Prognosis of CDKN2A germline mutation in patients with familial melanoma: a systematic review and meta-analysis.

Familial melanoma is defined as melanoma occurring in two or more first-degree relatives by the WHO. Germline mutations are isolated in a subset of them. It is well known that CDKN2A is the most frequently mutated high-risk gene in familial melanoma, however, the prognosis it confers to patients who carry its mutations is still controversial. This review aims to assess whether germline mutations imply a worse prognosis in patients with familial melanoma. A systematic review and meta-analysis were conducted by searching the electronic databases PubMed/MEDLINE, EMBASE, and Cochrane Library. Data from 3 independent populations were eventually included in the meta-analysis, involving 291 cases and 57 416 controls. The results of this systematic review and meta-analysis suggest that there is a tendency for patients with germline mutations in the CDKN2A gene to have a worse overall survival (HR = 1.30, 95% CI = 0.99-1.69, P  = 0.05) and melanoma-specific survival (HR = 1.5, 95% CI = 0.97-2.31, P  = 0.07). Carrier patients would not only have more incidence of melanoma and a higher risk of a second melanoma, but they also seem to have a worse prognosis. The inclusion of gene panel testing in clinical practice and the collaboration within consortia are needed to provide further evidence on the prognosis of these patients.

Novel uses of laser therapy in Goltz syndrome.

Goltz syndrome is an X-linked dominant, multisystem birth defect due to PORCN mutation. The skin findings follow Blaschko's lines and often show epidermal atrophy and herniation of subcutaneous fatty tissue. Regarding treatment, light sources can offer a good therapeutic option for some manifestations of this rare disease and improve the aesthetic appearance of the skin lesions. We report two new cases of Goltz syndrome in which the cutaneous findings remarkably improved with pulsed dye laser and carbon dioxide laser.

Biologic Therapy for Moderate to Severe Psoriasis. Real-World Follow-up of Patients Who Initiated Biologic Therapy at Least 10 Years Ago.

INTRODUCTION: The aim of this study was to evaluate response and drug survival of biologic therapy in patients with moderate to severe plaque-type psoriasis who initiated biologic therapy at least 10 years ago, in a real-world setting. METHODS: This was an observational retrospective follow-up study that included patients with moderate to severe plaque-type psoriasis who initiated biologic therapy between October 2006 and December 2009. Efficacy was expressed as the percentage of patients achieving a 50, 75 and 90% reduction from baseline in the Psoriasis Area and Severity Index (PASI 50, PASI 75, PASI 90, respectively) every 3 months during the first year of therapy and then every 12 months up to the end of follow-up or withdrawal from the study. RESULTS: A total of 56 patients were included in the study, representing 140 treatment lines (median 2, range 1-8); of these patients, 53 were still receiving biologic therapy at the end of the study. The mean duration of biologic therapy was 140.4 (range 47.6-175.4) months. Etanercept was used in 98.2% of patients, followed by efalizumab (42.9%), adalimumab (41.1%), ustekinumab (33.9%) and infliximab (16.1%). Treatment lines were switched in 62.1% of treatments: 24.3% due to secondary failure, 20.7% due to primary failure and 3.6% due to side effects. No patient treated with anti-interleukins had to discontinue treatment due to side effects. Ustekinumab had the highest drug survival. CONCLUSIONS: This study in the real-world-setting shows maintenance of long-term efficacy and safety of biologic therapy in patients with moderate to severe plaque psoriasis in daily practice who initiated biologic therapy 10 years ago.

Sentinel Lymph Node Biopsy vs. Observation in Thin Melanoma: A Multicenter Propensity Score Matching Study.

