Salt sensitivity of blood pressure in patients with psoriasis on ciclosporin therapy

BACKGROUND: Hypertension is one of the main side-effects of long-term therapy with ciclosporin. However, the influence of salt intake on the 24-h mean blood pressure of patients with psoriasis treated with ciclosporin is not known. OBJECTIVES: To evaluate, in patients with psoriasis, the sodium sensitivity of the ciclosporin-induced rise in blood pressure. METHODS: The 24-h ambulatory blood pressure was evaluated in 13 patients with psoriasis (age range 20-57 years) in two phases, before (phase I) and after the completion of 4 months of therapy with ciclosporin 3 mg kg(-1) daily (phase II). In both phases, the patients were studied in conditions of low sodium (LS) intake followed by a high sodium (HS) diet. RESULTS: Twenty-four-hour mean +/- SD blood pressure during LS and HS intake was, respectively, 86.3 +/- 1.6 mmHg and 85.5 +/- 1.8 mmHg during phase I, and 88.5 +/- 1.5 mmHg and 91.8 +/- 2.2 mmHg (P < 0.001 vs. phase I, HS; P < 0.05 vs. phase II, LS) during phase II. The median (interquartile range) sodium sensitivity index was greater during phase II than during phase I: - 0.0028 (- 0.0071 to 0.0009) vs. 0.0065 (- 0.0055 to 0.0258) (P < 0.02). The plasma levels and the daily urinary excretion of noradrenaline did not differ between phases I and II. CONCLUSIONS: The ciclosporin-induced rise in blood pressure is sodium sensitive. It is also suggested that sympathetic activation is not involved in the pathogenesis of ciclosporin-induced rise in blood pressure.     

CD30+ T-cell lymphoma in a patient with psoriasis treated with ciclosporin and infliximab

There is a known relationship between the use of immunosuppressive therapies and the development of lymphoproliferative malignancies. These lymphomas are mainly B-cell nonHodgkin's lymphomas associated with Epstein-Barr virus. Most cases concern classical immunosuppressive treatments including ciclosporin and methotrexate. A relationship between the new antitumour necrosis factor (TNF)-alpha agents and lymphoproliferative malignancies is debated. Patients with psoriasis on immunosuppressive therapies, mainly ciclosporin, are considered to have a low risk of developing lymphoid proliferation. We report a patient with erythrodermic psoriasis treated with ciclosporin and infliximab who developed a CD30+ T-cell lymphoma. This lymphoma regressed after stopping these treatments. In this case, the anti-TNF-alpha agent may have played a role in association with ciclosporin in the development of the lymphoproliferative disorder. Whereas the combination of anti-TNF-alpha therapies with methotrexate has been well studied, their combination with ciclosporin has been evaluated only in a few patients. Psoriatic patients who may require anti-TNF-alpha treatment have often been or will be treated with ciclosporin. The combination of ciclosporin and anti-TNF-alpha warrants further investigation.     

Severe psoriasis treated with a new macrolide: everolimus

Psoriasis is an immune-mediated disease with a chronic relapsing course, and the particularly severe forms that are refractory to traditional therapies are often difficult to manage. Everolimus (Certican; Novartis, Basel, Switzerland) is a new rapamycin-derived macrolide that is used in the prophylaxis of rejection in heart and kidney transplant patients. The mechanism underlying its immunosuppressant and antiproliferative activity is different from, but complementary to, that of calcineurin inhibitors such as ciclosporin. We describe a woman with severe psoriasis treated with everolimus combined with subtherapeutic doses of ciclosporin.     

Interleukin 12 production by monocytes from patients with psoriasis and its inhibition by ciclosporin A

BACKGROUND: Psoriasis is a T-helper (Th)1 cytokine-mediated chronic skin disease and interleukin (IL)-12 has been shown to play a major role in the development of Th1 responses. OBJECTIVES: To elucidate the role of IL-12 in the pathogenesis of psoriasis and to study the effect of ciclosporin A (CsA) on Th1 deviation of this disease. PATIENTS/METHODS: We investigated IL-12 production by stimulated monocytes from patients with psoriasis who were treated with or without CsA. Monocytes were stimulated with interferon-gamma plus lipopolysaccharide (LPS) or Staphylococcus aureus Cowan strain I (SAC). The amount of IL-12 p70 produced by stimulated monocytes was evaluated by enzyme-linked immunosorbent assay. RESULTS: Compared with those from normal controls, LPS- but not SAC-stimulated monocytes from patients with psoriasis produced significantly higher amounts of IL-12. Interestingly, LPS-stimulated monocytes from patients with psoriasis treated with CsA produced significantly decreased amounts of IL-12 compared with those patients not treated with CsA. CONCLUSIONS: Our results suggest that IL-12 production by monocytes may have a critical role in the pathogenesis of psoriasis, and that the therapeutic effect of CsA on psoriasis may be achieved by correcting the deviation of the Th1/Th2 balance.     

