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Biomedical subjects

M Lebwohl

Publications and source records attributed to M Lebwohl.

At least 19 recordsLinked to original sources
PubMed2005

Psoriasis treatment: traditional therapy.

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.

Adrenal Cortex Hormones↗
PubMed2005

Alefacept in the treatment of psoriasis in patients for whom conventional therapies are inadequate.

BACKGROUND: Many patients with moderate to severe chronic plaque psoriasis fail to respond to or are not appropriate candidates for conventional systemic therapies and/or phototherapy. OBJECTIVES: To assess the efficacy, quality of life and safety of alefacept among the proportion of patients who participated in the phase III studies and who were not suitable candidates for conventional systemic psoriasis therapies or phototherapy. METHODS: The patient's historical responses at the baseline visit during the phase III studies of alefacept were used to identify a subpopulation in whom the use of methotrexate, ciclosporin, retinoids, ultraviolet B or psoralen plus ultraviolet A was ineffective or inappropriate. Endpoints included Psoriasis Area and Severity Index (PASI), Dermatology Life Quality Index (DLQI) and adverse events. RESULTS: Most patients (69%) who were treated with alefacept in the phase III programme were not candidates for > or =1 of the above-mentioned therapies, and 41 and 21% were not candidates for > or =2 and > or =3, respectively. A reduction in PASI of > or =75% was achieved by 27, 23 and 26% of alefacept-treated patients who were not candidates for > or =1, > or =2 and > or =3 conventional systemic psoriasis therapies or phototherapy, respectively (all p < or = 0.001 vs. placebo). The corresponding results for PASI 50 were 53, 52 and 50% (all p < or = 0.001 vs. placebo). At 2 weeks after the last dose of alefacept, mean DLQI overall scores were reduced by -4.2, -3.9 and -5.2, respectively (all p < or = 0.001 vs. placebo). The incidence of adverse events was similar in the alefacept and placebo groups. CONCLUSIONS: The efficacy, quality of life effects and safety of alefacept in patients who were not candidates for conventional systemic psoriasis therapies or phototherapy were similar to those reported previously for the overall alefacept-treated population in the phase III studies.

Alefacept↗
PubMed2003

Actinic keratosis: epidemiology and progression to squamous cell carcinoma.

Actinic keratoses are a common problem in the population, and one of the most common conditions treated by dermatologists. Risk factors for the development of actinic keratosis are those associated with increased sun exposure and increased susceptibility to sun exposure such as low latitude, working outdoors, light skin, and history of sunburn. The role of the immune system is clear from the frequency of actinic keratoses in transplant patients. There is strong evidence that actinic keratoses can progress to squamous cell carcinoma, underscoring the need to identify and treat patients at risk.

Aged↗
PubMed2003

Retrospective study of the efficacy of narrowband UVB and acitretin.

BACKGROUND: In this retrospective analysis the effect of narrowband ultraviolet B treatment in combination with acitretin is reviewed in 40 patients with plaque psoriasis. Narrowband UVB is highly effective for plaque psoriasis, but requires multiple phototherapy treatments, making patient compliance problematic. Oral acitretin is moderately effective as monotherapy, but when combined with ultraviolet B or PUVA, its use has reduced the number of treatments required for clearing, and has resulted in clearing of patients otherwise refractory to these phototherapeutic modalities. There is only sparse data on the combination of acitretin with narrowband UVB. We therefore analyzed data on 40 patients treated with this combination. RESULTS: The majority of patients treated had psoriasis that was refractory to treatment with broadband ultraviolet B, monotherapy with narrowband UVB, monotherapy with acitretin, or the combination of acitretin and broadband UVB. In this difficult-to-treat group of patients, the combination of low dose acitretin (25 mg po daily) and narrowband UVB three times per week resulted in greater than 75% improvement in 29 (72.5%) patients. Only 5 (12.5%) patients had less than 50% improvement. The combination was well tolerated and associated with typical retinoid and narrowband UVB side effects including elevation of serum lipids, burn and cheilitis. CONCLUSION: The combination of acitretin with narrowband UVB results in faster improvement even in more difficult-to-treat patients. In combination the treatments appear to have synergistic effects.