The therapeutic value of sentinel lymph node biopsy (SLNB) in thin melanoma remains controversial. The aim of this study is to determine the role of SLNB in the survival of thin melanomas (≤1 mm). A multicenter retrospective observational study was designed. A propensity score matching was performed to compare patients who underwent SLNB vs. observation. A multivariate Cox regression was used. A total of 1438 patients were matched by propensity score. There were no significant differences in melanoma-specific survival (MSS) between the SLNB and observation groups. Predictors of MSS in the multivariate model were age, tumor thickness, ulceration, and interferon treatment. Results were similar for disease-free survival and overall survival. The 5- and 10-year MSS rates for SLN-negative and -positive patients were 98.5% vs. 77.3% (p < 0.001) and 97.3% vs. 68.7% (p < 0.001), respectively. SLNB does not improve MSS in patients with thin melanoma. It also had no impact on DSF or OS. However, a considerable difference in MSS, DFS, and OS between SLN-positive and -negative patients exists, confirming its value as a prognostic procedure and therefore we recommend discussing the option of SLNB with patients.

Effects of COVID-19 Lockdown on Tumour Burden of Melanoma and Cutaneous Squamous Cell Carcinoma.

The aim of this study was to compare tumour burden in patients who underwent surgery for melanoma and cutaneous squamous cell carcinoma during nationwide lockdown in Spain due to COVID-19 (for the period 14 March to 13 June 2020) and during the same dates in 2019 before the COVID-19 pandemic. In addition, associations between median tumour burden (Breslow thickness for melanoma and maximum clinical diameter for cutaneous squamous cell carcinoma) and demographic, clinical, and medical factors were analysed, building a multivariate linear regression model. During the 3 months of lockdown, there was a significant decrease in skin tumours operated on (41% decrease for melanoma (n = 352 vs n = 207) and 44% decrease for cutaneous squamous cell carcinoma (n = 770 vs n = 429)) compared with the previous year. The proportion of large skin tumours operated on increased. Fear of SARS-CoV-2 infection, with respect to family member/close contact, and detection of the lesion by the patient or doctor, were related to thicker melanomas; and fear of being diagnosed with cancer, and detection of the lesion by the patient or relatives, were related to larger size cutaneous squamous cell carcinoma. In conclusion, lockdown due to COVID-19 has resulted in a reduction in treatment of skin cancer.

Cutaneous lupus erythematosus: factors related to cutaneous activity and damage in a cohort of 260 patients from A Coruña, Spain.

BACKGROUND: Cutaneous lupus erythematosus is a chronic autoimmune disease that can leave important sequelae. OBJECTIVE: To determine the factors that predict the activity and damage of the skin disease, and the impact of tobacco on the efficacy of antimalarials using the Cutaneous Lupus Erythematosus Disease Area and Severity Index. MATERIALS AND METHODS: A consecutive case series was performed on 260 patients with cutaneous lupus erythematosus (α = 0.05; precision ± 6.5%). We carried out a descriptive analysis of the variables included, with a multivariate analysis to measure the association of variables with the Cutaneous Lupus Erythematosus Disease Area and Severity Index activity and damage (p value < 0.05). RESULTS: The Cutaneous Lupus Erythematosus Disease Area and Severity Index activity was greater in smokers than non-smokers (4.0 ±5.3 vs 1.2 ±3.4, p = 0.006). No significant differences were observed in the Cutaneous Lupus Erythematosus Disease Area and Severity Index activity when the efficacy of antimalarials was analyzed between smokers and non-smokers. Cutaneous Lupus Erythematosus Disease Area and Severity Index damage was higher in smokers than in non-smokers (2.0 ± 3.6 vs 1.2 ± 2.6, p = 0.029). Cutaneous Lupus Erythematosus Disease Area and Severity Index activity was associated with: (a) being an active smoker (odds ratio 3.04, 95% confidence interval 1.68-5.51, p < 0.001; regression coefficient 2.05, 95% confidence interval 0.69-3.42, p = 0.003); (b) the chronic cutaneous lupus erythematosus subtype (odds ratio 1.98, 95% confidence interval 1.02-3.84, p = 0.044); and (c) C-reactive protein increase (≥0.5 mg/dL) (regression coefficient 2.56, 95% confidence interval 0.40-4.71, p = 0.020). Cutaneous Lupus Erythematosus Disease Area and Severity Index damage was associated with: (a) the activity (regression coefficient 0.11, 95% confidence interval 0.01-0.20, p = 0.024); (b) the chronic cutaneous lupus erythematosus subtype (regression coefficient 2.46, 95% confidence interval 1.37-3.56, p < 0.001); (c) the use of topical treatment (regression coefficient 1.31, 95% confidence interval 0.01-2.61, p = 0.049); and (d) systemic treatment (regression coefficient 1.44, 95% confidence interval 0.35-2.53, p < 0.010). CONCLUSION: Smoking is related to an increase risk and a greater activity of cutaneous lupus erythematosus. The chronic cutaneous lupus erythematosus subtype and an increased C-reactive protein level were also associated with a higher disease activity. The sequelae were related to the activity, the chronic cutaneous lupus erythematosus subtype, and the use of topical and systemic treatment. The impact of tobacco on the efficacy of antimalarials may be caused by an increase in the severity of the disease more than by resistance in smokers.

