Influence of stress resilience in adolescence on long-term risk of psoriasis and psoriatic arthritis among men: A prospective register-based cohort study in Sweden.

BACKGROUND: Although stress is considered to be a negative factor for psoriasis, no convincing scientific evidence of this association exists, largely because of difficulties in measuring stress. Stress resilience is the ability to cope with and adapt to stressful events. Stress resilience can be measured in a standardized way and used as a marker for chronic stress. OBJECTIVES: The objective of this study is to investigate whether low stress resilience in adolescence increases the risk for onset of psoriasis and psoriatic arthritis later in life. METHODS: A cohort of Swedish men (mean age 18.3 years), enrolled in compulsory military service between 1968 and 2005, was created using data from the Swedish Military Service Conscription Register (n = 1,669,422). Stress resilience at conscription was estimated using standardized semi-structured interviews, and was divided into three categories: low, medium and high. The men were followed from conscription until new-onset psoriasis or psoriatic arthritis, death or emigration or at the latest until 31 December 2019. Cox regression models adjusted for confounders at conscription were used to obtain hazard ratios (HRs) with 95% confidence intervals (CIs) for incident psoriasis and psoriatic arthritis. RESULTS: Men in the lowest stress resilience category had an increased risk of psoriasis and psoriatic arthritis (HR 1.31 (95% CI 1.26-1.36) and 1.23 (95% CI 1.15-1.32), respectively), compared with those in the highest stress resilience category. When including only hospitalized patients the HRs for psoriasis and psoriatic arthritis in the lowest stress resilience group were 1.79 (1.63-1.98) and 1.53 (1.32-1.77), respectively. CONCLUSIONS: This large, prospective register study suggests that low stress resilience in adolescence is associated with an increased risk of incident psoriasis among men. The results indicate that patients with psoriasis have an inherent psychological vulnerability, and highlight the importance of addressing psychological well-being in the management of psoriasis.

European Dermatology Forum guidelines on topical photodynamic therapy 2019 Part 2: emerging indications - field cancerization, photorejuvenation and inflammatory/infective dermatoses.

In addition to approved indications in non-melanoma skin cancer in immunocompetent patients, topical photodynamic therapy (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 immune-competent individuals. PDT using a nanoemulsion of ALA in a daylight or conventional PDT protocol has been approved for use in field cancerization, although evidence of the potential of the treatment to prevent new SCC remained limited. High-quality evidence supports a strong recommendation for the use of topical PDT in photorejuvenation as well as for acne, refractory warts, cutaneous leishmaniasis and in onychomycosis, although these indications currently lack approvals for use and protocols remain to be optimized, with more comparative evidence with established therapies required to establish its place in practice. Adverse events across all indications for PDT can be minimized through the use of modified and low-irradiance regimens, with a low risk of contact allergy to photosensitizer prodrugs, and no other significant documented longer-term risks with no current evidence of cumulative toxicity or photocarcinogenic risk. The literature on the pharmacoeconomics for using PDT is also reviewed, although accurate comparisons are difficult to establish in different healthcare settings, comparing hospital/office-based therapies of PDT and surgery with topical ointments, requiring inclusion of number of visits, real-world efficacy as well as considering the value to be placed on cosmetic outcome and patient preference. This guideline, published over two parts, considers all current approved 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.

European Dermatology Forum guidelines on topical photodynamic therapy 2019 Part 1: treatment delivery and established indications - actinic keratoses, Bowen's disease and basal cell carcinomas.

Topical photodynamic therapy (PDT) is a widely approved therapy for actinic keratoses, Bowen's disease (squamous cell carcinoma in situ), superficial and certain thin basal cell carcinomas. Recurrence rates when standard treatment protocols are used are typically equivalent to existing therapies, although inferior to surgery for nodular basal cell carcinoma. PDT can be used both as lesional and field therapies and has the potential to delay/reduce the development of new lesions. A protocol using daylight to treat actinic keratoses is widely practised, with conventional PDT using a red light after typically a 3-h period of occlusion employed for other superficial skin cancer indications as well as for actinic keratoses when daylight therapy is not feasible. PDT is a well-tolerated therapy although discomfort associated with conventional protocol may require pain-reduction measures. PDT using daylight is associated with no or minimal pain and preferred by patient. There is an emerging literature on enhancing conventional PDT protocols or combined PDT with another treatment to increase response rates. This guideline, published over two parts, considers all current approved and emerging indications for the use of topical PDT in dermatology, prepared by the PDT subgroup of the European Dermatology Forum guidelines committee. It presents consensual expert recommendations reflecting current published evidence.

