Psoriasis: de Rie MA

Lecluse LL, Piskin G, Mekkes JR, Bos JD, de Rie MA. · Department of Dermatology, Academic Medical Center, University of Amsterdam, PO Box 22700, 1100 DE Amsterdam, The Netherlands. · Br J Dermatol. · Pubmed #18627374 No free full text.

Abstract: Infliximab (Remicade; Schering-Plough, Kenilworth, NJ, U.S.A.) is a chimeric monoclonal antibody that acts as a tumour necrosis factor-alpha inhibitor. Infliximab is registered for the treatment of rheumatoid arthritis, psoriatic arthritis, Crohn disease, ulcerative colitis, ankylosing spondylitis and plaque-type psoriasis. Like other foreign protein-derived agents, infliximab may lead to infusion reactions during and after infusion. Infusion reactions occur in 3-22% of patients with psoriasis treated with infliximab. Most of these reactions are mild or moderate and only few are severe. Nevertheless, they may lead to discontinuation of treatment. As infliximab for psoriasis is prescribed as a last resort and is in most cases very effective, discontinuation of treatment is undesirable. With proper care and prevention of the infusion reactions the need to discontinue treatment with infliximab can be diminished. The objective of this article is to present a guideline for the management of infliximab-related infusion reactions, based on the best available evidence. This guideline can be used in patients with psoriasis as well as in dermatology patients receiving infliximab for off-label indications such as hidradenitis suppurativa or pyoderma gangrenosum.

de Rie MA. · No affiliation provided · Dermatology. · Pubmed #10636696 No free full text.

This publication has no abstract.

de Rie MA, van Kuijk AW, Goedkoop AY, Tak PP. · Academisch Medisch Centrum/Universiteit van Amsterdam, Afd. Huidziekten, Amsterdam. · Ned Tijdschr Geneeskd. · Pubmed #17784693 No free full text.

Abstract: The symptoms ofpsoriatic arthritis vary from arthralgia and enthesitis to chronic erosive and mutilating arthritis, and are seen in 6-39% of all psoriasis patients. Because of increasing awareness of the clinical signs of psoriatic arthritis among both dermatologists and rheumatologists, the diagnosis ofpsoriatic arthritis is made more often; this is important since earlier diagnosis and treatment can avoid irreversible joint destruction. The overlap between the immunological mechanisms in the pathogenesis ofpsoriasis and psoriatic arthritis has led to the identification of common therapeutic targets, of which tumour-necrosis factor (TNF) is the most important. The successful treatment of psoriasis patients with TNF-a-blocking agents has not only brought about a marked improvement in the quality of life of many patients but has also improved the insight into the pathogenesis, for example by demonstrating that the role of acquired immunity is much more important than was previously thought. The Dutch Society of Dermatology and Venereology and the Dutch Society of Rheumatology have drawn up guidelines for the treatment of patients with psoriasis and psoriatic arthritis using these so-called biologics.

Bos JD, de Rie MA, Teunissen MB, Piskin G. · Department of Dermatology, Academic Medical Center, University of Amsterdam, P.O.Box 22700, 1100 DE Amsterdam, the Netherlands. · Br J Dermatol. · Pubmed #15948970 No free full text.

Abstract: 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.

Spuls PI, Tuut MK, van Everdingen JJ, de Rie MA, Anonymous00367. · Academisch Medisch Centrum/Universiteit van Amsterdam, afd. Dermatologie, Amsterdam. · Ned Tijdschr Geneeskd. · Pubmed #15553355 No free full text.

Abstract: The guideline for the treatment of adults with moderate to severe chronic plaque-type psoriasis vulgaris is based on published scientific evidence. The efficacy of the treatment, its safety, the side effects, the patients' discomfort, the patients' preference and the costs of treatment and follow-up are listed as criteria that play a role in the choice of treatment. Photo(chemo)therapy is the treatment of choice for severe forms of psoriasis. Phototherapy with ultraviolet-B light (UVB), especially narrow-band UVB, is preferred above photochemotherapy with ultraviolet-A light and psoralenes (PUVA). Of the oral treatments, methotrexate and ciclosporin are preferred above retinoids and fumarates because they yield a higher percentage of patients with partial or nearly complete remission. Fumarates are not officially registered in The Netherlands and Belgium.

de Rie MA, Goedkoop AY, Bos JD. · Department of Dermatology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands. · Dermatol Ther. · Pubmed #15379769 No free full text.

