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.

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.

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.

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.

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.

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.

Infliximab-induced lichen planopilaris.

OBJECTIVE: To report a case of lichen planopilaris in a patient treated with infliximab for longstanding refractory psoriasis. CASE SUMMARY: A 37-year-old man with recalcitrant plaque psoriasis was being treated with infliximab at a dosage of 5 mg/kg every 8 weeks, with good response. However, 11 months later the patient developed follicular keratotic papulo-pustules, perifollicular erythema, and scaling, with progressive hair loss of the frontal and parietal regions of the scalp and eyebrows. A skin biopsy from a representative lesion was consistent with the diagnosis of lichen planopilaris. DISCUSSION: Anti-tumor necrosis factor (TNF) agents have been associated with numerous cutaneous adverse events. Lichenoid reactions are uncommon but are an emerging cutaneous adverse effect. At least 13 cases of these eruptions have been recently described. Although lichenoid reactions in patients treated with TNF-alpha inhibitors may be clinically very diverse, we have found no previously reported cases of lichen planopilaris induced by these agents. An objective causality assessment revealed that the adverse event was probable. CONCLUSIONS: Since anti-TNF agents are being used for a rapidly expanding number of rheumatic, digestive, and dermatologic diseases, it is expected that lichenoid eruptions and other skin toxicities are likely to be seen with increasing frequency in clinical practice.

Melanoma under 18 years and pregnancy: report of three cases.

Melanoma is an uncommon tumour in childhood. Only isolated cases in pregnant patients younger than 18 years old have been previously described, therefore the biological behaviour of cutaneous melanoma in this group of age remains largely unknown. We report a single-institution experience with three patients who developed cutaneous melanoma before the age of 18 years and became pregnant concomitantly or during the course of the disease. High tumour thickness was attributed to later diagnosis and could be responsible for the aggressive biological behaviour in these patients. This delay was in part due to patients considering changes in nevi to be normal during pregnancy. The effect of pregnancy on the prognosis of patients with melanoma, particularly the role of hormonal and immunological factors on clinical outcome, survival and risk of developing metastases, as well as the differences between adolescent and adult populations are still controversial. Since there are no specific treatment strategies for this group of patients, treatment recommendations should be established according to adult experience.

Spitzoid melanoma in children: clinicopathological study and application of immunohistochemistry as an adjunct diagnostic tool.

INTRODUCTION: The term spitzoid melanoma (SM) is reserved for a rare group of tumors with striking resemblance to Spitz nevus, often developing in children diagnosed in retrospect after the development of metastases. OBJECTIVES: To determine the biological significance of SM and to analyze the effectiveness of adjuvant diagnostic techniques. MATERIALS AND METHODS: A retrospective, observational study of 38 cases of SM in patients younger than 18 years. Histological type, Clark level and Breslow thickness, radial and vertical growth phase, mitotic count/mm(2), ulceration, regression, vascular and perineural invasion, satellitosis, cytology and associated nevi were reviewed. An immunohistochemical analysis with HMB45 and Ki67 was performed in 10 cases. These features were correlated to patient's stage and outcome. RESULTS: Analysis of histological and immunohistochemical features should allow accurate diagnosis in most cases. Given the low mortality rate, no conclusions about the prognostic significance of histological parameters of the primary tumor could be established. CONCLUSION: We report the largest series of SM from a unique center. Although these patients may have a better prognosis than adults, some patients with SM develop metastasis and die, particularly after age 11 years. Therefore, we recommend using the same treatments as in adults.

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.

Necrotizing vasculitis with a polyarteritis nodosa-like pattern and selective immunoglobulin A deficiency: case report and review of the literature.

Selective immunoglobulin A deficiency (IgAD) is a primary immunodeficiency disease characterized by low levels (< 7 mg/dl) of serum immunoglobulin (Ig) A and normal serum levels of IgG and IgM. Patients with IgAD have increased risk for recurrent respiratory and gastrointestinal infections, autoimmune disease, asthma and allergy. A 26-year-old woman was admitted with sudden onset of painful cutaneous lesions on her lower extremities, pyrexia and arthromyalgia. Her medical history was remarkable for recurrent respiratory tract infections, self-limited episodes of acute diarrhea, atopy, splenomegaly and a 4-year history of a lung granulomatous lesion. Laboratory and imaging tests ruled out severe life-threatening infection, connective tissue disease and neoplasm. Serum protein electrophoresis showed a low IgA serum level (6.67 mg/dl), with normal serum levels of IgG and IgM, conducting to a diagnosis of selective IgAD. A skin biopsy showed necrotizing vasculitis without any sign of internal organ disease. We report a patient with IgAD and granulomatous involvement of lungs, spleen and medium-sized arteries of the skin. Although IgAD results from a failure of B-cell differentiation, we propose that deregulated immune response with production of cross-reactive antibodies and hyperstimulation of T cells and macrophages could contribute to this widespread granulomatous reaction.

Bowen's disease treated by carbon dioxide laser. A series of 44 patients.

BACKGROUND: Bowen's disease is a common form of intraepidermal (in situ) squamous cell carcinoma of the skin and mucous membrane. Treatment with destruction of the epidermis by any method is necessary to prevent invasive squamous cell carcinoma. OBJECTIVE: To report our experience with CO2 laser vaporization in the treatment of Bowen's disease and try to identify which factors could have any influence on results. METHODS: A total of 44 patients were treated with the CO2 laser in superpulsed mode, focalized at 2 W/cm2. RESULTS: In 86.3% of patients, a unique treatment session was required. 'Clearance after one treatment' was achieved in 86.3% of the total series of patients and only 7.9% of these patients developed recurrence of the lesion. In 11.3% of the cases, there was 'clearance after more than one treatment' without clinical recurrences in any of these patients during the follow-up. 'No response' was achieved in 2.2% of the total series of patients. CONCLUSION: We conclude that the CO2 laser in superpulsed mode is an effective, efficient, safe, functional and good cosmetics treatment for Bowen's disease and it provides the same recurrence rate as other more aggressive or more expensive modalities of treatment.

Mucinous carcinoma of the skin: evaluation of lymphatic invasion with D2-40.

Primary cutaneous mucinous carcinoma is a rare adnexal sweat gland neoplasm that mainly affects elderly people. Differential diagnosis includes mammary and gastrointestinal metastatic mucinous carcinoma (MC) and secondary cutaneous involvement by underlying neoplasms. An 83-year-old woman presented with an 8-year history of slow-growing infiltrate plaque in her right hemithorax, with ulceration on supraclavicular area, right upper limb edema and palpable axillary lymphadenopathies. She underwent partial excision of the tumor and local radiotherapy. Imaging studies showed widespread cutaneous dissemination with enlargement of ipsilateral axillary lymph nodes but without evidence of underlying breast cancer. Histopathological examination showed large amounts of mucin in the dermis including small islands of epithelial cells. They stained positive for cytokeratin 7, carcinoembryonic antigen, epithelial membrane antigen, gross cystic disease fluid protein-15, and c-erbB-2. Lymphatic invasion was demonstrated by D2-40-immunostained sections. A diagnosis of primary cutaneous mucinous carcinoma was made. Our aim was to reevaluate the differential clinical, histopathological, and immunohistochemical criteria for distinguishing primary cutaneous mucinous carcinoma from skin metastases of visceral mucinous carcinoma, especially those arising in breast. We also propose D2-40 as a reliable marker to detect lymphatic invasion that indicates a strong aggressive trend with shorter recurrence-free and predicts nodal metastases.