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Pedal dermatophyte infection in psoriasis.

BACKGROUND: Dermatophyte infections have been considered rare in psoriasis. However, there are data indicating that tinea unguium is as common or even more common in psoriasis compared with healthy controls. Tinea unguium is generally a secondary event to tinea pedis infection. OBJECTIVES: To study the prevalence of tinea pedis and tinea unguium in psoriasis compared with a control group. METHODS: Consecutive psoriasis outpatients aged 18-64 years attending a department of dermatology were examined. Samples for direct microscopy and culture were taken from the interdigital spaces, soles and toenails. Consecutive patients without signs of psoriasis or atopic dermatitis seeking examination of moles constituted the control group. RESULTS: In total, 239 patients with psoriasis and 245 control patients were studied. The prevalence of tinea pedis was 8.8%[95% confidence interval (CI) +/- 3.6%] in the psoriasis group and 7.8% (95% CI +/- 3.4%) in the control group. The corresponding figures for prevalence of tinea unguium were 4.6% (95% CI +/- 2.7%) and 2.4% (95% CI +/- 1.9%), respectively. The differences found in the psoriasis vs. the control groups were not statistically significant. CONCLUSIONS: This study does not support the hypothesis that the prevalence of tinea pedis and tinea unguium in patients with psoriasis differs from that in a normal population.

Adolescent↗

Activation of dendritic antigen-presenting cells expressing common heat shock protein receptor CD91 during induction of psoriasis.

BACKGROUND: Psoriasis is a common and chronic relapsing inflammatory skin disorder. Although a role for T cells in mediating the induction and maintenance of psoriatic lesions is well established, mechanisms responsible for activation of T cells by antigen-presenting cells (APCs) during disease relapse are poorly understood. OBJECTIVES: (i) To determine whether expression of the common heat shock protein (HSP) receptor CD91 correlated with development of psoriasis in a mouse model of psoriasis, (ii) to characterize the lesional cells on which CD91 was expressed, and (iii) to investigate whether CD91+ cells in psoriasis showed signs of activation. METHODS: Two systems were used in order to study the above-mentioned objectives: (i) skin biopsies taken directly from patients with psoriasis (either psoriatic plaques or symptomless prepsoriatic skin) or from healthy donors, respectively, or (ii) (human) skin biopsies collected during development of psoriasis using a novel xenograft mouse model of psoriasis. The skin samples were then either processed for analysis by light microscopy, or labelled with fluorochrome-conjugated antibodies and analysed by confocal laser scanning microscopy. RESULTS: We observed a markedly increased number of CD91+ cells which paralleled development of new psoriatic lesions in the psoriasis mouse model and in established psoriatic plaques compared with symptomless prepsoriatic or healthy skin. Morphology as well as cell-specific markers showed that CD91 was predominantly expressed by dermal dendritic APCs characterized by activation of nuclear factor-kappaB signalling and the presence of tumour necrosis factor-alpha, an important proinflammatory cytokine in the immunopathogenesis of psoriasis. In addition, HSP70, a ligand for CD91, was increased in keratinocytes in close vicinity to CD91-bearing APCs in psoriatic lesions. CONCLUSIONS: These findings indicate massive presence of CD91+ dendritic cells juxtaposed to lesional keratinocytes expressing HSP70, and suggest a novel pathophysiological pathway and therapeutic target for this chronic inflammatory skin disease.

Animals↗

Increased expression of the natural killer cell inhibitory receptor CD94/NKG2A and CD158b on circulating and lesional T cells in patients with chronic plaque psoriasis.

