1. Chapter 12 Acne & Roscea

2. Sebaceous glands Most sebaceous glands develop embryologically from – Hair germs (lie in the obtuse angle between the follicle and the epidermis) – Few free glands arise from the epidermis. Multilobed Contain cells full of lipid Holocrine secretion Sebum contains mixture of: – Triglycerides – Fatty acids – Wax esters – Squalene – Cholesterol It lubricates & waterproofs skin Protects it from drying Mildly bactericidal and fungistatic. Free sebaceous glands found in: – Eyelid (meibomian glands) – MM (Fordyce spots) – Nipple – Perianal region and genitalia

3. Androgenic hormones, especially dihydrotestosterone, stimulate sebaceous gland activity. Human sebaceous glands contain – 5α-reductase – 3α- & 17α-hydroxysteroid dehydrogenase (convert weaker androgens to dihydrotestosterone) The sebaceous glands react to – Maternal androgens for a short time after birth – Then lie dormant until puberty – When a surge of androgens produces a sudden increase in sebum excretion and sets the stage for acne.

4. Acne Disorder of the pilosebaceous apparatus Characterized by – Comedones – Papules & Pustules – Nodules & Cysts – Scars Prevalence Nearly all teenagers have some acne (acne vulgaris). It affects the sexes equally (12-14 y) The peak age for severity in – Females - 16–17y – Males 17–19 y

5. Fig. 12.1 Factors causing acne

6. 1.Sebum – Sebum excretion is increased. – However, alone not cause acne – Acromegaly or Parkinson’s disease, have high sebum excretion rates but no acne 2.Hormonal – The sebaceous glands respond excessively to the normal levels of these hormones (increased target organ sensitivity). – May be caused by higher activity of 5α-reductase in sebaceous glands – Hormonal Androgens from testes, ovaries, adrenals & sebaceous glands) are the main stimulants of sebum excretion – Other hormones (thyroid hormones & GH) have minor effects too. – Never develop acne: Castrated before puberty Androgen insensitivity – 50% of females with acne have slightly raised free testosterone levels – usually because of a low level of sex hormone binding globulin.

7. 3.Poral occlusion – Genetic and environmental factors (e.g. some cosmetics) – Epithelium overgrow – Follicles then retain sebum – Inc. concentration of bacteria and free fatty acids. – Rupture (Intense inflammation & tissue damage), mediated by Oxygen free radicals Enzymes (elastase, released by WBCs). 4.Bacterial Propionibacterium acnes – It colonizes the pilosebaceous ducts – Breaks down triglycerides – Releasing free fatty acids – Produces substances chemotactic for inflammatory cells – Induces the ductal epithelium to secrete pro-inflammatory cytokines via activation of Toll-like receptor 2 (TLR2).

8. 5.Genetic – Familial in about 50% of those with acne. – High concordance of the sebum excretion rate and acne in monozygotic, but not dizygotic twins.

9. Variants of acne 1.Infantile acne: transplacental stimulation by maternal androgens. 2.Mechanical: excessive scrubbing, picking or rubbing of chin straps or a fiddle (Fig. 12.2) can rupture occluded follicles. 3.Acne associated with virilization, including clitoromegaly, 4.May be caused by an androgen-secreting tumour of the adrenals, ovaries or testes or, rarely, by congenital adrenal hyperplasia caused by mild 21- hydroxylase deficiency. 5.Acne accompanying the polycystic ovarian syndrome is caused by modestly raised circulating androgen levels. 6.Drug-induced: corticosteroids, androgenic and anabolic steroids, gonadotrophins, oral contraceptives, lithium, iodides, bromides, antituberculosis and anticonvulsant therapy can all cause an acneiform rash. 7.Tropical: Heat and humidity are responsible for this variant, which affects white people with a tendency to acne. 8.Acne due to cosmetics.

