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Acne management

• Pathogenesis • Evaluation and DDx • Treatment

รศ. พญ. เพ็ญพรรณ วัฒนไกร หน่วยโรคผิวหนัง ภาควิชาอายุศาสตร์ รพ.รามาธิบดี

่ ่ I. Non- inflamed lesions ชนิดไม่อักเสบ สิวแบงเป็น 2 ประเภทใหญๆ

• A common disease of the pilosebaceous unit (หน่วยรูขนและต่อมไขมัน) OPEN COMEDONES / BLACK HEAD CLOSED COMEDONES / WHITE HEAD Blackheads [ สิวหัวดำ , สิวเส้ียน ] Open comedone Whiteheads [สิวหัวขำว] Closed comedone

• Significant psychologic and economic impact II. Inflamed lesions ชนิดอักเสบ

• Clinically characterized by comedones, PAPULES PUSTULES papules, pustules, and scarring

Red papules [สิวอักเสบ] NODULES SIZE : > 8 mm

Treatment of Acne Acne severity • pathogenesis of acne • (mild acne) mostly comedones / papules, pustules<10 • (moderate acne) papules , pustules <10 and/or nodules < 5

• (severe acne) papules , pustules, nodules, cysts จำนวนมำก , sinus tract

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Pathogenesis of acne 4 key factors causing acne Acne Rx: Target the pathogenesis 1 Excessive sebum production

2 Follicular Hyperkeratinization 1. removing obstructions of the follicles (comedolytics) Microcomedone formation 3 Increase P. acnes 2. reducing the rate of sebum secretion, colonization (anti-androgens) Comedones 3. reducing the follicular P. acnes (antimicrobials) 4 4. anti-inflammatory agents Inflammed papules Pustules,cysts,nodules

Scarring

FOR INTERNAL USE ONLY

Mode of action of Acne therapeutic agents Global Alliance consensus on Acne Rx

Antibacterial Follicular keratinization • Retinoids: • Topical retinoids BP – Normalize follicular Topical retinoids Tretinoin (Retin-A, Retacnyl , topical/oral ATB proliferation and azelaic acid Oral StievaA) differentiation Isotretinoin (Isotrex) – Target the formation of Adapalene (Differin® ) Inh seb gl comedone function – Anti-inflammatory Anti-inflam effect Estrogen,OC action • Systemic retinoids Oral Isotretinoin IL,oral steroids – Treatment and Isotretinoin : Roaccutane, Antiandrogens: maintenance Acnotin, Sotret spironolactone ATB inh PMN

chemotaxis

FOR INTERNAL USE ONLY

Global Alliance consensus on Acne Rx Global Alliance consensus on Acne Rx

• Antibiotics: • • Adapalene–benzoyl – Minimize the use of Topical • Combination therapy: ATBs/Antimicrobials peroxide (Epiduo antibiotics (<12 weeks) – Antimicrobials + Gel®,Galderma) Benzoyl peroxide – Avoid antibiotics as retinoids • Benzoyl peroxide– monotherapy – Mild to moderate clindamycin (Duac®, Stiefel ) Clindamycin acne • Isotretinoin-erythromycin Erythromycin (Eryacne) (Isotrexin gel, Stiefel) • BPO: – Faster and better

– Has a greater and faster results in reduction Azelaic acid (Skinoren ® 20%) effect in suppressing of lesions • Benzoyl peroxide– P. acnes > topical ATBs erythromycin – No antibiotic resistance Dapsone gel • Tretinoin-clindamycin

FOR INTERNAL USE ONLY FOR INTERNAL USE ONLY

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Evaluation of acne patients

• Severe/sudden acne Drug/other precipitant • Therapy-resistant acne • Unusual clinical • Rapid relapse post isotretinoin • Signs of hyperandrogenism – severe acne Syndrome associated – sudden onset – – irregular menstrual periods Hyperandrogen – deepening of the voice Endocrine abn. – precocious puberty – increase in libido

Hyperandrogenism POLYCYSTIC OVARY SYNDROME • Anovulation • PCOS • ovarian cysts • irregular menses, • CAH obesity, androgenic alopecia, hirsutism, acne • Adrenal neoplasia • increased risk of DM endometrial • Ovarian neoplasms carcinoma – Serum total 150 to 200 ng/dL – increased LH/FSH ratio (> 2.0)

Endocrinologic Testing symptoms of hyperandrogenism

• Routine endocrinologic evaluation (e.g., for • In young children may be manifested by body androgen excess) is not indicated for the odor, axillary or pubic hair, and clitoromegaly. majority of patients with acne.

