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1 Update in Acne 2».æ. æá æ «π æ» µ å..æ. π Õ ÿ «æ» µ åæ ß ÿæ â».æ. π «ÿ π π πå æ» µ å» æ πæ. å Õ Íß å ßæ ÿß Æ å «â Hormone».æ. æá æ «π æ» µ å Androgen Àâ sebu/m æ Ë Èπ æ π Èπ Androgen Á Àâ «Èπ Èß Àâ Anti-androgen À Õ Àâ Estrogen æ Ë 1 ß ÕÕ Õ πæ. µπå «µ ÿ«ÿ æ» µ å ÿã ß å À.πæ.π πæ ÿ æ» µ å ÿã ß å À ««µ ÿª ß å 1. æ ËÕ ßæ π Õß «2. æ ËÕ ß µ «3. æ ËÕ Àâ π «Ÿâ Ë â ªª ÿ µå â π «ªØ µ âõ àß È À Hormone treatment for acne - ªìπ ß Õ À ºŸâÀ ß Ë ªì𠫪 π ß (moderate) ß ÿπ ß (severe) Ë àµõ πõßµàõ µ π - «º ª µ ÕßµàÕ â àõ (endocrine acne) àπ PCOs (polycystic ovanrian syndrome), CAH (Congenital adrenal hyperplasia), Ovarian, Adrenal tumor - â à««õ Ëπ (topical retinoids, topical antimicrobial, oral antibiotic) - ªìπ ß Õ π «πºÿâà ß àõπ Àâ oral isotretinoin - â πºÿâ Ë «Hyperandrogenism Ëß Cushinoid features, increased libido, Acanthosis nigricans, Deepening of voice, Female pattern hair loss, Cliteromegaly, sudden onset acne, Hirsutism, Irreqular menses, resistant acne - Adult female acne Ëß menstrual flares - Persistant inflammatory papules/nodules in lower face/neck À endocrine evaluation Ë«ª à «ªìπ πõ ß PCOs Õ àߪ endocrinologist æ Ë µ ªÑ À Õß hormone therapy in Acne Õ µàõµâ πƒ Ï Õß androgen µàõ sebaceous gland Õ â π ÿà µà ß Ê ßπ È 1) Androgen receptor blockers (spironolactone, cyproterone acetate, drospirenone, Flutamide) 2) Adrenal androgen production blockers (glucocorticoids) 3) Ovarian androgen blocker (oral contraceptives) 4) enzyme inhibitors (5 alpha reductuse inh : Dutasteride) Ëß π ªí ÿ π ß à â â π «Dutasteride inhibite Èß type 1 type 2 5 alpha reductuse inhibitor MEDICALLink 1

2 Drug Mechanism Standard dose Side effects of action Cyproterone acetate Androgen receptor mg/d Breast tenderness, blocker day 5-14 of menstrual headache, nausea, cycle Breakthrough Androcur 25 mg bleeding, 2 mg ethinyl estradiol hepatotoxicity, (Diane) birth defects Oral contraceptive Ovarian androgen Low dose estrogen+ Menstrual (OC) blocker progestin irregularities, breast tenderness, GI welight gain Spironolactone Androgen receptor mg/d Menstrual (Aldactone) blocker irregularities, breast tenderness, hyperkalemia, hypotension, birth defects : Feminization Flutamide Androgen receptor mg/d Hepatotoxicity, (prostate cancer) blocker breast tenderness, GI, hot flashes, decreased libido, birth defects Glucocorticoids Adrenal androgen mg Adrenal suppression Late-onset CAH production blocker prednisolone at bed time Ë ƒ Ï Androgen receptor blocker µâõß «ß ËÕß birth defects : Ferminization Õß æ» Recommendation for hormonal therapy Recommendation Strength of recommendation Level of evidence OC A I Spironolactone B II Antiandrogens B II Oral steroids B II ÀÁπ«à Á ÿ π ªìπ Ëπà π Á ÿ π π ŒÕ å π «(Common OCs) OCs ª inhibit LH, FSH Àâ ovarian adrenal