BACKGROUND: Psoriasis is a common inflammatory cutaneous disorder characterized by activated T-cell infiltration. T lymphocytes bearing natural killer cell receptors (NKRs) have been suggested to play an important role in the pathogenesis of psoriasis. However, the expression pattern of activating and inhibitory NKRs on T lymphocytes from psoriatic patients and its significance in psoriasis needs further study. OBJECTIVES: To investigate the pathogenesis of NKR-expressing T cells in psoriasis. MATERIALS AND METHODS: Thirty patients with chronic plaque psoriasis and 20 healthy controls were enrolled in this study. The immunophenotypic profiles of NKRs, including CD56, CD16 (activating NKRs), CD158a, CD158b, CD94 and NKG2A (inhibitory NKRs), were analysed in peripheral blood T lymphocytes, as well as psoriatic lesional infiltrating T cells, by triple-fluorescence flow cytometry. RESULTS: A significant increase of inhibitory CD8+ CD158b+, CD4 CD8 CD158b+ and CD8+ CD94/NKG2A+ T cells was found in the peripheral blood of patients with psoriasis when compared with controls. Tissue-infiltrating T lymphocytes expressing inhibitory receptors CD158b, CD94 and NKG2A were found in psoriatic lesions. There was a significant positive correlation between the increased percentage of circulating CD8+ CD94/NKG2A+ T cells and the Psoriasis Area and Severity Index. CONCLUSIONS: In the present study, we demonstrated increased proportions of particular subsets of inhibitory CD158b+ and/or CD94/NKG2A+ T cells in patients with psoriasis. The elevation of these inhibitory NKR-expressing T cells was correlated with disease severity, which may signify the possibility of chronic antigen-driven stimulation and dysregulated cytokine production in the pathogenesis of psoriasis.

Adolescent↗

A follow-up study in 28 patients treated with infliximab for severe recalcitrant psoriasis: evidence for efficacy and high incidence of biological autoimmunity.

BACKGROUND: Infliximab, an antitumour necrosis factor-alpha chimeric monoclonal antibody, is effective for the treatment of severe psoriasis. While the induction of antinuclear antibodies (ANA) and antidouble-stranded-DNA antibodies (anti-dsDNA-ab) is frequently observed in patients with rheumatoid arthritis and Crohn disease receiving infliximab, the incidence of induced biological and clinical autoimmunity remains unknown in the context of psoriasis. OBJECTIVES: To investigate biological and clinical signs of autoimmunity in 28 patients receiving infliximab for severe, recalcitrant forms of psoriasis, and the clinical response to treatment. METHODS: Twenty-eight patients, 15 men and 13 women (median age 39.4 years) with psoriasis refractory to three or more systemic treatments were included. Twenty presented with plaque-type psoriasis [median Psoriasis Area and Severity Index (PASI) score 25.9; range 7.2-48], five with psoriatic erythroderma (median PASI score 54; range 48-72) and three with generalized pustular psoriasis (GPP). Psoriatic arthritis was present in 13 patients (46.4%). Infliximab 5 mg kg(-1) was given at week (W) 0, W2, W6 and every 8 weeks thereafter. Clinical data were assessed at baseline and before each infusion. Detection of ANA and of IgM and IgG anti-dsDNA-ab were performed at baseline and at W22 by immunofluorescence and enzyme-linked immunosorbent assay, respectively. RESULTS: The mean number of infliximab infusions was 5.5 (range 2-15). Among patients with plaque-type and erythrodermic psoriasis, 17 of 25 (68%) and three of five reached a PASI improvement of 75% or more, respectively, while rapid improvement of clinical and biological signs was observed in all three patients with GPP. The prevalence of positive detection of ANA raised from 12% at baseline to 72% at W22 (P = 0.0001), an increase which was also observed for IgM anti-dsDNA-ab (68% vs. 0%, P < 0.0001), while no significant change was observed for the IgG isotype (16% vs. 0%, P = 0.125). Three patients developed nonerosive polyarthritis, without any other criteria for systemic lupus. CONCLUSIONS: The incidence of biological autoimmunity is high in patients with refractory psoriasis receiving infliximab. The concomitant onset of polyarthritis in three cases raises the need to investigate the incidence of autoimmune manifestations in psoriatic patients receiving infliximab in further large-scale studies.

Adult↗

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.

Adolescent↗

Flare and change of psoriasis morphology during the course of treatment with tumour necrosis factor blockers.

Tumour necrosis factor (TNF) blockers represent an exciting advance in the management of psoriasis. However, the safety profile of these drugs is not completely established. We present a review of the literature, and report on eight patients: two with the unexpected appearance of psoriasis, and the remaining six with exacerbation and change in morphology of their existing psoriasis, all of which occurred during treatment with the TNF blockers adalimumab, etanercept and infliximab. The two new cases, neither of whom had any personal or family history of psoriasis, developed pustular psoriasis on the palms and/or soles. The other six patients, previously diagnosed with severe chronic plaque psoriasis (four patients), generalized pustular psoriasis (one) and erythrodermic psoriasis (one), developed eruptive guttate psoriasis between 15 days and 18 months after the beginning of therapy. These patients had never before presented guttate-type psoriatic lesions, and the lesions appeared in areas of the body that were free of psoriatic plaques at baseline.

