英利昔单抗-抗TNF—α嵌合性单克隆抗体治疗银屑病

英利昔单抗是一种鼠-人嵌合性单克隆抗体，他能通过结合肿瘤坏死因子(TNF)-α可溶性跨膜成分，抑制其与受体的结合而中和其生物活性。近来，在用英利昔单抗治疗其他相关疾病如Crohn病、银屑病性关节炎时发现银屑病皮损得到改善。且已有报道用英利昔单抗和甲氨蝶呤联合治疗银屑病取     

肿瘤坏死因子α抑制剂在皮肤科的应用

肿瘤坏死因子α是由多种细胞分泌的一种炎性因子,其抑制剂目前市场上有3种:英利昔单抗、依那西普及阿达木单抗.在皮肤科领域,美国食品药物管理局仅批准本类药物用于银屑病及银屑病性关节炎的治疗.但近年来越来越多的研究证实,TNF-α抑制剂可用于更多类型皮肤疾病的治疗,并成功治疗了如化脓性汗腺炎、坏疽性脓皮病和毛发红糠疹等多种其他类型的炎症性皮肤病.为此,概述肿瘤坏死因子α抑制剂在治疗皮肤疾病中的应用进展.     

依那西普在皮肤科临床应用的进展

依那西普是一种人工合成的可溶性肿瘤坏死因子α受体融合蛋白,可有效地拮抗肿瘤坏死因子α引起的一系列生物学效应。初步的临床试验表明,该药对于关节病型银屑病、中重度斑块状寻常型银屑病、红皮病型银屑病以及难治性皮肌炎、天疱疮、坏疽性脓皮病和化脓性汗腺炎等疾病具有较好的疗效。依那西普在临床应用中安全性较高,引起充血性心衰、脱髓鞘疾病等严重不良反应少见。其远期的临床疗效、安全性、适应症尚需进一步研究。     

肿瘤坏死因子α与系统性红斑狼疮

肿瘤坏死因子α是自身免疫反应的重要效应因子。对肿瘤坏死因子α及其受体p55、p75水平,外周血单个核细胞产生肿瘤坏死因子α的能力、肿瘤坏死因子α的基因表达及多态性等与系统性红斑狼疮的关系做了简要综述。     

噻唑烷二酮类药物在皮肤病临床应用进展

噻唑烷二酮类(TZDs)如罗格列酮等是治疗2型糖尿病的新降糖药,其作用靶点是过氧化物酶体的增殖活化受体PPARγ.TZDs刺激脂肪细胞分化,增强肌肉、脂肪细胞胰岛素敏感性,减少血管并发症,抑制肿瘤细胞生长,使皮肤角质层细胞的分化趋向正常化;还能减少炎性细胞因子、肿瘤坏死因子-α产生.现有临床研究表明,TZDs对银屑病、多毛症、黑素瘤、血管肉瘤、皮下脂肪萎缩和类脂质渐进坏死等多种皮肤病治疗有效.     

毛发疾病

20 0 2 184 4　可溶性肿瘤坏死因子 型受体在斑秃发病中的作用 /许冰 (浙江大学医学院附一院皮肤科 )∥中国皮肤性病学杂志 .- 2 0 0 1,15 (5 ) .- 2 93～2 94采用双抗体夹心 EL ISA法检测 71例斑秃患者及 4 5例正常人血清中可溶性肿瘤坏死因子 型受体 (s TNF- R )的含量。结     

咪喹莫特抗皮肤肿瘤的作用机制

咪喹莫特是一种新型的局部小分子免疫调节物，可以通过与免疫相关细胞表面的Toll样受体结合、促进干扰素-α、肿瘤坏死因子-α、白介素-12等多种前炎症细胞因子的分泌，进而激活天然与获得性免疫反应的方式，发挥抗肿瘤活性。通过上调Fas和／或下调bcl-2表达诱导肿瘤细胞凋亡，可能是咪喹莫特抗皮肤肿瘤的另一重要机制。     

