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Phototesting with a divergent UVB beam in the investigation of anti-inflammatory effects of topically applied substances
Linköping University, Department of Biomedicine and Surgery, Dermatology. Linköping University, Faculty of Health Sciences.
Linköping University, Department of Biomedical Engineering. Linköping University, The Institute of Technology.
Linköping University, Department of Biomedical Engineering. Linköping University, The Institute of Technology. (MINT)ORCID iD: 0000-0002-0012-7867
Linköping University, Department of Biomedicine and Surgery, Dermatology. Linköping University, Faculty of Health Sciences.
2003 (English)In: Photodermatology, Photoimmunology & Photomedicine, ISSN 0905-4383, E-ISSN 1600-0781, Vol. 19, no 4, 195-202 p.Article in journal (Refereed) Published
Abstract [en]

Background: Phototesting based on a single exposure to a divergent ultraviolet B (UVB) beam with radially decreasing UVB doses can be used to determine an individual's minimal erythema dose (MED). Laser Doppler perfusion imaging (LDPI) data can be combined with dosimetry data to produce objective dose–response plots in addition to the MED. The aim of this study was to investigate whether the divergent beam protocol could be used to demonstrate and quantify the anti-inflammatory effects of clobetasol diproprionate (Dermovate®), pharmaceutical-grade acetone and a gel vehicle, applied after skin provocation by UVB.

Method: Sixteen Caucasian subjects were illuminated with the divergent beam on three areas close together on the left side of their upper backs. Two of the provoked areas on each subject were treated with acetone, gel vehicle or Dermovate®, and one area was left untreated as a control. Skin blood perfusion was assessed 6 and 24 h after UVB illumination using LDPI. The reaction diameter, the mean perfusion, and the average dose–response plots for each group and treatment were extracted from the LDPI data.

Results: Application of the topical steroid clobetasol diproprionate after UVB provocation markedly decreased the inflammatory response. Acetone and the gel vehicle also showed mild anti-inflammmatory effects in two of the parameters but not for the mean perfusion response. The mean diameter differences between controls and treated reactions had predominantly positive 99% confidence intervals. Analysis of the dose–response data at doses higher than the MED showed a linear relationship (0.89≤R2≤0.98) for all reactions but with lower gradients in treated reactions, mostly marked for clobetasol diproprionate.

Conclusions:  The divergent beam protocol can be used to demonstrate and quantify the effects of topical agents on the UVB reaction, in terms of reaction diameter, mean perfusion and changes in dose–response characteristics. The dose–response approach seems to be applicable even in diagnostic testing of an individual patient's response to UVB.

Place, publisher, year, edition, pages
Wiley-Blackwell Publishing Inc., 2003. Vol. 19, no 4, 195-202 p.
Keyword [en]
acetone, anti-inflammatory effects, clobetasol diproprionate, erythema, gel vehicle, laser Doppler perfusion imaging, phototesting.
National Category
Microbiology in the medical area
Identifiers
URN: urn:nbn:se:liu:diva-12819DOI: 10.1034/j.1600-0781.2003.00037.xISI: 000184575000006Scopus ID: 2-s2.0-0042925506OAI: oai:DiVA.org:liu-12819DiVA: diva2:17120
Available from: 2007-12-05 Created: 2007-12-05 Last updated: 2017-12-14Bibliographically approved
In thesis
1. Towards a broader use of phototesting: in research, clinical practice and skin cancer prevention
Open this publication in new window or tab >>Towards a broader use of phototesting: in research, clinical practice and skin cancer prevention
2007 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

In western societies, skin cancer incidence has increased dramatically over recent decades, due predominantly to increased sun exposure habits. Ultraviolet (UV) light exposure and individual light sensitivity of the skin constitute two important factors affecting the risk for skin cancer development. Individuals with a heightened propensity to get sunburnt have a higher risk for skin malignancies, and need to protect themselves more systematically from the sun. Individual UVlight sensitivity can be determined either by self-estimation of tendency to burn and tan, as in the Fitzpatrick’s classification, or by use of a phototest. Although phototesting constitutes a considerably more objective method, it is only sparsely used, chiefly due to financial and resource related factors, and is mainly limited to investigation of photodermatoses or dose-management in photo therapy.

