EFFECT OF RETINOIC ACID IN PSORIASIS, II

Summary.— Clinical and histological features and mitotic counts have been studied in the lesions of 11 patients with psoriasis who were treated with topically applied retinoic acid ointment for a period of 3 months.
Serial biopsies were taken at monthly intervals from treated lesions in all 11 patients and from lesions treated with the unmedicated ointment base in 9.
There was no significant difference between treated and placebo groups regarding any of the parameters studied. Irritant effects of the retinoic acid were prominent in 7 patients.
The significance of these results is discussed in the light of the known mechanism of action of retinoic acid.     

RETINOIC ACID IN THE TREATMENT OF PSORIASIS

Summary.— Thirty-three patients with psoriasis applied retinoic acid ointment and betamethasone 17-valerate ointment to lesions on I side of their body, and a placebo ointment and identical betamethasone 17-valerate ointment to symmetrical lesions on the opposite side. Objective assessment of the treated areas showed a significant superiority of the retinoic acid and steroid over the placebo and steroid combination. The mode of action of retinoic acid in psoriasis is discussed.     

维A酸受体mRNA在寻常性银屑病外周血单一核细胞中表达水平的研究

目的　探讨寻常性银屑病患者外周血单一核细胞中维A酸受体 (RARα、RARγ、RXRα)mRNA的表达情况。方法　用RT PCR法对比研究了 2 0例寻常性银屑病患者和 10例正常对照组外周血单一核细胞中维A酸受体mRNA表达情况。结果　寻常性银屑病患者外周血单一核细胞中的维A酸受体mRNA的表达水平与正常对照组无差异。结论　用维A酸治疗寻常性银屑病过程中 ,免疫细胞是否为维A酸的作用靶细胞还不能确定。     

The therapeutic value of retinoic acid in chronic discoid, acute guttate, and erythrodermic psoriasis: clinical observations on twenty-five patients

Twenty-five patients with chronic discoid, acute guttate or erythrodermic psoriasis were treated with retinoic acid in various preparations, topical and oral, and the clinical response was observed for up to 3 months. Only four patients showed distinct clinical improvement. The possible side effects of topical retinoic acid therapy are mentioned.     

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.     

Ⅰ型转谷酰胺酶在银屑病皮损中的检测

目的 应用免疫组化技术原位检测型转谷酰胺酶在正常人及银屑病患者皮损内的分布,以期对本病角朊细胞的异常增殖有进一步的了解。方法 取银屑病患者遮盖部位皮损与正常人同部位皮肤作冰冻切片,以鼠抗人型转谷酰胺酶单克隆抗体为一抗,过氧化物酶标记的羊抗鼠抗体为二抗,AEC为反应底物。结果 正常人阳性区仅见于表皮角朊细胞颗粒层细胞间。银屑病皮损分布于除基底层外的表皮全层,着色程度以颗粒层最强,向棘层扩散但强度渐弱。与正常对照有显著性差异(P<0.01)。结论 型转谷酰胺酶在银屑病皮损中过早、过度表达。维A酸对该酶表达的抑制可能是其治疗银屑病的可能机理之一。     

Severe psoriasis--oral therapy with a new retinoid.

Ro 10-9359 is a retinoic acid derivative, selected for study because of a better tolerance than retinoic acid, shown in animal experiments. Doses of 25 mg b.i.d., 25 mg t.i.d. and 50 mg b.i.d. were administered orally to 27 patients suffering from severe chronic generalized psoriasis. The clinical efficacy was evaluated by means of a new index, psoriasis area and severity index (PASI) based on severity and area of psoriatic lesions. At doses of 25 mg t.i.d. or 50 mg b.i.d. Ro 10--9359 proved to be an extremely potent antipsoriatic drug. A more than 90% reduction of psoriatic lesions could be seen in 10 patients out of 20 after 4-8 weeks of treatment. This good effect lasted about 5 weeks after treatment. Side effects were frequent, but mostly mild and completely reversible after termination of treatment.     