CYLD基因与皮肤附属器肿瘤的研究进展

圆柱瘤、毛发上皮瘤、Brooke-Spiegler综合征均是临床少见的呈常染色体显性遗传的皮肤附属器肿瘤,其发生与CYLD基因突变密切相关。CYLD是一种肿瘤抑制基因,编码去泛索化蛋白酶,通过去泛素化核因子κB抑制蛋白激酶复合体的调节亚基、肿瘤坏死因子受体相关因子等信号分子负性调节核因子-κB途径,从而抑制肿瘤的发生。概述CYLD基因与皮肤附属器肿瘤的发生、基因型与表型的关系、皮肤肿瘤的治疗新进展。     

湿疹及皮炎

20100120特应性皮炎肿瘤坏死因子及可溶性受体检测/陈达灿(广州中医药大学二附院),刘炽,黄咏菁…∥中国中西医结合皮肤性病学杂志.-2009,8(4).-202～203采用ELISA进行检测。结果,与正常对照组相比,特应性皮炎(AD)患者血清肿瘤坏死因子(TNF)-α水平下降,但无显著差异,患者血清TNF可溶性受体(ST-NFR)水平显著高于对照组。认为AD患者血清中高水平STNFR可加强其中和循环中的TNF-α,继而引起TNF-α介导抗感染和抗炎症反应能力下降。表1参8(张江安)20100121婴儿湿疹患儿血清食物过敏原特异性IgG抗体的检测/卫风蕾(大连市儿童医院皮肤科)∥中国麻风皮肤     

肿瘤坏死因子α与系统性红斑狼疮

肿瘤坏死因子α是自身免疫反应的重要效应因子。对肿瘤坏死因子α及其受体Ｐ５５、Ｐ７５水平，外周血单个核细胞产生肿瘤坏死因子α的能力、肿瘤坏死因子α的基因主多态性等与系统性红斑狼疮的关系做了简要综述。     

Targeting tumor necrosis factor alpha. New drugs used to modulate inflammatory diseases.

Since its discovery, the understanding of the roles for TNF-alpha in human biology and disease has grown. Receptors for TNF are found on virtually all cell types, and many physiologic processes seem to be altered by TNF-alpha. The understanding of how TNF-alpha is involved in the pathophysiology of diseases, such as inflammatory diseases, has allowed the development of new drugs that can interfere with excess TNF-alpha and thus has allowed novel therapies for rheumatoid arthritis and Crohn's disease. As the role of TNF-alpha in other diseases becomes better understood, such TNF-alpha-modulating drugs may find further applications. In the skin, TNF-alpha is prominent cytokine that seems to be important in allergic and irritant contact dermatitis and inflammatory skin conditions. Modulating TNF-alpha activity in the skin may provide therapeutic benefits for a variety of skin conditions (Table 4). Tumor necrosis factor-alpha levels are elevated in skin lesions of psoriasis. A few reports have already suggested that etanercept and infliximab may offer a therapeutic effect in patients with psoriasis. Clinical studies evaluating the true efficacy of these drugs in psoriasis are under way. Specifically, the authors and others are involved in a double-blind, placebo-controlled study to assess the efficacy of etanercept for psoriasis. Thalidomide has been used off-label with some success to treat a number of dermatologic diseases, including several inflammatory skin conditions. Etanercept and infliximab might perhaps prove efficacious for inflammatory skin conditions as well. Finally, it is possible that drugs targeting TNF-alpha may have yet-unrecognized serious side effects. Because TNF-alpha seems to be a central cytokine in UVR-induced apoptosis, the chronic use of TNF-alpha-altering drugs might increase the risk for skin cancers. Tumor necrosis factor-alpha also plays some role in cutaneous wound healing; the effect these drugs might have on this process is also unknown at this time. Certainly, much is already [table: see text] known about TNF-alpha and how it plays many central roles. This understanding has allowed the development of useful new drugs for intractable disease. As the understanding of TNF-alpha and other cytokine biology increases, so will the number of potential therapeutic agents.     

Psoriasis and its treatment with infliximab-mediated tumor necrosis factor alpha blockade

The pathogenesis of psoriasis, a chronic immune-mediated inflammatory skin disease,involves increased concentrations and activity of several proinflammatory cytokines,including tumor necrosis factor alpha (TNF-alpha). Infliximab is a chimeric human-murine TNF-alpha antibody that selectively blocks the activity of TNF-alpha. In controlled clinical trials, infliximab treatment has produced rapid and sustained improvements in psoriasis lesions and psoriatic joint involvement, with a favorable short-term safety and tolerability profile.Treatment with infliximab may be associated with an increased risk of infection or infusion reaction: however, the side-effect profile of infliximab in patients with psoriasis remains to be fully characterized, and assessment of infliximab in this population is currently ongoing in phase 3 studies. Comprehensive evaluation in controlled trials may allow infliximab to take its place among the expanding group of biologic drugs for the treatment of moderate to severe psoriasis.     