• Adult women may present with recalcitrant or • Laboratory evaluation is indicated for patients late-onset acne, infrequent menses, hirsutism, who have acne and additional signs of male or female pattern alopecia, infertility, androgen excess. acanthosis nigricans, and truncal obesity.

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Acne=disease of the DDx in acne Sebaceous gland normal flora

Malassezia spp Staph. epidermidis

Propionibacterium acnes mite Demodex

Folliculitis Differential diagnosis Bacterial Folliculitis – staphylococcal, Gram-negative, • acne vulgaris eosinophilic, Pityrosporum, Demodex

• Bacterial folliculitis commonly • Acne/acneiform eruptions due to topical or systemic due to Staphylococcus aureus drugs • Gram-negative folliculitis • Due to Pseudomonas do not have comedos • variety of acne lesions aeruginosa,Klebsiella, Enterobacter, Proteus (comedones, pustules, spp. monomorphous papules, and nodules) • Usually in acne patients receiving long-term • on the face, back, or chest antibiotic

Drug-induced folliculitis ()

• • Less often, • Anabolic steroids (danazole azathioprine, and testosterone) cyclosporine, • androgenic hormones, vitamins B1-2-12 • iodides, bromides, vitamin D2, • lithium, phenobarbital, Pityrosporum folliculitis • isoniazid PTU propylthiouracil, gram stain: oval, round yeast with budding yeast • Anticonvulsant :phenytoin • inhibitors of the epidermal growth factor receptor (EGFR)

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Drug-induced folliculitis Epidermal Growth Factor Receptor (EGFR) (acneiform eruption) Inhibitor–Associated Eruption

• corticosteroids • gefitinib, cetuximab, erlotinib, • Anabolic steroids (danazole and testosterone) EGFR inhibitors are used to Rx • androgenic hormones, advance malignancies • iodides, bromides, • Clinically : eruptive, monomorphous follicular • lithium, pustules and papules • isoniazid • the face, scalp and upper • Anticonvulsant :phenytoin trunk • inhibitors of the epidermal growth factor receptor (EGFR)

กำรรักษำสิว ACNE ACNE (โรคสิว) การรักษาโดยใช้ยา การรักษาโดยใช้ยา ยารับประทาน ยาทาเฉพาะที่ ใช้กับสิวไม่รุนแรง - ปานกลาง ยาทาเฉพาะที่ ใช้ร่วมกับยารับประทานเพื่อรักษาสิวรุนแรง การรักษาโดยวิธีทางกายภาพ ยารับประทาน การกดสิว ใช้กับสิวรุนแรงปานกลาง - รุนแรงมาก การฉีดยาสตีรอยด์ใต้หัวสิว Chemical Peeling

Topical Therapy การรักษาโดยใช้ยาทาเฉพาะที่

• all topical treatments are preventative, • Topical retinoids 0.01-0.1% • use for 6–8 weeks is required to judge their • จับและกระตุ้น nuclear retinoic acid receptors effcacy. (RARs) • The entire acne affected area is treated, not • Affects the expression of genes involved in cell just the lesions, and proliferation, differentiation, melanogenesis • Long term usage is the rule. and inflammation • comedolytic and anti-inflammatory • Maintenance Rx

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Topical Therapy

• Topical retinoids 0.01-0.1% • Benzoyl peroxide (BPO)2.5-5% • SE irritation / sun sensitivity • nonspecific bactericidal effective against P • Low concentration acnes, and • Cream VS alcohol-based gel • bacterial resistance to benzoyl peroxide has • hs / every- other- day or short contact 30 min daily not been reported • + moisturizer • Ideal for combination Rx

Topical Therapy Topical Therapy

• Benzoyl peroxide 2.5-5% • Topical antibiotics (e.g., erythromycin and • SE dryness , irritation clindamycin) • Short contact to decrease irritation • effective acne treatments. • Topical application at least 1 hour to be • use of these agents alone - associated with effective development of bacterial resistance. • resistance is lessened if topical antibiotics are used in combination with BPO

Topical Therapy-Others Topical Therapy

• Salicylic acid= lipid soluble beta-hydroxy acid, • Salicylic acid comedolytic • Azelaic acid • conc. 0.5-2% • sulfur, resorcinol, sodium sulfacetamide, • Resorcinol= antimicrobial aluminum chloride, and zinc • Sulfur= ลดการสร้าง FFA, keratolytic • OTC – Acne cream SA0.5%+R2%+sulfer4% – Postacne cream: SA0.8%+sulfer3%+calamine – Acne lotion: SA0.8%+R8%+ZnO,talc