Acitretin↗
PubMed2003

Retrospective analysis of the treatment of psoriasis of the palms and soles.

In this retrospective analysis, the effect of currently used treatments in 26 patients with psoriasis of the palms and soles were analyzed. In general, patients are treated initially with topical medications including superpotent topical corticosteroids in combination with calcipotriene ointment or tazarotene gel or both. If satisfactory improvement is not achieved in 4-8 weeks, systemic retinoids are added, formerly etretinate and currently acitretin, except in women of childbearing potential. If the latter regimen is not effective within two months, soak PUVA is added to the regimen of oral retinoids and topical medications. If improvement is inadequate, or if the treatment regimen is not tolerated, methotrexate or cyclosporine have been added in the past. The availability of the excimer laser has recently modified our approach so that this therapy is used in combination with acitretin before soak PUVA. With the availability of biologic agents, methotrexate is avoided because of its hepatotoxicity and bone marrow toxicity and cyclosporine is avoided because of its nephrotoxicity. If oral acitretin plus topical therapy is not adequate to control the disease and the excimer laser is not an option because of its limited availability, alefacept, etanercept and infliximab are added when possible. Other biologic agents are likely to be added to this list in the future.

Adult↗
PubMed2003

Acitretin suppression of squamous cell carcinoma: case report and literature review.

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.

Acitretin↗
PubMed2003

Transition from methotrexate and cyclosporine to other therapies including retinoids, ultraviolet light and biologic agents in the management of patients with psoriasis.

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.

Acitretin↗
PubMed2003

The use of alefacept in the treatment of psoriasis.

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.

Adjuvants, Immunologic↗
PubMed2001

Genital lentigines in a 6-year-old boy with a family history of Cowden's disease: clinical and genetic evidence of the linkage between Bannayan-Riley-Ruvacalba syndrome and Cowden's disease.

BACKGROUND: In 1997, it was reported that a PTEN gene deletion, a common genetic mutation in Cowden's disease (CD), was identified in a patient with Bannayan-Riley-Ruvacalba (BRR), suggesting that the two diseases were allelic. However, the clinical overlap between the two diseases has largely remained unclear. OBJECTIVE: To confirm the genetic and clinical association in a family segregating both CD and BRR. METHODS: Clinical evaluation and genetic analysis using a denaturing gradient gel electrophoresis (DGGE), temporal temperature gradient electrophoresis (TTGE), and DNA sequencing techniques. RESULTS: Our patient presents with typical BRR clinical manifestations, including multiple lentigines on his penis, while his mother presents with typical manifestations of CD, including multiple malignancies. Genetic analyses of leukocytes from the patient and his mother showed mutations in exon 8 that was identified as the presumably truncating mutation R335X. CONCLUSION: This report provides clinical evidence that both BRR and CD are closely related and confirms the PTEN gene mutation in BRR and CD patients segregating in the same family, thus confirming the genetic linkage between the two genodermatoses.

Abnormalities, Multiple↗
PubMed2001

Combination therapy with vitamin D analogues.

Monotherapy with vitamin D analogues has been shown to be effective in the treatment of psoriasis. Vitamin D analogues have also been used in combination with other topical therapies, systemic therapies and phototherapy. In many instances, the efficacy of these other treatments can be maximized and adverse effects minimized when combined with vitamin D analogues. The combination of a topical corticosteroid with a vitamin D analogue can work synergistically to improve efficacy and reduce the side-effects from both treatments. However, caution must be used when mixing the two agents, as some topical corticosteroids will result in the degradation of the vitamin D analogue. Benefit from phototherapy is also increased when using vitamin D analogues, so that greater improvement occurs with fewer treatments. Effects on minimal erythema dose must be considered and the potential for ultraviolet blocking by vitamin D analogues may affect treatment. Some vitamin D analogues may also be susceptible to degradation by certain wavelengths of ultraviolet light. Combining vitamin D analogues with systemic agents exerts a dose-sparing effect, thus reducing the possibility of side-effects, but such combinations require further study. As long as treatments are used correctly, the benefits of combination therapy with vitamin D analogues usually outweigh the few drawbacks.