Photodynamic therapy is more effective than imiquimod for actinic keratosis in organ transplant recipients: a randomized intraindividual controlled trial.

BACKGROUND: Actinic keratoses (AKs) in solid organ transplant recipients (OTRs) are difficult-to-treat premalignancies and comparison of topical therapies is therefore warranted. OBJECTIVES: In an intraindividual study to compare the efficacy and safety of field treatment with methyl aminolaevulinate photodynamic therapy (MAL-PDT) and imiquimod (IMIQ) for AKs in OTRs. METHODS: OTRs (n = 35) with 572 AKs (grade I-III) in two similar areas on the face, scalp, dorsal hands or forearms were included. All patients received one MAL-PDT and one IMIQ session (three applications per week for 4 weeks) in each study area according to randomization. Treatments were repeated after 2 months (IMIQ) and 3 months (PDT) in skin with incomplete AK response. Outcome measures were complete lesion response (CR), skin reactions, laboratory results and treatment preference. RESULTS: The majority of study areas received two treatment sessions (PDT n = 25 patients; IMIQ n = 29 patients). At 3 months after two treatments, skin treated with PDT achieved a higher rate of CR (AK I-III median 78%; range 50-100) compared with IMIQ-treated skin areas (median 61%, range 33-100; P < 0·001). Fewer emergent AKs were seen in PDT-treated skin vs. IMIQ-treated skin (0·7 vs. 1·5 AKs, P = 0·04). Patients developed more intense inflammatory skin reactions following PDT, which resolved more rapidly compared with IMIQ (median 10 days vs. 18 days, P < 0·01). Patient preference (P = 0·47) and cosmesis (P > 0·30) were similar for PDT and IMIQ. CONCLUSIONS: Compared with IMIQ, PDT treatment obtained a higher rate of AK clearance at 3-month follow-up and achieved shorter-lasting, but more intense, short-term skin reactions.

Results of the 'Euromelanoma Day' screening campaign in Sweden 2008.

BACKGROUND: The 'Euromelanoma Day' skin cancer screening campaign is organized annually in several European countries since the year 2000. The national results have not been analysed in a Scandinavian country. OBJECTIVE: Our objective was to analyse the demographic characteristics and risk factors of the screened population during the 'Euromelanoma Day' in Sweden 2008. We also aimed to describe the clinical diagnoses found, the melanomas confirmed histopathologically and the treatments performed. METHODS: A public health education campaign to promote awareness of skin cancer risk factors and warning signs was carried out. Patients with suspicious lesions were advised to attend the screening. Questionnaires were used to collect relevant demographic, epidemiological and clinical data. RESULTS: In total, 2659 patients were screened. Women accounted for 62.3% of all patients; the median age was 57 years (range: 5-100 years); and 91.2% had skin phototypes II-III. Previous skin cancer was reported by 18.4% of all patients and 14.8% had a family history of melanoma. In total, 456 patients were diagnosed clinically with non-melanoma skin cancer. Twenty-four patients had histopathologically confirmed melanomas. Ten were in situ and 8 of the 14 invasive melanomas had a Breslow thickness that was less than 1 mm. Treatment or future medical care was carried out in 45.4% of all patients. CONCLUSION: The 'Euromelanoma Day' campaign attracted many individuals at risk for skin cancer. The detection rate of non-melanoma skin cancer and melanoma was relatively high compared to similar campaigns in other European countries. Most melanomas found had a favourable prognosis.

Nerve blocks enable adequate pain relief during topical photodynamic therapy of field cancerization on the forehead and scalp.

