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Background: Etanercept and efalizumab recently became available and reimbursed for routine use in severe psoriasis in the Netherlands. The criteria for reimbursement are Psoriasis Area and Severity Index (PASI) > or = 10 (or Skindex-29 > or = 35 if PASI > or = 8 and < 10) and ineffectiveness of ultraviolet (UV) B/psoralen plus UVA, methotrexate and ciclosporin, or a contraindication to or serious side-effect(s) during these treatments., Objectives: We hypothesized: (i) that efficacy would be lower than that obtained in published phase II and III studies because (a) resistance to all conventional therapies as a reimbursement condition would select for more resistant cases and (b) inclusion would be more restricted to severe cases (higher PASI), and (ii) that efficacy would be lower in obese patients due to the possible role of adipose tissue in tumour necrosis factor (TNF)-alpha homeostasis., Methods: We treated 50 patients (38 men, 12 women; mean PASI 15.8) with etanercept 25 mg or 50 mg twice weekly and evaluated in a retrospective analysis the efficacy and safety in comparison with data from published trials. Additionally, we related the clinical effect to the body mass index (BMI), for adipose tissue is thought to have a possible role in TNF-alpha homeostasis., Results: Based on the literature, 30% and 49% of the patients treated with etanercept 25 mg and 50 mg twice weekly, respectively, should have achieved 75% or more improvement in PASI compared with baseline (PASI 75), and 10% and 21%, respectively, should have achieved 90% or more improvement (PASI 90). Our data showed that 21% in the 2 x 25 mg group and 23% in the 2 x 50 mg group achieved PASI 75. PASI 90 was only attained in 7% of patients treated with 2 x 25 mg and 6% of those treated with 2 x 50 mg. Contrary to our hypothesis, the mean initial PASI was comparable with the mean PASI mentioned in the phase II and III clinical trials. Although fatigue is not identified as a side-effect of etanercept, 10% of our patients reported fatigue as an adverse event during etanercept treatment. High BMI, indicating overweight or obesity, was found both in patients with little efficacy and in patients achieving PASI 75 or better., Conclusions: Use of etanercept in real practice gives impressive results, but these are generally less favourable than those published in clinical trial reports. This is probably due to the stringent conditions for reimbursement, which select for more treatment-resistant patients. Fatigue as a possible side-effect of etanercept should also be an issue for further investigation. Finally, the BMI does not seem to influence the patients' response to etanercept, although further investigations would be needed to confirm this.

Background: Efalizumab (anti-CD11a), a humanized monoclonal antibody, blocks multiple T-cell-dependent functions implicated in the pathogenesis of psoriasis, including T-cell activation, migration to the skin, reactivation in psoriatic skin and interactions with keratinocytes., Objectives: This multinational, randomized, double-blind, placebo-controlled, parallel-group trial was designed to evaluate the safety and efficacy of subcutaneous efalizumab 1.0 mg kg-1 once weekly for 12 weeks compared with placebo in a population that included high-need patients, defined as those for whom at least two systemic therapies were unsuitable because of lack of efficacy, intolerance or contraindication., Patients/methods: Patients with moderate-to-severe plaque psoriasis [involvement of >or=10% of total body surface area and Psoriasis Area and Severity Index (PASI)>or=12.0 at screening] were randomized in a 2:1 ratio to receive efalizumab or placebo. The primary efficacy endpoint was the proportion of patients achieving >or=75% PASI improvement (PASI-75 response) at week 12 in the intention-to-treat population; secondary endpoints included changes in PASI, static Physician's Global Assessment, Physician's Global Assessment of change from baseline and percentage of body surface area affected. Results We enrolled 793 patients (529 received efalizumab and 264 placebo), including 526 high-need patients (342 received efalizumab and 184 placebo). Week 12 PASI-75 rates were 29.5% for efalizumab compared with 2.7% for placebo among high-need patients (P<0.0001) and 31.4% for efalizumab compared with 4.2% for placebo in the full study population (P<0.0001)., Results: for all secondary efficacy endpoints showed superiority of efalizumab over placebo in both the high-need and the full populations. Efalizumab demonstrated a favourable safety profile, without evidence of systemic toxicity, in both the high-need group and the overall study population., Conclusions: The efficacy and safety of efalizumab therapy were comparable between high-need patients and the more general moderate-to-severe psoriasis patient population. In view of its demonstrated efficacy and safety profile, efalizumab represents a valuable option for the treatment of adult patients with moderate-to-severe plaque psoriasis, including high-need patients.

Background: Involved regions of the skin in patients with atopic dermatitis (AD) have been shown to have higher transepidermal water loss (TEWL), indicating a compromised skin barrier. Whether uninvolved skin also has diminished barrier characteristics is controversial., Objectives: To study the penetration of sodium lauryl sulphate (SLS) into uninvolved skin of patients with AD compared with the skin of control subjects., Methods: Percutaneous penetration was assessed using the tape stripping technique on the stratum corneum (SC). Twenty patients with AD and 20 healthy subjects were exposed to 1% SLS for 4 h on the mid-volar forearm. After the end of exposure the SC was removed by adhesive tape. The amount of SLS was determined in each consecutive strip. Fick's second law of diffusion was used to deduce the diffusivity and the partition coefficient of SLS between water and the SC., Results: The SC thickness was similar in both groups; however, the TEWL was higher in patients with AD compared with that of the control group (mean+/-SD 8.4+/-4.3 and 6.3+/-2.0 g m-2 h-1, respectively). There was a correlation between SC thickness and TEWL in control subjects but no correlation was found in patients with AD. The diffusivity of SLS through uninvolved AD skin was higher compared with normal skin (mean+/-SD 12.7+/-5.8x10(-9) and 6.2+/-3.0x10(-9) cm-2 h-1, respectively), while the partition coefficient between SC and water was lower (mean+/-SD 137+/-64 and 196+/-107, respectively)., Conclusions: The results show a different penetration profile of SLS into the SC of patients with AD compared with control subjects. This indicates that even noninvolved skin in patients with AD has altered barrier characteristics, emphasizing the importance of skin protection and prevention of skin contact with chemicals.

Locally synthesized complement is believed to play an important role in host defense and inflammation at organ level. In the epidermis, keratinocytes have so far been shown to synthesize two complement components, C3 and factor B. Here, we studied the synthesis of factor H by human keratinocytes. We also studied the regulation of factor H synthesis in keratinocytes by several cytokines, namely IL-1alpha, IL-2, IL-6, TGF-beta1, TNF-alpha and IFN-gamma. Human keratinocytes expressed factor H mRNA and constitutively released small amounts of factor H protein into the culture medium. This release was strongly upregulated by IFN-gamma but not by other cytokines tested. Western blot analysis revealed that IFN-gamma augments the synthesis of both molecular species, factor H (FH; 155kDa) and factor H-like protein-1 (FHL-1; 45kDa), of factor H. Factor H released in response to IFN-gamma was functionally active. In conclusion, we demonstrate that keratinocytes are capable of synthesizing factor H and that this synthesis is regulated by IFN-gamma.