The general aim of this thesis was to develop and improve aspects of the phototest procedure in rder to broaden the utilisation of phototesting within the fields of research, clinical practice and skin cancer prevention. As a first step, a new phototesting technique, using a divergent UVB beam was evaluated. The principle of the method is to provoke a circular UVB-erythema in the skin, the diameter of which is related to the administered dose and thus the Minimal Erythema Dose (MED). In a test group of healthy subjects, naked eye reading by a trained observer resulted in a more exact, estimation of UVB-sensitivity, compared to traditional phototesting. Since the diffuse border of the provoked erythema was challenging for the untrained observer to read, the need for an objective, bio-engineering technique for test reading was clear. In this thesis, Laser Doppler perfusion imaging (LDPI) has been used. This data also enabled an objective description of doseresponse for the reaction, an outcome not possible in traditional testing. The divergent beam method was also shown to be useful as a model for evaluation of the effect of topically applied substances.

In order to broaden the utilisation of phototests in general, a test procedure built on patient performed self-reading of skin tests (a traditional phototest and an irritant patch test) was evaluated. The reliability of these self-readings was shown to be substantial when compared to the control readings of a trained observer.

Using the self-reporting procedure, phototesting was evaluated as a tool in primary prevention of skin cancer. The study focussed on sun habits and sun protection behaviour, and also on investigating the impact of different forms of presentation of the preventive information. Results showed significantly higher impact for a personally mediated preventive message than by letterform. For individuals with heightened UV-sensitivity the performance of a phototest led to a greater tendency to adopt sun protection behaviour than for subjects with a lower UV-sensitivity, suggesting that phototesting is a useful way to improve the outcome in terms of preventive behaviours for this group of susceptible, at-risk individuals.

Divergent beam phototesting, patient-performed self-reading, and the application of phototesting in skin cancer prevention emerge as three novel, previously little investigated, aspects of phototesting, for which promising results could be demonstrated.

Abstract [sv]

Under de senaste årtiondena har insjuknandet i hudcancer ökat dramatiskt i västvärlden, detta till stor del beroende på förändrade solvanor. Exponering för solens ultravioletta strålning (UVstrålning) samt den individuella ljuskänsligheten i huden utgör två viktiga faktorer av betydelse för uppkomsten av hudcancer. Individer med ökad benägenhet att bli rödbrända i solen löper också ökad risk för hudcancer av solexponering, och behöver således vara extra noga med att skydda sig mot solen. Hur känslig man är mot solljuset kan bedömas antingen genom självskattning (klassificering enligt Fitzpatrick), eller genom att använda ett ljustest. Det sistnämnda är en betydligt mer objektiv metod, men används ändå relativt sparsamt, sannolikt ofta beroende på brist på resurser, tid eller klinisk rutin.

Det övergripande syftet med avhandlingen var att utveckla och förbättra aspekter på ljustestningsförfarandet med inriktning på att kunna bredda användningen av ljustest inom forskning, klinisk verksamhet och hudcancerprevention. Som ett första steg undersöktes och utvärderades en ny ljustestteknik, baserad på en divergent (spridd) UV-stråle. Genom att belysa huden med ett cirkulärt UV-ljusfält framkallas en cirkulär rodnad (erytem), där diametern på rodnaden står i relation till den individuella ljuskänsligheten i huden. I jämförelse med traditionell ljustestningsmetodik visade sig metoden resultera i en noggrannare uppskattning av ljuskänslighet, samt möjligheten att beskriva ett dos-responsförhållande inom det rodnade hudområdet. Eftersom kanten på den framkallade rodnaden tenderade att bli ganska diffust avgränsad framkom dock, med undantag för speciellt tränade avläsare, svårigheter att läsa av testet med enbart ögats hjälp. Av den anledningen krävdes mer objektiv, hudfysiologisk mätmetodik. I de genomförda studierna användes så kallad Laser Doppler perfusion imaging (LDPI) för detta. Förutom uppskattning av ljuskänsligheten testades den divergenta UV-strålen också som modell för skattning av anti-inflammatorisk effekt av ämnen som appliceras på huden, exempelvis cortison, och visade sig användbar för detta.

I syfte att öka förutsättningarna för bredare användning av ljustest, genomfördes en studie där försökspersonerna själva fick avläsa ett traditionellt ljustest och rapportera in testresultatet. Resultaten jämfördes med avläsningar utförda av en kunnig avläsare, och visade på god tillförlitlighet.

