SEBACEOUS GLANDS DISORDERS

1. SEBACEOUS GLANDS DISORDERS Prof IHAB YOUNIS

2. SEBACEOUS GLANDS

3. Found on all areas of the skin except for the palms, soles, and dorsa of the feet • They are holocrine glands, i.e., their secretion is formed by complete cell destruction • Most sebaceous glands have their ducts opening into 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, Tyson's glands of the prepuce, and free glands in the female genitalia and in the areola of nipples

5. Hormonal control • Sebaceous gland development is an early event in puberty, and the prime hormonal stimulus for this glandular development is androgen • Although the sebaceous glands are very small throughout the prepubertal period, they are large at the time of birth, probably as a result of androgen stimulation in utero, and acne may be seen in the neonatal period • Sebum production is low in children

6. 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 • In both sexes, estrogen administration decreases the size of the sebaceous glands and the production of sebum

7. Composition and function • Sebum is composed of triglycerides and free fatty acids, wax esters, squalene, and cholesterol • Sebum controls moisture loss from the epidermis. The water-holding power of cornified epithelium depends on the presence of lipids • Sebum also protects against fungal and bacterial infections of the skin due to its contents of free fatty acids. Ringworm of scalp becomes rare after puberty

8. ACNE VULGARIS

9. Etymology • The word acne comes from the Greek word "akme“ which means the highest point. It was misspelled by the 6th century author, Aëtius, into “acne”

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 adolescencebut 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 the influence of maternal hormones and when the androgen-producing portion of the adrenal gland is disproportionately large. This neonatal acne resolves spontaneously • Some degree of acne affects 95% of 16-years old boys and girls but only 20% of sufferers need medical help

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 slowly 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. Four key factors are responsible for the development of an acne lesion: 1- Comedone formation (comedogenesis) 2- Excess sebum 3- Presence & activity of Propionibacterium acnes 4- Inflammation

15. 1- 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-S -Androgen hormone receptors are present in the portion of the follicle where the comedone forms

16. - 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, because of a deficiency in sex-hormone-binding globulin (SHBG) - Most men and women with acne have normal circulating levels of androgen hormones, thus an end-organ hyperresponsiveness to androgen hormones has been hypothesized

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

18. 2- Excess sebum(seborrhea) • Excess sebum may dilute the normal epidermal lipids resulting in diminished concentrations of linoleic acid. This relative decrease in linoleic acid may be what initiates comedone formation

19. 3- P. acnes • P. acnesis a microaerophilic organism • It has not been shown to be present in microcomedo, but its presence in later lesions is almost certain • P. acnesstimulates inflammation by producing proinflammatory mediators that diffuse through the follicle wall

20. Recent studies have shown thatP. acnesbinds 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 toP. acnesmay also explain why some individuals develop inflammatory acne vulgaris while others do not

21. 4- Inflammation • Interleukin–1–alpha has been used in a tissue model to induce follicular epidermal hyperproliferation 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

22. 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

23. Toll receptors regulate the production of cytokines which contribute to the production of inflammation in acne • Toll receptors look at P.acnes as abnormal as it is not often present in follicles from subjects without acne

24. 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

25. Types: 1- Comedonal acne : -Blackheads(open comedones):result when a pore is partially blocked, allowing some of the trapped sebum , bacteria & dead keratinocytes to slowly drain to the surface. The black color is due to the presence of melanin

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

27. 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

28. 2- Mild inflammatory acne is characterized by painful inflammatory papules and comedones

29. 3- Moderate inflammatory acne has comedones,inflammatory papules, and pustules & greater numbers of lesions

30. 4- Nodular acne is characterized by comedones, inflammatory lesions, and large nodules (the term nodulocystic acne is incorrect as acne cysts are not true cysts as they are NOT lined by epithelium). Scarring is often evident

31. 5-Acne conglobata: • Characterized by large numbers of deep nodules that frequently fuse to form multiple draining sinuses on the face and trunk • It commonly heals with scarring • It may last up to the age of 50 years

32. 6- Acne fulminans: • It is an uncommon, immunologically induced, systemic disease in which the offending antigen is P. acnes • Patients are young males, who quite suddenly develop extensive inflammatory lesions, especially on the trunk • Usually associated with fever, leukocytosis, arthralgia, inflammatory bone lesions, and transient glomerulonephritis

33. 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 commonly found on the cheeks • Hypertrophic scars and keloids can occur less commonly

34. 1 Classification of Acne Severity I-Mild: < 20 comedones, or < 15 inflammatory lesions, or < 30 total lesions II-Moderate 20 to 100 comedones, or 15 to 50 inflammatory lesions, or 30 to 125 total lesions III-Severe > 5 cysts, or total comedo count > 100, or total inflammatory count > 50, or > 125 total lesions

35. Factors affecting acne

36. 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 menstruation • Possibly it is due to a change of hydration of pilosebaceous epithelium

37. 3-Sweating • Excerbation occurs in up to 15% of cases living in hot humid environment • Ductal 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

38. Histopathology

40. Comedo development starts as an expanding mass of lipid-impregnated keratinous material, resulting in thinning and ballooning-out of the follicular wall • At the same time, the sebaceous glandsbegin to atrophy and are replaced by undifferentiated epithelial cells

41. Open comedo has a patulous orifice &keratinous material arranged in a lamellar compact fashion • Closed comedo has a narrow distended orifice &keratinous material is not compact

42. The initial event appears to be escape of lipid through an edematous comedo wall, with the development of a cellular reaction in the adjacent dermis. Once completerupture has occurred, the entire contents of the comedo are extruded into the dermis • Inflammatory reaction is much greater, and giant cells are common. Withinthe inflammatory infiltrate, P. acnes may be observed free and within polymorphs • Depending upon the site and extent ofinflammation, these ruptured lesions may appear as a pustule, a nodule, oras a nodule surmounted by a pustule

43. Pustule following rupture of a sebaceous follicle. The original walls of the follicle can be seen at the follicular orifice. 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. Multinucleated giant cells are present in the inflammatory infiltrate inthe dermis

44. Treatment

45. 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

46. A-Topical treatments

47. 1-Topical retinoids They are • Comedolytic • Aanti-inflammatory • They cause epidermal differentiation and, thus, normalize follicular hyperproliferation and hyperkeratinization • They may be used alone or in combination with other acne medications • Because irritation, redness and peeling are common, they are used once daily by night and exposure time is increased gradually

48. Four generations of topical retinoids are available: -1st generation:Tretinoin (Retin-A, Acnefree 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 )

49. The use of mild, nondrying cleansers and noncomedogenic moisturizers may help reduce irritation • Alternate-day dosing may be used if irritation persists • In general, the order of irritancy increases as one progresses from the use of cream preparations to gels to the solution • Topical retinoids have been associated with sun sensitivity. Instruct patients about sun protection

50. 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