Primary Cutaneous Lymphoma Registry of the Spanish Academy of Dermatology and Venereology (AEDV): Data for the First 5 Years. / Registro de linfomas cutáneos primarios (RELCP) de la AEDV: datos tras 5 años de funcionamiento.

BACKGROUND AND OBJECTIVE: Primary cutaneous lymphomas (PCL) are uncommon. Observations based on the first year of data from the Spanish Registry of Primary Cutaneous Lymphomas (RELCP, in its Spanish abbreviation) of the Spanish Academy of Dermatology and Venereology (AEDV) were published in February 2018. This report covers RELCP data for the first 5 years. PATIENTS AND METHODS: RELCP data were collected prospectively and included diagnosis, treatments, tests, and the current status of patients. We compiled descriptive statistics of the data registered during the first 5 years. RESULTS: Information on 2020 patients treated at 33 Spanish hospitals had been included in the RELCP by December 2021. Fifty-nine percent of the patients were men; the mean age was 62.2 years. The lymphomas were grouped into 4 large diagnostic categories: mycosis fungoides/Sézary syndrome, 1112 patients (55%); primary B-cell cutaneous lymphoma, 547 patients (27.1%); primary CD30+lymphoproliferative disorders, 222 patients (11%), and other T-cell lymphomas, 116 patients (5.8%). Nearly 75% of the tumors were registered in stage I. After treatment, 43.5% achieved complete remission and 27% were stable at the time of writing. Treatments prescribed were topical corticosteroids (1369 [67.8%]), phototherapy (890 patients [44.1%]), surgery (412 patients [20.4%]), and radiotherapy (384 patients [19%]). CONCLUSION: The characteristics of cutaneous lymphomas in Spain are similar to those reported for other series. The large size of the RELCP registry at 5 years has allowed us to give more precise descriptive statistics than in the first year. This registry facilitates the clinical research of the AEDV's lymphoma interest group, which has already published articles based on the RELCP data.

Prognostic factors in patients with primary cutaneous anaplastic large cell lymphoma: a multicentric, retrospective analysis of the Spanish Group of Cutaneous Lymphoma.

BACKGROUND: Reliable prognostic factors for patients with primary cutaneous anaplastic large cell lymphoma (PCALCL) are lacking. OBJECTIVE: To identify prognostic factors for specific survival in patients with PCALCL. METHODS: Using the convenience sampling method, patients with PCALCL diagnosed from May 1986 to August 2017 in 16 University Departments were retrospectively reviewed. RESULTS: One hundred eight patients were included (57 males). Median age at diagnosis was 58 years. All of them showed T1-3N0M0 stages. Seventy per cent of the cases presented with a solitary lesion, mostly at the limbs. Complete response rate after first-line treatment was 87%, and no advantage was observed for any of them (surgery, radiotherapy, chemotherapy or other approaches). Nodal and visceral progression rate was 11% and 2%, respectively. 5-year specific survival (SSV) reached 93%; 97% for T1 patients and 84% for T2/T3 patients (P = 0.031). Five-year SSV for patients developing early cutaneous relapse was 64%; for those with late or no relapse, 96% (P = 0.001). Estimated median SSV for patients showing nodal progression was 103 months (95% CI: 51-155 months); for patients without nodal progression, estimated SSV did not reach the median (P < 0.001). Nodal progression was an independent predictive parameter for shorter survival (P = 0.011). CONCLUSION: Multiple cutaneous lesions at presentation, early skin relapse and nodal progression portrait worse prognosis in patients with PCALCL.

First-line treatment in lymphomatoid papulosis: a retrospective multicentre study.

