Position statement for the management of comorbidities in psoriasis.

BACKGROUND: The association between psoriasis and some diseases has become relevant in recent years. Providing appropriate management of psoriasis from an early stage requires prompt diagnosis and treatment of concomitant diseases and to prevent any potential comorbidity. This approach should consider the adverse events of the drugs used to treat psoriasis potentially related to the onset of comorbidities. OBJECTIVE: To provide the dermatologist with an accurate and friendly tool for systematizing the diagnosis of psoriasis-associated comorbidities, which generally escapes the scope of the dermatology setting, and to facilitate decision-making about the referral and treatment of patients with comorbidities. METHODS: These position statement recommendations were developed by a working group composed of ten experts (four dermatologists, one cardiologist, one rheumatologist, one gastroenterologist, one nephrologist, one endocrinologist and one psychiatrist) and two health services researchers. The expert group selected the psoriasis comorbidities considered according to their relevance in the dermatology setting. The recommendations on diagnostic criteria are based on the current clinical practice guidelines for each of the comorbidities. The information regarding the repercussion of psoriasis medical treatments on associated comorbid diseases was obtained from the summary of product characteristics of each drug. RESULTS: Recommendations were developed to detect and refer the following psoriasis comorbidities: psoriatic arthritis, cardiovascular risk factors (diabetes, dyslipidaemia, obesity, hypertension and metabolic syndrome), non-alcoholic fatty liver disease, inflammatory bowel disease, kidney disease and psychological disorders (anxiety and depression). In addition, alcohol consumption and tobacco consumption were included. The tables and figures are precise, easy-to-use tools to systematize the diagnosis of comorbidities in patients with psoriasis and facilitate the decision-making process regarding referral and treatment of patients with an associated disease. CONCLUSION: The application of these position statement recommendations will facilitate the dermatologist practice, and benefit psoriasis patients' health and quality of life.

Psoriasis and Nonalcoholic Fatty Liver Disease. / Psoriasis e hígado graso no alcohólico.

Nonalcoholic fatty liver disease (NAFLD) is the most prevalent liver condition in the West. The prevalence and severity of NAFLD is higher and the prognosis worse in patients with psoriasis. The pathogenic link between psoriasis and NAFLD is chronic inflammation and peripheral insulin resistance, a common finding in diseases associated with psoriasis. NAFLD should therefore be ruled out during the initial evaluation of patients with psoriasis, in particular if they show signs of metabolic syndrome and require systemic treatment. Concomitant psoriasis and NAFLD and the likelihood of synergy between them place limitations on general recommendations and treatment for these patients given the potential for liver toxicity. As hepatotoxic risk is associated with some of the conventional drugs used in this setting (e.g., acitretin, methotrexate, and ciclosporin), patients prescribed these treatments should be monitored as appropriate. Anti-tumor necrosis factor agents hold the promise of potential benefits based on their effects on the inflammatory process and improving peripheral insulin resistance. However, cases of liver toxicity have also been reported in relation to these biologics. No evidence has emerged to suggest that anti-p40 or anti-interleukin 17 agents provide benefits or have adverse effects.

Kidney Disease and Psoriasis. A New Comorbidity? / Enfermedad renal y psoriasis. ¿Una nueva comorbilidad?

Psoriasis is a chronic inflammatory disease that has been associated with cardiovascular and metabolic comorbidities, particularly in young patients and patients with more severe forms of the disease. Recent studies have also linked psoriasis to kidney disease, and this would seem only logical, as the kidney is both a target of classic cardiovascular risk factors and susceptible to the toxic effects of some of the traditional drugs used to control psoriasis. In this article, we would like to draw readers' attention to this recently described comorbidity and stress the importance of early detection, as once chronic kidney disease develops, it cannot be reversed. When evaluating patients with psoriasis, particularly when they are candidates for systemic therapy, we believe it is important to order laboratory tests including glomerular filtration rate and a simple urine test to screen for albuminuria (albumin/creatinine ratio).

Activating two-dimensional semiconductors for photocatalysis: a cross-dimensional strategy.

