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Biomedical subjects

Mark Lebwohl

Publications and source records attributed to Mark Lebwohl.

At least 37 records · Page 2Linked to original sources
PubMed2005

Oral phosphate binders in the treatment of pseudoxanthoma elasticum.

BACKGROUND: Pseudoxanthoma elasticum (PXE) is a systemic connective tissue disorder involving elastic fiber calcification and fragmentation with major clinical manifestations occurring in the cutaneous, ocular, and cardiovascular systems. Normalization of the serum calcium-phosphate product through hemodialysis in a previous patient with perforating periumbilical PXE and elevated serum phosphate resulted in regression of skin lesions. OBJECTIVE: We sought to study the effect of pharmacologically limiting the intestinal absorption of phosphate in patients with PXE. METHODS: Patients received baseline skin examinations, target skin lesion evaluation, and photography; renal function tests and serum calcium and phosphate levels; urine calcium, phosphate, and creatinine levels; skin biopsy; and eye examinations and indocyanine-green angiography. Patients were treated with aluminium hydroxide tablets or liquid and returned every 2 to 4 months for skin photography and lesion evaluation. Repeated skin biopsies were performed on clinically improved target sites. Ophthalmologic evaluation was obtained at yearly intervals. RESULTS: Of 6 patients, 3 showed significant clinical improvement of skin lesions and all 3 of these patients showed histopathologic regression of disease in their target lesions. No deterioration of eye disease was seen in any of the 6 patients at 1-year follow-up. CONCLUSION: Our results demonstrate that the calcification seen in PXE may be reversible in some patients. This could hold true for eye and vascular lesions and for skin. Further studies supporting these results could reveal the first real treatment option for PXE.

Adult↗
PubMed2005

Tacrolimus ointment is more effective than pimecrolimus cream with a similar safety profile in the treatment of atopic dermatitis: results from 3 randomized, comparative studies.

OBJECTIVE: To compare the efficacy and safety of tacrolimus ointment and pimecrolimus cream in adult and pediatric patients with mild to very severe atopic dermatitis (AD). METHODS: One thousand and sixty-five patients were randomized to treatment in 3 multicenter, randomized, investigator-blinded, 6-week studies. RESULTS: Based on the Eczema Area Severity Index (EASI), tacrolimus ointment was more effective than pimecrolimus cream at the end of the study in adults (54.1% vs. 34.9%, respectively; P < .0001), in children with moderate/severe disease (67.2% vs. 56.4%, respectively; P = .04), in the combined analysis (52.8% vs. 39.1%, respectively; P < .0001), and at week 1 in children with mild disease (39.2% vs. 31.2%, respectively; P = .04). Tacrolimus was also more effective than pimecrolimus based on the Investigator Global AD Assessment (IGADA), improvement in percentage of total body surface area affected, and improvement in itch scores (P < or = .05), with a faster onset of action. There was no significant difference in the incidence of adverse events (AEs), including application site reactions in the 2 studies involving 650 children. Adults treated with tacrolimus experienced a greater number of local application site reactions on day 1; both groups reported a similar incidence of application site reactions thereafter. More pimecrolimus-treated patients than tacrolimus-treated patients withdrew from the studies because of a lack of efficacy (P < or = .03) or adverse events (P = .002; pediatric mild). CONCLUSION: Tacrolimus ointment is more effective and has a faster onset of action than pimecrolimus cream in adults and children with AD; their safety profiles are similar.

Adolescent↗
PubMed2005

An extended 16-week course of alefacept in the treatment of chronic plaque psoriasis.

