Melanoma predilection for the lower limbs of women compared with men.

The lower limb is a common site for melanoma in women, but the reason for this is not fully understood. To investigate this phenomenon in more detail, we assessed the specific subsites of primary melanoma occurring on the lower limbs of females compared with males across age groups. In a records-based study at an oncology hospital in north-west of England, among an unselected sample of patients with primary invasive melanoma treated between 2002-2015, information was collected on patient age at diagnosis, sex, and co-morbidities, and the tumor thickness and anatomical subsite (thigh, lower leg, foot for lower limb). Of a total sample of 1,522 patients, 316 (227, 72% female) had lower limb melanoma. The most common subsite was lower leg (142 cases with F:M ratio =3.74), followed by thigh (55 cases with F:M = 1.83) and feet (30 cases with F:M = 1.15). At ages <40 years the odds of thigh to foot melanoma was 20 times higher in females than in males (OR 20.0, 95% CI 2.6-152.6) and 7.5 times higher on the lower limb (OR 7.5, 95% CI 1.1-49.2). For ages 40+ years, the odds of females developing thigh melanoma compared to foot melanoma was similar in males versus females (OR 0.8), while the corresponding odds of lower leg melanoma in females versus males remained significantly increased at ages 40-59 and 60+ (OR 4.2 and 2.8 respectively). Our study demonstrates the female predilection for lower limb melanoma persists over most but not all subsites.However, there is heterogeneity in the female to male occurence of lower limb melanoma across subsites and at different ages, which may be linked to relative influence of genetic and environmental risk factors.

Skin cancer multiplicity in lung transplant recipients: a prospective population-based study.

BACKGROUND: Lung transplant recipients are at high risk of skin cancer, but precise annual incidence rates of treated skin cancers per patient are unknown. OBJECTIVES: To perform a prospective assessment of the total burden of histologically confirmed squamous cell carcinoma (SCC) and basal cell carcinoma (BCC) and associated factors in lung transplant recipients. METHODS: A population-based cohort of 125 Queensland lung transplant recipients aged 18 years and over, recruited between 2013 and 2015, were followed to the end of 2016. All underwent dermatological skin examinations at baseline and annually thereafter and patients self-reported all interim treated skin cancers, which were verified against pathology databases. Standard skin cancer risk factors were obtained via questionnaire, and details of medications were acquired from hospital records. RESULTS: During a median follow-up time of 1·7 years, 29 (23%) and 30 (24%) lung transplant recipients with a median duration of immunosuppression of 3·3 years developed SCC and BCC, respectively. The general population age-standardized incidence rates of SCC and BCC were 201 and 171 per 1000 person-years, respectively (based on first primary SCC or BCC during follow-up); however, on accounting for multiple primary tumours, corresponding incidence rates were 447 and 281 per 1000 person-years. Risk of multiple SCCs increased around sixfold in those aged ≥ 60 years and in those with previous skin cancer, and increased around threefold in those treated with the antifungal medication voriconazole. Multiple BCC risk rose threefold from age 60 years and tenfold for patients with previous skin cancer. CONCLUSIONS: Lung transplant recipients have very high incidence of multiple primary skin cancers. Close surveillance and assiduous prevention measures are essential. Linked Comment: Proby and Harwood. Br J Dermatol 2020; 183:416-417.

Clinical comparison of actinic changes preceding squamous cell carcinoma vs. intraepidermal carcinoma in renal transplant recipients.

Intraepidermal carcinoma (IEC) is a type of in situ squamous cell carcinoma (SCC), although progression of IEC is rare. We sought to investigate differences between the actinic skin changes preceding the development of both SCC and IEC. Photographs of 63 skin sites at which either SCC or IEC subsequently developed in 37 renal transplant recipients (RTRs) were examined for features of actinic change. We found that areas of skin with an actinic keratosis (AK) > 1 cm2 in size were four times more likely to develop SCC as opposed to IEC (OR = 4.42; 95% CI 1.25-15.60). Skin sites with ≥ 25% of the area affected by AK were again four times more likely to develop SCC than IEC. These results highlight the scale of visible actinic damage required for development of SCC compared with IEC, emphasizing the importance of treating areas of skin with marked visible actinic change to reduce SCC risk in RTRs.

Actinic keratosis-related signs predictive of squamous cell carcinoma in renal transplant recipients: a nested case-control study.