Adalimumab↗

Age and gender differences in the impact of psoriasis on quality of life.

BACKGROUND: The impact of psoriasis upon the quality of life contributes significantly to the overall morbidity associated with the disease. An older age at onset of psoriasis and being a man have been associated previously with lower psychosocial morbidity. In order to further evaluate these potentially important mitigating factors, we examined the relation of age and gender on some aspects of psoriasis-related psychosocial morbidity. METHODS: Two hundred and fifteen consenting psoriasis patients, representing a wide range of disease severity, were studied. They included 110 men and 105 women, age range 19-87 years (age: mean +/- SD: 48.0 +/- 15.9 years); all endorsed a list of 30 items (by checking a "Yes" or "No") pertaining to life events related to psoriasis that they had experienced in the previous one month. The patients self-rated the severity of their psoriasis. The patients were categorized into four age groups of 18-29 years (N = 28), 30-45 years (N = 77), 46-65 years (N = 76), and > 65 years (N = 34), respectively, for the statistical analyses. RESULTS: No age or gender differences in the severity of psoriasis were observed. Patients of both sexes in the 18 to 29 and 30 to 45 year age groups reported more frequent (P < or = 0.05) problems related to both appearance/socialization and occupation/finances, in contrast to patients in the 46-65 and over-65-year age groups. No gender differences (P < or = 0.05) were observed in the frequency of items related to appearance and socialization; however, men reported greater work-related stresses. CONCLUSION: Psoriasis has a greater impact upon the quality of life of patients in the 18 to 45 year age range and affects the socialization of both sexes equally. Men face greater work-related stresses as a result of their psoriasis.

Adult↗

Epidemiology of childhood psoriasis: a study of 419 patients from northern India.

BACKGROUND: We undertook this study in order to determine the pattern and prevalence of childhood psoriasis in northern India and to highlight the differences and similarities with previous studies. MATERIALS AND METHODS: In this retrospective epidemiologic study, the data from 419 children (less than 14 years of age) with psoriasis registered at the Psoriasis Clinic between January 1990 and December 2002 were included. RESULTS: The 419 children registered at the Psoriasis Clinic constituted 0.3% of the dermatology outpatients and 12.5% of the total psoriasis patients seen over a period of 13 years in the department. There were 219 (52.2%) boys and 200 (47.7%) girls, with a male to female ratio of 1.09 : 1. The age of onset ranged from 4 days to 14 years. The mean age of onset was 8.1 +/- 2.1 years in boys and 9.3 +/- 2.3 years in girls. The peak age of onset in boys was in the 6-10-year age group, whereas the majority of girls showed an onset of psoriasis between the ages of 10 and 14 years. A positive family history was present in only 19 (4.5%) patients. The extensors of the legs were the most common initial site affected [105 (25%) cases], followed by the scalp [87 (20.7%)]. Classical plaque psoriasis was the most frequent clinical presentation [254 (60.6%) patients], followed by plantar psoriasis [54 (12.8%)]. Nail involvement was observed in 130 (31%) cases. All types of nail changes described in psoriasis were seen in these patients. Pitting was the most common nail change, followed by ridging and discoloration. Five children (1.1%) (three girls and two boys) had psoriatic arthropathy. Precipitating factors that brought about the onset of the disease or were associated with exacerbation could be recalled in only 28 (6.6%) patients. Koebnerization was observed in 27.9% of patients. Pruritus was the most frequent symptom, reported by 365 (87.1%) children. Twenty-seven (6.4%) children had other concurrent mucocutaneous diseases (vitiligo, pityriasis alba, alopecia areata, ichthyosis vulgaris, halo nevus, aphthous stomatitis, urticaria, pityriasis versicolor, nummular eczema, salmon patch, and verrucous epidermal nevus). Eighteen children had systemic disorders, including seizures, bronchial asthma, mitral regurgitation, scleroderma, Down's syndrome, high arched palate, cholelithiasis, anterior mongoloid slant, and prognathism; however, these conditions were possibly chance findings only and no correlation with the age of onset or severity of the disease was found. CONCLUSIONS: Our findings differ from those of previous studies in showing a delayed onset, equal sex distribution, less frequent facial involvement, uncommon guttate lesions, more frequent involvement of the soles, and a less frequent history of familial occurrence.

Adolescent↗

The psoriasis disability index in Chinese patients: contribution of clinical and psychological variables.

