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.     

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。     

Large increments in psoralen-ultraviolet A (PUVA) therapy are unsuitable for fair-skinned individuals with psoriasis

The ideal psoralen-ultraviolet A (PUVA) regimen for chronic plaque psoriasis has yet to be established. There are four components to a PUVA regimen: the dose of psoralen, the starting dose of UVA, the frequency of treatment and the incremental UVA dose protocol. Recent studies have been directed at trying to optimize the efficacy of PUVA while minimizing acute side-effects and the risk of cutaneous carcinogenesis, believed to be independently related to the cumulative dose of UVA and the total number of treatments. The British Photodermatology Group recommends two twice-weekly PUVA regimens: one starts with 50% of the minimal phototoxic dose (MPD) and uses weekly increments of 40%, 30%, 25%, 20%, 15%, 10% and 5% of the previous dose to a maximum of 14.5 J/cm2; the other starts with a fixed dose based on skin type and uses weekly dose increments of 40%, decreasing to 20% once erythema develops. We undertook a prospective randomized controlled trial comparing these regimens in 85 Irish patients. The clearance rate with the MPD regimen was lower than with the skin type regimen, 67.5% vs. 95% (P < 0.05). The reasons for treatment failure were grade 3 erythema and severe PUVA itch. There was a trend suggesting that patients with skin types I and II, but not skin type III, required a higher cumulative UVA dose and fewer exposures to clear with the MPD regimen than the skin type regimen, although this did not reach statistical significance. Grades 2 or 3 erythema were very common in both treatment groups (52. 5% of the skin type group and 45% of the MPD group). This is the third study to suggest that patients with skin types I and II receive a higher total UVA dose when the starting dose is 50-70% of the MPD (rather than 0.5 J/cm2 for skin type I and 1.0 J/cm2 for skin type II) and when large dose increments are used. We suggest that smaller dose increments should be used in patients with skin types I and II.     

Anthralin minute entire skin treatment. A new outpatient therapy for psoriasis

Anthralin minute entire skin treatment (AMEST) was developed to improve the efficacy and cosmetic results of anthralin short-contact therapy. In a split comparison study to determine the optimal period of anthralin application, ten minutes of anthralin contact time gave maximum antipsoriatic activity with minimal side effects. Dosimetry variables for AMEST were determined based on the patient's pigmentation type, the erythematous response, the therapeutic effect, and so on. Such treatment of 43 patients resulted in complete clearing in 31 patients (72%), with 90% improvement in two patients (5%) and less than 90% clearing in seven patients (16%). Psoriatic lesions disappeared, leaving no spotty pigmentation that is known to occur following conventional anthralin therapy. The dosimetry variables employed in our study allowed AMEST with minimal skin irritation. Laboratory values did not change significantly during therapy. In addition, AMEST does not involve systemic medication and is easy to perform without special equipment; therefore, it is economic and can be used for outpatients and probably for home treatment.     

Clobetasol propionate lotion in the treatment of moderate to severe plaque-type psoriasis

Owing to its anti-inflammatory, antipruritic, vasoconstrictive, and immune-modulating properties, clobetasol propionate is used to treat psoriasis. This study was conducted to evaluate the efficacy, safety, and cosmetic acceptability of clobetasol propionate lotion compared with its vehicle and with clobetasol propionate cream in the treatment of moderate to severe plaque-type psoriasis. A total of 222 patients were treated. After 4 weeks of treatment, clobetasol propionate lotion was more efficient than vehicle lotion and of equivalent efficacy as clobetasol propionate cream. Cosmetic acceptability was significantly better with clobetasol propionate lotion than with clobetasol propionate cream. Clobetasol propionate lotion was efficient, safe, and well tolerated and offers a significantly higher cosmetic advantage in the treatment of moderate to severe plaque-type psoriasis compared with clobetasol propionate cream.     

