Acne_Vulgaris_ (6).pdf

Acne Vulgaris Acne is a chronic inflammatory disease of the pilosebaceous unit. Key features A multifactorial disorder of the pilosebaceous unit Significant psychologic and economic impact Clinically characterized by comedones, papules, pustules, cysts,and...

Acne Vulgaris Acne is a chronic inflammatory disease of the pilosebaceous unit. Key features A multifactorial disorder of the pilosebaceous unit Significant psychologic and economic impact Clinically characterized by comedones, papules, pustules, cysts,and potential scarring Epidemiology: Peak incidence during adolescence, Acne affects approximately 85% of young people between 12 and 24 years of age, Acne often continues to be problematic well into adulthood, 26% of women and 12% of men were still affected in their 40s. Pathogenesis: Multifactorial (1) Follicular hyperkeratinization; (2) Hormonal influences (3) Inflammation, in part mediated by P. Acnes Genetic factors: The number, size, and activity of sebaceous glands is inherited. The prevalence and severity of acne among identical twins is extremely high. Acne (including the nodulocystic variant) runs in families. (1) Follicular hyperkeratinization The microcomedo : The precursor of all clinically apparent acne lesions. It forms in the upper portion of the follicle within the the infundibulum. Corneocytes,which are normally shed into the lumen of the follicle and extruded, accumulate due to increases in both follicular keratinocyte proliferation and corneocyte cohesiveness, leading to the development of a hyperkeratotic plug. The inciting event for microcomedo formation is unknown, but data support a role for interleukin-1α (IL-1α). Acne Vulgaris 1  (2) Hormonal influences on sebum production The sebaceous gland is controlled primarily by androgens Androgens are produced both outside the pilosebaceous unit, mainly by and adrenal glands, and the gonads Locally within the sebaceous gland via the action of androgen-metabolizing enzymes such as 3β-hydroxysteroid dehydrogenase (HSD), 17β-HSD and 5α-reductase. Androgen receptors, found in the cells of the basal layer of the sebaceous gland and the outer root sheath of the hair follicle, AR are responsive to testosterone and 5α-dihydrotestosterone (DHT), the most potent androgens. DHT has a 5–10-fold greater affinity than testosterone for the androgen receptor the principal androgen mediating sebum production. Note: Acne prone skin has higher androgen receptor density and higher 5α- reductase activity. (3) Inflammation, in part mediated by P. Acnes Propionibacterium acnes and the Innate Immune System: P. acnes is a Gram-positive non-motile rod that is found deep within the sebaceous follicle. The pathogenicity of P. acnes includes the direct release of lipases, enzymes that contribute to comedo rupture, Stimulation of inflammatory cells and keratinocytes to produce proinflammatory mediators. Interactions between the skin’s innate immune system and P. acnes play an important role in acne pathogenesis. One mechanism is via Toll-like receptors (TLRs), a class of transmembrane receptors that mediates the recognition of microbial pathogens by immune cells (monocytes, macrophages,and neutrophils) as well as by keratinocytes. Through activation of the TLR2 pathway, P. Acnes stimulates the release of proinflammatory mediators such Acne Vulgaris 2  as IL-1α, IL-8, IL-12, tumor necrosis factor-α [TNF-α], and matrix metalloproteinases. IL-8 leads to neutrophil recruitment, the release of lysosomal enzymes, and subsequent disruption of the follicular epithelium. Clinical features: Acne is typically found in sites with well-developed sebaceous glands, most often the face and upper trunk. Non inflammatory AV Inflammatory AV papules, pustules, Nodules Cysts In patients with severe nodulo-cystic acne, these Closed comedones (whiteheads) are generally small (~1 mm), lesions frequently coalesce to form large, complex, inflamed plaques that can skin-colored papules with no apparent follicular opening. include sinus tracts. Open comedones (blackheads) Dilated follicular opening that is filled with an inspissated core of shed keratin. Melanin deposition and lipid oxidation within the debris may be responsible for the black color. Fate of AV: Early treatment of acne is essential for the prevention of lasting cosmetic disfigurement due to scarring. Erythema and postinflammatory hyperpigmentation often persist after resolution of inflammatory acne.. Scarring :Pitted or hypertrophic scars (most commonly on the trunk) are often sequelae of nodulocystic acne. Acne variants: Acne fulminans Acne conglobata Neonatal acne Infantile acne Acne excoriée Drug-induced acne Occupational acne Type Description, clinical picture Treatment Acne Vulgaris 3  Type Description, clinical picture Treatment - Uncommon - The most severe form of acne - Primarily affects adolescent males 13–22 years - Acute Combination of Acne fulminans onset of painful, suppurative, destructive, ulcerative nodules with hemorrhagic crusts on the face, chest and oral steroids, (AF) back. - Systemic manifestations : fever, weight loss and musculoskeletal pain. Leucocytosis, anemia