Methotrexate in Moderate to Severe Psoriasis: Review of the Literature and Expert Recommendations.

Methotrexate (MTX) is the most frequently used conventional systemic drug in the treatment of psoriasis. Despite over 50years of experience in this setting, certain aspects of the use of this drug in clinical practice are still little standardized and poorly understood. For this reason, a group of 15 experts took part in a consensus development conference to achieve consensus on a series of recommendations on the use of MTX in psoriasis. The guidelines, which were developed on the basis of a systematic review of the literature, were validated by 2 rounds of voting and categorized by level of evidence and grade of recommendation. Before MTX can be used to treat moderate to severe psoriasis, the patient must be evaluated to assess the suitability of the treatment, including consideration of vaccination status and screening for tuberculosis and pregnancy. The recommended starting dose for a patient with no risk factors is 10 to 20mg/wk, the therapeutic dose for most patients is 15mg/wk, and the maximum dose is 20mg/wk. Most patients who respond to treatment will show improvement within 8weeks. Parenteral administration of MTX is desirable when there is a risk of erroroneous dosing, nonadherence, gastrointestinal intolerance, or inadequate response to the therapeutic dose taken orally. Noninvasive methods are preferred for monitoring hepatotoxicity. MTX is a good treatment option for patients with a history of cancer, but is not recommended in patients with chronic hepatitisB infection or individuals who are seropositive for human immunodeficiency virus.

Use of biological treatments in patients with hidradenitis suppurativa.

INTRODUCTION: Hidradenitis suppurativa (HS) is a chronic skin disease which causes a great impact in the quality of life. Multiple therapeutic options have been proposed, and recently the potential use of biological drugs in severe cases has been postulated. MATERIAL AND METHODS: A retrospective study from seven tertiary Spanish centers reviewing the charts of patients with HS treated with biological drugs was performed. Retrieved information included epidemiological data, clinical features, pain intensity, Hurley stage, laboratory data and therapeutic outcomes. RESULTS: Nineteen patients were included in the study; 10 men (52.6%) and 9 women. Eight patients (42%) showed a Hurley severity stage II and 11 a stage III (57.8%). Adalimumab was prescribed as the first biological treatment in nine out of 19 cases (47.3%), whereas infliximab was prescribed in seven cases (36.8%), ustekinumab in two cases (10.5%) and etanercept in one (5.2%). A complete response was observed in three patients (two cases with infliximab and one case with ustekinumab), a partial improvement in 10 patients and in six patients no clinical improvement was noted. One patient referred worsening of the skin symptoms. In 6 cases, a second biological treatment was prescribed. In three of such cases, a partial improvement was noted, whereas in three cases no clinical improvement was observed. In two cases a switch to a third biological drug was indicated, with a partial improvement in one case. DISCUSSION AND CONCLUSIONS: Biological drugs could be a potential and effective therapeutic option for patients with severe HS. Complete and persistent clinical responses are rarely obtained (15%) and partial responses are achieved in approximately 50% of patients. No specific markers for a therapeutic response have been identified. No definitive conclusions regarding the most effective biological drug for HS could be drawn. Higher dosage schedules seem to be associated with higher response rates. The lack of response of one particular drug does not preclude a potential efficacy to another biological treatment.

Safety and effectiveness of ustekinumab and antitumour necrosis factor therapy in patients with psoriasis and chronic viral hepatitis B or C: a retrospective, multicentre study in a clinical setting.

BACKGROUND: Both the safety and efficacy of biologic therapy may be affected in the presence of highly prevalent chronic viral hepatitis. OBJECTIVE: To evaluate the safety and effectiveness of ustekinumab and antitumour necrosis factor therapy in patients with psoriasis and concomitant chronic viral hepatitis. METHODS: This was a retrospective, multicentre study. Twenty-five patients with psoriasis and concurrent hepatitis C virus (HCV) (20 patients) or hepatitis B virus (HBV) (five patients) infection who had received at least one biologic agent (etanercept, 21 treatments; adalimumab, four; ustekinumab, four; infliximab, two) were included. Clinical, imaging and laboratory data were recorded. RESULTS: In the case of HCV infection, the majority of the patients did not exhibit increases in their viral load or serum liver tests. Aspartate aminotransferase, alanine aminotransferase and gamma glutamyl transpeptidase were doubled from the baseline measurement in only one patient treated with etanercept. Two other cases exhibited viral load increases during the follow-up period. In total, 18 of the 26 treatments achieved a 75% improvement in their Psoriasis Area and Severity Index (PASI 75) score during the follow-up period. Two patients treated with etanercept were diagnosed with hepatocellular carcinoma. In the case of HBV infection, all of the patients were being treated with antiviral therapy, and none presented significant variations in viral load or serum liver enzymes. All patients achieved a PASI 75 during follow-up. CONCLUSIONS: Biologic therapy was effective and safe for the majority of our patients with HCV and HBV infection, although there may be a risk of reactivation or aggravation. We describe the first cases to receive ustekinumab. The use of biologics should be limited to those cases in which the risk-benefit ratio is justified.