BACKGROUND: Data regarding response to treatment in lymphomatoid papulosis (LyP) are scarce. AIM: To assess the daily clinical practice approach to LyP and the response to first-line treatments. METHODS: This was a retrospective study enrolling 252 patients with LyP. RESULTS: Topical steroids, methotrexate and phototherapy were the most common first-line treatments, prescribed for 35%, 20% and 14% of the patients, respectively. Complete response (CR) was achieved in 48% of treated patients. Eczematous lesions significantly increased relative risk (RR) of not achieving CR (RR = 1.76; 95% CI 1.16-2.11). Overall median time to CR was 10 months (95% CI 6-13 months), and 78% of complete responders showed cutaneous relapse; both results were similar for all treatment groups (P > 0.05). Overall estimated median disease-free survival (DFS) was 11 months (95% CI 9-13 months) but DFS for patients treated with phototherapy was 23 months (95% CI 10-36 months; P < 0.03). Having the Type A LyP variant (RR = 2.04; 95% CI 0.96-4.30) and receiving a first-line treatment other than phototherapy (RR = 5.33; 95% CI 0.84-33.89) were significantly associated with cutaneous early relapse. Of the 252 patients, 31 (13%) had associated mycosis fungoides unrelated to therapeutic approach, type of LyP or T-cell receptor clonality. CONCLUSIONS: Current epidemiological, clinical and pathological data support previous results. Topical steroids, phototherapy and methotrexate are the most frequently prescribed first-line treatments. Although CR and cutaneous relapse rates do not differ between them, phototherapy achieves a longer DFS. Presence of Type A LyP and use of topical steroid or methotrexate were associated with an increased risk of early relapse.

Recomendaciones de expertos para el tratamiento de la psoriasis en situaciones especiales / Expert recommendations on treating psoriasis in special circumstances

INTRODUCCIÓN Y OBJETIVOS: Existe gran cantidad de información sobre la terapia sistémica y biológica de la psoriasis moderada-grave. Sin embargo, pueden identificarse numerosas situaciones clínicas concretas en las que la evidencia clínica es controvertida y donde resulta útil la opinión consensuada de los expertos. MATERIAL Y MÉTODOS: Un comité científico revisó, de forma sistemática, la bibliografía disponible en 5 escenarios clínicos. En aquellas cuestiones en las que la evidencia era controvertida se llevó a cabo un cuestionario on line según la metodología Delphi, realizado por dermatólogos con experiencia en el manejo de la psoriasis moderada-grave. RESULTADOS: El cuestionario recogió opiniones de 23 dermatólogos y se alcanzó el consenso en 37 de las 66 aseveraciones propuestas (56%). Los resultados permitieron consensuar propuestas en diversas situaciones clínicas, aun cuando la evidencia no fuese firme. Así, tanto el tratamiento intermitente como la desintensificación se consideraron estrategias adecuadas en la optimización de la terapia biológica y en la reducción de costes. La determinación de niveles de fármaco y de anticuerpos antifármaco debería incluirse rutinariamente en el seguimiento de los pacientes psoriásicos tratados con terapia biológica. La coexistencia de artropatía psoriásica y de antecedentes cardiovasculares condiciona la elección de la terapia biológica, prefiriéndose los fármacos anti-TNF alfa como primera elección. En pacientes embarazadas o con deseos de gestación la evaluación personalizada, la gravedad de la psoriasis y la vida media del fármaco son factores relevantes en la toma de decisiones. CONCLUSIONES: La combinación de una revisión sistemática de la literatura y la discusión y opinión estructurada de los expertos permite realizar propuestas para situaciones clínicas concretas

INTRODUCTION AND OBJECTIVES: A great amount of information on systemic and biologic therapies for moderate to severe psoriasis is now available. However, applying the evidence in numerous clinical scenarios has engendered debate; under these circumstances, the consensus of experts is useful. MATERIAL AND METHODS: A scientific committee systematically reviewed the literature relevant to 5 clinical scenarios. An online Delphi survey of dermatologists with experience treating moderate to severe psoriasis was then carried out in order to shed light on questions that remained unresolved by the available evidence. RESULTS: Twenty-three dermatologists responded to the survey and consensus was reached on 37 (56%) of the 66 statements proposed. These results led to consensus on various clinical situations even though firm evidence was lacking. Thus, intermittent therapeutic regimens and strategies for reducing the intensity of treatment are considered appropriate for optimizing biologic treatment and reducing costs. The measurement of drug and antidrug antibody levels should be included routinely when following patients on biologics to treat psoriasis. Concomitant psoriatic arthritis or a history of cardiovascular conditions will influence the choice of biologic; in these situations, an agent with anti-tumor necrosis factor properties will be preferred. Tailored management is important when the patient is pregnant or intends to conceive; drug half-life and disease severity are important factors to take into consideration in these scenarios. CONCLUSIONS: A combination of systematic review of the literature and structured discussion of expert opinion facilitates decision-making in specific clinical scenarios

Expert recommendations on treating psoriasis in special circumstances.