BACKGROUND: Topical photodynamic therapy (PDT) is an effective method when treating extensive areas of sun-damaged skin with multiple actinic keratoses (AKs) (field cancerization) on areas such as the forehead and scalp, and offers excellent cosmetic outcome. The major side-effect of PDT is the pain experienced during treatment. OBJECTIVES: To investigate whether nerve blocks could provide adequate pain relief during PDT of AKs on the forehead and scalp. METHODS: Ten men with symmetrically distributed and extensive AKs on the forehead and scalp were included in the study. Prior to PDT one side of the forehead and scalp was anaesthetized by nerve blocks while the other side served as control. RESULTS: The mean visual analogue scale (VAS) score on the anaesthetized side was 1 compared with 6.4 on the nonanaesthetized side during PDT. This difference was significant (P<0.0001), implying that nerve blocks reduce VAS scores during PDT. CONCLUSIONS: The results of the study support the use of nerve blocks as pain relief during PDT of field cancerization on the forehead and scalp, although individual considerations must be taken into account to find the most adequate pain-relieving method for each patient.

Nerve blocks provide effective pain relief during topical photodynamic therapy for extensive facial actinic keratoses.

BACKGROUND: Photodynamic therapy (PDT) is a first-line therapeutic option for skin areas with multiple actinic keratoses (AKs). Its main drawback is the pain perceived during the irradiative phase, especially when treating field cancerization in the facial area. Effective pain-relieving strategies are needed. AIM: To determine the effectiveness of peripheral nerve blocks in achieving pain relief during PDT for extensive facial AKs. METHODS: In total, 16 patients with symmetrically distributed facial AKs, mainly on the forehead, were enrolled in the study. Nerve blocks were applied unilaterally, and the nonanaesthetized side of the treatment area served as control. Maximum pain during PDT was evaluated using a visual analogue scale (VAS). Pain experienced after PDT was evaluated by telephone interview within 2 weeks of treatment. Cure rates were assessed at follow-up at least 4 weeks after treatment. RESULTS: Pain was significantly reduced on the anaesthetized side (P < 10(-8)). The mean +/- SEM VAS score on the blocked side of the face was 1.3 +/- 0.3 compared with 7.5 +/- 0.5 on the nonanaesthetized side. Pain relief persisted 1-2 h after PDT. The nerve block was generally not experienced as painful (14/16 patients). Almost all patients (15/16 patients) would like to receive nerve blocks bilaterally if future PDT were needed. Excellent clinical results were observed in all patients after 4-20 weeks. CONCLUSION: Nerve blocks provide efficient pain relief during PDT when treating patients with field cancerization of the forehead. Nerve blocks were not found to affect the clinical outcome of PDT, and were generally well tolerated by the patients.

Bioavailability of aminolaevulinic acid and methylaminolaevulinate in basal cell carcinomas: a perfusion study using microdialysis in vivo.

BACKGROUND: Photodynamic therapy is becoming a popular treatment for superficial nonmelanoma precancerous and cancerous lesions, showing excellent cosmetic results. Nevertheless, the reported cure rates vary and the transdermal penetration of drugs has been discussed as a limiting factor, particularly for treatment of nodular basal cell carcinoma (BCC). OBJECTIVES: To investigate the transdermal penetration of aminolaevulinic acid (ALA) and methylaminolaevulinate (MAL) in BCC in vivo using a microdialysis technique. The different prodrugs were compared and the effect of curettage was studied. METHODS: Twenty patients with 27 histologically verified BCCs (13 superficial, 14 nodular) were included. All lesions were located at the front of the body (head and face excluded). The first 10 patients included were treated with MAL (13 BCCs), and the following 10 patients with ALA (14 BCCs). A light curettage was performed on every second lesion (curettage, n = 13; noncurettage, n = 14). Microdialysis catheters were inserted into the tumours at tissue depths varying from 0.4 to 1.9 mm. Dialysates were collected at 15-30-min intervals for 4 h and the interstitial concentrations of MAL and ALA were determined using high-performance liquid chromatography. RESULTS: No significant difference in interstitial drug concentration was observed between lesions treated with ALA or MAL during the 4-h measurement period. However, for the lesions with deeper catheter locations, i.e. at or below 1 mm (n = 11), drug concentrations above the detection limit were obtained in only six lesions. All but one BCC with superficial catheter location, i.e. < 1 mm (n = 16), exhibited detectable drug concentration (P = 0.026). The interstitial peak concentrations were reached within 90 min in 23 of the 27 BCCs, but were not found to be correlated with the depth of the catheters. No difference was found when comparing superficial and nodular BCCs, and the effect of curettage was found to be negligible. CONCLUSIONS: The results imply that there is no significant difference in transdermal penetration of ALA and MAL in tumour tissue. Detectable levels of drug were not obtained in almost 50% of the lesions where catheters were situated 1-1.9 mm in the lesion. Curettage was not found to affect the interstitial concentration, indicating that penetration of drug indeed might be a problem when treating BCCs thicker than 1 mm.