Oral R115866 in the treatment of moderate to severe plaque-type psoriasis

BACKGROUND: R115866 (Rambazole) is a new generation all-trans retinoic acid metabolism blocking agent, highly specific against the retinoic acid 4-hydroxylase. The drug alleviates hyperproliferation and normalizes differentiation of the epidermis in animal models of psoriasis. OBJECTIVE: To explore the efficacy, safety and tolerability of systemic R115866 in patients with moderate to severe plaque-type psoriasis. PATIENTS AND METHODS: In this open label, single-arm trial, patients were treated with R115866, 1 mg/day for 8 weeks, followed by a 2-week treatment-free follow-up period. Patients were monitored for efficacy and safety. RESULTS: Nineteen patients (intent-to-treat population) were treated and 14 completed the entire study. Two patients discontinued due to lack of efficacy and three due to adverse events. At the end of the treatment, 26% of the patients showed at least 50% reduction in Psoriasis Area Severity Index (PASI) compared to baseline. Further improvement was observed at the end of the 2-week follow-up period where 47% of the patients showed a 50% or greater reduction in PASI. Kinetic data showed no evidence of accumulation of either R115866 or retinoic acid in plasma. The most common adverse events were pruritus, xerosis, cheilitis and an increase in blood triglycerides. The majority of adverse events were mild to moderate. No deaths or serious adverse events were reported. CONCLUSION: Eight-week daily treatment with 1 mg R115866 resulted in a significant reduction in PASI from baseline to end of therapy. Additional improvement was seen after the 2-week follow-up period. The drug was well tolerated. R115866 merits further evaluation to optimize its clinical efficacy and safety profile in moderate to severe plaque-type psoriasis.     

Ustekinumab治疗中重度斑块状银屑病的系统评价

银屑病是一种慢性复发性炎症性皮肤病,在我国患病率约0.123％［１］,因其慢性、顽固难愈、复发率高,成为皮肤科领域重点研究防治的疾病之一。Ustekinumab在2009年获准治疗中重度斑块状银屑病,它可与人体白介素12/白介素23的p40亚单位结合,抑制其生物活性,达到治疗银屑病的作用［2］,但其疗效结论尚不统一,且缺乏长期有效性及安全性评价［3］。我们检索文献,对Ustekinumab治疗中重度斑块状银屑病的疗效和安全性进行系统评价……     

Nonmelanoma skin cancer associated with Hydroxyurea treatment: Overview of the literature and our own experience

Nonmelanoma skin cancer is the most common malignant tumor in the fair skin population, with each year several millions of diagnosed cases. Their most common risk factors are fair skin, a history of excessive ultraviolet light exposure, chronic inflammatory skin conditions, exposure to radiation, and contact with arsenic. Certain drugs can also be associated with a higher risk of nonmelanoma skin cancer. These include hydroxyurea, which acts as a metabolic inhibitor of ribonucleotide reductase and a potent nonalkylating myelosuppressive agent. It is used for the treatment of various myeloproliferative disorders, including chronic myeloid leukemia, polycythemia vera, and essential thrombocytopenia. Several publications describe an increased occurrence of skin manifestations following hydroxyurea treatment. A growing body of evidence indicates a possible role of hydroxyurea in skin cancer progression. In this review article, we summarize some relevant observations about the association of hydroxyurea and skin cancer, and we describe our own clinical experiences to provide up to date recommendations about the care of patients on hydroxyurea therapy.     

A new psoralen-containing gel for topical PUVA therapy: development,and treatment results in patients with palmoplantar and plaque-type psoriasis,and hyperkeratotic eczema

Summary Topical photochemotherapy with psoralen and its derivatives 4.5′,8-trimethylpsoralen (TMP) and 8-methoxypsoralen (8-MOP), with UVA irradiation, was evaluated with regard to minimum phototoxic dose, concentration, timing of UVA irradiation and systemic and local side-effects, in healthy volunteers. Psoralen (0.005%) in aqueous gel was found to be superior to TMP and 8-MOP in aqueous gel. No hyperpigmentation was seen after topical PUVA treatment with psoralen in aqueous gel. Patients with plaque-type psoriasis (n = 7), palmoplantar psoriasis (n = 7) and hyperkeratotic eczema (n = 2) were treated. Topical PUVA therapy was effective in most psoriasis patients, without the occurrence of local or systemic side-effects. Moreover, hyperkeratotic eczema patients who did not respond to conventional therapy showed partial remission. These results indicate that topical PUVA therapy with psoralen in aqueous gel is a useful therapeutic modality for treatment of psoriasis patients, and patients with recalcitrant dermatoses such as palmoplantar psoriasis and hyperkeratotic eczema.     

Methotrexate in psoriasis: 26 years' experience with low-dose long-term treatment.