BACKGROUND: The efficacy and safety of one and two courses of alefacept have been demonstrated in phase 2 and 3 clinical trials, with a course of alefacept defined as 12 weeks of once-weekly treatment followed by 12 weeks of observation. METHODS: This randomized, single-center study compared the safety and efficacy of a standard 12-week versus extended 16-week alefacept dosing period in 20 patients with chronic plaque psoriasis. RESULTS: Both dose groups showed marked improvement in mean Psoriasis Area and Severity Index (PASI) score from baseline through week 24 (between-group difference: not significant). In each group, 60% of patients achieved PASI 50 (> or =50% reduction from baseline PASI score) at any time between weeks 12 and 24. For patients who received 16 weeks of alefacept, the mean percentage change from week-12 PASI score was higher and continued to increase through week 24 compared with that for patients who received 12 weeks of alefacept (P < .05). Adverse events were similar between the two groups and comparable with those observed in phase 2 and 3 clinical studies of alefacept. CONCLUSIONS: This was an open-label, single-center study of 20 patients. Further study is warranted to assess the effect of alefacept when administered for more than 12 weeks. Extended dosing with alefacept appeared to have a similar safety profile to 12-week dosing and may offer further benefit to some patients for disease improvement.

Alefacept↗
PubMed2005

A clinician's paradigm in the treatment of psoriasis.

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.

Administration, Oral↗
PubMed2005

Development of the US PSORIQoL: a psoriasis-specific measure of quality of life.

BACKGROUND: Several instruments are available for assessing impairment and disability associated with psoriasis. The first true psoriasis-specific quality of life (QoL) questionnaire suitable for use in clinical trials, the Psoriasis Index of Quality of Life (PSORIQoL), has recently been developed in the UK. The aim of the current study was to produce and validate a conceptually equivalent US version of the PSORIQoL with equally good psychometric properties. METHODS: A lay translation panel was employed to ensure that the wording of the questionnaire was appropriate for a US population. Semi-structured interviews conducted with 37 patients tested the instrument's ease of completion, relevance and comprehensiveness. Finally, a test-retest validation mail survey was conducted with 72 patients to determine reliability, internal consistency and construct validity. RESULTS: Few changes were necessary to the wording of the questionnaire. Interviewees found the questionnaire easy to complete (requiring an average of 4 min) and the content relevant and comprehensive. The adapted measure had comparable psychometric properties to the original, with a test-retest reliability coefficient of 0.90, indicating excellent reproducibility. Internal consistency and initial indications of construct validity were also good, with scores on the measure related as expected to perceived general health and severity of psoriasis and the presence of visible lesions. CONCLUSIONS: The US PSORIQoL is a practical, reliable and valid instrument for measuring the impact of psoriasis and its treatment on QoL in clinical trials and in routine practice. It remains necessary to establish the instrument's responsiveness to changes in QoL associated with effective interventions.

Adult↗
PubMed2005

Long-term efficacy and safety of tretinoin emollient cream 0.05% in the treatment of photodamaged facial skin: a two-year, randomized, placebo-controlled trial.

BACKGROUND: Long-term (>1 year) placebo-controlled studies of tretinoin in the treatment of photodamaged skin have not been conducted. Recently, we conducted a 2-year placebo-controlled study of tretinoin emollient cream 0.05%, including histopathologic assessment of safety and analysis of markers of collagen deposition. OBJECTIVE: The objective of the study was to determine the long-term safety and efficacy of tretinoin emollient cream 0.05% in the treatment of moderate to severe facial photodamage. METHODS: A total of 204 subjects were treated with tretinoin or placebo (vehicle emollient cream) applied to the entire face once a day for up to 2 years. Clinical and histologic effects were assessed at regularly scheduled clinic visits. RESULTS: Treatment with tretinoin resulted in significantly greater improvement relative to placebo in clinical signs of photodamage (fine and coarse wrinkling, mottled hyperpigmentation, lentigines, and sallowness), overall photodamage severity, and investigator's global assessment of clinical response (p<0.05). Histologic evaluation showed no increase in keratinocytic or melanocytic atypia, dermal elastosis, or untoward effects on stratum corneum following treatment with tretinoin compared with placebo. Immunohistochemistry studies, conducted at three study centers, showed a significant increase relative to placebo in facial procollagen 1C terminal, a marker for procollagen synthesis, at month 12 (p=0.0074). CONCLUSION: Long-term treatment with tretinoin emollient cream 0.05% is safe and effective in subjects with moderate to severe facial photodamage.