INTRODUCTION AND OBJECTIVES: A great amount of information on systemic and biologic therapies for moderate to severe psoriasis is now available. However, applying the evidence in numerous clinical scenarios has engendered debate; under these circumstances, the consensus of experts is useful. MATERIAL AND METHODS: A scientific committee systematically reviewed the literature relevant to 5 clinical scenarios. An online Delphi survey of dermatologists with experience treating moderate to severe psoriasis was then carried out in order to shed light on questions that remained unresolved by the available evidence. RESULTS: Twenty-three dermatologists responded to the survey and consensus was reached on 37 (56%) of the 66 statements proposed. These results led to consensus on various clinical situations even though firm evidence was lacking. Thus, intermittent therapeutic regimens and strategies for reducing the intensity of treatment are considered appropriate for optimizing biologic treatment and reducing costs. The measurement of drug and antidrug antibody levels should be included routinely when following patients on biologics to treat psoriasis. Concomitant psoriatic arthritis or a history of cardiovascular conditions will influence the choice of biologic; in these situations, an agent with anti-tumor necrosis factor properties will be preferred. Tailored management is important when the patient is pregnant or intends to conceive; drug half-life and disease severity are important factors to take into consideration in these scenarios. CONCLUSIONS: A combination of systematic review of the literature and structured discussion of expert opinion facilitates decision-making in specific clinical scenarios.

Evaluación clínica y terapéutica de los pacientes con psoriasis moderada o grave en España. Estudio Secuence / Clinical and Therapeutic Evaluation of Patients with Moderate to Severe Psoriasis in Spain: The Secuence Study

Introducción: La evaluación de la gravedad de la psoriasis se considera esencial en el manejo terapéutico óptimo de los pacientes. Objetivos: Descripción de las características clínicas y perfil terapéutico de los pacientes con psoriasis moderada a grave en el ámbito español, evaluando su impacto en la calidad de vida de los pacientes. Material y métodos: Estudio observacional, de corte transversal, realizado en 90 unidades dermatológicas en España en 2009. Se incluyeron 442 pacientes diagnosticados de psoriasis moderada a grave que habían iniciado tratamiento con fármacos sistémicos, fototerapia y/o tratamientos tópicos entre 2004 y 2006. Resultados: Los pacientes con psoriasis más grave presentaron de forma significativa un mayor tiempo de evolución de la enfermedad, mayor prevalencia de enfermedades concomitantes y mayor afectación ungueal, del cuero cabelludo, de las flexuras y de la zona palmo-plantar, así como peor calidad de vida. Durante los 5 años previos al inicio del estudio el 68% de los pacientes recibieron tratamientos sistémicos convencionales, el 39,1% fármacos biológicos y el 22,3% fototerapia. En la actualidad el 57,5% estaban siendo tratados con algún fármaco biológico, el 32,6% recibían fármacos sistémicos convencionales y el 11% fototerapia. Conclusiones: La gravedad de la psoriasis se asoció en nuestro estudio con una marcada afectación de la calidad de vida. Independientemente de la gravedad de la psoriasis, el mayor predictor de mala calidad de vida fue la comorbilidad psiquiátrica. El tiempo medio de permanencia en otros tratamientos, incluyendo sistémicos convencionales o fototerapia, hasta el cambio a un primer biológico fue superior a los 2 años (AU)