[Design and validation of a questionnaire to measure treatment satisfaction in patients with moderate-to-severe psoriasis: the NEODERMA study]. / Diseño y validación de un cuestionario para medir la satisfacción con el tratamiento del paciente con psoriasis moderada y grave: estudio NEODERMA.

BACKGROUND AND OBJECTIVES: the aim of this study was to design and assess the validity, reliability, and sensitivity to change of the Spanish Satisfaction With Treatment of Psoriasis Questionnaire (SSTPQ) for use in patients with moderate-to-severe psoriasis. PATIENTS AND METHODS: a prospective, multicenter, observational, naturalistic study was designed. The instrument consisted of 12 items scored on a 5-point Likert scale with scores from 0 (very satisfied) to 5 (very unsatisfied), generating a total score of 0 to 48. Patients completed the questionnaire at baseline and then at 3-, 6-, 9-, and 12-month follow-up. At each visit, data were also collected on the Psoriasis Area and Severity Index (PASI), treatment adherence (Morisky-Green questionnaire), and overall treatment satisfaction on a Visual Analogue Scale (VAS) from 0 to 100. RESULTS: a total of 423 patients were included in the study and 68% completed 12 months of follow-up. Responses were provided to all items in 98.8% of cases. There was a weak correlation between changes in treatment satisfaction on the SSTPQ and changes in PASI score (r = 0.38 to 0.33); in contrast, there were strong correlations with changes in the VAS score for overall treatment satisfaction (r = -0.75 to -0.81). Good internal consistency was observed (Cronbach α = 0.92). The intraclass correlation coefficient was 0.89, with a mean difference in score at 3- and 6-month follow-up of 0.07. CONCLUSIONS: The results obtained suggest that the SSTPQ is a feasible, valid, and reliable tool for the assessment of treatment satisfaction in patients with moderate-to-severe psoriasis.

[Etanercept and chronic infection by HCV and HBV]. / Etanercept e infecci (R)n cr (R)nica por los virus de la hepatitis C y B.

Both psoriasis and chronic infections by HBV and HCV have high prevalence. Thus, it is relatively easy for them to coincide in the same patient. If the psoriasis requires systemic treatment, the dermatologist should consider the hepatic comorbidity when selecting an appropriate treatment. Cyclosporine, in addition to other well-known side effects, is an immunosuppressant that may condition worse evolution of the viral hepatitis. On the other hand, retinoids, psoralens and, above all, methotrexate may worsen the liver function. The anti-TNF-|A biological agents are not hepatotoxic and their theoretical contraindication in this context would be because of their action on the immune response and risk of reactivation of the hepatic infection. However, several studies have demonstrated that neither the viral load nor the hepatic inflammation parameters are generally modified negatively when they are used in hepatitis due to HCV. Their use in this context, with correct monitoring, seems, therefore, very reasonable. On the contrary, in chronic hepatitis B virus, there are cases of worsening, even with fatal outcome in some cases, and the use of these biological agents should be reserved for cases having greater need, and always be associated to antiviral treatment and strict monitoring. The review of the recent literature seems to allow the conclusion that the concomitant use of lamivudine would greatly reduce the risk of viral reactivation and, with this condition, the use of etanercept in some HBV+ patients may also be contemplated.

[Adverse reactions during biological therapy for psoriasis: results of a survey of the Spanish Psoriasis Group]. / Efectos adversos observados durante la terapia biológica en la psoriasis. Resultados de una encuesta al Grupo Español de Psoriasis.

