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Unique keratinization process in psoriasis: late differentiation markers are abolished because of the premature cell death.

The keratinization process in psoriasis is a unique phenomenon. We have proposed an organized system for keratinization in psoriasis based on the recognition of early and late differentiation markers combined with premature cell death. The early differentiation markers, such as involucrin, small proline-rich proteins (SPRR), cystatin A and transglutaminase l, are more conspicuously expressed in psoriasis, while the late differentiation markers, such as profilaggrin and loricrin, are abolished. Keratinization markers that are not observed in the normal epidermis are also detected; these include SKALP/elafin as well as K6 and K16. With a markedly diminished turnover time, the psoriatic epidermis rapidly synthesizes differentiation markers that are mostly under the control of the protein kinase C-AP1 transcriptional control system. Because of the premature cell death, however, the late differentiation markers are not expressed. During the improvement of the lesion and the therefore longer turnover time, the late differentiation markers rapidly catch up to reveal their expression. This explains the rapid appearance of keratohyalin granules (profilaggrin) in the healing lesion of psoriasis. Thus the keratinization process in psoriasis can be explained by the accelerated keratinization combined with premature cell death. The keratinization process in psoriasis is unique, because both accelerated keratinization and premature cell death co-exist, resulting in the disappearance of late differentiation markers such as profilaggrin and loricrin. It is interesting to note that the premature cell death is also under the control of protein kinase C signaling.

Apoptosis↗

Leukotactic properties of soluble substances in psoriasis scale.

In an attempt to elucidate the mechanisms underlying the production of transepidermal migration of leukocytes toward the stratum corneum in psoriatic lesions, the chemotactic properties of soluble substances in psoriasis scales were examined by a modified Boyden's chamber. All crude extracts of horny tissues studied, i.e. callus, scales of exfoliative dermatitis and of psoriasis vulgaris, showed chemotactic activity for human peripheral blood leukocytes. But only the chemotactic activity of the psoriasis scale extract was highly potent. This was greatly reduced after dialysis. Fresh serum was not required to manifest the chemotactic activity. By Sephadex G-200 chromatography, the scale extracts from psoriasis vulgaris and pustular psoriasis had potent activity eluted near the cytochrome C marker. The same fractions of other horny tissue extracts, bacterial filtrate prepared from cultured psoriasis scale fragments, and serum did not show such potent activity. On the basis of analysis by gel filtration and recent findings of immunopathological studies, a postulate was made that a complement derived chemotactic factor, possibly a C5 cleavage product, developed as a result of antigen-antibody reaction in the stratum corneum of psoriatic lesions.

Aged↗

Cutaneous polyamines in psoriasis.

The polyamines putrescine, spermidine and spermine are intimately associated with cellular growth and division. Previous studies of the polyamines and their rate limiting biosynthetic enzyme, ornithine decarboxylase, in psoriasis have shown significant changes compared with non-psoriatic skin. We have further studied cutaneous polyamines in patients with psoriasis and in normal subjects, epidermal shave biopsies were taken and assayed for ornithine decarboxylase activity and polyamine levels. Psoriasis lesions showed increased ornithine decarboxylase activity compared with uninvolved skin. The levels of ornithine decarboxylase activity in uninvolved psoriasis skin were also higher than in normals. There was increased putrescine in involved psoriasis compared with uninvolved and normal skin. Spermidine and spermine were increased in psoriasis skin and in uninvolved skin and compared with normals. The spermidine/spermine ratio was greatest in involved skin compared with uninvolved and normal. These results confirm abnormal polyamine metabolism in both the involved and uninvolved skin of psoriatics.

Humans↗

Altered cell-mediated immunity to group A haemolytic streptococcal antigens in chronic plaque psoriasis.

