Psoriasis: Lebwohl M

Menter A, Korman NJ, Elmets CA, Feldman SR, Gelfand JM, Gordon KB, Gottlieb A, Koo JY, Lebwohl M, Lim HW, Van Voorhees AS, Beutner KR, Bhushan R, Anonymous00035. · Baylor University Medical Center, Dallas, Texas, USA. · J Am Acad Dermatol. · Pubmed #19217694 No free full text.

Abstract: Psoriasis is a common, chronic, inflammatory, multi-system disease with predominantly skin and joint manifestations affecting approximately 2% of the population. In this third of 6 sections of the guidelines of care for psoriasis, we discuss the use of topical medications for the treatment of psoriasis. The majority of patients with psoriasis have limited disease (<5% body surface area involvement) and can be treated with topical agents, which generally provide a high efficacy-to-safety ratio. Topical agents may also be used adjunctively for patients with more extensive psoriasis undergoing therapy with either ultraviolet light, systemic or biologic medications. However, the use of topical agents as monotherapy in the setting of extensive disease or in the setting of limited, but recalcitrant, disease is not routinely recommended. Treatment should be tailored to meet individual patients' needs. We will discuss the efficacy and safety of as well as offer recommendations for the use of topical corticosteroids, vitamin D analogues, tazarotene, tacrolimus, pimecrolimus, emollients, salicylic acid, anthralin, coal tar, as well as combination therapy.

Gottlieb A, Korman NJ, Gordon KB, Feldman SR, Lebwohl M, Koo JY, Van Voorhees AS, Elmets CA, Leonardi CL, Beutner KR, Bhushan R, Menter A. · Department of Dermatology, Tufts-New England Medical Center, Tufts University School of Medicine, Boston, Massachusetts, USA. · J Am Acad Dermatol. · Pubmed #18423261 No free full text.

Abstract: Psoriasis is a common, chronic, inflammatory, multisystem disease with predominantly skin and joint manifestations affecting approximately 2% of the population. In this second of 5 sections of the guidelines of care for psoriasis, we give an overview of psoriatic arthritis including its cardinal clinical features, pathogenesis, prognosis, classification, assessment tools used to evaluate psoriatic arthritis, and the approach to treatment. Although patients with mild to moderate psoriatic arthritis may be treated with nonsteroidal anti-inflammatory drugs and/or intra-articular steroid injections, the use of disease-modifying antirheumatic drugs, particularly methotrexate, along with the biologic agents, are considered the standard of care in patients with more significant psoriatic arthritis. We will discuss the use of disease-modifying antirheumatic drugs and the biologic therapies in the treatment of patients with moderate to severe psoriatic arthritis.

Menter A, Gottlieb A, Feldman SR, Van Voorhees AS, Leonardi CL, Gordon KB, Lebwohl M, Koo JY, Elmets CA, Korman NJ, Beutner KR, Bhushan R. · Baylor University Medical Center, Dallas, Texas, USA. · J Am Acad Dermatol. · Pubmed #18423260 No free full text.

Abstract: Psoriasis is a common, chronic, inflammatory, multisystem disease with predominantly skin and joint manifestations affecting approximately 2% of the population. In this first of 5 sections of the guidelines of care for psoriasis, we discuss the classification of psoriasis; associated comorbidities including autoimmune diseases, cardiovascular risk, psychiatric/psychologic issues, and cancer risk; along with assessment tools for skin disease and quality-of-life issues. Finally, we will discuss the safety and efficacy of the biologic treatments used to treat patients with psoriasis.

Lebwohl M. · No affiliation provided · Arch Dermatol. · Pubmed #12020234 No free full text.

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Galadari I, Rigel E, Lebwohl M. · No affiliation provided · J Eur Acad Dermatol Venereol. · Pubmed #11730031 No free full text.

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Patel RV, Clark LN, Lebwohl M, Weinberg JM. · University of Miami Miller School of Medicine, Miami, Florida, USA. · J Am Acad Dermatol. · Pubmed #19344980 No free full text.

