An updated report on the incidence and epidemiological trends of keratinocyte cancers in the United Kingdom 2013-2018.

Introduction: The most common cancers in the UK are keratinocyte cancers (KCs): the combined term for basal cell carcinomas (BCCs) and cutaneous squamous cell carcinomas (cSCCs). Registration of KC is challenging due to high numbers and multiplicity of tumours per person. Methods: We provide an updated report on the descriptive epidemiology of trends in KC incidence for the resident populations of UK countries (England, Northern Ireland, Scotland and Wales) using population-based cancer registry and pathology report data, 2013-18. Results: Substantial increases in cSCC incidence in England, Scotland and Northern Ireland can be detected for the period of 2013-18, and the incidence of cSCC also increased in Wales from 2016 to 2018. In contrast, however, the pattern of annual change in the incidence of BCC across the nations differs. In England, the incidence of BCC declined slightly from 2016 to 2018, however, the overall trend across 2013-18 is not statistically significant. In Scotland, the incidence of BCC shows some variability, declining in 2017 before increasing in 2018, and the overall trend across 2013-18 was also not statistically significant. In Northern Ireland, the incidence of BCC increased significantly over the study period, and in Wales, the incidence of BCC increased from 2016 to 2018. One in five people will develop non-melanoma skin cancers (NMSC) in their lifetime in England. This estimate is much higher than the lifetime risk of melanoma (1 in 36 males and 1 in 47 females born after 1960 in the UK), which further highlights the burden of the disease and importance of early prevention strategies. Conclusions: We highlight how common these tumours are by publishing the first ever lifetime incidence of NMSC. Additionally, the first time reporting of the age standardised incidence of KC in Wales further confirms the scale of the disease burden posed by these cancers in the UK. With approximately one in five people developing NMSC in their lifetime, optimisation of skin cancer prevention, management and research are essential.

'Atrophic telogen effluvium' from cytotoxic drugs and a randomized controlled trial to investigate the possible protective effect of pretreatment with a topical vitamin D analogue in humans.

BACKGROUND: Hair loss from cytotoxic drugs is classically ascribed to the loss of fractured hairs (anagen effluvium). Telogen hair loss has also been described but some authors have denied any effect on the hair cycle. There are conflicting reports on a protective effect of pretreatment with a vitamin D analogue on cytotoxic drug-induced hair loss in rodents. OBJECTIVES: To investigate the process of cytotoxic hair loss and any protective effect on the hair of pretreatment with topical calcipotriol. METHODS: Breast cancer patients who were about to receive cycles of chemotherapy with cyclophosphamide 600 mg m(-2), methotrexate 40 mg m(-2) and 5-fluorouracil 600 mg m(-2) were recruited and randomized to receive calcipotriol scalp solution 50 microg mL(-1) or vehicle. The solution was applied twice daily from 4 days prior to chemotherapy and continued for 14 days in each treatment cycle. Shed, plucked and cut hairs were sampled. Absolute shed rates, the proportion of major hair types, the presence of proximal hair shaft changes, regrowth (using the new anagen hair count) and hair density were assessed. RESULTS: Ten patients receiving calcipotriol and 14 receiving vehicle completed three treatment cycles and nine from both groups completed six cycles. There was no detectable effect of calcipotriol on the proportion of patients experiencing minimal hair loss from chemotherapy, shed rates, plucked telogen and fractured hair counts, the morphology of shed and plucked hair, hair regrowth or hair density. Combining results of the treatment groups, there was a large variation in the impact of chemotherapy on hair loss, from total loss in five patients to no obvious loss in five. Excluding the latter, during chemotherapy shed telogen hairs (mean 81% of shed hairs) predominated over fractured (12%) and anagen hairs (6%) (P = 0.0002). The major pathological change was proximal hair shaft tapering, baseline mean 3% of shed hairs rising to 48% (P = 0.0005) during treatment, and there was a consequent decrease in normal telogen hairs, baseline mean 98% of all telogen hairs falling to 55% (P = 0.0005) during treatment. The pathological tapered telogen hairs had normal or small, sometimes diminutive, bulbs. Fracturing of hairs with diminutive bulbs produced typical 'exclamation mark' hairs. CONCLUSIONS: The cardinal effects of cytotoxic drugs found in this study were tapering of the proximal hair shaft and premature entry of the follicle into telogen, conflicting with the conventional view that affected hair follicles continue in anagen. There was a resulting effluvium of a mixture of tapering telogen hairs and fractured hairs. As entry into telogen is an integral part of the process, cytotoxic hair loss may be regarded as a variant of the conventional 'telogen effluvium' and we propose the term 'atrophic telogen effluvium'. There was no obvious protective effect on the hair loss of prior treatment with topical calcipotriol.

