Chronic Stable Plaque Psoriasis Research Articles

Comparative evaluation of efficacy and safety of calcipotriol versus calcitriol ointment, both in combination with narrow-band ultraviolet B phototherapy in the treatment of stable plaque psoriasis.

Vitamin D analogues and NBUVB are both well-recognised modes of therapy in the treatment of chronic stable plaque psoriasis. The objective of this open label intraindividual, left right study was to compare two different vitamin D analogues, calcipotriol and calcitriol, in combination with NBUVB phototherapy in psoriasis. Thirty patients with stable plaque psoriasis were enrolled for a 12-week clinical trial. The target lesion on the left side was treated topically with calcitriol ointment, while that on the right side was treated with calcipotriol ointment once daily. The whole body was irradiated with narrow-band ultraviolet B phototherapy (NBUVB) three times per week. Efficacy was assessed by target plaque scoring. Both therapies resulted in a statistically significant reduction in erythema, scaling, thickness, and target plaque score, seen as early as 2 weeks into therapy. However, the calcipotriol combination led to an earlier clearance of plaques and a lesser relapse rate than the calcitriol combination. The number of treatment sessions and cumulative NBUVB doses were significantly lower in the calcipotriol-treated group. Both vitamin D analogues appear to be safe, effective, and cosmetically acceptable, with calcipotriol being more efficacious, well tolerated, with a rapid onset of action and a better maintenance of response.

Clinical implications of intermittent Ramadan fasting on stable plaque psoriasis: a prospective observational study.

IntroductionPsoriasis is a chronic immune-mediated inflammatory disease. Environmental factors including diet have been supposed to play a role in its pathogenesis. Fasting in Ramadan consists of intermittent fasting in which participating Muslims refrain from eating and drinking from dawn up to sunset.AimTo validate the possible clinical consequences of Ramadan fasting for patients with psoriasis.Material and methodsThe study was conducted in Ramadan 2019. It included patients over 18 years who were diagnosed with stable chronic plaque psoriasis. PASI and BSA scores, body mass index and biochemical tests (including blood lipids, fasting blood glucose) were compared before and after a month of Ramadan fasting.ResultsThe study included 121 psoriasis patients. The mean PASI score was 4.36 ±3.22 at the beginning of the study, which was reduced to 3.51 ±1.26 at the end of the study. The difference was statistically significant (p = 0.001). There was no difference in the change of weight. We found a statistically significant difference in fasting plasma glucose, HDL and triglycerides. Only mild adverse events were noted during the study period.ConclusionsRamadan intermittent fasting has beneficial effects on severity of the disease in psoriasis patients with a reduction in PASI score and no serious health hazards. Thus, Ramadan intermittent fasting could be considered during treatment of psoriasis patients.

Comparative Effectiveness and Safety of Methotrexate Versus PUVA in Severe Chronic Stable Plaque Psoriasis

Background:Psoriasis is a chronic, inflammatory, immune-mediated, debilitating skin disease affecting approximately 2%–3% of the global population. Various treatment modalities are available for extensive psoriasis which include methotrexate, cyclosporine, retinoids, oral PUVA therapy, and biologic agents.Aims and Objectives:The aim of this study was to compare the effectiveness and safety of methotrexate vs. PUVA in severe chronic plaque psoriasis with BSA >20%.Materials and Methods:A randomized open-label clinical study was performed. Sixty patients with extensive stable plaque psoriasis were recruited in the study. Thirty patients received methotrexate at a dose of 0.4 mg/kg up to a maximum of 15 mg/week and the rest 30 were treated by PUVA, 8-methoxy psoralen tablet (20 mg) followed by UVA started at the dose of 1 j/cm2 thrice weekly with an increment of 20% dose every third sitting until 2.5 j/cm2 is reached. Both forms of treatment were continued for 10 weeks or until PASI 90 achieved, which-ever was earlier. Clinical examination, blood investigation, PASI scoring, and photograph were repeated in serial intervals during the study. At the end of study, the data were compiled, tabulated, and analyzed.Result:In the PUVA group, 90% achieved PASI-50 and 63.33% achieved PASI-90, in the methotrexate group all patients achieved both PASI-50 and PASI-90. Methotrexate acted significantly faster than PUVA in disease clearance. In the methotrexate group decreased platelet count in 13.33% patients, decreased hemoglobin (<10 gm/dl), elevated liver enzyme, each of these developed in 10% of patients. In the PUVA group, no serious side effects were observed.Conclusions:Methotrexate is more efficacious with lesser incidence of subjective complications and more incidence of laboratory complications compared to PUVA in extensive plaque psoriasis.

