Treatment of extramammary Paget's disease with imiquimod in a real-life setting: a multicenter retrospective analysis in Spain.

BACKGROUND: Topical imiquimod has shown to be an effective treatment for EMPD, although available evidence supporting its use is based on case reports and small series of patients. OBJECTIVES: To investigate the therapeutic outcomes and analyze potential clinico-pathological factors associated with imiquimod response in a large cohort of EMPD patients. METHODS: Retrospective chart review of 125 EMPD patients treated with imiquimod at 20 Spanish tertiary-care hospitals. RESULTS: During the study period, patients received 134 treatment regimens with imiquimod, with 70 (52.2%) cases achieving complete response (CR), 41 (30.6%) partial response and 23 (17.2%) no response. The cumulative CR rates at 24 and 48 weeks of treatment were 46.3% and 71.8%, respectively, without significant differences between first-time and previously treated EMPD. Larger lesions (≥6 cm; p = 0.038) and EMPD affecting >1 anatomical site (p = 0.002) were significantly associated with a worse treatment response. However, the CR rate did not differ significantly by the number of treatment applications (≤4 vs. > 4 times/week; p = 0.112). Among patients who achieved CR, 30 (42.9%) developed local recurrences during a mean follow-up period of 36 months, with an estimated 3 and 5-year recurrence free-survival of 55.7% and 36.4%, respectively. CONCLUSIONS: Imiquimod appears as an effective therapeutic alternative for both first-line and previously treated EMPD lesions. However, a less favorable therapeutic response could be expected in larger lesions and those affecting >1 anatomical site. Based on our results, a 3-4 times weekly regimen of imiquimod with a treatment duration of at least 6 months could be considered an appropriate therapeutic strategy for EMPD patients.

Therapeutic outcomes and survival analysis of Extramammary Paget's disease: A multicentre retrospective study of 249 patients.

BACKGROUND: Evidence regarding long-term therapeutic outcomes and disease-specific survival (DSS) in Extramammary Paget's disease (EMPD) is limited. OBJECTIVES: To assess the DSS and outcomes of surgical and nonsurgical therapeutic modalities in a large cohort of EMPD patients. METHODS: Retrospective chart review of EMPD patients from 20 Spanish tertiary care hospitals. RESULTS: Data on 249 patients with a median follow-up of 60 months were analyzed. The estimated 5-, 10-, and 15-year DSS was 95.9%, 92.9%, and 88.5%, respectively. A significantly lower DSS was observed in patients showing deep dermal invasion (≥1 mm) or metastatic disease (P < .05). A ≥50% reduction in EMPD lesion size was achieved in 100% and 75.3% of patients treated with surgery and topical therapies, respectively. Tumor-free resection margins were obtained in 42.4% of the patients after wide local excision (WLE). The 5-year recurrence-free survival after Mohs micrographic surgery (MMS), WLE with tumor-free margins, WLE with positive margins, radiotherapy, and topical treatments was 63.0%, 51.4%, 20.4%, 30.1%, and 20.8%, respectively. LIMITATIONS: Retrospective design. CONCLUSIONS: EMPD is usually a chronic condition with favorable prognosis. MMS represents the therapeutic alternative with the greatest efficacy for the disease. Recurrence rates in patients with positive margins after WLE are similar to the ones observed in patients treated with topical agents.

Pancreatic panniculitis revisited: A series of 34 patients.

BACKGROUND: Pancreatic panniculitis is a rare form of panniculitis generally associated with acute or chronic pancreatitis, and less frequently with pancreatic carcinoma. Clinically, it presents with subcutaneous nodules usually located in the lower extremities, however, it presents an almost pathognomonic histopathological finding with enzymatic fat necrosis in the adipose tissue. METHODS: In this retrospective case series of five hospitals, biopsy specimens of cutaneous lesions of pancreatic panniculitis were reviewed. Clinical information was obtained through medical records. RESULTS: A total of 34 cases were included, 23 women and 11 men, aged between 31 and 92 years. The most common associated pancreatic disease was acute pancreatitis (23 cases) and its main triggering cause was gallstones (17 cases). In two patients it was related to chronic pancreatitis and six cases were associated with malignancy. Histopathological findings were always the key to diagnosis. In the biopsies reviewed, mostly lobular panniculitis with the characteristic necrosis of the adipocytes was observed. In addition, nine of the cases presented with Splendore-Hoeppli phenomenon. CONCLUSIONS: We present the largest series of pancreatic panniculitis. Clinically, the female predominance and biliary lithiasis as the main cause of acute pancreatitis are to be emphasized. Histopathologically, a peripheral eosinophilic striated rim surrounding aggregates of ghost adipocytes consistent with Splendore-Hoeppli is an additional clue to its diagnosis.