Interstitial granulomatous dermatitis associated with the use of tumor necrosis factor alpha inhibitors

BACKGROUND: Tumor necrosis factor alpha (TNF-alpha) has been implicated in the pathogenesis of numerous inflammatory and autoimmune disorders. Accordingly, TNF-alpha inhibitors, such as thalidomide, infliximab (Remicade), adalimumab (Humira), and etanercept (Enbrel), have been used with success in the treatment of autoimmune disorders, including psoriasis, rheumatoid arthritis, inflammatory bowel diseases, and lymphoproliferative disorders. Although anti-TNF-alpha therapy is safe and well tolerated, various adverse cutaneous reactions have been reported. OBSERVATIONS: We encountered 5 patients who developed erythematous annular plaques on the trunk and extremities while receiving 4 different medications with inhibitory activity against TNF-alpha. One patient was treated with lenalidomide (Revlimid) for multiple myeloma, 2 received infliximab, and 1 received etanercept for severe rheumatoid arthritis; the last patient was in a clinical trial of adalimumab for psoriatic arthritis. Skin biopsy specimens revealed diffuse interstitial granulomatous infiltrates of lymphocytes, histiocytes, and eosinophils, palisading degenerated collagen. Withdrawal of the medications led to complete resolution of the skin lesions. CONCLUSION: Interstitial granulomatous dermatitis should be considered in the differential diagnosis of skin lesions occurring in the setting of anti-TNF-alpha therapy.     

Cutaneous side-effects in patients with rheumatic diseases during application of tumour necrosis factor-alpha antagonists

BACKGROUND: Patients with rheumatic diseases receiving antitumour necrosis factor (TNF)-alpha-based treatment may develop cutaneous reactions. OBJECTIVES: To analyse the new onset or aggravation of skin lesions in patients with a rheumatic disease during treatment with TNF-alpha antagonists. METHODS: We conducted a prospective analysis of 35 of 150 patients with a long history of rheumatic disease, including rheumatoid arthritis, ankylosing spondylitis (Bechterew's disease) and psoriatic arthritis, to test for the development of cutaneous manifestations during anti-TNF-alpha (infliximab, adalimumab or etanercept) treatment. RESULTS: Chronic inflammatory skin diseases such as psoriasis and eczema-like manifestations represented the majority of cases (16 of 35). Cutaneous infections caused by viral, bacterial and fungal agents were also observed in many patients (13 of 35). Skin diseases such as dermatitis herpetiformis, leucocytoclastic vasculitis and alopecia occurred in single cases only. CONCLUSIONS: We observed a broad, diverse clinical spectrum with a majority of chronic inflammatory and infectious skin diseases. However, we did not identify individual risk factors and a discontinuation of the anti-TNF-alpha treatment was not necessary if adequate dermatological treatment was performed. The onset of cutaneous side-effects in anti-TNF-alpha-based treatments should be determined by nationwide registries.     

Treatment of recalcitrant psoriatic arthritis with anti-tumor necrosis factor-α antibody

Currently available treatments for psoriatic arthritis are either not completely effective or toxic in some patients. As tumour necrosis factor (TNF)-alpha is involved in both the joint and skin involvement in psoriatic arthritis, blockade of TNF-alpha seems a reliable way to treat patients with this disease. We report two patients with progressive recalcitrant psoriatic arthritis treated with low-dose methotrexate (7.5 mg, once per week) in combination with intravenous chimeric monoclonal anti-TNF-alpha antibody (infliximab, 3 mg/kg body weight). Both showed a dramatic and rapid response in the reduction of pain, followed by improvement of laboratory and clinical signs of joint inflammation. Skin disease also responds after a short delay. The observation shows that infliximab is effective and well tolerated in patients with recalcitrant progressive psoriatic arthritis. Different kinetics of symptom release during treatment suggest a variable role for TNF-alpha in disease pathways of pain, joint inflammation and skin involvement.     

