Thalidomide treatment in cutaneous lesions of systemic lupus erythematosus: a multicenter study in China

Thalidomide is effective for treating severe cutaneous lupus patients. The aim of this study was to observe the optimum effective and maintenance doses of thalidomide to maximize clinical benefit and minimize side effects for patients with cutaneous lupus in China. Sixty-nine patients with lupus rash from eight hospitals in China were enrolled and treated with different doses of thalidomide. We started the dose of thalidomide at 25 mg daily and gradually increased administration dose once a week until erythema was markedly improved. The effective and maintenance doses were documented. The size of skin lesions was noted once a week. Systemic lupus erythematosus disease activity index (SLEDAI) score, levels of erythrocyte sedimentation rate (ESR), and serum TNF-α were measured before and after treatment. The remission rates were evaluated weekly until 8 weeks. Sixty-eight percent of patients showed an effective dose of 50 mg daily; another 13, 10, and 9 % of patients had an effective dose of 100, 75, and 25 mg daily, respectively. The maintenance dose was 50 mg daily for 71 % of the patients, and 100, 75, and 25 mg daily for 9, 14, and 6 % of the patients. SLEDAI score and serum ESR levels significantly decreased 4 weeks after thalidomide treatment. At the end of the fourth week, the rates of complete remission, partial remission, and no response were 56 % (n?=?39), 41 % (n?=?28), and 3 % (n?=?2). At the eighth week, the rate of total remission rose up to 100 %. The most common side effects were drowsiness and constipation. No peripheral neuropathy was observed in these patients. Thalidomide at a dose of 50 mg daily may offer a better benefit to risk ratio in the treatment of Chinese cutaneous lupus patients.     

Thalidomide in the treatment of the cutaneous manifestations of lupus erythematosus: experience in sixteen consecutive patients

We review the efficacy, tolerability and safety of low-dose thalidomide in the treatment of refractory disfiguring rash in 16 patients with cutaneous manifestations of lupus. Rashes, which included discoid lupus erythematosus (DLE), subacute cutaneous lupus (SCLE), photosensitive malar rash and non-specific chronic erythema, were diagnosed on clinical grounds, supported by skin biopsy in 11/16 patients. Using starting doses of 50-100 mg/day, 7/16 (44%) patients gained complete or near-complete remission of skin disease and 6/16 (37%) partial remission. Three out of 16 patients failed to respond. Maximum benefit was achieved within 16 weeks in all patients. Doses of 25-50 mg/day were effective in maintaining response. Rapid relapse occurred in 6/8 (75%) patients following drug withdrawal, but the response to thalidomide in those requiring repeat courses appeared to be maintained. There was no detectable improvement in systemic disease. One patient developed symptoms of mild peripheral neuropathy which resolved on drug withdrawal. Our experience suggests that thalidomide is effective in the treatment of severe skin manifestations of lupus refractory to other treatment and can be used safely in specialist rheumatological practice.      

Long-term thalidomide use in refractory cutaneous lesions of lupus erythematosus: a 65 series of Brazilian patients

Thalidomide has been reported as efficacious in refractory cutaneous lupus erythematosus (LE). The most fearful side-effects are teratogenicity and neuropathy. We reported clinical efficacy of long-term low-dose use of thalidomide in 65 patients with LE, emphasizing the prevalence of adverse effects, especially of neuropathy and its related factors. Data obtained from medical records included age, sex, disease duration, and the presence of diagnostic criteria for systemic lupus erythematosus (SLE), the extent and activity of cutaneous lesions and previous treatments. Sixty-three patients (98.9%) presented complete or partial improvement with thalidomide therapy. Drowsiness occurred in 50 patients (77%). Twenty-eight patients (43.2%) presented neuropathy symptoms. Nerve conduction studies were done in 21 (75%) of them and were abnormal in 12 (57%). With the interruption of thalidomide, 24 (82.5%) had complete or partial improvement of neuropathy symptoms and 23 (82%) of them had cutaneous relapse. There were no significant differences between those who developed or not neuropathy in treatment duration, age, total dose and systemic versus cutaneous LE. In conclusion, thalidomide can be used in refractory cutaneous LE with great efficacy and relative security. Controlled studies with schemes with lower doses or intermittent usage or alternative drugs are wanted to reduce the burden of cutaneous morbidity of lupus erythematosus.     

