Acne Vulgaris - Onset Acne Vulgaris • Lesions may begin as early as 8-10 years • Incidence increases steadily during adolescence MkABhtlMDMark A. Bechtel, M.D. • Girls often develop acne earlier than boys Director of Dermatology • Severe acne affects boys 10 times more The Ohio State University College of Medicine frequently than girls • Severe cystic acne may have a family history Acne Vulgaris Patients at Increased Risk for Developing Acne • A multifactorial disorder of the pilosebaceous unit • XYY chromosomal phenotype • Affects 40-50 million individuals each year in the U .S . • Polycystic ovarian syndrome • Peak incidence occurs during adolescence • Hyperandrogenism • May create self-consciousness and social • Hypercortisolism isolation • Precocious puberty • Affects 85% of young people 12-24 years of age 1 Principal Factors in the Pathogenesis of Acne Pathogenesis of Acne • The formation of the microcomedone is the • Increased sebum production initial step in development of acne • Abnormal keratinization of the follicular • The microcomedo begins in keratinized epithelium lining of the upper portion of the pilosebaceous follicule, the infundibulum. • Proliferation of propionibacterium acnes • Retention and accumulation of corneocytes • inflammation produces hyperkeratosis in the proximal infundibulum of the pilosebaceous lumen Propionibacterium acnes Acne Lesions • Gram-positive, non-motile rod, anaerobic • Non inflammatory lesions 9 Closed comedo (whitehead) • Naturally produces porphyrins (Coproporphyrin III), which fluoresces with 9 Open comedo (blackhead) a Woods light • Inflammatory lesions • Plays a role in production of lipases, 9 Papules enzymes that contribute to comedo rupture 9 Pustules and production of several proinflammatory 9 Cysts mediators. 9 Abscesses • Activates Toll-like receptor 2 (TLR2). 2 3 Neonatal Acne Infantile Acne • Occurs in more than 20% of healthy • Presents at 3-6 months of age newborns • Comedo formation more prominent • Lesions appear at about 2 weeks of age and us uall y resolve b y 3 months • Cystic acne and scarring may occur • Malassezia furfur (yeast organism) may be • Reflects hormonal imbalances intrinsic to the etiology stage of development of infant • Inflamed papules over nose and cheeks • Infant boys – elevated LH and testosterone • May improve with ketoconazole cream • Infant boys and girls – elevated DHEA Acne Fulminans • The most severe form of cystic acne • Primarily young men 13-16 years of age • Painful cysts, hemorrhagic crusts, severe scarring • Osteolytic bone lesions, fever, arthralgias, myalgias, enlarged liver-spleen • Isotretinoin, systemic and intralesional steroids, Dapsone 4 Acne Mechanica • Occurs secondary to repeated mechanical and frictional obstruction of the pilosebaceous outlet • Comedo formation results • Rubbing of helmets, chin straps, collars Acne Conglobata • Severe nodulocystic acne without systemic manifestations • Part of the follicu lar occlu sion tetrad – dissecting cellulitis of scalp, hidradenitis suppurativa, and pilonidal cysts • Isotretinoin, systemic and intralesional steroids 5 Acne Excoriée • Comedones and inflammatory papules are neurotically excoriated • Patients develop crusted erosions that scar • Many patients have an underlying psychiatric component, anxiety disorder, or obsessive-compulsive disorder • Antidepressants or psychotherapy may be beneficial. Drug-induced Acne • Anabolic steroids • Corticosteroids • Phenytoin • Lithium • Isoniazid • Iodides • Bromides • Inhibitors of epidermal growth factor receptor (EGFR) 6 Occupational Acne Chloracne • Follicle-occluding substances in the • Occupational acne caused by exposure to workplace chlorinated aromatic hydrocarbons • Cutting oils, petroleum-based products, coal tar derivatives, chlorinated aromatic hydrocarbons Basic Objectives of Acne Therapy • Reduction of sebum output • Reduction of bacterial numbers • Alteration of cell adherence • Alteration of abnormal keratinization • Reduction of inflammation 7 Management of Acne Topical Antibiotics • Topical therapies • Systemic therapies • Bacteriostatic effect on P. acnes 9 Benzoyl peroxides 9 Oral antibiotics • Anti-inflammatory effects 9 Topical antibiotics 9 Isotretinoin • Bacterial resistance may occur with monotherapy 9 Topical retinoids 9 Oral contraceptives • Topical agents include erythromycin, 9 Salicylic acid 9 Spironolactone clindamycin, sodium sulfacetamide, and sulfur 9 Azelaic acid products 9 Topical Dapsone • Preparations available as gels, solutions, 9 Combination topicals pledgets, and combined with benzoyl peroxide Combination Antibiotics Benzoyl Peroxides and Benzoyl Peroxides • Potent bactericidal effect • Decreases number of P. acnes and FFA • Benzoyl peroxides have been combined • Due to lack of