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Psoriasis

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15341. Genetics of psoriasis: the potential impact on new therapies. (Abstract)

Genetics of psoriasis: the potential impact on new therapies. There is considerable epidemiologic evidence that genes play a key role in the pathogenesis of psoriasis. It is also clear that multiple genes are involved and that the disease is genetically heterogeneous. Important interactions with the environment are also implicated in its development. A number of genetic loci have been identified by genome wide linkage scans and two loci have been replicated: PSORS1 on chromosome 6, within (...) the major histocompatibility complex, and PSORS2 on chromosome 17q. Understanding the genetic basis of psoriasis will represent a major advance in our understanding of the disease and will reveal novel disease-specific biologic pathways. This information will be used to develop more specific diagnostic and prognostic tools and also lead to the development of individualized treatment plans. Benefits of the latter include more effective and safer treatments and potentially major pharmaco-economic gain.

2003 Journal of American Academy of Dermatology

15342. Quality of life issues in psoriasis. (Abstract)

Quality of life issues in psoriasis. Psoriasis is associated with significant psychosocial morbidity and a decrease in health-related quality of life. It is important to view psoriasis as a serious disease and resist the tendency to underestimate its impact on overall patient well-being. The disability experienced by psoriasis sufferers is comparable to that of patients with other chronic illnesses such as heart disease, diabetes, cancer, and depression. Aggressive intervention is warranted (...) in order to improve patient quality of life and decrease the potential for psychosocial sequelae. Health-related quality of life measures are becoming a necessary adjunct to traditional clinical assessments in the evaluation and treatment of psoriasis patients by the individual clinician. They also provide valuable information to government agencies and third party payers in the determination of resource allocation and reimbursement.

2003 Journal of American Academy of Dermatology

15343. The design of clinical trials in psoriasis: lessons for clinical practice. (Abstract)

The design of clinical trials in psoriasis: lessons for clinical practice. Understanding the process by which drugs are approved gives clinicians a better understanding of the medications they prescribe and how these medications are best used to care for patients. The development of new drugs in the United States proceeds through a series of studies culminating in well-designed, large-scale human trials. These studies result from a coordinated collaboration between industry and the Food (...) and Drug Administration (FDA). The results of these studies determine whether drugs are approved for use or not. They also determine the labeling and marketing of products and guide (but do not fully determine) physicians' use of the drug. This article follows a hypothetical drug for use in psoriasis through the approval process, in order to illustrate the process and its implications for clinical practice.

2003 Journal of American Academy of Dermatology

15344. Current systemic therapies for psoriasis: where are we now? (Abstract)

Current systemic therapies for psoriasis: where are we now? Many systemic agents are used in the treatment of psoriasis. They provide good control of psoriasis in the majority of patients and have improved their life quality indices. Frequently, combination therapy is utilized to synergize the efficacy of these medications. Many dermatologists are hesitant in prescribing systemic agents because of their adverse effects. However, such potential toxicities arising from these medications can

2003 Journal of American Academy of Dermatology

15345. Phototherapy treatment of psoriasis today. (Abstract)

Phototherapy treatment of psoriasis today. The use of the various forms of phototherapy remains an essential treatment option for psoriasis vulgaris. Expertise concerning the mechanisms involved with the actions of therapeutic ultraviolet light and the proper delivery of office-based treatments resides within the specialty of dermatology. New therapies for the treatment of moderate to severe psoriasis will soon become available which have specific actions on the cutaneous immune system (...) . A better understanding of the known mechanisms of action for ultraviolet light therapy makes it appropriate to include this area of treatment with new biologic agents. Photochemotherapy and various forms for delivery of narrow band ultraviolet B can be used as treatments, either as monotherapy or in combination with other agents, to effectively treat moderate and severe psoriasis.