SARS-CoV-2 infection in patients with melanoma: results of the Spanish Melanoma Group registry

Background The Spanish Melanoma Group (GEM) developed a national registry of patients with melanoma infected by SARS-CoV-2 (“GRAVID”). Methods The main objective was to describe the COVID-19 fatality rate in patients with melanoma throughout the pandemic, as well as to explore the effect of melanoma treatment and tumor stage on the risk of COVID-19 complications. These are the final data of the register, including cases from February 2020 to September 2021. Results One hundred-fifty cases were registered. Median age was 68 years (range 6–95), 61 (40%) patients were females, and 63 (42%) patients had stage IV. Thirty-nine (26%) were on treatment with immunotherapy, and 17 (11%) with BRAF-MEK inhibitors. COVID-19 was resolved in 119 cases, including 85 (57%) patients cured, 15 (10%) that died due to melanoma, and 20 (13%) that died due to COVID-19. Only age over 60 years, cardiovascular disorders, and diabetes mellitus increased the risk of death due to COVID-19, but not advanced melanoma stage nor melanoma systemic therapies. Three waves have been covered by the register: February–May 2020, August–November 2020, and December 2020–April 2021. The first wave had the highest number of registered cases and COVID-19 mortality. Conclusion Tumor stage or melanoma treatments are non-significant prognostic factors for COVID-19 mortality. During the pandemic in Spain there was a downward trend in the number of patients registered across the waves, as well as in the severity of the infection (AU)

SARS-CoV-2 infection in patients with melanoma: results of the Spanish Melanoma Group registry.

BACKGROUND: The Spanish Melanoma Group (GEM) developed a national registry of patients with melanoma infected by SARS-CoV-2 ("GRAVID"). METHODS: The main objective was to describe the COVID-19 fatality rate in patients with melanoma throughout the pandemic, as well as to explore the effect of melanoma treatment and tumor stage on the risk of COVID-19 complications. These are the final data of the register, including cases from February 2020 to September 2021. RESULTS: One hundred-fifty cases were registered. Median age was 68 years (range 6-95), 61 (40%) patients were females, and 63 (42%) patients had stage IV. Thirty-nine (26%) were on treatment with immunotherapy, and 17 (11%) with BRAF-MEK inhibitors. COVID-19 was resolved in 119 cases, including 85 (57%) patients cured, 15 (10%) that died due to melanoma, and 20 (13%) that died due to COVID-19. Only age over 60 years, cardiovascular disorders, and diabetes mellitus increased the risk of death due to COVID-19, but not advanced melanoma stage nor melanoma systemic therapies. Three waves have been covered by the register: February-May 2020, August-November 2020, and December 2020-April 2021. The first wave had the highest number of registered cases and COVID-19 mortality. CONCLUSION: Tumor stage or melanoma treatments are non-significant prognostic factors for COVID-19 mortality. During the pandemic in Spain there was a downward trend in the number of patients registered across the waves, as well as in the severity of the infection. GOV IDENTIFIER: NCT04344002.

Cutaneous vascular calcification. Perieccrine calcification as a diagnostic key for calciphylaxis.

BACKGROUND: Attempts have been made to establish discriminative criteria between classic calciphylaxis (CPX) and those cases in which cutaneous vascular calcification (CVC) represents an incidental finding (epiphenomenon). METHODS: Retrospective, observational cohort study of patients with CVC to distinguish clinicopathological features between CVC as classic CPX (CVC in cutaneous lesions with erythematous-violaceous plaques with or without ulceration) or as an epiphenomenon (CVC in cutaneous lesions with known diagnosis). Different clinicopathological parameters and the presence of perieccrine calcification and pseudoxanthoma elasticum (PXE)-like changes were evaluated. RESULTS: Sixty-six patients were studied. The CPX group showed a significantly higher percentage of renal failure, hypertension, altered laboratory parameters, painful lesions, and mortality rate. Histopathologically, the CPX group was associated with more than one vessel per field involved with subintimal concentric calcification and perieccrine calcification (observed exclusively in the CPX group), while PXE-like changes, although more frequent in the CPX group, were also observed in the epiphenomenon group. CONCLUSION: Perieccrine calcification and the presence of more than one vessel per field involved by concentric pattern calcification could be used as a diagnostic marker of CPX. Although PXE-like changes are not an exclusive marker, they could suggest CPX diagnosis.

Method R: Efficacy of a cosmetic routine comprising six topical lipid-encapsulated products.