Abstract: BACKGROUND: There are multiple therapeutic options for the treatment of moderate to severe psoriasis. The process of choosing among potential treatment options requires both the physician and the patient to weigh the benefits of individual modalities against their potential risks. Traditional systemic therapies for psoriasis, including methotrexate (MTX) and cyclosporine (CsA), have a well-documented array of toxicities, particularly end-organ toxicities. Over the past several years, the use of biologic therapies for the treatment of moderate to severe psoriasis has been a major clinical and research focus. With the advent of these novel immunosuppressive therapies, one of the central safety issues surrounding these agents is their potential to increase the risk of malignancy. OBJECTIVE: Our objective was to review the risk of malignancy associated with therapies for moderate to severe psoriasis, including phototherapy, traditional systemic therapies, and biologic therapies. We reviewed the existing body of literature in order to define the known incidence of malignancy associated with psoralen and ultraviolet A (PUVA), narrowband and broadband ultraviolet B (UVB), MTX, CsA, mycophenolate mofetil (MMF), and biologic therapies, including alefacept, efalizumab, infliximab, etanercept, adalimumab, and ustekinumab. RESULTS: PUVA, when given long term, is associated with increased risks of cutaneous squamous cell carcinoma and malignant melanoma. Reviews of studies on UVB, both narrowband and broadband, do not indicate any increased risk of nonmelanoma skin cancer or melanoma. The traditional systemic psoriasis therapies-MTX, CsA, and MMF-may be associated with an increased risk of lymphoproliferative disorders during treatment, demonstrated in clinical trials in patients with rheumatoid arthritis and documented in case reports concerning psoriasis patients. The risk of malignancy with biologic therapy is still unclear. However, the majority of studies examining this carcinogenic risk suggest that tumor necrosis factor-alpha inhibitors may cause a slightly increased risk of cancer, including nonmelanoma skin cancer and hematologic malignancies. LIMITATIONS: The majority of studies cited in this review lack the power and randomization of large clinical trials, as well as the long-term follow-up periods which would further substantiate the hypothetical link between these antipsoriatic treatment regimens and the potential for malignancy. Because of the substantial lack of clinical data, the majority of studies evaluated focus on the treatment of patients with rheumatoid arthritis, which is a systemic inflammatory disorder comparable to psoriasis. Additionally, the increased risk of malignancy associated with psoriasis itself is a confounding factor. CONCLUSION: Many of the therapies for moderate to severe psoriasis, including PUVA, traditional systemic therapies, and some biologic therapies, may increase the risk of malignancy. Appropriate patient counseling and selection, as well as clinical follow-up, are necessary to maximize safety with these agents. Further long-term study is necessary to more precisely quantify the risks associated with biologic therapies.

Rozenblit M, Lebwohl M. · Mount Sinai School of Medicine, 5 E. 98th Street, New York, NY 10029-6501, USA. · Dermatol Ther. · Pubmed #19222517 No free full text.

Abstract: The prevalence of psoriasis is estimated to be 2.2% in the United States, and 6-39% of patients with psoriasis also develop psoriatic arthritis. New advances have been made in developing treatment options. A new human tumor necrosis factor (TNF)-alpha antibody, golimumab, has been shown to significantly improve symptoms of psoriatic arthritis. In addition, clinical trials of certolizumab pegol, a PEGylated Fab' fragment of an anti-TNF-alpha monoclonal antibody, show promising results for treating rheumatoid arthritis and suggest that it may be applicable for treating psoriasis and psoriatic arthritis in the future. New biologic therapies also include antibodies to interleukin-12 and interleukin-23. Phase II studies suggest that ustekinumab is effective in alleviating symptoms of psoriasis and psoriatic arthritis. However, longer studies with radiographic evaluation will be required before their impact on joint destruction can be assessed.

Halverstam CP, Lebwohl M. · Department of Dermatology, Mount Sinai School of Medicine, Box 1048, New York, NY 10029-6574, USA. · Clin Dermatol. · Pubmed #18755374 No free full text.

