Assessing the Skin and UV Neoplasia Transplant Risk Assessment Calculator in an Irish cohort of thoracic organ transplant recipients.

The Skin and UV Neoplasia Transplant Risk Assessment Calculator (SUNTRAC) is a tool that can be used to decide when to first screen for skin cancer in organ transplant recipients (OTRs). The objective of this study was to assess the applicability of this tool in thoracic OTRs. Based on data from patient files, the OTRs were categorized into four risk groups according to the SUNTRAC tool. The time of the first post-transplant skin cancer in each OTR was recorded. The proportion of OTRs with post-transplant skin cancer in the low-, medium-, high- and very high-risk groups was 0%, 28.3%, 58.3% and 100%, respectively. This positive correlation suggests that SUNTRAC can be used to determine when to first screen for skin cancer in heart and lung OTRs.

Mammalian target of rapamycin (mTOR) inhibitors and skin cancer risk in nonrenal solid organ transplant recipients: systematic review and meta-analysis.

BACKGROUND: Solid organ transplant recipients have an increased risk of malignancy compared with the general population. Mammalian target of rapamycin (mTOR) inhibitors have been used as immunosuppressants in transplant recipients. There remains a lack of evidence of this treatment in nonrenal solid organ transplantation. We aimed to perform a systematic review and meta-analysis to assess the effects of mTOR inhibitors on secondary nonmelanoma skin cancer (NMSC) malignancies in nonrenal transplant recipients. METHODS: A systematic review and meta-analysis was performed according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Eligible studies for the present systematic review and meta-analysis included those in which patient cohorts underwent heart, liver, lung, and pancreas (i.e. nonrenal solid organ) transplantation, with treatment group being those treated with an mTOR inhibitor such as sirolimus or everolimus, and control group being placebo, or alternative non-mTOR inhibitor treatment such as calcineurin inhibitors or as per standard treatment protocol. RESULTS: From the six included studies, we found no significant difference in the odds of either primary or secondary NMSC (OR 0.73, 95% CI 0.41-1.29, P = 0.28). Pooled analysis of patients with secondary NMSC demonstrated a trend toward significant benefit with mTOR inhibitor treatment (OR 0.61, 95% CI 0.37-1.02, P = 0.06) but no protective effect for primary NMSC (OR 0.53, 95% CI 0.03-9.96, P = 0.67). CONCLUSIONS: Our results suggest that in nonrenal transplant recipients, mTOR inhibitors may have a protective effect against secondary NMSC but not primary NMSC posttransplantation. Extrapolating the findings of reduced NMSC in renal transplant populations to nonrenal transplant cases should be cautioned.

Extensive warfarin-induced skin necrosis successfully treated with negative pressure wound therapy.

A 55-year-old woman presented with an extensive warfarin-induced skin necrosis while an inpatient for treatment of a pulmonary embolism and thromboembolic stroke. She had a background of diabetes mellitus, hypertension and dyslipidaemia. Her warfarin was stopped and she was anticoagulated with low-molecular weight heparin. The wound was successfully treated with a combination of antibiotic, debridement and negative pressure wound therapy.

Clobetasol propionate, 0.05%, vs hydrocortisone, 1%, for alopecia areata in children: a randomized clinical trial.

IMPORTANCE: Alopecia areata is an idiopathic cause of hair loss with limited therapeutic repertoire. OBJECTIVE: To compare the efficacy and safety of a high- vs low-potency topical corticosteroid in pediatric patients. DESIGN, SETTING, AND PARTICIPANTS: This single-center, randomized, blind, 2-arm, parallel-group, superiority trial was carried out over a 24-week period at a tertiary referral academic dermatology clinic at The Hospital for Sick Children in Toronto, Ontario, Canada. Forty-two children attending the outpatients clinic, 2 to 16 years of age with alopecia areata affecting at least 10% of scalp surface area, were eligible; 1 declined to participate. There were no withdrawals from the study. INTERVENTIONS FOR CLINICAL TRIALS: Patients were randomly assigned to receive clobetasol propionate, 0.05% cream, or hydrocortisone, 1%, cream. Patients applied a thin layer of the assigned cream twice daily to the areas of hair loss for 2 cycles of 6 weeks on, 6 weeks off, for a total of 24 weeks. MAIN OUTCOMES AND MEASURES: The primary outcome was the change in scalp surface area with hair loss over 24 weeks following enrollment. RESULTS All participants were assessed at 6, 12, 18, and 24 weeks (except 1 participant who missed the 6-week visit). After adjusting for baseline hair loss, the clobetasol group had a statistically significant (P < .001) greater decrease in the surface area with hair loss, compared with the hydrocortisone group at all time points except at 6 weeks. One patient with extensive alopecia areata experienced skin atrophy that resolved spontaneously in 6 weeks. There was no difference observed in the number of patients with abnormal urinary cortisol at the beginning and the end of the study. CONCLUSIONS AND RELEVANCE: Topical clobetasol propionate, 0.05%, cream is efficacious and safe as a first-line agent for limited patchy childhood alopecia areata. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT01453686.

