The Research On The Mechanism Of Topical Occlusion And Its Application In Palmoplantar Keratoderma

Background Occlusion refers to skin covered directly or indirectly by impermeablefilms or substances such as diapers, tape, chambers, gloves, textiles garments, wounddressings, transdermal devices, etc. In addition, certain topical vehicles that contain fatsand/or polymers oils (petrolatum, paraffin, etc.) may also generate occlusive effects.Topical occlusion, because of its simplicity, is widely utilized in many kinds of clinicaldermatosis such as wound healing and chronic inflammatory dermatosis. However, skinocclusion increases stratum corneum water content and may be a dangerous factor in thedevelopment of irritant dermatitis. No consensus on the effect of occlusion has beenreached. So, the research on the mechanism of topical occlusion and its therapeuticaleffect and safety on refractory skin disease should be further investigated.Objectives We investigate skin response to short-term occlusion on normal skin ofhuman, small white mouse and try to find some significant changes that were inducedby occlusion. Because palmoplantar keratoderma is common and difficult to treat, weassess the efficacy of local occlusion with drugs based on previous therapeutic scheduleon palmoplantar keratoderma.Methods In phase1of this study, we use bioengineering instruments to investigatethe effect of occlusion by the changes of stratum corneum (SC) hydration, skin surfacepH and skin color on normal skin of32volunteers. Short-term effects of occlusion oncefor2h,4h and8h compared with the control (non-occlusion) were assessed in fourgroups using non-invasive methods. Skin physiology indexes were all detected15 minutes after removal of occlusion materials. At the same time, Confocal scanning lasermicroscope was performed to further investigate the effect of short-term occlusion onthe occluded skin.In phase2of the study, the response to occlusion on normal skin of12kunming micedivided into four groups for4h,8h,12h and24consecutive hours was compared withnon-occluded skin under the occluded site of itself respectively. Skin physiologyindexes: stratum corneum (SC) hydration and skin surface pH were also assessed bynon-invasive methods. Then histological changes were analysed by the murine skinbiopsy.In phase3of the study, palmoplantar keratoderma patients (n=30) were treated withocclusion (time=8h) each night and previous therapeutic schedule for4weeks. Aftercollecting clinical data of pre-therapy, post-treatment for2weeks and4weeks, theefficacy of the treatment was assessed.All experimental data were analyzed by SPSS16.0statistical software package.Results In phase1, occlusion of each duration induced measurable alterations inhuman skin physiology. It caused a significant increase (F=3.442, P=0.030) in SChydration and significant decrease (F=5.687, P=0.004) in skin surface pH ascompared with the control. In comparison to each other, hydration did not changeobviously along with the increasing duration of occlusion. However, skin surface pHdecreased significantly (P=0.014) as the group of8h occlusion compared with2h andbecame obviously decreased with the prolonged occlusion. No significant effectconcerning skin color of each group was existent. After oclluded for4h in human,CSLM showed that keratinocytes represented by prickle cells of the epidermis increased，intercellular space widened, image of CSLM brightened in the occluded sitescompared with the same areas of pre-occlusion and became obvious for8h occlusion.In phase2, we investigated the analogous significant changes in the same physiologyindexes above-mentioned in the murine skin after occlusion, compared with thesurrounding untreated skin of each mouse. There is a significant increase (T=-4.495, P=0.001) in SC hydration and significant decrease (T=3.045, P=0.011) in skin surfacepH as compared with the control. Murine skin biopsy at each duration showed increasedkeratinocyte size, the widened intercellular space and also became obvious with theprolonged occlusion. However, local vacuolization of keratinocyte occurred with lesssmooth skin surface and increased SC thickness in the epidermis after occlusion of24h.Vacuolization of keratinocyte was not found when occluded for12h.In phase3, acumulated scores of clinical sings and symptoms were found a significantdifference in the three study groups,2=59.51(P <0.001). The total clinical effectiverate was20%after the treatment for2weeks, compared to86.7%for4weeks, with asignificant difference between the two groups,2=26.79(P <0.001). Pruritus, burningsensation, erythema, inflammatory papule, telangiectasis and exfoliation were foundin non-occluded area with different degree in3patients. The adverse effects disappearedgradually after discontinuation of the previous treatment firstly and symptomatictreatment.Conclusion (1) Short-termed occlusion was capable of inducing increased SChydration and a decreased skin surface pH either in human or in mouse. The effect ofshort-termed occlusion on both human and mouse is similar.(2) CSLM showed somechanges in the epidermis: swelling keratinocytes, widened intercellular space in theoccluded sites and brighter images of CSLM indicated water content increased after occlusion for4h and8h became more obvious.(3) Similar epidermal morphologychanges were happened in the murine skin after short-termed occlusion compared withhuman. Local vacuolization of keratinocyte, also called vacuolar degeneration andhydropic degeneration, occurred after occlusion of24h, but was not found afteroccluded for12h. Based on the results, the time no more than12h of single occlusionwas defined.(4) The treatment of local occlusion combined with the previoustherapeutic schedule on palmoplantar keratoderma was an effective and safe therapy.