Thalidomide in the treatment of cutaneous lupus refractory to conventional therapy

OBJECTIVE: We describe a prospective treatment study of thalidomide in a series of 22 patients with cutaneous lupus refractory to other treatments. METHODS: From 1992 to 1998, 22 patients with cutaneous lupus (9 with discoid lupus erythematosus, 7 with subacute cutaneous lupus, 4 with profundus lupus, 2 with nonspecific rash) were treated with thalidomide. Initial treatment was started at 100 mg daily. If the cutaneous lesions vanished, the dose was lowered to 50-25 mg daily as a maintenance therapy and it was considered a complete remission. If the lesions improved but remained, this was considered a partial response and treatment was continued until the lesions were not further modified. Periodically, adverse effects were evaluated. RESULTS: Three patients discontinued treatment because of side effects such as vertigo, persistent drowsiness, or paresthesia. Rash improved in 16/19 patients (84%). Complete remission occurred in 12/16 (75%). In 9 (65%) the rash resolved, but recurred 4-16 weeks after withdrawal of thalidomide; when it was used again, they improved. Partial response was achieved in 4/16 (25%) patients. No response occurred in 3/19 (16%). Many patients noted improvement within 2 weeks after starting thalidomide and maximum benefit was achieved within 3 months. Five of the 14 women had amenorrhea during the treatment with thalidomide. CONCLUSION: Thalidomide is effective in the treatment of cutaneous lupus refractory to other treatments. However, only some patients had a remission; the remainder relapsed when treatment was withdrawn, or required low doses of thalidomide to preserve inactive lesions. Amenorrhea was observed as a new secondary effect of thalidomide.     

Thalidomide and rituximab in Waldenstrom macroglobulinemia

Thalidomide enhances rituximab-mediated, antibody-dependent, cell-mediated cytotoxicity. We therefore conducted a phase 2 study using thalidomide and rituximab in symptomatic Waldenstrom macroglobulinemia (WM) patients naive to either agent. Intended therapy consisted of daily thalidomide (200 mg for 2 weeks, then 400 mg for 50 weeks) and rituximab (375 mg/m(2) per week) dosed on weeks 2 to 5 and 13 to 16. Twenty-five patients were enrolled, 20 of whom were untreated. Responses were complete response (n = 1), partial response (n = 15), and major response (n = 2), for overall and major response rate of 72% and 64%, respectively, on an intent-to-treat basis. Median serum IgM decreased from 3670 to 1590 mg/dL (P < .001), whereas median hematocrit rose from 33.0% to 37.6% (P = .004) at best response. Median time to progression for responders was 38 months. Peripheral neuropathy to thalidomide was the most common adverse event. Among 11 patients experiencing grade 2 or greater neuropathy, 10 resolved to grade 1 or less at a median of 6.7 months. Thalidomide in combination with rituximab is active and produces long-term responses in WM. Lower doses of thalidomide (ie, 相似文献   

Frequent good partial remissions from thalidomide including best response ever in patients with advanced refractory and relapsed myeloma

Twenty-three patients with advanced and heavily pretreated myeloma were treated with thalidomide. Starting dose was 200 mg/d, and 20 patients had dose escalations up to 400 (n = 5), 600 (n = 12) or 800 mg/d (n = 3), usually in divided doses. Nineteen patients were refractory to recent chemotherapy, and four had untreated relapse after prior intensive therapy. Ten out of 23 patients (43%) achieved partial response (PR; nine with refractory and one with relapsed disease), six patients had minor response or stabilization of the disease and four had disease progression. Another three patients died early from advanced myeloma at less than 3 weeks of thalidomide therapy. Of the 10 patients with PR, seven had a better response than after any prior therapy, despite vincristine-doxorubicin-dexamethasone (VAD)-based treatment in all but one and high-dose melphalan with autologous stem cell support in four. Time to achieve PR was rapid in patients receiving thalidomide in divided doses (median 31 d). Responses also included reduced bone marrow plasma cell infiltration and improved general status. Normalized polyclonal gammaglobulin levels were seen in four cases. Six out of 10 patients with PR remained in remission with a median time on treatment of 23 weeks (range 15-50 weeks). Sedation was common but usually tolerable, and some patients continued full- or part-time work. Four patients had skin problems, three patients had pneumonia, one hypothyrosis, one sinus bradycardia and one minor sensory neuropathy. Thalidomide may induce good partial remissions in advanced refractory myeloma with tolerable toxicity, and should be evaluated in other settings for myeloma patients. Divided thalidomide doses seem to reduce time to achieve remission and may improve response rate.     