Abstract: 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.

de Rie MA, Pavel S. · Academisch Medisch Centrum/Universiteit van Amsterdam, afd. Huidziekten, Meibergdreef 9, 1105 AZ Amsterdam. · Ned Tijdschr Geneeskd. · Pubmed #12404906 No free full text.

Abstract: Photodermatology has become an important part of the dermatologist's area of focus. This subspeciality is not only involved with studying basic biological processes such as the effects of ultraviolet (UV) irradiation on the skin's immune system (photo-immunology), melanocytes or DNA (carcinogenesis), but also with clinical issues such as photoprotection, photosensitive skin diseases (photodermatoses) and phototherapy. Increasing knowledge about the effects of UV irradiation on the skin, with or without photosensitising agents, has led to the development of new forms of photo(chemo)therapy. These allow good therapeutic results to be achieved in the treatment of not only psoriasis, but also other chronic inflammatory skin diseases, with minimal side effects. DNA can absorb UV irradiation. This can lead to irreversible DNA damage and mutations in genes responsible for cell cycle control. These events can lead to skin cancer. The presence of pheomelanin, which is an inferior type of UV light-absorbing melanin, can add to this process of DNA damage. The three most important types of skin cancer are basal cell carcinoma (more than 30,000 new patients per year in the Netherlands), squamous cell carcinoma and melanoma.

Heydendael VM, Spuls PI, Ten Berge IJ, Opmeer BC, Bos JD, de Rie MA. · Department of Dermatology, Academic Medical Center, University of Amsterdam, PO Box 22660, the Netherlands. · Br J Dermatol. · Pubmed #12100194 No free full text.

Abstract: BACKGROUND: Cyclosporin is an effective treatment for severe plaque psoriasis. Unfortunately, its use may be limited by time- and dose-related nephrotoxicity. Serum trough levels may be useful for monitoring the risk of nephrotoxicity. OBJECTIVES: To determine whether monitoring of trough levels is necessary in psoriasis patients undergoing short-term treatment with cyclosporin. METHODS: A computerized and manual literature search identified studies on adults with plaque-type psoriasis treated with cyclosporin < or = 5 mg kg-1 daily, in which trough levels were measured in whole blood. Number of patients, treatment duration, formulation and dosage, renal function tests and trough levels were extracted. The association between renal function and trough levels was investigated. Additionally, in a randomized controlled trial on cyclosporin vs. methotrexate in moderate to severe psoriasis, cyclosporin trough levels were measured frequently in 20 patients during 12 weeks of treatment. The Pearson correlation coefficient between serum creatinine and cyclosporin trough levels was calculated. RESULTS: Fifty-six articles were found concerning cyclosporin trough level measurements in psoriasis patients, of which eight were analysed. Many studies were excluded due to inappropriate cyclosporin dosages used. As data were heterogeneous and lacked various key parameters, a correlation study and a meta-analysis could not be performed. Instead, a quantitative description of the literature was given. No high mean trough levels or elevations of serum creatinine were described. In our clinical study, all the mean trough levels in 17 patients treated with cyclosporin 3 mg kg-1 daily were within the therapeutic range (< 200 ng mL-1). Elevated trough levels were found in two of three patients treated with cyclosporin 3-5 mg kg-1 daily. No signs of renal dysfunction were seen. CONCLUSIONS: The literature does not provide a definitive answer on whether monitoring cyclosporin trough levels in patients with psoriasis should be standard practice. Our own data show no need for cyclosporin trough level monitoring during short-term treatment with cyclosporin 3 mg kg-1 daily. However, when cyclosporin doses are > 3 mg kg-1 daily, monitoring may be indicated.