Invasive Trichophyton rubrum infection occurring with infliximab and long-term prednisone treatment

BACKGROUND: A 64-year-old woman presented with erythematous plaques, tender nodules, and pustules of the dorsal right hand and both legs following long-term treatment with systemic steroids and infliximab. Skin biopsy demonstrated dermal inflammation with foci of necrosis and multinucleated giant cells containing fungal spores. Tissue culture grew Trichophyton rubrum. OBJECTIVE: To report a case that demonstrates the pathophysiology of invasive T. rubrum infection, the mechanisms of action and uses of tumor necrosis factor alpha (TNF-alpha)-inhibiting drugs, and how these drugs may increase patients' risk of invasive dermatophytosis. CONCLUSION: Dermatophytes such as T. rubrum rarely cause invasive disease. This unusual presentation of invasive T. rubrum occurred with immunosuppression by infliximab and systemic steroids. Patients should have a thorough examination for signs of latent infection before TNF-alpha inhibitors are prescribed, including inspection of the skin and nails for signs of dermatophytosis.     

Cutaneous adverse reaction to infliximab: report of psoriasis developing in 3 patients

Infliximab is a chimeric immunoglobulin G1kappa monoclonal antibody against tumor necrosis factor alpha (TNF-alpha), a proinflammatory cytokine that participates in both normal immune function and the pathogenesis of many autoimmune disorders. Treatment with infliximab reduces the biologic activities of TNF-alpha and thus is indicated in the treatment of rheumatoid arthritis, Crohn disease, ankylosing spondylitis, psoriatic arthritis, plaque psoriasis, and ulcerative colitis. To our knowledge, there have been 13 case reports of new-onset psoriasis, psoriasiform dermatitis, and palmoplantar pustular psoriasis that developed during treatment with infliximab. We report 3 additional cases of biopsy-proven new-onset psoriasis that developed while the patients underwent treatment with infliximab for inflammatory bowel disease. Although the mechanism for the development of psoriasis in these patients is unclear, several possible explanations are proposed. With increasing use of infliximab and other TNF-alpha inhibitors in clinical practice, more cases of similar reactions to these drugs probably will be reported and are necessary to determine the importance of this eruption.     

Infliximab monotherapy in psoriasis: a case of rapid clinical and histological response

BACKGROUND: Psoriasis is a common chronic relapsing, inflammatory, hyperproliferative skin disorder with genetic predisposition. There is currently no experimental model for psoriasis and the pathogenesis is not fully understood. Psoriatic plaques have been shown to contain increased levels of cytokines, including tumor necrosis factor alpha (TNF-alpha). Anti-tumor necrosis factor therapy with infliximab has been shown to be highly effective in recalcitrant psoriasis. METHODS: We evaluated the efficacy and timeline of histological changes in a psoriatic plaque following infliximab infusion. A patient with severe recalcitrant plaque psoriasis was clinically and histologically assessed for improvement. RESULTS: We found rapid clinical improvement with infliximab accompanied by histopathological changes. The earliest effects were seen on neutrophils and lymphocytes whereas keratinocyte normalization was not evident at the early stages. CONCLUSION: Infliximab is not only an effective agent in the treatment of psoriasis but appears to have a very rapid onset of action.     

Rapid response to infliximab in severe pustular psoriasis,von Zumbusch type

Tumor necrosis factor-alpha (TNF-alpha) is a chemokine secreted by T cells which is thought to play a critical role in the pathophysiology of psoriasis. The monoclonal antibody, infliximab, complexes with TNF-alpha, rendering it inactive. A recent clinical trial has reported the clinical benefit and safety of infliximab in moderate to severe plaque psoriasis. We report a case of rapid response and clinical benefit using infliximab in severe pustular psoriasis of von Zumbusch.     

Psoriasis and psoriatic arthritis induced in a patient treated with infliximab for Crohn's disease

The induction of psoriasis as a side effect of treatment with TNF-alpha inhibitors is one of a few rare complications of treatment, the pathogenic mechanism of which has not yet been completely clarified. The clinical presentation of these reactions may show the typical characteristics of psoriasis, palmoplantar pustulosis and psoriasiform exanthema; the individual variations of which may combine to give different presentations in individual patients. We present the case of a patient who, after administration of infliximab indicated for Crohn's disease, developed not only skin manifestations but also those of psoriatic arthritis.