Background: Evaluation of disease severity is considered essential in the optimal management of psoriasis. Objectives: To describe the clinical characteristics and therapeutic profile of patients with moderate to severe psoriasis in Spain and to assess the impact of the disease on the patients’quality of life. Materials and methods: This was an observational, cross-sectional study carried out in 90 dermatology units in Spain in 2009. We included 442 patients diagnosed with moderate to severe psoriasis who had started treatment with systemic agents, phototherapy, and/or topical treatments between 2004 and 2006. Results: More severe psoriasis was significantly associated with the following: longer disease duration; higher prevalence of concomitant disease; greater involvement of the nails, scalp, flexures, palms, and soles; and poorer quality of life. In the 5 years before the start of the study,68% of the patients had received conventional systemic treatments, 39.1% biologic agents, and22.3% phototherapy. At present, 57.5% of the patients are being treated with biologic agents,32.6% with conventional systemic treatments, and 11% with phototherapy. Conclusions: Severity of psoriasis was associated with a marked impact on quality of life. Regardless of disease severity, psychiatric comorbidity was the strongest predictor of poor quality of life. On average, patients had received other treatments, such as conventional systemic treatments or phototherapy, for more than 2 years before switching to biologic agents for the first time (AU)

Clinical and therapeutic evaluation of patients with moderate to severe psoriasis in Spain: the secuence study.

BACKGROUND: Evaluation of disease severity is considered essential in the optimal management of psoriasis. OBJECTIVES: To describe the clinical characteristics and therapeutic profile of patients with moderate to severe psoriasis in Spain and to assess the impact of the disease on the patients' quality of life. MATERIALS AND METHODS: This was an observational, cross-sectional study carried out in 90 dermatology units in Spain in 2009. We included 442 patients diagnosed with moderate to severe psoriasis who had started treatment with systemic agents, phototherapy, and/or topical treatments between 2004 and 2006. RESULTS: More severe psoriasis was significantly associated with the following: longer disease duration; higher prevalence of concomitant disease; greater involvement of the nails, scalp, flexures, palms, and soles; and poorer quality of life. In the 5 years before the start of the study, 68% of the patients had received conventional systemic treatments, 39.1% biologic agents, and 22.3% phototherapy. At present, 57.5% of the patients are being treated with biologic agents, 32.6% with conventional systemic treatments, and 11% with phototherapy. CONCLUSIONS: Severity of psoriasis was associated with a marked impact on quality of life. Regardless of disease severity, psychiatric comorbidity was the strongest predictor of poor quality of life. On average, patients had received other treatments, such as conventional systemic treatments or phototherapy, for more than 2 years before switching to biologic agents for the first time.

Clinical and Therapeutic Evaluation of Patients with Moderate to Severe Psoriasis in Spain: The Secuence Study. / Evaluación clínica y terapéutica de los pacientes con psoriasis moderada o grave en España. Estudio Secuence.

BACKGROUND: Evaluation of disease severity is considered essential in the optimal management of psoriasis. OBJECTIVES: To describe the clinical characteristics and therapeutic profile of patients with moderate to severe psoriasis in Spain and to assess the impact of the disease on the patients' quality of life. MATERIALS AND METHODS: This was an observational, cross-sectional study carried out in 90 dermatology units in Spain in 2009. We included 442 patients diagnosed with moderate to severe psoriasis who had started treatment with systemic agents, phototherapy, and/or topical treatments between 2004 and 2006. RESULTS: More severe psoriasis was significantly associated with the following: longer disease duration; higher prevalence of concomitant disease; greater involvement of the nails, scalp, flexures, palms, and soles; and poorer quality of life. In the 5 years before the start of the study, 68% of the patients had received conventional systemic treatments, 39.1% biologic agents, and 22.3% phototherapy. At present, 57.5% of the patients are being treated with biologic agents, 32.6% with conventional systemic treatments, and 11% with phototherapy. CONCLUSIONS: Severity of psoriasis was associated with a marked impact on quality of life. Regardless of disease severity, psychiatric comorbidity was the strongest predictor of poor quality of life. On average, patients had received other treatments, such as conventional systemic treatments or phototherapy, for more than 2 years before switching to biologic agents for the first time.

Intralesional rituximab in the treatment of indolent primary cutaneous B-cell lymphomas: an epidemiological observational multicentre study. The Spanish Working Group on Cutaneous Lymphoma.