Abstract: Although most psoriasis patients respond to standard therapies, many circumstances warrant the use of nonstandard or off-label treatments. For instance, patients with treatment-resistant psoriasis or those who have had multiple adverse effects to other therapies may be good candidates for off-label treatments. Similarly, patients with unusual and hard-to-treat forms of psoriasis such as pustular psoriasis and palmoplantar psoriasis or specific comorbidities may benefit from certain nonstandard therapies. Drugs that may be used as alternatives to standard therapies include mycophenolate mofetil, tacrolimus or pimecrolimus, isotretinoin, colchicine, sulfasalazine, paclitaxel, dapsone, azathioprine, and hydroxyurea. Other unconventional therapies include climatotherapy at the Dead Sea and grenz ray therapy.

Clark L, Lebwohl M. · Department of Dermatology at Columbia University, New York, New York, USA. · J Am Acad Dermatol. · Pubmed #18083274 No free full text.

Abstract: BACKGROUND: The prevalence of obesity is rapidly increasing in the United States. Patients with psoriasis, in particular, tend to be above normal weight. Three of the 5 biologics used to treat psoriasis are fixed-dosed treatments: alefacept, etanercept, and adalimumab. Dosing regimens do not account for weight. OBJECTIVE: We attempted to determine whether the efficacy of the biologics is affected by weight. METHODS: We review the existing body of literature, including subgroup analyses, relating to efficacy and weight for infliximab, efalizumab, alefacept, and etanercept. No relevant literature was found for adalimumab. RESULTS: Weight-based dosed medications do not seem to lose efficacy with increasing weight. Both etanercept and alefacept may have compromised efficacy in heavier individuals. LIMITATIONS: The data are limited to subgroup analyses and smaller studies, often with no statistical significance reported. CONCLUSIONS: Additional studies are warranted, specifically designed to address the issue of obesity and response to therapy of the biologics. Alternative dosing for etanercept and alefacept should be further evaluated in patients above normal weight.

Clark LN, Lebwohl M. · Department of Dermatology, Mount Sinai School of Medicine, New York, NY 10029, USA. · Int J Dermatol. · Pubmed #17910704 No free full text.

Abstract: Collectively, new developments in the field of medical dermatology will ultimately lead to improved patient care. We review several new findings in the dermatologic literature including the following: new questions regarding the malignant potential of anti-tumor necrosis factor agents, which are widely used for the treatment of moderate to severe psoriasis as well as psoriatic arthritis; anti-interleulin-12, a promising anticytokine for the treatment of psoriasis; diagnostic advances in the detection of latent Mycobacterium tuberculosis; advances in the primary prevention of human papillomavirus and herpes zoster; and new therapeutic options with existing medications for neuropathic pain and pruritus.

Zeichner JA, Lebwohl M. · Department of Dermatology, Mount Sinai Medical Center, 5 East 98th Street, Box 1048, New York, NY 10029, USA. · Dermatol Clin. · Pubmed #17430757 No free full text.

Abstract: The biologic agents are effective drugs to treat psoriasis. They provide physicians with additional options for patients who cannot tolerate traditional therapies or for whom traditional therapies are not sufficient. While these new TNF-alpha inhibitors and anti-T-cell agents have potential complications, they are generally safe with proper monitoring. Both physicians and patients should be aware of the risks involved with each medicine so that the correct drug is chosen to suit each patient.

Halverstam CP, Zeichner J, Lebwohl M. · Department of Dermatology, Mount Sinai School of Medicine, New York, NY 10029-6574, USA. · J Cutan Med Surg. · Pubmed #17241599 No free full text.

Abstract: BACKGROUND: Long-term systemic retinoid therapy has been associated with skeletal side effects. There have been reports of diffuse idiopathic skeletal hyperostosis (DISH) syndrome, calcification of ligaments, and osteoporosis, as well as premature fusion of epiphyses and modeling abnormalities of long bones, occurring in patients on chronic high-dose isotretinoin, etretinate, and acitretin therapy. Low-dose acitretin has been used for many years as monotherapy or in combination with other systemic therapies for psoriasis. Evidence to date suggests that the frequency of symptomatic bony effects is quite low in these patients. OBJECTIVE: To present the radiologic findings of a patient on long-term, low-dose acitretin and etretinate and to review the literature on the radiologic evidence of skeletal side effects during retinoid therapy. METHODS: Case report and literature search. RESULTS: A patient on low-dose acitretin had no significant radiologic abnormalities associated with retinoid use after 9 years of treatment. A review of the literature revealed conflicting reports on the incidence of radiologic abnormalities in patients on retinoid treatment. CONCLUSION: The evidence to date does not substantiate a clear link between radiologic skeletal abnormalities and long-term, low-dose acitretin or etretinate therapy.

