Skin Changes Skin and Mucosa

elastic฀ ibres฀ are฀ increased,฀ as฀ also฀ in฀ smokers฀ who฀ are฀ simultaneously฀ suffering฀ from฀ ฀smoking-related฀lung฀diseases.฀Cigarette฀smoking฀increases฀neutrophil฀elastase฀activity฀in฀ plasma฀ [519,฀520] ฀and฀a 1 -proteinase฀inhibitor฀is฀inactivated฀in฀the฀process฀ [521] .฀This฀imbal- ance฀is฀possibly฀not฀only฀responsible฀for฀lung฀changes฀in฀smokers,฀but฀also฀has฀implications฀ for฀the฀skin.฀In฀addition,฀tobacco฀smoke฀inhibits฀lysyl฀oxidase,฀an฀enzyme฀necessary฀for฀the฀ cross-linking฀of฀elastin฀ [522] ,฀resulting฀in฀the฀production฀of฀subfunctional฀elastin.฀Radical฀ formation฀also฀inactivates฀this฀enzyme฀and฀the฀a 1 -proteinase฀inhibitor฀ [523,฀524] .฀Only฀pass- ing฀reference฀will฀be฀made฀here฀to฀the฀fact฀that฀smokers฀have฀reduced฀plasma฀concentrations฀ of฀retinol,฀and฀a-฀and฀b-carotene฀ [525] .฀Microcirculatory฀alterations฀in฀smokers฀see฀Chap.฀6฀ are฀an฀additional฀adverse฀component. Tobacco฀ smoke฀ condensate฀ alters฀ the฀ function฀ of฀ human฀ skin฀ ibroblasts฀ and฀ affects฀ extracellular฀matric฀turnover฀in฀vitro.฀The฀biosynthesis฀of฀type฀I฀and฀III฀collagens฀is฀decreased฀ [526] ฀and฀ibroblast-mediated฀gel฀contraction฀is฀reduced฀ [527] .฀This฀effect฀appears฀in฀paral- lel฀with฀wound฀healing.฀As฀compared฀with฀non-smokers,฀the฀synthesis฀rates฀of฀type฀I฀and฀III฀ collagens฀were฀lower฀by฀18฀and฀22,฀respectively,฀while฀matrix฀metalloproteinase-8฀was฀ increased฀by฀100฀ [528] .฀Thus,฀the฀balance฀of฀extracellular฀matrix฀turnover฀in฀skin฀is฀also฀ altered,฀possibly฀leading฀to฀skin฀deterioration฀in฀the฀long฀term. According฀one฀publication฀from฀the฀early฀1990s,฀smoking฀exerts฀hardly฀any฀effect฀on฀ acne฀ vulgaris฀ [529] .฀ It฀ was฀ even฀ suspected฀ that฀ nicotine฀ or฀ some฀ other฀ constituent฀ of฀ tobacco฀smoke฀might฀display฀anti-inlammatory฀activity.฀Only฀recently฀has฀a฀published฀ study฀in฀896฀patients฀shown฀that฀acne฀prevalence฀is฀clearly฀higher฀among฀smokers฀40.8,฀ OR฀=฀2.04;฀95฀CI:฀1.40–2.99฀as฀compared฀with฀non-smokers฀25.2.฀A฀dose-฀dependent฀ correlation฀ was฀ also฀ reported฀ between฀ acne฀ severity฀ and฀ daily฀ cigarette฀ consumption฀ p฀=฀0.001฀ [530] .฀By฀contrast,฀no฀association฀has฀been฀shown฀between฀atopic฀dermatitis฀ and฀cigarette฀smoking฀OR฀=฀1.1;฀CI:฀0.65–1.86;฀p฀=฀0.8฀ [531] .

7.8.2 Psoriasis

While฀an฀association฀between฀psoriasis฀and฀smoking฀is฀controversially฀debated,฀an฀asso- ciation฀ does฀ exist฀ with฀ kidney฀ cancer฀ [532–534] .฀ The฀ authors฀ of฀ one฀ epidemiological฀ study฀from฀Norway฀have฀reported฀an฀association฀between฀psoriasis฀and฀smoking฀ [535] .฀ However,฀ as฀ with฀ all฀ epidemiological฀ studies,฀ it฀ is฀ problematic฀ to฀ separate฀ cleanly฀ the฀ chronic฀course฀of฀psoriasis฀from฀smoking฀habits฀that฀extend฀over฀a฀period฀of฀decades.฀ Case–control฀and฀cohort฀studies฀have฀shown฀that฀smoking฀is฀associated฀with฀an฀increased฀ risk฀for฀psoriasis฀OR฀=฀2.7;฀CI:฀1.44–5.42;฀2.1;฀CI:฀1.1–4.0;฀3.3;฀CI:฀1.4–7.9฀ [536–539] ฀ and฀only฀one฀study฀has฀shown฀no฀risk฀increase฀ [540] .฀Smoking฀among฀patients฀with฀pso- riasis฀is฀strongly฀associated฀with฀pustular฀lesions฀OR฀=฀10.5;฀CI:฀3.3–33.5฀ [541] .฀Since฀ the฀predisposition฀for฀psoriasis฀may฀be฀inherited,฀an฀additive฀risk฀increase฀has฀been฀dem- onstrated฀where฀psoriasis฀patients฀still฀smoke฀OR฀=฀18.8;฀CI:฀6.4–54.8฀ [542] .฀Psoriasis฀ is฀ sustained฀ by฀ smoking,฀ with฀ the฀ result฀ that฀ smoking฀ cessation฀ should฀ be฀ an฀ urgent฀฀ goal฀for฀these฀patients.฀Transdermal฀nicotine฀therapy฀has฀little฀or฀no฀effect฀on฀the฀skin฀ lesions฀ [543] .