AGGRESSIVE WEIGHT LOSS PROGRAM WITH A KETOGENIC INDUCTION PHASE FOR THE TREATMENT OF CHRONIC PLAQUE PSORIASIS

Chronic plaque psoriasis is an inflammatory skin disease associated with obesity,characterized by low-grade inflammation. Weight loss (WL) has been demonstrated to reduce psoriasis severity and inflammation. Very low-calorie ketogenic diet (VLCKD) has been associated with a significant reduction in visceral adipose tissue and keton bodies likely have anti-inflammatory proprieties. We evaluate the efficacy of an aggressive WL program with a ketogenic induction phase as first-line treatment of chronic plaque psoriasis. We conducted a single-arm trial conducted (NCT03531528). Adult overweight/obese patients (N=37)with stable chronic plaque psoriasis underwent a 10-week two-phase WL program consisting in a 4-week protein-sparing, VLCKD (<500 kcal/day; 1.2 grams of protein/kg of ideal body weight/day) and a 6-week balanced, hypocaloric (25-30 kcal/kg of ideal body weight/day), low glycemic index, Mediterranean-like diet. The primary endpoint was the reduction in the Psoriasis Area and Severity Index (PASI) at week 10. Major secondary endpoints included:improvement of PASI 50% and 75%,reduction in body surface area (BSA) involved,improvement of itch severity (visual-analogue scale) and Dermatology Life Quality Index (DLQI) at week 10. With a mean body weight reduction of 12.0%,dietary intervention resulted in a significant reduction in PASI: mean change, -10.6 [95%CI, -12.8 to -8.4] (P<0.001). A reduction in PASI 50% and 75% was recorded in 36 (97.3%) and 24 (64.9%) patients, respectively. Treatment resulted also in a significant reduction of BSA involved and an improvement in itch severity and DLQI (P<0.001 for all). In adult overweight patients with stable chronic plaque psoriasis an aggressive dietary WL program consisting in a ketogenic regimen followed by a balanced, hypocaloric Mediterranean-like diet appeared an efficacious first-line strategy for improving disease severity. Comparative studies with other dietary regimens and long-term efficacy data are warranted.

Genotoxic changes in peripheral lymphocytes after therapeutic exposure to crude coal tar and ultraviolet radiation

Goeckerman therapy is based on combined exposure to UV radiation (UVA, UVB) and crude coal tar (PAHs). Some indicators suggest a genotoxic hazard, however, the level of genotoxic risk of the therapy has not yet been investigated sufficiently. This study aims to assesss the genotoxic risk. The studied group consisted of patients with chronic stable plaque psoriasis treated by Goeckerman therapy (n = 29). Heparin-treated peripheral blood samples were collected one day before the first treatment and immediately after the last procedure. The lymphocytes were isolated from the blood. The level of genotoxicity was evaluated using an alkaline version of the Comet assay which detects DNA single strand breaks (DNA-SSBs), a neutral version of the Comet assay which detects DNA double strand breaks (DNA-DSBs), and using chromosomal aberrations. The level of DNA-SSBs increased insignificantly (median; Q1-Q3): 1.4 (0.4; 0.1-1.4) vs. 2.5 (0.6; 0.3-2.7) %tDNA (P = 0.11) and the level of DNA-DSBs increased significantly: 7.8 (6.5; 3.4-10.5) vs. 20.7 (19.3; 14.2-24.6) % DNA (P < 0.001). The total number of aberrated cells (P < 0.001) and structurally aberrated cells (P < 0.001) increased significantly. The elevated levels of the DNA-DSBs and the chromosomal aberrations in the peripheral lymphocytes indicated a genotoxic hazard. However, the elevated level of the chromosomal abnormalities was below the upper level of the reference range for healthy Czech adults. While, the genotoxic risk appears to be low, Goeckerman treatment represents a further contribution to the lifetime load of genotoxic factors.