2003 Journal of American Academy of Dermatology

15346. Development and use of alefacept to treat psoriasis. (Abstract)

Development and use of alefacept to treat psoriasis. Activated memory T cells, expressing CD2, are key components in the pathogenesis of psoriasis. Alefacept binds to CD2, blocks co-stimulatory signaling, and selectively induces apoptosis of pathogenic T cells. Our objective is to present safety and efficacy results which lead to the new drug application (NDA) of alefacept for the treatment of psoriasis. We reviewed the key phase II and III trials in over 1300 patients and found that during (...) treatment and follow-up of patients receiving 12 weekly intramuscular or intravenous injections of alefacept, about 1/3 will achieve a reduction in psoriasis area and severity index (PASI) of > or =75% and nearly 2/3 a reduction in PASI of > or =50%. Patients who achieved a > or =75% reduction from baseline PASI during or after a single course maintained a > or =50% reduction in PASI for a median duration of >7 months. Among patients who received 2 courses of alefacept, 40% and 71% of patients achieved

2003 Journal of American Academy of Dermatology

15347. Infliximab for psoriasis. (Abstract)

Infliximab for psoriasis. This review summarizes the use of inflximab in psoriasis and other immune-mediated inflammatory disorders (IMIDs). The magnitude and speed of the response to infliximab monotherapy of moderate to severe psoriasis vulgaris is substantial, being similar to those achieved with cyclosporin. In contrast with cyclosporin, clinical improvement after the initial 3 intravenous influsions of infliximab is maintained for as long as 6 months in approximately half the patients (...) with the absence of any additional treatment. Additionally, infliximab monotherapy normalizes keratinocyte proliferation and differentiation and markedly decreases epidermal inflammation. These results provide a convincing argument for the role of TNF-alpha in the pathogenesis of psoriasis and for the clinical development of infliximab for the treatment of psoriasis.

2003 Journal of American Academy of Dermatology

15348. Combining the new biologic agents with our current psoriasis armamentarium. (Abstract)

Combining the new biologic agents with our current psoriasis armamentarium. Combination therapy, rotational therapy, and sequential therapy have been used for psoriasis in attempts to achieve greater efficacy and greater safety. The purpose of this manuscript is to review potential advantages and disadvantages of new biologic agents as we look forward to their use in combination regimens with other systemic, topical, and light therapies. Data on the efficacy and toxicity of existing systemic (...) therapies and new biologic agents is reviewed with an emphasis on potential additive or synergistic benefits or toxicities. The mechanism of action of biologic agents differs from systemic agents currently in use, suggesting that there may be additive effects in treating psoriasis. The absence of hepatotoxicity and nephrotoxicity are important advantages when considering combination therapy with biologic agents. The advantages of the use of biologic therapies in combination or rotation with other

2003 Journal of American Academy of Dermatology

15349. Investigational therapies for psoriasis. (Abstract)

Investigational therapies for psoriasis. As the pathogenesis of psoriasis is better understood, specific targeted therapies are being developed. In addition to alefacept, etanercept, efaluzimab, and infliximab, discussed in separate articles in this issue, numerous other investigational therapies are currently in clinical trials, some of which will likely be approved in the future. We review the most promising of these therapies and their mechanisms of action.

2003 Journal of American Academy of Dermatology

15350. Inpatient hospital care for psoriasis: a vanishing practice in the United States. (Abstract)

Inpatient hospital care for psoriasis: a vanishing practice in the United States. Inpatient hospital care was a traditional approach to treat severe psoriasis. Since 1980, only modest innovations in psoriasis therapy have been introduced, but regulation and financing of inpatient hospital care have changed greatly.We documented changes in the use of inpatient care in acute care hospitals for psoriasis in a cohort of individuals with severe psoriasis and nationally.Using interviews, we (...) quantified hospitalizations for psoriasis and other reasons among the PUVA Follow-up Study cohort. We used National Hospital Discharge Survey data to determine national trends in hospitalization rates.In 2 decades, national rates of hospitalization primarily for psoriasis decreased more than 80%. Among our cohort of persons with severe psoriasis, the age-adjusted rate of hospital days for psoriasis decreased more than 60% during this period.Currently, hospitalization in acute care hospitals is seldom

2003 Journal of American Academy of Dermatology

15351. Climatotherapy at the Dead Sea is a remittive therapy for psoriasis: combined effects on epidermal and immunologic activation. (Abstract)

Climatotherapy at the Dead Sea is a remittive therapy for psoriasis: combined effects on epidermal and immunologic activation. The beneficial effect of climatotherapy at the Dead Sea (CDS) for psoriasis has been established clinically but there is a striking lack of studies assessing its in vivo effect at the molecular and cellular levels.We sought to study the response of activated immunologic cells and keratinocytes in psoriatic lesions to CDS.A total of 27 patients with chronic, stable (...) , plaque-type psoriasis treated with CDS for 28 consecutive days were evaluated with the Psoriasis Area and Severity Index score and quantitative histologic measures.After 4 weeks of treatment, the overall Psoriasis Area and Severity Index score decreased by 81.5%. Complete clearance was achieved in 48% of the patients, and moderate to marked improvement in 41%. The average duration of remission was 3.3 months. Histologically, there was an overall reduction in malpighian layer thickness by 63.4