Update on therapy--thalidomide in the treatment of lupus

Thalidomide has been shown to be an effective treatment for cutaneous forms of lupus erythematous refractory to other therapies. Thalidomide has very serious side effects, including teratogenicity and neuropathy, which limit its clinical use in lupus to such severe refractory cases. Efficacy has been confirmed in several studies, although recurrence after discontinuation of treatment is frequent. More recent experience suggests that lower doses than originally used may be effective, which may result in a reduction in side effects. Much effort has been expended in studying the mechanisms of action of thalidomide, although as yet it is unclear which of the mechanisms identified to date contribute to its efficacy in treating cutaneous forms of lupus erythematosus. Identification of patients suitable for thalidomide therapy requires a rigorous selection process. Potential side effects should be clearly explained, particularly teratogenicity as many patients are young women. Written consent and a negative pregnancy test must be obtained prior to commencement of therapy. Reliable contraceptive measures should be strictly observed by patients taking thalidomide. Close clinical and neurophysiological supervision using nerve conduction studies should be undertaken.     

An open-label pilot study of low-dose thalidomide in chronically active, steroid-dependent Crohn's disease

BACKGROUND & AIMS: Thalidomide decreases production of tumor necrosis factor alpha, a proinflammatory cytokine associated with Crohn's disease (CD). In this study the safety, tolerance, and efficacy of low-dose thalidomide were evaluated for treatment of moderate-to-severe, steroid-dependent CD. METHODS: Twelve adult male patients with Crohn's Disease Activity Index (CDAI) scores of > or = 250 and < or = 500 despite > or = 20 mg prednisone/day were enrolled. The first 6 patients received 50 mg thalidomide every night, the next 6 received 100 mg every night. Steroid doses were stable during the first 4 weeks of treatment, then tapered during weeks 5-12. CDAI was used to assess response. RESULTS: (1) Disease activity improved consistently in all patients during weeks 1-4: 58% response, 17% remission. (2) Clinical improvement was generally maintained despite steroid taper during weeks 5-12. All patients were able to reduce steroids by >/=50%. Forty-four percent discontinued steroids entirely. In weeks 5-12, 70% of patients responded and 20% achieved remission. (3) Side effects were mild and mostly transient, with the most common being drowsiness, peripheral neuropathy, edema, and dermatitis. CONCLUSIONS: Low-dose thalidomide appears to be well tolerated and effective over a 12-week period. Results of this pilot study support the need for controlled multicenter trials of thalidomide for treatment of CD.     

Thalidomide for chronic sarcoidosis

STUDY OBJECTIVES: Thalidomide therapy has been shown to modify granulomatous diseases, such as tuberculosis and leprosy. Lupus pernio is a skin manifestation of sarcoidosis that does not remit spontaneously, and was used as a marker of efficacy of thalidomide for sarcoidosis. DESIGN: An open-label, dose-escalation trial of thalidomide. SETTING: Patients were seen at one of four specialized sarcoidosis clinics in the United States. PATIENTS: Fifteen patients with lupus pernio and other manifestations of sarcoidosis unresponsive to prior therapy were enrolled. INTERVENTIONS: Skin lesions were assessed with visual examination by the treating physician, and photographic evaluation by a blinded panel of physicians reviewing photographs of the lesions before and after therapy. MEASUREMENTS AND RESULTS: Fourteen patients completed 4 months of therapy. All patients experienced some improvement in their skin lesions subjectively, and 10 of 12 evaluable patients showed improvement using photograph scoring. Five patients were better after 1 month (treated with 50 mg/d of thalidomide), seven more patients improved after 2 months (treated with 100 mg/d of thalidomide in the second month), and two patients required an additional month of 200 mg of thalidomide to achieve a response. Patients reported increased somnolence (n = 9), numbness (n = 7), dizziness (n = 2), constipation (n = 6), rash (n = 1), and increasing shortness of breath (n = 1). One patient discontinued therapy because of new-onset dyspnea, due to probably unrelated new-onset congestive heart failure. CONCLUSION: Thalidomide was an effective form of treatment for chronic cutaneous sarcoidosis. The drug was well tolerated and may be a useful alternative to systemic corticosteroids.     