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Topical Therapy การรักษาโดยใช้ยารับประทาน

• Azelaic acid: dicarboxylic acid • 20% cream • Antimicrobial , comedolytic, competitive inh of tyrosinase • Rx mild – mod acne with PIH

Oral antibiotics

• INDICATIONS • First line ATB : , macrolides • moderate and severe acne and treatment resistant forms of inflammatory acne. • • chest, back, truncal acne Other antibiotics, such as amoxycillin, clindamycin and • patients in whom absolute control is essential; scarring, post inflammatory hyperpigmentation. trimethoprime/sulfamethoxazole are second line treatments.

Problems with Antibiotics use in general

• P. acnes sensitive; • Vaginal candidiasis; • inexpensive; 500-1000 mg/d • Bacterial resistant strains; • dietary restriction, dairy products • gram-negative folliculitis; • tooth discoloration (under age 9); avoid during • pseudomembranous colitis (especially pregnancy; clindamycin and broad spectrum antibiotics). • photosensitivity

• 500-1000 mg/day 1 hour a.c. or 2 p.c. • Use in children >= 12 years

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Doxycycline Erythromycin

• Lipophilic: • increasing P acnes resistance; • P. acnes very sensitive; resistance rare; • gastrointestinal upset photosensitivity, • hepatotoxicity more with estolate form; • More expensive; better GI absorption • inexpensive; • avoid during pregnancy and in children • ok in pregnancy, children < 9 years of age; • 100-200mg/d pc • not first line ATB therapy in acne. • 1000 mg/d pc

Trimethoprim-Sulfamethoxazole Clindamycin

• Lipophilic; • P. acnes very sensitive; • P. acnes very sensitive; • somewhat lipophilic; • gram –ve folliculitis • pseudomembranous colitis makes it third-line • crystalluria (push fluids); drug. • FDE, hepatitis, bone marrow suppression; • Mainly used topical form, in combination+BPO • hypersensitivity reactions (erythema multiforme, SJS, toxic epidermal necrolysis).

Amoxicillin แนวทำงเพื่อลด ATB resistance

• 250 mg twice daily to 500 mg three times • Topical ATB in mild acne use with BPO/RA a day • alternative Rx and may be useful in • Oral ATB in moderate to severe acne pregnancy

• ก าหนดระยะเวลาการใช้ ATB 3-6m และประเมินผลการรักษา ใน 6-12 wk

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Hormonal Rx Oral isotretinoin

Antiandrogens: Spironolactone • Isotretinoin is a systemic retinoid that is highly effective in the treatment of severe, agents that decrease endogenous production of recalcitrant acne vulgaris androgens by ovary or adrenal gland • Oral Isotretinoin effects • oral contraceptives, 1. normalization of epidermal differentiation, • glucocorticoids, • gonadotropin-releasing hormone (GnRH) agonists 2. depresses sebum excretion by 70%, 3. anti-inflammatory, 4. reduces P acnes.

Indications oral isotretinoin Oral isotretinoin, Administration and dosage • severe acne not responding to antibiotics and • varies from 0.5 to 1 mg/kg. divided in two topical therapy. doses. • less severe forms of acne that produce scarring or excessive psychologic distress • no clinical response expected earlier than 1 to • acne that has demonstrated resistance to other 2 months from initiation of treatment , conventional systemic treatments such as oral • A flare of acne several weeks after initiation of antibiotics. treatment in 6% of patients. • acne variants: acne conglobata, • The usual duration of treatment varies with a (in combination with corticosteroids) total cumulative treatment dose of 120 to 150 • acne with gram-negative folliculitis mg/kg.

Low dose isotretinoin Oral isotretinoin

• (eg, 0.1 to 0.40 mg/kg daily, or 10 mg daily to • 40–60% of patients remain acne-free after 10 mg thrice weekly) a single course of isotretinoin. • effective and very well tolerated. • Less Remissions when patients do not • Relapse complete a cumulative dosage 1/3 of the relapsing pt need only topical Rx 2/3 oral treatments.

