Longitudinal Study of Different Progression Patterns in High-Risk Cutaneous Squamous Cell Carcinoma. / Estudio longitudinal de los diferentes patrones de progresión en el carcinoma cutáneo de células escamosas de alto riesgo.

BACKGROUND AND OBJECTIVE: Cutaneous squamous cell carcinoma (cSCC) is the second leading cause of skin cancer mortality in Europe. Few studies have analyzed the different pathways of this tumor progression in its natural history. The main objective of this study was to analyze the different metastatic and progression pathways and their temporal occurrence in the evolution of cSCC. MATERIAL AND METHOD: We conducted a multicenter, retrospective, and observational study of consecutive high-risk sSCCs included in the SQUAMATA project. RESULTS: A total of 222 out of the 1346 patients included relapsed. The most frequent route of progression was the lymphatic one (62.6%). A total of 20.2% of the cases with lymphatic progression developed distant metastases. Only 1 case (3.1%) of distant metastasis followed local recurrence without previous lymphatic metastasis. The median time to disease-related mortality was longer in patients who developed systemic metastases than in those who died of locoregional progression. CONCLUSIONS: The mortality of patients with cSCC is mostly due to the regional progression of their lymphatic metastases. The appearance of distant metastases is practically always (96.9%) associated with previous lymphatic metastatic progression. Therefore, in the future, new studies will be needed to assess the regional management of cSCC in both surgical and adjuvant therapies.

Validation of the Spanish Version of the PURE-4 Questionnaire for the Early Detection of Psoriatic Arthritis in Psoriatic Patients. / Validación de la versión española del cuestionario PURE-4 para la detección precoz de la artritis psoriásica en pacientes con psoriasis.

BACKGROUND AND OBJECTIVE: Psoriasis often precedes the onset of psoriatic arthritis (PsA), so dermatologists often face the challenge of early identifying signs of PsA in patients with psoriasis. Our aim was to validate the Spanish version of the PURE-4 questionnaire as a screening tool for PsA, evaluate its performance in terms of sensitivity, specificity, feasibility, reliability, and build validity. METHODS: This was a cross-sectional, observational, multicenter trial of adult patients with psoriasis. Initially, patients were assessed by a dermatologist and completed 2 self-administered versions (in print and online) of the PURE-4 questionnaire. Afterwards, the rheumatologist, blinded to the PURE-4 results, assessed the presence/absence of PsA, being the reference to determine the performance of the PURE-4 questionnaire. RESULTS: A total of 268 patients were included (115 [42.9%] women; mean age, 47.1±12.6). The prevalence of PsA according to rheumatologist diagnosis was 12.7% (34 patients). The mean PURE-4 score for patients with psoriasis diagnosed with PsA was 2.3±1.1, and 1.3±1.3 for patients without PsA (P<.001). The cutoff value ≥2 demonstrated the best performance for detecting PsA, with a negative predictive value of 95.1% (95% confidence interval, 90.3-97.6). CONCLUSIONS: The PURE-4 questionnaire demonstrated good performance in detecting PsA, with an optimal cutoff point ≥2. This simple tool could facilitate early referral of patients to the rheumatology unit.

Sentinel lymph node biopsy plus wide local excision vs. wide location excision alone for primary cutaneous melanoma: a systematic review and meta-analysis.

BACKGROUND: Sentinel lymph node biopsy and wide local excision of the primary melanoma (SLNB) is now a standard staging procedure for patients with melanomas 1 mm or more in thickness, but its therapeutic benefit is not clear. OBJECTIVE: To determine whether there is an association between performance of SLNB and patient prognosis. METHODS: Studies assessing the association between performance of SLNB and patient prognosis were pooled from MEDLINE, EMBASE, PubMed, Cochrane Database of Systematic Reviews and Google Scholar. From each study, first author's last name, publication year, origin country, type of study design, characteristics of participants and the Hazard risk (HR) for melanoma specific survival (MSS) with the corresponding 95% confidence interval (95% CI) were collected. Methodological assessment of the studies was evaluated using the Newcastle-Ottawa scale (NOS) and the 'Risk of bias' tool detailed in the Cochrane Handbook for Systematic Reviews of Interventions. Meta-analyses for the global HR were performed. In addition, in order to explore the sources of heterogeneity among the studies, sensitivity analyses are also provided. RESULTS: A total of six studies with 8764 patients who had undergone SLNB and 11054 patients who had undergone wide location excision alone (WLEA) were identified for the analysis. The indicators suggest that the heterogeneity is low: τ2  = 0; H = 1 [1; 1.74]; I2  = 0% [0%; 66.5%]. Evidence for publication bias was not found (Egger's test P = 0.4654). The pooled MSS HR from fixed effects analysis was determined to be 0.88 (95% CI = 0.80-0.96). CONCLUSIONS: Although no significant survival difference was observed in four of the six series, the pooling summary data from all the studies that deal with this issue suggested that SLNB is associated with a significantly better outcome compared with WLEA for localized melanoma.