Neurological toxicity of long-term (>1 yr) thalidomide therapy in patients with multiple myeloma

OBJECTIVE: Thalidomide is remarkably active in advanced relapsed and refractory multiple myeloma (MM), so that its use has been recently proposed either in newly diagnosed patients or as maintenance treatment after conventional or high-dose therapy. This latter therapeutic approach has risen the concern of side-effects of long-term therapy with this drug. METHODS: We analysed long-term toxicity of 40 patients (27 M, 13 F, median age = 61.5 yr) who received salvage therapy with thalidomide +/- dexamethasone for longer than 12 months (median 15, range 12-44) at our centre. All the patients had achieved at least a stable disease upon treatment with thalidomide alone (200-400 mg/d, n = 20) or thalidomide (200 mg/d) and dexamethasone (40 mg/d for 4 d every 4 wk) (n = 20). RESULTS AND CONCLUSIONS: Neurotoxicity was the most troublesome and frequent toxic effect that was observed after long-term treatment, the incidence averaging 75%. Among these 30 patients symptoms included paraesthesias, tremor and dizziness. Neurotoxicity was grade 1 in six patients (15%); grade 2 in 13 patients (32.5%), thus determining thalidomide dose reduction to 100 mg/d; and grade 3 in 11 patients (27.5%) who had subsequently to interrupt therapy despite their response. Electromyographic study, performed in patients with grade >/=2 neurotoxicity, revealed a symmetrical, mainly sensory peripheral neuropathy, with minor motor involvement. The severity of neurotoxicity was not related to cumulative or daily thalidomide dose, but only to the duration of the disease prior to thalidomide treatment, although no patients presented neurological symptoms at study entry. These results suggest that long-term thalidomide therapy in MM may be hampered by the remarkable neurotoxicity of the drug, and that a neurological evaluation should be mandatory prior to thalidomide treatment, in order to identify patients at risk of developing a peripheral neuropathy.     

Low-dose thalidomide regimens in therapy of relapsed or refractory multiple myeloma

Thalidomide has been estimated as a useful drug in therapy of refractory or relapsed multiple myeloma. Recently, several studies have shown very good results in therapy combination of thalidomide, cyclophosphamide and dexamethasone, but still high doses of thalidomide associated with serious adverse events have been used. In our study, we performed low-dose thalidomide regimens; the aim of this study was to verify the effect and to assess their toxicity. For younger patients up to 65 years we used a "CTD-junior" regimen, consisting of oral thalidomide 200 mg daily, pulsed intravenous cyclophosphamide 800 mg on day 1 and pulsed oral dexamethasone 40 mg on days 1-4 and 12-15, for every three weeks. For patients over 65 years, the "CTDsenior" regimen was used, with oral thalidomide 50-100 mg daily (according to tolerability), oral cyclophosphamide 50 mg daily and pulsed dexamethasone 20 mg on days 1-4 and 15-18, for every four weeks. From the group of 97 patients with progressive form of multiple myeloma or with resistance to conventional chemotherapy, 85 patients were evaluated. According to the EBMT criteria, we observed in 8% complete remission (CR), in 50% partial response (PR) and in 22% minimal response (MR). Ten patients (12%) were stabilized and seven patients (8%) progressed. Toxicity of both regimens was mild and well manageable, when weakness, obstipation, neuropathy of lower extremities, glycoregulation worsening and mild leucopenia occurred most often. These results showed that low doses of thalidomide are still effective, when combined with other drugs. Both CTD regimens are safe also for patients with advanced and heavily pretreated multiple myeloma.     

