Barrier repair in chronic plaque-type psoriasis

Purpose: To investigate barrier repair after mild trauma in lesional skin of psoriasis patients with chronic plaque-type disease and to compare this with non-involved psoriatic skin and normal controls.
Methods: Transepidermal water loss (TEWL) readings were taken from involved psoriatic skin and non-involved skin of psoriasis patients as well as the skin of normal controls. Three readings were performed at each site: the basal state, immediately after 20 tape strippings and 1 week post stripping.
Results: Higher baseline, post-stripping and 1-week recovery TEWL readings in psoriatic-involved skin compared to non-involved and normal control skin. No significant difference in barrier recovery rate in psoriatic-involved skin compared to non-involved and normal control.
Conclusion: Although there appears to be a derangement of barrier function in lesional skin of psoriasis patients compared to non-lesional skin and the skin of healthy controls, the barrier recovery function of lesional psoriatic skin is still fully operational.     

Short-term cyclosporin monotherapy for chronic severe plaque-type psoriasis

Cyclosporin is an effective treatment for psoriasis but its efficacy is only palliative. The aim of this study was to evaluate the percentage of patients in whom a short term therapy may be used without relapse after discontinuation of cyclosporin. In this multicenter, open, non-controlled study fifty-eight patients were included who had severe and extensive chronic plaque-type psoriasis. Treatment duration was 28 weeks. The absence of relapse was defined as the requirement to resume systemic treatment at 16 weeks after discontinuation of Sandimmun .The overall efficacy of Sandimmun at W20 was 72%. No relapse or premature withdrawal occurred in 18 cases out of 39 (47%). In these cases local treatment was sufficient following discontinuation. Thus we show the potential value of a single 5 month course of cyclosporin treatment. In this study tapering of cyclosporin was not useful. In 50% of cases short-term cyclosporin treatment was not followed by resumption of systemic treatment and constitutes an improvement in qualify of life.     

卡泊三醇倍他米松软膏联合窄谱中波紫外线治疗斑块状银屑病的随机对照研究

【摘要】 目的 探讨卡泊三醇倍他米松软膏联合窄谱中波紫外线（NB-UVB）治疗斑块状银屑病的疗效及安全性。 方法 随机、单盲平行对照、多中心临床试验,108例斑块状银屑病患者随机纳入试验组或对照组,疗程4周。对照组单纯进行NB-UVB照射;试验组NB-UVB照射方法同对照组,卡泊三醇倍他米松软膏每晚外用。治疗前、治疗2周、4周时观察疗效及安全性,治疗结束后1、2、4周进行随访。 结果 两组患者治疗2周后,试验组有效率15.09%,对照组有效率2.04%,总体疗效分析差异有统计学意义。治疗4周后,试验组有效率77.36%,对照组26.53%,两组差异有统计学意义（P ＜ 0.01）。治疗前两组PASI评分比较,差异无统计学意义;治疗2周、4周以及随访1周、2周、4周时,两组PASI评分比较,差异均有统计学意义。试验组未发现不良反应,对照组有1例双小腿非皮疹部位出现疼痛性红斑。两组间不良反应发生率比较,差异无统计学意义。 结论卡泊三醇倍他米松软膏联合NB-UVB治疗斑块状银屑病是一种见效快、安全的治疗方法。     

The psoriasis area and severity index is the adequate criterion to define severity in chronic plaque-type psoriasis

BACKGROUND: Chronic plaque-type psoriasis is a major dermatosis, but a significant question is still unanswered: What defines severity in chronic plaque-type psoriasis? While objective assessments like the Psoriasis Area and Severity Index (PASI) have frequently been used in clinical trials, quality of life (QOL) questionnaires are currently becoming more and more popular. OBJECTIVE: This article summarizes the most important objective and subjective measurements of severity in psoriasis. For every dermatologist it is critically important to distinguish between severe psoriasis and psoriasis that severely affects QOL. Even if the PASI also has disadvantages, it is the most adequate instrument available to evaluate severity in plaque-type psoriasis. RESULT: We provide reasons why PASI >12 defines severe, PASI 7-12 moderate and PASI <7 mild chronic plaque-type psoriasis.     