bacterial resistance, should be an with erythromycin and clindamycin integral part of acne therapy • Combining benzoyl peroxide with • May decrease size and number of comedones erythromycin or clindamycin greatly • Side effect include contact sensitivity and reduces bacterial resistance to the bleaching of clothes antibiotic component • Formulations include washes, gels, soap bars, and combinations with topical antibiotics 8 Topical Retinoids Adapalene (Differin®) • May help normalize follicular keratinization • Increase epidermal cell turnover and decreases • A derivative of naphthoic acid cell cohesiveness • Receptor specific (RAR-gamma) • Inhibits formation of comedones and helps expel • Product is not degraded by sunlight and existing comedones can be applied at same time as benzoyl • Minimal risk of tetratogenicity peroxide • Caution with sunlight exposure • May be less irritating and have less • May enhance penetration of co-administered comedolytic activity than tretinoin medication into the sebaceous follicule • May have anti-inflammatory effects • Available as gel and cream Tretinoin – Retin A®, Avita® Tazarotene (Tazorac®) • First topical retinoid – all trans-retinoic acid • A synthetic acetylenic retinoid • Product is photolabile – apply at night • Receptor specific for RAR-beta and RAR • May cause a pustular flare during initial 3-4 gamma weeks • Category X – avoid in pregnancy • Most common side effects are topical irritation and increased risk of sunburn • Light stable • Available in gels, creams, solutions, and • Skin irritation most common side effect microspheres impregnated with tretinoin • Available as cream or gel 9 Azelaic Acid (Azelex®, Finacea®) Commonly used oral antibiotics in the treatment of acne • Dicarboxcylic acid derivative • Antimicrobial, anti-inflammatory, and • Tetracycline comedolyyytic activity • DliDoxycycline • May help decrease post-inflammatory hyperpigmentation • Minocycline • More effective when combined with other • Erythromycin topicals Other oral antibiotics used Oral Antibiotics in acne treatment • Suppress the growth of P. acnes • Trimethoprim-sulfamethoxazole • With decrease in P. acnes, the FFA levels fall • Trimethoprim • Cephalosporins • Interfere with local chemical and cellular inflammatory mechanisms • Ampicillin • Tetracycline, erythromycin, and • Azithromycin clindamycin inhibit neutrophil chemotaxis • Clindamycin 10 Spironolactone Isotretinoin (Accutane®, Sotret®) • Blocks binding of androgens to androgen • 13-cis retinoic acid receptors • Indicated for severe nodulocystic acne • Recalcitrant acne in adult women refractory to conventional treatment • Avoid during pregnancy due to effects on • Exact mechanism of action is not known, male genitalia but the drug does act on sebaceous glands • May cause menstrual irregularities, breast and reduces sebum production by 90% tenderness, and hyperkalemia • Reduction in P. acnes and normalization of • Combine with birth control pill follicular keratinization Side Effects of Oral Antibiotics Isotretinoin • Minocycline – pseudotumor cerebri, blue discoloration of skin and teeth, vertigo, drug • Dosing varies from 0.5 – 2.0 mg/kg/day for induced lupus, immune hepatitis 16-20 weeks • Doxycycline – photosensitivity and epigastric discomfort • Risk of relapse is reduced if cumulative • Tetracycline – GI irritation, candidal vaginitis, dose reaches 120-150 mg/kg enamel changes in patients under 10 • Approximately 40% of patients relapse • Erythromycin – GI upset, hepatotoxicity • Caution when starting in patients with • Clindamycin – pseudomembranous colitis severe inflammatory acne • Trimeth-sulfa – TEN, neutropenia, aplastic anemia, liver toxicity 11 Isotretinoin Side Effects • Teratogenic in humans – pregnancy prevention critical • Possible association with depression and suicide • Xerosis, chelitis, alopecia, dry eyes, muscle aches, epistaxis • Pseudotumor cerebri, hepatotoxicity, hypertriglyceridemia, vertebral hyperostosis 12 FDA Advisory Panel on Isotretinoin Endocrine Abnormalities and Acne-Hyperandrogenism • Suspect in female patients with severe acne, • Proposed a new risk management program hirsutism, irregular menstrual periods, and androgenetic alopecia • Previous risk management programs did • May be associated with insulin resistance and not significantly reduce pregnancies acanthosis nigricans • Initial tests (off oral contraceptives) include total and free testosterone, DHEAS, and 17- hydroxyprogesterone • If hypercortisolism is suspected, obtain a morning serum cortisol level. Isotretinoin Pregnancy Risk Abnormal Endocrine Labs Management Program (IPRMP) • Congenital adrenal hyperplasia • All interested parties have obligations 9 DHEAS levels 4000-8000 ng/ml 9 Wholesalers • Adrenal tumor 9 Pharmacy 9 DHEAS