androgen secretion EE ß ª µÿâπ sex hormone binding globulin (SHBG) æ ËÕ ª androgen Àâ Androgen ÕÕ ƒ Ï â ß progestins ƒ Ï ªìπ antiandrogen πõ π È Á ÿ π ß à«õ º ª µ Õߪ Õπ à«ovarian cancer, Endometrial cancer colorectal cancer à«bone loss ªÑÕß π fibrocystic/benign breast disease, ªÑÕß π PID ectopic pregnancy, ÿ π ß â π «Hirsutism, perimenopausal symptoms, endometriosis ÿ π ª Õ â«estrogen progesterone «Õ ÿ π π low dose : Ethinyesteradiol (EE < 50 microgram (35/30/20) π ËÕß side effects ; thromboembolism MI πâõ «à ) À Progestogen ß ƒ Ï Èß Estrogenic, Androgenic, Anti-androgenic, Antiminerocorticoid à«â«à synthetic progestogens (progerstins) àß ªìπ 3 ÿà 1) 17-Hydroxyprogesterone (Medroxyprogestoerone Acetate, Megestrol, Chlormodinone Acetate Cyproterone Acetate Ëß ƒ Ï ªìπ Androgen receptor blocker 2)19-Nortestosterone (Norgestrel, Levonogestrel) àπ Gestodene, Desogestrel, Norgestimate ªìπ lowest intrinsic androgenic activity 3) 17 alpha-spironolactone derivative â à Drospireone ƒ Ï antiandrogen+antiminerocorticoid 2 MEDICALLink æ Ë 2 µ «Õ à ß OC Ë â «OC/ ( ) Estrogen ( ) Progesterone (mg) Yasmin/239 Ethinylesteradiol 30 Drospirenone 3 Diane-35/159 Ethinylesteradiol 35 Cyproterone acetate 2 Mercilon/120 Ethinylesteradiol 20 Desogertrel 0.13 Marvelon/57.5 Ethinylesteradiol 30 Desogestrel 0.15 Indication to add Hormonal treatment+other acne Rx - women who require conraception - Adult female with mod-severe acne - Hyperandrogenism - Seborrhea/hirsutism/Androgenetic alopecia π º µ ±å Õ ÿ π ŒÕ å π «Ëª Õ â«low dose estrogen+progestrogen Ë ƒ Ï antiandrogen àπ Ethinyl Estradiol 35/mg+Cyproterone acetate 2 mg (Diane-35), Ethinyl Estradiol 30 +Drospirenone 3 mg (Yasmin) When and how to take a pill - ºß 21 Á Àâ Ë «π Õß ª Õπ πµàõ ª π 21 Á π ÈπÀ ÿ 7 «π à«ß ËÀ ÿ ª Õπ ª Õπ π«π Ë 2-3 À ßÀ ÿ - ºß 28 Á Àâ π π 28 «π â«ë ºß ª àµâõß À ÿ «π ÿ π Õ à ßπâÕ 6 cycle π «Side effects Õß OCs â à nausea, vomiting, GI complaints, Breast tenderness, pain, enlargement and secretion, Headache, Migraine, Melasma, Fluid retention, Weight gain, Change in vaginal secretion, Changes in sexual drive/mood changes, Contact lens intolerance, Hypersensitivity reaction âõàâ â OC - cardiovascular disease, HT (> 160/100 mmhg), angina pectoris, complicated valvular heart disease - Hx. Thromboembolic disorders, major surgery with prolonged immobilization - severe obesity and/or hypercholesterolemia - smokers older than the age of 35 - known or suspected breast cancer, endometrial cancer, hepatic adenoma/carcinomas or other estrogen dependent neoplasm - abnormal uterine bleeding - pregnancy or lactation (6 weeksû postpartum) - hypersensitivity - Migraines symptoms

