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.

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.

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.

Accrual of non-melanoma skin cancer in renal-transplant recipients: experience of a Victorian tertiary referral institution.

BACKGROUND: Cutaneous carcinogenesis is increased in immunosuppressed organ transplant recipients (OTR). Tumour accrual is a useful measure for the rate of cutaneous carcinogenesis. There are few studies in tumour accrual rates in OTR in Australia. METHODS: This was a prospective study of renal transplant recipients in a single tertiary referral centre over 5 years (60 months). Outcome measures included tumour accrual, and numbers of skin cancers according to clinical risk factors (age, sex, anatomical location, skin phototype, duration of immunosuppression, history of graft rejection, acitretin use, occupational sun exposure and family history of skin cancer). RESULTS: A total of 142 patients were included in the study, with a median follow-up duration of 1.9 years. Of these patients, 53 (37%) developed a total of 341 invasive non-melanoma skin cancers (NMSC) (253 squamous cell carcinoma [SCC] and 88 basal cell carcinoma [BCC]) over the study period. Accrual for SCC and BCC were 0.89 SCC/patient per year and 0.31 BCC/patient per year, respectively. The overall NMSC accrual was 1.20 NMSC/patient per year. SCC accrual increased with the duration of immunosuppression. NMSC accrual increased with a history of graft rejection. CONCLUSIONS: The current study provides prospective, histologically verified and quantitative evidence for the increase of cutaneous carcinogenesis in renal transplant recipients in Victoria, Australia.

Which patients with dermatological conditions are admitted via the emergency department?

BACKGROUND AND OBJECTIVES: Most dermatology admissions to tertiary hospitals in Australia are initially assessed in the emergency department (ED). This 3-year retrospective study examined the types of dermatological conditions that necessitated admission, the factors that predicted admission and the implications for dermatological resource allocation. METHODS: The ED database was searched using the International Statistical Classification of Diseases, 10(th) revision (ICD-10) diagnosis codes and keywords in the presenting complaint and triage notes fields. The two lists were then merged and duplicates removed. All admissions were analysed and the medical records of admissions to the dermatology unit were reviewed to determine their final diagnosis. RESULTS: In total, 4817 patients with dermatological conditions presented over the 3-year period. Of these, 937 (20%) required admission, of whom 108 (12%) were admitted under the dermatology unit. The most common conditions requiring admission were cellulitis (n = 534, 56%), boils, furuncles and pilonidal sinuses (n = 183, 19%), and non-specific skin infections (n = 32, 3%). The most common conditions admitted under dermatology were psoriasis (n = 27, 25%), eczema (n = 25, 23%), and cellulitis (n = 16, 15%). Key predictors of admission were Australasian triage code, referral by a health-care professional or corrections officer and arrival by ambulance. CONCLUSION: Approximately one-fifth of dermatological presentations required admission, mostly for infective processes that did not require specific dermatological care. The predictors of admission reflect the severity of the condition and patients demonstrating these predictors should be referred to the Dermatology unit for admission.