Mycosis fungoides--a review of the management of 28 patients and of the recent literature.

BACKGROUND: Mycosis fungoides is an uncommon cutaneous T-cell lymphoma characterized by malignant monoclonal proliferation of T-helper lymphocytes. Its course is variable with a potential for lymphatic and hematogenous involvement. We report the investigations, staging, treatment, follow-up, and outcome of 28 patients. This is the first such study reported from Ireland. METHODS: Twenty-eight patients with mycosis fungoides (14 women, 14 men; average age, 52.5 years) were reviewed over 12 years in the dermatology clinic which assesses an average of 4500 patients per year. All mycosis fungoides patients were referred from their family physicians. The diagnosis was made in all cases from a combination of clinical findings, histology, and immunohistochemistry. TNM staging revealed 11 patients at diagnosis stage IA (T1), 12 at stage IB (T2), four at stage IIB (T3), and one at stage III (T4). RESULTS: The usual male preponderance was not found. Eight patients needed multiple biopsies to establish the diagnosis. Detailed investigations were not useful in the early stages. Patients were followed up over a 12-year period. Thirteen patients died as a result of cutaneous lymphoma. Two patients with stage IA disease progressed rapidly and died, a feature reported in only 10% of patients at this stage. Five patients showed unusual features, including a long history prior to presentation, the development of the rarely reported bullous mycosis fungoides, and aggressive disease beginning at a young age. CONCLUSIONS: Mycosis fungoides is rare; we reviewed 28 patients over 12 years. The prognosis is poor at the later stages; 13 patients died. Two patients who died were unusual in that they rapidly progressed from stage IA disease; however, in the majority of patients with this stage, the prognosis is excellent. Detailed investigations were unhelpful in early stage disease. Close clinical follow-up is essential to identify disease progression.

Congenital alopecia areata.

Alopecia areata, the alleged autoimmune process leading to nonscarring hair loss, is not uncommon. It has been classified as an acquired cause of alopecia; however, recently it has been reported in the neonatal period. We report 4 cases of congenital alopecia areata with follow-up from 3 to 5 years. The diagnosis was made clinically in all cases. All patients had prolonged periods of quiescence of hair loss ranging from 6 to 24 months. Treatments used included minoxidil 2% and a range of topical steroids including hydrocortisone 1%, betamethasone valerate 0.05%, fluocinonide 0.05%, and clobetasol propionate 0.05%. The best regrowth observed resulted from the use of clobetasol propionate 0.05%, giving full regrowth in 50% of those treated. Alopecia areata can occur at all ages and, thus, can be classified as both an acquired and a congenital disorder resulting in hair loss.

Extracellular matrix protein 1 gene (ECM1) mutations in lipoid proteinosis and genotype-phenotype correlation.

The autosomal recessive disorder lipoid proteinosis results from mutations in extracellular matrix protein 1 (ECM1), a glycoprotein expressed in several tissues (including skin) and composed of two alternatively spliced isoforms, ECM1a and ECM1b, the latter lacking exon 7 of this 10-exon gene (ECM1). To date, mutations that either affect ECM1a alone or perturb both ECM1 transcripts have been demonstrated in six cases. However, lipoid proteinosis is clinically heterogeneous with affected individuals displaying differing degrees of skin scarring and infiltration, variable signs of hoarseness and respiratory distress, and in some cases neurological abnormalities such as temporal lobe epilepsy. In this study, we sequenced ECM1 in 10 further unrelated patients with lipoid proteinosis to extend genotype-phenotype correlation and to add to the mutation database. We identified seven new homozygous nonsense or frameshift mutations: R53X (exon 3); 243delG (exon 4); 507delT (exon 6); 735delTG (exon 7); 785delA (exon 7); 892delC (exon 7) and 1190insC (exon 8), as well as two new compound heterozygous mutations: W160X/F167I (exon 6) and 542insAA/R243X (exons 6/7), none of which were found in controls. The mutation 507delT occurred in two unrelated subjects on different ECM1 haplotypes and may therefore represent a recurrent mutation in lipoid proteinosis. Taken with the previously documented mutations in ECM1, this study supports the view that exons 6 and 7 are the most common sites for ECM1 mutations in lipoid proteinosis. Clinically, it appears that mutations outside exon 7 are usually associated with a slightly more severe mucocutaneous lipoid proteinosis phenotype, but neurological features do not show any specific genotype-phenotype correlation.