The prevalence, aetiological agents and therapy of onychomycosis in patients with psoriasis: a prospective controlled trial

BACKGROUND: Nail involvement morphologically resembling onychomycosis frequently accompanies psoriatic lesions. The role of psoriasis as a predisposing factor for onychomycosis and the possible influence of psoriasis on responsiveness of onychomycosis to treatment are controversial. AIM: To investigate the frequency of onychomycosis, the aetiological agents responsible for it, and the efficacy of terbinafine 250 mg/day in patients with psoriasis compared with controls in order to reveal the role of psoriatic process on fungal growth. METHODS: Over a 1-year period, 168 patients with psoriasis and 164 nonpsoriatic controls were recruited. In the case of clinically suspected of fungal infection, further mycological investigations were performed. Systemic terbinafine therapy 250 mg daily for 12 weeks was administered to the patients with onychomycosis. Patients were followed up clinically and mycologically for 24 weeks. RESULTS: Onychomycosis was diagnosed in 22 patients with psoriasis (13.1% of the psoriasis group, which constituted 28.6% of patients with suspicion of onychomycosis) and 13 controls (7.9% of control group; 40.6% of controls with suspicion of onychomycosis). The prevalence rates of onychomycosis were similar in both groups. The most commonly isolated fungi were dermatophytes in the psoriasis group and nondermatophytic moulds in controls. Dermatophytes were more common in psoriatic than control nails (P = 0.02). All patients in each group were cured at the end of the therapy. CONCLUSION: It seems that nail psoriasis constitutes a risk factor not for onychomycosis, but specifically for dermatophytic nail infections. Because of the similar therapeutic results in each group, different antifungal treatment protocols may not be needed in psoriasis. However, to confirm this, new comprehensive studies are necessary.     

EFFECT OF PLASTIC OCCLUSIVE DRESSINGS ON PSORIATIC EPIDERMIS

SUMMARY.— Serial biopsies have been performed on psoriatic lesions from the forearm in 13 patients in whom the lesions were occluded with plastic occlusive dressings for 2 weeks, and in 13 control psoriatic subjects.
A complete granular layer was not present in the occluded or control lesions prior td the study. In the occluded lesions a complete layer developed in 25 of the subsequent 65 biopsies but in only 2 of the 65 biopsies in the control group. In 10 of the 13 subjects the occluded lesions showed a complete granular layer at some stage during occlusion, although the time when it first appeared was variable. In 4 of these 10 patients the granular layer became incomplete after reformation during the period of study.
Mitotic counts of the occluded psoriatic lesions showed a slight but significant fall at the end of the 2-week period but this did not occur in the control lesions. There was no significant depression of the mitotic count at the time when the granular layer first reformed.
It is suggested that plastic occlusive dressings have some effect on psoriasis, and possible mechanisms of action are discussed.     

Oral treatment of pustulosis palmo-plantaris with a new retinoid, Ro 10-9359.

Ro 10-9359 is a retinoic acid derivative, selected for study because of a better tolerance than retinoic acid, shown in animal experiments. Earlier clinical experience has proved Ro 10-9359 to be an extremely potent antipsoriatic drug. The well-known association between psoriasis and pustulosis palmoplantaris was a motivation to evaluate Ro 10-9359 also in the last-mentioned disease, which is notoriously known to be resistant to treatment. In this study 30 patients were given either 75 mg/day of Ro 10-9359 or 200 mg twice every week according to a randomized pattern. All patients had suffered from the disease for at least 2 years without any spontaneous remission during the year preceding the trial. After a treatment period of about 2 weeks with Ro 10-9359 hyperkeratotic scales had usually disappeared, and 2 weeks later there were in general significantly less pustular lesions. The treatment continued for 8 weeks, and at this time the average reduction of the number of pustules was 80%. The daily dosage seemed to give better results and was also better tolerated than was the twice-weekly dosage. Side effects were common, but generally mild. On average, the remission lasted 1 month after cessation of therapy.     

Long-term treatment of severe nodulo-cystic acne with 13-cis retinoic acid

15 patients with severe nodulo-cystic acne were treated with 13-cis retinoic acid (Ro 4-3780) for 6 to 12 months. The initial dose was 40 mg/day in all the cases. In 14 out of 15 cases this dose was progressively reduced depending on improvement of the acne lesions and on the occurrence of side effects. In one case the initial dose was later increased to 60 mg/day because of lack of response to the treatment. A 75 p. 100 improvement in the severity of the acne lesions was achieved within 4 to 5 months. Complete disappearance of the lesions was achieved in most of the patients after between 6 and 12 months of treatment. The most frequent clinical side effects were dryness of the lips, cheilitis with rhagades and facial dermatitis. Abnormal increased values of hepatic enzymes and triglycerides were found in some patients.     

