year follow-up study, 61%
of patients were free from acne
• Of those who relapsed, 23%
required a second course
• Ninety-six percent had relapsed
within 3 years of therapy
• Patients given a cumulative dose
of 120 mg/kg overall were less
likely to relapse
• Using isotretinoin during pregnancy
resulted in spontaneous abortion or
birth defects in 83% of cases
• Women who are of childbearing age
must be fully informed of the risk of
pregnancy. The patient must either
avoid sexual exposure totally or
should employ two highly effective
contraception techniques
• Contraception must be started at
least 1 month before therapy
• The patient must have a negative
serum pregnancy test at the time
when therapy is decided upon
and on the second or third day of
the next menstrual period or 11
days after the last unprotected
intercourse in a woman who is
amenorrheic
• Contraception should continue
throughout the course of
isotretinoin and for 1 month after
stopping treatment
• The pregnancy test should be
repeated monthly to maintain
patient awareness
• The drug is not mutagenic, there
is no risk to a fetus conceived by
a male who is taking isotretinoin
• Cheilitis of varying degrees is
found in almost all cases
• Other side effects that are likely to
be seen in over 50 % of patients
are dryness of mucous
membranes & skin, conjunctivitis,
and pruritus
• Less frequent side effects include
bone and joint pain; thinning of
hair; headache
• Laboratory abnormalities include
elevations in triglycerides, ESR,
platelet count, liver function tests,
and white blood cells in the urine
and decreases in RBCs, white cell
counts, and high-density lipoprotein
levels
• The elevation of triglycerides,
which is dose-related, is of
particular concern because it is
often accompanied by a decrease
in the high-density lipoprotein
levels, which may increase the
risk of coronary artery disease
• Associated mood changes and
depression have been reported
• The patient is considered at high
risk for abnormal healing and
development of excessive
granulation tissue following
procedures. Delay procedures,
such as dermabrasion,laser
resurfacing, tattoos, leg waxing
for up to a year after completion
of therapy