Goedkoop AY, Kraan MC, Teunissen MB, Picavet DI, de Rie MA, Bos JD, Tak PP. · Division of Clinical Immunology and Rheumatology, Academic Medical Centre/University of Amsterdam, Meibergdreef 9, NL-1105 AZ Amsterdam, The Netherlands. · Ann Rheum Dis. · Pubmed #15194570 links to  free full text

Abstract: 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.

Rentenaar RJ, Heydendael VM, van Diepen FN, de Rie MA, ten Berge IJ. · Laboratory for Experimental Immunology, Academic Medical Center, Amsterdam, The Netherlands. · J Clin Immunol. · Pubmed #15163892 No free full text.

Abstract: Cyclosporin A and methotrexate are highly effective drugs in the treatment of psoriasis. It was hypothesized that these therapies might modulate T helper cell cytokine secretion patterns or T cell migration patterns. Flow cytometric determination of interferon-gamma (IFNgamma) and interleukin 4 (IL4) producing T helper cell frequencies, as well as of cutaneous lymphocyte associated antigen (CLA) expressing T cell frequencies was performed in patients suffering from severe psoriasis, before, during, and after a scheduled immunosuppressive regimen with either cyclosporin A or methotrexate. Both cyclosporin A and methotrexate treatment reduced the psoriasis area severity index score after 12 weeks of treatment. Cyclosporin A treatment reduced the frequencies of IL4-producing CD4(pos) T cells, without significantly affecting the T helper 1 to T helper 2 (Th1/Th2) balance but in conjunction with the decreasing number of peripheral blood eosinophil counts. In methotrexate-treated patients, the Th1/Th2 balance was unaffected. Cessation of both therapies resulted in increased numbers of IFNgamma- as well as IL4-producing CD4(pos) T cells as compared to before initiation of oral therapy. Methotrexate, but not cyclosporin A, treatment reduced the frequencies of circulating skin-homing CLA(pos) T cells. This effect was reversed by 4 weeks after withdrawal of methotrexate therapy. We conclude that (1) neither cyclosporin A nor methotrexate affects the balance between Th1 and Th2 cells; (2) exaggerated cytokine production by T helper cells after cessation of oral cyclosporin A or methotrexate drug treatment may contribute to the reappearance of psoriatic skin lesions; and (3) decrease of circulating skin-homing T cells may be responsible for part of the therapeutic effect of methotrexate in severe psoriasis.

Heydendael VM, de Borgie CA, Spuls PI, Bossuyt PM, Bos JD, de Rie MA. · Department of Dermatology, Academic Medical Center, University of Amsterdam, The Netherlands. · J Investig Dermatol Symp Proc. · Pubmed #15083779 No free full text.

Abstract: 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.

Goedkoop AY, de Rie MA, Picavet DI, Kraan MC, Dinant HJ, van Kuijk AW, Tak PP, Bos JD, Teunissen MB. · Department of Dermatology, Academic Medical Center, University of Amsterdam, P.O. Box 22660, 1100 DD Amsterdam, The Netherlands. · Arch Dermatol Res. · Pubmed #14968366 No free full text.

Abstract: 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.

Heydendael VM, Spuls PI, Opmeer BC, de Borgie CA, Reitsma JB, Goldschmidt WF, Bossuyt PM, Bos JD, de Rie MA. · Department of Dermatology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands. · N Engl J Med. · Pubmed #12917302 links to  free full text

Abstract: BACKGROUND: Methotrexate and cyclosporine are well-known systemic therapies for moderate-to-severe chronic plaque psoriasis. We conducted a randomized, controlled trial comparing methotrexate and cyclosporine in terms of effectiveness, side effects, and the quality of life. METHODS: A total of 88 patients with moderate-to-severe psoriasis were randomly assigned to treatment for 16 weeks with either methotrexate (44 patients; initial dose, 15 mg per week) or cyclosporine (44 patients; initial dose, 3 mg per kilogram of body weight per day) and were followed for another 36 weeks. The primary outcome was the difference between groups in the psoriasis area-and-severity index after 16 weeks of treatment, after adjustment for base-line values; scores were determined in a blinded fashion by trained observers. RESULTS: Two patients were excluded from the analysis after randomization because they were found to be ineligible, and one patient withdrew his consent. Twelve patients in the methotrexate group had to discontinue treatment because of reversible elevations in liver-enzyme levels, and 1 patient in the cyclosporine group had to do so because of an elevation in the bilirubin level, but all 13 were included in the analysis. After 16 weeks of treatment, the mean (+/-SE) score for the psoriasis area-and-severity index decreased from 13.4+/-3.6 at base line to 5.0+/-0.7 among 43 patients treated with methotrexate, whereas the score decreased from 14.0+/-6.6 to 3.8+/-0.5 among 42 patients treated with cyclosporine. After adjustment for base-line values, the mean absolute difference in values at 16 weeks was 1.3 (95 percent confidence interval, -0.2 to 2.8; P=0.09). The physician's global assessment of the extent of psoriasis, the time to and the rates of remission, and the quality of life were similar in the two groups. CONCLUSIONS: No significant differences in efficacy were found between methotrexate and cyclosporine for the treatment of moderate-to-severe psoriasis.