Lebwohl M, Herrmann LG. · Department of Dermatology, Mount Sinai School of Medicine, New York, New York, USA. · Cutis. · Pubmed #16869176 No free full text.

Abstract: There is a substantial body of data demonstrating that atopic dermatitis and various other skin diseases are associated with disturbances of skin barrier function as evidenced by an increase in transepidermal water loss (TEWL), a decrease in water-binding properties, and a reduction in skin surface lipids, specifically levels of ceramides. The results of clinical studies suggest that these deficits can be addressed through the judicious use of appropriate moisturizers, which have been shown to improve skin hydration, reduce susceptibility to irritation, and restore the integrity of the stratum corneum. Some emollients also supply the compromised stratum corneum with vital lipids and accelerate barrier recovery. Moisturizers serve as an important first-line therapeutic option for patients with atopic dermatitis and other chronic skin diseases and can be highly beneficial in improving the clinical signs and symptoms of these challenging dermatologic conditions.

Lebwohl M, Kathryn M. · Department of Dermatology, Mount Sinai School of Medicine, New York, NY, USA. · J Drugs Dermatol. · Pubmed #16703775 No free full text.

Abstract: Acitretin, the only oral retinoid indicated for the treatment of psoriasis, has shown activity when used in combination, rotational, and sequential therapy regimens with other therapies. When used with phototherapy, significantly greater activity has been observed at lower doses than with either approach as monotherapy. While initial anecdotal evidence is promising, clinical trials are needed to evaluate whether sequential or rotational use of biologic agents with acitretin may yield improved efficacy and an acceptable safety profile with decreased risk of immunosuppression. Acitretin and other retinoids also work as chemopreventative agents in psoriasis patients with extensive exposure to psoralen ultraviolet A (PUVA) and in solid-organ transplant patients where a number of studies have reported decreased numbers of squamous cell cancers when treated with acitretin.

Pariser DM, Gordon KB, Papp KA, Leonardi CL, Kwon P, Compton PG, Rundle AC, Walicke PA, Lebwohl M. · Department of Dermatology, Eastern Virginia Medical School, Norfolk, VA, USA. · J Cutan Med Surg. · Pubmed #16699904 No free full text.

Abstract: BACKGROUND: Effective psoriasis therapies are needed for long-term symptom control. OBJECTIVE: Assess efalizumab (Raptiva) efficacy in a large cohort of psoriasis patients. METHODS: Data from three Phase III, randomized, double-blind, parallel-group, placebo-controlled, multicenter studies were pooled. Patients (n = 1,651) with moderate to severe plaque psoriasis received 12 weeks of subcutaneous efalizumab 1 or 2 mg/kg/wk or placebo. RESULTS: All efficacy measures reached statistical significance within each of the individual studies (p < 0.001) and overall. More efalizumab-treated patients achieved > or = 75% and > or = 50% Psoriasis Area and Severity Index (PASI) improvement at week 12 than did placebo-treated patients (27.8% vs 3.8% [p < 0.001] and 56.1% vs 14.6% [p < 0.001], respectively). Significant PASI improvements occurred as early as week 2 (12.5% vs 7.9%, p =0.0001). Adverse events were generally mild to moderate. CONCLUSION: Efalizumab resulted in early and significant improvement for all efficacy endpoints and was well tolerated in patients with moderate to severe chronic plaque psoriasis.

Carey W, Glazer S, Gottlieb AB, Lebwohl M, Leonardi C, Menter A, Papp K, Rundle AC, Toth D. · Royal Victoria Hospital, Montreal, Quebec, Canada. · J Am Acad Dermatol. · Pubmed #16488339 No free full text.