Background: Lichen planus (LP) is a common inflammatory skin disease of unknown aetiology. Viral causes have been suggested., Objectives: To find candidate viruses associated with LP., Methods: Lesional and nonlesional skin samples, peripheral blood mononuclear cells and serum were obtained from patients with LP. Ultrastructural, viral DNA, immunohistochemical and serological analyses were performed, and comparisons were made with psoriatic and normal skin., Results: Electron microscopy revealed typical 120-200-nm enveloped particles with a 100-nm nucleus resembling human herpesvirus (HHV) virions both in dermis and in epidermis of lesional LP tissue. HHV-7 DNA was found in 11 of 18 lesional LP samples, as opposed to only one of 11 nonlesional LP samples (P =0.06), two of 11 lesional psoriasis samples (P = 0.05) and none of four normal skin samples. No relation was found between LP skin and DNA of other known HHVs (HHV-1-6 and 8). With immunohistochemistry, significantly more HHV-7+ cells were found in lesional LP epidermis than in normal epidermis. Lesional LP dermis contained significantly more HHV-7+ cells than nonlesional LP, psoriatic or normal dermis. Moreover, LP skin contained overwhelmingly and consistently more plasmacytoid dendritic cells (upregulated in virally induced conditions) than nonlesional LP samples., Conclusions: We conclude that HHV-7 replicates in LP lesions, but not in psoriasis, another inflammatory skin condition. HHV-7 is possibly involved in the pathogenesis of LP. These preliminary data make further research on this topic of interest.

Keratinocytes contribute to cutaneous immune responses through the expression of cytokines. We investigated whether human keratinocytes can express IL-23, a newly defined IFN-gamma-inducing cytokine composed of a unique p19 subunit and a p40 subunit shared with IL-12. Cultured keratinocytes from normal and lesional psoriatic skin were found to express constitutively mRNA for both subunits of IL-23. Low but significant levels of the heterodimeric IL-23 protein could be detected in cell lysates and supernatants from stimulated keratinocytes by immunoblotting and ELISA. Functional analysis showed that these low levels of keratinocyte-derived IL-23 were sufficient to enhance the IFN-gamma production by memory T cells. Immunostaining of skin sections confirmed expression of both subunits of IL-23 by keratinocytes in situ and also revealed expression of this cytokine in the dermal compartment. IL-23 expression was significantly higher in psoriatic lesional skin, compared with normal and psoriatic nonlesional skin. The immunostained preparations of cultured cells and IL-23 levels in culture supernatants did not show any difference between normal and psoriatic keratinocytes indicating no intrinsic aberration of IL-23 expression in keratinocytes from psoriatic skin. Double staining of cytospin preparations demonstrated that IL-23 p19 is also expressed by epidermal Langerhans cells, dermal dendritic cells, and macrophages. Psoriasis is a chronic inflammatory skin disease mediated by IFN-gamma-expressing type 1 memory T cells. As IL-23 is important to activate memory T cells to produce IFN-gamma, its augmented expression of IL-23 by keratinocytes and cutaneous APC may contribute to the perpetuation of the inflammation process in this disease.

Traditionally the evaluation of the cellular infiltrate and protein expression in skin tissue sections is done by manual quantification. However, for reliable evaluation of histology in the development of new anti-psoriatic treatments there is a need for a more time-efficient and reproducible method. To test the use of digital image analysis (DIA) in this situation we compared the assessment of immunohistochemically stained skin sections with the more traditional manual quantification (MQ) and semi-quantitative analysis (SQA). The number of CD3+ T cells and the expression of E-selectin were evaluated in stained paired skin biopsies from 11 patients with chronic plaque psoriasis before and after initiation of anti-psoriasis therapy. We observed significant correlations between MQ and DIA for the number of T cells (epidermis: r=0.88, P< or =0.01, dermis r=0.87, P< or =0.01). Both DIA and MQ were equally effective in detecting reductions of T-cell numbers in active-treated patients. MQ took 20 h, compared to 6 h for DIA. We also observed significant correlations between SQA and DIA for the expression of E-selectin (r=0.88, P< or =0.01), although DIA was more sensitive than SQA to detect (early) changes. SQA took 10 h, compared to 4 h for DIA. In conclusion, the quantification of the inflammatory infiltrate in psoriatic lesional skin by DIA generated similar results as MQ and SQA in a reliable, reproducible and higher time efficient fashion.

The current understanding of the function of natural killer (NK) T cells in innate immunity and their potential to control acquired specific immunity, as well as the remarkable efficacy of antitumour necrosis factor-alpha biological treatments in psoriasis, forces us to refine the current T-cell hypothesis of psoriasis pathogenesis, and to give credit to the role of innate immunity. Psoriasis might be envisioned to be a genetically determined triggered state of otherwise dormant innate immunity. This aggravated state of innate immunity is represented by the activity of NK T cells, dendritic cells, neutrophils and keratinocytes, leading to the recruitment and activation of preferentially type 1 T cells, possibly in an antigen-independent way. Keratinocytes in psoriasis then are sensitive to the effects of T-cell activation and cytokine production, interferon (IFN)-gamma, by responding with psoriasiform hyperplasia. The chronic inflammation of psoriatic lesions suggests that this might be due to a deficiency in downregulation processes (e.g. a defect in the regulatory T-cell repertoire) and/or the persistence of an unknown trigger resulting in an exaggerated innate immune response.

Background: Atopic dermatis (AD) is a chronic disease that often requires long-term treatment. Topical corticosteroids are the usual therapy for patients with AD, but prolonged usage can result in skin atrophy and other side-effects., Objectives: In a randomized, double-blind, comparative study, to compare the efficacy and safety of a 6-month treatment period with 0.1% tacrolimus ointment vs. a corticosteroid ointment regimen in adults with moderate to severe AD., Methods: Treatment was applied twice daily for a maximum of 6 months. Patients in the tacrolimus treatment group (n = 487) applied 0.1% tacrolimus ointment to all affected areas over the whole body. The patients treated with the corticosteroid regimen (n = 485) applied 0.1% hydrocortisone butyrate ointment to affected areas on the trunk and extremities and 1% hydrocortisone acetate ointment to affected areas on the face and neck. The study primary endpoint was the response rate, i.e. the proportion of patients with at least 60% improvement in the modified Eczema Area and Severity Index (mEASI) between baseline and month 3., Results: By month 3, more patients in the 0.1% tacrolimus group responded to treatment (72.6% vs. 52.3% in the corticosteroid group, P < 0.001). The patients treated with 0.1% tacrolimus also showed greater improvement in mEASI, EASI, affected body surface area and physician and patient assessments of global response. Patients applying 0.1% tacrolimus ointment experienced more skin burning (52.4% vs. 13.8% in the corticosteroid group; P < 0.001). In most patients, skin burning was mild to moderate in severity and decreased rapidly after the first week of treatment. There was no increase in the incidence of infections or malignancies over time in either treatment group., Conclusions: Long-term treatment with 0.1% tacrolimus ointment is significantly more efficacious than a corticosteroid ointment regimen in adults with moderate to severe AD.