Piskin G, Heydendael VM, de Rie MA, Bos JD, Teunissen MB. · Department of Dermatology, Room L3-359, Academic Medical Center, University of Amsterdam, P.O. Box: 22700, The Netherlands. · Arch Dermatol Res. · Pubmed #12624782 No free full text.

This publication has no abstract.

Kraan MC, van Kuijk AW, Dinant HJ, Goedkoop AY, Smeets TJ, de Rie MA, Dijkmans BA, Vaishnaw AK, Bos JD, Tak PP. · Division of Clinical Immunology and Rheumatology F4-218, Academic Medical Center/University of Amsterdam, Meibergdreef 9, NL-1105 AZ Amsterdam, The Netherlands. · Arthritis Rheum. · Pubmed #12384938 links to  free full text

Abstract: 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.

de Rie MA, de Hoop D, Jönsson L, Bakkers EJ, Sørensen M. · Academisch Medisch Centrum, Amsterdam, The Netherlands. · Dermatology. · Pubmed #11244227 No free full text.

Abstract: BACKGROUND: The high prevalence and chronic nature of psoriasis leads to high costs in relation to the treatment and control of the disease. A number of clinical trials have shown that a combination therapy of calcipotriol cream (Daivonex/Dovonex), Leo Pharmaceutical Products) and ultraviolet B phototherapy (UVB) decreases the total number of UVB exposures required compared to UVB treatment alone. From a societal point of view, the addition of calcipotriol to UVB therapy could achieve cost savings due to the fewer UVB treatments needed and the reduced travelling and time off work for patients. Fewer UVB exposures may also have other beneficial effects, i.e., shortened waiting lists and less risk to patients of developing cancer or photoaging of the skin. OBJECTIVE: To compare the cost-effectiveness of treating psoriatic patients in the Netherlands with calcipotriol cream used daily combined with twice weekly UVB treatments to emollient used daily combined with UVB given 3 times weekly. METHODS: Based on the clinical results from a Canadian trial, a decision-analytical model was constructed to simulate treatment outcomes and estimate the costs of managing psoriatic patients in the Netherlands over a period of 20 weeks from initiation of therapy. Unit costs and details of standard treatment protocols were collected from Dutch dermatology centres in hospitals and the community for use in the model. Other therapies, such as topical corticosteroids, tar or dithranol were not investigated in this analysis. RESULTS: The total cost of managing psoriatic patients in the Netherlands over a 20-week period is estimated as EUR 1,175.90 for those treated with calcipotriol and UVB and EUR 1,212.14 for patients treated with emollient and UVB. Thus, the former treatment, adding calcipotriol to UVB phototherapy, provides a minor cost saving of EUR 36.24 (3%) compared to the cost of UVB treatment alone. Sensitivity analyses demonstrated that these results are sensitive to changes in the cost of UVB treatment. CONCLUSION: Calcipotriol treatment combined with UVB phototherapy is a cost-neutral alternative to UVB phototherapy used with an emollient. The patients achieve treatment success in the same time on both treatments but the former, with calcipotriol, requires less exposure to UVB radiation. The additional drug costs from using calcipotriol are offset by savings from the fewer UVB sessions required. Essential beneficial effects for patients are less inconvenience, less risk of developing photoaging of the skin and less exposure to potentially carcinogenic radiations.