3 - DM with nephropathy, retinopathy, neuropathy, vascular disease - Pancreatitis/Jaundice or severe liver disease - severe Kidney disease/acute renal failure review Cancers with OCs use æ «à no significant increase in risk of breast cancer, less advanced than in non-ocs users â OCs à«antibiotics æ «à estrogen levels are unaffected by ATBs (Tetracycline, doxycycline) OC Hormonal treatment of acne - female with acne who need contraception - 2 nd line treatment moderate-severe acne - Acne with enderine abnormality, hyperandrogenism - late-onset acne - Combihation Rx à â À / «Light Heat À Acne..æ. π Õ ÿ «æ» µ åæ ß ÿæ â π ÿà moderate to server acne Ë Àâ systemic antibiotic Õ ªí À drug resistance â Àâ isotretinoin ÁÕ side effect Õ ß â âπ light and heat therapy â π «1) ÿàß ªÑ À Ë P. acnes 2) ÿàß ªÑ À Ë pilosebaceous unit 1) ÿà Ë ÿàß ªÑ À Ë P. acnes π ËÕß π à«ß proliferation phase Õß P. acnes â ß protoporphyrin IX coproporphyrin III Ëß æ ßß π ß 320 nm, 415 nm 630 nm â Appropriate light source (415,630 nm) Photo-excitation of P. acnes upregulates TGF- Porphyrins formation of anti-inflammatory+ singlet O-within Neocollagenesis Rapid+selective destruction æ Ë ª æ Õß Light therapy Photodynamic therapy : 5-ALA+Irradiation ËÕ 5-ALA ˺ «Àπ ß 5-ALA ª Õ Ÿà Ë sebaceous gland > Õß photoactive heme precursor (protoporphyrin IX) ËÕ â irradiation Ë À â ß free radical siglet oxygen P. acnes â PDT Èß P. acnes sebaceous gland ß à«π À irradiation â à â Blue light Ëß ÀÁπº Ë 1 ÕπÀ ß Blue light ƒ Ï ÈßµàÕ Inflammatory acne comedone À â pulse dye laser red light Á À⺠π «àπ π µàæ «à Photodynamic Therapy (PDT) inflammatory acne æ Ë remission «à Light therapy Õ à ß «À â IPL π «ÀÁπº ËÕ â 5-ALA à«â«2) ÿ à Ë ÿ àß ªÑ À Ë pilosebaceous unit â à infrared laser+heat, Radiofrequency π ß (light) «âõπ (heat) Àâ coagulation shrinkage Õß sebaceous gland Àâ temporary arrest of sebaceous output æ «à thermal damage to duct epithelium sebocyte À Radiofrequency Á ⺠À Õπ â infrared laser æ ß µàæ ßß π «âõπ Ë â øøñ π â photothermal energy π ÿà π Èπà ⪠πå π ËÕß bacteriostatic effects normalization of keratinization within pilosebaceous unit ૫⪠πå scar collagen remodelling Thermal coagulation of sebaceous lobule & hair follicle sebaceous gland secretion Inflamed acne ** Independent of isotretinoin use À Infrared laser æ «à - Er : Glass laser 1540 depth perpetration~400 m Ëßµ ß µ Àπàß Õß sebaceous gland Ëßπà ⺠π mm diode laser Áæ «à π «âº acne â «à Blue light À ÿª π ËÕß Õß light and heat therapy for acne âõ âõ âõ ßπ È Advantage Disadvantage - noninvasive - Costly - No downtime - Can be painful - Compliance - Dyspigmentation - Fast inflammation reduction - Vesiculation, crusting, edema - Concurrent scar and overall skin - Studies reguired texture treatment - Erythema reduction Topical therapy of acne First line - Tretinoin & related compounds - Benzoyl peroxide - Antibiotics Second line - Azelaic acid - Salicylic acid - Sulfur - comedone ertraction Third line Intralesional steroids Systemic therapy of acne First line - Tetracycline - Erythromycin Second line - Minocycline - Sulfa group - Hormones Third line - Isotretinoin MEDICALLink 3