Background: Patients with psoriasis have to cope with their disease for many years or even throughout their entire life. To provide optimal care, a disease management programme was developed. This programme consisted of disease education, disease management training, and psychological support, together with topical treatment., Objective: To test a disease management programme in dermatological practice, to assess patients' satisfaction with this programme, and adherence to topical treatment. Additionally, disease severity and quality of life were assessed., Methods: An initial clinical investigation was conducted in 10 European treatment centres. A total of 330 patients were included. Patient satisfaction, adherence, disease severity and quality of life were measured with study-specific and standardized self-report questionnaires., Results: Patients reported a high degree of satisfaction with the programme, and a high degree of adherence to topical treatment. Disease severity and quality of life significantly improved. The programme was well received by the participating professionals., Conclusions: The disease management programme was found to be a useful tool in the management of psoriasis, providing patients with relief from the burden of psoriasis in everyday life. A full-scale evaluation is recommended.

In view of the central pathogenic importance of leukocyte extravasation in inflammatory skin diseases, therapeutic interference with this - surprisingly complex - process is clearly a promising new approach for treating these dermatoses. Despite some disappointments during the clinical use of these agents and despite their crippling price tag, the recent incorporation of biologicals that target defined molecular controls of leukocyte extravasation into dermatological and rheumatological practise, consequently, has greatly enriched our therapeutic options for battling major, chronic, inflammatory dermatoses such as psoriasis. However, the - as yet unresolved and still rather controversially discussed - critical question is: Which of the multiple steps that control leukocyte extravasation in the human system really offer the most promising, most pragmatic, and safest molecular targets for therapeutic intervention for which disease entity? The current debate intends to stimulate public and rational debate of this crucial issue, beyond the evident commercial interests that are touched by whatever stand one takes.

Exposure to an erythemal dose of ultraviolet B (UVB) is known to induce interleukin (IL-10) expression in human skin. It is generally believed that this IL-10 is predominantly expressed by CD11b+ HLA-DR+ macrophages that infiltrate the UVB-exposed skin. This cytokine is presumed to contribute to the immunosuppressive effects of UVB by inhibiting cell-mediated immune responses. We recently demonstrated that neutrophils, which also invade UVB-irradiated skin, express CD11b and HLA-DR as well. In addition, we showed that the presence of these neutrophils affects T-cell responses in primary T-cell cultures derived from UVB-exposed skin. Since neutrophils invade UVB-exposed skin and, like macrophages, express CD11b and HLA-DR, we sought to determine whether neutrophils represent another source of IL-10. Skin biopsies were obtained from four healthy volunteers before and 2 days after exposure to four minimal erythema doses of UVB. A series of immunohistochemical double-staining procedures using the following markers was performed: IL-10, CD11b, HLA-DR, CD36, neutrophil elastase, and CD66b. As expected IL-10 could be detected in CD11b+ HLA-DR+ CD36+ macrophages in the epidermis and dermis of UVB-exposed skin. Surprisingly, the majority of the abundant IL-10 expression was found in CD11b+ HLA-DR+ elastase+ CD66b+ neutrophils. Cytospin preparations from dermal cell suspensions confirmed the IL-10 expression by neutrophils displaying characteristic multilobular nuclei. Thus, neutrophils in UVB-exposed skin express IL-10 and should be recognized as active coplayers in the creation of the UVB-induced immunosuppressive microenvironment.

It is assumed that skin is protected against sunburn by melanin. In patients with vitiligo, there are white patches in the normal pigmented skin. We noticed that there is a difference in burning capacity of these white patches between people with different skin types. With UVB 311 nm lamps, we irradiated both lesional and non-lesional skin with increasing doses in 33 patients with vitiligo, divided into 5 groups according to skin type (II-VI). Twenty-four hours later we assessed the minimal erythema dose and found a correlation between skin type and UV sensitivity in both lesional skin and normal skin. We suggest that there must be a protection mechanism, other than that offered by melanin pigmentation. The antioxidant status may play a role in this phenomenon.

For more than five decades, topical corticosteroids and emollients have been the mainstay of therapy for atopic dermatitis. However, the potential for side-effects limits the clinical utility of corticosteroids in providing long-term disease control. With a unique mode of action that differs from that of corticosteroids, the steroid-free topical calcineurin inhibitors (TCIs), tacrolimus ointment and pimecrolimus cream, provide skin-selective treatment that targets key factors involved in the pathogenesis of this chronic disease. An extensive series of clinical trials involving more than 16,000 patients with predominantly moderate to severe atopic dermatitis in tacrolimus studies and over 2000 patients with primarily mild to moderate disease in pimecrolimus studies has shown that both TCIs provide effective and well-tolerated treatment for atopic dermatitis. Randomized controlled trials have demonstrated that tacrolimus is superior to conventional hydrocortisone-based regimens and does not cause skin atrophy or other steroidal side-effects. Both tacrolimus and pimecrolimus prevent disease flares and provide progressive and sustained disease improvement with long-term therapy. These and other clinical benefits of TCIs are discussed, together with the safety profiles of tacrolimus and pimecrolimus and their use in clinical practice. In addition, this review summarizes findings from the many trials carried out with these agents and outlines how TCIs can provide long-term treatment and control of a chronic skin disease that may persist for years.

