Leena Koulu

Cancer incidence among Finnish psoriasis patients treated with 8-methoxypsoralen bath PUVA

BACKGROUND Long-term oral 8-methoxypsoralen (8-MOP) and UVA (PUVA) therapy increases the risk of nonmelanoma skin cancer and possibly also of cutaneous malignant melanoma. Topical application of 8-MOP PUVA induces malignant tumors in rodent skin, but little is known about its carcinogenicity in human skin. OBJECTIVE Our purpose was to investigate the carcinogenicity of 8-MOP bath PUVA in humans. METHODS This was a cohort study of 158 patients with psoriasis, for whom 8-MOP bath PUVA had been initiated during 1979 to 1992. The average number of 8-MOP bath PUVA treatments was 36 (range, 6 to 204) and the mean cumulative UVA dose was 92 J/cm2 (range, 3 to 884 J/cm2) by the end of 1995. The patients were not treated with any other forms of PUVA. Cancer incidence subsequent to 8-MOP bath PUVA up to the end of 1995 was determined by linking the cohort with the records of the Finnish Cancer Registry. The standardized incidence ratios (SIR) were calculated for skin cancer and some common internal cancers, using the expected numbers of cases based on the regional cancer incidence rates. RESULTS There was one case of basal cell carcinoma, but no cases of other types of skin cancer. A total of 6 noncutaneous cancers were observed (SIR, 1.3; 95% confidence interval, 0.5 to 2.8). CONCLUSION No association between cutaneous cancer and 8-MOP bath PUVA was found, but the statistical power of this study alone is not adequate to warrant definite conclusions. The results can be used in a meta-analysis as soon as other studies on the carcinogenicity of 8-MOP bath PUVA are published.

Effect of a single UVB or PUVA exposure on immediate and delayed skin hypersensitivity reactions in humans

SummaryA single UVB or PUVA exposure given 4 days prior to skin testing affected skin responses both to contact allergens and to histamine and the histamine liberator, compound 48/80. The delayed contact hypersensitivity reactions were attenuated by UVB in 75% and by PUVA in 79% of the tests. The immediate skin reactions to histamine and compound 48/80 were diminished by UVB in 81% and by PUVA in 46% of the cases.While the epidermal Langerhans cell (LC) density was distinctly affected by irradiation, the attenuation of skin hypersensitivity reactions seemed to be independent of the degree of LC depletion. A significant correlation was, however, found between the strength of the erythemal reaction induced by the irradiation and the attenuation of the skin hypersensitivity test reactions; this was true for both delayed and immediate skin reactions in the case of UVB and for immediate skin reactions in the case of PUVA. The mechanism behind the attenuating effect of UV radiation on skin hypersensitivity reactions remains unknown, but it probably does not result from a stabilization of the mast cell membrane, as histamine and compound 48/80 induced reactions were suppressed to a similar extent.

Blackcurrant seed oil for prevention of atopic dermatitis in newborns: a randomized, double-blind, placebo-controlled trial.

Background The present increased incidence of atopic diseases has been associated with an altered intake of essential fatty acids (EFAs). The composition of blackcurrant seed oil (BCSO) corresponds to the recommended dietary intake of EFAs, and as a dietary supplement could, in small doses, modify the imbalance of EFAs in an efficient way.

Skin phototoxicity variations during repeated bath PUVA exposures to 8‐methoxypsoralen and trimethylpsoralen

When applying psoralens topically to the skin by a 15‐min bathing procedure, a dilute trioxsalen solution (0.2 mg/l) produced a ten‐ to fifteen‐fold stronger skin photosensitization than a two‐fold more concentrated methoxsalen solution. There were both inter‐ and intra‐individual variations in psoralen‐induced photosensitivity when the treatments were repeated five times in each of five test subjects. In particular, the skin UV‐A sensitivity increased progressively at each subsequent psoralen bathing, but this did not seem to be due to an accumulation of the psoralen in the skin.

UV-Induced Tolerance to a Contact Allergen Is Impaired in Polymorphic Light Eruption

Polymorphic light eruption (PLE) is a common skin disorder provoked by exposure to UVR. Its clinical symptoms resemble those of a contact allergic reaction. PLE is generally considered a T-cell-mediated autoimmune reaction toward a yet unidentified antigen formed in UVR-exposed skin. Predisposition to such an immune reaction may result from aberrant epitope formation, increased immune reactivity to a universal epitope, or diminished propensity to UVR-induced immunosuppression or to the induction of tolerance. In a study comprising a total of 24 PLE patients and 24 healthy sex- and age-matched controls, we found that both groups demonstrated similar immunosuppression of contact sensitization to diphenylcyclopropenone by earlier exposure to solar-simulating UVR. However, only 1 out of 13 PLE patients (8%) versus 6 out of 11 controls (55%) that had been immunosuppressed by UVR exhibited a state of immunotolerance toward the same allergen after 10-24 months (P=0.023). We conclude that the impaired propensity to UVR-induced allergen-specific immunotolerance may promote recurrent PLE.