OBJECTIVES: To provide a description of medical and psychological aspects of Chinese psoriasis patients, and to examine the specific contribution of demographic, medical and psychological variables to the Psoriasis Disability Index. METHODS: Ninety-three Chinese psoriasis patients underwent a clinical assessment using the Psoriasis Area and Severity Index (PASI) and completed a questionnaire that included questions on demographic and medical data, the Hospital Anxiety and Depression Scale (HADS) and the Psoriasis Disability Index (PDI). RESULTS: Psoriasis patients with cosmetic involvement had higher levels of anxiety and depression and higher disability scores than those without cosmetic involvement. Thirty-four per cent of the patients reported a significant level of anxiety (HADS-anx. > 11). The clinical severity of psoriasis was not associated with psychological and PDI scores. Multiple regression analysis indicated that psychological variables were associated with PDI scores, and explained 30% of the variance. However, demographic and psoriasis severity variables explained only 6% of the variance. CONCLUSION: Psoriasis patients suffer from anxiety and depression. Psychological factors are much stronger determinants of the PDI than demographic, disease related variables. Clinical management of the disease should consider both clinical and psychological factors.

Adaptation, Psychological↗

Current management of psoriasis in the United Kingdom: patterns of prescribing and resource use in primary care.

The current management of psoriasis and its associated resource use in the United Kingdom (UK) was investigated in this retrospective analysis of 789,300 primary care patient records. Most patients with psoriasis (94%) were managed on topical psoriasis agents only, 4% were prescribed systemic psoriasis agents and 2% had no recorded psoriasis treatment at all during the 12-month study period. Co-medications to treat physical or psychological comorbidities were required by 22% of patients. Referral rates into secondary care were low, 5% of patients prescribed systemic psoriasis agents and 0.7% of patients prescribed topical psoriasis agents had secondary care appointments documented in their medical records. This study demonstrates that most patients with psoriasis in UK primary care are managed on topical agents even though there are surrogate markers, such as resource use and co-medication prescriptions, which indicate that their psoriasis is not optimally controlled.

Administration, Cutaneous↗

The chemotactic activity of T-lymphocytes in response to interleukin 8 is significantly decreased in patients with psoriasis and atopic dermatitis.

Involvement of T-lymphocytes in the pathogenesis of psoriasis and atopic dermatitis is well established. The question arises as to whether not only tissue infiltrating but also circulating T-lymphocytes are involved in the disease process. Therefore we sought to determine whether T-lymphocytes from patients with psoriasis and atopic dermatitis show abnormal biological behavior to the proinflammatory chemokine interleukin 8 (IL-8) in vitro as studied by their chemotactic activity. In addition, the expression of T-cell activation markers such as HLA-DR and interleukin 2 receptor (IL-2R) were analysed with FACS-technique. In all, 25 patients with psoriasis (13 patients with severe psoriasis and 12 patients with mild psoriasis) and 11 patients with atopic dermatitis were investigated. For comparison. T-lymphocytes from 14 healthy controls were tested equally. The results show that T-cell chemotactic responses to IL-8 were significantly decreased in patients with severe psoriasis as compared to healthy controls. T-cells from patients with atopic dermatitis demonstrated an even more pronounced decrease in chemotactic response as compared to T-cells from psoriasis patients or healthy controls. In contrast, increased expression of activation markers HLA-DR and IL-2R were demonstrated in circulating T-cells from patients with severe psoriasis and atopic dermatitis in comparison to healthy controls. It can be concluded that circulating T-cells in patients with severe psoriasis and atopic dermatitis show a decreased in vitro chemotactic response to IL-8. Furthermore, the in vivo phenotypic activation state of T-lymphocytes in these patients seemed to be associated with their decreased in vitro functional capacity.

Adolescent↗

Alcohol intake: a risk factor for psoriasis in young and middle aged men?