Merkel cell carcinoma and Merkel cell polyomavirus: a systematic review and meta-analysis.

Several observational studies have assessed the correlation between Merkel cell carcinoma and Merkel cell polyomavirus with variable results. The objective of this systematic review was to determine whether there is a correlation between Merkel cell carcinoma and Merkel cell polyomavirus. Studies assessing the relationship between Merkel cell carcinoma and Merkel cell polyomavirus from January 2008 to August 2014 were pooled from Medline, Embase, PubMed, Cochrane Database of Systemic Reviews and Google Scholar. From each study we collected the first author's last name, publication year, country of origin, type of study design, characteristics of participants, possible variables incorporated into the multivariable analyses and the risk ratio (RR) for Merkel cell carcinoma associated with Merkel cell polyomavirus combined with the corresponding 95% confidence interval (CI). Methodological assessment of the study was evaluated using the Newcastle-Ottawa scale. Crude RR was calculated from the data provided in each article. Meta-analyses for the global RR and for the proportion of positives in both case and control samples were performed. In addition, in order to explore the sources of heterogeneity among the studies, meta-regression and sensitivity analyses are also provided. A total of 22 studies were identified for the analysis. The pooled RR from random-effects analysis was determined to be 6.32 (95% CI, 4.02-9.93). Global proportions of positive samples were 0.79 (95% CI, 0.72-0.84) and 0.12 (95% CI, 0.08-0.19) in the case and control groups, respectively. The findings support the association between Merkel cell carcinoma and Merkel cell polyomavirus. However, a non-negligible percentage of positive results have been identified in controls. Some caution must be taken in the interpretation of these results because heterogeneity between studies was found.

Bilateral Sertoli cell adenoma in gonads, associated with serous cystadenoma.

Complete androgen insensitivity syndrome is an extremely infrequent disease. The patients exhibit female phenotype because of insensitivity to the androgen receptor and may develop tumors, especially in their undescended gonads. We report a case of bilateral Sertoli cell adenoma in gonads with unilateral serous cystadenoma, in an elderly phenotypic woman with primary amenorrhea. We also provide radiological and pathological studies.

Psoriasis, psoriatic arthritis and type 2 diabetes mellitus: a systematic review and meta-analysis.

Several observational studies have assessed the association between psoriasis, psoriatic arthritis (PsA) and type 2 diabetes mellitus, with inconclusive results. We set out to investigate the association between psoriasis, PsA and type 2 diabetes mellitus. Observational studies assessing the relationship between psoriasis or PsA and type 2 diabetes mellitus up to December 2012 were identified by electronic and hand searches in Medline, Embase, PubMed, the Cochrane Database of Systematic Reviews and Google Scholar. For each study we collected the first author's last name, publication year, country of origin, study design, characteristics of participants (sample size, age and sex), the variables incorporated into the multivariable analyses, and the odds ratios (ORs) of psoriasis associated with diabetes along with the corresponding 95% confidence intervals (CIs). From the data provided in each article, the crude OR was also calculated. Forty-four observational studies (in 37 articles) were identified for the final analysis. The pooled OR from random-effects analysis was determined to be 1·76 (95% CI 1·59-1·96). The highest risk was for patients suffering from PsA (OR 2·18, 95% CI 1·36-3·50). We also observed a dose effect in the risk of suffering from type 2 diabetes mellitus, as patients considered as having severe psoriasis had higher risk (OR 2·10, 95% CI 1·73-2·55) than the pooled OR. We perform meta-regression and sensitivity analyses to explore sources of heterogeneity among the studies and to determine how they would influence the estimates, and found no significant influence in the results of the meta-analyses. The findings support the association between psoriasis, PsA and type 2 diabetes mellitus. Some caution must be taken in the interpretation of these results because there may be heterogeneity between studies.

Psoriasis and hypertension: a case-control study.