Type-1 cytokine-producing T cells are important in the pathogenesis of psoriasis vulgaris, for which efficient therapy is provided by means of narrow-band ultraviolet-B (NB-UVB). The expression of the type-1 cytokine interferon-gamma (IFN-gamma) is regulated by interleukin-12 (IL-12), IL-15, IL-18 and IL-23; however, not much is known about the effect of this therapy on the levels of these cytokines in lesional psoriatic skin in situ. In this study, we investigated the effects of NB-UVB therapy on the expression of IFN-gamma-inducing cytokines. Ten patients with chronic plaque-type psoriasis selected to be treated with NB-UVB therapy were recruited for these experiments and the expression of cytokines IL-12, IL-15, IL-18, IL-23 and IFN-gamma in lesional psoriatic skin before, during and after therapy was determined with the help of immunohistochemistry. Double staining was performed in order to determine the cell types expressing these cytokines. The decrease in the psoriasis area and severity index was accompanied by a significant decrease in the expression of IFN-gamma, and concomitantly, significant reduction of IFN-gamma inducers -- IL-12, IL-18 and IL-23. Thus, we concluded that the decrease of IFN-gamma expression in psoriasis lesions after NB-UVB therapy could be a result of diminished expression of IL-12, IL-18 and IL-23 in lesional skin. Therapies targeting these three cytokines should, therefore, be considered in the treatment of psoriasis.

Psoriasis is a chronic, immune-mediated disorder that usually requires long-term treatment for control. Approximately 25% of patients have moderate to severe disease and require phototherapy, systemic therapy or both. Despite the availability of numerous therapeutic options, the long-term management of psoriasis can be complicated by treatment-related limitations. With advances in molecular research and technology, several biological therapies are in various stages of development and approval for psoriasis. Biological therapies are designed to modulate key steps in the pathogenesis of psoriasis. Collectively, biologicals have been evaluated in thousands of patients with psoriasis and have demonstrated significant benefit with favourable safety and tolerability profiles. The limitations of current psoriasis therapies, the value of biological therapies for psoriasis, and guidance regarding the incorporation of biological therapies into clinical practice are discussed.

In psoriatic lesions, T cells and keratinocytes are in an activated state. Ligation of CD40 expressed on activated keratinocytes with CD154 expressed on activated T cells is thought to be involved in the pathogenesis of psoriasis. However, the presence of CD40(+) and CD154(+) cells in psoriatic skin has not been thoroughly studied. The present study has therefore examined their presence by immunohistochemistry in the lesional and non-lesional skin of ten patients. The influence of CD154-CD40 ligation on the release of chemokines (IL-8, RANTES, and MCP-1) and complement components (C3 and factor B) from keratinocytes was also investigated in vitro. Studies using single and double staining showed that clusters of CD40(+) keratinocytes were present in both lesional and non-lesional skin; CD40(+)CD1a(+) Langerhans cells in lesional, non-lesional, and normal skin; and numerous CD40(+)CD83(+) cells in lesional skin. CD1a(+) and CD83(+) cells always expressed CD40 strongly. Numerous T cells were seen in lesional skin. A small number of T cells expressed CD154. CD154(+) T cells were seen in the lesional epidermis of seven of ten patients-in six, in juxtaposition to CD40(+) cells including keratinocytes. In non-lesional epidermis, CD154(+) T cells were seen in two patients-in one, in juxtaposition to CD40(+) keratinocytes. In vitro studies showed that IFN-gamma-treated keratinocytes released small amounts of IL-8, RANTES, and MCP-1; ligation of these cells with CD154-transfected J558 cells or soluble CD154 greatly enhanced the release. This ligation did not enhance the release of C3 and factor B. These results warrant further studies on the role of CD40 ligation in the pathogenesis of psoriasis., (Copyright 2004 Pathological Society of Great Britain and Ireland.)

On exposure to UV-B, the epidermal component trans-urocanic acid (UCA) is not only photoisomerized into cis-UCA but will also, at least in part, be photooxidized into UCA oxidation products (UOPs). We hypothesized that UOPs can mimic UV-induced systemic immunosuppression comparable to the suppressive properties already established for cis-UCA. A crude mixture of UOPs showed a significant suppression of the sensitization phase of the systemic contact hypersensitivity (CHS) response to picryl chloride (PCl). Three of the UOPs were selected for this study: imidazole-4-carboxylic acid (ImCOOH), imidazole-4-carboxaldehyde (ImCHO) and imidazole-4-acetic acid (ImAc). Effects on the sensitization, elicitation and postelicitation phases of CHS to PCl in BALB/c mice were studied and compared with the effects of cis-UCA. ImCHO was equally effective at suppressing the sensitization phase as cis-UCA. The triplet combination of the imidazoles (1:1:1) showed more pronounced suppression than that induced by cis-UCA. The most effective compounds for the suppression of the elicitation phase appeared to be ImAc and cis-UCA. Significant suppression of the postelicitation phase was only obtained with the triplet combination of ImCHO, ImCOOH and ImAc, the combination that appeared to be effective at all three tested phases. Because these three UOPs are present in UV-B-exposed human stratum corneum, these compounds may play a role in UV-B-induced immunosuppression.

Despite the eradication of naturally occurring smallpox in 1977, stores of the virus have been maintained in laboratories in the United States and Russia. It is feared that certain rogue states and terrorist organizations may have illicitly acquired the virus with the intent of unleashing it as an agent of bioterrorism. The United States and other nations have begun vaccinating individuals in the military and health care workers who might become exposed. Primary care providers and dermatologists will be called upon to evaluate potential index cases and vaccination reactions. In this report, the authors review the essential clinical aspects of smallpox and potential reactions to smallpox vaccination. Special attention is given to eczema vaccinatum, which can occur in vaccinees and their family contacts with active or quiescent atopic dermatitis or a personal history of eczema.

Background: Tumour necrosis factor alpha (TNFalpha) blockade using infliximab, a chimeric anti-TNFalpha antibody, is an effective treatment for both psoriasis and psoriatic arthritis (PsA)., Objective: To analyse the early effects of infliximab treatment on serial skin and synovial tissue biopsy samples., Methods: Twelve patients with both active psoriasis and PsA received a single infusion of either infliximab (3 mg/kg) (n = 6) or placebo (n = 6) intravenously. Synovial tissue and lesional skin biopsy specimens were obtained at baseline and 48 hours after treatment. Immunohistochemical analysis was performed to analyse the inflammatory infiltrate. In situ detection of apoptotic cells was performed by TUNEL assay and by immunohistochemical staining with anti-caspase-3 antibodies. Stained tissue sections were evaluated by digital image analysis., Results: A significant reduction in mean (SEM) T cell numbers was found in both lesional epidermis (baseline 37 (11) cells/mm, 48 hours 26 (11), p = 0.028) and synovial tissue (67 (56) cells/mm(2)v 32 (30), p = 0.043) after infliximab treatment, but not after placebo treatment (epidermis 18 (8) v 43 (20), NS; synovium 110 (62) v 46 (21), NS). Similarly, the number of macrophages in the synovial sublining was significantly reduced after anti-TNFalpha treatment (100 (73) v 10 (8), p = 0.043). The changes in cell numbers could not be explained by induction of apoptosis at the site of inflammation., Conclusions: The effects of anti-TNFalpha therapy in psoriasis and psoriatic arthritis may be explained by decreased cell infiltration in lesional skin and inflamed synovial tissue early after initiation of treatment.