The emerging two-dimensional (2D) semiconductors substantially extend materials bases for versatile applications such as semiconductor photocatalysis demanding semiconductive matrices and large surface areas. The dimensionality, while endowing 2D semiconductors the unique properties to host photocatalytic functionality of pollutant removal and hydrogen evolution, hurdles the activation paths to form heterogenous photocatalysts where the photochemical processes are normally superior over these on the mono-compositional counterparts. In this perspective, we present a cross-dimensional strategy to employ thenD (n= 0-2) clusters or nanomaterials as activation partners to boost the photocatalytic activities of the 2D semiconductors. The formation principles of heterogenous photocatalysts are illustrated specifically for the 2D matrices, followed by selection criteria of them among the vast 2D database. The computer investigations are illustrated in the density functional theory route and machine learning benefitted from the vast samples in the 2D library. Synthetic realizations and characterizations of the 2D heterogenous systems are introduced with an emphasis on chemical methods and advanced techniques to understand materials and mechanistic studies. The perspective outlooks cross-dimensional activation strategies of the 2D materials for other applications such as CO2removal, and materials matrices in other dimensions which may inspire incoming research within these fields.

Localized acquired cutis laxa secondary to interstitial granulomatous dermatitis.

We report the case of a 68-year-old woman who had interstitial granulomatous dermatitis associated with seronegative polyarthritis. Two years later, this had evolved to become localized acquired cutis laxa.

Clinical Management of Cutaneous Adverse Events in Patients on Chemotherapy: A National Consensus Statement by the Spanish Academy of Dermatology and Venereology and the Spanish Society of Medical Oncology. / Manejo clínico de los eventos adversos cutáneos en pacientes tratados con quimioterapia: consenso nacional de la Academia Española de Dermatología y Venereología y de la Sociedad Española de Oncología Médica.

Although the arrival of new chemotherapy drugs and combinations has brought progress in terms of cancer patient survival, they entail many adverse effects that can compromise treatment, and hence prognosis, of the disease. Cytostatic agents can cause dermatological toxicity, among other side effects. The most familiar adverse effect of chemotherapy is alopecia. Although not serious, this changes the outward appearance of cancer patients. Other adverse effects include hypersensitivity and photosensitivity reactions, hand-foot syndrome, epidermal necrolysis, recall reactions, scleroderma-like reactions, Raynaud's phenomenon, eccrine squamous syringometaplasia, neutrophilic eccrine hidradenitis, nail abnormalities, pigmentation changes and extravasation injuries. Onset of these adverse effects often causes dose reduction and/or delayed treatment, which can affect patient survival and quality of life. It is therefore important to prevent their occurrence and treat them promptly, which requires cooperation between medical oncologists and dermatologists. This article reviews chemotherapy-associated dermatological toxicity, along with its diagnosis and therapeutic management.

Clinical management of cutaneous adverse events in patients on targeted anticancer therapies and immunotherapies: a national consensus statement by the Spanish Academy of Dermatology and Venereology and the Spanish Society of Medical Oncology.

Progress in the understanding of many tumors has enabled the development of new therapies, such as those targeted at specific molecules involved in cell growth (targeted therapies) or intended to modulate the immune system (immunotherapy). However, along with the clinical benefit provided by these new treatments, new adverse effects have also appeared. Dermatological toxicities such as papulopustular eruptions, xerosis, and pruritus are common with EGFR inhibitors. Other adverse effects have also been described with PDGFR, BCR-ABL, and MAPK tyrosine kinase inhibitors, antiangiogenic drugs, and inhibitors at immune checkpoints such as CTLA-4 and PD-1/PD-L1. Onset of these adverse effects often causes dose reductions and/or delays in administering the prescribed therapy, which can affect patient survival and quality of life. It is, therefore, important to prevent the occurrence of these adverse effects, or to treat unavoidable ones as soon as possible. This requires cooperation between medical oncologists and dermatologists. This article reviews the various dermatological toxicities associated with targeted therapies and immunotherapies, along with their diagnosis and therapeutic management.

[Horseshoes kidney isthmus carcinoma. A case report]. / Carcinoma renal de istmo en riñn en herradura. A propósito de un caso.

Horseshoe kidney is the most frequent fusion abnormality of the kidney. The incidence of renal carcinoma in patients with horseshoe kidney is similar to those with normal anatomy. Its special anatomical features must be borne in mind for both surgical approach and conservative surgery. We present a horseshoe kidney isthmus carcinoma case report in which we performed conservative surgery of both renal units.

Antitumor effects of granulocyte-macrophage colony-stimulating factor production by melanoma cells.