BACKGROUND: Biologic therapies have been a major breakthrough in the treatment of psoriasis because they are more selective and have a better short-term and medium-term safety profile. There are reliable data to support both the efficacy and the safety of these drugs. However, it is always useful to report the clinical experience of dermatologists who are experts in the use of biologic agents to treat psoriasis, particularly with regard to their safety. MATERIAL AND METHODS: We present the results of a survey administered to the members of Spanish Psoriasis Group and based on a series of questions referring to the clinical safety of these agents. A total of 988 patients treated with efalizumab, infliximab, etanercept, and adalimumab were reported by 15 members of the group. RESULTS: There was a particularly high proportion of reactions (34%) to infliximab infusions. Blood test abnormalities were detected in 13.25% of patients and infections in 12.24%, with one case of pulmonary tuberculosis. Attention is drawn to the adverse effects profile of efalizumab: de novo arthritis in 5.8% and rebound in 20.9% of patients. CONCLUSION: The safety data provided by our study should be taken into account in view of the large number of patients recruited by dermatologists experienced in the use of this type of therapy.

[Proliferating trichilemmal cyst. Apropos of a case]. / Quiste triquilémico proliferante. A propósito de un caso.

Malignant change in some keratinous cysts is a possible but rare condition. It seems acceptable that many publications concerning squamous cell carcinomas arising from previous cysts, actually correspond to the entity which Wilson-Jones called "proliferating epidermoid cyst" and they must be considered as pseudomalignant lesions, despite the presence of some features that may lead to a diagnosis of carcinoma. Although it is rare, which is nowadays called "proliferating Trichilemmal cyst", should be widely acknowledged since its misdiagnosis as squamous cell carcinoma leads to surgical treatment which is more drastic than necessary. Herein is presented an unusually situated case of proliferating Trichilemmal cyst and a review of the principal characteristics that have been pointed out in this tumor.

[Congenital nodular fibromatosis associated with skeletal malformations]. / Fibromatosis nodular congénita asociada a malformaciones esqueléticas.

Juvenile fibromatosis has been largely studied by several authors. Most of them have pointed out the existence of some disorders which are difficult to classify and possess peculiar features. The authors report the case of a girl who presented several tumoral lesions located on the soles and toes from birth. The clinical aspect and the histological study didn't allow us to include this patient in any determinates group. She also presented some associated skeletal alterations.

[Immunoblastic sarcoma associated with dermatitis herpetiformis]. / Sarcoma inmunoblástico asociado a dermatitis herpetiforme.

Association between dermatitis herpetiformis and gluten enteropathy is well established. An increased incidence of malignant disease has been reported in patients with coeliac disease and also in dermatitis herpetiformis. Linear IgA dermatitis herpetiformis has a much lower incidence of associated enteropathy compared with patients with papillary dermatitis herpetiformis, but the risk of malignancy could be the same. We report a case of linear IgA dermatitis herpetiformis in which immunoblastic sarcoma subsequently developed.

[Multiple clear-cell acanthoma]. / Acantoma de células claras múltiple.

Clear cell acanthoma is a benign tumor reported by Degos et al. in 1962. Most commonly the acanthoma presents as a solitary nodule on the lower limb in late middle-aged persons. We've found only 11 papers about multiple clear cell acanthoma. We describe a 73 years old patient who had 21 lesions, the highest number found in the literature.

[Reactions to infliximab infusions in dermatologic patients: consensus statement and treatment protocol. Working Group of the Grupo Español de Psoriasis de la Academia Española de Dermatología y Venereología ]. / Reacciones a la infusión de infliximab en pacientes dermatológicos. Grupo de Estudio, Grupo Español de Psoriasis de la Academia Española de Dermatología y Venereología.

Infliximab is a chimeric monoclonal antibody that binds to and blocks tumor necrosis factor alpha and is the most effective biologic agent approved for the treatment of moderate-to-severe psoriasis. It is administered by intravenous infusion, usually in day hospitals on an outpatient basis. The main problem with the administration of infliximab is the possibility of infusion reactions, which may be immediate or delayed; these reactions are related to the immunogenicity of this monoclonal antibody, leading to the production of anti-infliximab antibodies. Infusion reactions to infliximab are not usually anaphylactic (ie, they are not mediated by immunoglobulin E), and re-exposure of the patient using specific protocols to prevent and treat these reactions is therefore possible. The extensive experience in the use of infliximab for the treatment of rheumatic conditions and chronic inflammatory bowel disease has made it possible to develop infusion reaction management protocols; these can be applied to dermatologic patients, who constitute a growing proportion of patients treated with intravenous biological agents. The aim of this review is to draw up a consensus protocol for the treatment of infusion reactions in dermatologic patients treated with infliximab.

[Consensus document on the evaluation and treatment of moderate-to-severe psoriasis. Spanish psoriasis group of the Spanish Academy of Dermatology and Venereology]. / Documento de consenso sobre la evaluación y el tratamiento de la psoriasis moderada/grave del grupo español de psoriasis de la Academia Española de Dermatología y Venereología.