The proliferative lymphocyte response to sonicated group A, beta-haemolytic streptococci (Strep-A) was measured by thymidine incorporation in 78 patients with psoriasis (guttate, chronic plaque or both). Lymphocytes from 72 of these patients were also cultured with streptokinase/streptodornase (SK/SD), and 20 of the patients with chronic plaque psoriasis were further tested with PPD, Candida albicans and sonicated Streptococcus mutans, a bacterial type not associated clinically with psoriasis. The median stimulation index (SI) of the psoriasis group to the Strep-A preparation was significantly higher than that of a group of 27 non-psoriatic individuals (P less than 0.05). Within this group, only the patients with chronic plaque psoriasis (n = 42) showed a significantly increased proliferative response compared to the non-psoriatic controls (median SI = 123.8 and 31.9, respectively, P less than 0.01). Although the lymphocyte response of the chronic plaque group to SK/SD was also markedly higher than that of the control group, this difference did not reach statistical significance. In addition, these patients did not show significantly increased responses to any of the other antigens tested, including S. mutans. No correlation was observed between the degree of proliferation to Strep-A and disease extent or activity. Similarly, ASO titres, which were raised in 11 out of 23 guttate and three out of nine chronic plaque psoriasis patients tested, did not correlate with the proliferative responses observed.

Adolescent↗

Psoriasis: an audit of patients' views on the disease and its treatment.

This audit aimed to establish the effect of out-patient clinic attendance on patients' attitudes to their psoriasis, its severity and its treatment. A secondary aim was to determine if there was any correlation between the patients subjective concept of disease severity and objective medical assessment. The audit was carried out by means of paired questionnaires completed by patients at their first visit to the out-patient clinic and at a review visit 3 months later. On each of these occasions an objective assessment of psoriasis severity score was made by the dermatologist. We were able to confirm previous reports of major psychosocial effects of psoriasis on the life-style of many patients. At their first visit 67% (30/45) of patients stated that their life-style was affected by psoriasis, while at review 3 months later this figure was 40% (18/45). Overall 76% (34/45) of patients felt their psoriasis had improved following attendance at the clinic, while 11% (5/45) of patients felt it had deteriorated over the 3-month period. However, all patients stated they found attendance at the out-patient clinic to be of benefit. There was a significant correlation between the psoriasis severity score by the patient and by the dermatologist (P less than 0.001).

Adolescent↗

Age at onset and different types of psoriasis.

The age at onset of psoriasis has been analysed for 11,366 psoriasis patients. The age at onset for siblings of probands has been analysed for 805 probands having one affected sibling and for 179 probands having two affected siblings. The age at onset curve for all probands shows a dominating maximum at about puberty but also indications for two more maxima at about 30 and 50 years of age, respectively. A more relevant picture of the risk of getting psoriasis at different ages is obtained if the onset for old people having psoriasis is investigated. The three maxima come out more clearly in this case, and the puberty maximum is not so dominating. For the families with one proband and two affected siblings there is a statistically significant correlation (P < 0.001) between the age at onset of the proband and of the siblings, and also between the siblings. The correlation coefficient is between 0.30 and 0.45. For the probands with one affected sibling, the ages at onset of the siblings mainly fall in the same range as those of the probands. These data indicate three groups of patients with respect to age at onset. However, the overlap between the different groups is considerable. The data presented are compatible with three, possibly genetically different, variants of psoriasis vulgaris. By studying the occurrence of psoriasis among parents of the probands, the gene frequency can be estimated assuming a recessive mode of inheritance. It then turns out that the gene frequency of the group with the earliest age at onset has a gene frequency of about 0.25, the next earliest, 0.18, and the latest, 0.14.

Adolescent↗

Leflunomide in the treatment of psoriasis: results of a phase II open trial.

BACKGROUND: Psoriasis is recognized as the most prevalent T-cell-mediated inflammatory disease in humans, with predominantly activated T-helper (Th) 1 cell effectors. Leflunomide exerts its anti-inflammatory activities by preventing the generation of proinflammatory Th1 effectors and promoting Th2 cell differentiation. OBJECTIVES: To determine the safety and efficacy of leflunomide in patients with moderate to severe plaque-type psoriasis. METHODS: In an open-label phase II trial, eight patients with psoriasis received oral leflunomide 20 mg daily for 12 weeks. Patients were evaluated for improvement in psoriasis, quality of life, histological changes and toxicity. RESULTS: Antipsoriatic effects were obtained in all but two patients. A significant decrease was observed in the mean +/- SD Psoriasis Area and Severity Index score, from 20.08 +/- 6.85 before treatment to 12.51 +/- 11.83 after (P = 0.03). The antipsoriatic efficiency was confirmed histologically, with a significant mean +/- SD decrease in epidermal thickness, from 0.73 +/- 0.19 micro m before to 0.31 +/- 0.16 microm after (P = 0.01). The quality of life score showed an improvement, from 8.58 +/- 2.38 (mean +/- SD) before to 5.33 +/- 1.95 after (P = 0.02). The treatment was well tolerated; adverse reactions primarily consisted of transitory gastrointestinal events. CONCLUSIONS: Our data suggest that leflunomide for plaque-type psoriasis is a safe and clinically effective option as monotherapy. However, double-blind, placebo-controlled studies are needed.