7.8.3 Skin Tumours

The฀development฀of฀squamous฀cell฀carcinoma฀of฀the฀skin฀as฀a฀result฀of฀smoking฀has฀not฀been฀ proven.฀PPP,฀a฀condition฀associated฀with฀immunological฀changes,฀was฀found฀to฀be฀associ- ated฀with฀smoking฀in฀56฀out฀of฀59฀patients,฀all฀of฀whom฀had฀started฀smoking฀before฀the฀onset฀ of฀PPP฀ [507] . The฀development฀of฀squamous฀cell฀carcinoma฀of฀the฀skin฀in฀smokers฀is฀controversial,฀ with฀a฀causal฀relationship฀being฀supported฀by฀some฀published฀evidence฀ [544–546] ฀and฀ refuted฀elsewhere฀ [545–551] .฀The฀risk฀of฀squamous฀cell฀carcinoma฀is฀possibly฀increased฀in฀ men฀over฀the฀age฀of฀60฀years฀RR฀=฀2.01;฀CI:฀1.21–3.34,฀with฀daily฀cigarette฀consumption,฀ duration฀of฀smoking฀and฀exposure฀to฀intense฀sunlight฀being฀crucial฀for฀the฀development฀of฀ the฀condition฀ [546] .฀The฀opposite฀view฀is฀presented฀in฀a฀study฀of฀73,366฀female฀nurses:฀ basal฀cell฀carcinoma฀was฀more฀likely฀to฀develop฀in฀women฀with฀red,฀blonde฀or฀light-brown฀ hair,฀and฀very฀much฀less฀likely฀to฀occur฀in฀women฀with฀naturally฀dark-brown฀hair.฀Risk฀was฀ positively฀associated฀with฀tendency฀to฀sunburn฀as฀a฀child฀or฀adolescent฀and฀with฀the฀life- time฀number฀of฀severe฀episodes฀of฀sunburn,฀but฀not฀at฀all฀with฀cigarette฀smoking฀ [547] .฀ One฀case-control฀study฀from฀1992฀in฀88฀men฀did฀not฀ind฀evidence฀to฀support฀an฀associa- tion฀between฀smoking฀and฀the฀development฀of฀skin฀cancer฀ [548] .฀Similarly,฀no฀association฀ has฀been฀detected฀between฀cigarette฀smoking฀and฀melanoma฀ [549] ;฀however,฀smoking฀has฀ been฀linked฀with฀forms฀of฀anogenital฀skin฀cancer฀vulva,฀vagina,฀cervix,฀anus,฀penis฀ [547] .฀ The฀risk฀for฀the฀development฀of฀carcinoma฀of฀the฀penis฀is฀reported฀to฀be฀increased฀in฀ciga- rette฀ smokers฀ 10฀ cigarettesday฀ twofold฀ [552] ฀ or฀ threefold฀ 45฀ pack-years฀ [553] .฀ More฀than฀50฀of฀women฀with฀cancer฀in฀the฀anal฀region฀are฀smokers฀ [554] ,฀and฀smokers฀ have฀a฀7.7-fold฀increased฀risk฀for฀anal฀cancer฀compared฀with฀non-smokers฀ [555] .฀Cancer฀ of฀the฀vulva฀was฀detected฀when฀10–20฀cigarettesday฀were฀smoked฀for฀more฀than฀20฀years฀ [556–558] . Cancer฀of฀the฀lip฀occurs฀in฀smokers฀generally฀in฀conjunction฀with฀exposure฀to฀strong฀ sunlight฀ [559,฀560] ;฀however,฀other฀authors฀have฀found฀no฀such฀association฀ [561] .฀Heavy฀ cigarette฀smoking฀15฀pack-years฀and฀13฀other฀variables฀were฀tested฀by฀Cox฀multivariate฀ analysis฀for฀their฀ability฀to฀predict฀death฀in฀196฀patients฀with฀clinical฀Stage฀I฀melanoma.฀ Smoking฀may฀be฀regarded฀as฀an฀adverse฀prognostic฀marker฀p฀=฀0.0065,฀and฀melanoma฀ lesion฀thickness฀was฀clearly฀greater฀in฀smokers฀than฀in฀non-smokers฀ [562] .

7.8.4 Breast Cancer

Where฀they฀have฀been฀made฀at฀all,฀assessments฀of฀changes฀in฀the฀female฀breast฀in฀associa- tion฀with฀smoking฀vary฀widely.฀According฀to฀one฀Canadian฀study฀in฀women฀with฀biopsy- conirmed฀ ibroadenoma,฀ cigarette฀ smoking฀ was฀ associated฀ with฀ a฀ reduced฀ risk฀ of฀ ibroadenoma฀RR฀=฀0.66;฀CI:฀0.40–1.10.฀An฀inverse฀correlation฀was฀even฀found฀in฀as฀ much฀as฀the฀risk฀was฀slightly฀higher฀where฀smoking฀habits฀were฀lighter฀RR฀=฀0.49;฀CI:฀ 0.24–0.98฀ [563] .฀Unequivocal฀evidence฀has฀not฀been฀found฀for฀the฀development฀of฀breast฀