Nicotinamide for Skin-Cancer Chemoprevention in Transplant Recipients.

BACKGROUND: Immunosuppressed organ-transplant recipients have an increased incidence of, and mortality from, skin cancer. Nicotinamide (vitamin B3) enhances the repair of ultraviolet (UV) radiation-induced DNA damage, reduces the cutaneous immunosuppressive effects of UV radiation, and reduces the incidence of keratinocyte cancers (including squamous-cell and basal-cell carcinomas) and actinic keratoses among high-risk immunocompetent patients. Whether oral nicotinamide is useful for skin-cancer chemoprevention in organ-transplant recipients is unclear. METHODS: In this phase 3 trial, we randomly assigned, in a 1:1 ratio, organ-transplant recipients who had had at least two keratinocyte cancers in the past 5 years to receive 500 mg of nicotinamide or placebo twice daily for 12 months. Participants were examined for skin lesions by dermatologists at 3-month intervals for 12 months. The primary end point was the number of new keratinocyte cancers during the 12-month intervention period. Secondary end points included the numbers of squamous-cell and basal-cell carcinomas during the 12-month intervention period, the number of actinic keratoses until 6 months after randomization, safety, and quality of life. RESULTS: A total of 158 participants were enrolled, with 79 assigned to the nicotinamide group and 79 to the placebo group. The trial was stopped early owing to poor recruitment. At 12 months, there were 207 new keratinocyte cancers in the nicotinamide group and 210 in the placebo group (rate ratio, 1.0; 95% confidence interval, 0.8 to 1.3; P = 0.96). No significant between-group differences in squamous-cell and basal-cell carcinoma counts, actinic keratosis counts, or quality-of-life scores were observed. Adverse events and changes in blood or urine laboratory variables were similar in the two groups. CONCLUSIONS: In this 12-month, placebo-controlled trial, oral nicotinamide therapy did not lead to lower numbers of keratinocyte cancers or actinic keratoses in immunosuppressed solid-organ transplant recipients. (Funded by the National Health and Medical Research Council; ONTRANS Australian New Zealand Clinical Trials Registry number, ACTRN12617000599370.).

Clinical overlap of PHACE and LUMBAR syndromes.

Segmental infantile hemangiomas affecting the upper body are associated with PHACE(S) (Posterior fossa anomalies, Hemangioma, Arterial anomalies, Cardiac anomalies, Eye anomalies, and Sternal defects) syndrome, whereas segmental infantile hemangiomas affecting the lower body are the cutaneous hallmark of LUMBAR (Lower body hemangioma and other skin defects, Urogenital anomalies and Ulceration, Myelopathy, Bony deformities, Anorectal malformations and Arterial anomalies, and Renal anomalies) syndrome. We present two individuals with concurrent features of both PHACE and LUMBAR syndromes demonstrating an overlap phenotype. The overlapping features seen in our patients suggest that these syndromes occur on the same phenotypic spectrum and derive from a common embryonic pathophysiology.

A long-term cohort study of acitretin for prevention of keratinocyte carcinoma in solid organ transplant recipients.

BACKGROUND: Solid organ transplant recipients (SOTR) are at high risk of keratinocyte carcinoma (KC). Long-term evidence for acitretin as chemoprophylaxis in this population is lacking. OBJECTIVE: To determine the benefit of long-term acitretin for KC chemoprevention in SOTR. METHODS: A retrospective cohort study of SOTR treated with acitretin at an Australian transplant dermatology clinic was performed. General estimating equations were used to evaluate change in rates of histologically confirmed KC in the 6-12 months prior to acitretin and following a minimum 6 months of treatment. A control group of patients within the same service was included, comprising SOTR who were not treated with acitretin. RESULTS: Twenty-two patients received acitretin treatment for at least 6 months, eighteen for at least 5 years and four for at least 9 years. The median KC rate pretreatment was 3.31 per year (IQR 1.93, 5.40). There was a significant reduction in the rate of KC in the first year of acitretin treatment (IRR 0.41, 95% CI 0.22, 0.76, P = 0.005), and this effect was observed for 5 years (IRR at 5 years 0.34, 95% CI 0.17, 0.67, P = 0.002). The control group had no statistically significant change in KC rate over time in the study. CONCLUSIONS: Acitretin appears to be well-tolerated and effective in reducing KC in SOTR for at least 5 years. Study limitations include its retrospective nature, small sample size and lack of blinding.

Allergic contact dermatitis in children and proposal for an Australian Paediatric Baseline Series.

BACKGROUND: Allergic contact dermatitis (ACD) is an increasingly common diagnosis in children. The objectives of this study were to review our experience with ACD in children in tertiary settings, to ascertain the spectrum of allergens in this population and to subsequently propose the first Australian Paediatric Baseline Series for patch testing. METHODS: We conducted a retrospective analysis of patch test data from 1993 to 2017 from two tertiary referral patch-testing centres in Melbourne, Victoria. RESULTS: A total of 511 children were patch tested during the study period. Of these, 58.3% (298/511) of children tested had a positive patch test, and 65.1% (194/298, or 38.0% of the total) had a relevant positive patch test. The most common relevant patch test reactions were fragrance mix, methylchloroisothiazolinone/methylisothiazolinone (MCI/MI) and methylisothiazolinone (MI), Myroxylon pereirae, nickel sulphate, and colophonium. CONCLUSION: Allergic contact dermatitis is not uncommon in children, and patch testing should be considered in children with suspected ACD or with recalcitrant atopic dermatitis. Based on our experience over 25 years, we propose the first Australian Paediatric Baseline Series.

Outcome Measurement Instruments for Provoked Vulvodynia: A Systematic Review.

OBJECTIVE: The objective of this study was to detail the outcome measurement instruments used in randomized control trials and observational studies investigating therapeutic interventions for provoked vulvodynia. MATERIALS AND METHODS: We searched Ovid Medline, Embase, Emcare, and PyschINFO libraries from database inception through April 2017. We included randomized control trials and observational studies of provoked vulvodynia that used instruments to measure the outcome of therapeutic interventions. RESULTS: A total of 2299 articles were retrieved and 25 were eligible for inclusion in accordance with the selection criteria. The included studies measured 26 different outcomes, using 110 outcome measurement instruments. Patient-reported outcomes were most commonly measured (144/166, 86%), followed by physician-reported outcomes (20/166, 12%). The most commonly measured outcomes were patient-reported psychological impact of disease (27/166, 16%), patient-reported improvement in dyspareunia (25/166, 15%), and patient-reported reduction in pain (24/166, 14%). The Pain Catastrophizing Scale, the Beck Depression Inventory, and the State Trait Anxiety Questionnaire were the most commonly used instruments to measure psychological impact.The most commonly measured clinician-rated outcome was an improvement in pain (17/166, 10%), which was most frequently assessed by the cotton swab test. Only 34 (31%) outcome measurement instruments were specific to vulvodynia (26/110, 23%) or sexual functioning (8/110, 7%). CONCLUSIONS: There is a wide range of outcome measurement instruments used in provoked vulvodynia studies, resulting in inconsistency of reporting and difficulty in comparing and combining findings for systemic review. There is a pressing need for the development of validated, reliable instruments and consensus on a core outcome set for further research purposes.