Role of photodynamic therapy in psoriasis: a brief review

Background and purpose: Photodynamic therapy (PDT) is a light treatment modality which involves either systemic or local application of a photosensitizing compound, which preferentially deposits in the target cells, and is then followed by selective illumination of the lesion with visible light. The purpose of this study was to review the literature to examine the success, side effects, and different protocols used thus far to treat psoriasis using PDT. Methods: A thorough review of the literature was performed and analyzed. Results and conclusions: After a thorough review of the literature, PDT remains a potential treatment for psoriasis. Clinical improvement has been observed in most studies. The major limiting factor seen in many of the studies was the side effect of pain and burning sensations associated with PDT. This highlights the need for other photosensitizers with better tolerability profiles.     

The use of ciclosporin in psoriasis

Ciclosporin is a cyclic undecapeptide discovered in the 1970s to possess a potent inhibitory action on T lymphocytes. The subsequent discovery, in 1979, that it was remarkably effective in treatment of psoriasis transformed thinking about the nature of the disease, which subsequently became generally recognized as autoimmune in nature. Ciclosporin remains one of the most effective and rapidly acting treatments currently available for psoriasis. Virtually all the diverse manifestations of this disease can respond. The main side effects are nephrotoxicity and hypertension. There is considerable variation between individuals in susceptibility to these so careful monitoring is required. Ciclosporin should be used in single or intermittent short courses for all except the most severe cases as this is safer than continuous treatment. The rate of improvement depends very much on the dose, which ranges from 2 to 5.0 mg/kg/day. Ciclosporin can be combined with any topical treatment and a useful dose-sparing effect can be achieved in this way if patients are compliant. In severe cases ciclosporin is often used in combination with other systemic antipsoriatic drugs in order to spare the dose of each agent and reduce toxicity. Concurrent or intercurrent use of ultraviolet therapy is discouraged due to the increased risk of non-melanoma skin cancer. This article reviews the mode of action, pharmacokinetics, indications, contraindications, side effects, dosage regimens, pretreatment screening and monitoring, drug interactions, and use of treatment combinations with ciclosporin in the management of psoriasis.     

Combining etanercept with traditional agents in the treatment of psoriasis: a review of the clinical evidence

Psoriasis is a chronic, systemic inflammatory disorder manifesting primarily in skin and potentially in joints, frequently necessitating treatment with conventional systemic therapies, phototherapy or biological agents. Patients with moderate to severe disease suffer a diminished quality of life, experience significant comorbidities and have a higher mortality. Although traditional treatments are effective in the short‐term, their use is often limited by concerns over long‐term toxicity, including end‐organ damage and risk of malignancy. Combination therapy is a commonly used approach and is often more effective than any single agent. Lower doses of two treatments in combination can also minimize potential side effects from a single agent at higher doses. Etanercept is a recombinant human tumour necrosis factor (TNF)α receptor (p75) protein fused with the Fc portion of IgG1 that binds to TNFα. This article reviews the evidence on the efficacy and safety of etanercept in combination with methotrexate, acitretin, narrowband UVB and cyclosporin. The largest body of evidence assesses the combination with methotrexate, although evidence is available for the other combinations. Data suggest that although highly effective as monotherapy, etanercept in combination with a conventional systemic agent can enhance efficacy and allow drug sparing. Potentially, the combination may also result in faster treatment responses and permit safe transitioning from one systemic agent to another. Evidence to date suggests that these benefits can be achieved without significant additional toxicity, although long‐term data on the efficacy and safety of the combination in psoriatic populations is limited and further evaluation is warranted.     