Topical methyl aminolaevulinate photodynamic therapy for treatment of facial acne vulgaris: results of a randomized, controlled study.

BACKGROUND: There is a need for alternative treatments for moderate to severe acne vulgaris. Preliminary experience suggests that topical methyl aminolaevulinate photodynamic therapy (MAL-PDT) may have potential. OBJECTIVES: To investigate the efficacy and tolerability of MAL-PDT for treatment of moderate inflammatory facial acne. PATIENTS/METHODS: Thirty patients aged 15-28 years with moderate to severe acne were included in a blinded, prospective, randomized, placebo-controlled multicentre study. Each side of each patient's face was randomly assigned to treatment with MAL (160 mg g1) or placebo cream, applied for 3 h prior to illumination. A second treatment was given 2 weeks later. On each occasion, patients assessed the intensity of pain using a 10-cm visual analogue scale. Inflammatory and noninflammatory acne lesions were counted at baseline and 4 and 10 weeks after the last PDT treatment. The investigator assessed the global severity of acne at baseline (seven patients had severe acne on at least one side of the face) and each study visit using a six-point rating scale. Data were analysed on an intention-to-treat basis, including all 30 patients. RESULTS: There was a statistically significant greater reduction in the total inflammatory lesion count with MAL-PDT compared with placebo PDT at week 12; median reduction 54% [95% confidence interval (CI) 35-64%] vs. 20% (95% CI 8-50%), P = 0.0006. MAL-PDT was associated with more pain than placebo PDT, although intensity varied across centres and was reduced with repeated treatment. Local adverse events were consistent with this treatment modality. CONCLUSIONS: MAL-PDT is effective in the treatment of moderate to severe inflammatory facial acne. Further studies are warranted to optimize this promising procedure.

Bispectral fluorescence imaging of aggressive basal cell carcinoma combined with histopathological mapping: a preliminary study indicating a possible adjunct to Mohs micrographic surgery.

BACKGROUND: Fluorescence imaging is an attractive diagnostic technique for skin tumour demarcation with potential to move to clinical use. Bispectral fluorescence imaging combines skin autofluorescence with delta-aminolaevulinic acid-induced fluorescence. To evaluate the technique, fluorescence data must be compared with the histopathological extent of the tumour, which is the purpose of the current study. OBJECTIVES: To investigate the agreement between bispectral fluorescence images and the histopathological tumour boundary of ill-defined basal cell carcinomas (BCCs). After fluorescence imaging the tumours were removed using Mohs micrographic surgery (MMS) to obtain histopathological maps of the tumour boundaries. METHODS: Twelve patients with aggressive BCC of mean diameter 16 mm (range 5-32) in the face were included in the study. The patients were subjected to bispectral fluorescence imaging within the 2 months prior to MMS. The fluorescence images and histopathological maps were aligned using image warping. RESULTS: Five patients (42%) showed good agreement with the histopathological mapping and the remaining seven patients (58%) showed partial agreement. Bispectral investigation combining autofluorescence with protoporphyrin IX (PpIX) fluorescence generally yielded better agreement with the histopathological boundaries of the tumours compared with using only the PpIX fluorescence. CONCLUSIONS: In this preliminary study the fluorescence has been compared with the histopathological tumour boundaries. The result implies that the technique can be applied as a useful tool for indicating tumour boundary of aggressive BCCs. Further refinement is needed to be able to indicate the exact tumour border.