BACKGROUND: Several studies stated that patient with psoriasis carried an increased risk of psoriasis but some studies did not demonstrate this association. OBJECTIVES: The aim of this study was to evaluate the prevalence of hypertension in psoriasis based on a sample of Spanish population. METHODS: This was a hospital-based case-control study involving 661 psoriatic patients (cases) and 661 control matched by gender and age. Meta-analysis of the previous studies was made. RESULTS: The prevalence of hypertension was significantly higher in psoriasis patients than controls (30.3%, 21.3%, respectively, P < 0.001). In a multivariate analysis, hypertension was associated with psoriasis after controlling for age, gender, diabetes, obesity and smoking (OR = 1.44, 95% confidence interval: 1.07-1.94). CONCLUSION: The results of this study support the association between psoriasis and hypertension.

Acute renal failure caused by imiquimod 5% cream in a renal transplant patient: review of the literature on side effects of imiquimod.

Imiquimod is an immunomodulator of the imidazoquinoline group which possesses antiviral and antitumour activities. Although its mechanism of action has not been entirely elucidated yet, imiquimod 5% cream has been shown to be an efficient, long-lasting and safe therapy for multiple actinic keratoses in non-immunosuppressed patients and in transplant recipients. We report the case of a 44-year-old patient with a third renal transplant who developed an acute tubular necrosis confirmed by renal biopsy after the use of imiquimod 5% cream. The result of a literature search revealed a wide variety of side effects attributable to the use of imiquimod.

[Nail psoriasis in individuals with psoriasis vulgaris: a study of 661 patients]. / Psoriasis ungueal: estudio en 661 pacientes con psoriasis vulgar.

BACKGROUND AND OBJECTIVES: The nails are affected in a substantial number of patients with psoriasis. Nevertheless, few epidemiological studies have reported the characteristics of patients with nail psoriasis. Here we describe the epidemiology of nail psoriasis and the main characteristics of affected patients. PATIENTS AND METHODS: We undertook a prospective case-control study at Hospital Universitario Marqués de Valdecilla and Hospital Universitario Central de Asturias in Spain between January 2007 and December 2009. RESULTS: Of a total of 661 patients included, 47.4% were diagnosed with nail psoriasis, which was 13.5% more prevalent in men. The group of patients with nail disease had more severe psoriasis (12.82 vs 8.22 points on the psoriasis area and severity index) and a longer disease duration (20.30 vs 13.94years), and included a larger percentage of patients with psoriatic arthritis (29.7% vs 11.5%), a positive family history of the disease (53.7% vs 42.8%), and a body mass index greater than 30 (31.6% vs 23.9%). A larger percentage of the patients with nail disease had early-onset psoriasis (74.1% vs 65.5%) and fewer were carriers of the human lymphocyte antigen Cw*0602 allele (33% vs 50.3%). CONCLUSIONS: Nail disease is frequent in psoriasis and is associated with greater severity of psoriasis and a larger number of comorbidities.

[Psoriasiform skin reactions during treatment with etanercept]. / Reacciones cutáneas psoriasiformes durante el tratamiento con etanercept.

Anti-TNFs have a wide spectrum of skin lesions, psoriasis being found among them paradoxically. A 42-year old woman with a history of rheumatoid arthritis since 19 years of age was referred to the Dermatology service due to pustular psoriasis on both soles during treatment with etanercept. Due to her incapacity to walk and the pain reported by the patient, etanercept was replaced with adalimumab with clinical improvement and total disappearance of the lesions at six weeks of switching the anti-TNF. Tumor necrosis factor inhibitors are drugs that act in T cell mediated diseases. The appearance of psoriasiform rashes is more frequent than reported in the literature. They appear in all the indications and with all the anti-TNFs. Adalimumab is the most frequent. Three types of reactions are produced, the pustular one being the most frequent. It predominates in women and may appear chronologically at any time during the treatment. Regarding the treatment, it is recommendable to continue with the anti-TNFs.

[Treatment of scalp psoriasis: review of the evidence and Delphi consensus of the Psoriasis Group of the Spanish Academy of Dermatology and Venereology]. / Tratamiento de la psoriasis del cuero cabelludo. Revisión de la evidencia y Consenso Delphi del Grupo de Psoriasis de la Academia Española de Dermatología y Venereología.

Scalp lesions are common in psoriasis and difficult to treat. Scientific evidence on the topic is scant and fragmentary, especially with respect to long-term treatment. This consensus statement is based on a critical assessment of the results of a MEDLINE search for clinical trials of the efficacy and safety of therapies used to treat scalp psoriasis. The recommendations were developed by an expert panel using the Delphi process to reach a consensus and then ratified by the members of the Psoriasis Group of the Spanish Academy of Dermatology and Venereology. The recommended induction therapy for scalp psoriasis is either a topical corticosteroid or a topical treatment combining calcipotriol and betamethasone. The choice of an appropriate vehicle is crucial in improving effectiveness and patient adherence to treatment. The only formulations that have been studied in the long-term treatment of scalp psoriasis are a combination of calcipotriol and betamethasone in gel and calcipotriol alone in solution.