10. Fig. 12.2 Papulopustular lesions in an odd distribution. The patient played the violin (‘fiddler’s neck’).

11. Presentations - Common type Lesions are confined to the face, shoulders, upper chest and back. Seborrhoea (greasy skin) Open comedones (blackheads), because of plugging by keratin & sebum Closed comedones (whiteheads), caused by overgrowth of the follicle openings by surrounding epithelium. Inflammatory papules, nodules and cysts Conglobate (Latin globus meaning ‘ball’) – Severe form of acne with all of the above features – As well as abscesses or cysts – With intercommunicating sinuses that contain thick serosanguinous fluid or pus. On Resolution, it leaves – Depressed or hypertrophic scars – Sometimes joined by keloidal bridges. – Hyperpigmentation Psychological depression is common in persistent acne.

12. Fig. 12.3 The seborrhoea, comedones and scattered inflammatory papules of teenage acne. Fig. 12.5 Conglobate acne with inflammatory nodules, pustulocystic lesions and depressed scars.

15. Infantile acne Rare Present at or appears soon after birth. More common in males May last up to 3 years. Its morphology is like that of common acne May be the forerunner of severe acne in adolescence. Fig. 12.6 Infantile acne. Pustulocystic lesions on the checks.

16. Fulminans Acne Rare Conglobate acne is accompanied by – Fever – Joint pains – High ESR Acne associated with suppurative hidradenitis & perifolliculitis of scalp. Tropical Mainly on the trunk May be conglobate Sweat causes follicular occlusion by causing the perifollicular epidermis to swell.

17. Exogenous acne Cause or exacerbate acne Exogenous Tars Chlorinated hydrocarbons Oils & oily cosmetics. Suspicion should be raised if – Distribution is odd – Comedones predominate Fig. 12.7 A group of open comedones (blackheads) following the use of a greasy cosmetic.

18. Late onset acne Mainly in women Often limited to the chin Nodular and cystic lesions predominate. It is stubborn and persistent. Fig. 12.8 Late-onset acne in a woman. Often localized to the chin.

19. Drug-induced Suspicion should be raised when acne – Dominated by papulopustules rather than comedones – Appears suddenly in a nonteenager – Use of drug known to cause acneiform lesions. Some athletes still use anabolic steroids to enhance their performance. Polycystic ovarian syndrome Consider this in – Obese females with – Oligomenorrhoea or secondary amenorrhoea or infertility – Glucose intolerance – Dyslipidaemia – Hypertension may be other features. Fig. 12.9 Steroid-induced acne in a seriously ill patient.

20. Congenital adrenal hyperplasia Rare Hyperpigmentation Ambiguous genitalia History of salt-wasting in childhood Jewish background. Androgen-secreting tumours Rapid onset of virilization – Male-pattern balding – Hirsutism – Deepening of voice – Breast atrophy – Clitoromegaly – As well as acne

21. Course 90%: clears by the age of 23–25 y Some 5% F & 1% M still need treatment in their 30 th Investigations None are usually necessary. Cultures to exclude – Pyogenic, anaerobic infection or G-ve folliculitis. – Androgen-secreting tumour – To rule out congenital adrenal hyperplasia caused by 21- hydroxylase deficiency. Measurement of plasma testosterone, sex hormone-binding globulin, LH, FSH, dehydroepiandrosterone sulphate, androstenedione, 17- hydroxyprogesterone, urinary free cortisol Ultrasound & Ct of the ovaries and adrenals. No OCPs when these hormone levels are measured.

22. Congenital adrenal hyperplasia High levels of 17-hydroxyprogesterone Androgen secreting tumours High androgen levels Polycystic ovarian syndrome is characterized by Modestly elevated testosterone, androstenedione & dehydroepiandrosterone sulphate levels Reduced sex hormone-binding level LH : FSH ratio more than 2.5 : 1. Pelvic ultrasound may reveal multiple small ovarian cysts Some acne patients have ovarian cysts without biochemical evidence of the polycystic ovarian syndrome.

23. DDx 1.Rosacea – Affects older individuals – Comedones are absent – The papules and pustules occur only on the face – Centrofacial erythematous background. 2.Pyogenic folliculitis (excluded by culture). 3.Hidradenitis suppurativa – Associated with acne conglobata – Axillae and groin 4.Pseudofolliculitis barbae – Caused by ingrowing hairs – Occurs on the necks of men with curly facial hai – Clears up if shaving is stopped. 5.Always suspect cosmetic acne, especially in post-adolescent women with acne limited to the face.