Slutligen, med hjälp av den beskrivna självavläsningsproceduren, undersöktes i en primärvårdspopulation, om ljustestning kan vara användbart för att förebygga hudcancer, med inriktning på att påverka individers solvanor, solskyddsbeteende och attityder gentemot solning. I studien jämfördes även olika modeller för att presentera ett preventionsbudskap, och där ett muntligt sådant, förmedlat vid ett läkarbesök, hade ett betydligt bättre genomslag än motsvarande, enbart skriftlig, information. För individer med hög ljuskänslighet bidrog ljustestet till ökat solskyddsbeteende, vilket indikerar att ljustest skulle kunna vara ett användbart verktyg i eftersträvan att förebygga hudcancer speciellt i denna grupp av individer med förhöjd hudcancerrisk.

Sammanfattningsvis utgör ljustestning med divergent UV-stråle, självavläsning av ljustest samt användning av ljustest vid hudcancerprevention tre nya, tidigare sparsamt undersökta aspekter på ljustestning, för vilka den här avhandlingen visar lovande resultat.

Place, publisher, year, edition, pages
Institutionen för klinisk och experimentell medicin, 2007
Series
Linköping University Medical Dissertations, ISSN 0345-0082 ; 1024
Keyword
Phototesting, divergent beam, skin cancer prevention, self-reading, minimal erythema dose, sun protection behaviour
National Category
Dermatology and Venereal Diseases
Identifiers
urn:nbn:se:liu:diva-10378 (URN)978-91-85895-62-5 (ISBN)
Public defence
2007-11-30, Aulan, Hälsans hus, Campus US, Linköpings universitet, Linköping, 09:00 (English)
Opponent
Supervisors
Available from: 2007-12-05 Created: 2007-12-05 Last updated: 2009-08-22
2. Single exposure phototesting and assessment of pigmented skin lesions: quantitative methods in terms of blood perfusion estimates
Open this publication in new window or tab >>Single exposure phototesting and assessment of pigmented skin lesions: quantitative methods in terms of blood perfusion estimates
2003 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

This thesis concerns the development of quantitative phototesting for the investigation of individual skin sensitivity to ultraviolet (UV) radiation, and the assessment of pigmented skin lesions (PSL) in terms of blood perfusion estimates. In both cases, laser Doppler perfusion imaging (LDPI) was used to quantify the perfusion.

The proposed phototesting method is based on a single exposure to a divergent UVB beam, which produces a continuous, radially attenuating dose field covering an area with a diameter of 4.5 cm. In order to meet the demands posed by this approach, two-dimensional dosimetry was developed, the entire dose field was adapted to the standard erythemal action spectrum for humans, and a spatially resolving technique (LDPI) was used for objective quantification of the skin response. Data analysis methods were developed, enabling the determination of minimal erythemal dose (MED) and the extraction of dose-response information. The method was evaluated on a normal material (20 subjects), proving a good reproducibility of the MED and enhanced possibilities to extract individual dose-response information. In the study of anti-inflammatory effects (16 subjects) of topically applied substances, linear curve-fitting (0.89 ≤ R2 ≤ 0.98) was shown to adequately describe the relationship between dose and response in the dose range immediately above the MED. The gradient of the derived post MED-lines was used as a measure of the response aggressiveness. The results are promising and warrant further evaluation, e.g. in the investigation of patients with suspected photodermatoses.

This thesis also presents a method for the extraction and presentation of blood perfusion data of pigmented skin lesions in conjunction with optical information on the lesions' spatial extent. The boundaries of pigmented lesions could successfully be delineated, using standard image processing steps, in the total light intensity images given by LDPI. Classical blood perfusion measures such as mean perfusion and perfusion quotients was confined to the ROI, making relevant comparison to corresponding values of neighbouring healthy tissue possible. This data analysis approach was used on a pooled group of PSL showing promising results. The method may prove to be a useful adjunct in the discriminative assessment of pigmented skin lesions.

Place, publisher, year, edition, pages
Linköping: Linköpings universitet, 2003. 68 p.
Series
Linköping Studies in Science and Technology. Dissertations, ISSN 0345-7524 ; 839
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-24502 (URN)6626 (Local ID)91-7373-722-4 (ISBN)6626 (Archive number)6626 (OAI)
Public defence
2003-09-19, Viktoriasalen, Universitetssjukhuset, Linköping, 09:15 (Swedish)
Opponent
Available from: 2009-10-07 Created: 2009-10-07 Last updated: 2013-01-02

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Falk, MagnusIlias, MichailWårdell, KarinAnderson, Chris

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Microbiology in the medical area

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