Adolescent↗

Genetic polymorphisms of the HCR gene and a genomic segment in close proximity to HLA-C are associated with patients with psoriasis in Taiwan.

BACKGROUND: Although psoriasis vulgaris (PV) is strongly associated with HLA-Cw*0602, it has been proposed that the association of Cw*0602 is due to linkage disequilibrium and that other nearby genes are involved in PV susceptibility. The alpha-helix coiled-coil rod homologue (HCR) gene, located 110 kb telomeric to the HLA-C locus, is presumed to be one of the PV candidate genes. Recently, a 10-kb genomic segment, centromeric to HLA-C, defined by two new single nucleotide polymorphisms (SNPs) n.7*A and n.9*C, was found to have a stronger association with psoriasis than the HCR gene. Until now, no study of the association of the HCR gene, SNPs n.7, and n.9 has been conducted on Chinese patients with psoriasis. OBJECTIVES: We aimed to determine whether the genetic polymorphisms of the HCR gene, SNPs n.7*A, and n.9*C were associated with an increased risk of psoriasis in Chinese patients. METHODS: Using direct sequencing of the HCR gene and the genomic region containing SNPs n.7 and n.9, we investigated the HCR gene, SNPs n.7, and n.9 for disease association in 115 Chinese patients with psoriasis and 103 control subjects. The HCR SNPs were confirmed by denaturing high performance liquid chromatography. Genotyping for HLA-Cw*0602 was also carried out using sequence-based typing. RESULTS: We observed a different allelic distribution between patient and control groups at nucleotide positions 386, 404, 1802 and 2406 of the HCR gene, and SNPs n.7, and n.9. The associations were much stronger in early onset PV patients (for HCR-386*T and HCR-404*T, odds ratio = 5.63, Pc < 0.0001). The HLA-Cw*0602 also displayed a similar association with PV (odds ratio = 5.4, Pc < 0.0001). Moreover, SNP n.7*A, SNP n.9*C, Cw*0602, HCR-386*T, HCR-404*T and HCR-1802*T were in linkage disequilibrium with each other. Haplotype-based association analysis showed SNP n.7*A-SNP n.9*C-Cw*0602-HCR-386*T-HCR-404*T-HCR-1802*T-HCR-2406*G as a major susceptibility haplotype in this Chinese population (for early onset patients, odds ratio = 5.15, Pc < 0.0001). CONCLUSIONS: Our results indicate that the HCR gene, SNP n.7*A, and SNP n.9*C as well as Cw*0602 are major susceptibility markers for psoriasis in Chinese patients.

Adolescent↗

Detection of psychological distress in patients with psoriasis: low consensus between dermatologist and patient.

BACKGROUND: Researchers have indicated that 30-40% of patients with psoriasis suffer significant psychological distress. For the appropriate clinical management of the patient with psoriasis it is important that dermatologists are able to recognize this distress. OBJECTIVES: To examine the level of agreement between dermatologists and patients with psoriasis as to the presence of clinically significant psychological distress. METHODS: Forty-three consultations between dermatologists and patients with psoriasis were assessed. Following the consultation two assessments were undertaken: the patients completed measures of anxiety and depression, and the consulting dermatologists recorded whether they believed the patient to be psychologically distressed and, if so, their subsequent action. At the end of the study, all dermatologists who participated completed the Jefferson Scale of Physician Empathy. RESULTS: Self-report questionnaires indicated that 37% and 12% of patients were identified as probable clinical cases for anxiety and depression, respectively. In general, the level of agreement between patient rating and dermatologist rating as to the presence of anxiety or depression was low (kappa statistic 0.24 and 0.26, respectively). Dermatologist empathy level did not appear to influence identification of distress. In only 39% of cases were the psychological difficulties of significantly distressed patients raised by dermatologists during the consultation. CONCLUSIONS: Agreement between dermatologists and patients with psoriasis regarding the presence of clinically significant psychological distress was low. When dermatologists did identify patients as being anxious and/or depressed, in the majority of cases no further action was taken following the consultation. This study highlights a number of areas for improvement in the psychological management of patients with psoriasis.