24. Treatment Marked psychological effects. Optimistic approach is essential & regular encouragement worthwhile. Remove & treat underlying cause Local treatment is enough for most patients with comedopapular acne Although both local and systemic treatment are needed for pustulocystic scarring acne Fig. 12.10 A successful systemic treatment of acne – the picture tells its own story.

25. Local 1.Gentle cleansing with soap and water 2.Benzoyl peroxide 3.Retinoids 4.Azelaic acid 5.Topical antibiotics 6.Cosmetic camouflage Systemic 1.Oxytetracycline and tetracycline 2.Minocycline 3.Doxycycline 4.Erythromycin 5.Trimethoprim with/out sulfamethoxazole 6.Ampicillin Hormonal 1.Co-cyprindiol 2.Spironolactone 3.Isotretinoin Physical 1.Pulsed dye 585 nm laser 2.Peeling procedures and epidermabrasion 3.Cysts incised and drained 4.Triamcinolone acetonide Acne scar treatment 1.Dermabrasion 2.Lasers Skin resurfacing 3.Dermal fillers

26. Local treatment Benzoyl peroxide – Antibacterial agent is applied only at night initially – Used twice daily if does not cause too much dryness & irritation. – It is most effective for inflammatory lesions – Not affected by propionibacterial antibiotic resistance. Retinoids The vitamin A (retinol) analogues (tretinoin, isotretinoin, adapalene, tazarotene) – Normalize follicular keratinization – Down-regulate TLR2 expression – Reduce sebum production. – Especially effective against comedones. – Be warned about Skin irritation (start with small amounts) Photosensitivity – Contraindicated in Concomitant eczema Pregnant women with acne

27. Isotretinoin 0.05% is made up in a gel base Applied once or twice daily. It irritates less than tretinoin. Adapalene (0.1% or 0.3% gel) Retinoid-like drug Indicated for mild to moderate acne. Work quicker and tolerated better than tretinoin. Tazarotene (0.5% or 0.1% gel) Applied once daily More effective than tretinoin (0.1% microsponge).

28. Azelaic acid Bactericidal for P. acnes Also anti-inflammatory Inhibits comedones formation by reducing keratinocytes proliferation. Should be applied twice daily, but not used for more than 6 months. Topical antibiotics : (clindamycin, erythromycin and sulfacetamide) Antibacterial resistance of P. acnes is a growing problem, with most erythromycin-resistant strains being cross-resistant to clindamycin. Combining antibiotics with benzoyl peroxide reduces P. acnes numbers and the likelihood of resistant strains emerging The addition of zinc acetate complex to erythromycin enhances the antibiotic’s anti-inflammatory effect. Cosmetic camouflage Cover-ups scarring Obscure post-inflammatory pigmentation

29. Oxytetracycline and tetracycline 500 mg twice daily (starting dosage) Should not be used for less than 3 months It should be taken on an empty stomach – 1 h before meals – 4 h after food Because the absorption is decreased by – Milk – Antacids – Calcium – Iron – Magnesium salts The dosage should be tapered in line with clinical improvement Serious side-effects are rare  candidal vulvovaginitis may force a change to a narrower spectrum antibiotic such as erythromycin.

30. Minocycline 50 mg twice daily or 100 mg once or twice daily Now preferred by many dermatologists Much more expensive Absorption is not significantly affected by food or drink. Much more lipophilic, so probably concentrates better in the sebaceous glands. It can be effective even when oxytetracycline has failed, But can cause – Abnormalities of liver function – Lupus-like syndrome

31. Doxycycline 100 mg once or twice daily Cheaper alternative to minocycline More frequently associated with phototoxic skin reactions. Tetracyclines should not be taken in – Pregnancy – Children under 12 years They are deposited in – Growing bone – Developing teeth Causing stained teeth and dental hypoplasia. Rarely, the long-term administration of minocycline causes a greyish pigmentation, like a bruise, especially – On the faces – Over the shins

32. Erythromycin Dosage as for oxytetracycline Women who might become pregnant. Its major drawbacks are – Nausea – Widespread development of resistant Proprionibacteria. Trimethoprim is used with/out sulfamethoxazole 3 rd -line antibiotic for acne, when a tetracycline and erythromycin have not helped. WBC counts should be monitored. Ampicillin is another alternative.