Percutaneous absorption of the sunscreen benzophenone-3 after repeated whole-body applications, with and without ultraviolet irradiation.

BACKGROUND: Benzophenone-3 (BZ-3; 2-hydroxy-4-methoxybenzophenone, oxybenzone) is commonly used to absorb ultraviolet (UV) radiation. BZ-3 penetrates the skin and can be found in the urine. The amount varies between 0.4% and 2%. This seems to be the main metabolic pathway in rats. OBJECTIVES: To investigate the total amount of BZ-3 excreted in the urine after repeated topical whole-body applications of a sunscreen and to see if UV radiation has any effect on the amount excreted. METHODS: Twenty-five volunteers applied a commercially available sunscreen containing 4% BZ-3 morning and night for 5 days. Their urine was measured during those 5 days and during a further 5 days after the last application. They were divided into groups A (unirradiated) and B. Group B received UV radiation according to skin type: UVA between 400 and 707 J cm(-2), and UVB between 0.46 and 2.0 J cm(-2). BZ-3 in urine was analysed with a high-performance liquid chromatography method. RESULTS: The volunteers excreted 1.2-8.7% (mean 3.7%) of the total amount of BZ-3 applied. There was no significant difference between the two groups (P < 0.99, t-test). CONCLUSIONS: We show that a large amount of BZ-3 is absorbed. BZ-3 is accumulated in the body as the volunteers excreted BZ-3 5 days after the last application.

Photodynamic therapy of actinic keratosis at varying fluence rates: assessment of photobleaching, pain and primary clinical outcome.

BACKGROUND: Although photodynamic therapy (PDT) is becoming an important treatment method for skin lesions such as actinic keratosis (AK) and superficial basal cell carcinoma, there are still discussions about which fluence rate and light dose are preferable. Recent studies in rodents have shown that a low fluence rate is preferable due to depletion of oxygen at high fluence rates. However, these results have not yet been verified in humans. OBJECTIVES: The objective was to investigate the impact of fluence rate and spectral range on primary treatment outcome and bleaching rate in AK using aminolaevulinic acid PDT. In addition, the pain experienced by the patients has been monitored during treatment. PATIENTS/METHODS: Thirty-seven patients (mean age 71 years) with AK located on the head, neck and upper chest were treated with PDT, randomly allocated to four groups: two groups with narrow filter (580-650 nm) and fluence rates of 30 or 45 mW cm(-2), and two groups with broad filter (580-690 nm) and fluence rates of 50 or 75 mW cm(-2). The total cumulative light dose was 100 J cm(-2) in all treatments. Photobleaching was monitored by fluorescence imaging, and pain experienced by the patients was registered by using a visual analogue scale graded from 0 (no pain) to 10 (unbearable pain). The primary treatment outcome was evaluated at a follow-up visit after 7 weeks. RESULTS: Our data showed a significant correlation between fluence rate and initial treatment outcome, where lower fluence rate resulted in favourable treatment response. Moreover, the photobleaching dose (1/e) was found to be related to fluence rate, ranging from 4.5 +/- 1.0 J cm(-2) at 30 mW cm(-2), to 7.3 +/- 0.7 J cm(-2) at 75 mW cm(-2), indicating higher oxygen levels in tissue at lower fluence rates. After a cumulative light dose of 40 J cm(-2) no further photobleaching took place, implying that higher doses are excessive. No significant difference in pain experienced by the patients during PDT was observed in varying the fluence rate from 30 to 75 mW cm(-2). However, the pain was found to be most intense up to a cumulative light dose of 20 J cm(-2). CONCLUSIONS: Our results imply that the photobleaching rate and primary treatment outcome are dependent on fluence rate, and that a low fluence rate (30 mW cm(-2)) seems preferable when performing PDT of AK using noncoherent light sources.

Topical methyl aminolaevulinate photodynamic therapy in patients with basal cell carcinoma prone to complications and poor cosmetic outcome with conventional treatment.