Brands S, Brakman M, Bos JD, de Rie MA. · Department of Dermatology, Academic Medical Centre, University of Amsterdam, and the Department of Dermatology, Reinier de Graaf Gasthuis, Delft, The Netherlands. · J Am Acad Dermatol. · Pubmed #10570386 No free full text.

Abstract: BACKGROUND: Broad-band UVB phototherapy has appeared to be effective in clearing psoriatic lesions. After the advent of calcipotriol ointment, promising results have been obtained by combining these two therapeutic modalities. Also, an additional effect of narrow-band UVB phototherapy on treatment with calcipotriol ointment has been demonstrated. OBJECTIVE: Our purpose was to compare treatment with low-dose narrow-band UVB phototherapy both with and without calcipotriol ointment. METHODS: We included 53 patients suffering from plaque-type psoriasis. All patients underwent low-dose narrow-band UVB phototherapy. Nearly half of the patients were randomized to apply calcipotriol ointment (50 microg/g) twice daily on the affected skin. The Psoriasis Area and Severity Index (PASI) was used to evaluate psoriatic lesions. RESULTS: In this study we showed that low-dose narrow-band UVB phototherapy is effective in the treatment of psoriasis and that calcipotriol ointment does not improve treatment outcome. CONCLUSION: Calcipotriol ointment does not improve treatment with low-dose narrow-band UVB phototherapy.

de Korte J, van der Valk PG, Sprangers MA, Damstra RJ, Kunkeler AC, Lijnen RL, Oranje AP, de Rie MA, de Waard-van der Spek FB, Hol CW, van de Kerkhof PC. · Department of Dermatology, Academic Medical Centre, University of Amsterdam, Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands. · Br J Dermatol. · Pubmed #18067483 No free full text.

Abstract: BACKGROUND: Calcipotriol ointment and short-contact dithranol cream therapy are well-established topical treatments for psoriasis. Quality of life, i.e. the physical, psychological, and social functioning and well-being of the patient, has become an essential outcome measure in chronic skin disease. OBJECTIVES: To compare the quality-of-life outcomes of calcipotriol ointment with that of short-contact dithranol cream in a supervised treatment regimen, and to determine the degree of improvement in quality of life these topical treatments can accomplish. METHODS: In a multicentre randomized controlled trial in six centres in the Netherlands, 106 patients with chronic plaque psoriasis were included, 54 receiving calcipotriol ointment twice daily and 52 dithranol cream once daily in a 12-week intensive treatment programme. Patients were treated at the day-care centre, using the care instruction principle of daily visits during the first week and twice-weekly visits subsequently for up to 12 weeks. Quality of life was assessed with the Skindex-29 and the Medical Outcomes Study 36-item Short-Form General Health Survey (SF-36). RESULTS: At the end of treatment, no statistically significant differences were found between the calcipotriol and the dithranol group in any of the quality-of-life domains or scales of the Skindex-29 and the SF-36. Over time, a significant improvement of quality of life was found on all three scales of the dermatology-specific Skindex-29, predominantly of a moderate magnitude. In the calcipotriol group, a significant change of a small magnitude was found in the Physical Component Summary of the SF-36. No significant changes were found in the Mental Component Summary (or on any of the eight scales composing the questionnaire) of the SF-36. CONCLUSIONS: The hypothesis was confirmed, that no statistically significant differences in improvement of quality of life could be found between calcipotriol ointment and dithranol short-contact cream in a day-care setting. Given this result, both calcipotriol and dithranol can be welcome alternatives for the patient. Calcipotriol, being more practical and patient friendly, can be considered as a first-line approach in clinical practice. However, in patients recalcitrant to calcipotriol and/or other topical treatments, preference should be given to the dithranol regimen. Topical treatment in combination with interventions explicitly focusing on improvement of coping behaviour and psychosocial functioning may further increase the degree of improvement in the psychosocial domains of quality of life. The results of this study are likely to give further evidence to the notion that the generic SF-36 is little or not responsive to small to moderate changes in quality of life in mild to moderate psoriasis.

