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.

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.

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.

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.

[Proliferative cutaneous epithelioid angiomatous nodule]. / Nódulo angiomatoso epitelioide cutáneo proliferativo.

The cutaneous epithelioid angiomatous nodule is an uncommon benign vascular proliferation that has only recently been described. Clinically, it usually presents as a solitary, fast-growing, small reddish papulous or nodular lesion on the trunk or limbs of adults. Histopathologic study reveals a proliferation of epithelioid cells and predominantly solid, well delimited, unilobular growth in the superficial dermis. Well defined vessels are often found permeating the lesion, which also shows a certain degree of inflammatory infiltration. The cells contain abundant pink cytoplasm, often with vacuoles, and vesicular nuclei with prominent nucleoli. The morphology of these cells is relatively uniform, without atypia or pleomorphism, although mitoses are not uncommon. We report 2 new cases of cutaneous epithelioid angiomatous nodules, the first in a 28-year-old pregnant woman and the second in a 27-year-old man. In both cases, the usual characteristics of this entity were present, but with the peculiarity of a high mitotic index. We discuss the differential diagnosis of cutaneous epithelioid angiomatous nodules with other vascular proliferations that exhibit epithelioid cytology.

[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.

[Brooke-Spiegler syndrome: an heterogeneous entity]. / Síndrome de Brooke-Spiegler: una entidad heterogénea.

The Brooke-Spiegler syndrome is a rare, autosomally dominant disease with a predisposition to develop different adnexal tumors. Clinically it is characterized by the presence of multiple cylindromas, trichoepitheliomas, and occasionally, spiradenomas. Although Brooke-Spiegler syndrome, familial cylindromatosis and multiple familial trichoepithelioma were initially described as separate entities, the recently identified identical mutations in the gene of cylindromatosis suggest that they represent fenotypic variations of the same entity. In this article we present the case of a woman and her daughter, both affected by this rare genodermatosis.

Aquagenic keratoderma.

Aquagenic keratoderma has been described as a transitory condition involving young females and defined clinically by the appearance of palmar lesions accentuated after immersion in water. According to previous case reports, these lesions are characterized histologically by hyperkeratosis and dilated eccrine ducts. Some aberration in the eccrine ducts has been suggested as a possible pathogenic mechanism. We report a new case in a female adolescent. With regard to the normal aspect of the epidermis in our case, the clinical changes should be ascribed to a structural alteration of the horny layer without any visible microscopy change or functional alteration of the stratum corneum involving the organism in the adolescence period.

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.

The association between idiopathic scoliosis and the number of acquired melanocytic nevi.

BACKGROUND: Several syndromes in which melanocytic nevi and scoliosis were present in the same patient have been described. No control study has been made to date to determine whether there is a relationship between these disorders. OBJECTIVE: We attempted to demonstrate the association between acquired melanocytic nevi (AMN) and idiopathic scoliosis (IS). METHODS: We studied 93 patients with IS, aged 10 to 18 years, from our hospital. Controls were randomly selected from 2 schools; Adam's forward bending test was used to exclude persons with clinical scoliosis, and the control group finally comprised 101 pupils. An observational, cross-sectional study was done. All AMN 2 mm or larger observed on the body were counted by one dermatologist. Other variables reported as risk factors in the number of nevi were also considered. Reliability of AMN counts was previously demonstrated. RESULTS: The median number of AMN was 18 (range, 10-42) in the IS group and 8 (range, 3-13) in controls (P <.001). The persons with scoliosis had more non-AMN dermatologic lesions than the controls (P <.05). Light phenotype correlated with many AMN. On multivariate analysis only scoliosis and age accounted independently for the number of AMN. CONCLUSION: IS is associated with many AMN. Multiple AMN may become a diagnostic marker for IS, and these two malformations might constitute a syndromic association.

Adverse reactions to injectable aesthetic microimplants.

New inert materials such as polymerized silicones, Bioplastique, Artecoll, and Dermalive are now being used as injectable aesthetic microimplants. These substances are better than the old ones because they tend not to migrate and do not usually produce much of a host immune response. Adverse reactions after injection of these materials are rare, although there are a few reported cases as a result of bad technique or anomalous granulomatous reactions. We report on four patients with unsightly results after cosmetic microimplants, including one of Artecoll, one of Dermalive (to the best of our knowledge, the latter is the first such case reported), and two of silicone. This report describes the histopathologic features of cutaneous reactions to these injectable aesthetic materials.

Unilateral multiple facial angiofibromas: a mosaic form of tuberous sclerosis.

Tuberous sclerosis has many forms of clinical presentation. Rarely, multiple facial angiofibromas of unilateral distribution have been reported. We describe 2 patients with such a presentation and hypothesize that this is a mosaic form of tuberous sclerosis.