Translation and Validation of the Self-Assessment Psoriasis Area Severity Index.

BACKGROUND: The self-assessment psoriasis area severity index (SAPASI) is a patient-administered psoriasis assessment tool for which we present a validated translation from English to Swedish. METHODS: Validity was evaluated in this single-centre study using the psoriasis area severity index (PASI) as the standard. Test-retest reliability was assessed using repeated SAPASI measurements. RESULTS: Significant correlations (p < 0.0001) using Spearman's correlation coefficient (r) were found between PASI and SAPASI scores (r = 0.60) for 51 participants (median baseline PASI 4.4, interquartile range [IQR]: 1.8-5.6) and repeated SAPASI measurements (r = 0.70) among 38 participants (median baseline SAPASI 4.0, IQR: 2.5-6.1). Bland-Altman plots showed generally higher SAPASI scores than PASI scores. CONCLUSION: The translated version of SAPASI is valid and reliable, although patients generally tend to overrate their disease severity compared to PASI. Keeping this limitation in mind, SAPASI has the potential of being implemented as a time- and cost-efficient assessment tool in a Scandinavian context.

Impact of Bariatric Surgery on Moderate to Severe Psoriasis: A Retrospective Nationwide Registry Study.

Studies of the effects of bariatric surgery on psoriasis are few, with conflicting results. By linking the Swedish National Register for Systemic Treatment of Psoriasis (PsoReg) with the Scandinavian Obesity Surgery Registry (SOReg), individuals with psoriasis who had undergone bariatric surgery in Sweden during 2008 to 2018 were identified, and matched with data for patients with psoriasis in PsoReg. Psoriasis Area Severity Index (PASI) and Dermatology Life Quality Index (DLQI) were compared between the groups. Altogether, 50 operated individuals (median body mass index (BMI) 38.7 kg/m2]) and 91 non-operated individuals (median BMI 33.0 kg/m2) were included. Control of disease at baseline was good in both groups. Linear mixed models showed no significant difference in psoriasis disease burden, measured as changes in mean PASI (ΔPASI) (-1.2, p = 0.43) and DLQI (ΔDLQI) (-2.2, p = 0.34). In summary, this study demonstrated no significant effect of bariatric surgery on psoriasis disease burden in patients with relatively well-controlled moderate to severe psoriasis.

Cardiorespiratory fitness in late adolescence and long-term risk of psoriasis and psoriatic arthritis among Swedish men.

BACKGROUND: Psoriasis is a chronic immune-mediated disease and psoriatic arthritis is a common coexisting condition. Cardiorespiratory fitness is the overall capacity to perform exertion exercise. Low levels of cardiorespiratory fitness are associated with negative health outcomes. Individuals with psoriasis have lower cardiorespiratory fitness compared with individuals without psoriasis. There are no previous studies exploring the association between cardiorespiratory fitness and new-onset psoriasis and psoriatic arthritis. METHODS: With the objective to investigate whether low cardiorespiratory fitness in late adolescence increases the risk for onset of psoriasis and psoriatic arthritis, a cohort of Swedish men in compulsory military service between 1968 and 2005 was created using data from the Swedish Military Service Conscription Register. Cardiorespiratory fitness, estimated by maximum capacity cycle ergometer testing at conscription, was divided into three groups: high, medium, and low. Diagnoses were obtained using the Swedish National Patient Register and cohort members were followed from conscription until an event, new-onset psoriasis or psoriatic arthritis, occurred, or at the latest until 31 December 2016. Cox regression models adjusted for confounders at conscription were used to obtain hazard ratios with 95% confidence intervals for incident psoriasis and psoriatic arthritis. RESULTS: During the follow-up period (median follow-up time 31 years, range 0-48 years), 20,679 cases of incident psoriasis and 6,133 cases of incident psoriatic arthritis were found among 1,228,562 men (mean age at baseline 18.3 years). There was a significant association between low cardiorespiratory fitness and incident psoriasis and psoriatic arthritis (hazard ratio 1.35 (95% confidence interval 1.26-1.44) and 1.44 (95% confidence interval 1.28-1.63), respectively). CONCLUSIONS: These novel findings suggest that low cardiorespiratory fitness at an early age is associated with increased risk of incident psoriasis and psoriatic arthritis among men, and highlight the importance of assessing cardiorespiratory fitness early in life.

Report on fluorescence lifetime imaging using multiphoton laser scanning microscopy targeting sentinel lymph node diagnostics.