de Groot M, Teunissen MB, Ortonne JP, Lambert JR, Naeyaert JM, Picavet DI, Arreaza MG, Simon JS, Kraan M, Bos JD, de Rie MA. · Department of Dermatology, Academic Medical Center, University of Amsterdam, PO Box 22700, 1100 DE Amsterdam, The Netherlands, · Arch Dermatol Res. · Pubmed #17647003 links to  free full text

Abstract: Several reports have indicated that the chemokine receptor CCR5 and its ligands, especially CCL5 (formerly known as RANTES), may play a role in the pathogenesis of psoriasis. The purpose of this investigation was to examine the expression of CCR5 and its ligands in chronic plaque psoriasis and to evaluate the clinical and immunohistochemical effect of a CCR5 receptor inhibitor. Immunohistochemical analysis showed low but significant increased total numbers of CCR5 positive cells in epidermis and dermis of lesional skin in comparison to non-lesional skin. However, relative expression of CCR5 proportional to the cells observed revealed that the difference between lesional and non-lesional skin was only statistically significant in the epidermis for CD3 positive cells and in the dermis for CD68 positive cells. Quantification of mRNA by reverse transcriptase-polymerase chain reaction only showed an increased expression of CCL5 (RANTES) in lesional skin. A randomized placebo-controlled clinical trial in 32 psoriasis patients revealed no significant clinical effect and no changes at the immunohistochemical level comparing patients treated with placebo or a CCR5 inhibitor SCH351125. We conclude that although CCR5 expression is increased in psoriatic lesions, this receptor does not play a crucial role in the pathogenesis of psoriasis.

Opmeer BC, Heydendael VM, deBorgie CA, Spuls PI, Bossuyt PM, Bos JD, de Rie MA. · Department of Clinical Epidemiology, Biostatistics and Bioinformatics, Academic Medical Center, University of Amsterdam, P.O. Box 22660, 1100 DD, Amsterdam, The Netherlands. · J Clin Epidemiol. · Pubmed #17573985 No free full text.

Abstract: OBJECTIVE: The importance of validly identifying and incorporating patients' views for improving health care is generally acknowledged. Common approaches to assess patients' preferences are based on the quality adjusted life year (QALY) framework, but this ignores a number of aspects that may be relevant. As an alternative, we assessed patients' treatment preferences and trade-offs for five common systemic therapies for psoriasis. STUDY DESIGN AND SETTING: Twenty-nine patients with moderate-to-severe psoriasis expressed treatment preferences for five oral and phototherapies and indicated the relative importance of various treatment attributes, such as adverse effects, discomforts, and safety measures. In a structured interview, they were presented with clinical scenarios that contained descriptions of process and outcome characteristics and illustrations of the anticipated treatment benefit. RESULTS: Over all paired comparisons, methotrexate (33%), cyclosporin (30%), acitretin (15%), UV-B (14%), and PUVA (8%) were preferred to the other treatment. Patients were willing to trade-off their initial preference for more improvement of psoriasis. CONCLUSIONS: Psoriasis patients generally prefer oral to phototherapies and consider most adverse effects and several discomforts important for selecting treatment. Our scenario-based structured interview approach to treatment preferences allowed us to incorporate a broad spectrum of potentially relevant decision components in a clinically meaningful way.

de Groot M, Appelman M, Spuls PI, de Rie MA, Bos JD. · Department of Dermatology A0-252, Academic Medical Centre, University of Amsterdam, PO Box 22700, 1100 DE Amsterdam, the Netherlands. · Br J Dermatol. · Pubmed #16965432 No free full text.

Abstract: 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.

van de Kerkhof PC, van der Valk PG, Swinkels OQ, Kucharekova M, de Rie MA, de Vries HJ, Damstra R, Oranje AP, de Waard-van der Spek FB, van Neer P, Lijnen RL, Kunkeler AC, van Hees C, Haertlein NG, Hol CW. · Department of Dermatology, Academisch Medisch Centrum, Meibergdreef 9, 1105 AC Amsterdam, The Netherlands. · Br J Dermatol. · Pubmed #16965431 No free full text.