BACKGROUND: Conventional treatment of basal cell carcinoma (BCC) causes morbidity and/or disfigurement in some patients because of the location (e.g. mid-face) and size of the lesion. OBJECTIVES: Following reports that such difficult-to-treat BCC lesions have been treated successfully with topical methyl aminolaevulinate (MAL) photodynamic therapy (PDT), a multicentre study was performed to determine the response of such BCC to MAL-PDT. METHODS: An open, uncontrolled, prospective, multicentre study was conducted comprising patients with superficial and/or nodular BCC who were at risk of complications, poor cosmetic outcome, disfigurement and/or recurrence using conventional therapy. Patients were given one or two cycles within 3 months of topical MAL-PDT, each consisting of two treatments 1 week apart. Tumour response was assessed clinically at 3 months after the last PDT, with histological confirmation of all lesions in clinical remission. The cosmetic outcome was rated. Patients with a BCC in remission will be followed up for 5 years for recurrence, of which the 24-month follow-up is reported here. Ninety-four patients with 123 lesions were enrolled and treated with MAL-PDT at nine European primary care and referral university hospitals. An independent blinded study review board (SRB) retrospectively excluded nine patients and a total of 15 lesions from the efficacy analysis, for not having a difficult-to-treat BCC according to the protocol. RESULTS: The lesion remission rate at 3 months was 92% (45 of 49) for superficial BCC, 87% (45 of 52) for nodular BCC, and 57% (four of seven) for mixed BCC, as assessed by clinical examination, and 85% (40 of 47), 75% (38 of 51), and 43% (three of seven), respectively, as assessed by histological examination and verified by the SRB. At 24 months after treatment, the overall lesion recurrence rate was 18% (12 of 66). The cosmetic outcome was graded as excellent or good by the investigators in 76% of the cases after 3 months follow-up, rising to 85% at 12 months follow-up, and 94% at 24 months follow-up. CONCLUSIONS: Topical MAL-PDT is effective in treating BCC at risk of complications and poor cosmetic outcome using conventional therapy. MAL-PDT preserves the skin and shows favourable cosmetic results.

A spectroscopic study of the photobleaching of protoporphyrin IX in solution.

Photodynamic therapy (PDT) has developed into an important new clinical treatment for cancer during the past 30 years. The method is non-invasive and based on the photochemical activity of a photosensitising agent present in cells and tissues. In so-called ALA-PDT, protoporphyrin IX (Pp IX) is induced from aminolaevulinic acid (ALA) applied topically or systemically. It has been shown that Pp IX is photodegraded by a photo-oxidation process and that its photoproducts have a characteristic absorption band around 670 nm, as observed both in solution and in cells incubated with ALA. In this study, the involvement of oxygen in the photobleaching process was verified by studying the effect of oxygen depletion using the freeze-pump-thaw (FPT) method. A solution of Pp IX in dimethylformamide (DMF) was exposed to light in the wavelength region 600-700 nm (peak centred at 620 (+/-25) nm) both in the presence and in the absence of oxygen. The bleaching process was observed by absorbance and fluorescence measurements. Photobleaching was observed in the presence of oxygen, as verified by the build-up of a photoproduct absorbing at 670 nm. When the sample was deoxygenated with the FPT method, the photoproduct absorption peak at 670 nm was missing. These results confirm that the formation of photoprotopor-phyrin is a photo-oxidation process and that no photobleaching takes place in the absence of oxygen. When comparing our results to the studies carried out by N(2) bubbling, the N(2) bubbling seems to be insufficient to remove the oxygen completely from the solution.

Pain caused by photodynamic therapy of skin cancer.

Pain resulting from photodynamic therapy (PDT) of skin cancer was investigated. The study included 69 lesions (60 patients) with different types of skin tumours or precursors. Protoporphyrin IX, which is produced by the topical application of delta-aminolevulinic acid, was used as a photosensitizing agent. Twenty-three of the lesions (19 patients) were examined with a fluorescence imaging system which demarcates the tumour area from the healthy skin and visualizes the contrast between the fluorescence from healthy skin and that from the tumour. EMLA is used on all patients as part of our routine PDT protocol but despite this the major side-effect of PDT is pain during treatment. There is a large variation in pain intensity experienced by the patients, as measured by a visual analogue scale (VAS). Patients with actinic keratoses experienced more pain than those with Bowen's disease or basal cell carcinoma. The mean VAS score was higher when treating lesions located on the head than when treating lesions on the torso or the extremities. Also, treatment of large skin areas resulted in more pain than treatment of small areas, and men experienced more pain than women. The pain experienced by the patients did not correlate with treatment dose, Fitzpatrick skin type, age or fluorescence intensity.