Genetic polymorphisms in biotransformation enzymes for benzo[a]pyrene and related levels of benzo[a]pyrene-7,8-diol-9,10-epoxide-DNA adducts in Goeckerman therapy.

Goeckerman therapy (GT) for psoriasis combines the therapeutic effect of crude coal tar (CCT) and ultraviolet radiation (UVR). CCT contains polycyclic aromatic hydrocarbons, some of which can form DNA adducts that may induce mutations and contribute to carcinogenesis. The aim of our work was to evaluate the relationship between concentrations of benzo[a]pyrene-7,8-diol-9,10-epoxide-DNA adducts (BPDE-DNA adducts) and rs4646903 (CYP1A1 gene), rs1048943 (CYP1A1), rs1056836 (CYP1B1), rs1051740 (EPHX1), rs2234922 (EPHX1) and rs8175347 (UGT1A1) polymorphic sites, and GSTM1 null polymorphism in 46 patients with chronic stable plaque psoriasis who underwent GT. The level of BPDE-DNA adducts was determined using the OxiSelect BPDE-DNA Adduct ELISA Kit. Polymerase chain reaction (PCR) and restriction fragment length polymorphism analysis (rs4646903, rs1048943, rs1051740, and rs2234922), fragment analysis (rs8175347), real-time PCR (rs1056836), and digital droplet PCR polymorphism (GSTM1) were used. CYP1B1*1/*1 wild-type subjects and CYP1B1*3/*1 heterozygotes for rs1056836 formed significantly higher amounts of BPDE-DNA adducts than CYP1B1*3/*3 homozygotes (p=0.031 and p=0.005, respectively). Regarding rs1051740, individuals with EPHX1*3/*1 heterozygosity revealed fewer adducts than EPHX1*1/*1 wild-type subjects (p=0.026). Our data suggest that CYP1B1/EPHX1 genotyping could help to predict the risk of DNA damage and to optimize doses of coal tar and UVR exposure in psoriatic patients in whom GT was applied.

Influence of dermal exposure to ultraviolet radiation and coal tar (polycyclic aromatic hydrocarbons) on the skin aging process

BackgroundUltraviolet radiation (UVR) and crude coal tar (CCT) containing PAHs can accelerate the skin-aging process (SAP). However, UVR induces the formation of an important protective factor in SAP (vitamin D). ObjectiveTo determine the relation of SAP to selected risks and benefits of combined dermal exposure to UVR and coal tar (PAHs). MethodsThe study group consisted of patients with chronic stable plaque psoriasis and treated by Goeckerman therapy (GT; daily dermal application of UVR and 5% CCT ointment). The levels of urinary 1-hydroxypyrene (1-OHP), oxidative stress (DNA and RNA damage), genotoxic damage (chromosomal aberration in peripheral lymphocytes; ABC), 25-hydroxy-vitamin D [25(OH)D] and the PASI score were evaluated before and after GT. ResultsIntensive dermal absorption of PAHs was confirmed by increased levels of 1-OHP (p<0.01). After the therapy, we found an increased level of oxidative stress (p<0.05), an increased level of genotoxic damage (ABC; p<0.001), a high efficiency of the treatment (p<0.001) and an elevated production of 25(OH)D (p<0.01). We also found a relationship between the duration of UVR and the genotoxic damage (p<0.01), vitD (p<0.05) and the PASI score (p<0.05). Furthermore, we found a relationship between oxidative stress and 25(OH)D (p<0.05) and between genotoxic damage and the PASI score (p<0.05). ConclusionDermal exposure to UVR and coal tar (PAHs) enhances the level of oxidative stress and genotoxic damage and thus contributes to SAP. However, the exposure is very effective as a treatment and elevates the production of 25(OH)D, the protective factor in SAP. According to our results, UVR is probably a more hazardous factor in SAP.

