英夫利西单抗联合改变病情抗风湿药治疗难治性银屑病关节炎的临床疗效及随访观察

目的 探讨英夫利西单抗联合2种以上改变病情抗风湿药(DMARDs)治疗难治性银屑病关节炎( PsA)的临床疗效与安全性.方法 本研究为开放性临床研究.选择2种及2种以上DMARDs治疗3个月以上无效的PsA患者,分别于0、2、6、14周(之后每间隔8周使用1次)静脉滴注英夫利西单抗(3 mg/kg),联合DMARDs治疗.以PsA疗效标准(PsARC)为主要疗效指标,修改的美国风湿病学会疗效标准提高20％(ACR20)为次要疗效指标,对关节病变进行评估,以银屑病皮损面积和严重性指数(PASI)提高50％、75％ (PASI 50、PASI 75)为银屑病皮损疗效指标,对皮肤病变进行评估;并分析具体评价指标[包括压痛关节数、肿胀关节数、疼痛视觉模拟评分、患者总体评价(PGA)、医生总体评价、皮肤病生命质量指数( DLQI)、健康评估问卷(HAQ)]的变化.记录在整个观察过程中发生的所有不良反应.统计学方法采用x2检验和重复测量数据的方差分析检验.结果 共21例患者纳入研究,21例患者全部完成14周的临床疗效评估,其中5例完成26～104周临床观察,2例进行了长达104周的临床观察.治疗14周时21例患者达到PsARC的比例分别为84％,达到ACR20的比例分别为77％,达到PASI 50改善的比例为76％,达到PASI 75改善的比例为68％.14周时患者压痛关节数、肿胀关节数、疼痛视觉模拟评分、PGA、医生总体评价、DLQI、HAQ均显著低于基线水平(P＜0.05),且与治疗前相比差异具有统计学意义.5例患者进行了26～104周随访观察,其中2例进行了长达104周的临床观察,4例患者病情平稳,1例患者于104周时皮疹与关节症状反复.最常见的不良反应为上呼吸道感染和皮肤及其附属器官的损害,其次是肝功能异常.结论英夫利西单抗联合DMARDs治疗PsA有效、安全、可行.     

Thymoma‐associated multi‐organ autoimmunity: A case of graft‐versus‐host disease‐like erythroderma complicated by Good syndrome successfully treated by thymectomy

Thymoma‐associated multi‐organ autoimmunity disease (TAMA) is a rare paraneoplastic disorder, clinicopathologically similar to graft‐versus‐host disease (GVHD). Many reported cases follow a difficult course; half of them die from serious infectious diseases subsequent to immunosuppression induced by chemotherapy for unresectable thymoma, or intensive therapies including systemic steroids for complicating autoimmune diseases and GVHD‐like symptoms. We report a patient whose skin symptoms were improved subsequently to total thymectomy. The patient also presented with hypogammaglobulinemia, which led to the diagnosis of complicated Good syndrome. Taking account of her immunodeficient condition, antibiotics and i.v. immunoglobulin were administrated promptly on onset of bacterial pneumonia, which was successfully treated. According to a review of the published work, treatments with systemic steroids for skin symptoms have limited effects and may contribute to serious infection. Our case indicates that successful treatment of thymoma itself may lead to the amelioration of the disease. The management priority should be given to the treatment of thymoma and the control of subsequent immune abnormality other than GVHD‐like erythroderma.     

Recent clinical experience with etodolac in the treatment of osteoarthritis of the knee

Summary Fifty-two patients with psoriatic arthritis (PA), treated with auranofin (AF), were entered into a one year prospective, open study. The total group showed a significant increase in frequency of HLA antigens A1 and B38, and a reduction of B5 when compared to healthy controls. There was a remission or an important improvement of disease in the 51 % of 45 patients who completed the study. The rate of withdrawal due to side effects was low (8.8%) and the toxicity was mild in nature (diarrhoea and mucocutaneous rash). We prospectively sought predictors of response using HLA antigens, and clinical and laboratory parameters at the beginning of therapy. The only 3 factors found to be related to outcome were duration of psoriasis, physician and patient assessment of disease activity. No laboratory data or HLA specificities could be associated with substantial response to AF therapy.     

Gallbladder carcinoma presenting as exfoliative dermatitis (erythroderma)

Although exfoliative dermatitis (erythroderma) secondary to malignancy is commonly associated with lymphomas or leukemias, coincident gastrointestinal (GI) malignancy and erythroderma is rare. The authors recently encountered a patient with gallbladder carcinoma presenting as erythroderma. A 77-yr-old Japanese man presented with a 3-mo history of erythematous eruptions with pruritus over almost the entire body. After confirming the diagnosis of erythroderma, asymptomatic gallbladder carcinoma was found. Further investigations detected no malignancies in other organs. An extended cholecystectomy was performed. Histologic examination of resected specimens revealed poorly differentiated adenocarcinoma with negative resection margins. The eruptions with pruritus resolved within 1 wk after the operation. This is the first report, to our knowledge, of coincident biliary malignancy and erythroderma. The experience of the current patient suggests that erythroderma secondary to GI malignancy may resolve spontaneously after curative resection of the tumor.     

Pathophysiologic basis for growth failure in children with ichthyosis: an evaluation of cutaneous ultrastructure, epidermal permeability barrier function, and energy expenditure

OBJECTIVE: Because an impaired epidermal permeability barrier is present in many of the ichthyoses, we examined the contribution of barrier failure to caloric requirements in children with ichthyosis and growth failure. STUDY DESIGN: Transepidermal water loss (TEWL) and ultrastructural parameters of the permeability barrier were evaluated in 10 hospitalized children with ichthyosis and growth failure. Nutritional intake, resting energy expenditure, and calories lost as heat of evaporation were determined. RESULTS: Mean basal TEWL rates were markedly elevated in all study patients in comparison to the expected upper limit of normal (39.6+/-20.6 vs 8.7 mL/m(2) per hour). The severity of abnormalities in the ultrastructure of permeability barrier-related structures, assessed semiquantitatively, correlated significantly to mean basal TEWL rates (P <.001). Total body daily TEWL was elevated (746 +/- 468 vs 209 mL/d), resulting in a caloric drain of 433 +/- 272 kcal/d (21 +/- 9.8 kcal/kg per day) through heat of evaporation. Nutrient intake exceeded requirements in all, but resting energy expenditure exceeded predicted in 5 of 6 patients and correlated significantly with mean basal TEWL rates (P <.005). CONCLUSIONS: A defective permeability barrier in children with ichthyosis can result in ample chronic losses of water and calories to impair growth.