The treatment of psoriasis has been revolutionized by the introduction of biologic agents; these agents achieve skin clearance and long-term improvement without the risk of toxicity that has limited use of the classic systemic treatments. The role of systemic treatment in the management of psoriasis is being reviewed on the basis of a large volume of scientific evidence on the efficacy and safety of biologic agents, and new therapeutic goals and strategies are being devised for patients with moderate-to-severe psoriasis. This has led to the need to establish severity criteria that will provide the rationale for the indication of the different systemic agents currently available for the treatment of moderate-to-severe psoriasis, as well as therapeutic goals, efficacy measures, therapeutic strategies, screening protocols, and choice of treatment based on the risk-benefit ratio of the different agents. These criteria must be established through consensus by experienced dermatologists and based on available scientific evidence. The present document reflects the consensus of the Spanish Psoriasis Group on these different issues in the management of moderate-to-severe psoriasis.

[Update of the topical treatment of psoriasis]. / Revisión actualizada del tratamiento tópico de la psoriasis.

Topical therapy continues to be one of the pillars of psoriasis management. Topical corticosteroids and vitamin D analogs are the drugs of choice during the induction phase, and vitamin D analogs continue to be drugs of choice for maintenance therapy. Tazarotene and dithranol are suitable options in patients with certain, specific characteristics. The calcineurin inhibitors can be considered to be second-line treatment for psoriasis of the face and flexures. The efficacy and safety of the fixed-dose combination of betamethasone and calcipotriol in the induction phase is greater than that of either drug alone. The combination of corticosteroids with salicylic acid achieves better results than corticosteroids in monotherapy. None of the drugs evaluated stands out over the others in all clinical situations, and their use must therefore be individualized in each patient and adjusted according to the course of the disease.

[Spanish evidence-based guidelines on the treatment of moderate-to-severe psoriasis with biologic agents]. / Directrices españolas basadas en la evidencia para el tratamiento de la psoriasis moderada a grave con agentes biológicos.

Psoriasis vulgaris is an inflammatory skin disease that is generally chronic and that affects between 1 % and 2 % of the population in industrialized Western countries. It is associated with a marked decline in quality of life. A wide range of treatments are currently available, although surveys conducted before the advent of biologic agents reflected a strong degree of dissatisfaction with the treatments then available. Extensive scientific evidence has been gathered on the safety of biologic agents, and this has led to a review of the role of systemic treatment in general and has allowed new therapeutic goals and strategies to be contemplated in patients with moderate-to-severe psoriasis. In this new situation, there is a need for Spanish guidelines on the treatment of moderate-to-severe psoriasis with biologic agents, drafted by consensus among specialists and ratified by the Spanish Psoriasis Group of the Spanish Academy of Dermatology and Venereology (AEDV). These guidelines should be evidence-based with regard to the pharmacologic characteristics, mechanism of action, administration route and regimen, efficacy, contraindications, adverse effects, and cost estimates of biologic agents approved for the treatment of moderate-to severe psoriasis in Spain.

Calciphylaxis associated with alcoholic cirrhosis.

Calciphylaxis is an uncommon disease characterized by calcification of dermal vessels that determines skin necrosis. Calciphylaxis has been almost exclusively reported in association with renal failure and altered phosphor-calcium metabolism. Only a few cases have been described in hyperparathyroidism, malignancies, and, recently, cirrhosis. We report a patient that developed calciphylaxis related to end-stage alcoholic cirrhosis, without any alteration in the phosphocalcic and parathyroid hormone metabolisms. Possible contributing factors were repeated albumin infusions and low levels of protein C and S.

A prospective evaluation of the cost of psoriasis in Spain (EPIDERMA project: phase II).

OBJECTIVE: To estimate the direct and indirect costs related to psoriasis in Spain. METHODS: We performed a 12-month, multicentre, prospective longitudinal and observational study. Overall expense of care was assessed as the sum of direct and indirect costs. RESULTS: A total of 797 patients with varying demographics and different degrees of severity of psoriasis were included in the study. The mean total cost of psoriasis, including direct and indirect items, was 1,079 euro per patient and year. The major sources of expenditure were prescription drugs (46.6%), followed by medical activities (34.5%). Mean costs in patients with moderate and severe psoriasis were approximately 1.5 and 2.5 times higher than in those with mild psoriasis, respectively. CONCLUSIONS: In Spain, psoriasis is associated with substantial costs both to the National Health System and to the patients.