Adult↗

Dual wavelength (532 and 633 nm) laser Doppler imaging of plaque psoriasis.

BACKGROUND: Increased blood flow occurs in plaques of psoriasis, and an increase in blood flow has been shown to occur in uninvolved skin adjacent to the active edge. OBJECTIVES: In order to gain more insight into the pathophysiology of the active edges of plaques of psoriasis, we investigated different components of the microcirculation in the lesional and nonlesional skin of patients with psoriasis, using dual wavelength laser Doppler imaging (LDI). METHODS: The cutaneous blood flow in 23 plaques on the forearms of 20 patients with chronic plaque psoriasis was recorded using dual wavelength LDI. Perfusion was determined within the plaque (P), in uninvolved skin adjacent to the plaque (A) and in nonadjacent skin (U). RESULTS: Perfusion in plaques was increased as imaged by either 633 nm (red wavelength) or 532 nm (green wavelength) compared with both adjacent and nonadjacent uninvolved skin: median (interquartile range) P/A(RED) = 3.7 (2.5-4.9), P/A(GREEN) = 1.3 (1.2-1.6), P/U(RED) = 4.2 (2.7-6.1), P/U(GREEN) = 1.5 (1.3-1.9). CONCLUSIONS: Vascular perfusion is increased within plaques of psoriasis compared with adjacent and nonadjacent uninvolved skin. The results suggest an area of increased perfusion in skin adjacent to plaques, when compared with nonadjacent skin, for both deeper (large) and superficial (small) vessels (imaged by 633 and 532 nm, respectively). We believe that this dual wavelength tool may be a suitable and useful way of assessing pathophysiology and treatment response in psoriasis.

Adolescent↗

Psoriasis in Norway as observed in a population-based Norwegian twin panel.

BACKGROUND: Psoriasis is a chronic T-cell-mediated immunological skin disease. The occurrence of the disease appears to differ with geography and ethnicity. There is a need for epidemiological data obtained from defined population-based studies, and the sex-specific differences observed in the natural history of the disease require more attention. OBJECTIVES: To describe the occurrence and risk of psoriasis in Norway by age and sex. PATIENTS/METHODS: A population-based health survey was conducted in 1998 in Norwegian twins aged 19-31 years. The present study is based upon the self-reported history of psoriasis among the 8045 questionnaire responders. RESULTS: Altogether, 334 (4.2%) reported a positive history of psoriasis. There were no sex differences in the overall prevalence rates, but significantly higher point-prevalences emerged in females in the teenage-year intervals. A fairly linear increase in incidence rates by every 4-year age-interval peaked at a lower age in females. The mean age at onset was also significantly lower in females (14.8 years) than in males (17.3 years). The absolute risk of developing psoriasis appeared higher for females across the entire age range. However, by the age of 31 the cumulative risks were similar in females and males (0.056 and 0.053, respectively). CONCLUSIONS: In this historical cohort of Norwegian twins, we find a high prevalence of psoriasis in congruence with previously reported data among whites in north-western Europe. We have found sex-specific characteristics in point-prevalences and incidence rates which may contribute to the understanding of the earlier age at onset of the disease in females.

Adult↗

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.

Abdominal Pain↗

Fumaric acid esters for severe psoriasis: a retrospective review of 58 cases.

