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.).

Follicular mucinosis with novel dermoscopic finding: the toothpaste sign.

We describe a case of follicular mucinosis presenting with patchy alopecia affecting the eyebrows. On dermoscopy, white gelatinous material (presumed to be mucin) was visible along the hair shafts of the eyebrow lesions. We propose to call this novel dermoscopic finding the 'toothpaste sign'.

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.

Melanoma in a cohort of organ transplant recipients: Experience from a dedicated transplant dermatology clinic in Victoria, Australia.

BACKGROUND: There is limited information on the profile of melanomas diagnosed in a specialist transplant dermatology clinic. OBJECTIVE: To describe the incidence and characteristics of incident primary melanomas in a cohort of organ transplant recipients (OTRs) attending a specialized transplant dermatology clinic and determine the number of pigmented lesions needed to excise for every melanoma diagnosed. METHODS: A retrospective study of 327 OTRs monitored by an Australian clinic during a 10-year period. RESULTS: There were 11 incident melanomas diagnosed during a total follow-up of 1280 patient-years. The mean interval between the first transplant and diagnosis was 5.5 years. Only 2 melanomas were >1 mm in Breslow thickness. Seven melanomas (64%) arose de novo. A contiguous nevus was present in 4 cases. Metastatic disease did not develop in the melanoma patients during the follow-up period, and all remain alive. The needed to excise for every melanoma diagnosed ratio was 16:1. LIMITATIONS: The crude incidence rates were age standardized, unlike the comparison rates of melanoma in the general population, and the cohort was small. CONCLUSION: Most melanomas diagnosed in OTR patients attending a specialized transplant dermatology service were detected early. Our data suggest early detection may reduce the proportion of OTRs presenting with thick melanomas, thus improving prognosis and patient outcomes. A needed to excise for every melanoma diagnosed ratio of 16:1 is not unreasonable for this cohort of high-risk patients. To our knowledge, this is the first time this ratio has been calculated for a cohort of OTRs.

Beyond skin deep: addressing comorbidities in psoriasis.

Psoriasis is a chronic inflammatory disease that is commonly encountered in primary care and is associated with significant morbidity that extends beyond the skin manifestations. Psoriasis is associated with an elevated risk of psoriatic arthritis, cardiovascular disease, obesity, insulin resistance, mental health disorders, certain types of malignancy, inflammatory bowel disease and other immune-related disorders, and hepatic and renal disease. Enhanced recognition of these comorbidities may lead to earlier diagnosis and potentially better overall health outcomes. Psoriatic nail involvement, severe skin disease and obesity are associated with a greater risk of psoriatic arthritis. Individuals with psoriasis should be routinely screened for psoriatic arthritis to allow for early intervention to improve long term prognosis. Life expectancy is reduced in people with psoriasis due to a variety of causes, with cardiovascular disease and malignancy being the most common aetiologies. Psoriasis affects several factors that contribute to worsened quality of life and increased risk of depression and anxiety. Effective therapies are now available that have been shown to concurrently improve skin disease, quality of life and psychiatric symptoms. As the concordance between psychosocial impact and objective disease severity does not always correlate, it is essential to tailor management strategies specifically to the needs of each individual. Cigarette smoking and excess alcohol consumption are among the most important modifiable risk factors that increase the likelihood of psoriasis development and severity of skin disease. This provides a compelling rationale for smoking cessation and limiting alcohol intake in people with psoriasis beyond their traditional harmful health consequences.

Atypical severe progressive perioral ulceration due to herpes simplex virus on the background of undiagnosed HIV/AIDS.

Perioral ulcerative plaques have a broad list of differential diagnoses. We describe an unusual presentation of chronic progressive perioral ulceration due to herpes simplex type (HSV)-1 on a background of undiagnosed human immunodeficiency virus infection with acquired immunodeficiency syndrome. Whilst chronic mucocutaneous HSV is an AIDS-defining condition with both HSV-1 and HSV-2 implicated, typical reported cases describe vesicular eruptions rather than perioral ulcerative plaques. This case highlights that common infections may present atypically in immunocompromised individuals and may be a clue to underlying systemic illness.

Skin cancer history, sun-related attitudes, behaviour and sunburn among renal transplant recipients versus general population.

BACKGROUND/OBJECTIVES: Renal transplant recipients (RTR) have both an excessive skin cancer incidence and a high mortality rate. In Australia RTR receive extensive public education on skin cancer and many undergo further education pre/post-transplant. This study examines whether RTR have sufficiently rigorous sun protection behaviour compared with the general population. METHODS: Altogether 179 RTR from two large Melbourne hospitals involving skin clinic teams in patient care were recruited to undergo cross-sectional telephone interviews. Comparisons were made with residents (25-69 years) surveyed using equivalent measures and methods in adjacent summers (2006-2007, n = 904; 2010-2011, n = 942) for regular population monitoring surveys. Multivariate analyses of weekend behaviour were adjusted for related ambient temperature records. RESULTS: RTR were more compliant with sun protection behaviour on the weekend prior to interview than the residents surveyed. For example, for 2006-2007 and 2010-2011, the odds ratio and confidence intervals (CI 95%) were respectively: used sunscreen: 2.0 (1.1-3.8) and 2.8 (1.4-5.3); wore a long-sleeved top: 4.5 (2.4-8.5) and 3.6 (1.9-7.0). RTR sunburn prevalence (5%) appeared similar to that of residents (odds ratios comparing 2006-2007 and 2010-2011 0.6 [95% CI, 0.2-1.6] and 0.7 [95% CI, 0.3-1.9]). Despite generally good sun protection behaviour, many RTR (47%) had skin cancers treated. CONCLUSION: The intensive education of RTR may have contributed to their better sun protection. Some RTR with excessive exposure to UV radiation introduction of may benefit from implementation of further photoprotection strategies. These findings may be particularly relevant to other RTR groups receiving education about sun protection.

