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SEBACEOUS GLANDS DISORDERS(PART I)

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Presentation on theme: "SEBACEOUS GLANDS DISORDERS(PART I)"— Presentation transcript:

1 SEBACEOUS GLANDS DISORDERS(PART I)
Prof IHAB YOUNIS

2 SEBACEOUS GLANDS

3 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)

4 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

5 It controls moisture loss from the epidermis
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

6 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

7 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

8 ACNE VULGARIS

9 Etymology The word acne comes from the Greek word "akme“ which
means “Point” Common English: Pimples العد الشائع

10 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

11 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

12 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

13 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

14 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

15 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

16 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

17 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

18 ii- Changes in lipid composition(see later)
iii- Inflammation(see later)

19 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

20 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

21 Hypersensitivity to P. acnes may also explain why some individuals develop inflammatory acne vulgaris while others do not

22 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

23 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

24

25 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

26 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

27 Whiteheads are normally quicker in life cycle than blackheads
- Whiteheads(closed comedones):result when a pore is completely blocked. Whiteheads are normally quicker in life cycle than blackheads

28 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

29 2- Mild inflammatory acne is characterized
by painful inflammatory papules and comedones

30 3- Moderate inflammatory acne has comedones,inflammatory papules, and pustules & greater numbers of lesions

31 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)

32 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

33 Classification of acne
Cysts Total lesions Inflamm. lesions Comed-ones Type - OR<30 OR<15 <20 Mild OR30-125 OR15-50 20-100 Moderate OR>5 OR>125 OR>50 >100 Severe

34 Factors affecting acne

35 2-Premenstrual flaring
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

36 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

37 5-Other factors Studies show conflicting results concerning the effect of stress and smoking on acne

38 Histopathology

39 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

40 Pustule following rupture of a sebaceous follicle
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.

41 Treatment

42 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

43 A-Topical treatments

44 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

45 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 )

46 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

47 2-Topical antibiotics Mainly used for their role against P. acnes
They may also have anti-inflammatory properties Topical antibiotics are not comedolytic

48 Bacterial resistance (up to 58%) developed to many of these agents
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

49 Erythromycin(Acnebiotic,Acne zincomycin) Clindamycin (Clindasol)
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

50 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

51 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

52 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

53 B- SystemicTreatment

54 I-Systemic Antibiotics

55 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

56 Interactions -Bioavailability ↓ with antacids -Can decrease effects of oral contraceptives increased risk of pregnancy -Can effects of anticoagulants

57 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

58 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

59 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

60 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

61 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

62 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

63 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

64 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

65 II-Hormonal therapy

66 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

67 Estrogen supresses sebaceous gland leading to decreasing sebum production by 25%
Used in unresponsive cases in young women after more conventional regimens have failed

68 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

69 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

70 Start patients on 50 to 100 mg/day taken with meals
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

71 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

72 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

73 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

74 III- Isotretinoin (Roaccutane;Netlook, 10,20,30 mg cap)

75 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

76 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

77 Six months later

78 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

79 Indications 2- scarring 3-Associated psychological distress
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

80 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

81 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

82 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

83 Clinical results can be obtained with dosages as low as 0
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

84 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

85 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

86 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

87 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

88 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

89 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

90 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

91 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

92 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

93 Thank you


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