[Estimated Effect of COVID-19 Lockdown on Skin Tumor Size and Survival: An Exponential Growth Model]. / Estimación del efecto en el tamaño y la supervivencia de los tumores cutáneos debido al confinamiento por COVID-19: modelo basado en un crecimiento exponencial.

BACKGROUND AND OBJECTIVES: Spain is in a situation of indefinite lockdown due to the ongoing coronavirus disease 2019 (COVID-19) pandemic. One of the consequences of this lockdown is delays in medical and surgical procedures for common diseases. The aim of this study was to model the impact on survival of tumor growth caused by such delays in patients with squamous cell carcinoma (SCC) and melanoma. MATERIAL AND METHODS: Multicenter, retrospective, observational cohort study. We constructed an exponential growth model for both SCC and melanoma to estimate tumor growth between patient-reported onset and surgical excision at different time points. RESULTS: Data from 200 patients with SCC of the head and neck and 1000 patients with cutaneous melanoma were included. An exponential growth curve was calculated for each tumor type and we estimated tumor size after 1, 2, and 3 months of potential surgical delay. The proportion of patients with T3 SCC (diameter >4cm or thickness >6 mm) increased from 41.5% (83 patients) in the initial study group to an estimated 58.5%, 70.5%, and 72% after 1, 2, and 3 months of delay. Disease-specific survival at 2, 5, and 10 years in patients whose surgery was delayed by 3 months decreased by 6.2%, 8.2%, and 5.2%, respectively. The proportion of patients with ultrathick melanoma (>6 mm) increased from 6.9% in the initial study group to 21.9%, 30.2%, and 30.2% at 1, 2, and 3 months. Five- and 10-year disease-specific survival both decreased by 14.4% in patients treated after a potential delay of 3 months. CONCLUSIONS: In the absence of adequate diagnosis and treatment of SCC and melanoma in the current lockdown situation in Spain, we can expect to see to a considerable increase in large and thick SCCs and melanomas. Efforts must be taken to encourage self-examination and facilitate access to dermatologists in order to prevent further delays.

Massive lower gastrointestinal haemorrhage, successfully treated with corticosteroids, as main symptom of Schönlein-Henoch purpura.

Schönlein-Henoch purpura is a small vessel disease that affects mainly skin and kidney, although several gastrointestinal symptoms may occur including abdominal pain, intussusception, perforation or bleeding. Massive lower gastrointestinal haemorrhage is rare and even more as the main symptom of the disease. We present a case of a 2-year-old boy with Schönlein-Henoch purpura who developed a massive lower gastrointestinal bleeding requiring blood transfusion. In this patient both Schönlein-Henoch purpura and gastrointestinal haemorrhage were successfully treated with intravenous methylprednisolone, avoiding surgical intervention. Physicians need to have a high index of suspicion when evaluating these patients, even more when dermatologic signs are scarce. Glucocorticosteroid therapy may be effective when treating severe gastrointestinal symptoms.

Lectin-like transcript 1 (LLT1) expression is associated with nodal metastasis in patients with head and neck cutaneous squamous cell carcinoma.

The interaction of lectin-like transcript 1 (LLT1) with CD161 inhibits Natural Killer cell activation. Overexpression of LLT1 contributes to the immunosuppressive properties of tumor cells. However, there are little data about LLT1 expression in human solid tumors. The objective of this paper is to investigate the relationship between LLT1 expression with the clinicopathologic features and its impact on the prognosis of head and neck cutaneous squamous cell carcinoma (cSCC). LLT1 expression was analyzed on paraffin-embedded tissue samples obtained from 100 patients with cSCC by immunohistochemistry. The estimator of Fine and Gray was used to estimate the cumulative incidence curves for relapse. Proportional Hazard models and Hazard ratios (HRs) were used for studying the risk of tumor relapse and mortality. LLT1 strong expression was a significant risk factor for nodal metastasis with crude and adjusted ratios (HRs) of 3.40 (95% CI 1.39-9.28) and 3.25 (95% CI 1.15-9.16); and for cSCC specific death of 6.17 (95% CI 1.79-21.2) and 6.10 (95% CI 1.45-25.7). Strong LLT1 expression is an independent predictor of nodal metastasis and poor disease-specific survival and it might be helpful for risk stratification of patients with cSCC.