OBJECTIVE: To evaluate the efficacy, safety and side-effects of methotrexate (MTX) in psoriasis. DESIGN: A 26-year retrospective study. SETTING: Department of Dermatology, Leipzig University, Leipzig, Germany. PATIENTS: One hundred and fifty-seven patients with extensive plaque psoriasis, erythrodermic, pustular and arthropathic forms, were treated with low-dose methotrexate (15-20 mg maximum weekly dosage [Weinstein schedule]), the majority for long-term periods. The mean cumulative dose was 3394 mg, the mean duration 237 weeks. RESULTS: The effect of MTX treatment was good in 76%, moderate in 18% and poor in 6% of subjects; 61% experienced side-effects, most frequently due to liver function abnormalities, bone marrow suppression, nausea, gastric complaints and hair loss. In 20% of cases the subjects were forced to discontinue therapy; 9% refused therapy due to physical and psychological discomfort, 2% wanted to become pregnant, 16% were lost to follow-up, 6% died from multimorbidity and old age. Three subjects (2%) developed cancer of the lung, breast or cervix uteri, possibly in relation to long-term MTX treatment. Altogether there were no deaths or life-threatening side-effects attributable to MTX treatment, and no cases of progressive liver cirrhosis apart from two extensive skin necroses due to overdosage (misunderstanding, suicidal attempt) that were treated successfully with citrovorum factor. CONCLUSION: Low-dose MTX (<15-20 mg/week) is an effective therapy for extensive and severe forms of psoriasis if patients are selected carefully and monitored regularly, particularly with respect to liver and bone marrow toxicity. This helps to reduce severe side-effects even during long-term treatment. Drug interactions must be avoided. MTX therapy according to the guidelines is relatively safe and still has a place in the systemic treatment of psoriasis with 40 years of experience and an acceptable safety record.     

Our experience with etanercept in the treatment of psoriasis

Psoriasis is a chronic inflammatory disorder that usually requires long-term control. Etanercept has been shown to be effective in this disease. The efficacy and safety of etanercept were assessed in patients with psoriasis. In this 16-week open clinical trial, 29 patients with clinically stable psoriasis and psoriatic arthritis received etanercept (25 mg twice weekly) subcutaneously. All patients were evaluated for the psoriasis area, severity index (PASI) and Ritchie's articular index (RAI) which measures arthritis disease activity. Improvement by 75 percent in PASI, considered significant for psoriasis remission, was observed in nearly sixty percent of patients after 12-week etanercept therapy. The percentage of PASI improvement was nearly 25% at two weeks, 52.3% at four weeks and 78% at 12 weeks of etanercept treatment, and was maintained for the next four weeks. Comparable results were obtained in the improvement of psoriatic arthritis symptoms, as improvement of 75 percent in RAI was observed in 58.3 percent of patients after 12 weeks of etanercept therapy. The percentage of RAI improvement was nearly 26% at two weeks, 40.5% at four weeks and 73.6% at 12 weeks and 77.1% at 16 weeks of etanercept treatment. Etanercept was generally well tolerated, as most events were of mild severity. The treatment with etanercept led to significant improvement in patients with psoriasis over a period of 16 weeks.     

Clinical experience with etanercept in the treatment of psoriasis

BackgroundEtanercept is one of the new biologic agents available for treating psoriasis. It has proved an effective option in a high percentage of patients, leading to sustained improvements in the psoriasis area severity index (PASI). Likewise, it is effective at controlling psoriatic arthritis, and its safety profile is excellent, with a much lower specific organ toxicity than traditional drugs and few side effects. Many of the data published to date are derived from clinical trials with this medication, but further studies are needed on the use of this therapy to manage patients in daily clinical practice.MethodsThis was a retrospective observational study of 36 patients with psoriasis who received etanercept between March 2004 and March 2006. We describe the experience of using this agent at our hospital, with the clinical outcomes and the problems we have faced.ResultsThe PASI score was assessed before treatment and at 3 and 6 months of patient follow-up. After 3 months of treatment, 13 patients (36.11 %) had achieved a 50 % improvement in PASI score (PASI₅₀), and 16 patients (44 %) had achieved a 75 % improvement (PASI₇₅). Two of the patients (5.56 %) experienced an improvement in their disease without reaching PASI₅₀ and only 4 patients (11.11 %) did not show clinical improvement or deteriorated. After 6 months, efficacy improved, with 27 patients (75 %) achieving PASI₇₅, 6 patients (16.67 %) achieving PASI₅₀, and 2 patients (5.56 %) showing no benefit from treatment. After 6 months, 13 of the patients (36.1 %) had achieved a 90 % improvement in PASI score. No adverse events of sufficient significance to warrant discontinuation of treatment were reported. At present, 11 of the patients remain on etanercept treatment as efficacy has been sustained and they have not experienced any adverse events of note.ConclusionsOur clinical experience with the use of etanercept for treating plaque psoriasis shows a favorable efficacy and safety profile. We propose a standardized procedure for consultations with psoriasis patients involving extensive data collection on each visit and the creation of a national surveillance system for patients under treatment with biologic agents.     