BACKGROUND: Squamous cell carcinoma (SCC) and intraepidermal carcinoma (IEC) commonly arise in actinically damaged skin. OBJECTIVES: To identify clinical features of actinic change that correlate with an increased risk of SCC or IEC in the short-to-medium term as guidance for prioritizing field treatment. METHODS: In a nested case-control study, cases were renal transplant recipients who developed an incident SCC or IEC within 18 months following baseline examination and photography. Controls without SCC or IEC were matched to cases on age, sex and duration of immunosuppression. Predefined skin sites on the head, neck and upper limbs were examined using baseline photographs to assess objectively the following features of actinic damage: presence of actinic keratosis (AK) patch (defined as AK > 1 cm2 ), number of AK patches, number of AKs and area affected by AK. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated using McNemar's test to identify differences in SCC/IEC risk combined and SCC risk alone between case and control skin sites. RESULTS: Thirty-nine cases were matched to 39 controls. Significant associations with the presence of an AK patch, number of AK patches, number of AKs and area affected by AKs were identified. The presence of an AK patch conferred an 18-fold increased risk of SCC (OR 18·00, 95% CI 2·84-750) and more than a sixfold increased risk of SCC/IEC combined (OR 6·60, 95% CI 2·56-21·66). CONCLUSIONS: AK patches are predictive of SCC/IEC development within 18 months. This can be used to guide site selection for field treatment in patients with widespread actinic damage.

Azathioprine and Risk of Skin Cancer in Organ Transplant Recipients: Systematic Review and Meta-Analysis.

Azathioprine, a purine antimetabolite immunosuppressant, photosensitizes the skin and causes the production of mutagenic reactive oxygen species. It is postulated to increase the risk of squamous cell carcinoma (SCC) and other skin cancers in organ transplant recipients (OTRs), but evidence from multiple, largely single-center studies to date has been inconsistent. We aimed to resolve the issue of azathioprine's carcinogenicity by conducting a systematic review of the relevant literature and pooling published risk estimates to evaluate the risks of SCC, basal cell carcinoma (BCC), keratinocyte cancers (KCs) overall and other skin cancers in relation to azathioprine treatment. Twenty-seven studies were included in total, with risk estimates from 13 of these studies able to be pooled for quantitative analysis. The overall summary estimate showed a significantly increased risk of SCC in relation to azathioprine exposure (1.56, 95% confidence interval [CI] 1.11-2.18). No significant associations between azathioprine treatment and BCC (0.96, 95% CI 0.66-1.40) or KC (0.84, 95% CI 0.59-1.21) risk were observed. There was significant heterogeneity between studies for azathioprine risk estimates and the outcomes of SCC, BCC and KC. The pooled findings of available evidence support the contention that treatment with azathioprine increases the risk of SCC in OTRs.

Evidence-based management of vitiligo: summary of a Cochrane systematic review.

Vitiligo affects around 1% of the world's population. Despite it being relatively common, there is still no effective treatment. The objective of this study was to update the Cochrane systematic review of randomized clinical trials (RCTs) to evaluate the efficacy of treatments for vitiligo. We carried out searches of a range of databases to October 2013 for RCTs of interventions for vitiligo regardless of language or publication status. At least two reviewers independently assessed study eligibility and methodological quality and extracted data using data extraction forms approved by the Cochrane Skin Group. Our primary outcomes of interest were quality of life, > 75% repigmentation and adverse effects. We retrieved 96 studies, of which 39 were new studies, with an overall total of 4512 participants. Repigmentation was assessed in all studies, although only five reported on all three of our primary outcomes. Regarding our two secondary outcomes, six studies measured cessation of spread but none assessed long-term permanence of repigmentation at 2 years' follow-up. Most of the studies evaluated combination treatments, which generally showed better repigmentation than monotherapies. Of the new studies, seven were surgical interventions. The majority of the studies had fewer than 50 participants. The quality of the studies was poor to moderate at best. Very few studies specifically included children or participants with segmental vitiligo. Five years after the last update of this review, there are still important variations in study design and outcome measures in clinical trials for vitiligo, limiting the evidence for the efficacy of different therapeutic options. The best evidence from individual trials showed short-term benefit from topical corticosteroids and various forms of ultraviolet radiation combined with topical preparations. Long-term follow-up and patient-rated outcomes should be incorporated into study design, and more studies should assess psychological interventions.

Generalized pustular psoriasis associated with Epstein-Barr virus.

Generalized pustular psoriasis (GPP) is a rare and severe variant of psoriasis. We report a case of a 79-year-old woman who presented with generalized pustular psoriasis and significant Epstein-Barr virus (EBV) viraemia. Serial measurements of EBV DNA showed a correlation with the deterioration in her clinical condition. We speculate that EBV reactivation triggered the development of GPP, and propose that further investigation is required into the association between EBV and GPP.