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Abstract Background and Objectives: The flare up induced by isotretinoinduring the first two months of acne treatment is a common unwanted effect. The increased inflammatory immune response due to destruction of p. acnes bacteria is suspected. High intensity narrow band 405'-420nmlight sources, (iClear/ClearLight/Clear100)were found to be effective both in the photodestruction of p. acnes bacteria in vitro and in vivo, and in the reduction of proinflammatorycytokines in keratinocytescultures.The purpose of the current study was to examineif the exposureto a high intensity405-420nm light has an effect on the incidenceand the severityof isotretinoininduced acne flare ups. Study Design/Material and methods: 40 Patients with a severe acne received 8 sessions of blue light (iClear, CureLight Ltd.), twice a week during a month, and had a follow up visit every month for 3 months. Oral isotretinoin was prescribed to all patients (0.6mg/kg) for 8 months. The group A was treated by the blue light for four weeks prior to starting isotretinoin.The group B started blue light and isotretinoinsimultaneously. Results: Both groups (22 patients) had less flare ups than expected with full dose of isotretinoin «30%). Flare ups occured morefrequentlyand lasted longer in group A (11 patients)than in group B (11 patients). Conclusions: Acne phototherapy by high intensity narrow band 405-420nm light when associated during the first month with oral isotretinoin. is diminishing the occurrence of flare ups induced by isotretinoin. Introduction . Isotretinoin (AccutanefRoaccutane@) therapy of acne has been associated with inflammation. exacerbation, and acne fluminans [1, 2, 3; 4, 5, 6, 7]. Flare ups usually appear 3-5 weeks after commencing isotretinoin therapy. These flare ups cause a major social and psychological burden to the patients and may induce severe long lasting scarring. Severity varies from one patient to another. Young acne patients, males and patients with large white comedones prior to therapy are more susceptible to develop acne flare ups during isotretinoin therapy. It was observed that improvement occurs upon suspension of isotretinoin or reduction of the dose, and that increases in dosage aggravates inflammatory symptoms. Clark and Cunliffe [2]. studied 980 patients treated with isotretinoin. They reported a flare of acne in 59 patients. Most patients had the flares within 3-5 weeks of commencing treatment. Mean percentage increase in acne grade was 38%. Severity of flares was closely related to extent and size of non inflamed large comedones >1.5 mm present prior to treatment. Pre-existing sebaceous gland occlusion has been emphasized as a predisposing factor in several other reports [2, 8, 9]. Clark and Cunliffe hypothesize that the decreased size of the sebaceous glands caused by the Isotretinoin cause an abrupt destruction of p. acnes causing the release of large number of antigens. These antigens provoke an outstanding local inflammatory response clinically manifested as acne flare up or acne fulminans. The role of the initial dose is controversial. Some authors note aggravation at doses of 1 mg/kg/day [2, 10], but cases of acne fulminans have been reported with doses lower than 0.5 mg/kg/day [1, 11]. Karvonen et al. described seven patients with acn-efulminans induced by isotretinoin. The mean isotretinoin dose in these patients was 37 mg/day and flare up started on average 7 weeks after isotretinoin was started. The initial site of acne does not appear to be a predictor of aggravation, as patients acne flared on both the trunk and face. Treatment of flares is controversial. The following have been proposed: continuation of isotretinoin alone [1, 12] or associated with systemic steroid therapy [7, 13]; reduction of the dose of isotretinoin in association with systemic steroid therapy [14, 15]; and suspensIon of isotretinoin [16] and"institution of systemic steroid therapy [4, 6,10,14] at doses of 0.5 to 1 mg/kg/day. High intensity narrow" band 405-420nm light sources, (iClear/ClearLight/Clear100) were found to be effective both in the photodestruction of p. acnes bacteria in vitro and in vivo, and in the reduction of proinflammatory cytokines in keratinocytes cultures. [17-21] The purpose of the current study was to examine if the exposure to a high intensity 405-420nm light has an effect on the incidenceand the severityof isotretinoininducedacne flare ups. Material and methods Fortypatientswere enrolledin the study.All patientswith a severeacne received8 sessionsof blue light (iClear,CureLight Ltd.), twice a week during a month,and had a follow up visit everymonth for 3 m<!