Tazarotene cream in the treatment of psoriasis: Two multicenter,double-blind,randomized, vehicle-controlled studies of the safety and efficacy of tazarotene creams 0.05% and 0.1% applied once daily for 12 weeks

BACKGROUND: Tazarotene in a gel formulation is widely used in the treatment of psoriasis. OBJECTIVE: To determine the efficacy and safety of tazarotene 0.1% and 0.05% creams in the treatment of psoriasis. METHODS: A total of 1303 patients participated in 2 clinical trials. Patients applied tazarotene creams 0.1% and 0.05% or vehicle once daily to all psoriatic lesions for 12 weeks followed by a 12-week posttreatment period. RESULTS: Both creams were significantly more effective than vehicle on the basis of an overall assessment of psoriasis, a global response to treatment, and reduction in plaque elevation and scaling. Therapeutic effect was maintained during the posttreatment period. Common adverse events included signs and symptoms of skin irritation. CONCLUSION: Tazarotene creams were associated with significant reductions in the severity of the clinical signs of psoriasis and were found to be safe with acceptable tolerability. Tazarotene cream 0.1% was generally more effective, although slightly less well tolerated, than the 0.05% cream.     

The effects of oral liarozole on epidermal proliferation and differentiation in severe plaque psoriasis are comparable with those of acitretin

The imidazole derivative liarozole is a potent inhibitor of cytochrome P450-dependent 4-hydroxyla-tion of endogenous all- trans retinoic acid, thereby increasing the levels of all- trans retinoic acid in both plasma and skin. As part of a large, double-blind, randomized clinical study, we investigated the cell biological alterations in uninvolved and lesional skin of 20 patients with severe plaque psoriasis, who were treated with either liarozole or acitretin. The extent and severity of the skin lesions, as recorded by the Psoriasis Area and Severity Index score, was significantly reduced ( P 005) after 12 weeks of treatment in both the acitretin- and the liarozole-treated group. A significant decrease in the markers for inflammation (neutrophils), epidermal proliferation (Ki-67-positive cells), normal differentiation (transglutaminase) and abnormal differentiation [cytokeratin 16 and skin-derived antileucoproteinase (SKALP), also known as elafin] was seen in both groups. No significant differences were noted in clinical scores or cell biological scores between the liarozole- and acitretin-treated group. None of the markers returned to the levels seen in uninvolved skin or in normal human skin. The expression of epidermal fatty acid binding protein (E-FABP) was only minimally decreased after 12 weeks of treatment, a substantial part of the stratum spinosum remaining positive. SKALP levels in serum fell in both groups with similar kinetics and showed a statistically significant correlation with clinical scores. A remarkable finding in the uninvolved skin of patients treated with liarozole or acitretin was the distinct focal expression of SKALP in the granular layer and the expression of E-FABP in the spinous layers, which is not found in normal human skin. Although the mechanism of action differs fundamentally, liarozole and acitretin show similar effects with respect to clinical effects and cell biological changes in the lesional and non-lesional skin.     

寻常性银屑病患者维甲酸受体α内含子碱基突变

目的　分析银屑病患者维甲酸受体外显子附近的内含子碱基序列 ,寻找寻常性银屑病患者基底细胞维甲酸受体低表达的原因。方法　选取对维甲酸有不同反应性的寻常性银屑病患者有核细胞 ,提取其DNA ,通过聚合酶链反应扩增维甲酸受体α(RARα)的外显子序列 ,对扩增产物进行序列分析。结果　与已报告的维甲酸受体碱基序列相比 ,第七内含子第 17位碱基存在差异 ,出现T→G改变 ,而第 18位和第 5 5位出现碱基T的缺失 ,但选取的寻常性银屑病患者间未发现彼此间内显子碱基序列存在差异。结论　寻常性银屑病患者维甲酸受体α第七内含子碱基序列发生突变 ,由于目前对第七内含子的功能知之甚少 ,还不能确定其在维甲酸受体表达中具体的作用 ,但从目前对内含子的研究结果推测其可能与维甲酸受体的表达有关。     

A comparison of dapsone with 13-cis retinoic acid in the treatment of nodular cystic acne