4 Summary of acne therapy Type of acne initial therapy Maintenance therapy Mild acne Topical retinoid Success Topical retinoid (Comedones) or or Topical retinoid+bp or Topical retinoid+bp Topical antibiotic or BP alone or observation Failure Mild to moderate ance Topical retinoid+topical/ oral antibiotic (mild papules & pustuls) Topical retinoid+bp+oral antibiotic Failure Moderate to severe acne Systemic isotretinoin (severe nodulocystic) or Success Hormonal therapy (woman) æ Ë 3 Problems in treatment of acne Õ àß â ªìπ 1) Medications â à side effects, complications, Inadequate dosage drug interactions 2) Patients â à Inappropriate treatment, Fail to respond to adequated Rx, Exposed to aggravating factors, Over expectant, «ßª àπ «Ë µ «, Ÿ, ß, Dysmorphic scar À ß «À, Acne excoriee, Hyperpigmentation À ß «À Whatûs new in acne Update on pathogenesis».æ. π «ÿ π π πå æ» µ å» æ Diet and acne» æ «à Õ Ë ªìπ high alycemic index Àâ «æ Ë Èπ π ËÕß æ Ë Èπ Õß insulin æ Ë sebum production Smith â» ª Àâ low glycemic-load diet à«àâ inflammatory acne ÈπÀ Õ à æ 50% reduction in inflammatory lesion π ÿà low glycenic load ËÕ ÿà «ÿ Ëß ß 25% æ «à ºŸâªÉ«on low glycemic load diet πè Àπ ß free androgen index, æ Ë insulin sensitivity à«â«ßπ Èπ ß ß ªí Õ Ëπ Àâæ πõ low glycemic diet Ë Àâ «Èπ» Milk consumption & acne π À Õ ÿª«à æ «à à dietary effect Ë æ ßæÕ π Àâ ««Update on Acne therapy -» ª CDP/BP (1% clindamycin phosphate & 5% BP) VS Adapalene π mild to mod acne æ «à CDP/BPO Àâ earlier onset of action significantly more effective against inflamed lesion æ «à â â CDP/BPO à«adapalene æ Ë ª æ Ëß Èπ -» ª 0.1% Adapalence/2.5% BP ªìπ combination gel adapalence, BP, vehicle alone æ «à 0.1% Adapalence/2.5% BP Àâª æ «à Àâ µà µ «Ë «Ê Èß total lesion count inflammatory lesion 4 MEDICALLink æ Ë 4 - Adapalence pretreatment àõπ clindamycin» æ «à pretreatment à«æ Ë efficacy Õß clindamycin - Adapalence Maintenance» Õß Thiboutot π 253 Ë severe acne vulgaris ª æ À«à ß Adapalence gel 0.1% Vehicle gel π Maintenance therapy æ «à ÿà Ë â Adapalence significantly larger maintenance rate ËÕ ÿà «ÿ (75% VS 54%) - Tretinoin Gel Microsphere» ª À«à ß 0.04% 0.1% æ «à 0.1% inflammatory â â ß 0.04% µà À⺠â ß ß «à ß «â 0.04% - 15% Azelaic acid gel» ª 15% AZA VS 5% BP VS 1% clindamycin æ mean reduction Õß papule pustule acne ªìπ 70%, 77% 65% µ - 5% Dapsone gel» æ «à inflammatory lesion ⺠π 2 ª Àå ËÕ vehicle º inflammatory lesion Õ à ß π ß µ Ë 4 ª Àå - Zinc salts» invitro study «cytokine secretion, Toll-like receptor 2 expression by immunohistochem, IL-8 production by ELISA æ «à Zinc salts inhibit TLR 2 surface expression by Kerationcyte Ëßπà ªìπ anti-inflammatory mechanism of zinc salts in acne - 5% Topical Tea Tree Oil Gel» π π â mild-mod acne æ «à acne sevenity index Õ à ß π ËÕ venicle - CDP/Tretinoin combination gel (Clindamycin phosphate 1.2% & tretinoin 0.025%) ªìπ U.S. FDA approved for the treatment of acne vulganis æ «à ⺠àπ π