33. Hormonal Co-cyprindiol Combined antiandrogen–oestrogen treatment May help persistent acne in women. These drugs are not for males. Spironolactone Blocks the androgen receptor Reduces sebum production Inadequate response: may add OCP after 3 months The usual dosage is 25–100 mg/day with food. Serum electrolytes should be checked in – Older patients – Patients with concomitant medical problems Pregnancy should be avoided as there is a risk of causing abnormalities of the fetal male genitalia.

34. Isotretinoin Oral retinoid Flares acne at first, but this effect is usually short lived Inhibits – Sebum excretion – Growth of P. acnes – Acute inflammatory processes Nodulocystic acne Given for 4–6 months only 0.5–1 mg/kg body weight/day CBC, LFTs and fasting lipid levels should be checked – Before the start of the course – 1 and 4 months after starting Adverse psychiatric events (Depression), drug should be stopped immediately Other side-effects (reversible) – Dry skin – Dry and inflamed lips and eyes – Nosebleeds – Facial erythema – Muscle aches – Hyperlipidaemia – Hair loss More serious side-effects (rare) – Changes in night-time vision – Hearing loss. Highly teratogenic, so effective contraception must be taken – 1 month before starting isotretinoin – Throughout treatment – 1 month after

35. Table 12.1 Avoidance list for patients taking isotretinoin.

36. Fig. 12.11 Acne scarring: worth treating a test area with a resurfacing laser.

38. Rosacea Cause is still unknown Usually women Affects the face of adults Peak incidence is in the 30 th & 40 th Can also be seen in the young or old. It may coexist with acne but is distinct from it.

39. Clinical course The cheeks, nose, centre of forehead and chin are most commonly affected The periorbital & perioral areas are spared 1.Intermittent flushing is followed by 2.Fixed erythema and telangiectases. 3.Discrete domed inflamed papules, papulopustules Rarely, plaques or nodules develop. Many patients have only red skin or flushing. Erythematotelangiectatic rosacea, vascular features predominate Papulopustular rosacea, inflammatory lesions are predominant.

40. Complications 1.Keratitis (serous  blindness) 2.Blepharitis 3.Conjunctivitis 4.Rhinophyma – Caused by hyperplasia of the sebaceous glands and CT – Striking complication – More common in males. 5.Lymphoedema, below the eyes & on the forehead 6.Rebound flare of pustules (potent topical steroids) – Worse than the original rosacea – When this treatment is stopped Fig. 12.13 Marked rhinophyma.

41. Fig. 12.15 The result of the prolonged use of potent topical steroids for rosacea. Note the extreme telangiectasia.

42. Fig. 12.12 Typical rosacea with papules and pustules on a background of erythema. Note the patient also has a patch of scaly seborrhoeic eczema on his brow. Rosacea, unlike acne 1.Affect old age 2.Usually symmetrical 3.No comedones or seborrhoea 4.Erythematous background 5.Papules & pustules only in the face. 6.Its course is prolonged, with exacerbations and remissions.

43. Differential diagnosis Flushing stage: 1.Menopausal symptoms 2.Carcinoid syndrome 3.Superior vena caval obstruction Erythematotelangiectatic rosacea 1.SLE 2.Photodermatitis Papulopustular rosacea 1.Acne 2.Seborrhoeic eczema 3.Perioral dermatitis Fig. 12.14 A perioral dermatitis following withdrawal of the potent topical steroid that had been wrongly used to treat seborrhoeic eczema.

44. Treatment Treatment is best directed toward the subtype Erythematotelangiectatic Sunscreens Vascular lasers Intense pulsed light sources Papulopustular rosacea – Mild: Topical 0.75% metronidazole gel 15% azelaic acid and sulfacetamide/sulphur lotions – Moderate: topical & oral antibiotics (Tetracyclines or erythromycin) – Sever: Systemic metronidazole or isotretinoin (stubborn rosacea). Rhinophymas Surgical excision Cryotherapy Electrocautery Argon or CO2 laser ablation