Forty male patients with nodular/cystic acne were randomly allocated to receive either 100mg dapsone daily, or 40 mg 13-cis retinoic acid, daily for a period of 16 weeks. The following parameters were assessed during Treatment and for a follow-up period of 20 weeks: lesion counts (pustules, nodules and cysts), photographic evaluation, patient visual analogue scale, sebum excretion rate and skin surface microflora. Seventeen patients from each group completed the study. Only marginal clinical benefit was observed with dapsone, which produced no significant effect either on sebum excretion rate, or on skin surface microflora. By contrast, patients on 13-cis retinoic acid showed significant reductions in sebum excretion rate and skin surface microflora, which were maximal at 16 weeks (P < 0.001 and P < 0.01, respectively), and significant improvements in all clinical parameters which were maintained at follow-up 5 months later. We conclude that dapsone is clearly inferior to 13-cis retinoic acid in the treatment of nodular cystic acne.     

10例寻常型银屑病合并大疱性类天疱疮临床分析

目的：总结寻常型银屑病合并大疱性类天疱疮患者的临床特征及治疗方法。方法：回顾性分析2016年1月至2018年12月我院住院患者中诊断为寻常型银屑病合并大疱性类天疱疮的临床资料。结果：共发现10例寻常型银屑病合并大疱性类天疱疮患者,其中男9例,女1例,平均年龄为（59.90±10.18）岁,银屑病均先于大疱性类天疱疮发病。8例患者水疱发生于银屑病斑块上,2例水疱发生于外观正常的皮肤上。9例患者采用糖皮质激素和/或免疫抑制剂治疗,1例患者应用口服四环素、烟酰胺配合光疗治疗。出院后随访150~1065天,7例患者无新发水疱,银屑病皮损病情稳定;2例失访,1例死亡。结论：寻常型银屑病合并大疱性类天疱疮临床相对少见,中老年患者居多,糖皮质激素联合免疫抑制剂治疗有效。     

Topical treatment of cutaneous lesions of acquired immunodeficiency syndrome-related Kaposi sarcoma using alitretinoin gel: results of phase 1 and 2 trials

OBJECTIVE: To evaluate the efficacy and safety of topical alitretinoin gel (9-cis-retinoic acid [LGD1057], Panretin gel; Ligand Pharmaceuticals, Inc, San Diego, Calif) in cutaneous Kaposi sarcoma (KS). DESIGN: Open-label, within-patient, controlled, dose-escalating phase 1 and 2 clinical trials. In all patients, 1 or more cutaneous KS lesions were treated with alitretinoin gel, and at least 2 other lesions served as untreated controls for up to 16 weeks. Alitretinoin (0.05% or 0.1% gel) was applied twice daily for the first 2 weeks and up to 4 times daily thereafter, if tolerated. SETTING: Nine academic clinical centers. PATIENTS: One hundred fifteen patients with biopsy-proven acquired immunodeficiency syndrome (AIDS)-related KS. MAIN OUTCOME MEASURES: AIDS Clinical Trials Group response criteria. RESULTS: Statistically significant clinical responses were observed in 31 (27%) of 115 patients for the group of treated index lesions compared with 13 (11%) for the group of untreated control lesions (P<.001). Responses occurred with low CD4(+) lymphocyte counts (<200 cells/microL) and in some patients with refractory response to previous systemic anti-KS therapy. The incidence of disease progression was significantly lower for treated index lesions compared with untreated control lesions (39/115 [34%] vs 53/115 [46%]; P =.02). Alitretinoin gel generally was well tolerated, with 90% of treatment-related adverse events confined to the application site and only mild or moderate in severity. CONCLUSIONS: Alitretinoin gel has significant antitumor activity as a topical treatment for AIDS-related KS lesions, substantially reduces the incidence of disease progression in treated lesions, and is generally well tolerated.     