Calcitriol↗
PubMed2001

Altered expression of angiopoietins and Tie2 endothelium receptor in psoriasis.

Psoriasis is a chronic inflammatory skin disease in which epidermal proliferation is closely associated with excessive microvascular expansion within the papillary dermis. Angiopoietins have recently been identified as the major ligands of the endothelial- specific receptor Tie2. Angiopoietin 1 induces Tie2 signaling as a receptor activator and maintains blood vessel formation, whereas angiopoietin 2 destabilizes vessels by blocking Tie2 signaling as an antagonist of angiopoietin 1 and acts with vascular endothelial growth factor to initiate angiogenesis. In this study we examined the potential role of angiopoietins and the Tie2 receptor in vascular changes of psoriasis. Angiopoietin 1, angiopoietin 2, and Tie2 were upregulated in involved psoriasis skin compared to uninvolved psoriasis skin, healthy skin, and chronic spongiotic dermatitis skin. Angiopoietin 1 was expressed by stromal cells in the highly vascularized papillary dermis of involved psoriasis skin. Angiopoietin 2 was expressed by endothelial cells in the vicinity of the proliferating epidermis that abundantly expressed vascular endothelial growth factor. Vascular endothelial growth factor and basic fibroblast growth factor, which were overexpressed in involved psoriasis skin, enhanced angiopoietin 2 and Tie2 expression in dermal microvascular endothelial cell cultures. Thus, our findings suggest that upregulation of angiopoietin 1, angiopoietin 2, and Tie2 is closely associated with the development of microvascular proliferation in psoriasis, and that the angiopoietin-Tie2 system may act coordinately with vascular endothelial growth factor and basic fibroblast growth factor to promote neovascularization in psoriasis. Moreover, successful antipsoriatic treatment was accompanied by noticeable reduction of angiopoietin 2 expression, suggesting that alteration of angiopoietin 2 expression may be particularly important in controlling vascular proliferation in the treatment of psoriasis.

Angiopoietin-1↗
PubMed2001

Acne therapy: clinical pearls.

Several classes of medications successfully treat acne. Systemic and topical retinoids, systemic and topical antimicrobials, and systemic hormonal therapy are the major categories. Failure of therapy may result from drug interactions, antibiotic resistance, or coexisting conditions; therefore, a detailed history including these points should be used to decide which therapy is appropriate for each patient. Furthermore, one must consider the potential side effects of each treatment and make sure that (1) the benefits outweigh the risks of the treatment, (2) the side effects can be avoided by adding another agent, or (3) the side effects can be safely treated.

Acne Vulgaris↗
PubMed2001

Pseudoxanthoma elasticum: significance of limited phenotypic expression in parents of affected offspring.

The inheritance pattern of pseudoxanthoma elasticum (PXE) is controversial. Inheritance patterns are confounded by delayed diagnosis and mild or limited phenotypic expression among certain family members. Because testing for the genetic mutation(s) responsible for PXE is not routine, genetic counseling must be done with caution. We describe 4 families in which one or more children were diagnosed with PXE. Detailed examination of the parents was carried out, including skin biopsy and ophthalmologic examination. In 3 of the 4 families, one parent had limited phenotypic expression, such as ocular findings without skin lesions or very mild skin lesions with no ocular findings. In the other family, one parent had very mild skin and ocular disease. All 4 affected parents had diagnostic skin biopsy findings. In none of the 4 families was the inheritance pattern clear-cut. Although the inheritance pattern of PXE has been debated, clinically significant stigmata of PXE, which are not always readily apparent, can occur in successive generations. Therefore all first-degree relatives of affected patients should receive a full dermatologic examination as well as a funduscopic examination. If even mild typical skin or eye findings are present, then skin biopsy should be performed.

Adolescent↗
PubMed2001

The penetration of 0.005% fluticasone propionate ointment in eyelid skin.