OBJECTIVE: To clarify the nature of the association between alcohol intake and psoriasis. DESIGN: Case-control study of men aged 19-50 with onset of skin disease in 1976 or later. SETTING: Outpatient clinics of the departments of dermatology of the university central hospitals in Helsinki, Oulu, and Tampere from September 1987 to April 1989. SUBJECTS: 144 Patients with psoriasis and 285 unmatched controls with other skin diseases. MAIN OUTCOME MEASURES: Results of clinical examination and self administered questionnaire assessing lifestyle and alcohol intake during two specified periods--namely, 12 months before the onset of skin disease and 12 months before the date of examination. RESULTS: Recalled mean alcohol intake before the onset of skin diseases was 42.9 g/day among the patients with psoriasis and 21.0 g/day among the controls. In logistic regression analysis psoriasis was associated with alcohol intake but not with coffee consumption, smoking, age, marital state, or social group. The odds ratio for psoriasis at an alcohol intake of 100 g/day compared with no intake was 2.2 (95% confidence interval 1.3 to 3.9). The controls decreased their alcohol intake after the onset of the disease but the group with psoriasis did not. Analysis of serum enzyme values showed that gamma-glutamyltransferase activity was significantly correlated with alcohol intake (r = 0.35), the mean activity being 75.0 U/l among patients with psoriasis and 41.9 U/l among controls. CONCLUSIONS: Alcohol is a risk factor for psoriasis in young and middle aged men, and psoriasis may sustain drinking.

Adult↗

Does inflammatory linear verrucous epidermal nevus represent a segmental type 1/type 2 mosaic of psoriasis?

BACKGROUND: A 6-year-old girl with a symmetric linear eruption on both of her legs, clinically and histologically resembling inflammatory linear verrucous epidermal nevus (ILVEN) or linear psoriasis (LP), with concomitant psoriasis of the guttata type and a positive family history of psoriasis is presented. The questions as to whether LP actually exists and ILVEN represents a distinct entity are still under debate. OBJECTIVE AND METHODS: The recent literature concerning case reports of ILVEN and LP is reviewed. RESULTS: Case reports of ILVEN and LP can be subdivided into four different groups: (1) ILVEN with or without concomitant psoriasis, only in part reacting to antipsoriatic treatment, (2) ILVEN without concomitant psoriasis, (3) LP with concomitant psoriasis vulgaris, with both groups 2 and 3 reacting successfully to antipsoriatic treatment, and (4) LP without concomitant psoriasis vulgaris and with no family history of psoriasis (very rarely reported). CONCLUSION: It is hypothesized that inflammatory linear verrucous eruption besides nevoid psoriasis/LP represents a further segmental type 1/type 2 mosaic of psoriasis which, if a (verrucous) epidermal nevus exists, shows a high affinity of occurrence in close context to such a nevus. Heritability is thought to be possible.

Administration, Topical↗

Validity and reliability of patient reported outcomes used in psoriasis: results from two randomized clinical trials.

BACKGROUND: Two Phase III randomized controlled clinical trials were conducted to assess the efficacy, safety, and tolerability of weekly subcutaneous administration of efalizumab for the treatment of psoriasis. Patient reported measures of psoriasis-related functionality and health-related quality of life and of psoriasis-related symptom assessments were included as part of the trials. OBJECTIVE: To assess the reliability, validity, and responsiveness of the patient reported outcome measures that were used in the trials - the Dermatology Life Quality Index (DLQI), the Psoriasis Symptom Assessment (PSA) Scale, and two itch measures, a Visual Analog Scale (VAS) and the National Psoriasis Foundation (NPF) itch measure. METHODS: Subjects aged 18 to 70 years with moderate to severe psoriasis for at least 6 months were recruited into the two clinical trials (n = 1095). Internal consistency reliability was evaluated for all patient reported outcomes at baseline and at 12 weeks. Construct validity was evaluated by relations among the different patient reported outcomes and between the patient reported outcomes and the clinical assessments (Psoriasis Area and Severity Index; Overall Lesion Severity Scale; Physician's Global Assessment of Change) assessed at baseline and at 12 weeks, as was the change over the course of the 12 week portion of the trial. RESULTS: Internal consistency reliability ranged from 0.86 to 0.95 for the patient reported outcome measures. The patient reported outcome measures were all shown to have significant construct validity with respect to each other and with respect to the clinical assessments. The four measures also demonstrated significant responsiveness to change in underlying clinical status of the patients over the course of the trial, as measured by the independently assessed clinical outcomes. CONCLUSIONS: The DLQI, the PSA, VAS, and the NPF are considered useful tools for the measurement of dermatology-related limitations of functional ability and the frequency, severity and impact of psoriasis symptoms on patients' lives and psoriasis-related quality of life.

Adolescent↗

Identification of mitophagy-related biomarkers with immune cell infiltration in psoriasis.