寻常性银屑病患者外周血和皮损中Th17细胞及相关因子的表达

目的 探讨寻常性银屑病患者外周血和皮损中Th17细胞及相关因子IL-17、IL-22表达,分析其与疾病严重程度及病程的相关性。方法 抽取44例寻常性银屑病患者和28例正常人对照者外周血,用三色法流式细胞仪检测外周血Th17细胞,ELISA法检测血清中IL-17、IL-22表达。取20例寻常性银屑病患者皮损和8例正常人对照者皮肤,用量子点免疫荧光双标法检测Th17细胞表达。结果 寻常性银屑病患者外周血Th17细胞百分比（4.71% ± 2.55%）高于正常人对照组（0.55% ± 0.39%）,两组差异有统计学意义（P < 0.01）。银屑病患者Th17细胞与银屑病病情严重度评分（PASI）呈显著正相关（r = 0.53,P < 0.01）,但与病程无相关性（r = 0.09,P > 0.05）。银屑病患者血清中IL-17（24.02 ± 12.31 ng/L）、IL-22（18.32 ± 8.14 ng/L）表达均高于正常人对照组（IL-17为7.16 ± 4.04 ng/L,IL-22为6.52 ± 4.15 ng/L）,差异均有统计学意义（P < 0.01和 < 0.05）。银屑病患者血清IL-17、IL-22表达与PASI呈显著正相关（r = 0.47,P < 0.01;r = 0.53,P < 0.01）,与病程无相关性（r = 0.03,P > 0.05;r = 0.19,P > 0.05）。银屑病患者皮损中可见Th17细胞浸润,主要集中在真皮浅层血管周围;而正常人皮肤中仅有微量CD4+ T细胞表达,未见Th17细胞。 结论 Th17细胞参与银屑病的发病,提示阻断相关因子IL-17、IL-22的药物可成为治疗银屑病的又一新靶点。     

Effect of propylthiouracil on adenosine deaminase activity and thyroid function in patients with psoriasis

BACKGROUND: T-cell activation has been implicated in the pathogenesis of psoriasis; adenosine deaminase (ADA) activity has been considered as a marker of T-cell activation. The antithyroid drug propylthiouracil (PTU) has recently been shown to have beneficial effects on psoriatic lesions, probably by acting on the immune system. OBJECTIVES: To investigate whether ADA activity may be related to psoriasis and whether oral PTU affects ADA activity and gives clinical improvement in psoriatic patients. METHODS: ADA activities were measured in plasma, erythrocyte and tissue samples of patients with psoriasis before and after 2 months of treatment with either PTU 100 mg three times daily or PTU plus thyroxine 25 microg once daily (to prevent possible hypothyroidism, which may be induced by PTU) as well as in healthy controls. The severity of the disease was evaluated before and after treatment according to Psoriasis Area and Severity Index (PASI) scores. Routine analyses and thyroid function tests were also carried out during the study. RESULTS: All patients showed significant clinical improvement in their lesions and decreased PASI scores after the treatments. Elevated baseline ADA activities in skin and plasma were found to be lower, and decreased baseline erythrocyte ADA was higher, after the treatments in all patients, and they were not different from control values. Although thyroid function tests were not affected by the treatments, serum thyroid-stimulating hormone levels were found to be higher after the treatments, and there was a larger increase in patients treated with PTU alone. However, none of the patients had clinical hypothyroidism or cytopenia. CONCLUSIONS: ADA activity may be clinically useful for indicating T-cell activation in psoriasis. Because of its antiproliferative and immunomodulatory effects, antioxidant potential and low toxicity, PTU may be an effective agent in the treatment of psoriasis.     

Topical 8-methoxypsoralen increases the efficacy of narrowband ultraviolet B in psoriasis

Background: A combination of oral psoralen with narrowband ultraviolet B (UVB), defined as 'psoralen-narrowband UVB', was shown to have a superior efficacy than UVB alone and even a comparable efficacy to psoralen and ultraviolet A in psoriasis.
Objective: To find out whether topical psoralen-narrowband UVB provides any additional benefit to narrowband UVB alone in psoriasis.
Methods: Nineteen patients with plaque psoriasis were included. Phototherapy was given three times per week. Two symmetrical lesions were selected as target lesions. In the first 12 sessions of phototherapy, the target lesion on one side was treated with 1% 8-methoxypsoralen (MOP) gel 30 min before UVB radiation whereas the target lesion on the other side served as a control. Target lesion scores were assessed at baseline, third, sixth, ninth and 12th sessions. Side effects were recorded.
Results: Sixteen patients completed the study. Target lesion scores decreased significantly on both sides ( P <0.0001). The mean percentage of decreases was greater on the 8-MOP-applied sides compared with the control sides for all assessments, but the difference was statistically significant only at the ninth session (37.7% vs. 58.6%, P =0.043). Pigmentation was frequently seen in 8-MOP gel-applied lesions.
Conclusion: Topical 8-MOP gel plus narrowband UVB has greater efficacy than narrowband UVB alone in psoriasis.