Combined bendamustine, prednisolone and thalidomide for refractory or relapsed multiple myeloma after autologous stem-cell transplantation or conventional chemotherapy: results of a Phase I clinical trial

Thalidomide is an effective agent for advanced refractory or relapsed multiple myeloma (MM), although dose-limiting toxicity (DLT) may limit its use. This Phase I study found that a combination of low-dose thalidomide with bendamustine and prednisolone (BPT) maintained or increased efficacy, whilst avoiding DLT in 28 patients with MM that was refractory or that had relapsed after conventional chemotherapy or high-dose therapy with stem-cell support. BPT comprised fixed doses of bendamustine (60 mg/m(2)) and prednisolone (100 mg), and escalating doses of thalidomide (50, 100, 200 mg). Treatment cycles were repeated every 28 d until the occurrence of maximum response, DLT, or disease progression. Twenty-four patients responded after at least two cycles (four complete remission, six very good partial remission, 14 partial remission). Median progression-free and overall survival for all patients was 11 and 19 months respectively. Only mild/moderate non-haematological side effects were observed and no patient developed dose-limiting haematotoxicity. Transient grade 3-4 neutropenia was reported in 12 patients, and grade 3-4 thrombocytopenia occurred in two patients. We conclude that BPT therapy was well tolerated in patients with relapsed or refractory MM, with a response rate higher than 80%. The maximum tolerated dose of thalidomide was not reached in this study.     

Thalidomide maintenance following high-dose therapy in multiple myeloma: a UK myeloma forum phase 2 study

Thalidomide maintenance has unresolved issues regarding dosage and toxicity. We evaluated this in five dose cohorts in 100 patients. At a median follow-up of 32.3 months, 23 patients had stopped thalidomide for disease progression, 54 for side effects. 3-year overall and progression-free survival was 76% and 41% respectively. Dosage did not influence disease outcome but greatly affected toxicity. Fifteen patients converted from partial remission to complete remission on thalidomide at a median of 13.5 months. Maintenance doses >200 mg were largely unachievable and peripheral neuropathy was the main toxicity. Lower doses enabled more patients to stay on the drug for a useful period of time.     

Thalidomide plus oral melphalan compared with thalidomide alone for advanced multiple myeloma

Thalidomide, the prototype of a new class of agents active against multiple myeloma (MM), exerts synergistic/additive effects when combined with other drugs. The aim of this study was to compare the toxicity and efficacy of thalidomide alone and in combination with oral melphalan. Patients with advanced MM received 100 mg/day oral thalidomide escalated weekly up to 600 mg/day (n=23; T group), alone or with 0.20 oral mg/kg/die melphalan administered monthly for four consecutive days (n=27; TM group). A>/=50% paraprotein reduction was observed in 59% of TM compared with 26% of T patients (P=0.009); three TM patients were found to have an absence of paraprotein by immunofixation. After a median follow-up of 13 months (range 6-32), progression-free survival (PFS) at 2 years was significantly longer in the TM group (61 versus 45%; P=0.0376), whereas overall survival did not differ significantly. Toxicity was not significantly greater with the combination therapy; although DVT was more frequent (11 versus 4%), as was grade 3 leukopenia (30 versus 13%; P=0.073), there were no cases of severe infection. Thalidomide administered with oral melphalan improved response rates and PFS in patients with advanced MM without significantly increasing severe toxicity.     

Salvage therapy with thalidomide in patients with advanced relapsed/refractory multiple myeloma

BACKGROUND AND OBJECTIVES: Few therapeutic options are presently available for patients with multiple myeloma (MM) who relapse after autologous or allogeneic stem cell transplantation, or for patients who are refractory to conventional chemotherapy and not eligible for salvage high-dose therapy. Thalidomide, a glutamic acid derivative with anti-angiogenic properties, has been recently proposed as an effective therapy for patients with advanced refractory disease. The aim of this study was to evaluate the activity of thalidomide in a large series of MM patients. DESIGN AND METHODS: From October 1999 to January 2001, 65 patients (46 males/19 females) from 8 Italian institutions were treated with thalidomide. Twenty-six patients had relapsed after autologous stem cell transplantation, either single (n = 12) or double (n= 12); 38 patients had shown disease progression after >= 2 lines of conventional chemotherapy, 2 patients had relapsed after allotransplant, one single patient had not received previous treatment. Sixty-one (93.8%) patients were in stage III, median b2 microglobulin was 2.9 mg/L, and median bone marrow plasma cell infiltration was 50%. Thalidomide was initially administered at a dose of 100 mg/day; if well tolerated, the dose was to be increased serially by 200mg every other week to a maximum of 800 mg/day. RESULTS: The median administered dose of thalidomide was 400 mg/day. WHO grade > II toxic effects were constipation (52%), lethargy (34%), skin rash (11%), peripheral neuropathy (14%) and leukopenia (3%). Sixty patients are presently evaluable for response; of these, 17 (28.3%) showed > or = 50% reduction in serum or urinary M protein concentration and 11 (18.3%) showed > or = 25% tumor reduction, for a total response rate averaging 46.6%. After a median of 8 months' follow-up, 15/28 patients are alive and progression-free (at 2 to 16 months), 12 patients have relapsed, and 1 patient died of pulmonary edema while still in partial remission. Among pre-treatment variables that were analyzed for their potential relationship with tumor response, only the concentration of vascular endothelial growth factor (VEGF) in the conditioned media obtained upon culture of bone marrow plasma cells was statistically significant. Plasma cells from patients who responded favorably to thalidomide secreted a significantly lower amount of VEGF than plasma cells from resistant patients (126.45 165 pg/mL vs 227.11 70 pg/mL, p=0.04). INTERPRETATION AND CONCLUSIONS: These data confirm that thalidomide is active in patients with advanced relapsed/refractory MM and represent the basis for ongoing clinical trials aimed at testing the role of this drug as front line therapy for newly diagnosed disease.     