Objectives: To document and compare the costs of treatment of psoriasis with 2 established systemic agents that differ substantially in their unit costs: methotrexate vs cyclosporine., Design: Cost-minimization analysis within a randomized controlled trial., Setting: Outpatient dermatology department at an academic hospital., Patients: Adults with moderate to severe plaque psoriasis, with no previous methotrexate or cyclosporine treatment., Intervention: Sixteen weeks of treatment with methotrexate or cyclosporine and an additional 36 weeks of follow-up., Main Outcome Measures: Direct and indirect medical and nonmedical costs associated with resource utilization during treatment and follow-up., Results: Average cumulative total costs associated with 16 weeks of treatment were 1593 US dollars for methotrexate and 2114 US dollars for cyclosporine (521 US dollars less for methotrexate); during 36 weeks of follow-up, these costs were 2418 US dollars and 2306 US dollars, respectively. The overall difference in cumulative 1-year costs was 409 US dollars, or approximately 10% of the total costs., Conclusions: After 1 year, the overall difference in total costs between methotrexate and cyclosporine for 16 weeks of treatment and follow-up is relatively small. Systemic medication costs are only a fraction of the costs directly and indirectly generated by utilization of health care resources and associated with individual patients rather than with methotrexate or cyclosporine. Economic arguments can be supportive of but not decisive for individual patient decisions and guidelines for systemic therapy. Rational decision making for the treatment of psoriasis may include costs only within a long-term horizon and may consider the societal and patient benefits of different alternatives.

The type 1 T cell-derived cytokine interferon gamma (IFN-gamma) is overexpressed in psoriatic lesional skin. Recently, we have shown that a single high erythemal dose of broad-band ultraviolet B (UVB) irradiation reduces type 1 and favors type 2, i.e. interleukin-4 (IL-4), cytokine expression in normal and psoriatic skin. In this study, we wanted to see whether conventional narrow-band UVB (NB-UVB) therapy (i.e. repeated exposure to nonerythemal doses) also affects type 1/type 2 cytokine expression of T cells present in chronic plaque type psoriatic lesions. Staining of cryostat sections showed decreased expression of both IFN-gamma and IL-4 in situ after NB-UVB therapy. CD4(+) dermal T cell lines, derived from psoriatic lesional skin, displayed significantly decreased intracellular IFN-gamma expression during and after NB-UVB therapy as compared to pretreatment values. Intracellular IL-4 expression was increased in most patients after therapy. Analysis of the supernatants of these stimulated dermal T cells revealed that IFN-gamma production decreased significantly following NB-UVB therapy, whereas IL-4 expression increased in the T cell supernatants from most patients, confirming the intracellular determinations. In addition, IL-10 and transforming growth factor-beta levels in the supernatants appeared to be increased in the majority of patients following UVB therapy. Apart from the well-known killing effect of UVB on T cells, our results show that the improvement in psoriatic skin following NB-UVB therapy is also due to a reduced capacity of the surviving dermal T cells to express the proinflammatory cytokine IFN-gamma.

Alefacept, a LFA-3/IgG1 fusion protein, interferes with the activation and proliferation of T cells by binding to the CD2 receptor on their surfaces. The clinical efficacy of this drug has been demonstrated in chronic plaque psoriasis. We performed a single-center, open-label study to investigate the immunohistochemical effects in psoriatic lesional skin. A group of 11 patients with plaque psoriasis all received 12 weekly doses of 7.5 mg alefacept intravenously. Skin biopsies were obtained at baseline and on days 8, 43 and 92, and were evaluated by digital image analysis after immunohistochemical staining. After completion of treatment, 8 out of the 11 patients experienced a reduction in PASI of 50% or more compared to baseline. Immunohistochemical analysis displayed a gradual decrease in the number of cutaneous T cells during therapy, with a significant reduction in epidermal CD8+ cells and dermal CD4+ cells on day 92. Patients with a reduction in PASI of 50% or more after therapy had a clearance of effector/memory T cells from the epidermis, in contrast to patients with a reduction in PASI of less than 50%. These findings support the hypothesis that effector/memory T cells play a prominent role in the pathogenesis of psoriasis, and that alefacept is capable of reducing these cells in lesional psoriatic skin.

Objective: To determine the outcome in placebo-treated patients with plaque-type psoriasis., Data Sources: Online search of MEDLINE and EMBASE until January 2001 and the Cochrane Library (2001, issue 1), supplemented by references, reviews, guidelines, and textbooks., Study Selection: Randomized controlled induction of remission trials of patients with chronic plaque-type psoriasis with systemic treatments with a placebo group not treated with antipsoriatic medication. Identified studies were examined by 2 independent reviewers. Through MEDLINE, 290 studies could be identified. Twenty-seven placebo-controlled studies were included (488 patients)., Data Extraction: Two independent reviewers extracted data on first author, year of publication, design, comparison, placebo treatment, number of patients, treatment duration, type of psoriasis and baseline severity in the placebo group, mean relative change in outcome measures, and/or percentage of patients with worsening of psoriasis; no change; minimal, moderate, or good improvement; or complete clearance., Data Synthesis: Owing to substantial heterogeneity and differences in the way outcomes were reported, no summary estimates could be obtained. The outcome of placebo treatment was poor in most studies. Some reported a mean relative change of 11% to 47%. The highest percentages of patients ended up in the worsening, no change, or minimal improvement categories. Also, complete clearance was possible. No explanation for the differences in outcome between placebo groups could be found. Description of placebo groups was often insufficient., Conclusions: The effect of treatment in placebo groups varied across studies in an unpredictable way. To evaluate the variability, improvement of the standardization of study designs, entry criteria, and outcome measures is necessary in psoriasis trials.

Psoriasis is a chronic scaling and inflammatory skin disease that can affect patients' quality of life and daily functioning. We studied the scores of 85 patients suffering from moderate to severe plaque-type psoriasis, participating in a randomized controlled trial. We compared their scores on a generic quality-of-life instrument with data from two reference populations. We examined associations between clinical severity, as measured by the components of the Psoriasis Area and Severity Index (PASI), and the respective quality-of-life subdimensions, measured by the Medical Outcome Survey Short Form 36 (SF-36), to find out what elements of disease activity are related with impaired quality of life. Compared to the reference population, quality of life was impaired in terms of bodily pain and social functioning. There were no significant correlations between overall disease severity, as measured by PASI, and the SF-36 subdimensions. When examining the PASI components, we found significant correlations between desquamation on the upper limbs and mental health and bodily pain (r = -0.23 and r = -0.28, respectively) and between desquamation on the scalp and mental health (r = -0.29). In conclusion, we found that psoriasis patients had a lower quality of life than a reference population, without a significant relation between disease severity or disease area and quality of life. Yet psoriasis lesions located on visible body parts are significantly correlated with aspects of quality of life.