BACKGROUND: Psoriasis is an inflammatory disorder characterized by scaly erythematous plaques and significant comorbidities. Recent studies have suggested that impaired mitophagy, the cellular mechanism for removing dysfunctional mitochondria, may contribute to the pathogenesis of psoriasis. METHODS: In this study, we analyzed bulk RNA sequencing data from 167 healthy individuals and 177 patients with psoriasis obtained from the Gene Expression Omnibus database (GSE30999 and GSE54456). Mitophagy-related genes were isolated using weighted gene co-expression network analysis. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were performed and protein-protein interaction networks were constructed for the functional enrichment of genes associated with mitophagy. The correlations between genes associated with mitophagy, signaling pathways, and immune cell infiltration were analyzed. The potential diagnostic value of genes associated with mitophagy was evaluated using receiver operating characteristic (ROC) curves, which were validated in imiquimod-induced psoriatic skin lesions in mice. RESULTS: We identified 3,839 differentially expressed genes between healthy individuals and patients with psoriasis, and 23 genes were selected as hub genes showing a high correlation with mitophagy in psoriasis. GO and KEGG analyses revealed that hub and associated genes were significantly correlated with skin functions, such as epidermal development and keratinocyte differentiation. In addition, mitophagy-related genes were negatively associated with pro-inflammatory and pro-proliferation pathways in psoriasis. Among the immune cells, CD4+ T cells were most significantly affected by mitophagy-related genes. ROC analysis demonstrated that mitophagy-related genes, especially ACER1, C1ORF68, CST6, FLG2, GJB3, GJB5, GPRIN2, KRT2, and SPRR4 were potential biomarkers of psoriasis for use in diagnosis or treatment. CONCLUSIONS: Mitophagy-related genes play crucial roles in psoriasis and have potential use as biomarkers, providing insights into disease mechanisms and therapeutic targets. Further research may lead to the development of new strategies for psoriasis management.

Psoriasis↗

Psychological stress, distress and disability in patients with psoriasis: consensus and variation in the contribution of illness perceptions, coping and alexithymia.

OBJECTIVES: The purpose of this study was to examine the relative contribution of medical variables, illness perceptions, coping and alexithymia to the variance in stress, distress and disability in patients with psoriasis. DESIGN: Cross-sectional study. METHOD: A group of 225 patients with psoriasis completed the Hospital Anxiety and Depression Scale (HADS), The Penn State Worry Questionnaire (PSWQ), the COPE, the Illness Perception Questionnaire (IPQ), Toronto Alexithymia Scale (TAS-20), and two measures specific to psoriasis, the Psoriasis Disability Index (PDI), and the Psoriasis Life Stress Inventory (PLSI). The severity of patients' psoriasis was clinically assessed by dermatologists on the Psoriasis Area and Severity Index (PASI). RESULTS: In general, demographic variables, clinical history and extent of disease were consistently the least useful variables in terms of explaining variance in stress, distress or disability. Their utility was limited to accounting for small but significant variations in disability, but even in this case, they accounted for just over half as much variance as illness perceptions. Illness perceptions were uniformly the most important variables in terms of the variance accounted for in outcome. Coping varied widely in its explanatory power; its effects were negligible in both disability (PDI) and everyday stress (PLSI), and it was moderately important in accounting for additional variance in depression and anxiety. However, coping was important in explaining the variance in pathological worrying. Alexithymia accounted for significant additional variance chiefly for anxiety and to a lesser extent for depression, worrying and psoriasis-related life stress. CONCLUSION: The observed importance of cognitive factors in stress, distress and disability invite us to consider the utility of multivariate models of outcome in psoriasis.

Adaptation, Psychological↗

TNF alpha inhibitors in the treatment of psoriasis and psoriatic arthritis.