Incidence rate and clinicopathological features of 62 atypical fibroxanthomas in a North-Western Spanish population.

BACKGROUND/OBJECTIVES: Atypical fibroxanthoma (AFX) is a mesenchymal neoplasm of unknown incidence. It has been determined that AFX is a tumour with low aggressiveness as long as it is properly diagnosed. Our objectives were to exclude pleomorphic dermal sarcomas or other skin tumours incorrectly diagnosed as AFX in our centre after applying strict diagnostic criteria and to assess the behaviour of appropriately diagnosed AFX. METHODS: We conducted an observational retrospective analysis of 73 patients diagnosed with AFX in our centre between 1998 and 2018. After selecting cases fulfilling AFX criteria, we made an analysis of predictive factors for local recurrence. Crude and sex-adjusted incidence rates were calculated. RESULTS: Out of 73 cases, 62 were eventually diagnosed as AFX. We examined for absence of tumour necrosis, lymphovascular or perineural invasion and infiltration of deep structures. Cytokeratin AE1-AE3, desmin and CD34 were negative in all cases. The remaining tumours were reclassified. The incidence of AFX in our health-care area was estimated at 0.59 cases every 100 000 inhabitants per year. In our series, 72.6% of the patients were men with mean age at diagnosis of 81 years. Average tumour diameter was 12 mm. The most common location was head and neck (96.8%). Only four local recurrences were detected over a mean of 47-month follow-up. CONCLUSIONS: We report a series of AFX in our health-care area. We verify its indolent course when it is properly diagnosed.

Use of lip photoprotection in patients suffering from actinic cheilitis.

BACKGROUND: Actinic cheilitis (AC) is a chronic condition that affects mainly the lower lip. OBJECTIVES: To investigate the use of lip photoprotection in patients with AC. MATERIALS AND METHODS: A cross-sectional multicentre study of patients, ≥45 years of age, was performed in eight dermatology departments in the Galicia region over a period of one year. From 1,239 patients included in the study, 410 were diagnosed with AC and complete data were available for 408. An analysis of lip photoprotection habits and possible associations in patients with AC is reported. RESULTS: Mean age of patients with AC was 71.9 years and 53.8% were women. More than 90% of AC patients (370/408) had never used lip photoprotection. In the group of patients who used it, 62.16% of them had only used a single stick within the previous year. The only variable significantly associated with the use of lip sun protection was low Fitzpatrick's skin types I and II (p=0.039). Study limitations include the inclusion of patients 45 years or older and the use of a semiquantitative scale for measuring the frequency of application of lip photoprotection. CONCLUSION: To our knowledge, this is the first European study focused on lip photoprotection in patients suffering from AC. Only a minority of AC patients protect their lips from UV radiation. Specific lip sun protection recommendations should be promoted, especially in high-risk populations.