Tofacitinib versus etanercept or placebo in moderate-to-severe chronic plaque psoriasis: a phase 3 randomised non-inferiority trial

New therapeutic options are needed for patients with psoriasis. Tofacitinib, an oral Janus kinase inhibitor, is being investigated as a treatment for moderate-to-severe chronic plaque psoriasis. In this study, we aimed to compare two tofacitinib doses with high-dose etanercept or placebo in this patient population. In this phase 3, randomised, multicentre, double-dummy, placebo-controlled, 12-week, non-inferiority trial, adult patients with chronic stable plaque psoriasis (for ≥12 months) who were candidates for systemic or phototherapy and had a Psoriasis Area and Severity Index (PASI) score of 12 or higher and a Physician's Global Assessment (PGA) of moderate or severe, and had failed to respond to, had a contraindication to, or were intolerant to at least one conventional systemic therapy, were enrolled from 122 investigational dermatology centres worldwide. Eligible patients were randomly assigned in a 3:3:3:1 ratio to receive tofacitinib 5 mg or 10 mg twice daily at about 12 h intervals, etanercept 50 mg subcutaneously twice weekly at about 3-4 day intervals, or placebo. Randomisation was done by a computer-generated randomisation schedule, and all patients and study personnel were masked to treatment assignment. The co-primary endpoints were the proportion of patients at week 12 with at least a 75% reduction in the PASI score from baseline (PASI75 response) and the proportion of patients achieving a PGA score of "clear" or "almost clear" (PGA response), analysed in the full analysis set (all patients who were randomised and received at least one dose of study drug). This study is registered with ClinicalTrials.gov, number NCT01241591. Between Nov 29, 2010, and Sept 13, 2012, we enrolled 1106 eligible adult patients with chronic plaque psoriasis and randomly assigned them to the four treatment groups (330 to tofacitinib 5 mg twice daily, 332 to tofacitinib 10 mg twice daily, 336 to etanercept 50 mg twice weekly, and 108 to placebo). Of these patients, 1101 actually received their assigned study medication (329 in the tofactinib 5 mg group, 330 in the tofacitinib 10 mg group, 335 in the etanercept group, and 107 in the placebo group). At week 12, PASI75 responses were recorded in 130 (39·5%) of 329 patients in the tofacitinib 5 mg group, 210 (63·6%) of 330 in the tofacitinib 10 mg group, 197 (58·8%) of 335 in the etanercept group, and six (5·6%) of 107 in the placebo group. A PGA response was achieved by 155 (47·1%) of 329 patients in the tofacitinib 5 mg group, 225 (68·2%) of 330 in the tofacitinib 10 mg group, 222 (66·3%) of 335 in the etanercept group, and 16 (15·0%) of 107 in the placebo group. The rate of adverse events was similar across the four groups, with serious adverse events occurring in seven (2%) of 329 patients in the tofacitinib 5 mg group, five (2%) of 330 in the tofacitinib 10 mg group, seven (2%) of 335 in the etanercept group, and two (2%) of 107 in the placebo group. Three (1%) of 329 patients in the tofacitinib 5 mg group, ten (3%) of 330 in the tofacitinib 10 mg group, 11 (3%) of 335 in the etanercept group, and four (4%) of 107 patients in the placebo group discontinued their assigned treatment because of adverse events. In patients with moderate-to-severe plaque psoriasis, the 10 mg twice daily dose of tofacitinib was non-inferior to etanercept 50 mg twice weekly and was superior to placebo, but the 5 mg twice daily dose did not show non-inferiority to etanercept 50 mg twice weekly. The adverse event rates over 12 weeks were similar for tofacitinib and etanercept. This study indicates that in the future tofacitinib could provide a convenient and well-tolerated therapeutic option for patients with moderate-to-severe plaque psoriasis. Pfizer Inc.