>nths. Oral isotretinoinwas prescribedto all patients(O.6mg/kg)for 8 months. GroupA was treated by the blue light for four weeks previouslyto the beginingotisotretinoin. Group B started blue light and isotretinoinsimultaneously. Results Both groups (22 patients) had less flare ups than expected with full dose of isotretinoin «300;0). Flare ups occured more frequentlyand lasted longer in group A than in group B. Figures1-3. Conclusions A recently published study by Holland et al. shows a clear relationship between tendency to scarring after acne to peri follicular inflammatory process in the individual patient [22]. Acne phototherapy with high intensity violet/blue light recently gained an important place in the armamentarium of acne therapy [17-21]. It was proven to be effective as an alternat!veto antibiotic anti acne therapy and for patients that do not need, can not or are reluctant to have isotretinoin oral therapy. This study shows that acne phototherapy with violet/blue light (iClear, CureLight Ltd.) is effective in diminishing the number and severity of isotretinoin induced flare up. This is more significant when acne phototherapy is performed during the first month of oral isotretinoin treatment. It is hypothesized that violet/blue anti acne phototherapy reduces the bacterial antigen load expected 2-3 weeks after start of isotretinoin therapy and decreases the inflammato,ryprocess which is the major cause for the isotretinoin induced acne flares. This study shows that non thermal selective acne phototherapy maybe an important tool when prescribing isotretinoin for acne and may reduce the incidence and severity of the acne flare up induced by these drugs. References: [1] Choi EH and Bang D. Acne fulminans and 13-cis-retionic acid. J Dermatol 1992;19:378-83. [2] Clark SM, Cunliffe WJ. Acne flare and isotretinoin. Incidence and treatment. Br J Dermatol 1995;133(SUppl 45): 26. [3] D'incan M, Reverte M, Loriette Y, Ferrier-Lebouedec MC, Souteyrand p, Acn~ fulminans avec osteolyse aseptique SUNenue sous isotretinoine. Rev Int Pediatr 1994;252:25-Z [4] Faverge B, Attou D, Boncin M, Gratecos L. Acn~ fulminans de I'adolescent et isotr~tino.ine. Arch Pediatr 1996;3:188-9. [5] Jenkinson HA Isotretinoin-induced acne fulminans. Br J Dermatol 1992;127(Suppl 40): 62-3. [6] Joly P, Prost C, Gaudemar M, Revuz J. Acn~ fulminans d~clench~e par la prise d'isotretino.ine. Ann Dermatol Venerrn 1991;118:369-72. [7] Mantoux F, Benet L, Gorlier C, Ortonne Jp, Lacour JP. Acne fulminans triggered by isotretinoin. Ann Dermatol Venereol 1998;125(Suppl 1): 1554-5'; [8] Lehucher-Ceyrac D, Chaspoux C, Sulimovic L, Morel p, Lefrancq H. Aggravation de I'acn~ sous isotr~tinoine. Ann Dermatol Venereol 1998;125:496-9: [9] Bottomley WW, Cunliffe WJ. Severe flares of acne following isotretinoin. Acta Deerm Venereol 1993;73:74. [10] Ogylvie AU, Ghanne Y, Von Dendriesch P. Akne fulminans und generalisierts pustulloses exanthem wahrend der Behal1dlung fOr eiher akne vulgar:is mit isotretinoin. Z Hautkrank 1995;70:637-40. [11.] Katz RA, Jorgensen H, Nigra TP. Flare of cystic acne from oral isotretinoin. J Am Acad Dermatol 1983;8:132-3. [12] Blanc D, Zultak M, Wendling D. Lonchampt F. Eruptive pyogenic granuloma and acne fulminans in two sibling treated with isotretinoin. Dermatologica 1988;177:16-8. [13] Kellet JK Beck MH, Chalmers RC. Erythema nodosum and circulating immune complex in acne fulmiflans after treatment with isotretinoin. Br MedJ 1985;290:820. [14] Konrad E, Rahmel B, Rassner G. Acne fulminans bei isotretinoin-behandlung. Akt Dermatol 1991 ;17:182-3. [15] Traupe H, Von Muhlendahl E, Bramswig J, Happle R. Acne of the fulminans type following testosterone therapy in three excessively tall boys. Arch Dermatol 1988;124:414-Z [16] LasserreJ, Aquilina C. Aggravation paradoxale de I'acn~ par I'isotr~tinoine. Nouv Dermatol 1995;3:171-2. [17] Acne Phototherapy with a High-Intensity, Enhanced, Narrow-Band, Blue Light Source: an Open Study and In Vitro Investigation Kawada A, Aragane Yoshinori, Kameyama H, Sangen Y, Tezuka T, Journal of Dermatological Science, Vol. 30: 129-135,2000. [18] Stillman S, Green S, Harth Y. Shalita AR. High intensity narrow band blue light is effective in the treatment of acne vulgaris: an in vitro and in vivo study. J Eur Acad Dermatol Venereol. 2000;14(Suppl 1). . [19] Eradication of Propionibacterium Acnes by Its Endogenic prophyrins and High Intensity narrow Band 407-420nm Light, Ashkenazi H, Malik Z, Harth y, Nitzan y, FEMS immunology and medical Microbiology 1460, 2002 (1-8). [20] Effective treatment of acne vulgaris by high intensity narrow band light 405-420nm. Elman M, Slatkine M, Harth Y. Journal of Cosmetic and Laser Surgery. J Cosmet Laser Ther. 2003 Jun;5(2):111.-Z II: [21] Anti-Inflammatory Properties of Narrow Band Blue light. Shnitkind E, Yaping E. Green S, Lee W-L, Shalita A, Annual Meeting of1he Society of := Investigative Dermatology, USA, MAY, 2002. g [22] Holland DB, Jeremy AH, Roberts SG, Seukeran DC, Layton AM, Cunliffe WJ. Inflammation in acne scarring: a comparison of the respqnses in lesions ~ ~ from patientsproneand not proneto scar.Br J Dermatol. 2004 Jan;150(1):72-81. ~