Survival analysis and sentinel lymph node status in thin cutaneous melanoma: A multicenter observational study.

Mitotic rate is no longer considered a staging criterion for thin melanoma in the 8th edition of the American Joint Committee on Cancer Staging Manual. The aim of this observational study was to identify prognostic factors for thin melanoma and predictors and prognostic significance of sentinel lymph node (SLN) involvement in a large multicenter cohort of patients with melanoma from nine tertiary care hospitals. A total of 4249 consecutive patients with thin melanoma diagnosed from January 1, 1998 to December 31, 2016 were included. The main outcomes were disease-free interval and melanoma-specific survival for the overall population and predictors of SLN metastasis (n = 1083). Associations between survival and SLN status and different clinical and pathologic variables (sex, age, tumor location, mitosis, ulceration, regression, lymphovascular invasion, histologic subtype, Clark level, and Breslow thickness) were analyzed by Cox proportional hazards regression and logistic regression. SLN status was the most important prognostic factor for melanoma-specific survival (hazard ratio, 13.8; 95% CI, 6.1-31.2; P < 0.001), followed by sex, ulceration, and Clark level for patients who underwent SLNB. A mitotic rate of >2 mitoses/mm2 was the only factor associated with a positive SLN biopsy (odds ratio, 2.9; 95% CI, 1.22-7; P = 0.01. SLN status is the most important prognostic factor in thin melanoma. A high mitotic rate is associated with metastatic SLN involvement. SLN biopsy should be discussed and recommended in patients with thin melanoma and a high mitotic rate.

Actinic Cheilitis Prevalence and Risk Factors: A Cross-sectional, Multicentre Study in a Population Aged 45 Years and Over in North-west Spain.

Actinic cheilitis is thought to be a premalignant lesion or a superficial squamous cell carcinoma. The prevalence of actinic cheilitis in Europe is unknown. The aim of this study was to determine the prevalence of actinic cheilitis in the Galicia region (north-west Spain). Secondary objectives were the description of risk factors of actinic cheilitis. A cross-sectional multicentre study in patients ≥ 45 years of age was performed in 8 dermatology departments in Galicia region during a 1-year period. The prevalence of actinic cheilitis was 31.3%. Significant and independent risk factors of actinic cheilitis after multivariate analysis were age ≥ 60 years, Fitzpatrick skin phototype II, outdoor working for more than 25 years, and previous history of non-melanoma skin cancer. This is the first cross-sectional multicentre study of the prevalence of actinic cheilitis in Europe. Actinic cheilitis was present in almost one-third of the screened patients. Lip examination should be performed in all patients with chronic actinic damage.

Positive correlation between etanercept concentration and the decrease in Psoriasis Area and Severity Index scale value.

Background In the case of psoriatic patients, only a limited number of studies have related serum biological therapies and antidrug antibodies levels to clinical response. With respect to etanercept, the available evidence has not shown any relationship yet. Objective The aim of this study was to determine if there is any correlation among etanercept serum levels, the presence of anti-etanercept antibodies and clinical response to this treatment in psoriatic patients. Setting A 1500-bed hospital (A Coruña University Hospital Complex). Method A retrospective observational study in psoriatic patients treated with etanercept (50 mg once weekly) was carried out. Psoriasis Area and Severity Index scale and adverse reactions were recorded at the time of the extraction sample. The pharmacokinetic monitoring was evaluated at the previous time points by extracting peripheral blood samples before the dose administration. Etanercept and anti-etanercept antibodies concentrations were quantified by two sandwich-type ELISA immunoassays. The patients were classified into three groups (good, partial and nonresponders) in accordance with the treatment efficacy at the blood assessment moments. The Kruskall-Wallis test and Spearman correlation assay were used to assess the efficacy and incidence of adverse effects according to the etanercept concentration and anti-etanercept antibodies, considering p values of <0.05 as statistically significant. This statistical analysis was conducted using SPSS software (version19.0). Main outcome measures Etanercept and anti-etanercept antibodies trough serum levels and clinical response. Results 38 patients were included. 26 patients (68.4 %) were good, 5 (13.2 %) were partial and 7 (18.4 %) were non-responders. There was no significant difference with respect to etanercept levels: 2.7 µg/mL (range 0.7-5.6) versus 2.2 µg/mL (range 1.0-3.5) versus 1.73 µg/mL (range 0.1-2.3), respectively (p = 0.085). Nevertheless, a positive correlation between percentage decrease in the Psoriasis Area and Severity Index scale value with respect to the baseline value and etanercept concentration was found (p = 0.011). No anti-etanercept antibodies were detected; nor was there a significant difference in the incidence of adverse effects (p = 0.8523). Conclusions Our results showed a positive correlated between etanercept concentration and the percentage decrease in the Psoriasis Area and Severity Index scale value. The incidence of anti-etanercept antibodies in psoriatic patients was low.