Abstract: BACKGROUND: Calcipotriol has become a first-line treatment for psoriasis. Its efficacy and safety have been shown in many comparative clinical trials carried out in outpatients. In a comparative study in patients visiting the outpatient department once every 14 days, it was shown that calcipotriol was more effective and better tolerated compared with dithranol. OBJECTIVES: To compare the clinical efficacy of calcipotriol ointment with that of dithranol cream in a supervised treatment regimen. METHODS: In a multicentre randomized controlled trial in six centres in the Netherlands, 106 patients with chronic plaque psoriasis were included, 54 receiving calcipotriol ointment twice daily and 52 dithranol cream once daily. Patients were treated at the day-care centre, using the care instruction principle of daily visits during the first week and twice-weekly visits subsequently for up to 12 weeks. RESULTS: This study failed to prove that calcipotriol is as efficacious as dithranol when used in a day-care setting (noninferiority test). The mean percentage reduction in Psoriasis Area and Severity Index from baseline to end of treatment was 57.0% in the calcipotriol group vs. 63.6% in the dithranol group. However, the two-sided test for superiority indicated no statistically significant difference between the treatment groups (P = 0.39). At the end of treatment, 15% of the patients treated with calcipotriol ointment and 25% of those treated with dithranol cream did not require any further treatment. Although calcipotriol ointment appeared to be more effective during the first 8 weeks, a difference was no longer apparent at 12 weeks. In comparison with the high number of drop-outs due to cutaneous side-effects in the calcipotriol group, the frequency of a tolerable degree of irritation appeared to be higher in patients treated with dithranol. However, concomitant corticosteroid treatment of dithranol irritation in seven patients may have contributed to this difference between both treatments. Moreover, patients receiving therapy with calcipotriol ointment experienced fewer application-related skin and subcutaneous tissue disorders than patients treated with dithranol cream: 21 of 53 (40%) and 37 of 52 (71%), respectively. This difference is statistically significant (P = 0.001). CONCLUSIONS: The hypothesis that calcipotriol ointment might be at least as effective as dithranol cream in the day-care setting could not be proven in the present study. Whereas calcipotriol has become a mainstay in the routine outpatient treatment of psoriasis not requiring a day-care setting, dithranol treatment, being difficult as a routine outpatient therapy, has increased efficacy and improved tolerability if the treatment is carried out in a day-care setting.

Goedkoop AY, de Rie MA, Teunissen MB, Picavet DI, van der Hall PO, Bos JD, Tak PP, Kraan MC. · Department of Dermatology, Academic Medical Center, University of Amsterdam, P.O. Box 22660, 1100 DD Amsterdam, The Netherlands. · Arch Dermatol Res. · Pubmed #16012877 No free full text.

Abstract: 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.

Goedkoop AY, Kraan MC, Picavet DI, de Rie MA, Teunissen MB, Bos JD, Tak PP. · Division of Clinical Immunology and Rheumatology, Department of Internal Medicine, Academic Medical Center/University of Amsterdam, Amsterdam, The Netherlands. <> · Arthritis Res Ther. · Pubmed #15225368 links to  free full text

Abstract: 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 <or= 0.02). The mean DAS was reduced from 6.0 +/- 0.5 to 3.6 +/- 0.6 (P <or= 0.02). We found some fluctuations in DAS response as compared with the change in PASI, with the latter exhibiting a steady decrease over time. After 4 weeks the cell infiltrate was reduced in both skin and synovium. There was a significant reduction in the number of blood vessels in dermis and synovium at week 4. A significant reduction in the expression of alphavbeta3 integrin, a marker of neovascularization, was also found in both skin and synovium at week 4. In addition, a significant reduction in the expression of adhesion molecules was observed in both skin and synovium at week 4. We also observed a trend toward reduced expression of vascular endothelial growth factor in both skin and synovium. In conclusion, low-dose infliximab treatment leads to decreased neoangiogenesis and deactivation of the endothelium, resulting in decreased cell infiltration and clinical improvement in psoriasis and psoriatic arthritis.

Boersma BR, de Rie MA. · No affiliation provided · Ned Tijdschr Geneeskd. · Pubmed #11233041 No free full text.

This publication has no abstract.