2003 Journal of American Academy of Dermatology

15352. CD4+ T-cell-directed antibody responses are maintained in patients with psoriasis receiving alefacept: results of a randomized study. (Abstract)

CD4+ T-cell-directed antibody responses are maintained in patients with psoriasis receiving alefacept: results of a randomized study. Alefacept, human LFA-3/IgG(1) fusion protein, selectively reduces memory-effector (CD45RO(+)) T cells, a source of the pathogenic mediators of psoriasis.To evaluate the effect of alefacept on immune function, T-cell-dependent humoral responses to a neoantigen (PhiX174) and recall antigen (tetanus toxoid) were assessed.Patients with psoriasis were randomized

2003 Journal of American Academy of Dermatology Controlled trial quality: uncertain

15353. Oral retinoid use reduces cutaneous squamous cell carcinoma risk in patients with psoriasis treated with psoralen-UVA: a nested cohort study. (Abstract)

Oral retinoid use reduces cutaneous squamous cell carcinoma risk in patients with psoriasis treated with psoralen-UVA: a nested cohort study. Small open studies of patients at high risk for squamous cell carcinoma (SCC) of the skin suggest that oral retinoid use reduces the risk of these tumors. Among patients at lower risk, randomized trials of low doses of retinoids did not demonstrate significant chemopreventive effects. Patients with psoriasis treated with oral psoralen-UVA have a high risk (...) of SCC development. Oral retinoids are used to treat psoriasis. We performed a nested cohort study to assess whether oral retinoids reduce skin cancer risk among patients with psoriasis exposed to psoralen-UVA.From 1985 to 2000, 135 patients (11.3% of surviving patients in our cohort) used retinoids for at least 26 weeks in 1 year or more. For these 135 patients, we compared each person's SCC and basal cell carcinoma incidence during years of substantial oral retinoid use and other years. We used

2003 Journal of American Academy of Dermatology

15354. Tacrolimus ointment for the treatment of psoriasis on the face and intertriginous areas. (Abstract)

Tacrolimus ointment for the treatment of psoriasis on the face and intertriginous areas. The safety and efficacy of 0.1% tacrolimus ointment for the treatment of psoriasis on the face, intertriginous areas, or both were evaluated in an open-label, clinical trial of 21 patients with psoriasis. Patients applied 0.1% tacrolimus ointment twice daily for 8 weeks. Efficacy was assessed through the investigator's evaluation of the individual signs and symptoms of psoriasis, and the physician's global (...) (end of treatment). Only 2 patients reported adverse events, which were limited to itching and the feeling of warmth at the application site. None of the patients had atrophy, telangiectasia, or striae develop during the study. In summary, tacrolimus 0.1% ointment may be a safe and effective treatment option for patients with psoriasis on the face, intertriginous areas, or both.

2003 Journal of American Academy of Dermatology

15355. Pseudoainhum in chronic psoriasis. (Abstract)

Pseudoainhum in chronic psoriasis. Pseudoainhum is a term used to describe the presence of constricting bands of the extremities due to a variety of underlying causes. Progression of the lesions can cause irreversible damage and autoamputation of the affected digit. This report documents a rare association of pseudoainhum and psoriasis and emphasizes the importance of recognizing this condition.

2003 British Journal of Dermatology

15356. Ultraviolet B 308-nm excimer laser treatment of psoriasis: a new phototherapeutic approach. (Abstract)

Ultraviolet B 308-nm excimer laser treatment of psoriasis: a new phototherapeutic approach. Excimer laser-derived 308-nm ultraviolet (UV) B therapy is a new alternative for treating psoriasis by phototherapy. Some studies have been made showing the effectiveness of intralesional phototherapy technology in treating psoriasis. However, there has been no information available so far with regard to the cumulative dosage on a larger group of patients and on therapy optimized treatment strategies.One (...) hundred and twenty psoriatic patients were treated according to standard protocol to define the effectiveness. Our aim was to develop new parameters and determine whether effectiveness could be improved and whether treatment exposure, the cumulative UVB dose and adverse effects could be minimized.Initially, the excimer laser's effectiveness in treating psoriasis was evaluated in an open prospective study according to standard protocol. This included 120 adult patients (67 female/53 male) with chronic