The use of immunomodulating gene therapy in the treatment of malignant disease is under intensive investigation. In this study, we examined the potential of melanoma-derived granulocyte-macrophage colony-stimulating factor (GM-CSF) to inhibit melanoma progression in a murine model. The HGH18 murine melanoma cell line was transfected with the murine GM-CSF gene in a SV40 expression vector that resulted in melanoma clones that produced varying amounts of GM-CSF. Syngeneic mice inoculated s.c. with HFH18 parental melanoma cells or HFH18 cells transfected with the GM-CSF gene n the noncoding 3'-5' orientation [HFH18/GM-CSF(-) cells] develop large tumors that reach a mean tumor volume of 3300 mm3 by day 30. In contrast, animals inoculated with two melanoma clones producing high levels of GM-CSF [HFH18/GM-CSF(++) and HFH18/GM-CSF(+ + +)] either completely reject the tumor cells or develop tumors with a mean volume of only 40 mm3. In comparison, animals inoculated with a melanoma clone producing low levels of GM-CSF [HFH18/GM-CSF(+)] develop large tumors averaging 2000 mm3, thus demonstrating a dose-response effect of tumor inhibition by melanoma-derived GM-CSF. Additionally, vaccination with irradiated GM-CSF-producing melanoma cells conferred optimal immunogenicity against a subsequent challenge with HFH18 cells. Tissue sections from excised GM-CSF-producing tumor cell inoculation sites but not from HFH18 parental or HFH18/GM-CSF(-) inoculation sites demonstrate a dense inflammatory infiltrate composed of neutrophils, tissue macrophages, and numerous CD4- and CD8-positive lymphocytes but few melanoma cells. Large numbers of dendritic cells and cells expressing the B7-2 costimulatory molecule are detected only within HFH18/GM-CSF(+ + +) melanoma inoculation sites. Our results lend further support to clinical trials of GM-CSF gene therapy in the treatment of advanced malignant melanoma, possibly by the recruitment of dendritic antigen-presenting cells.

Inhibition of murine melanoma growth by granulocyte-macrophage colony stimulating factor gene transfection is not haplotype specific.

Granulocyte-macrophage colony stimulating factor (GM-CSF) has been shown to inhibit the growth and progression of murine melanoma cells in syngeneic C57BL/6 (H-2b) recipient animals. We now demonstrate that this effect is not specific to melanomas derived from a single strain of mice by examining the subcutaneous growth of K1735 murine melanoma cells (H-2k) transfected with GM-CSF in a syngeneic mouse model. Non-GM-CSF-secreting melanoma cells (parental K1735 and K1735 cells transfected with the GM-CSF gene in antisense orientation) generated tumours that reached a mean volume of 4000 mm3 30-40 days, with a mean survival of 40 days after tumour cell injection. In contrast, 90% of the mice injected with three different clones of GM-CSF-producing K1735 melanomas developed no measurable tumours and were healthy and tumour-free when followed for over 300 days post-inoculation. Additionally, mice injected with GM-CSF-secreting K1735 cells developed long-lasting immunity to the parental melanoma cell line challenge in vivo. A dense neutrophilic and lymphocytic inflammatory infiltrate as well as large numbers of dendritic cells were detected only at the inoculation sites of the GM-CSF-producing melanoma cells. Thus, these studies demonstrate for the first time that GM-CSF inhibits melanoma growth in a second genetically distinct MHC tumour-host model system and further support the use of GM-CSF in clinical trials in the treatment of advanced malignant melanoma in humans.

Segmental arrangement of multiple, partly congenital and partly acquired melanocytic nevi.

A 15 year-old girl presented with numerous congenital melanocytic nevi, occasionally hairy, with a segmental distribution at the left pre-auricular region. On the left side of the back of the neck there were multiple melanocytic nevi with a warty appearance, which had started to appear when she was 5 and which had remained stable from the time she was 10. These lesions had a distribution reminiscent of an epidermal nevus with a pattern similar to Blaschko's lines. On general physical examination there was a moderate degree of idiopathic scoliosis, with a left lumbar curvature. Biopsies were taken from both types of nevus which were diagnosed as congenital compound melanocytic nevus and acquired compound melanocytic nevus respectively. We consider that the segmental distribution of the melanocytic nevi of this patient supports the theory that a genetic defect determined the appearance of both these congenital and acquired lesions.

Merkel cell tumor presenting as a painful patch lesion on the right arm.