Long-term continuous versus intermittent cyclosporin: therapy for psoriasis

A multicenter randomized controlled study was conducted to assess the long-term efficacy and safety of cyclosporin A therapy for psoriasis using either a continuous or an intermittent regimen. Initially, both regimens consisted of 3-5 mg/kg/day administration of CyA. Once remission was obtained, CyA dose was maintained between 0.5 and 3 mg/kg/day under the continuous regimen, while under the intermittent regimen, CyA dose was tapered off and, when necessary, topical corticosteroids were used until relapse occurred. Thirty-one patients were followed for at least 48 months (mean follow-up period: 55.9+/-4.6 months): 15 received continuous therapy, and 16 received intermittent therapy. With both regimens, the PASI (Psoriasis Area and Severity Index) score was maintained at 5-12 points throughout the follow-up period. The score was decreased by more than 70% from baseline with both regimens: the responses between them were not significantly different. However, overall control of psoriasis, as assessed from the averaged PASI score, was better in the patients receiving continuous therapy. Although the overall frequency of adverse reactions was similar for the two regimens, cancer occurred in two patients on continuous therapy (gastric cancer and hepatocellular carcinoma in one patient each). We could not, however, definitely attribute the cancers in the two patients to continuous therapy itself. There was a significantly higher incidence of renal impairment in elderly patients receiving either regimen when compared with younger patients. In conclusion, CyA administered to psoriasis patients under both regimens exhibited long-term efficacy and tolerability. Despite a lower overall efficacy, it seems proper to conclude that intermittent therapy is more useful than continuous therapy due to the occurrence of malignancies with continuous therapy. Further investigation is required to determine whether intermittent therapy is really safer than continuous therapy, and, if so, how it should be designed to minimize long-term adverse reactions and achieve overall control comparable to that of continuous CyA therapy.     

Recommendations for the use of etanercept in psoriasis: a European dermatology expert group consensus

BACKGROUND: Psoriasis is a chronic, inflammatory skin disorder that has a significant impact on quality of life and, particularly in moderate to severe cases, adversely affects the patient's overall health and well-being. Biological treatments, such as etanercept, are being widely adopted across Europe for treatment of moderate to severe psoriasis due to favourable safety and efficacy profiles. The increase in usage, combined with a growing body of clinical evidence, has identified a need to clarify the best use of etanercept within its current treatment label. OBJECTIVE: To prepare a series of recommendations agreed by an expert group of dermatologists, relating to the most effective use of etanercept for psoriasis in Europe, within the product license. METHODS: An expert panel of dermatologists from across Europe completed a Delphi survey to address the current use of etanercept in psoriasis in Europe. In June 2005 the results were presented to the expert panel at their nominal group meeting, and a consensus was agreed. RESULTS: It was recommended that, where possible, patients are initiated on the 50 mg twice-weekly (BIW) dose. Etanercept should be given until remission is achieved (maximum 24 weeks) and retreatment should be initiated according to the physician's judgement. Before commencing treatment, contraindications, such as infection or previous malignancy (within 5 years), should be ruled out. CONCLUSIONS: The consensus presented herein provides valuable clarification of use of etanercept according to the label, which may have wider implications relating to the use of all biological therapies in psoriasis.     

Update on the use of ciclosporin in immune-mediated dermatoses

Immune-mediated dermatoses, such as psoriasis and atopic dermatitis, affect a significant proportion of the population. Although most cases are not life threatening, these diseases can have a profound effect on the sufferer's quality of life and that of their family. Systemic therapy, such as ciclosporin, is often indicated for severe or recalcitrant disease. The efficacy of ciclosporin in the treatment of psoriasis and atopic dermatitis has been established and clinical data also demonstrate its efficacy in treating less common but equally challenging conditions such as pyoderma gangrenosum, lichen planus, autoimmune bullous disease, recalcitrant chronic idiopathic urticaria and chronic dermatitis of the hands and feet. The risk of potential adverse events associated with ciclosporin is greatly reduced if current treatment and monitoring guidelines are followed.     

Update on the use of ciclosporin in immune-mediated dermatoses

Immune-mediated dermatoses, such as psoriasis and atopic dermatitis, affect a significant proportion of the population. Although most cases are not life threatening, these diseases can have a profound effect on the sufferer's quality of life and that of their family. Systemic therapy, such as ciclosporin, is often indicated for severe or recalcitrant disease. The efficacy of ciclosporin in the treatment of psoriasis and atopic dermatitis has been established and clinical data also demonstrate its efficacy in treating less common but equally challenging conditions such as pyoderma gangrenosum, lichen planus, autoimmune bullous disease, recalcitrant chronic idiopathic urticaria and chronic dermatitis of the hands and feet. The risk of potential adverse events associated with ciclosporin is greatly reduced if current treatment and monitoring guidelines are followed.     