Pulsed dye laser vs. photodynamic therapy in the treatment of refractory nail psoriasis: a comparative pilot study

Background  Nail psoriasis is often refractory to traditional treatments, and patients with nail psoriasis usually demand a therapeutic option. Both photodynamic therapy (PDT) and pulse dye laser (PDL) have proved effective for plaque-type psoriasis, but they have not been evaluated in nail psoriasis. On the other hand, delta-aminolaevulinic acic has been shown to penetrate into the nail matrix and nail bed occluded with bioadhesive patches.
Objectives  To compare the efficacy of PDT and PDL in the treatment of nail psoriasis
Methods  We studied 61 nails treated with PDT and 60 nails treated with PDL in a group of 14 patients. The PDT used PDL as the light source. Sessions were applied monthly treating one hand with PDT and the other with PDL. The hand treated with PDT was occluded with methyl-aminolaevulinic acic (MAL, Metvix^®) for 3 h using a bioadhesive patch. The nails treated were evaluated at baseline, and after 3 and 6 months according to the Nail Psoriasis Severity Index (NAPSI) score.
Results  A decrease in NAPSI score was observed with both treatments and in both nail matrix and nail bed involvement. No statistical differences were found between PDT and PDL ( P =  0.632, P  = 0.084, P  = 0.535, at baseline, and 3 and 6 months, respectively), and between nail matrix and nail bed NAPSI scores ( P =  0.423 and P  = 0.853, respectively). The subjective impression of the patients was good, especially regarding the decrease in the pain.
Conclusions  PDL seems to be effective in the treatment of nail psoriasis and improves nail matrix and nail bed involvement. MAL does not seem to play role in the clinical response.

Conflicts of interest

None declared.     

Calcipotriol vs. tazarotene as combination therapy with narrowband ultraviolet B (311 nm): efficacy in patients with severe psoriasis

BACKGROUND: Phototherapy has been shown to be one of the most effective treatment modalities for patients with psoriasis. Nevertheless, photocombination therapies capable both of reducing cumulative ultraviolet (UV) doses and of accelerating clearance of skin lesions are important and of high interest. There have been no published studies comparing the effect of narrowband UVB irradiation in combination with topical application of tazarotene vs. calcipotriol. OBJECTIVES: To determine, in a half-side manner, whether a combination of UVB (311 nm) and tazarotene is superior to UVB (311 nm) plus calcipotriol or vice versa. METHODS: Ten patients suffering from widespread symmetrical psoriasis were treated for at least 4 weeks with topical calcipotriol and tazarotene in a half-side distribution. Additionally, the whole body was irradiated with narrowband UVB (311 nm) four times a week. Before treatment and once weekly during therapy a modified Psoriasis Area and Severity Index was estimated for each body half. The total treatment time, number of treatment sessions and cumulative UVB dose necessary for clearance of skin lesions were determined in an observer-blind fashion for each patient. Furthermore, all patients completed a quality of life questionnaire. RESULTS: Clearance of psoriasis was observed after a median of 19 treatment sessions (range 14-28) and a median cumulative UVB dose of 22.98 J cm-2 (range 9.24-58.22) simultaneously for both body halves. On the side treated with topical tazarotene gel, four patients complained of itching and dryness of the skin, and skin irritation was observed in three of them. Six patients preferred the application of tazarotene gel, while four preferred calcipotriol. CONCLUSIONS: Our clinical comparison of narrowband UVB with either topical calcipotriol or topical tazarotene revealed no significant therapeutic difference between both regimens. Although these results need to be confirmed in larger patient groups, we feel that both photocombination therapies can broaden the therapeutic options for moderate to severe psoriasis vulgaris and may reduce the cumulative UVB dose during therapy.     

Amcinonide vs. betamethasone dipropionate ointments in the treatment of psoriasis

A randomized, double-blind study compared the efficacy and safety of amcinonide and betamethasone dipropionate ointments, applied twice daily for two weeks, in the treatment of patients with moderate to severe psoriasis. Thirty-four patients were enrolled; thirty patients had had psoriasis for more than one year, and in the majority of patients, it was stable or slowly exacerbating. Significant improvement from baseline was observed with both ointments at weeks 1 and 2. The two drugs showed comparable cosmetic acceptability. Adverse cutaneous symptoms experienced were burning (both groups), itching (amcinonide), and stinging (beta-methasone); no serious adverse effects were reported.