Data on physical, psychological, and social functioning of patients with psoriasis have been presented in many studies. The introduction of quality-of-life questionnaires has made it possible to systematically compare these data across studies. The aim of this study was to present an overview of quality-of-life data and to describe the relationship between demographic and clinical variables and quality of life in patients with psoriasis. Computerized bibliographic databases were screened for publications from January 1966 to April 2000. Predefined selection criteria were used to identify quality-of-life studies in psoriasis. Two investigators independently assessed and, subsequently, agreed on inclusion. Data were extracted on the objectives, methods, sample characteristics, and results of the studies. A total of 118 publications were found. Seventeen studies met the inclusion criteria. Patients with psoriasis reported physical discomfort, impaired emotional functioning, a negative body and self-image, and limitations in daily activities, social contacts and (skin-exposing) activities, and work. More severe psoriasis was associated with lower levels of quality of life. There was a tendency that higher age was associated with slightly lower levels of physical functioning and slightly higher levels of psychological functioning and overall quality of life. Sex and quality of life were found to be unrelated.

Background: Topical corticosteroids are the usual treatment for atopic dermatitis (AD) in children but can have side-effects., Objectives: This study compared the efficacy and safety of 0.03% tacrolimus ointment applied once or twice daily over a 3-week period with the twice daily application of 1% hydrocortisone acetate (HA) ointment in children with moderate to severe AD., Patients and Methods: Patients applied ointment daily to all affected body surface areas. The primary study endpoint was the percentage change in the modified Eczema Area and Severity Index (mEASI) between baseline and treatment end., Results: Six hundred and twenty-four patients, aged 2-15 years, applied 0.03% tacrolimus ointment once daily (n = 207), twice daily (n = 210) or 1% HA twice daily (n = 207). By the end of treatment, application of 0.03% tacrolimus ointment both once or twice daily resulted in significantly greater median percentage decreases in mEASI (66.7% and 76.7%, respectively) compared with 1% HA (47.6%; P < 0.001). Furthermore, the median percentage decrease in mEASI was significantly greater for patients applying 0.03% tacrolimus twice daily compared with once daily (P = 0.007). Patients with severe AD benefited especially from twice daily application of 0.03% tacrolimus ointment compared with once daily application (P = 0.001). Transient mild to moderate skin burning occurred significantly more often in the 0.03% tacrolimus groups (P = 0.028) but resolved in most cases within 3-4 days. Laboratory parameters showed no clinically relevant changes., Conclusions: 0.03% tacrolimus ointment applied once or twice daily is significantly more efficacious than 1% HA in treating moderate-severe AD in children. Twice daily application of 0.03% tacrolimus ointment results in the greatest improvement in mEASI, and is especially effective in patients with severe baseline disease.

Vasculitis is a rare cause of leg ulceration. It is unclear why severe skin infarction develops in some patients with vasculitis, whereas others have only mild symptoms such as purpura, erythema, or urticaria. A coincidence of vasculitis and hypercoagulability may lead to more extensive thrombotic occlusion and hence explain the occurrence of large ulcers in a subset of patients. Our aim was to investigate whether patients with vasculitis ulcers have an increased incidence of hypercoagulability. Thirteen consecutive patients admitted to the hospital with necrotic ulcers caused by histologically confirmed vasculitis were screened for clotting disorders. In 7 of 13 patients (53%), hypercoagulable conditions were found. Five patients had factor V Leiden (38%), and 2 had lupus anticoagulant (15%). The normal frequency of these conditions is 5% to 6% and 3.6%, respectively. These data indicate that there is an increased incidence of hypercoagulable disorders in patients with vasculitis ulcers. We recommend screening these patients routinely for hypercoagulability.

Psoriasis is a chronic disease that affects the skin and joints. Clinical hallmarks comprise erythematous plaques covered by silvery scaling and a chronic recurrent course. Histologically, psoriasis is characterized by the hyperproliferation of the epidermis, elongated and prominent blood vessels and a thick perivascular lymphocytic infiltrate. Psoriasis is now considered an auto-immune disease. Although many different therapies are available, there is clearly a need for new treatments. Our improvement of understanding of the pathogenesis of psoriasis together with the possibility to develop bioactive proteins ("biologicals") targeted at specific steps in the pathogenesis of psoriasis, have opened a new field of promising future treatments. In the development and assessment of new therapeutical modalities for psoriasis, a clear definition of a patient's psoriasis severity is essential. The impact of a given therapy can only then be evaluated, based on the changes in the severity score during and after application of the treatment., (Copyright 2004 Blackwell Publishing, Inc.)

Psoriasis and psoriatic arthritis are inflammatory diseases that respond well to anti-tumour necrosis factor-alpha therapy. To evaluate the effects of anti-tumour necrosis factor-alpha treatment on expression of adhesion molecules and angiogenesis in psoriatic lesional skin and synovial tissue, we performed a prospective single-centre study with infliximab therapy combined with stable methotrexate therapy. Eleven patients with both active psoriasis and psoriatic arthritis received infusions of infliximab (3 mg/kg) at baseline, and at weeks 2, 6, 14 and 22 in an open-label study. In addition, patients continued to receive stable methotrexate therapy in dosages ranging from 5 to 20 mg/week. Clinical assessments, including Psoriasis Area and Severity Index (PASI) and Disease Activity Score (DAS), were performed at baseline and every 2 weeks afterward. In addition, skin biopsies from a target psoriatic plaque and synovial tissue biopsies from a target joint were taken before treatment and at week 4. Immunohistochemical analysis was performed to detect the number of blood vessels, the expression of adhesion molecules and the presence of vascular growth factors. Stained sections were evaluated by digital image analysis. At week 16, the mean PASI was reduced from 12.3 +/- 2.4 at baseline to 1.8 +/- 0.4 (P

Overexposure to ultraviolet radiation (UVR) causes skin damage. An increasing awareness of this must result in people consciously wanting to protect themselves from UVR by means of clothing. The first part of the European standard on UVR-protective clothing--about test methods--is now available. In the second part the classification and labelling of UVR-protective clothing are detailed. The degree of protection the clothing provides against UVR is expressed as the ultraviolet-protection factor (UPF). The UPF is inversely proportional to the quantity of UVR which the clothing allows through. UVR-protective clothing which satisfies the European standard will bear the European UPF label '40+'. To obtain this label the entire clothing must have a UPF of at least 40. The wording: 'Sun exposure causes skin damage', 'Only covered areas are protected' and 'The protection offered by this item may be reduced with use or if the material is stretched or wet' must be added to the label.