BACKGROUND: The use of corticosteroids to treat periorbital dermatoses carries significant risk of serious side effects such as glaucoma, cataracts, and blindness. Studies to assess levels of corticosteroid penetration in the eyelid are lacking. OBJECTIVE: We assessed corticosteroid penetration in eyelid skin in vitro to obtain information leading to the establishment of safer dosing regimens. METHODS: Fluticasone propionate ointment, 0.005%, was applied (approximately 2-5 mg/cm(2)) to samples of human eyelid skin, and penetration was assessed by using modified Franz diffusion cells. Drug concentration was determined at 12, 24, 36, and 48 hours after application by liquid chromatography tandem mass spectrometry. RESULTS: Only very small amounts of fluticasone propionate penetrated the skin (range, 0.618% +/- 0.339% to 1.467% +/- 0.695%). CONCLUSION: Further studies are warranted to examine the safety and efficacy of 0.005% fluticasone propionate ointment for the treatment of eyelid dermatoses.

Administration, Topical↗
PubMed2001

Consensus conference: acitretin in combination with UVB or PUVA in the treatment of psoriasis.

Although adjunctive treatment with retinoids in concert with either psoralen-ultraviolet A (PUVA) or ultraviolet B (UVB) phototherapy has been a treatment option for chronic, moderate to severe plaque psoriasis for nearly two decades, acitretin-UV therapy is an underutilized therapeutic modality. According to a recent member survey by the National Psoriasis Foundation, many psoriasis patients are frustrated with available treatment options, which they perceive as ineffective, inconvenient, and/or excessively conservative. Treatment of psoriasis with acitretin in concert with UVB or PUVA is emerging as a viable clinical strategy. Compared with either acitretin or UV light monotherapy alone, the combination regimen enhances efficacy and limits treatment frequency, duration, and cumulative doses. These effects translate into care that is more effective, better tolerated, more convenient, less costly, and, perhaps, safer during long-term treatment than phototherapy alone. Drawing from an extensive literature search and the expertise of its participants, this consensus conference advances clinical recommendations as well as "clinical pearls" for health providers who treat patients with chronic, moderate to severe plaque psoriasis and suggests avenues for future research.

Acitretin↗
PubMed2001

Treatment of psoriasis. Part 1. Topical therapy and phototherapy.

UNLABELLED: New developments in the topical therapy and phototherapy of psoriasis have greatly improved our ability to safely and effectively treat this debilitating disease. Topical corticosteroids remain the most commonly prescribed agents for psoriasis, but they are frequently prescribed with other agents. Investigations of corticosteroids claiming an improved benefit/risk ratio have yielded promising results, but more work is needed. Use of anthralin and tar has declined with the availability of the noncorticosteroids calcipotriene and tazarotene. Other experimental topical therapies are in various stages of development. Broadband ultraviolet B (UVB) remains the most commonly used phototherapy light source, but many patients are being treated with a new form of ultraviolet light, narrowband UVB. Although PUVA remains one of the most effective psoriasis treatments, its use is declining because of its association with cutaneous malignancies. New radiation sources such as lasers have been added to our armamentarium of available therapies and even newer light source-based treatments are being examined. LEARNING OBJECTIVE: At the conclusion of this learning activity, participants should be familiar with the varying topical treatments for psoriasis as well as the different modalities of phototherapy. Participants should also have a better understanding of side effects associated with each treatment, which should help in determining options for therapy.

Administration, Topical↗
PubMed2001

Treatment of psoriasis. Part 2. Systemic therapies.

The array of systemic medications used in the treatment of psoriasis is rapidly expanding. In the United States, methotrexate, retinoids, and cyclosporine are the only systemic drugs approved by the Food and Drug Administration for the treatment of psoriasis. Monitoring and dosage recommendations for these medications are reviewed. Other drugs that are currently available include tacrolimus, mycophenolate mofetil, hydroxyurea, 6-thioguanine, and sulfasalazine. Experience with these drugs is summarized, and dosage and monitoring recommendations in published literature are presented. Combinations of different treatments are addressed and investigational therapies that are in development are reviewed.

Cyclosporine↗