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Adverse effects Adverse effects

• Birth defects (pregnancy: category X) • Early epiphyseal closure – • Retinoid embryopathy is characterized by • ไม่ควรใช้ในเด็ก อายุ < 18 craniofacial, cardiovascular, central nervous system, and thymus abnormalities

• Two forms of contraception must be used, from 1 month before therapy until 1 month after

common side effects Less common SE

• pruritus, mucocutaneous SE dryness of skin eyes, lips, mouth, and nose (treatment with • hepatitis emollients), • photosensitivity (advise sun protection). • Lipid abnormalities (dietary management), • myalgia,and arthralgia (reduction of intense • psychiatric side effects, including depression, physical activity or use of analgesics) suicide ideation, and suicide controversial • SE dose-related, reversible, and respond to symptomatic therapy.

 กำรรักษำเสริม adjunctive therapy COSMETICS / SKIN CARE

• gentle skin cleansing • use moisturizers , non-comedogenic, non-acnegenic products • Avoid : oil-based , waterproof , pressed powder • Water-based, silicone-based (cyclomethicone, dimethicone), loose powder

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DIET in acne กดสิว

• ? may be link between milk, high-glycemic index • Topical foods and acne. Comedolytic 3-4 wks prior for easier extraction • ? the role of chocolate, sweets, milk, high- glycemic index foods, and fatty foods in acne requires further study

การฉีดยาใต้หัวสิว Chemical Peeling Intralesional injections • AHA, glycolic acid peels • effective in the treatment of individual acne • BHA salicylic acid peels inflammed papules, nodules. • 1-10 mg/ml, 0.05-0.25 ml/lesion • SE atrophy, hypopigmentation -TCA

Laser / Light Take home message • Acne vulgaris is a common disorder of the sebaceous glands • สิ่งที่อาจเกิดขึ้นหลังท าเลเซอร์ • characterized clinically by comedones, • pain -discomfort, erythema, edema, crusting , papules, pustules, cysts and scarring. • hyper-hypopigmentation Before • Many other acneform eruptions exist

After

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Evaluation of acne patients Acne treatment

• Hyperandrogenism • Endocrine abn. • Drug • Aim to Target the 4 pathogenic factors of acne • Unusual clinical • Folliculitis presentation – Infection • sudden acne – non-infection • Distribution • Comedones • PCOS/Rare • Monomorphous syndrome

Mode of action of Acne therapeutic agents Acne Rx the clinical severity grade Antibacterial Follicular keratinization BP topical/oral ATB Topical retinoids • extent of affected areas azelaic acid Oral isotretinoin

• types of lesions Inh seb gl function noninflammatory comedones; Anti-inflam effect Estrogen,OC inflammatory papules, pustules, nodules Oral Isotretinoin IL,oral steroids Antiandrogens: spironolactone ATB inh PMN • presence or absence of scarring and/or

chemotaxis dyspigmentation.

Acne Rx

• Topical • Systemic • retinoids and • antibiotics, • antimicrobials • oral isotretinoin, • benzoyl peroxide, • hormonal Rx in • antibiotics, females • azelaic acid

Combination therapies work better

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Acne treatment Take home message

• Begin with topical treatment whenever • With early and adequate treatment, the risk of appropriate, permanent scarring can be reduced

• systemic therapy whenever necessary, • All acne treatments work relatively slow improvement is generally after 2-3 months of Rx • limit use of antibiotics—oral or topical— whenever possible

Take home message

• Doctor’s Knowledge แนวทำงกำรดูแลรักษำโรค • Patient’s education / Patient’s compliance Acne Clinical Practice Guideline Acne

• รองศาสตราจารย์นายแพทย์นภดล นพคุณ • play an important role in the overall • ศาสตราจารย์แพทย์หญิงเพ็ญวดี ทิมพัฒนพงศ์ • รองศาสตราจารย์แพทย์หญิงวัณณศรี สินธุภัค response and outcome. • รองศาสตราจารย์แพทย์หญิงเพ็ญพรรณ วัฒนไกร • แพทย์หญิงรัศนี อัครพันธ์ • แพทย์หญิงนลินี สุทธิไพศาล • ร้อยโทหญิงแพทย์หญิงรัชยาณี คเนจร ณ อยุธยา • รองศาสตราจารย์นายแพทย์นิยม ตันติคุณ • นายแพทย์รัฐภรณ์ อึ๊งภากรณ์ • นายแพทย์วิบูลย์ โรจนวานิช • แพทย์หญิงภาวิณี ฤกษ์นิมิตร • นายแพทย์เจตน์ วิทิตสุวรรณกุล

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