BACKGROUND: Fumaric acid esters (FAE) have been used to treat severe psoriasis in northern Europe for over 20 years. A recent systematic review has shown FAE to be an effective systemic treatment for severe psoriasis. However, FAE remain unlicensed in the U.K. OBJECTIVES: To present data relating to the efficacy and tolerability of FAE in severe psoriasis and report our experiences of FAE therapy at one U.K. centre. METHODS: Patients who had received FAE for severe psoriasis at one U.K. regional referral centre between June 1999 and October 2003 were identified from pharmacy records. Their records were analysed retrospectively. RESULTS: Fifty-eight patients (25 women, 33 men) were identified. Fifty-five (95%) of the 58 patients had previously used other systemic antipsoriatic therapies with over 70% previously using two or more agents. Thirty-two patients (55%) showed improvement in their psoriasis with 10 (17%) being rated as 'clear' or 'virtually clear' by the attending physician. No improvement was seen in 28% patients and 16% showed worsening of their disease. Adverse events were common and were reported in 66% patients. These mainly consisted of abdominal pain (61%), diarrhoea (55%), flushing (45%), nausea (21%) and malaise (15%). They led to discontinuation of treatment in 15 patients after a mean period of 4.7 months. Lymphocytopenia developed during treatment in 57% of patients, all of whom had had a baseline value within the normal range. In only one patient was this considered severe enough to warrant withdrawal of treatment. CONCLUSIONS: Our study has shown that FAE are an effective therapy in selected patients with severe psoriasis, even in those who have previously been intolerant of systemic therapy or where it has failed.

Adolescent↗

Controlled study of excimer and pulsed dye lasers in the treatment of psoriasis.

BACKGROUND AND OBJECTIVES: The excimer laser delivers high energy monochromatic ultraviolet (UV) B at 308 nm. Advantages over conventional UV sources include targeting of lesional skin, reducing cumulative dose and inducing faster clearance. Studies of the pulsed dye laser (PDL) in psoriasis report between 57% and 82% response rates; remission may extend to 15 months. To our knowledge, this is the first study assessing both excimer and PDL in psoriasis. METHODS: We conducted a within-patient controlled prospective trial of treatment of localized plaque psoriasis. Twenty-two adult patients, mean Psoriasis Area and Severity Index 7.1, were recruited. Fifteen patients completed the full treatment, of which 13 were followed up to 1 year. Two selected plaques were treated with excimer twice weekly and V Beam PDL, pretreated with salicylic acid (SA), every 4 weeks, respectively. Two additional plaques, treated with SA alone or untreated, served as controls. The primary outcome measures were: (i) changes in plaque-modified Psoriasis Activity and Severity Index (PSI) scores from baseline to end of treatment; (ii) clinical response to treatment (CR(T)), assessed by serial photographs; (iii) percentage of plaques clear at the end of treatment; and (iv) percentage of plaques clear at 1-year follow-up. The secondary outcome measures were: (i) number of laser treatments to clearance; (ii) time to relapse; (iii) frequency of side-effects; and (iv) qualitative observations with SIAscope. RESULTS: The mean improvement in PSI was 4.7 (SD 2.1) with excimer and 2.7 (SD 2.4) with PDL. PSI improvement was significantly greater in excimer than PDL (P = 0.003) or both control plaques (P < 0.001). CR(T) indicated 13 patients responded best with excimer, two patients best with PDL, and in seven patients there was no difference between the two lasers. CR(T) was significantly greater for excimer than PDL (P = 0.003) or both controls (P < 0.001). CR(T) was also significantly greater for PDL than SA alone (P = 0.004) or untreated control (P =0.002). Nine (41%) patients cleared with excimer, after mean 8.7, median 10 weeks treatment. Seven of these nine patients were followed up to 1 year; four remained clear, two relapsed at 1 month, and one at 6 months. Six (27%) patients cleared with PDL, after mean 3.3, median four treatments. All six patients were followed up to 1 year; four remained clear, one relapsed at 4 months and one at 9 months. Despite common side-effects including blistering and hyperpigmentation, patient satisfaction was high. Serial images obtained with the SIAscope during treatment indicated different mechanisms of action of the two lasers. CONCLUSIONS: Excimer and V Beam PDL are useful treatments for plaque psoriasis. Although the excimer appears to be on average more efficacious, a subset of patients may respond better to PDL. Long-term remission is achievable with both lasers.

Adult↗

Psychological factors in prurigo nodularis in comparison with psoriasis vulgaris: results of a case-control study.