Tomesa balneophototherapy in mild to severe psoriasis: a retrospective clinical trial in 174 patients

Psoriasis is a chronic inflammatory skin disease with a high social and psychological impact on the quality of life of patients. Tomesa balneophototherapy is based on bathing in a magnesium-rich salt solution combined with exposure to narrowband ultraviolet B phototherapy. We conducted a retrospective clinical trial on 174 patients affected by mild to severe psoriasis undergoing Tomesa balneophototherapy. The basal course consisted of three to five sessions per week for a total of 30 sessions. Subsequently, patients could continue with a maintenance course of one session per week for a total of 30 sessions. We recorded a significant reduction of the mean Psoriasis Area and Severity Index (PASI) index with an achievement of at least PASI 75 in 52.1% of the 119 patients who completed the basal course and an improvement of the 'quality of life' of patients. The good efficacy obtained by this treatment, and the psychological impact on the quality of life of patients, demonstrated that Tomesa balneophototherapy could be a good option for the treatment of a chronic disease associated with psychological distress, like psoriasis.     

红皮病性银屑病52例临床分析

目的：探讨红皮病性银屑病的诱发因素,临床表现及治疗效果。方法：对52例红皮病性银屑病患者进行临床回顾分析。结果：男女发病率之比为4：1,多种因素可诱发或加重红皮病性银屑病,滥用糖皮质激素,中药的不合理治疗以及感染是其主要诱因。结论：合理规范的治疗是影响红皮病性银屑病预后的重要因素。甲氨蝶呤仍是治疗红皮病性银屑病的一线药物、阿维A联合复方甘草甜素（商品名：美能）治疗红皮病烂银屑病也有确切疗效。美能作为治疗红皮病性银屑病的联合用药效果良好,值得临床推广应用。     

Erythema annulare centrifugum-type psoriasis: a particular variant of acute-eruptive psoriasis

A case of erythema annulare centrifugum-type psoriasis in a 58-year-old white woman with a history of chronic plaque psoriasis is described. Initial failure of antipsoriatic treatments and an untypical histology complicated the diagnosis. After several trials acitretin at a low maintenance dose combined with oral fish oil and topical calcitriol led to sustained long-term remission. The spectrum of clinical differentiation of this rare disease, the histological characteristics and its nosological classification are discussed. It is suggested that this dermatosis represents a variant of acute psoriasis, rather than a variant of pustular psoriasis.     

Systemic ciclosporin and tacrolimus in dermatology

Ciclosporin and tacrolimus are calcineurin inhibiting immunosuppressant agents useful in the treatment of immune-mediated inflammatory dermatoses. Available data and clinical experience demonstrate ciclosporin's efficacy in treating psoriasis, atopic dermatitis, pyoderma gangrenosum, lichen planus, autoimmune bullous disease (in combination with corticosteroids), recalcitrant chronic idiopathic urticaria, and chronic dermatitis of the hands and feet. Although the role of topical tacrolimus in atopic dermatitis is well established, such experience with the oral formulation of tacrolimus has been limited. However, there are several case studies and anecdotal reports of the successful use of oral tacrolimus in various dermatoses. In this article we discuss the utility of systemic ciclosporin and tacrolimus in dermatology.     

Erythrodermic psoriasis in a dialyzed patient successfully treated with Secukinumab

Erythrodermic psoriasis is a severe, life‐threatening condition with additional complications, when occurring in hemodialyzed patients, as the majority of treatments are contraindicated. A 44‐years‐old man, of Philippine origins, with a 15‐years‐history of psoriasis treated with cyclosporine developed progressive hypertension and renal insufficiency. Despite drug dismission, renal function worsen to end‐stage, and hemodialysis was necessary three times a week. Phototherapy was not able to control the skin condition, progressing to erythroderma, and after nephrology consultation, the patient consent to the off‐label secukinumab treatment, at the standard regimen (300 mg subcutaneously once weekly at weeks 0‐4 followed by 300 mg every 4 weeks). Seven days after the first injection, a rapid improvement was noted, with the psoriasis area severity index (PASI) score passing from 31.5 to 17.6. At the 52‐week‐follow‐up visit, the patient was completely clarified, without any side effects. The case supports secukinumab effectiveness and safety in difficult patients, including erythrodermic psoriasis with end‐stage renal failure, as drug plasma levels seem not to be affected by hemodialysis. Results are rapidly achieved, and long term maintained, with the additional advantage of a very comfortable monthly administration.