Administration, Topical↗
PubMed2005

Impaired skin barrier function in dermatologic disease and repair with moisturization.

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.

Ceramides↗
PubMed2004

Evaluation of safety and clinical activity of multiple doses of the anti-CD80 monoclonal antibody, galiximab, in patients with moderate to severe plaque psoriasis.

BACKGROUND: Reduction in lesional, activated T cells induces improvement in psoriatic plaques. Galiximab (IDEC-114), an IgG(1) anti-CD80 antibody, binds to CD80, a costimulatory molecule involved in T-cell activation. OBJECTIVE: A Phase I/II, multidose, multischedule, dose-finding study of galiximab to evaluate safety, pharmacokinetics, and clinical activity was conducted in 35 patients with moderate to severe plaque psoriasis. METHODS: Seven cohorts of five patients received galiximab intravenously on three different schedules at different dose levels. RESULTS: Adverse events (AEs) commonly occurred as mild and self-limiting. Improvements were observed in most cohorts without evidence of a dose response in Psoriasis Area and Severity Index (50% or greater reduction in PASI score in 40% of patients), Physician's Global Psoriasis Assessment (PGA rating of Good or above in 57% of patients), and Psoriasis Severity Scale (PSS, baseline mean of 7.6 decreased by Study Day 127 to 5.0). An association was observed between reduction in CD3(+) cell count in histologic studies and reduction in PASI score. No antibodies to galiximab were detected. CONCLUSION: Galiximab appears to be safe and well tolerated with preliminary evidence of clinical and histologic response.

Adult↗
PubMed2004

Review of therapy of psoriasis: the prebiologic armamentarium.

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.

Administration, Oral↗
PubMed2004

Combination therapy to treat moderate to severe psoriasis.

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.

Acitretin↗
PubMed2004

Psoriasis.

Explore the source record for details and available documents.

Humans↗
PubMed2004

Imiquimod 5% cream for the treatment of actinic keratosis: results from two phase III, randomized, double-blind, parallel group, vehicle-controlled trials.

BACKGROUND: The immune system plays a critical role in the development and pathogenesis of actinic keratosis (AK). Imiquimod has been shown to stimulate the cutaneous immune response and be effective for the treatment of nonmelanoma skin cancers. OBJECTIVE: Two phase III, randomized, double-blind, vehicle-controlled studies evaluated the efficacy of imiquimod 5% cream compared with vehicle in the treatment of AK lesions on the face and balding scalp. METHODS: A total of 436 participants at 24 centers in the United States and Canada were randomized to either imiquimod 5% or vehicle cream. Study cream was applied one time per day, 2 days per week for 16 weeks. Clearance of AK lesions was clinically assessed at an 8-week posttreatment visit. RESULTS: The complete clearance rate was 45.1% for the imiquimod group and 3.2% for the vehicle group. The difference in complete clearance rates (imiquimod minus vehicle) was 41.9% with a 95% confidence interval of 34.9% to 49%. The partial (> or =75%) clearance rate was 59.1% for the imiquimod group and 11.8% for the vehicle group. The difference in partial clearance rates (imiquimod minus vehicle) was 47.3% with a 95% confidence interval of 39.5% to 55.1%. The median percent reduction in AK lesions was 83.3% for the imiquimod group and 0% for the vehicle group. Local skin reactions were common. Severe erythema was reported by 17.7% of participants who received imiquimod and 2.3% of participants who received vehicle. Overall, imiquimod was very well tolerated. CONCLUSION: Imiquimod 5% cream used 2 times per week for 16 weeks is an effective and well-tolerated treatment for AK.