Primary small cell cutaneous neuroendocrine carcinoma (Merkel cell carcinoma) is an uncommon, highly malignant, primary cutaneous neuroendocrine carcinoma. Clinically it is seen as a 0.5- to 5.0-cm pinkish purple papule or nodule, usually not ulcerated, on the head, neck, or, less frequently, the roots of the limbs. We present the case of a woman with an atypical clinical presentation of a Merkel cell tumor.

[Bullous dermatomyositis]. / Dermatomiositis ampollosa.

The authors present a case of bullous dermatitis with clinical and biological polymyositis. The cause of the blisters can be found in an intense oedema of the superficial and middle dermis and is favoured by liquefaction of the basal layer and fibrinoid degeneration of the superficial dermis. It is diagnosed as dermatomyositis with malignancy even though it has been impossible to confirm the nature of the tumor. The diagnosis is being argued with other diseases that occasionally are vesiculobullous.

[Hydroa vacciniforme, a well defined photodermatosis (clinical, histopathological and photobiological aspects, apropos of 3 personal cases]. / El "Hydroa vacciniforme", una fotodermatosis bien definida. (aspectos clínicos, histopathológicos y fotobiológicos a propósito de tres casos personales)

Three cases of "hydroa vacciniforme" are reported. The clinicopathological findings are emphasized. In two cases the patients presented keloids on the blister scars and in one of them there was association with focal epilepsia. The occular complications in the "hydroa vacciniforme" are uncommon but severe. The studies of cellular photobiology ("in vitro" irradiation of lymphocytes with U.V. rays) showed an imapirement of the ADN dark1repair, as demonstrated by other authors.

[Netherton syndrome]. / Síndrome de Netherton.

The authors reported a case of Netherton's syndrome. This patient presented cutaneous lesions of ichthyosis linearis circumflexa, tricorrexis invaginata and atopy signs associated with cystinuria. Cutaneous and hair lesions were treated with etretinate.

[Histopathological aspects of chromium ulcers]. / Aspectos histopatológicos de las úlceras por cromo.

The authors describe two cases of "cromeholes". Both patients were working in electroplating. The pathology of these lesions demonstrate that it refers to caustic ulcers with necrosis of the epidermis and superficial dermis, with tendency to hyperplasia of neighbouring epidermis and important infiltration of the vessels and specially of the sweat glands.

[Adquired epidermolysis bullosa. Immunopathological and ultrastructural studies]. / Epidermólisis ampollosa adquirida. Estudio inmunopatológico y ultraestructural.

A case of epidermolysis bullosa acquisita (EBA) in a 64 year old man is reported. The direct immunofluorescence showed a positive lineal anti IgG basement membrane on the affected skin (blisters and provocation tests) and on the univolved healthy skin. The electron microscopic studies showed a "dermolysis". In this patient it was not possible to find any pathological association. The EBA is usually associated with different processus but, sometimes, it could be isolated. Probably this clinicopathological field includes diverse badly delimited entities.

Comparative antitumor effect among GM-CSF, IL-12 and GM-CSF+IL-12 genetically modified tumor cell vaccines.

Genetically modified cells have been shown to be one of the most effective cancer vaccine strategies. An evaluation is made of the efficacy of both preventive and therapeutic antitumor vaccines against murine melanoma, using C57BL/6 mice and irradiated B16 tumor cells expressing granulocyte and macrophage colony-stimulating factor (GM-CSF), interleukin-12 (IL-12) or both. Tumor was transplanted by the injection of wild-type B16 cells. Tumor growth and survival were measured to evaluate the efficacy of vaccination. Specific humoral response and immunoglobulin G (IgG) switch were evaluated measuring total IgG and IgG1 and IgG2a subtypes against tumor membrane proteins of B16 cells. In preventive vaccination, all treated groups showed delayed tumor growth. In addition, the group vaccinated to express only GM-CSF achieved 100% animal survival (P<0.005). Vaccination with GM-CSF+IL-12-producing B16 cells yielded lesser results (60% survival, P<0.005). Furthermore, all surviving animals remained disease-free after second tumor implantation 1 year later. The therapeutic vaccination strategies resulted in significantly delayed tumor growth, mainly using B16 cells producing GM-CSF+IL-12 cytokines, with 70% tumor growth inhibition (P<0.001)-although none of the animals reached overall survival. The results obtained suggest that the GM-CSF+IL-12 combination only increases the efficacy of therapeutic vaccines. No differences in classical regulatory T cells were found among the different groups.