Skin application of the nonsteroidal anti-inflammatory drug ketoprofen downmodulates the antigen-presenting ability of Langerhans cells in mice
Does ketoprofen (KP), an inhibitor of prostaglandin (PG) synthesis, affect Langerhans cell (LC) function? Ears of BALB/c mice were painted with picrylchloride (PCl) hapten, KP, or both. PCl altered the morphology of LCs and reduced their number, and simultaneous application of 10% KP maintained LC morphology and number. KP at 5% or 10% clearly decreased the PCl-augmented expression of MHC class II and CD86 on LCs. In tissue culture of freshly isolated epidermal cells, 5 mmol L-1 KP inhibited the culture-promoted expression of these molecules on LCs, whereas 100 lmol L-1 indomethacin was not inhibitory. The further addition of PGE2 to the KP-containing epidermal cell culture did not restore the expression of these molecules. Moreover, topical application of 10% KP to the sensitizing sites suppressed the development of contact hypersensitivity to PCl. KP may have the potential to inhibit antigen-presenting ability of LCs, in a PGE2-independent manner. Br J Dermatol 2008; 159:306–313.
Interaction between p53 codon 72 polymorphism and melanocortin 1 receptor variants on suntan response and cutaneous melanoma risk
Nan et al. assessed the association of the p53 codon 72 polymorphism with tanning response, and its interaction with MC1R variants on tanning response and skin cancer risk, in a nested case–control study within the Nurses' Health Study (219 cases of melanoma, 286 of squamous cell carcinoma, 300 of basal cell carcinoma and 874 controls) and among controls from four nested case–control studies. The p53 Pro allele was positively associated with childhood tanning response only among women with black/dark brown hair. Compared with the Arg/Arg genotype, odds ratios of childhood tanning tendency for Arg/Pro and Pro/Pro genotypes were 1.59 (95% confidence interval, CI 0.96–2.65) and 1.56 (95% CI 0.55–4.40), respectively. The association between MC1R variants and childhood tanning tendency was similar in both p53 Arg/Arg genotype and Pro allele carriers. The association of the p53 Pro/Pro genotype with melanoma risk was strongest among women with light pigmentation, and with MC1R variants, with the joint risk categories having the highest overall risk. The study suggests the involvement of p53 codon 72 polymorphism in the skin tanning response and potential interaction with skin pigmentation on melanoma risk. Br J Dermatol 2008; 159:314–321.
An evidence base for reconsidering current follow-up guidelines for patients with cutaneous melanoma less than 0.5 mm thick at diagnosis
Despite current guidelines, there is uncertainty about the required duration and frequency of follow-up visits for patients with invasive primary cutaneous melanoma <0.5 mm thick. Between 1992 and 2001, 430 patients were diagnosed in the West of Scotland with melanoma <0.5 mm. Five deaths were reported in this group of patients, but on pathological review two were thicker than 0.5 mm at diagnosis (1.5 mm and >3 mm, respectively), and the remaining three all developed thicker second primary melanomas (2.7, 12.0 and 19.0 mm) with a recurrence pattern and timing indicating that these thicker primaries were the cause of death. Fourteen further patients developed a second primary melanoma, but all are currently alive and disease free. The data indicate that recurrence and subsequent death from melanomas <0.5 mm is a very rare event, and that quarterly follow up for 3 years will yield very few events. Br J Dermatol 2008; 159:337–341.
The changing face of dermatological practice: 25 years' experience
Benton et al. examined the change in outpatient workload over a 25-year period in the south east of Scotland. During a 1-month period, 2118 new and 2796 review consultations were available for analysis (new/review 1: 1.3, female/male 1.3: 1, age 0–106 years). Eighty-nine per cent of new referrals came from primary care and 11% from secondary care. Fifty-seven per cent of referrals were for diagnosis and 38% for management advice. Benign tumours accounted for 33.4%, malignant tumours 11.6%, eczema 16% and psoriasis 7.4% of new cases. For return patients, 20% had skin cancer, 16.5% eczema, 13.4% psoriasis and 9% acne. The referral rate had risen over 25 years from 12.6 per 1000 population in 1980 to 21 per 1000 in 2005, with secondary care referrals increasing from 61 in November 1980 to 230 in November 2005. Attendances for benign and malignant skin tumours had increased sixfold since 1980. Patients with eczema and psoriasis accounted for one third of clinic visits. New referrals had risen by 67%, with those from other hospital specialties almost quadrupling since 1980 to 11% of the total in 2005. Br J Dermatol 2008; 159:413–418.
Evidence of high levels of anxiety and depression in polymorphic light eruption and their association with clinical and demographic variables
Evidence of anxiety and depression was examined in patients with polymorphic light eruption (PLE). In a cross-sectional design, patients with PLE (n=145) who had attended a hospital dermatology department completed validated questionnaires assessing for anxiety, depression, social anxiety and coping strategies. Participants were aged 16–78 years (mean
SD 4411.9), 81% female, with a mean age at onset of PLE of 28 years. Evidence of high levels of anxiety and depression was found in PLE, with 22.1% and 8.3% of patients scoring as probable cases for anxiety and depression, respectively. Higher levels of anxiety were associated with younger age at onset of PLE (r=0.25, P<0.01) and facial involvement (t=2.84, P<0.01), and depression was also associated with facial involvement (t=3.60, P<0.01). Furthermore, higher levels of depression and anxiety were associated with the use of maladaptive coping strategies, and depression was found to be the principal predictor of quality of life. Br J Dermatol 2008; 159:439–444.