BACKGROUND: Intravenous rituximab is a safe and effective option for the treatment of systemic non-Hodgkin B-cell lymphoma. The effectiveness of intralesional rituximab (ILR) in primary cutaneous B-cell lymphomas (PCBL) has been described in a small number of patients. OBJECTIVES: To evaluate the effectiveness, tolerance and adverse effects of ILR in patients with follicle centre (FCL) and marginal zone (MZL) PCBL. METHODS: This was an epidemiological observational multicentre study of patients with PCBL treated with ILR. RESULTS: Seventeen patients with MZL and 18 with FCL PCBL were included. The median number of lesions treated was two per patient. The treatment regimen used in 74% of the patients was a course of three injections in a single week at 1-month intervals. The dose per lesion and day of treatment was 10 mg in 71% of the patients. The median cumulative dose of rituximab per lesion was 60 mg (range 13-270) and per patient was 150 mg (range 20-360 mg). Complete response (CR) and partial response were achieved in 71% and 23% of patients, respectively. The median time to CR in patients who received 10 mg of ILR per lesion was 8 weeks. Similar response rates were observed in MZL and FCL. Median disease-free survival was 114·1 weeks. No parameters that significantly predicted CR were identified. Adverse reactions were recorded in 19 patients; the most frequent was localized pain at the injection site. Median follow-up was 21 months. CONCLUSIONS: Intralesional rituximab is a well-tolerated and effective treatment for FCL and MZL PCBL. It should be considered a useful alternative in patients with recurrent lesions and in which the sequelae of radiotherapy or surgery would be significant.

[Attitude of the adult patient with atopic dermatitis to the disease and its treatment: the ACTIDA Study]. / Actitud del paciente adulto con dermatitis atópica frente a su patología y tratamiento. Estudio ACTIDA.

OBJECTIVE: To determine the attitude of adult patients with atopic dermatitis (AD) to their disease and its treatment. MATERIAL AND METHODS: A multicenter, cross-sectional study was performed in patients with at least 2 outbreaks of AD in the previous year. RESULTS: Two hundred twenty-seven dermatologists recruited 1441 analyzable patients, the majority women, with a mean of 3.6 outbreaks per year. Most of the patients (97.2%) indicated that they always or sometimes requested medical evaluation of a new outbreak. In the most recent outbreak, 72.2% had used combined therapy, regardless of the severity of the episode; 2-drug combinations were the most common. The majority of dermatologists prescribed combined therapy, most commonly a 2-drug combination for mild or minimal disease, and 3 or more drugs for moderate to very severe outbreaks. CONCLUSIONS: Treatments used by patients for an outbreak of AD are similar to those prescribed by dermatologists in recent outbreaks.

Actitud del paciente adulto con dermatitis atópica frente a su patología y tratamiento. Estudio ACTIDA / Attitude of the adult patient with atopic dermatitis to the disease and its treatment: The ACTIDA Study

Introducción y objetivos: Conocer la actitud de los pacientes adultos frente a la dermatitis atópica (DA) y su tratamiento. Material y métodos: Estudio transversal, multicéntrico, realizado en pacientes con al menos 2 brotes en el último año. Resultados: Doscientos veintisiete dermatólogos reclutaron 1.441 pacientes analizables, mayoritariamente mujeres con 3,6 brotes al año de media. La mayoría de los pacientes (97,2%) indicó que solicitaba, al menos ocasionalmente, asesoramiento médico ante nuevos brotes. El 72,2% recurrió a la terapia combinada (TC) en el último brote, independientemente de su intensidad, siendo las combinaciones de 2 fármacos (TC2) las más utilizadas. Los dermatólogos indicaron mayoritariamente TC, siendo la TC2 más frecuente para formas leves y casi sin enfermedad, y la TC de más de 2 fármacos en brotes moderados a muy graves. Conclusiones: Los tratamientos empleados por los pacientes ante un brote de DA son similares a los indicados por los dermatólogos (AU)

Objective: To determine the attitude of adult patients with atopic dermatitis (AD) to their disease and its treatment. Material and methods: A multicenter, cross-sectional study was performed in patients with at least 2 outbreaks of AD in the previous year. Results: Two hundred twenty-seven dermatologists recruited 1441 analyzable patients, the majority women, with a mean of 3.6 outbreaks per year. Most of the patients (97.2%) indicated that they always or sometimes requested medical evaluation of a new outbreak. In the most recent outbreak, 72.2% had used combined therapy, regardless of the severity of the episode; 2-drug combinations were the most common. The majority of dermatologists prescribed combined therapy, most commonly a 2-drug combination for mild or minimal disease, and 3 or more drugs for moderate to very severe outbreaks. Conclusions: Treatments used by patients for an outbreak of AD are similar to those prescribed by dermatologists in recent outbreak (AU)

Bexarotene activates the p53/p73 pathway in human cutaneous T-cell lymphoma.