Alcohol Intake Measured by Phosphatidylethanol in Blood and the Lifetime Drinking History Interview Are Correlated with the Extent of Psoriasis

Background: Psoriasis has been reported to be associated with alcohol consumption. Objective: To investigate the level of alcohol intake in individuals with psoriasis and correlate intake with the extent of disease and pruritus. Methods: Twenty-nine outpatients (15 females and 14 males) with stable chronic plaque psoriasis of moderate severity were recruited. The Psoriasis Area and Severity Index (PASI) and the degree of pruritus (visual analogue scale) were compared with measures of drinking habits as determined by the Lifetime Drinking History (LDH), the Alcohol Use Disorders Identification Test and whole-blood phosphatidylethanol (PEth), an alcohol-specific biomarker. Results: The majority of patients were social drinkers with moderate alcohol consumption as determined by PEth and LDH. Alcohol consumption correlated significantly with the PASI score. There was no correlation between alcohol use and pruritus. Conclusion: The level of alcohol consumption is correlated with the extent of psoriasis.

Heterogeneity of Inflammatory and Cytokine Networks in Chronic Plaque Psoriasis

The clinical features of psoriasis, characterized by sharply demarcated scaly erythematous plaques, are typically so distinctive that a diagnosis can easily be made on these grounds alone. However, there is great variability in treatment response between individual patients, and this may reflect heterogeneity of inflammatory networks driving the disease. In this study, whole-genome transcriptional profiling was used to characterize inflammatory and cytokine networks in 62 lesional skin samples obtained from patients with stable chronic plaque psoriasis. We were able to stratify lesions according to their inflammatory gene expression signatures, identifying those associated with strong (37% of patients), moderate (39%) and weak inflammatory infiltrates (24%). Additionally, we identified differences in cytokine signatures with heightened cytokine-response patterns in one sub-group of lesions (IL-13-strong; 50%) and attenuation of these patterns in a second sub-group (IL-13-weak; 50%). These sub-groups correlated with the composition of the inflammatory infiltrate, but were only weakly associated with increased risk allele frequency at some psoriasis susceptibility loci (e.g., REL, TRAF3IP2 and NOS2). Our findings highlight variable points in the inflammatory and cytokine networks known to drive chronic plaque psoriasis. Such heterogeneous aspects may shape clinical course and treatment responses, and can provide avenues for development of personalized treatments.

Psoriasis among Sarawakian natives in a tertiary skin centre in Sarawak

A prospective cross-sectional study was done between December 2007 and June 2009 in the skin clinic, Sarawak General Hospital, to determine the clinical characteristics of 138 Sarawakian natives with a clinical diagnosis of psoriasis. Women made up 50.7% and the mean age of the patients was 45.2 years. Of the group, 94.2% had chronic stable plaque psoriasis, 86.9% had a body surface area involvement of less than 10%, 60.9% had nail disease, 22.5% had joint disease and 55.1% had minimal effects to their quality of life because of their psoriasis.

Topical tazarotene vs. coal tar in stable plaque psoriasis

The efficacy of topical tazarotene has not previously been compared with the conventional topical treatment of crude coal tar (CCT) in stable plaque psoriasis. To assess the comparative efficacy and tolerability of topical tazarotene 0.1% gel and CCT 5% ointment in stable plaque psoriasis. In this nonblinded side-to-side comparison study, patients with chronic stable plaque psoriasis, who had bilaterally symmetrical plaques on the limbs, applied 0.1% tazarotene gel on the right side and 5% CCT ointment on the left side once daily for 12 weeks followed by an 8-week treatment-free follow up period. Severity of psoriatic lesions and response to treatment was evaluated by scoring erythema, scaling and induration (ESI). Of 30 patients recruited, 27 could be assessed. In the per-protocol analysis, the mean percentage reduction in ESI score at the end of the treatment period was 74.15% +/- 9.43 and 77.37% +/- 10.93 with tazarotene and CCT, respectively (P > 0.05). A reduction in ESI score of > 75% was seen in 11 (40.74%) and 16 (59.26%) patients with tazarotene and CCT, respectively, at the end of 12 weeks. Side-effects were seen in 48.14% of patients treated with tazarotene, but in no patient treated with CCT. Tazarotene 0.1% gel has comparable clinical efficacy to CCT 5% ointment. CCT ointment remains a cost-effective therapy for plaque psoriasis.