Delta-aminolevulinic acid in superficial basal cell carcinomas and normal skin-a microdialysis and perfusion study.

Delta-aminolevulinic acid (ALA) is used for photodynamic therapy of basal cell carcinoma (BCC) as it is converted to protoporphyrin IX in tumour tissue. During illumination with 635 nm light a photochemical reaction takes place, singlet oxygen is generated and the tumour destroyed. In this study we used the microdialysis technique to quantify the concentration of ALA at a certain depth in tumour and healthy skin. The penetration ability of ALA was investigated as a function of time in BCCs (n = 14) and in normal skin (n = 4) after topical application. The microdialysis catheters were inserted intracutaneously and the depth position recorded by means of ultrasound. Microdialysate sample concentrations of amino acids and ALA were determined by high performance ion-exchange chromatography. A laser Doppler perfusion imager measured perfusion in the BCCs. The data show that the average depth of the microdialysis catheters was 0.5 mm. The interstitial ALA concentration in the BCCs increased from 0 to 3.1 mmol/L 15 min after application of ALA, whereas no measurable amounts of ALA were found in healthy skin. The blood perfusion was 2.5-fold increased in the BCCs. The interstitial levels of amino acids were not significantly changed during the ALA treatment. In summary, we found that ALA rapidly penetrates tumour skin. We conclude that microdialysis seems to be well suited for pharmacodynamic studies of ALA in skin.

Basal cell carcinoma--new aspects of diagnosis and treatment.

The incidence of basal cell carcinoma is increasing. New aspects of diagnosis and treatment are discussed in this thesis. Interferon can be used for the treatment of BCC. In paper I, 15 patients received 13.5 x 10(6) IU of alfa-2b-interferon intralesionally. Four patients healed completely whereas a 75% reduction was seen in 5 cases. Intralesional alfa-2b-interferon can reduce the number of excisions during Mohs Micrographic Surgery. Topical photodynamic therapy involves the application of ALA on the skin. In tumour cells selectively, formation of the photosensitizer Pp IX occurs. After 4 hours of occlusion of ALA the area is irradiated with light at a wavelength of 630 nm. Tumour cells are selectively destroyed during this procedure. 144/157 SBCC healed in this series and 14/18 Mb Bowen (paper II). The method is only suited for thin BCCs as the result on thicker lesions is poor (2/10 healed). The cosmetic result was generally good or excellent. Another way of utilising the tumour selectivity of Pp IX is for diagnostic purposes. Instead of illuminating with 630 nm, 365, 366 and 405 nm are used to induce a specific fluorescence. In the present paper (III), 50% of facial BCCs with ill-defined borders could be completely visualised and another 23% partly outlined. The technique did not seem to work in 27% of the cases. The critical factor using ALA is probably the relatively poor penetrance through the skin. In paper IV, microdialysis is used for pharmacokinetic studies of ALA for the first time. The concentration of ALA increases rapidly in lesional skin whereas there is virtually no penetration in healthy skin. Also, the blood perfusion in BCCs was investigated by means of laser Doppler Perfusion Imager. The perfusion in skin overlying a BCC was 2.5 fold higher compared to normal skin. For BCCs with ill-defined borders Mohs Micrographic Surgery is generally recommended. Regarding Mohs Micrographic Surgery, Sweden is underserved as only 1% of BCCs are treated with Mohs Micrographic Surgery as opposed to 30% in the US. Consequently, the Swedish cases are probably more severe. The long-term results are reported in paper V. Two hundred and twenty-eight tumours were followed for at least 5 years. The rate of recurrence was 8%. This figure is slightly higher than in international materials but surprisingly low considering the type of tumours.