5 - Garcinia mangostana (Thai medical plant) ƒ Ï anti-oxidant, reactive oxygen species TNF-alpha production Ëß Èß pro-inflammatory cytokine production Ëßπà π â π acne vulganis â - Azithromycin V.S.Tetracylcine» ª πºÿâªé«290 Ëß ªìπ severe acne ÿà â Azithromycin 500 mg/ dayx3 days/week for 1 month π Èπ â Azithromycin 250 mg «π «âπ «πµàõõ 2 Õπ ÿ à Ë Õß Õ â Tetracycline 1 g/day for 1 month π Èπ Tetracycline 500 mg /day µàõõ 2 Õπ æ «à ÿà Ë â Azithromcycin inflammatory acne Èπ 84% 79.7% π ÿà Tetracycline - Etanercept æ case report «à severe acne â«etanercept ⺠- Treatment of resistant P.acnes æ «à Minocycline resistant P. acne â - Acne Dressing (3M Health care) ªìπ hydrocolloid dressing æ «à overall severity of acne Õ à ß π ß µ ËÕ ÿà «ÿ - Cationic antimicrobial peptides potent antimicrobial activity against P. acnes inhibit secretion Õß proinflammatory cytokines (TNF-alpha, IL-1) Õ π â «πõπ µ Acneiform dermatitis πæ. å Õ Íß å ßæ ÿß Æ å - Bacterial folliculitis Pseudofolliculitis - gram positive Eosinophilic folliculitis - gram negative Drug-induced - pseudomonas - Glucocorticoid - Fungal - Phenytoin - dermatophyte - Lithium, INH - pityrosporum - Halogenated cpd - Demodex - High dose vit B - EGFR inhibitor Demodex Õ â«folliculitis Ë â acne â Demodex Ë 2 π Demodex folliculorum (follicles) Demodex brevis (sebaceous glands) ª µ Demodex π«π < 5 per follicle (1 cm 2 ) æ Ë cheeks > nose > forehead > chin Àâ ß clinic seborrheic dermatitis-like, folliculitis, granulomatous rosacea-like «π ËÕæ > 5 demodex in 1 cm 2 à«õ ß clinical Ë«ª π«π Õß Demodex Õ à æ π å severity Õß æ Ë 5 Demodex infection : treatment - Metronidazole gel (Robaz) - oral tetracycline - Benzoyl peroxide - oral metronidazole 200 mg bid, tid - Topical antibiotic - oral Ivermectin (200 g/kg/dose) - sulfur preparation - scabiacides Pityrosporum folliculitis - Aggravating factors : warm weather, occlusion, excessive sebum production - May also develop in association with antibiotic therapy (especially tetracycline) or iatrogenic immunosuppression (eg.organ transplant recipients) - Diagnosis by - clinical presentation - KOH : demonstration of yeasts in mid-dermis - Biopsy : show round thick wall yeast cell in hair follicle (RTWY) Important factors for P folliculitis - high temperature - systemic antibiotic (* tetracycline) - high humidity - Immunosuppression - local occlusion - Diabetes mellitus - Greasy skin - Systemic corticosteroids Pityriasis versicolor management - Topical agent for 2-4 weeks - 20% Na