Low-dose vs. high-dose thalidomide for advanced multiple myeloma: a prospective trial from the Intergroupe Francophone du Myélome

This multicentre prospective randomised trial compared the efficacy and safety of two doses of thalidomide in patients with relapsed or refractory myeloma. The study was designed to test the non-inferior efficacy and to confirm the better tolerability of low-dose thalidomide as compared to a higher dose. Four hundred patients were randomly assigned to receive either 100 or 400 mg/day of thalidomide. Dexamethasone treatment was added in both arms for patients with stable disease or treatment failure at 12 weeks. The primary endpoint was 1-year overall survival (OS). Thalidomide 100 mg/day was better tolerated than 400 mg/day with less high-grade somnolence, constipation, nausea/vomiting and peripheral neuropathy (P < 0.001, P = 0.007, P = 0.03 and P = 0.007, respectively). In the per-protocol population (PP), the estimated 1-year OS rates were of 74.5% (n = 149) and 67.3% (n = 156) in the 400 and 100 groups, respectively. The upper limit of the difference between these rates was of 15.6% higher than the non-inferiority acceptable limit of 12.75%, and the hypothesis of non-inferiority of 100 could not be established (P = 0.14). On the other hand, when intent-to-treat (ITT) population was analysed, the non-inferiority was demonstrated because the 1-year OS rates were of 72.8% (n = 195) and 68.8% (n = 205) in the same groups, leading to an upper limit of the difference of 11.49% lower than the non-inferiority acceptable limit. In addition, in patients alive 12 weeks postrandomisation and those who received thalidomide plus dexamethasone, there were no significant differences in response rates, time to progression, progression-free survival and OS between the two groups. Collectively, low-dose thalidomide 100 mg/day has significant activity in advanced myeloma with an improved safety profile and can be a good salvage therapy in combination with dexamethasone.     

沙立度胺联合MP化疗方案治疗多发性骨髓瘤23例

目的：观察沙立度胺联合MP方案治疗多发性骨髓瘤的疗效及其不良反应。方法：确诊的多发性骨髓瘤患者23例。沙立度胺-MP方案：沙立度胺自MP方案开始持续给药，每晚睡前口服，剂量从每天100mg开始，每周日剂量递增50mg，至患者不能耐受或最高至每日400mg；MP方案每月1个疗程。结果：部分缓解16例（69．6％），进步4例（17．4％），总有效率为87．0％（20／23）。有效的患者中10例在4周内起效，沙立度胺每天100～400mg，中位剂量每天225mg。常见的不良反应为皮疹、便秘、嗜睡、乏力、头昏、水肿等。结论：沙立度胺加MP方案治疗多发性骨髓瘤不良反应少，耐受性好，且反应率可能提高。     

Behçet's disease in UK children: clinical features and treatment including thalidomide