Oral pimecrolimus in the treatment of moderate to severe chronic plaque-type psoriasis: a double-blind, multicentre, randomized, dose-finding trial

BACKGROUND: There is a need for safe and effective alternative treatments for patients with moderate to severe psoriasis. OBJECTIVES: Pimecrolimus is a calcineurin inhibitor that is being investigated in oral form for the treatment of psoriasis. PATIENTS AND METHODS: A double-blind, randomized, parallel-group, dose-finding study was performed. Healthy adult outpatients with moderate to severe chronic plaque-type psoriasis (n = 143) were randomized to receive oral placebo or pimecrolimus 10 mg, 20 mg or 30 mg twice daily (b.d.) for 12 weeks. Main outcome measures: The Psoriasis Area and Severity Index (PASI) was used to assess clinical severity of psoriasis. Results were analysed at weeks 7 (primary endpoint) and 13. Safety was assessed by monitoring all adverse events, laboratory investigations (blood chemistry, urinalysis, haematology) and physical examinations. RESULTS: The change from baseline in PASI at week 7 showed a dose-dependent effect. The differences between each of the two higher doses of pimecrolimus and placebo were statistically significant (P < 0.001; ANOVA). The mean percentage decreases from baseline in PASI in the placebo group and pimecrolimus 10 mg, 20 mg and 30 mg b.d. groups at week 7 were 3.1%, 22.2%, 51.3% and 54.0%, respectively. Most adverse events were of mild or moderate severity. The only adverse event to show a dose-response relationship was a transient feeling of warmth. No clinically relevant effects on laboratory parameters were observed, and no increase in skin infection with pimecrolimus was seen. CONCLUSIONS: Oral pimecrolimus produces a dose-dependent reduction in psoriasis severity, with doses of 20 mg and 30 mg b.d. being the most effective and well tolerated.     

Efficacy of a far erythemogenic dose of narrow-band ultraviolet B phototherapy in chronic plaque-type psoriasis

The aim of the present study was to examine the effect of far erythemogenic dose of narrow-band ultraviolet B (NB-UVB; starting dose at 35% minimal erythematous dose [MED]) on clinical response by measuring the severity, extent of disease and the changes in quality of life. Fifty patients with chronic plaque-type psoriasis were enrolled. Therapy was held for 3 days a week. The severity of the disease was assessed based on the Psoriasis Area and Severity Index (PASI) score and Dermatology Life Quality Index (DLQI) scores. The percentage improvement of PASI at 30 sessions was 68.99%. The improvement in DLQI scores at 30 sessions was 79.67%. Pearson correlation coefficients showed that PASI scores were not correlated with DLQI scores at the beginning of treatment ( P  = 0.330, r  = 0.14), but after the 30th session of NB-UVB therapy improvements in quality of life were correlated ( P  < 0.05, r  = 0.399). Therefore, far erythemogenic dose of NB-UVB is considered to be effective treatment for plaque-type psoriasis in our patients. However, we cannot confirm that it is safer than higher MED starting dose in term of cumulative UV irradiation.     

Programmed cell death of keratinocytes in infliximab-treated plaque-type psoriasis

BACKGROUND: Tumour necrosis factor (TNF)-alpha blockade using infliximab, a chimeric anti-TNF-alpha antibody, is an effective treatment for plaque-type psoriasis, inducing remission in about 80% of patients. OBJECTIVES: To examine infliximab-induced programmed cell death (PCD) of keratinocytes in psoriatic plaques on serial skin biopsy samples. METHODS: Five patients with moderate to severe plaque-type psoriasis received infliximab infusions intravenously (5 mg kg(-1)) at weeks 0, 2 and 6. Biopsies of nonlesional and lesional skin (days 0, 5, 14 and 21) were obtained. Conventional microscopy was used to examine the morphology of the psoriatic keratinocytes. In situ detection of apoptosis was performed by electron microscopy and by immunohistochemical staining with anti-p53 and anti-caspase-3 antibodies. Results Infusion of infliximab induced a clinical response in all five patients with psoriasis, with a mean Psoriasis Area and Severity Index improvement of 24.8% already at day 5. This was accompanied by significant histopathological changes in the skin biopsy samples after infliximab treatment. Light and electron microscopic evaluation revealed apoptosis-like morphological changes in lesional keratinocytes, i.e. nuclear condensation, chromatin fragmentation and cytoplasmic vesiculation, visible already after the first infusion. These damaged keratinocytes stained positively for p53, but not for active caspase-3. CONCLUSIONS: The effects of infliximab in psoriasis extend beyond merely anti-inflammatory actions, and may include caspase-independent PCD of lesional keratinocytes. The PCD of keratinocytes may be an important mechanism that could explain at least in part the rapid and sustained therapeutic effect of infliximab in psoriasis.     