Rapid onset bilateral palmar keratoderma in a psoriasis patient wearing orthopaedic hand splints

A 37-year-old man with a history of chronic stable plaque psoriasis fractured both hands during a fall on his outstretched hands. Ten days later, following surgery and the application of tight fitting orthopaedic hand splints, the splints were removed because of a 7-day history of painful and pruritic palms. It was evident that the injury to his hands and the firm application of his splints had resulted in a dramatic flare of his psoriasis. This manifested in two clinical forms that he had not developed previously. He had a strikingly symmetrical palmar keratoderma that had köbnerized maximally in the regions where the splints apposed his palms firmly. In addition, he had pustular psoriasis affecting the fingertips of both hands. After removal of the splints he responded to a combination of oral acitretin, and 6% coal tar and 6% salicylic acid in aqueous cream applied topically.

Remission and relapse of chronic plaque psoriasis treated once a week with clobetasol propionate occluded with a hydrocolloid dressing versus twice daily treatment with clobetasol propionate alone

BACKGROUND: Many studies have shown the clinical efficiency of occlusion therapy for psoriasis, particularly corticosteroids used under hydrocolloid dressings. However, there are no data from comparative clinical studies evaluating the remission and relapse characteristics of such occlusion therapy compared with orthodox topical steroid monotherapy. METHODS: In a randomised, open-label, parallel group study from three centres, the remission and relapse characteristics were investigated for the use of a hydrocolloid dressing (HCD) over clobetasol propionate 0.05% lotion once a week compared with the same steroid in ointment formulation used unoccluded twice a day in 61 patients with stable chronic plaque psoriasis. RESULTS: There was a pronounced treatment difference in favour of the HCD + clobetasol propionate lotion group with respect to time to clearance, but there was little evidence for a difference with respect to time to relapse. CONCLUSION: The combination of the HCD + clobetasol propionate lotion provides a fast and highly effective remission induction.

Occurrence of Hepoxilins and Trioxilins in Psoriatic Lesions

We recently found that normal human epidermis produces relatively high amounts of hepoxilins and trioxilins in vitro. Therefore, the aim of this study was to demonstrate the presence of these compounds in psoriatic lesions. Extracts from scales of patients with chronic stable plaque psoriasis were analyzed by a combination of high performance liquid chromatography and gas chromatography-mass spectrometry techniques. We found that the levels of hepoxilin B3 were more than 16-fold higher in psoriatic scales than in normal epidermis (3.2+/-2.3 and < 0.2 ng per mg, respectively), whereas hepoxilin A3 was not detected in any sample. Trioxilins were semiquantitated and referred to 12-hydroxyeicosatetraenoic acid, ratios of trioxilins A3 and B3 12-hydroxyeicosatetraenoic acid in psoriatic lesions were 0.65+/-0.23 and 0.32+/-0.28, respectively, and they were not detected in normal epidermis. The presence of a great amount of trioxilin A3 strongly suggests that hepoxilin A3 was present in psoriatic lesions and it was totally degraded to trioxilin A3 during the analysis procedure. Our results demonstrate that hepoxilins and trioxilins are produced by human skin in vivo and that the levels of these compounds are increased in psoriasis. The reported biologic activities of hepoxilins indicate that they could amplify and maintain the inflammatory response. Our results reinforce the idea that these compounds could play a role as mediators in the inflammatory response in skin, particularly in psoriasis.

New drugs in pediatric dermatology.

A number of important therapeutic agents have recently become available for the treatment of infectious and inflammatory skin diseases. Five of these drugs, calcipotriol, EMLA (eutectic mixture of local anesthetics), interferon-alpha 2a, cyclosporine, and acyclovir, are reviewed. Calcipotriol, a vitamin D analogue, has been shown to be useful but not curative in chronic stable plaque psoriasis in adults. Its use in children is being studied. EMLA is proving to be useful in the prevention of pain prior to minor procedures. The use of interferon-alpha 2a promises to be highly effective in the treatment of the complications of vascular lesions. Cyclosporine is a powerful immunomodulating agent. It has been used in the treatment of atopic dermatitis and psoriasis. Adverse effects limit its widespread use as a systemic agent. Topical cyclosporine has limited efficacy due to its poor penetration. Acyclovir has revolutionized the treatment of herpes simplex virus infections, particularly in reducing the morbidity and mortality of neonatal herpes. Whether it is indicated in varicella infection in normal children is questionable.