SIGNIFICANCE: Sentinel lymph node (SLN) biopsy is an important method for metastasis staging in, e.g., patients with malignant melanoma. Tools enabling prompt histopathological analysis are expected to facilitate diagnostics; optical technologies are explored for this purpose. AIM: The objective of this exploratory study was to investigate the potential of adopting multiphoton laser scanning microscopy (MPM) together with fluorescence lifetime analysis (FLIM) for the examination of lymph node (LN) tissue ex vivo. APPROACH: Five LN tissue samples (three metastasis positive and two negative) were acquired from a biobank comprising tissues from melanoma patients. Tissues were deparaffinized and subjected to MPM-FLIM using an experimental MPM set-up equipped with a time correlated single photon counting module enabling FLIM. RESULTS: The data confirm that morphological features similar to conventional histology were observed. In addition, FLIM analysis revealed elevated morphological contrast, particularly for discriminating between metastatic cells, lymphocytes, and erythrocytes. CONCLUSIONS: Taken together, the results from this investigation show promise for adopting MPM-FLIM in the context of SLN diagnostics and encourage further translational studies on fresh tissue samples.

Multiple Primary Melanomas: A Common Occurrence in Western Sweden.

Patients diagnosed with a single primary cutaneous melanoma are at increased risk of developing multiple primary melanomas. The aim of this study is to describe the epidemiology of multiple primary melanomas (invasive and in situ) in Western Sweden. Data from the Swedish Melanoma Registry from 1990 to 2013 revealed that 898 patients (7.4%) developed 2,037 multiple primary lesions and 11,254 patients developed single lesions. The proportion of subsequent lesions that were melanoma in situ was 47%, compared with 26% of first melanomas (p < 0.0001).The median and mean time to diagnosis of a subsequent melanoma was 38 and 58 months (95% confidence interval (CI), 53-62 months). In total, 49% of subsequent melanomas were detected within 3 years. Patients and physicians should be aware of the high proportion of multiple primary melanomas in Western Sweden, especially during the first years of follow-up.

Modelling the Future: System Dynamics in the Cutaneous Malignant Melanoma Care Pathway.

Incidence rates for cutaneous malignant melanoma are increasing worldwide. Estimates of the future number of melanoma cases are important for strategic planning of the care pathway. The aim of this study was to use system dynamics modelling to evaluate the long-term effects of changes in incidence, population growth and preventive interventions. Historical data on invasive melanoma cases in Western Sweden from 1990 to 2006 were obtained. Using computer simulation software, a model estimating the accumulated number of melanoma cases for 2014 to 2023 was developed. Five future scenarios were designed: stable incidence, business-as-usual, 25% reduced patient's delay, 50% reduced doctor's delay, and a combination of the last two, called improved overall secondary prevention. After 10 years, improved overall secondary prevention would have resulted in a 42% decrease in melanomas > 4 mm and a 10% increase in melanomas ≤ 1 mm, compared with business-as-usual. System dynamics is a valuable tool, which can help policymakers choose the preventive interventions with the greatest impact.

European Dermatology Forum Guidelines on topical photodynamic therapy.

Topical photodynamic therapy (PDT) is a widely approved therapy for actinic keratoses, squamous cell carcinoma in-situ, superficial and certain thin basal cell carcinomas. Recurrence rates are typically equivalent to existing therapies, although inferior to surgery for nodular basal cell carcinoma. PDT can be used both as a lesional or as a field therapy and has the potential to delay/reduce the development of new lesions. PDT has also been studied for its place in the treatment of, as well as its potential to prevent, superficial skin cancers in immune-suppressed patients, although sustained clearance rates are lower than for immunocompetent individuals. Many additional indications have been evaluated, including photo-rejuvenation and inflammatory and infective dermatoses. This S2 guideline considers all current and emerging indications for the use of topical photodynamic therapy in Dermatology, prepared by the PDT subgroup of the European Dermatology Forum guidelines committee. It presents consensual expert recommendations reflecting current published evidence. An unabridged version of this guideline is available online at: http://www.euroderm.org/edf/index.php/edf-guidelines.

The risk of skin cancer in psoriasis patients treated with UVB therapy.

Phototherapy is an effective and widely used treatment for generalised plaque psoriasis. Despite the mutagenic effects of UVB this type of therapy is still assumed to be a safe treatment option. We have performed a cross sectional study to assess the risk of skin cancer in the cohort of psoriasis patients treated with UVB. A total of 162 white patients (116 men and 46 women, mean ± standard deviation age 56.0 ± 13.5 years) were included in the study. All patients have previously been treated with UVB at least 100 times in the last 5 years. Eight patients (4.9%, 0.95 CI: 2.2-9.5%) out of the 162 included in the study had histopathologically verified skin cancer. We found that the risk of skin cancer in psoriasis patients treated with UVB correlated with the number of treatments (controlling for age) but not with the type of UVB lamp. How-ever, the overall risk of malignancy in the UVB-treated patients was not greater than in the general population.