Topical corticosteroids are the mainstay of treatment for atopic dermatitis; however, their clinical utility is limited by potential side effects. Recently, the steroid-free topical immunomodulators tacrolimus ointment and pimecrolimus cream have become available. These agents provide effective treatment without causing skin atrophy or other steroidal side effects, and their physiochemical properties, such as relatively large molecular size and high lipophilicity, limit diffusion through skin and into the bloodstream, providing skin-selective treatment. Clinical trials with more than 1,700 paediatric and adult patients have demonstrated that treatment with either agent is associated with minimal systemic absorption of tacrolimus or pimecrolimus. Additionally, studies have shown that percutaneous absorption of tacrolimus decreases as treatment continues and clinical improvement occurs. This self-limiting facet of the treatment, together with the skin-selectivity of topical immunomodulators, is reflected in the good safety and tolerability profiles of these agents, which promise to significantly improve the long-term management of atopic dermatitis.

Type 1 cytokine producing T cells play an important role in the pathogenesis of psoriasis. Ultraviolet-B (UVB) irradiation is effective in the treatment of this disease. In normal skin, UVB causes a change in dermal microenvironment, leading to a decrease of IFN-gamma expressing type 1 T cells and a concurrent increase of IL-4 expressing type 2 T cells. The aim of this study was to show whether UVB irradiation causes a like-wise shift of type 1 and type 2 responses in psoriatic skin. For this purpose, biopsies were obtained from the lesional skin of psoriatic patients before, 2 days and 14 days after a single exposure to 4 MED UVB. Sections from these biopsies were immunostained (CD3, IFN-gamma and IL-4) or RNA was extracted and analyzed for the expressions of IFN-gamma and IL-4 by PCR. In addition, primary cultures of T cells from dermal cell suspensions were stained intracellularly for IFN-gamma and IL-4 expression and CD4+ and CD8+ T subsets were analyzed by flow cytometry. IFN-gamma was abundantly expressed in situ before irradiation and decreased in all patients after UVB irradiation, whereas IL-4 expression was variably expressed before irradiation and increased in different degrees after irradiation. Cytokine mRNA expressions determined by PCR showed a clear decrease of IFN-gamma and increase of IL-4 following UVB irradiation. Both CD4+ and CD8+ dermal T cells were found to produce less IFN-gamma and more IL-4 following UVB irradiation as determined by flow cytometry. Decrease in IFN-gamma expression and increase in IL-4 expression of dermal T cells in psoriatic lesions after UVB irradiation may lead to decrease in local immunoreactivity. These changes could be part of the therapeutic effects of UVB on psoriasis.

Background: The value of laboratory tests in chronic urticaria is still controversial., Objective: Our aim was to assess this value in clinical studies, and to identify factors explaining the variation in the number of identified causes., Methods: A total of 4 electronic databases were searched, and a manual literature search was performed. Only unselected patient series with more than 50 adult patients were included. From each included study predefined items were recorded to assess their quality (consecutive patients, use of standardized diagnostic criteria) and validity (follow-up, assessment of treatment effects, level of evidence)., Results: A total of 29 studies were included, involving 6462 patients. The verification of the validity of the results and the level of evidence of the included studies were limited., Conclusion: No relationship between the number of identified diagnoses and the number of performed laboratory tests, the different settings, the study design, or the publication period was found. On the basis of this systematic review and the relevant literature, a clinical guideline in the form of a flowchart is presented.

Chronic ulceration of the lower leg is a frequent condition, with a prevalence of 3-5% in the population over 65 years of age. The incidence of ulceration is rising as a result of the ageing population and increased risk factors for atherosclerotic occlusion such as smoking, obesity and diabetes. Ulcers can be defined as wounds with a 'full thickness depth' and a 'slow healing tendency'. In general, the slow healing tendency is not simply explained by depth and size, but caused by an underlying pathogenetic factor that needs to be removed to induce healing. The main causes are venous valve insufficiency, lower extremity arterial disease and diabetes. Less frequent conditions are infection, vasculitis, skin malignancies and ulcerating skin diseases such as pyoderma gangrenosum. But even rarer conditions exist, such as the recently discovered combination of vasculitis and hypercoagulability. For a proper treatment of patients with leg ulcers, it is important to be aware of the large differential diagnosis of leg ulceration.

Purpose: To evaluate the efficacy of medium-dose UVA1 phototherapy in patients with localized scleroderma., Method: A controlled pilot study with medium-dose UVA1 (48 J/cm2) was performed. The results were evaluated by means of a skin score and two objective methods for quantifying sclerosis (cutometer and fast Fourier transform method). Patients were treated 4 times a week for 5 weeks. The follow-up period was 12 weeks., Results: All patients responded to therapy. Skin score and cutometer results showed improvement of skin elasticity of treated skin compared to control skin. Fast Fourier transform measurements showed no change in bundle orientation ratio and spacing., Conclusion: We concluded that treatment for 12 weeks 4 times a week with medium-dose UVA1 may be a beneficial therapy and a well-tolerated treatment modality for localized scleroderma (morphea). After 12 weeks, improvement of skin sclerosis can be detected by skin score and cutometer measurements but not by the fast Fourier transform method., (Copyright 2003 S. Karger AG, Basel)

Background: Upon a single high dose of UVB irradiation of psoriatic lesional skin, IFN-gamma expression is decreased, whereas IL-4 expression is enhanced. A similar type 1 to type 2 shift was found in dermal T cells derived from irradiated lesional skin as compared to unexposed lesional psoriatic skin. We have found recently that the IL-4 protein detected in situ upon UVB exposure of normal skin was not associated with T cells but with infiltrating neutrophils., Objective: To determine which cell types express IL-4 in psoriatic skin after UVB irradiation., Methods: Skin biopsies were obtained from healthy controls and psoriasis patients before and after local UVB exposure. Double immunohistochemical stainings were performed to determine the identity of IL-4-expressing cells., Results: In the irradiated skin of both healthy controls and patients, IL-4-positive cells coexpressed elastase and CD15, but not CD3., Conclusion: IL-4-expressing cells found in psoriatic skin after a single high-dose UVB exposure appeared to be neutrophils., (Copyright 2003 S. Karger AG, Basel)

We carried out a pilot study on the feasibility and accuracy of store-and-forward teledermatology based on patient-provided images and history as a triage tool for outpatient consultation. Patients referred by their general practitioner provided a history and images via the Internet. The information was reviewed by one of 12 teledermatologists and the patient then visited a different dermatologist in person within two days. Three independent dermatologists compared the remote and in-person diagnoses in random order to determine diagnostic agreement. Broader agreement was also measured, by comparing the main disease groups into which the two diagnoses fell. The teledermatologists indicated whether an in-person consultation or further investigations were necessary. There were 105 eligible patients, aged four months to 72 years, who were willing to participate. For the 96 cases included in the analysis, complete diagnostic agreement was found in 41% (n=39), partial diagnostic agreement in 10% (n=10) and no agreement in 49% (n=47). There was disease group agreement in 66% of cases (n=63). Nearly a quarter (23%) of participating patients could have safely been managed without an in-person visit to a dermatologist.