and antibiotics and ESR & CRP. isotretinoin. - A severe form of nodulocystic acne but without systemic manifestations. - Part of the follicular Acne conglobata occlusion tetrad, along with: 1. Dissecting cellulitis of the scalp, 2. Hidradenitis suppurativa, and 3. Pilonidal sinus - 20% of healthy newborns - Lesions usually appear at about 2 weeks of age and generally resolve within Neonatal acne the first 3 months of life. - Small papulopustules (not comedones) arise primarily on the cheeks, forehead, eyelids and chin - An inflammatory response to Malassezia spp. Topical tretinoin - Initially presents at 3–12 months of age - Comedo formation is prominent and pitted scarring may develop Infantile acne and benzoyl - Androgen production intrinsic to this stage of development. - Usually resolves within 1–2 ys peroxide - Young women - Typical comedones and papules are systematically excoriated leaving crusted erosions Antidepressants or Acne excoriée that may scar. - Linear erosions - Anxiety, obsessive compulsive, or body dysmorphic disorder. psychotherapy Drug-induced Monomorphous eruption of inflammatory papules and pustules acne - Exposure to follicle-occluding substances in the workplace. - Offending agents include cutting oils, Occupational acne petroleum-based products, chlorinated aromatic hydrocarbons, and coal tar derivatives. - Comedones dominate the C/P Treatment 1. Topical treatment Drugs Mechanism of action Notes Topical retinoids tretinoin, 1. comedolytic: Normalizing follicular keratinization and corneocyte adapalene, tazarotene. cohesion comedonal acne 2. anti-inflammatory 1. Antimicrobial- Potent bactericidal agent that reduces P. Acnes - Microbial resistance to benzoyl peroxide Benzoyl peroxide within the follicle. - Particularly effective when used in combination has not been reported with other therapies (retinoid) 2. weakly comedolytic Acne Vulgaris 4  Drugs Mechanism of action Notes Topical antibiotics Clindamycin and - Alone/ In combination with benzoyl peroxide or a retinoid. - Formulations : Creams ,gels to solutions erythromycin - It is available as a topical 20% cream, - is a naturally occurring dicarboxylic acid found in cereal grains. - which has been shown to be effective in Inhibiting the growth of P. acnes, azelaic acid reduces inflammatory inflammatory and comedonal acne. - Azelaic acid acne. - It demonstrates comedolytic properties. - It may help to Azelaic acid is applied twice daily and its lighten postinflammatory hyperpigmentation. use is reported to have fewer local side effects than topical retinoids. 2. Oral treatment Drugs Mechanism of action Notes Antibiotics: 1. Tetracycline derivatives, doxycycline and 1. antimicrobial- Suppression of the growth of P. minocycline. 2. Macrolides acnes, reducing bacteria-mediated inflammation. 2- - Moderate to severe inflammatory acne. such as erythromycin and Intrinsic anti-inflammatory properties. azithromycin. Whe to Consider Hormonal Therapy Hyperandrogenemism, PCOS Late-onset (adult women) 1. serosuppressive - Combined oral contraceptive pills, or persistent inflammatory A (>25yo) Prominence of Hormonal therapy Anti block both ovarian & adrenal androgens pro acne at lower face, neck · Perimenstrual flare Resistant androgen 1. oral contraceptive (duction - The antiandrogen cyproterone acetate to conventional therapies Alternative to repeat pills (androgen receptor blockade). isotretinoin The standard contraceptive formulation combines: cyproterone acetate (2 mg) with ethinyl estradiol (35 or 50 mcg). Dose: 50–100 mg twice daily -Side effects Dose-related Hormonal therapy -Androgen receptor blocker -Inhibitor of 5α-reductase. Irregular menses, Breast tenderness, Headache & fatigue. Spironolactone *Risk of feminization of a male fetus Indications severe, nodulocystic acne refractory to treatment, including oral antibiotics and/or results in scarring. Dosing: initiate 0.5 mg/kg/day taken with a fatty meal, continue 1 mg/kg/day Cumulative dose of 120–150 1. Seboatrophy significantly suppress sebum mg/kg 4-5 ms Low-dose course -In moderate acne (e.g. production, up to 90%. 2. Normalizing follicular Isotretinoin 13-cis-retinoic 0.25–0.4 mg/kg/day; 6ms) Relapse rate : up to 40 % keratinization (comedolytic) 3. Inhibits P.acne growth acid Adverse effects -Mucocutaneous dryness (most common) (indirect antimicrobial). 4. Reduce inflammatory -Teratogenicity (most serious) -Elevated serum TG (25- response (anti inflammatory). 45%) &/or cholesterol levels (30%) -Elevated transaminases -Musculoskeletal system: myalgias, fatigue -↑ intracranial tension (combination with tetracyclines leads to psedotumor cerebri= benign increase in ICP) 3. Surgical Treatment -Comedo extraction -Low-concentration chemical peels; The α-hydroxy acids (including glycolic acid), salicylic acid, and trichloroacetic acid -Intralesional injection of corticosteroid Post acne scarring: -Dermabrasion, -Laser resurfacing, -Deeper chemical peels * Filler substances discrete depressed scars *Punch grafting “ice-pick” scarring *Full-thickness surgical excision larger hypertrophic or aggregated pitted scars. Acne Vulgaris 5 Acne Vulgaris 6