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

• 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

Sebum composition and function

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

• الشائع العد

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 foreign-body 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

TypeComed-

onesInflamm. lesions

Total lesions

Cysts

Mild<20 OR<15OR<30-

Moderate20-100OR15-50OR30-125-

Severe>100OR>50OR>125OR>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 anti-inflammatory 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 yellow-brown 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-Trimethoprim-sulfamethoxazole

(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 pre-treatment 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