Anti-E-selectin is ineffective in the treatment of psoriasis: a randomized trial.

BACKGROUND: Skin-homing, memory T lymphocytes play an important role in the pathogenesis of psoriasis by interacting with the vascular addressin, E-selectin and trafficking into lesional skin. Thus an attractive option for targeted therapy of the disease would be blockade of skin-homing T cells with an antibody directed at E-selectin. OBJECTIVE: We performed a multicentre, randomized, placebo-controlled trial to investigate the clinical efficacy and side-effect profile of a humanized monoclonal antibody to E-selectin, CDP850, in the treatment of moderate to severe chronic plaque psoriasis. METHODS: Patients with moderate/severe chronic plaque psoriasis were selected for study. Nine male subjects (mean age 37 years, range 25-47) were given 20 mg kg-1 CDP850 intravenously as a single dose and four subjects (three males, one female; mean age 40 years, range 23-50) received placebo infusion. Clinical response to treatment was assessed using the psoriasis area and severity index (PASI). Skin biopsies were taken for immunohistochemical analysis at the baseline, pretreatment, visit and also at day 2 and weeks 1 and 4 postinfusion. RESULTS: The treatment was well-tolerated with a minimal side-effect profile. Plasma E-selectin levels were significantly decreased in those subjects who received CDP850 compared with those who had placebo for the entire study period. At the end of study (8 weeks postinfusion), there was no significant reduction in PASI from baseline for either the CDP850 or placebo-treated groups. Immunohistochemical analysis of biopsies taken from lesional psoriatic skin showed that 2 days after dosing with CDP850, staining for E-selectin was decreased, although not absent, on dermal vascular endothelial cells when compared with baseline (P < 0.01). This decrease in E-selectin expression was maintained 4 weeks after infusion (P < 0.05). It was not, however, accompanied by a significant reduction in numbers of neutrophils or lymphocytes in the dermis. There was a statistically significant increase in CD1a-positive epidermal Langerhans cells compared with pre-dose levels at week 1 (P < 0.05). CONCLUSIONS: This clinicopathological study shows that anti-E-selectin (CDP850), although a well-tolerated, logical and safe therapy, does not appear to possess a therapeutic role in the treatment of chronic plaque psoriasis.

Urinary thymine dimers and 8-oxo-2'-deoxyguanosine in psoriasis.

Psoralen in conjunction with UVA (PUVA) is perhaps the most effective treatment for psoriasis. It is, however, a risk factor for skin cancer in these patients and there is a need to develop non-invasive assays reflective of treatment-induced DNA damage. We report here the assessment of two important lesions, thymine dimer (T<>T) and 8-oxo-2'-deoxyguanosine (8-OHdG), in the urine of psoriasis patients. It was found that, once corrected for urine concentration, the psoriatic group had significantly higher (P<0. 0001) urinary levels of thymine dimers compared to the control group. No significant differences in urinary 8-OHdG levels were noted between the psoriatic, atopic dermatitis and control groups. Therefore biomonitoring of therapy from the very start with this simple and non-invasive assay could perhaps be an effective measure of the risk involved with the treatment allowing optimization for minimal-risk therapy.

Long-term outcome of severe chronic plaque psoriasis following treatment with high-dose topical calcipotriol.

We have previously reported the effectiveness of high-dose calcipotriol in extensive psoriasis. We now report the long-term outcome in patients following this treatment. Twenty-eight patients with severe psoriasis were treated as in-patients with high-dose topical calcipotriol for 2 weeks. There was a mean reduction in the psoriasis area and severity index of 65%. Sixty-nine per cent were controlled for 3 months and 42% for 6 months. The relapse rate was comparable with that following Ingram's regimen, the in-patient stay was shorter and the treatment more acceptable. Careful monitoring of calcium homeostasis is mandatory.

Etretinate may work where acitretin fails.

Acitretin (Ro 10-1670, Neotigason), a second-generation monoaromatic retinoid, is the main acid derivative and active metabolite of etretinate (Ro 10-9359, Tigason). Three patients who were unresponsive to treatment with acitretin but who responded to etretinate are reported. Twenty-nine patients in the U.K. are currently receiving etretinate on a named-patient basis. Possible explanations for the functional discrepancy between the two drugs are discussed.