Long-Term Efficacy of Etanercept for Plaque-Type Psoriasis and Estimated Cost in Daily Clinical Practice.

BACKGROUND: There are numerous clinical trials proving efficacy and safety profiles of etanercept. Newer studies, however, include patients with significant comorbidities, unstable psoriasis, or concomitant treatments. OBJECTIVE: The objective of this study was to provide data on long-term response to etanercept and estimate the cost in daily practice. METHODS: This is an observational retrospective study including patients with plaque-type psoriasis receiving etanercept 50 mg/wk for more than 6 months at the Dermatology Department of the University Hospital of La Coruña (Spain). Psoriasis severity was determined using the Psoriasis Area and Severity Index (PASI) at baseline and then at 12 weeks, 24 weeks, and annually until treatment discontinuation. RESULTS: A total of 102 patients aged 24 to 78 years were included. Response rates of 58.8% and 66.3% for PASI 75 score (reduction of at least 75% in PASI score compared with baseline) were achieved after 12 and 24 weeks of treatment, respectively. Among patients who continued treatment, the PASI 75 score was maintained by 75.3% at 1 year, 82.5% at 2 years, and 88.2% at 3 years. The percentage of patients receiving other systemic treatments was 38.2%. Adverse effects were reported in 13.7%, all of them mild, except one case of urinary sepsis. The average cost per patient was €244.68 ± €45.27 per week and €34.95 ± €6.46 per day. CONCLUSIONS: We provide data on long-term response to etanercept and its costs in a real-world setting. Response rates were higher than in some clinical trials, with progressive efficacy and not related to body mass index. Etanercept cost was comparable with that estimated in other studies. Combination with a conventional systemic agent can enhance efficacy without additional adverse events.

Efficacy and safety of adalimumab in psoriatic patients previously treated with etanercept in a real-world setting.

INTRODUCTION: Knowledge on the efficacy and safety of adalimumab in psoriasis patients switching from etanercept is scarce, especially on the influence that causes of etanercept discontinuation may have on adalimumab response. OBJECTIVES: To evaluate the response, adverse effects and factors that may influence the efficacy and safety of adalimumab in psoriasis patients who failed on etanercept therapy in a real-world setting. METHODS: Data from all moderate to severe plaque psoriasis patients who switched from etanercept to adalimumab were extracted from a registry of biological therapies of our department. Primary endpoint was the percentage of patients achieving PASI 50 at weeks 12, 24, and 52. Secondary endpoints were the percentages of patients achieving PASI 75 and PASI 90, patients who maintained PASI values <5 and <3, and the safety of adalimumab. RESULTS: Of 35 patients who fulfilled the study criteria, 82.9% achieved PASI 50 at week 12, 74.3% at week 24, and 74.3% at week 52 on adalimumab treatment. Eleven of 16 primary and 11 of 17 secondary nonresponders to etanercept responded to adalimumab. There were no treatment discontinuations due to side effects. CONCLUSIONS: Previous etanercept failure seems not influence the success and safety of adalimumab treatment in moderate to severe plaque psoriasis.

