痤疮全身治疗英文版.ppt
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1、ACNE: Systemic Treatment,Andreas D. Katsambas Athens - Greece,16th EADV Congress Vienna - Austria 16-20 May 2007,Acne: Treatment,Acne,There is no single anti-acne medication that acts against all four pathophysiological factors of acne. (Except Isotretinoin),Systemic Treatment, Oral Antibiotics Isot
2、retinoin Hormones,Acne: Systemic therapies and their associated activities,Oral Antibiotics,Indications Moderate to severe acne Acne resistant to topical treatment Acne covering large part of body surface,Oral Antibiotics in Acne, Suppress P. Acnes growth Minimize inflammatory mediators synthesized
3、by P. Acnes Tetra and Ery have inherent anti-inflammatory actions (decrease of chemotactic factors and neutrofils recruitment) Reduce comedogenesis by decreasing perifolicular lymphocytic infiltrate,Mode of Action,Jeremy A et al J Inv Derm. 121:20-27; 2003,Anti-microbial therapies for acne vulgaris:
4、 anti-inflammatory actions of anti-microbial drugs in their effectiveness,Antimicrobial drugs (new quinolones, macrolides, tetracyclines) exert their therapeutic effect both by bacteriocidal actions and anti-inflammatory or anti-immunological actions. Antioxidative action towards neutrophils Inhibit
5、ion of cytokine/chemokine production and adhesion molecule expression by keratinocytes Suppression of the antigen-presenting ability of Langherans cells,Murata K, Tokura Y. J UOEH. 2007; 29(1): 63-71,Oral Antibiotic for Acne,First Line: Alternatives: Tetracycline Erythromycin Doxycycline TMP/SMX Min
6、ocycline Lymecycline Azithromycin,Oral antibiotics for acne: First Line,1. A. Katsambas et al. Clinics in Derm. 22: 412-418; 2004 2. Egger SS et al. Scweiz Runsch Med Prax. 95(35: 1297-303; 2006,Oral antibiotics for acne: Alternatives,White GM. Standard oral antibiotics for acne. 14:29-57; 1999. Mod
7、ified,Sub-antimicrobial doses of Doxycyline in Moderate Acne,Dose: 20 mg bd. for several months Result: Decrease of comedones and inflammatory lesions Comment: Doxycyline inhibits matrix metalloproteinase and cytokines,Skidmore et al. Arch Derm. 139: 459; 2003,Oral Antibiotics: Poor Responders, Resi
8、stant P. Acnes Gram (-) folliculitis Very high Sebum Excretion Rate Problematic Side Effects,Causes,P. Acnes Resistance,Prevalence of P. Acnes resistance on the skin of acne patients. 10 year surveillance date: 1991 34,5% to one or more used anti-acne antibiotics 1997 55,5% to one or more used anti-
9、acne antibiotics 2000 64% to one or more used anti-acne antibiotics,Coates P, Cunliffe W et al. Br J Derm. 146 (5): 840 (2002),Propionibacteria Resistance Rates in Europe,J. Ross, I. Snelling, A Katsambas et al. Br J Derm 148: 467478 (2003),Main reason for increased P. Acnes resistance,The extensive
10、 use of topical formulations of Erythromycin and Clindamycin,Eady E et al. Dermatology 206(1): 54 (2003),P. Acnes resistance to Erythromycin,Addition of zinc salts (zinc gluconate 30mg/24h) reduces resistance of P. Acnes strains to erythromycin.,Dreno B et al. Eur J Dermatol. 15(3): 152-5; 2005,P. A
11、cnes Resistance,Erythromycin High Clindamycin .High Tetracycline Medium Doxycycline Medium Trimethoprin .Medium Resistance to Minocycline Very rare Management: Isotretinoin Minocycline,J. Ross, I. Snelling, A Katsambas et al. Br J Derm 148: 467478 (2003),Guidelines to avoid P. Acnes Resistance, Oral
12、 antibiotic should not be used as monotherapy2 Oral antibiotics should not be used for more than 4 months Antibiotics should be combined with Topical Retinoids to enhance efficacy against comedones and inflammatory lesions Topical BPO or Azelaic Acid may be added to oral antibiotics to reduce the de
13、velopment of P. Acnes resistance.,1. Thielitz H, Gollnick H. Hautarzt 56(11): 1040; 2005 2. Ochsendorf F. J Dtsch Dermatol Ges. 4(10): 828-41; 2006,Topical Retinoids (TR) and Oral Antibiotics (OA), TR increases follicular cell turnover More OA is transported into the follicular canal where P. Acnes
14、resides Increased tissue concentration of OA Reduced potential for low-concentration induced OA resistance,Katsambas A et al. Clin Derm 22:439-444; 2004,Future Combinations,A comparison of the efficacy and safety of lymecycline plus adapalen gel 0.1% vs. lymecycline plus gel vehicle in moderate infl
15、ammatory acne,Cunliffe W et al. JAAD 49(3): S218; 2003,Future Combinations,Results: Combination therapy (lymecycline 300mg/d + adapalen gel 0.1%) was faster and significantly more effective than oral lymecycline 300mg/d + vehicle in clearing both inflammatory lesions and comedones. Irritation was mi
16、lder in Lym. + vehicle but not S.S.,Cunliffe W et al. JAAD 49(3): S218; 2003,Poor Responders: Cause Gram (-) Folliculitis, Sudden onset of many pustules Sudden deterioration of acne Management: Isotretinoin (1mg/kgr) Ampicilin,Poor Responders: Cause Very High Sebum Excretion Rate (S.E.R),The excess
17、of sebum dilute the antibiotic and produce lower and ineffective concentration of the antibiotic in the pilosebaceous unit. Management: Double dose of antibiotic (Minocycline 200mg/d) (Doxycyclin 200mg/d) Isotretinoin Estrogen + Anti-androgens,Poor Responders,Cause Management Resistant P. Acnes Isot
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