Poor correlation between spectrophotometric intracutaneous analysis and histopathology in melanoma and nonmelanoma lesions.

Spectrophotometric intracutaneous analysis (SIAscopy) is an imaging technique developed for diagnostics of pigmented skin lesions. By image analysis, the displayed images indicate the potential distribution and position of melanin, blood, and collagen within the lesion. A topographic comparison was performed between SIAscopic findings and histopathology. In total, 60 patients with suspicious pigmented skin lesions were included. The lesions were SIAscopically imaged and documented before excision and histopathological preparation. Topographical comparisons between SIAscopy findings and histopathology were made. A sensitivity and specificity of 24% and 84%, respectively, were obtained for invasive melanomas. The positive and negative predicted values were 58% and 54%, respectively. The features indicating dermal melanin, blood displacement and collagen holes did only show "no" to "slight" agreement with histopathology, i.e., κ ≤ 0.21. It was concluded that (i) SIAscopy-based diagnosis has low diagnostic accuracy for melanoma, (ii) single SIAscopic features do not provide reliable diagnostic information relating to the lesions internal structure on histopathology examination and (iii) SIAscopy cannot be used as a guide for localizing the maximum tumor thickness when performing the histopathological examination. The importance of validating new optical tools for tumor diagnostics with histopathological findings was demonstrated.

Anti-Stokes fluorescence from endogenously formed protoporphyrin IX--implications for clinical multiphoton diagnostics.

Multiphoton imaging based on two-photon excitation is making its way into the clinics, particularly for skin cancer diagnostics. It has been suggested that endogenously formed protoporphyrin IX (PpIX) induced by aminolevulinic acid or methylaminolevulinate can be applied to improve tumor contrast, in connection to imaging of tissue autofluorescence. However, previous reports are limited to cell studies and data from tissue are scarce. No report shows conclusive evidence that endogenously formed PpIX increases tumor contrast when performing multiphoton imaging in the clinical situation. We here demonstrate by spectral analysis that two-photon excitation of endogenously formed PpIX does not provide additional contrast in superficial basal cell carcinomas. In fact, the PpIX signal is overshadowed by the autofluorescent background. The results show that PpIX should be excited at a wavelength giving rise to one-photon anti-Stokes fluorescence, to overcome the autofluorescent background. Thus, this study reports on a plausible method, which can be implemented for clinical investigations on endogenously formed PpIX using multiphoton microscopy.

Patients' experiences of pain and pain relief during photodynamic therapy on actinic keratoses: an interview study.

Photodynamic therapy (PDT) is a well-known, effective method for treating extensive areas of multiple actinic keratoses in the face and scalp. The main side-effect of PDT is the pain experienced during treatment. The objective of this study was to explore and describe patients' experiences of PDT. The study used individual interviews, and analysis was carried out using phenomenography. The patients had all been treated with PDT for actinic keratoses on the face and scalp, and experienced PDT with and without nerve blocks. The results are presented in 3 themes and 10 categories. Most patients reported that the nerve blocks given prior to PDT altered their experience of pain. Alternative options are needed to reduce pain during PDT based on patients' needs and body site. This study adds a patient perspective highlight-ing patients' own voices as a qualitative complement to statistical analysis using the visual analogue scale.

Incidence of cutaneous melanoma in Western Sweden, 1970-2007.

The aim of this study was to describe the increasing incidence of cutaneous malignant melanoma (CMM) in Western Sweden during the period 1970-2007. A secondary aim was to show a geographical variation in incidence between coastal and inland areas, considering the effects of the local average duration of sunshine, and the sun exposure-related behavior in the populations. The Swedish Cancer Registry provided data on invasive melanomas during 1970-2007. Meteorological maps showed the annual average duration of sunshine during 1961-1990. A survey from 2007 with 2871 participants, carried out by the National Board of Health and Welfare, provided data on self-reported sun exposure. During the period studied, the age-standardized incidence for men in Western Sweden more than quadrupled to 31.1/100 000 inhabitants, whereas it tripled for women to 27.1/100 000. Coastal areas, including Gothenburg city, had a high average duration of sunshine (1701-1900 h of sun/year), whereas inland areas had lower average duration of sunshine (≤1700 h). The incidence of CMM was higher in coastal areas and in Gothenburg city, compared with inland areas. This may be linked to ultraviolet radiation, a consequence of the higher average duration of sunshine. The sun exposure survey showed additional factors, which possibly led to the increased incidence, for example high sun exposure on holidays abroad. The alarming increase in the incidence of CMM in Western Sweden, during the period 1970-2007, shows the need for additional primary preventive measures, for example sun protection programs targeted at populations in this area.