INTRODUCTION AND OBJECTIVE: Efficacy of cosmetic routines is reportedly available in several dermatological conditions, such as acne or rosacea. However, clinical evidence about objective advantages of skincare routine remains limited despite advertising often claims benefits. METHOD: We aimed to assess the subject satisfaction level and the benefit from daily use of an advanced skincare routine named Method R. We used four different approaches to try and demonstrate the efficacy of the method: Transdermal delivery test, ex-vivo efficacy test, Visioscan® VC 20, and patient survey. MetR consists of a six-step routine that shows an increased epidermal penetration and activity due to liposomation. RESULTS: Transdermal delivery test and ex-vivo efficacy test show increased efficacy for liposomated actives. The skincare routine is well tolerated, and is associated with a marked efficacy in global quality of skin, dyschromia/pigmentation, brightness, and hydration according to patient perception. The subject satisfaction level is high and the routine is safe. The continuous use of the routine for one month or more results in objective changes when measured with Visioscan® VC 20 plus.

Psoriasis Therapy and Skin Cancer: A Review.

INTRODUCTION: psoriasis is a chronic immune-mediated disease that is associated with several comorbidities, including an increased risk of malignancies, particularly skin cancer. A large number of studies have investigated whether psoriasis itself, psoriasis-associated comorbidities, or psoriasis treatment could lead to an increased risk of neoplasms. METHODS: we reviewed the literature using the most important databases (PubMed, MEDLINE, ETHERIA). All articles pertaining to skin cancer associated with psoriasis disease and psoriasis therapy were included. In this review, we also discuss some of the potential underlying mechanisms for these associations, particularly regarding the multiple psoriasis therapies currently available, and their possible implications in higher incidences of skin cancer in these patients. CONCLUSION: evidence suggests that these patients might have a higher risk of cutaneous malignancies, especially for NMSC, compared with psoriasis-free patients. The reasons for this increased risk remain to be determined. However, high dose PUVA therapy, the immunosuppressive treatments used, and the comorbidities and habits frequently described in these patients seem to play a role in the pathogenesis of these tumors. Because of these facts, periodic screening for skin cancer is recommended in this population.

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.

Growth arrest and DNA damage-inducible proteins (GADD45) in psoriasis.

The interplay between T cells, dendritic cells and keratinocytes is crucial for the development and maintenance of inflammation in psoriasis. GADD45 proteins mediate DNA repair in different cells including keratinocytes. In the immune system, GADD45a and GADD45b regulate the function and activation of both T lymphocytes and dendritic cells and GADD45a links DNA repair and epigenetic regulation through its demethylase activity. Here, we analyzed the expression of GADD45a and GADD45b in the skin, dendritic cells and circulating T cells in a cohort of psoriasis patients and their regulation by inflammatory signals. Thirty patients (17 male/13 female) with plaque psoriasis and 15 controls subjects (7 male/8 female), were enrolled. Psoriasis patients exhibited a lower expression of GADD45a at the epidermis but a higher expression in dermal infiltrating T cells in lesional skin. The expression of GADD45a and GADD45b was also higher in peripheral T cells from psoriasis patients, although no differences were observed in p38 activation. The expression and methylation state of the GADD45a target UCHL1 were evaluated, revealing a hypermethylation of its promoter in lesional skin compared to controls. Furthermore, reduced levels of GADD45a correlated with a lower expression UCHL1 in lesional skin. We propose that the demethylase function of GADD45a may account for its pleiotropic effects, and the complex and heterogeneous pattern of expression observed in psoriatic disease.

Hydrochlorothiazide use and risk of non-melanoma skin cancer in Spain: A case/non-case study.

OBJECTIVE: In 2018, the Pharmacological Risk Assessment Committee alerted to a potential relationship between accumulated hydrochlorothiazide dosage and the risk of non-melanoma skin cancer. To study this relationship we used data from the Spanish Pharmacovigilance System for Medicinal Products of Human Use. MATERIALS AND METHODS: Following a case search for every thiazide potentially associated with (SMQ/MedDRA) "Malignant Skin Neoplasms and not Otherwise Specified Skin Neoplasms", a series of disproportionality analyses were conducted by estimating the reporting odds ratio (95% confidence interval). Registered adverse drug reactions and disproportionality through the reported odds ratio were the main outcome measures. RESULTS: For basal cell carcinoma, reporting odds ratio was 4.8 (2.2 - 10.7); squamous cell carcinoma 3.2 (0.9 - 10.5); malignant melanoma, 0.8 (0.2 - 3.5). We found both disproportionality and association between hydrochlorothiazide and basal cell carcinoma, but none of these were found regarding malignant skin melanoma. In the case of squamous cell carcinoma, the lower confidence interval limit was below 1, thus the disproportionality value was not statistically significant. The accumulated hydrochlorothiazide dose was 36,714 mg for basal cell carcinoma; 98,288 mg for squamous cell carcinoma; and 38,444 mg for malignant melanoma. CONCLUSION: The results in Spain, where sun exposure is significant, are consistent with the data in the Pharmacological Risk Assessment Committee's alert, which were obtained in Denmark for both basal cell carcinoma and malignant melanoma. However, the results for squamous cell carcinoma did not reach statistical significance, although the reporting odds ratio value suggested a potential relationship between hydrochlorothiazide and squamous cell carcinoma.