BACKGROUND: It has been suggested that psychological factors such as repressing anger and altruistic interpersonal behaviour may play a role in the aetiology of chronic itching in prurigo nodularis (PN). Whether these issues are specific for PN or are also common in other chronic skin diseases, e.g. psoriasis, has not been investigated until now. OBJECTIVES: To investigate psychosomatic problem areas and psychiatric comorbidity in patients with PN in comparison with patients with psoriasis. METHODS: Ninety-four patients with PN and 91 patients with psoriasis were administered the Hospital Anxiety and Depression Scale, Toronto Alexithymia Scale, State-Trait Anger Expression Inventory, Inventory of Interpersonal Problems, Screening for Somatoform Disorders and the Whiteley Index for hypochondriasis. RESULTS: After Bonferroni post hoc adjustment, the metrical scales demonstrated no significant differences between patients with PN and those with psoriasis. There was only a tendency to less 'anger-out' and to less autocratic/dominant and more insecure/submissive behaviour in the patients with PN. Patients with PN were, in general, comparable with those with psoriasis with regard to alexithymia, somatization symptoms, hypochondriasis, anxiety and depression, with 18% cases of anxiety and 22% cases of depression. CONCLUSIONS: The hypotheses formulated in the literature on the specific aetiology of PN could not be proven for the majority of patients with PN in our study. Concerning their psychopathology, patients with PN were comparable with those with psoriasis. Therefore the clinical management of PN should include psychosomatic assessment.

Adult↗

How does psoriasis affect quality of life? Assessing an Ingram-regimen outpatient programme and validating the WHOQOL-100.

UNLABELLED: BACKGROUND, OBJECTIVES AND METHODS: This paper reports a longitudinal study of the quality of life (QOL) of outpatients receiving treatment for psoriasis in secondary care that was designed to validate a new QOL measure for use in psoriasis: the WHOQOL-100. Additional aims were to monitor the changes to the QOL of psoriasis patients (n = 83) following a course of topical treatment--a modified Ingram regimen--and to compare their QOL with healthy people (n = 105). RESULTS: General QOL was much improved following treatment; psychological facets of body image and appearance, self-esteem and negative feelings were particularly responsive to clinical change, in addition to positive feelings and cognitive capacity. Domains on spirituality, independence and physical health also improved. Compared with healthy controls, pretreatment psoriasis patients showed poorer physical, psychological, independence and spiritual QOL. Validity and reliability were investigated and found to be good to excellent. Internal consistency was very good in 23 facets out of 25. Domains and facets were strongly correlated (weaker for spirituality) largely reaffirming the WHOQOL concept. While physical, independence and psychological domains have some components similar to the Short Form-36, the social and environment domains represent novel conceptual areas for the WHOQOL. Facets about positive and negative feelings were validated by results from the Profile of Mood States. Psoriasis severity was associated with QOL in only six facets out of 25. CONCLUSIONS: The WHOQOL-100 is reliable and valid, and hence a new and important measure for assessing quality of life in psoriasis.

Adolescent↗

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.

Adult↗

HLA Cw*06 is not essential for streptococcal-induced psoriasis.

BACKGROUND: Streptococcal throat infections and HLA Cw6 (Cw*06) have been implicated in the pathogenesis of psoriasis, particularly in the guttate form. OBJECTIVES: To study 105 Irish patients with psoriasis to investigate the relationship between streptococcal infections and Cw*06. METHODS: The patients were divided into two groups: those with guttate psoriasis or guttate flare (guttate group, GG, n=64) and those with chronic plaque psoriasis (chronic plaque group, CPG, n=41). RESULTS: The incidence of Cw*06 was 86% in the GG and 73% in the CPG, which was not significantly different (P=0.1725) but the incidence in both groups was significantly higher than in an Irish control group (18%) (P<0.0001 vs. GG and P<0.0001 vs. CPG). Evidence for streptococcal infection was higher in the GG (56%) than in the CPG (32%) (P=0.0231). Of those patients with evidence of streptococcal infection, 30 of 36 GG (83%) and nine of 13 CPG (69%) patients possessed the Cw*06 genotype. CONCLUSIONS: Thus, not all patients with streptococcal-related psoriasis carry Cw*06. The role of Cw*06 in psoriasis, if any, has yet to be determined.

Adolescent↗