5-year recurrence rates of Mohs micrographic surgery for aggressive and recurrent facial basal cell carcinoma.

Mohs micrographic surgery allows for complete microscopic examination of the surgical margin when treating aggressive and recurrent facial basal cell carcinomas. This leads to the highest cure rates and maximal preservation of healthy tissue. The 5-year recurrence rates of 587 aggressive and/or recurrent facial basal cell carcinomas treated during 1993 to 2003 at our centre were studied retrospectively. The resulting 5-year recurrence rates using Kaplan-Meier survival analysis were 2.1% for primary (previously untreated) tumours, 5.2% for recurrent basal cell carcinomas and 3.3% overall. In total, 87.9% of the tumours required at least two stages of Mohs micrographic surgery. The surgical defect's size after complete excision was, on average, approximately twice the size of the defect after excision of the clinically visible tumour with a 2-3 mm margin. Mohs micro-graphic surgery is underused in Scandinavia despite being the treatment of choice for aggressive and recurrent facial basal cell carcinomas.

Predictors of pain associated with photodynamic therapy: a retrospective study of 658 treatments.

Pain is the most common side-effect of photodynamic therapy (PDT). Our main objective was to identify pain predictors in PDT. In total, we performed 658 treatments on 377 patients at our department during 2004. Larger sized treatment areas were the strongest pain predictor, and actinic keratoses were more painful to treat than basal cell carcinomas and Bowen's disease. The most sensitive areas to treat were the face and scalp. Gender and age did not influence pain. Although treatment outcome was not our primary objective, 62% of 95 superficial basal cell carcinomas that were followed for 3 years showed complete clearance. Also, perforation of nodular basal cell carcinomas did not lead to better clinical results. In conclusion, the size of the treatment area, the diagnosis and the lesion location influence pain during PDT. Nevertheless, there is a large variance in visual analogue scale assessment within each group, thereby limiting the ability to predict pain.

Fluorescence diagnostics of basal cell carcinomas comparing methyl-aminolaevulinate and aminolaevulinic acid and correlation with visual clinical tumour size.

Fluorescence diagnostics based on aminolaevulinic acid (ALA) fluorescence has been suggested as an in vivo pre-surgical tool for tumour demarcation. We performed fluorescence diagnostics of 35 basal cell carcinomas (BCCs) undergoing photodynamic therapy (PDT) using methyl-aminolaevulinate (MAL). In addition, a semi-automated thresholding algorithm was implemented to detect the potential tumour region. The mean tumour fluorescence contrast was found to be 1.65 ± 0.06 during the first MAL-PDT session, and increased to 1.84 ± 0.07 at the second treatment (p < 0.01). This could imply that disruption of the skin barrier and inflammatory responses after the first session of PDT led to higher accumulation of proto-porphyrin IX during the second session of PDT. The tumour areas detected based on fluorescence in small BCCs (< 1 cm(2)) were in general (n = 18/23) larger than the visual clinical tumour size. In addition, the fluorescence contrast using MAL (1.65 ± 0.06) was found to be significantly higher (p<10(-4)) than the contrast (data from previous study) after application of ALA (1.20 ± 0.06). Thus, MAL generally provides higher tumour contrast than ALA in BCCs, and should be preferred for use in fluorescence diagnostics. Correlation between fluorescence, lack of treatment response and/or pain was not observed.

Single low-dose red light is as efficacious as methyl-aminolevulinate--photodynamic therapy for treatment of acne: clinical assessment and fluorescence monitoring.

This controlled study investigated single low-dose red light photodynamic therapy and methyl-aminolevulinate (MAL) for treatment of moderate to severe facial acne in 19 patients. The right cheek was treated with MAL (160 mg/g) for 3 h prior to illumination. The left cheek received red light only. Both cheeks were illuminated with narrow-band red light (635 nm) at a light dose of 15 J/cm2. The global severity of acne was assessed at baseline and at follow-up, 10 and 20 weeks after treatment. Fluorescence images, clinical photographs and skin surface biopsies were obtained. Both MAL-photodynamic therapy and control areas showed a significant decrease in acne score at follow-up; no significant difference was found compared with control. MAL-photodynamic therapy was associated with adverse effects such as erythema and stinging. Fluorescence images revealed poor selectivity of MAL-induced fluorescence to the acne lesions, suggesting a general photoablating mechanism rather than selective destruction of sebaceous glands. No significant reduction in Propionibacterium acnes or sebum excretion was found.