OBJECTIVE: To study the clinical spectrum of Beh?et's disease (BD) in childhood, and to report our experience of using thalidomide. METHOD: Ten children, diagnosed with BD, were studied retrospectively. RESULTS: The median (range) age at first presentation was 4 (1.2-12.0) yr, at diagnosis was 11 (3-15) yr and the follow-up period was 4.1 (0.6-6.3) yr. Oral ulcers were present in all patients (100%), genital ulcers were present in six (60%), peri-anal ulcers were present in three (30%), skin manifestations were present in nine (90%), intracranial hypertension was present in two (20%), mild gastrointestinal symptoms were present in five (50%), joint symptoms were present in six (60%), ocular lesions were present in five (50%), but only one child had anterior and posterior uveitis. Therapeutically, a range of drugs was used, including colchicine, that resulted in good responses in five children. Thalidomide (1 mg/kg/week to 1 mg/kg/day) was used in five children who were unresponsive to other immunosuppressive agents. It resulted in complete remission in three children and less frequent milder oral ulcers in two. Neuropathy developed in two children and in one it was irreversible. CONCLUSION: BD in children is similar to the disease in adults. Thalidomide provided a useful therapeutic option for severe oral and genital ulceration which was unresponsive to other therapies. Awareness of the danger of axonal neuropathy and teratogenesis at all times during thalidomide therapy is crucial. A low dose is probably as effective as higher doses.     

Clinical experience with thalidomide in the management of severe oral and genital ulceration in conditions such as Beh?et's disease: use of neurophysiological studies to detect thalidomide neuropathy.

OBJECTIVE--To examine the efficacy, dose, and safety profile, including neurophysiological testing of thalidomide used in 59 patients (including 23 with Behçet's disease) to treat severe oral or genital ulceration (OGU). METHODS--We identified prospectively subjects (including women of childbearing potential) who had persistent OGU over periods lasting one to 40 years and whose active ulceration was not controlled by other therapies. They were treated with thalidomide. Retrospectively, we identified the number of subjects with complete resolution of the ulcers at one and two months of thalidomide therapy, and the dose required to maintain that improvement in those individuals who relapsed after stopping thalidomide. The decrease from the baseline sensory nerve action potential (baseline SNAP) amplitude value (derived from median, radial and sural nerve SNAPs) at which the development of paraesthesiae was likely to occur was also determined. RESULTS--Complete resolution of the ulcers occurred in 81% of patients within one month of thalidomide therapy at doses of 200 mg/day. No further thalidomide was required by 20% of patients responding and in the remainder improvement was maintained with smaller doses (7-200 mg/day). Using an approximate 50% decrease from baseline SNAP as an indication to discontinue thalidomide, the incidence of symptomatic neuropathy was 13.5%. No patients with a decrease of less than 42% developed neuropathy, and a further 13.5% were asymptomatic with a decrease in SNAP between 42 and 69%. Other side effects were seen in 44% of patients. There were no pregnancies and no requirement for urgent pregnancy testing. CONCLUSIONS--Thalidomide provided a useful therapeutic option in severe oral and genital ulceration which had not responded to other therapies. The physician must remain vigilant to the continuing danger of axonal neuropathy and teratogenesis at all times during thalidomide therapy.     

停用依那西普后沙利度胺对维持强直性脊柱炎患者病情缓解的影响

目的 评价停用依那西普后沙利度胺可否维持强直性脊柱炎(AS)患者病情的缓解.方法 105例经过为期12周的依那西普治疗后达到了AS疗效评价标准(ASAS)20改善标准并能定期接受随访的患者随机分为3组,第1组给予沙利度胺150 mg.每日1次,晚上口服;第2组给予柳氮磺吡啶(SASP)1.0 g,每日2次口服;第3组仅给予原先使用的非甾体抗炎药(NSAIDs)维持治疗.每个月定期随访1次,随访内容包括:Bath AS疾病活动性指数(BASDAI)、Bath AS功能指数(BASFI)、患者对病情的总体评价(PGA)、脊柱痛等的变化.以病情复发作为随访终点.结果 有100例患者最终完成了随访,其中沙利度胺组30例.SASP组33例,NSAIDs组37例,平均随访时间(5±4)个月,最长的患者随访了12个月.随访结束时沙利度胺组维持病情缓解率为40%(12例),SASP组为15%(5例),NSAIDs组为11%(4例),沙利度胺组的维持缓解率要显著高于SASP组(P=0.0265)和NSAIDs组(P=0.0053),而SASP组和NSAIDs组维持缓解率的差异无统计学意义(P=0.5881).结论 沙利度胺有助于停用依那西普后维持AS患者病情的缓解.