Effect of oral methoxsalen photochemotherapy on human langerhans cell number

SummaryIn human adult volunteers, oral 8-methoxypsoralen and UVA (PUVA) caused an almost linear dose-response effect in depleting adenosine triphosphatase positive epidermal Langerhans cells (LC) when irradiations of 1–5 J/cm2 were used. A higher dose did not appreciably augment the LC depleting effect although the intensity of the PUVA-induced skin inflammation increased. After a single PUVA dose of 5 J/cm2, a nadir in LC density was achieved on day 8 after irradiation, with a decrease from the starting mean count of 704 ± 58 cells/mm2 to 195 ± 173 cells/mm2. On day 15 after irradiation, the LC count was still low (261±249 cells/mm2). In comparison, a single erythematogenic irradiation with a medium-pressure mercury lamp emitting mainly UVB caused an LC depletion which was less intensive, peaked earlier and was almost completely restored by day 15. With both modalities morphological changes were induced in the LC, manifested initially as a shortening of the dendritic processes and later as cell enlargement and dendrite elongation.

Systemic suppression of human peripheral blood phagocytic leukocytes after whole-body UVB irradiation.

We examined systemic effects of whole‐body UVB irradiation on human peripheral blood phagocytes. We found that 24 h after a single erythemal dose of UVB radiation two phagocyte functions, adhesion and phagocytosis, were reduced by 50%. This functional suppression was accompanied by a significant decrease in the expression of complement receptors (CR1 and CR3) and IgG Fc receptors (FcRII and FcRIII). The greatest reduction (47%) was observed in CR3, which is important for both adhesion and phagocytosis. A kinetic analysis showed that both CR1 and CR3 levels started to decrease 15 min after the UVB exposure, reaching the lowest levels at 4.5‐ and 24‐h time points, respectively. The down‐modulation of CRs after whole‐body UVB exposure was not due to a defective receptor synthesis or translocation from internal stores to plasma membrane because the maximal CR levels in stimulated cells were not affected by UVB. No change in the serum soluble ICAM‐1 was detected after UVB, which rules out CD11b epitope masking by sICAM‐1. UVB did not release low‐receptor‐density myeloid progenitor cells from storage pools into circulation. Interleukin 10, a mediator of UVB‐induced immunosuppression, was unable to modulate CR expression in vitro. When seven suberythemal whole‐body UVB exposures were given repeatedly within 2 weeks, a significant decrease in CR expression was seen, which was greatest after three irradiations. Our data suggest that an exposure to UVB has systemic effects in humans which, possibly due to the down‐modulation of preexisting cell‐surface receptors, suppress some important functions of circulating phagocytic cells. J. Leukoc. Biol. 65: 573–582; 1999.

Black currant seed oil supplementation of mothers enhances IFN-γ and suppresses IL-4 production in breast milk.

The first year of infancy is crucial for the development of atopic immune response. Inadequate early Th1 and Treg responses and increased production of Th2 cytokines are associated with atopy. Breast milk contains several immunomodulatory cytokines and other factors that might influence the maturation of the infants immune system. We assessed the cytokines in breast milk of mother of newborn infants and their associations with black currant seed oil (BCSO) supplementation during pregnancy, mothers atopic status and the development of infants atopic dermatitis.

Cutaneous lupus erythematosus after treatment with paclitaxel and bevacizumab for metastatic breast cancer: a case report

IntroductionThe monoclonal anti-vascular endothelial growth factor antibody bevacizumab is increasingly used in the treatment of several malignant tumors. The usual side effects of this drug are hypertension and proteinuria. Paclitaxel is widely used in the treatment of breast cancer and head and neck carcinomas. Neither of these two drugs typically causes skin disorders. Paclitaxel-related cutaneous lupus erythematosus has been described before, but in earlier cases patients had a history of autoimmune disease.Case presentationWe report a case of a 65-year-old Caucasian woman who presented with cutaneous lupus erythematosus after receiving paclitaxel-bevacizumab combination treatment as first-line therapy for metastatic breast cancer. Her cutaneous symptoms and increased serum anti-SSA and anti-SSB antibodies disappeared shortly after the discontinuation of therapy.ConclusionWe conclude that cutaneous lupus erythematosus can also be seen in patients without earlier anamnesis of autoimmune disorders and that, furthermore, bevacizumab might cause atypical cutaneous side effects.

Perceived impact of psoriasis on leisure-time activities

BackgroundPsoriasis has an influence on various aspects of patients’ everyday life. When estimating the total burden of the disease, the influence on leisure-time should also be taken into account.ObjectivesTo evaluate the perceived impact of psoriasis on leisure-time activities.Material and methodsThe questionnaire study was based on 262 patients with psoriasis. The patients were asked to list their leisure-time activities, any activities they had reduced or given up completely because of psoriasis, the time spent on current leisure-time activities and the time they would have spent in a hypothetical situation if they did not have psoriasis. Using a visual analogue scale (VAS) of 0–100, the patients assessed how well they could currently perform their leisure-time activities and how well in a hypothetical situation without psoriasis. The difference between the VAS scores depicted the level of disadvantage caused by psoriasis.ResultsMore than half the patients (51.9%) had reduced or completely given up at least one leisure-time activity. The disadvantage score (VAS) of psoriasis was 16.9. Younger age was associated with higher disadvantage (r = 0.154, p<0.05). Sports activities were completely given up by 30.2% and reduced by 23.7%. Social activities and those which could be expected to cause embarrassment were given up by 29.0% and reduced by 21.4% of the patients.ConclusionA majority of patients with psoriasis reduce or give up leisure-time activities because of their condition, so the influence of psoriasis on leisure-time is considerable.