BACKGROUND: Bexarotene is the first synthetic retinoid X receptor-selective retinoid (rexinoid) approved for the treatment of cutaneous T-cell lymphoma (CTCL). However, little is known about the signalling pathways by which it exerts its anticarcinogenic effect. OBJECTIVES: To characterize the effects of bexarotene in CTCL cell lines and elucidate the underlying molecular pathways of its antineoplastic effect. METHODS: The cell lines Hut-78, HH and MJ were used. Cell viability was assessed with the XTT assay. The self-renewal potential of cells after bexarotene treatment was studied with the methylcellulose clonogenic assay. Flow cytometry was used to analyse the effects on cell cycle, Ki-67 expression and apoptosis induction. Cell cycle and apoptosis-related protein expression were determined by Western blot and immunofluorescence. RESULTS: Bexarotene induced a loss of viability and more pronounced inhibition of clonogenic proliferation in HH and Hut-78 cells, whereas the MJ line exhibited resistance. Bexarotene upregulated and activated Bax in sensitive lines, although not enough to signal significant apoptosis. Instead, all data point to the inhibition of proliferation, rather than apoptosis, as the main mechanistic action of the rexinoid. Bexarotene signals both G(1) and G(2)/M arrest by the modulation of critical checkpoint proteins. We further found that bexarotene activates p53 by phosphorylation at Ser15, which influences the binding of p53 to promoters for cell cycle arrest, induces p73 upregulation, and, in concordance, also modulates some p53/p73 downstream target genes, such as p21, Bax, survivin and cdc2. Bexarotene-mediated ataxia telangiectasia mutated protein (ATM) activation in all studied lines suggests that ATM is likely to be the p53/p73 upstream activator. CONCLUSIONS: Our data indicate for the first time that bexarotene exerts its effect in CTCL mainly by triggering the p53/p73-dependent cell cycle inhibition pathway, probably by upstream ATM activation. Therefore, bexarotene-modulated genes represent potential biomarkers to assess the response to treatment of patients with CTCL.

Trasplante autólogo de progenitores hematopoyéticos seguido de bexaroteno oral en paciente con micosis fungoide avanzada / Autologous hematopoietic stem cell transplantation folowed by oral bexarotene in a patient with advanced mycosis fungoides

Exponemos el caso de una paciente de 17 años que presentó una micosis fungoide de evolución rápida y agresiva, con múltiples tumores cutáneos y transformación fenotípica celular a linfoma de células grandes. Fue tratada inicialmente con 3 ciclos de quimioterapia en dosis altas (MEGA-CHOP) sin respuesta, por lo que se decidió realizar un trasplante autólogo de progenitores hematopoyéticos. Este tratamiento consiguió una remisión parcial de la enfermedad, y con la posterior introducción del bexaroteno oral se logró la remisión completa, que se ha mantenido durante más de 3 años con muy buena tolerancia al bexaroteno oral. Analizamos las ventajas y desventajas de la utilización del trasplante autólogo de progenitores hematopoyéticos y del uso de bexaroteno oral (AU)

We describe the case of a 17-year-old patient with rapidly progressing and aggressive mycosis fungoides, with multiple cutaneous tumors and large cell transformation. She was initially treated with 3 cycles of high-dose chemotherapy with mega-CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisone) without response, leading to the decision to undertake autologous hematopoietic stem cell transplantation. Partial remission of the disease was achieved with this treatment and subsequent introduction of oral bexarotene led to complete remission, which has been maintained for more than 3 years with good tolerance of oral therapy. We discuss the advantages and disadvantages of autologous hematopoietic stem cell transplantation and the use of oral bexarotene (AU)

[Autologous hematopoietic stem cell transplantation followed by oral bexarotene in a patient with advanced mycosis fungoides]. / Trasplante autólogo de progenitores hematopoyéticos seguido de bexaroteno oral en paciente con micosis fungoide avanzada.