Abstract: Psoriasis is a chronic disease, the severity of which varies among patients and changes unpredictably over time in individual patients. Psoriasis can be exacerbated during treatment by infection, endocrine factors, hypocalcemia, medications, psychologic stress, skin trauma, or other factors. Patients who discontinue treatments may experience a return of disease--relapse--or worsening of disease--rebound. The National Psoriasis Foundation (NPF) proposed standardized definitions of relapse and rebound. Efalizumab, a recombinant humanized immunoglobulin G-1 monoclonal antibody, is approved for the management of psoriasis. During efalizumab clinical trials, a small percentage of patients experienced protocol-defined adverse events related to psoriasis. After publication of the NPF definition of rebound, post hoc exploratory analyses of the efalizumab clinical trial data were performed. The efalizumab clinical trial investigators discussed their observations, the analyses, and their individual approaches to the treatment of patients receiving or discontinuing efalizumab therapy, the conclusions of which are described herein.

Lebwohl M. · Department of Dermatology, Mount Sinai School of Medicine, New York, New York 10029, USA. · J Am Acad Dermatol. · Pubmed #15968265 No free full text.

Abstract: Psoriasis is a chronically recurring inflammatory disease that affects the skin, scalp, and joints. It ranges in severity from mild to severe, and patients with moderate to severe disease experience significant deterioration in quality of life. The goals of psoriasis treatment are to gain initial and rapid control of the disease process, decrease the percentage of body surface area involved, decrease plaque lesions, achieve and maintain long-term remission, minimize adverse events, and improve patient quality of life. Therapy varies depending on disease severity and spread and will shift from control of acute flares to long-term maintenance. Topical treatment for mild psoriasis includes the use of topical corticosteroids, calcipotriene, tazarotene, topical tars, anthralin, and keratolytics. Treatment of moderate to severe psoriasis includes systemic therapies, such as methotrexate, acitretin, cyclosporine, and biologic agents. Treatment can be effected using combination, rotational, or sequential regimens. Treatment algorithms developed by a 2002 consensus conference are described. Because some degree of therapy will always be necessary, ranging from maintenance of long-term remission to control of acute psoriasis flares, each patient requires an individualized plan.

Lebwohl M, Ting PT, Koo JY. · The Mount Sinai School of Medicine, New York, NY, USA. · Ann Rheum Dis. · Pubmed #15708945 links to  free full text

Abstract: Even before the recent development of biological agents, a long list of effective treatments has been available for patients with psoriasis. Topical therapies such as corticosteroids, vitamin D analogues, and retinoids are used for localised disease. Phototherapy including broadband ultraviolet B (UVB), narrowband UVB, PUVA, and climatotherapy are effective for more extensive disease. Systemic therapies such as methotrexate, retinoids, and ciclosporin are effective for patients with refractory or extensive cutaneous disease.

Aaronson DS, Lebwohl M. · Mount Sinai School of Medicine, 5 East 98th Street, Box 1048, New York, NY 10029-6574, USA. · Dermatol Clin. · Pubmed #15450334 No free full text.

Abstract: This article discusses the prebiologic armamentarium, which continues to play a significant role in certain patients for the treatment of psoriasis. With the creation of the newer"biologics," however, the treatment of psoriasis is being re-evaluated.

Lebwohl M. · Department of Dermatology, The Mount Sinai School of Medicine, New York, NY 10029, USA. · J Am Acad Dermatol. · Pubmed #15243505 No free full text.

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Lebwohl M, Menter A, Koo J, Feldman SR. · Department of Dermatology, Mount Sinai School of Medicine, Mt. Sinai Medical Center, 5 E. 98th Street, 12th Floor, New York, NY 10029-6574, USA. · J Am Acad Dermatol. · Pubmed #14988684 No free full text.