The effect of combined fish oil and evening primrose oil (Efamol Marine) on the remission phase of psoriasis: A 7-month double-blind randomized placebo-controlled trial

A total of 51 patients with chronic stable plaque psoriasis extensive enough to warrant hospital admission were entered in a double-blind placebo-controlled trial. They were treated with conventional tar and dithranol, and at the same time randomly allocated to receive either 12 × 500 mg capsules of combined fish oil and evening primrose oil (Efamol Marine) or 12 capsules of placebo (liquid paraffin) daily to ascertain whether their remission period could be prolonged. They were assessed 1, 4 and 7 months after discharge. Of the 51 patients, 37 completed 4 months and 23 completed 7 months. All patients improved substantially during hospitalization, and this improvement continued until 1 month after discharge, but then diminished. No significant difference was noted in the rate of deterioration between those patients on Efamol Marine and those on placebo.

Enzymatic quantification of polymorphonuclear leucocytes in normal and psoriatic skin following standardized injury.

Summary The intra-epidermal accumulation of polymorphonuclear leucocytes (PMN) following sellotape stripping of psoriatic non-lesional skin and normal skin of healthy individuals has been quantified with the elastase assay. Far more PMN accumulated in the skin in unstable psoriasis than in stable psoriasis. No significant difference was found, however, in PMN accumulation between the psoriatics as a whole and the controls. PMN accumulation was followed by the induction of an elastase inhibitor in psoriatic patients and controls. No significant differences could be found in inhibitory activity between controls and psoriatics. Our results suggest that the degree of PMN accumulation following surface trauma is essentially normal in stable chronic plaque psoriasis, but increases in unstable phases of the disease.

The in vitro 5-lipoxygenase and cyclo-oxygenase inhibitor L-652,343 does not inhibit 5-lipoxygenase in vivo in human skin.

1 3-hydroxy-5-trifluoromethyl-N-[2-(2-thienyl)-2-phenyl-ethenyl]-benzo(B) thiophene-2-carboxamide (L-652,343) is a 5-lipoxygenase and cyclo-oxygenase inhibitor in vitro. 2 In psoriasis increased concentrations of arachidonic acid transformation products are found in the lesional skin which may be important in the pathogenesis of the disease. We have measured the effect of orally administered L-652,343 on the concentration of LTB4 and prostaglandins in the lesional skin. 3 Eight patients with stable chronic plaque psoriasis received 500 and 250 mg of L-652,343, 12 h apart. A chamber technique was used to collect skin exudate samples from abraded plaques before and at 4, 24 and 48 h after the first dose. Exudates were analysed for LTB4 by a neutrophil chemokinesis assay and for PGE2 and PGD2 by RIA. 4 PGE2 and PGD2 levels were significantly reduced at 4 and 24 h after the first dose of L-652,343 but LTB4 levels were not affected indicating inhibition of the cyclo-oxygenase pathway but not of the 5-lipoxygenase pathway. This shows the importance of confirming that the action of 5-lipoxygenase inhibiting drugs in vitro occurs in vivo.

Leukotriene B4 fails to induce penetration of polymorphonuclear leukocytes into psoriatic lesions.

The intraepidermal accumulation of polymorphonuclear leukocytes following the epicutaneous application of leukotriene B4 (LTB4) was studied in lesional and clinically uninvolved skin of five patients with chronic stable plaque psoriasis. The lesions were found to be wholly unresponsive to LTB4, doses of 100 ng failing to produce either micropustules or exocytosis. This phenomenon was sharply localized; the response immediately adjacent to the lesion being identical to that in more distant uninvolved skin. We speculate that both the reduced response to LTB4 in the psoriatic patient and also the tolerance to LTB4 seen after repeated applications, result from the induction of a P450-linked hydroxylase.