环孢素维持治疗银屑病随机对照研究的文献分析

检索MEDLINE、Embase、Cochrane图书馆、SinoMed、CNKI和万方数据库中1974年1月1日至2018年7月1日环孢素维持治疗银屑病的随机对照临床研究,评价不同环孢素给药方案治疗银屑病的疗效和安全性。共纳入9篇随机临床对照试验文献,均报道环孢素治疗银屑病有效,其中2篇文献研究发现连续治疗方案在长达24周的维持治疗期内是安全有效的,2篇发现间断治疗比连续治疗更安全有效。     

Narrowband UV-B phototherapy vs photochemotherapy in the treatment of chronic plaque-type psoriasis: a paired comparison study.

OBJECTIVE: To compare the therapeutic efficacy of narrowband (TL-01) UV-B phototherapy vs photochemotherapy (psoralen-UV-A [PUVA]) in patients with chronic plaque-type psoriasis. DESIGN: Open, nonrandomized, intraindividually controlled paired comparison study. SETTING: Phototherapeutic unit in a university hospital. PATIENTS: Twenty-five patients with chronic plaque-type psoriasis. INTERVENTIONS: Paired irradiations with threshold erythemogenic doses of narrowband UV-B and PUVA were given to the patients' dorsal aspect including the arms and legs. Treatment was performed 3 times weekly until complete or almost complete clearing with one or both regimens or over a maximum period of 18 exposures. MAIN OUTCOME MEASURES: Assessment of the Psoriasis Area and Severity Index (PASI) in each half of the patient's dorsal aspect before and after treatment with the 2 regimens. RESULTS: The median pretreatment PASI score of 16 (range, 6.2-23.4) was reduced by 84% to 2.5 (range, 0-12.6) by the narrowband UV-B treatment and by 89% to 1.8 (range, 0-8.2) by the PUVA treatment. Statistical analysis of these data showed a tendency for PUVA being superior to narrowband UV-B although the difference remained below the level of significance (P = .17). However, a clear effect of the pretreatment PASI score on the therapeutic outcome was found. Patients with higher baseline PASI scores responded significantly better to PUVA than to narrowband UV-B (P = .03). CONCLUSIONS: Our data demonstrate that in many patients with plaque-type psoriasis, narrowband UV-B is comparably as effective as PUVA and, given the lack of photosensitizer-related adverse reactions and the possibly lower long-term cancer risk, can be considered as first-line treatment. Treatment with PUVA, on the other hand, remains the mainstay for patients with high PASI scores who do not respond or whose psoriasis cannot be controlled adequately by narrowband UV-B.     

A randomized, controlled clinical trial comparing photochemotherapy with dithranol in the initial treatment of chronic plaque psoriasis

224 patients with widespread plaque psoriasis were randomly allocated to treatment with PUVA or dithranol. 103 of the 113 patients treated with PUVA (91.2%) cleared satisfactorily compared with 91 out of in patients treated with dithranol (82%). However, dithranol cleared psoriasis significantly faster than PUVA (20.4±0.9 days compared to 34.4±1.8 days). Photochemotherapy produced no evident short-term adverse effects on the bone marrow, liver, or kidneys.     

Improved health-related quality of life following a randomized controlled trial of alefacept treatment in patients with chronic plaque psoriasis

BACKGROUND: Psoriasis has a negative impact on patients' quality of life. Treatment strategies should address both the cutaneous manifestations of the disease and their impact on quality of life. OBJECTIVES: To evaluate the effect of alefacept on quality of life in 553 patients with chronic plaque psoriasis. METHODS: In this multicentre, double-blind, parallel-groups study, patients were randomized to receive alefacept for two courses, alefacept in course 1 and placebo in course 2, or placebo in course 1 and alefacept in course 2. In each course, alefacept 7.5 mg or placebo was administered once weekly by 30-s intravenous injection for 12 weeks followed by 12 weeks of observation. The Dermatology Life Quality Index (DLQI), Dermatology Quality of Life Scales (DQOLS) and Short Form-36 Health Survey (SF-36) were administered at baseline, 2 weeks after the last dose in both courses, at the beginning of course 2, and at the end of the observation period in both courses. RESULTS: In course 1, alefacept significantly reduced (improved) mean DLQI scores compared with placebo: 4.4 vs. 1.8 at 2 weeks after the last dose (P<0.0001) and 3.4 vs. 1.4 at 12 weeks after the last dose (P<0.001). Patients who received two courses of alefacept experienced additional enhancement of quality of life measures during the second course. Similar results were observed for the DQOLS. The SF-36 survey confirmed that alefacept had no negative impact on general quality of life. CONCLUSIONS: Alefacept improved quality of life in patients with chronic plaque psoriasis and maintained this benefit for at least 12 weeks following cessation of treatment. A second course of alefacept provided additional quality of life benefit.