We describe the case of a 17-year-old patient with rapidly progressing and aggressive mycosis fungoides, with multiple cutaneous tumors and large cell transformation. She was initially treated with 3 cycles of high-dose chemotherapy with mega-CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisone) without response, leading to the decision to undertake autologous hematopoietic stem cell transplantation. Partial remission of the disease was achieved with this treatment and subsequent introduction of oral bexarotene led to complete remission, which has been maintained for more than 3 years with good tolerance of oral therapy. We discuss the advantages and disadvantages of autologous hematopoietic stem cell transplantation and the use of oral bexarotene.

Interleukin-2 enhances the growth of human melanoma cells derived form primary but not from metastatic tumours.

Previously, we demonstrated that in vitro treatment of B16F10 murine melanoma cells with interleukin-2 (IL-2) enhances proliferation and metastasis. To further investigate the role played by IL-2 in human melanomas, we studied the expression of IL-2/IL-2 receptor and the effect of IL-2 on the proliferation of melanoma cell lines derived from primary (A375 and RMS cell lines) and metastatic (Hs294T cell line) tumours. We found a constitutive expression of cytoplasmic IL-2 and alpha, beta and gamma-subunits of the IL-2R on the surface of the three melanoma cell lines. The presence of IL-2 in the culture increased the proliferation rate in A375 and RMS cell lines, but no effect was observed in Hs294T metastatic cells. Biologically active IL-2 could be found in the supernatant of the three melanoma cell lines, particularly in A375 and RMS cells, in which an inhibition of the proliferation rate was observed when IL-2 was blocked. Moreover, the combination of anti-IL-2R beta and anti-IL-2R gamma blocking antibodies induced a significant down-regulation of cell proliferation in the three melanoma cell lines, and the combination of anti-IL-2R alpha, anti-IL-2R beta and anti-IL-2R gamma blocking antibodies inhibited IL-2-mediated growth stimulation in A375 and Hs294T cell lines. In RMS cells, a more significant effect was observed when only IL-2R gamma was blocked. Finally, exogenous IL-2 modulated the IL-2 endogenously produced by melanoma cells. These data show that IL-2 may modulate the growth of melanoma cells through autocrine or/and paracrine mechanisms.

Soluble interleukin-2 receptor, intercellular adhesion molecule-1 and interleukin-10 serum levels in patients with melanoma.

Serum soluble interleukin-2 receptor (sIL-2R), intercellular adhesion molecule-1 (sICAM-1) and interleukin-10 (IL-10) have each been reported as useful markers for melanoma progression. To evaluate the clinical relevance of these three markers, we simultaneously analysed their serum levels in patients with melanoma. A longitudinal study with a 3-year follow-up was performed and different stages of the disease were considered. Mean values of sIL-2R were significantly higher than in normal controls in all stages and correlated with the disease progression. The prognosis of patients with levels > 529 U/ml of sIL-2R was significantly poorer than in patients with sIL-2R levels < 529 U/ml. Levels of sICAM-1 were also elevated in melanoma patients, specially at the time of the metastatic disease. Serum IL-10 levels were more frequently detectable in the patients that developed metastasis during follow-up, and the prognosis of patients with detectable IL-10 levels was significantly poorer than in those patients with IL-10 undetected levels. Statistical analysis based on Logistic and Cox regression models showed that only sex, stage and sIL-2R value are factors significantly associated with metastatic progression. Moreover, high levels of sIL-2R could be a risk factor for malignant progression in melanoma.

A case of the elephant man phenotype with giant rhinophyma and benign symmetric lipomatosis.

We described an unusual male patient with two disfiguring diseases, benign symmetric lipomatosis and giant rhinophyma, which gave him a grotesque appearance. His physical appearance had isolated him from the rest of society and was probably the main reason for his alcohol abuse.