2003 British Journal of Dermatology

15357. Treatment of severe recalcitrant plaque psoriasis with single-dose intravenous tumour necrosis factor-alpha antibody (infliximab). (Abstract)

Treatment of severe recalcitrant plaque psoriasis with single-dose intravenous tumour necrosis factor-alpha antibody (infliximab). Infliximab is a chimeric anti-tumour necrosis factor-alpha antibody that has been demonstrated to have marked efficacy in the treatment of psoriasis. Seven patients with chronic plaque psoriasis were treated with single-dose intravenous infliximab (5 mg/kg), and the Psoriasis Area and Severity Index (PASI) and Dermatology Life Questionnaire Index (DLQI) were used (...) as a measure of treatment efficacy. There was an average improvement in PASI scores of 69% at 2 weeks post infusion. There was an improvement in DLQI of 61%. Four of the seven patients were also seen at 10 weeks post infusion and the improvement in PASI and DLQI was sustained. All patients tolerated the initial infusion well without adverse events. The results indicate that single-dose infliximab is an effective and efficacious therapy for recalcitrant psoriasis and has a prolonged therapeutic effect.

2003 Australasian Journal of Dermatology

15358. Matrix metalloproteinase-19 is expressed by keratinocytes in psoriasis. Full Text available with Trip Pro

Matrix metalloproteinase-19 is expressed by keratinocytes in psoriasis. Keratinocyte hyperproliferation, inflammatory infiltrates, neoangiogenesis and alterations in cytokine levels are hallmarks of psoriatic skin. Matrix metalloproteinases (MMPs) have been associated with the remodeling of the extracellular matrix during inflammation, neovascularization, and malignant transformation. We have previously shown that particularly MMP-12 is abundantly expressed by macrophages and MMP-9 (...) in psoriatic keratinocytes and skin as assessed by quantitative real-time polymerase chain reaction. In lichen planus and lichenoid chronic dermatitis, MMP-19 staining was found in keratinocytes in areas where the basement membrane was abnormal. MMP-28 was not detected in psoriatic or non-lesional skin. Our results suggest that keratinocytes as well as the previously reported cell types (smooth muscle, endothelial and macrophages) can express MMP-19 in psoriasis and lichen planus. Upregulation of MMP-19

2003 Acta Dermato-Venereologica

15359. Microorganisms in intertriginous psoriasis: no evidence of Candida. Full Text available with Trip Pro

Microorganisms in intertriginous psoriasis: no evidence of Candida. Infection can be a trigger and an aggravating factor in psoriasis. Antibacterial and/or antifungal agents are commonly used in the treatment of intertriginous psoriasis, because it is believed that flexures in psoriasis are often colonized by Candida species and Staphylococcus aureus. Bacterial and fungal cultures were studied from 32 psoriatic patients with no topical treatment in the intertriginous areas, from 13 psoriatic (...) patients treated with topical steroids and from 19 patients with no psoriasis or other affections of the skinfolds. Untreated psoriatic patients were colonized by S. aureus significantly more often than the control group but infection seemed to be unlikely. Candida was not found in any of the groups. It is proposed that intertriginous psoriasis be treated with topical steroids alone and that the routine use of antimycotic and antibacterial combinations should be avoided.

2003 Acta Dermato-Venereologica

15360. The prevalence of onychomycosis in patients with psoriasis and other skin diseases. Full Text available with Trip Pro

The prevalence of onychomycosis in patients with psoriasis and other skin diseases. Onychomycosis among psoriasis patients is reported with varying prevalence. This prospective, controlled study investigates the occurrence of onychomycosis among inpatients with psoriasis versus inpatients with other skin diseases. The inclusion period was 15 months. Scrapings from clinically abnormal nails (both fingernails and toenails) were examined using microscopy and culture. The prevalence (...) of onychomycosis in patients with psoriasis was 17/79 = 21.5% compared to 18/142 = 12.7% for patients with other skin diseases (p = 0.13). In 17 mycologically positive psoriasis patients, dermatophytes, yeasts and moulds were isolated in 8, 10 and 4 cases, respectively, and in 18 mycologically positive patients with other skin diseases in 12, 7 and 5, respectively. Onychomycosis occurred more frequently in men than in women (psoriasis patients (p = 0.02), patients with other skin diseases (p = 0.03

2003 Acta Dermato-Venereologica

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