thiosulfate - 2% sulfur oinment - 40% propylene glycol - 2.5% selenium sulfide shampoo : 5-10 minutes dailyx3 days - 2% ketoconazole shampoo: 5-10 minutes dailyx3 days - imidazole derivatives - ketoconazole cream - 1% allylamine cream/spray/gel - oral antifungals - ketoconazole (200 mg tab) 200 mg/dayx10-14 days π π 4-6 weeks for P folliculitis mg single dose - Itraconazole (100 mg cap) 200 mg/d days - fluconazole - oral griseofulvin and allylamine are not effective Drug- induced folliculitis - most common in acne-prone patient and age groups - common drugs : corticosteroids, androgenic hormones, iodides, bromides, lithium, isoniazid, anticovlsants, corticotrpin (ACTH), calcineurin inhibitors - can develop within 2 weeks of starting the offending agent, but the risk is proportional to the close and duration of therapy P. folliculitis Steroid acne Clinical Monomorphous Monomorphous Location Back, chest, - systemic steroid : back, chest upper arm, upper arm, face seldom face - Topical : area of application Corticosteroid Not relevant - mandatory Laboratory - KOH-budding RTWY - RTWY may be found Investigaton - Bx : RTWY, folliculitis - folliculitis Treatment - antifungal - antibiotic, anti-acne - antifungal **RTWY = Round thick wall yeast cell à «Õ P. folliculitis steroid folliculitis πà ªìπ same condition æ ß µà µÿâπ factor µà ß π MEDICALLink 5

6 CME (Quiz) 1). âõ àß È À âœõ å π π «A. â À «ª π ß ÿπ ß B. â à««õ Ëπ àπ topical retinoid, topical antimicrobial C. â à«oral Isotretinoin D. âõ A. âõ B. Ÿ E. Ÿ ÿ âõ 2). âõ Õß â Light and Heat therapy π «A. Non-invasive and No downtime B. Save Cost C. Fast Inflammation Reduction D. âõ A. âõ B. Ÿ E. âõ A. âõ C. Ÿ 3). πõ Ë â «âõ Ë ªìπ First Line Treatment A. Retinoic acid and related compounds B. Benzoyl Peroxide C. Topical Antibiotic D. âõ A. âõ B. Ÿ E. Ÿ ÿ âõ 4). «âõ Ë â À Maintenance Therapy A. Topical Retinoid B. Benzoyl Peroxide C. Topical Antibiotic D. âõ A. âõ B. Ÿ E. âõ A. âõ C. Ÿ 5). «âõ Ë À â «Mild to Moderate Acne A. Topical Retinoid B. Topical Retinoid+Benzoyl Peroxide C. Topical Retinoid+Topical Antibiotic D. Topical Retinoid+Benzoyl Peroxide+Oral Antibiotic E. Ÿ ÿ âõ 6 MEDICALLink

7 ( ÿ µ µ Õ π È) µõ ÿ πµ «ß Õ âõ Ÿ Àâ π æ ËÕª πå Õßµ «à π Õß πæ./æ...π ÿ... æ å... ËÕ Ÿà... Ë ª Õ «æ «...» æ å... Ë 024 ª Õπ ÿ æ π å 2553 Àâ ËÕßÀ X ( ) π àõß«à ß Ë Ÿ µâõß Ë ÿ æ ß µõ «(æ µ Õ π È) ANSWER ANSWER ANSWER A B C D E ËÕß Update in Acne Ë / À µ µõ π Õπæƒ (æ µ Õ π È) ( µõ à Õ â) ª àß µõ Õß à π Ë Õß çmedicallink-cmeé Õ æ Ë 19, 21 Õ æ 86 ππ æ «ß ß Àπ Õ µ ß ÿß æœ µàõ 6069 π «3 Õπ ß Õß àß µõ ÈßÀ ª Ë»Ÿπ å» µàõ π ËÕß Õß æ å (».πæ.) æ ËÕµ «µõ Èπ π Á µ Àâ à πµàõ ª À Àµÿ æ åºÿâµõ Ÿ µâõßõ à ßπâÕ 6 π 10 âõ â 2 Àπ૵ Ë«ß 1 ÿ 10 âõ ÿ Õ à àß µõ ß MEDICALLink 7

8 Á â«max STAMP ÿ àß Õ æ Ë 19, 21 Õ æ 86 ππ æ «ß ß Àπ Õ µ ß ÿß æœ MEDICALLink