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.).

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.

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'.

Consensus-Based Recommendations on the Prevention of Squamous Cell Carcinoma in Solid Organ Transplant Recipients: A Delphi Consensus Statement.

IMPORTANCE: There is a paucity of evidence to guide physicians regarding prevention strategies for cutaneous squamous cell carcinoma (CSCC) in solid organ transplant recipients (SOTRs). OBJECTIVE: To examine the development and results of a Delphi process initiated to identify consensus-based medical management recommendations for prevention of CSCC in SOTRs. EVIDENCE REVIEW: Dermatologists with more than 5 years' experience treating SOTRs were invited to participate. A novel actinic damage and skin cancer index (AD-SCI), consisting of 6 ordinal stages corresponding to an increasing burden of actinic damage and CSCC, was used to guide survey design. Three sequential web-based surveys were administered from January 1, 2019, to December 31, 2020. Pursuant to Delphi principles, respondents thoroughly reviewed all peer responses between rounds. Supplemental questions were also asked to better understand panelists' rationale for their responses. FINDINGS: The Delphi panel comprised 48 dermatologists. Respondents represented 13 countries, with 27 (56%) from the US. Twenty-nine respondents (60%) were Mohs surgeons. Consensus was reached with 80% or higher concordance among respondents when presented with a statement, question, or management strategy pertaining to prevention of CSCC in SOTRs. A near-consensus category of 70% to less than 80% concordance was also defined. The AD-SCI stage-based recommendations were established if consensus or near-consensus was achieved. The panel was able to make recommendations for 5 of 6 AD-SCI stages. Key recommendations include the following: cryotherapy for scattered actinic keratosis (AK); field therapy for AK when grouped in 1 anatomical area, unless AKs are thick in which case field therapy and cryotherapy were recommended; combination lesion directed and field therapy with fluorouracil for field cancerized skin; and initiation of acitretin therapy and discussion of immunosuppression reduction or modification for patients who develop multiple skin cancers at a high rate (10 CSCCs per year) or develop high-risk CSCC (defined by a tumor with approximately ≥20% risk of nodal metastasis). No consensus recommendation was achieved for SOTRs with a first low risk CSCC. CONCLUSIONS AND RELEVANCE: Physicians may consider implementation of panel recommendations for prevention of CSCC in SOTRs while awaiting high-level-of-evidence data. Additional clinical trials are needed in areas where consensus was not reached.

How Coronavirus Disease 2019 Changed Dermatology Practice in 1 Year Around the World: Perspectives from 11 Countries.

Coronavirus disease 2019 (COVID-19) brought the world to its knees. As each nation grappled with launching an effective response while simultaneously minimizing repercussions on health care systems, economies, and societies, the medical and scientific landscape shifted forever. In particular, COVID-19 has challenged and transformed the field of dermatology and the way we practice. In this article, dermatologists from 11 countries share insights gained from local experience. These global perspectives will help provide a better framework for delivering quality dermatologic care and understanding how the field has evolved during this medical crisis.

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.

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.

Superficial fungal infections.

BACKGROUND: Tinea is a common fungal infection that can affect the skin, nails and hair. Tinea infection has a variety of clinical manifestations and affects all age groups, ranging from tinea pedis in adults to tinea capitis in pre-pubertal children. OBJECTIVE: This article provides an updated overview of the common clinical manifestations and practical approaches to the diagnosis and management of tinea infections. DISCUSSION: While tinea may be suspected on the basis of clinical grounds, it is important to be aware of the various conditions considered in the differential diagnosis that may mimic tinea infections. Topical and systemic antifungal modalities are available and are selected on the basis of the subtypes and severity of tinea infection. Untreated, tinea can cause significant morbidity and predispose to complications, including cellulitis and ulcers on the feet and alopecia on the scalp.

Skin Cancer Following Solid Organ Transplantation: A Review of Risk Factors and Models of Care.

The number of solid organ transplants has been increasing annually worldwide. Advances in transplantation surgery and community awareness of organ donation have been key contributors. Combined with increased understanding of immunosuppression, there are a growing number of solid organ transplant recipients in the community as a result of improved long-term outcomes. There remains a high incidence of deaths worldwide post-transplant due to non-melanoma skin cancer (NMSC), which has greater morbidity and mortality in this population than in the general community. Many transplant candidates are not screened prior to organ transplantation and not followed up dermatologically after transplant. After a comprehensive review of the MEDLINE database, we present an update of literature on risk factors for melanoma and non-melanoma skin cancer development in transplant recipients. Medications used by transplant recipients, including immunosuppressants and antibiotics, are discussed along with their respective risks of skin cancer development. We conclude with evidence-based recommendations for models of care, including patient education and dermatological review of transplant recipients.