Psoriasis is a chronic inflammatory skin disease that can lead to significant physical and psychologic distress for patients. Psoriatic arthritis (PsA), originally thought to be quite a mild disorder, is now recognized as a progressive and destructive arthritis. To date, therapies for both these conditions have been non-specific and unable to maintain long-lasting remission. In addition, many of the current therapies have significant adverse effects, limiting their usefulness. However, elucidation of the pathogenesis of psoriasis and PsA at a molecular level and the development of selective biologic agents have led to an enormous expansion of the armamentarium available to psoriasis patients. Two agents (infliximab and etanercept) selectively block the role of the cytokine tumor necrosis factor (TNF)-alpha and have proved effective in clinical trials in the treatment of both the skin and the joint manifestations of psoriasis. A third anti-TNF alpha agent (adalimumab Humira) is licensed for the treatment of rheumatoid arthritis; however, no studies have been published to date on its use in PsA or psoriasis. It is known that TNF alpha is elevated in both the skin and synovium of psoriatic patients and the effectiveness of its blockade by these two agents in psoriasis and PsA confirms its role in their pathogenesis. Randomized, double-blind, placebo-controlled trials have been performed with both agents in the treatment of psoriasis and PsA; in the case of etanercept these have been to support US FDA approval for use in psoriatic arthropathy. These studies are supported by smaller cohorts in open-label studies and anecdotal reports in the literature. Anti-TNF alpha therapy has proved to have disease-reducing activity in PsA and psoriasis and appears to be well tolerated. These studies have generally featured small numbers of patients and, until a larger cohort of treated patients is available, vigilance must be exercised. A considerable body of post-marketing safety data exists on the use of infliximab in rheumatoid arthritis and Crohn disease and for etanercept in rheumatoid arthritis and PsA. Certain issues, particularly the risk of infection, have emerged as features of the use of these agents. It remains to be seen whether effects seen in other disease entities may be extrapolated to psoriatic patients. More long-term data and experience are needed to define the role of anti-TNF alpha agents in the management of psoriasis and PsA. In particular, more studies are required to elucidate the finer points of co-medication; in some studies both agents have been used with other medications but there have been no formal trials of various possible combinations.

Antibodies, Monoclonal↗

Calcipotriol ointment. A review of its use in the management of psoriasis.

UNLABELLED: Calcipotriol, a vitamin D3 analog, acts not only to inhibit cell proliferation and enhance cell differentiation in the skin of patients with psoriasis, but also appears to have effects on immunologic markers that are thought to play a role in the etiology of the disease. In several well designed, short term studies in adults, calcipotriol ointment 50 micrograms/g twice daily provided similar or superior efficacy to several other antipsoriatic agents in adult patients with mild to moderate psoriasis. In patients with nonscalp psoriasis, the drug provided superior efficacy to twice daily placebo (vehicle ointment), twice daily fluocinonide 500 micrograms/g, once daily tacalcitol 4 micrograms/g and twice daily coal tar 5% plus allantoin 2% and hydrocortisone 0.5%. Furthermore, calcipotriol therapy generally provided superior efficacy to twice daily betamethasone valerate 1 to 1.2 mg/g or once daily dithranol 1 to 20 mg/g, and similar efficacy to twice daily betamethasone dipropionate plus salicylic acid or once daily maxacalcitol 6 to 50 micrograms/g. Limited data indicated that calcipotriol ointment 50 micrograms/g also improved overall disease severity in children. In combination with other antipsoriatic agents [acitretin, cyclosporine, betamethasone valerate, halobetasol (ulobetasol)], ultraviolet B or psoralen ultraviolet A (PUVA) phototherapy, calcipotriol ointment 50 micrograms/g twice daily improved the beneficial effects of these drugs on overall disease severity in adult patients with moderate to severe psoriasis. Furthermore, in separate trials, calcipotriol combination therapy reduced the dosage of acitretin required to achieve clearance of psoriasis and the duration of PUVA and dosage of UVA phototherapy, potentially improving the benefit/risk ratio for these other antipsoriatic treatments. Calcipotriol was generally well tolerated in short and long term studies in adult patients, with the majority of adverse events being mild to moderate in intensity and transient. The most common adverse events associated with calcipotriol therapy were dermatologic in nature and included lesional or perilesional irritations, face and scalp irritations, worsening of psoriasis and miscellaneous dermatologic events. Notably, there have been very few reports of patients developing hypercalcemia or hypercalciuria during calcipotriol therapy, with most occurring in patients who exceeded the recommended dosage of 100 g/week. Although data in children are limited, the drug was well tolerated with the nature and incidence of adverse effects similar to those observed in adult patients. CONCLUSIONS: Extensive clinical experience, along with several short and long term clinical trials, has shown calcipotriol ointment to be an effective and well tolerated topical agent in adult patients with psoriasis. In addition, calcipotriol ointment proved beneficial in combination with other topical, phototherapy or systemic antipsoriatic treatments, reducing the dosage and/or duration of some of these treatments and potentially improving their benefit/risk ratio. Calcipotriol ointment is valuable as a first- or second-line therapy option for the management of mild to moderate psoriasis and in combination with other antipsoriatic agents for more severe psoriasis.

Administration, Topical↗