Psoriasis is a chronic, inflammatory disease with lesions that produce considerable physical discomfort and often lead to substantial disruption in patients' daily activities. The use of currently available, nonspecific, systemic immunosuppressive therapies for patients with moderate to severe psoriasis is limited by an inability to maintain disease remission safely. Advances in recombinant DNA technology paralleled with increased understanding of the immunopathology of psoriasis have led to the development of numerous biologic agents for the treatment of this disease. These new biologic therapies target specific steps in psoriasis pathology, including direct effects on T cells, T cell activation, T cell migration, and cellular production and secretion of cytokines. By selectively targeting the activities of T cells that are directly involved in psoriasis pathogenesis, these novel agents offer improved safety profiles and enhanced efficacy. In this article, the mechanisms of T cell pathogenicity that guided the development of these new biologic therapies are reviewed along with clinical data on the progress of these agents.

Objective: To investigate whether alefacept (a fully human lymphocyte function-associated antigen 3 [LFA-3]/IgG1 fusion protein that blocks the LFA-3/CD2 interaction) is able to reduce the signs and symptoms of joint inflammation in patients with active psoriatic arthritis (PsA)., Methods: Eleven patients with active PsA were treated with alefacept for 12 weeks in an open-label and explorative study. Clinical joint assessment and laboratory assessments were performed at baseline and after 4, 9, 12, and 16 weeks of treatment. Serial synovial tissue (ST) biopsy specimens from an inflamed index joint (knee, ankle, wrist, or metacarpophalangeal joint) were obtained by arthroscopy at baseline and after 4 and 12 weeks of treatment., Results: At the completion of treatment, 6 of 11 patients (55%) fulfilled the Disease Activity Score (DAS) response criteria. Nine patients (82%) fulfilled the DAS response criteria at any point during the study. There was a statistically significant reduction in CD4+ lymphocytes (P < 0.05), CD8+ lymphocytes (P = 0.05), and CD68+ macrophages (P < 0.02) in the ST after 12 weeks of treatment compared with baseline. The ST and peripheral blood of those patients fulfilling the DAS response criteria contained more CD45RO+ cells at baseline and displayed a significant reduction in these cells compared with nonresponding patients., Conclusion: The changes in ST, together with the improvement in clinical joint scores, after treatment with alefacept support the hypothesis that T cell activation plays an important role in this chronic inflammatory disease. Furthermore, since alefacept, a T cell-specific agent, led to decreased macrophage infiltration, the data indicate that T cells are highly involved in synovial inflammation in PsA.

Objective: To critically appraise the suitability of current quality-of-life (QOL) questionnaires for psoriasis research., Data Sources: Computerized searches of 5 bibliographic databases. QUESTIONNAIRE SELECTION: Predefined criteria were used to identify QOL questionnaires in dermatologic studies. Two investigators independently assessed and agreed on multidimensional generic, dermatology-specific, and psoriasis-specific QOL questionnaires for inclusion., Data Extraction: Data were extracted on the internal structure, reliability, and validity of the included questionnaires., Data Synthesis: Three generic, 3 dermatology-specific, and none of the psoriasis-specific questionnaires met the inclusion criteria: the Nottingham Health Profile (NHP), the Medical Outcomes Study 36-Item Short Form Health Survey (SF-36), the Sickness Impact Profile (SIP), the Dermatology Quality of Life Scales (DQOLS), the Dermatology-Specific Quality of Life Instrument (DSQL), and the Skindex-29. The generic NHP, SF-36 and SIP are well established, reliable, and valid. Although the data are not conclusive, the SF-36 was useful to assess effects of psoriasis on its component scales. The dermatology-specific DQOLS, DSQL, and Skindex-29 are relatively new and, therefore, less widely tested. Available psychometric data demonstrated the reliability and validity of all 3 dermatology-specific questionnaires. The Skindex-29 was also useful to assess change., Conclusions: None of the identified psoriasis-specific questionnaires met the inclusion criteria. Data on the suitability of the included questionnaires for psoriasis research were relatively sparse. The included generic questionnaires allow comparisons with nondermatologic diseases but do not allow assessment of relevant dermatology-specific aspects and are not sensitive to subtle effects of psoriasis on QOL. On the basis of the psychometric data of the present review, we find the Skindex-29 to be the most valuable dermatology-specific questionnaire for psoriasis research. Combination of the Skindex-29 with the generic SF-36 combines the merits of both types of questionnaires and we therefore recommend this combination.

To determine the effect of UVB exposure on the balance of type-1 or type-2 T-cells in skin, we examined the expression of key markers interferon (IFN)-gamma and interleukin (IL)-4 in cryostat sections. IFN-gamma mRNA was clearly detectable in nonirradiated control skin, and IFN-gamma protein was found in 2% of the dermal CD3pos T-cells, whereas IL-4 mRNA was hardly detectable, and no IL-4 protein was found. In contrast, IL-4 mRNA expression increased upon irradiation, and IL-4 was found in 2% of the T-cells at day 2 after UVB-exposure. Concomitantly, IFN-gamma mRNA expression decreased, and IFN-gamma protein became absent. We also analyzed T-cells present in primary dermal cell cultures, which were used as an in vitro equivalent of the in vivo situation. As compared with T-cells from control skin, T-cells in dermal cell cultures from UVB-exposed skin displayed an increased IL-4 and decreased IFN-gamma expression. No such skewing occurred when the T-cells from irradiated skin were cloned in the absence of a dermal microenvironment. Except for an occasional positive T-cell, type-1-associated cell-surface markers (CCR5, CXCR3) or type-2 markers (CCR3, CD30, CRTH2) were undetectable in situ. But these markers were expressed on cultured dermal T-cells from UVB-exposed and control skin at a comparable level, but did not correlate with the IFN-gamma and IL-4 production. Altogether, UVB-induced changes of the dermal microenvironment favor the development of type-2 T-cells.