Vitamin D production in psoriasis patients increases less with narrowband than with broadband ultraviolet B phototherapy.

BACKGROUND: Phototherapy of psoriasis is an effective treatment. In addition to standard broadband ultraviolet radiation B (UVB), (280-320 nm), narrowband phototherapy (NBUVB) (monochromatic UV between 311 and 312 nm) has become an important treatment for psoriasis. The same wavelength range of UVB (290-315 nm) induces synthesis of vitamin D. The aim was to compare the effect of broadband with NBUVB therapy on vitamin D synthesis in patients with psoriasis. METHODS: Sixty-eight Caucasian patients (17 women and 51 men) mean age 54.1 +/- 16.0 years, with active plaque psoriasis, were treated with broadband UVB (n=26) or NBUVB (n=42) two to three times/week for 8-12 weeks. The serum concentrations of 25-hydroxyvitamin D (25(OH)D3), 1,25-dihydroxyvitamin D (1,25(OH)(2)D3), intact parathyroid hormone (PTH), calcium and creatinine were measured before the first exposure and after the last dose of radiation. RESULTS: In broadband UVB treated patients, 25(OH)D3 increased from 37.9 +/- 16.9 to 69.4 +/- 19.7 ng/ml (P<0.0001) and in patients treated with NBUVB from 34.8 +/- 11.9 to 55.3 +/- 17.6 ng/ml (P<0.0001) and P=0.008 between the treatment groups. PTH decreased on broadband UVB (P<0.05). The serum concentrations of 1,25(OH)(2)D3, calcium or creatinine remained unaltered. CONCLUSION: Serum 25(OH)D3 in psoriasis patients increased less with NBUVB than with broadband UVB phototherapy. Psoriasis improved on both regimens.

Air oxidation increases skin irritation from fragrance terpenes.

BACKGROUND: Linalool and limonene are common fragrance terpenes that autoxidize on air exposure. The pure compounds are not allergenic but their oxidation products can cause contact allergy. Little has been investigated regarding the irritancy of oxidized terpenes. AIM: The aim of this study was to investigate the irritating effect of pure and oxidized R-limonene and linalool in concentration series and to study the MNIC (Maximum Non Irritant Concentration) of autoxidized linalool and limonene. PATIENTS/METHODS: Patch testing was performed in dermatitis patients and controls with sequentially diluted concentrations of oxidized and non-oxidized linalool, and oxidized and non-oxidized R-limonene. Readings were made with visual assessment and using laser Doppler imaging. RESULTS: The non-oxidized terpenes were non-irritating in all tested concentrations. Both linalool and especially R-limonene were more irritating after oxidation compared with the pure compounds. No difference in response was seen between dermatitis patients and controls. CONCLUSION: Autoxidation of the fragrance terpenes linalool and R-limonene increases irritation. Oxidized linalool is less irritating than oxidized R-limonene. In this study, we found no advantages in using laser Doppler technique compared with visual assessment.

Photodynamic therapy with methyl aminolevulinate for prevention of new skin lesions in transplant recipients: a randomized study.

BACKGROUND: Organ transplant recipients on long-term immunosuppressive therapy are at increased risk of non-melanoma skin lesions. Repeated field photodynamic therapy using topical methyl aminolevulinate (MAL) may have potential as a preventive treatment. METHODS: This open randomized, intrapatient, comparative, multicenter study included 81 transplant recipients with 889 lesions (90% actinic keratoses (AK)]. In each patient, the study treatment was initially administered to one 50 cm area on the face, scalp, neck, trunk, or extremities (n=476 lesions) twice (1 week apart), with additional single treatments at 3, 9, and 15 months. On each occasion, the area was debrided gently and MAL cream (160 mg/g) applied for 3 hr, before illumination with noncoherent red light (630 nm, 37 J/cm2). The control, 50 cm2 area (n=413 lesions) received lesion-specific treatment (83% cryotherapy) at baseline and 3, 9, and 15 months. Additionally, all visible lesions were given lesion-specific treatment 21 and 27 months in both treatment and control areas. RESULTS: At 3 months, MAL photodynamic therapy significantly reduced the occurrence of new lesions (65 vs. 103 lesions in the control area; P=0.01), mainly AK (46% reduction; 43 vs. 80; P=0.006). This effect was not significant at 27 months (253 vs. 312; P=0.06). Hypopigmentation, as assessed by the investigator, was less evident in the treatment than control areas (16% vs. 51% of patients; P<0.001) at 27 months. CONCLUSION: Our results suggest that repeated field photodynamic therapy using topical MAL may prevent new AK in transplant recipients although further studies are needed.