Long-term response to etanercept monotherapy in moderate to severe psoriasis: assessment in daily practice by the maintenance of low values of PASI and BSA.

INTRODUCTION: Efficacy and safety profiles of etanercept have been proved in numerous clinical trials; however, efficacy is determined by means of PASI 75 and few studies consider the maintenance of long-term response. The aims of this study were to provide data on long-term response to etanercept monotherapy in daily practice and to propose a method to assess the efficacy based on the maintenance of low PASI and BSA. METHODS: Patients with moderate-severe psoriasis treated with etanercept 50 mg weekly, achieving at least PASI 50 at 12 weeks, were included. Response was expressed as the percentage of patients maintaining PASI and BSA ≤5 and ≤3, respectively. RESULTS: We included 76 patients (73.7% male and 26.3% female). PASI remained ≤5 in 71.1%, 61.3%, 54.4%, 38.3%, 8.6% and 5.9% of patients and ≤3 in 51.3%, 46.8%, 42.1%, 34%, 8.6% and 5.9% at 3, 12, 18, 24, 36 and 42 months. CONCLUSIONS: The maximum response is achieved between 6 and 9 months and remains stable in about 50% of cases until 18-24 months. Response maintains beyond 42 months in 6%. Maintenance of low PASI and BSA may be a most useful measure than the initial PASI reduction, which not always means enough improvement for the patient.

Long-term efficacy of infliximab in hidradenitis suppurativa.

INTRODUCTION: Hidradenitis suppurativa (HS) is a chronic disease with painful, inflamed lesions in the apocrine gland-bearing areas of the body and unsatisfactory treatment. TNFα blockers have been proposed as promising treatments, but only few randomized, short-term, small controlled trials have been conducted. The aim of this study was to evaluate long-term response of HS patients treated with infliximab (IFX). MATERIAL AND METHODS: A long-term, prospective study of 10 patients with moderate-severe refractory HS treated with IFX was performed, including assessment of therapy safety, disease severity, and activity. Previous reports on IFX treatment for HS were reviewed. RESULTS: Lack of response was observed in 20% and relapse in 50% of patients, after a median period of 37 weeks. The median number of doses administered was 7.5 during 49 weeks. No life-threatening adverse events were detected. Systematic review of 61 previously published cases showed lack of response was associated with previous surgery, young age at diagnosis, and long time of evolution of the disease. CONCLUSIONS: Long-term IFX therapy might be an efficient, well-tolerated, safe option for patients with short-time evolution, severe HS. Relapse is common after 8 months of continuous treatment, especially in patients with more severe disease and in those treated with IFX in monotherapy.

Melanoma in children.

CONTEXT: Cutaneous melanoma in childhood (CMC) is rare; therefore, its prognostic factors and biologic behavior, and the effectiveness of adjuvant techniques for CMC remain mostly unknown. OBJECTIVE: To review the most useful, evidence-based practice criteria for establishing the diagnosis of CMC, for which universally accepted criteria are lacking, in order to facilitate the interpretation and comparison of the results from different institutions, and to perform systematic reviews and meta-analysis. DATA SOURCES: A comprehensive review of the most relevant previous single-institution series reported in the literature since 1990, including our cumulative experience of 137 cases of primary cutaneous and mucosal melanoma in patients younger than 18 years. Special characteristics of melanoma in children are discussed, regarding clinical settings and risk factors, helpful histologic features, and immunohistochemical patterns for diagnosis and prognosis. CONCLUSIONS: Careful analysis of histologic features as well as the additional information provided by immunohistochemistry should allow for a correct diagnosis in most cases of melanoma in children. Although it seems that pediatric patients with melanoma have higher survival probability than adults, still a number of children will develop metastasis and die of their disease, particularly when melanoma is diagnosed after puberty. Until further studies more accurately determine the prognosis, a prudent approach to CMC diagnosis and therapy seems to follow the same principles as those established for adult melanoma.