Abstract: In patients with moderate-to-severe psoriasis, remission can be difficult to achieve and sustain. Both acutely acting and long-term maintenance agents are needed. Speed and efficiency of available monotherapies tend to be inversely proportional to safety. Combination, rotational, and sequential approaches are often more effective and safer than single-agent therapy. Combining agents with complementary adverse effect profiles is preferable. Apparent synergistic enhancement is seen with most paired combinations of the four major therapies: acitretin, phototherapy (ultraviolet B/psoralen plus ultraviolet A), cyclosporine, and methotrexate. Of those, only cyclosporine in combination with psoralen plus ultraviolet A is contraindicated because of increased cancer risk. Combinations of each of those major therapies with topical agents (retinoids, steroids, vitamin D derivatives, and others) have been used with varying efficacy and safety. The immunomodulators, hydroxyurea and thioguanine, have also shown some success in combination therapy. The new biologic agents with their novel modes of action and adverse effect profiles may prove to be important adjuncts in combination/rotational/sequential approaches. In some cases, monotherapy (with either systemic agents or phototherapy) adequately controls moderate to severe disease. A regimen using a single agent has the advantages of lower cost and greater adherence by the patient. For any number of reasons, however, including loss of efficacy, adverse effects, or cumulative or acute toxicity-and especially the inability to clear resistant lesions-a single modality will not be adequate. Using two or more therapies is thus the rule rather than the exception for most patients with moderate-to-severe psoriasis, but picking a combination that serves to balance safety and efficacy needs careful consideration, especially since no evidence-based treatment guidelines exist.

Wong VK, Lebwohl M. · Department of Dermatology, Mount Sinai School of Medicine, New York, NY, USA. · Skin Therapy Lett. · Pubmed #14610613 links to  free full text

Abstract: Alefacept (AMEVIVE or LFA#TIP, Biogen) is the newest effective systemic therapy for chronic plaque psoriasis and was approved by the US FDA in January 2003. Clinical studies have shown that alefacept, given via weekly IM or IV injections for 12 weeks, was well tolerated, with no reported serious adverse events. Most significantly, it was found that alefacept provides a long-lasting remittive effect. These findings support the use of alefacept as a viable treatment of psoriasis, without the toxicities associated with some of the current systemic treatments available.

Maryles S, Rozenblit M, Lebwohl M. · Department of Dermatology, Mount Sinai School of Medicine, 1 Gustave Levy Place, New York, NY 10029-6574, USA. · J Dermatolog Treat. · Pubmed #14578093 No free full text.

Abstract: Patients with psoriasis typically face longterm therapy for their chronic disease. Often, the therapeutic agents that physicians use to treat them may become less effective or may cause safety or toxicity issues. The clinician must then decide the next therapy for his/her patient and assess benefit/risk of the next therapeutic agent or combination. In moving the patient from one therapy to the next, specific characteristics of the transition must be assessed, and how to stop the existing therapy, and introduce the new agent(s). The decision making process must take into account the longterm risks to the patient. This article focuses on the transition for patients with psoriasis being managed with methotrexate and cyclosporine to retinoids, phototherapy, and newer agents.

Lebwohl M, Tannis C, Carrasco D. · Department of Dermatology, Mount Sinai School of Medicine, 1 Gustave Levy Place, Box 1047, New York, NY 10029-6574, USA. · J Dermatolog Treat. · Pubmed #14578092 No free full text.

Abstract: Retinoids have been used for the treatment and suppression of cutaneous malignancies in patients with basal cell nevus syndrome, xeroderma pigmentosum, and in patients with recurrent skin cancers as a result of immunosuppression for renal transplantation. We report a 40-year-old male who began to develop multiple squamous cell carcinomas of the skin after treatment with PUVA for severe psoriasis. The numbers of squamous cell carcinomas increased when acitretin was discontinued and decreased when he was taking the drug at a dose of 25 mg daily. Acitretin should be considered as a maintenance therapy for psoriasis patients developing squamous cell carcinomas as a result of PUVA therapy.

Callen JP, Krueger GG, Lebwohl M, McBurney EI, Mease P, Menter A, Paller AS, Pariser DM, Weinblatt M, Zimmerman G, Anonymous00189. · No affiliation provided · J Am Acad Dermatol. · Pubmed #14576671 No free full text.

This publication has no abstract.