Dermatology teaching in Australian Medical Schools.

BACKGROUND/OBJECTIVES: Although skin disease and skin cancers cause significant morbidity and mortality in Australia, limited time is dedicated to dermatology teaching in most medical courses. The aim of this study was to define the current state of dermatology teaching in Australian medical schools with a view to developing a national core curriculum for dermatology. METHODS: An electronic questionnaire was circulated to the dermatology teaching leads and relevant medical program coordinators of the 18 medical schools in Australia. RESULTS: Replies were received from 17 medical schools. Dermatology was included as part of the core curriculum in 15 schools. Time set aside for dermatology teaching varied, as reflected by the number of lectures delivered (0-21, mean 5, median 3) and minimum clinics attended (0-10, mean 1.2, median 0). Only four medical schools had a compulsory clinical attachment in dermatology. Furthermore, satisfying requirements in dermatology was mentioned in the university examination regulations in only six schools. Certain core learning outcomes were addressed in most schools, including the structure and function of the skin, common conditions such as atopic dermatitis and psoriasis and cutaneous malignancies. However, there were important omissions, ranging from common problems like dermatophyte infections and drug reactions to the recognition of dermatological emergencies. CONCLUSIONS: These results are a compelling impetus to improve current standards of dermatology teaching, learning and assessment. The introduction of a national core curriculum would provide guidelines for dermatology teaching in medical schools, enabling the more effective utilisation of available time for key learning outcomes.

Pseudoepitheliomatous hyperplasia secondary to allergic contact dermatitis to Grevillea†Robyn Gordon.

We report a case of pseudoepitheliomatous hyperplasia (PEH) in a 55-year-old woman following allergic contact dermatitis (ACD) to Grevillea Robyn Gordon. We believe this to be the first reported case of PEH secondary to ACD, and postulate that this was an exaggerated response to severe ACD as a result of a lack of topical treatment.

Two cases of amoxycillin-induced follicular acute localised exanthematous pustulosis.

We report two cases of Caucasian women who developed folliculocentric pustulosis after exposure to amoxycillin. A literature review found that most amoxycillin-related pustular eruptions were reported as acute generalised exanthematous pustulosis (AGEP) or acute localised exanthematous pustulosis (ALEP). Histopathology from both our cases showed sterile suppurative folliculitis, which resolved on the cessation of amoxycillin.

Rosacea.

BACKGROUND: Rosacea is a chronic and common cutaneous condition characterised by symptoms of facial flushing and a broad spectrum of clinical signs. The clinical presentation for rosacea is varied, and there are four primary subtypes, which may overlap - erythrotelangiectatic, inflammatory, phymatous and ocular. It is important to recognise the different subtypes because of the differences in therapy. OBJECTIVE: The objective of this article is to provide evidence-based clinical updates to clinicians, specifically general practitioners (GPs), to assist with their everyday practice, and effective assessment and treatment of rosacea. DISCUSSION: Therapeutic modalities are chosen on the basis of the subtypes and clinical features identified; often a combination of these therapies is required.

Small molecule targeting malaria merozoite surface protein-1 (MSP-1) prevents host invasion of divergent plasmodial species.

Malaria causes nearly 1 million deaths annually. Recent emergence of multidrug resistance highlights the need to develop novel therapeutic interventions against human malaria. Given the involvement of sugar binding plasmodial proteins in host invasion, we set out to identify such proteins as targets of small glycans. Combining multidisciplinary approaches, we report the discovery of a small molecule inhibitor, NIC, capable of inhibiting host invasion through interacting with a major invasion-related protein, merozoite surface protein-1 (MSP-1). This interaction was validated through computational, biochemical, and biophysical tools. Importantly, treatment with NIC prevented host invasion by Plasmodium falciparum and Plasmodium vivax--major causative organisms of human malaria. MSP-1, an indispensable antigen critical for invasion and suitably localized in abundance on the merozoite surface represents an ideal target for antimalarial development. The ability to target merozoite invasion proteins with specific small inhibitors opens up a new avenue to target this important pathogen.

The fish tank strikes again: metachronous nontuberculous mycobacterial skin infection in an immunosuppressed host.

An 82-year-old woman on long-term prednisolone for chronic obstructive airways disease presented with a 2-month history of nodules on her left forearm. This occurred 10 years after nodules on her right forearm caused by a culture-proven Mycobacterium marinum infection. Histopathological examination, polymerase chain reaction and culture of biopsy specimens were positive for M. chelonae. To our knowledge this is the first case of metachronous nontuberculous mycobacterial skin infection reported, and it highlights the diagnostic and therapeutic challenges of such infections.