Adjuvants, Immunologic↗
PubMed2004

Pimecrolimus cream 1% in the treatment of intertriginous psoriasis: a double-blind, randomized study.

BACKGROUND: Inverse psoriasis can be difficult to treat because of the high sensitivity of intertriginous areas to cutaneous side effects, such as irritation and striae. Pimecrolimus, a well-tolerated, nonatrophogenic, skin-selective inflammatory cytokine inhibitor, has been shown to be effective in the treatment of psoriasis when applied topically under occlusion. OBJECTIVE: This study evaluated the efficacy and safety of pimecrolimus cream 1% versus vehicle twice a day in the treatment of inverse psoriasis. Methods This was a double-blind, randomized, vehicle-controlled study in 57 patients with moderate to severe inverse psoriasis. Patients were evaluated using Investigator's Global Assessment of overall severity, Target Area Score, and Patient Self-Assessment. RESULTS: A significant between-group difference was observed early on, with 54% of the pimecrolimus group versus 21% of the vehicle group having an Investigator's Global Assessment score of 0 or 1 (clear or almost clear) at week 2 ( P = .0169). By week 8, 71% of the pimecrolimus group had an Investigator's Global Assessment score of 0 or 1. Change from baseline in Target Area Score was -2.4 (pimecrolimus group) compared with -0.7 (vehicle) at day 3 ( P < .0001). By week 8, 82% of patients using pimecrolimus scored their disease as well or completely controlled versus 41% of the vehicle group ( P = .0007). Adverse events were similar between groups. CONCLUSION: Pimecrolimus cream 1% is an effective treatment for inverse psoriasis with a rapid onset of action, and is safe and well-tolerated.

Administration, Topical↗
PubMed2004

Tacrolimus ointment is effective for facial and intertriginous psoriasis.

BACKGROUND: Intertriginous and facial involvement are manifestations of psoriasis that require a different approach than is used for typical plaque psoriasis on other skin areas. Topical corticosteroids are the primary treatment for psoriasis; however, the side effects of corticosteroids are magnified on intertriginous and facial skin. Topical tacrolimus offers the potential for anti-inflammatory effect without the atrophy or other local side effects associated with the use of topical corticosteroids. OBJECTIVE: To determine the efficacy and tolerability of 0.1% tacrolimus ointment for the treatment of facial or intertriginous psoriasis. METHODS: One hundred sixty-seven patients 16 years or older were evaluated in an 8-week, randomized, double-blind, vehicle-controlled, multi-center study. Upon entry into the study, patients were randomized 2:1 to apply the tacrolimus ointment 0.1% or vehicle twice daily to all psoriatic lesions of the face or intertriginous areas for 8 weeks. The physician's global assessment was used to assess improvement from baseline. The inverse psoriasis severity for patients was measured using a 6-point scale from clear to very severe. RESULTS: As early as day 8, more patients ( P = .004) had cleared or achieved excellent improvement in the 0.1% tacrolimus ointment group compared to the vehicle group (24.8% vs 5.8%). At the end of the 8-week treatment period 65.2% of the tacrolimus ointment group and 31.5% of the vehicle were clear or almost clear ( P < .0001) based on a Static Severity Score. Adverse events were similar in the 0.1% tacrolimus ointment and vehicle groups. Conclusion Tacrolimus ointment is an effective treatment for psoriasis of the face or intertriginous areas.

Adolescent↗
PubMed2004

Frequency of culture-proven dermatophyte infection in patients with suspected tinea pedis.

BACKGROUND: This study examined the incidence of culture-proven tinea pedis in patients who presented with a foot rash clinically suspected to be tinea pedis. METHODS: Cultures were taken from 874 patients in 4 dermatology clinics across the country. The incidence of patients with positively cultured tinea pedis was compared with the total number of patients in the study. RESULTS: The surprisingly low percentage of patients correctly diagnosed with tinea pedis was determined to be 32%. The remaining 68% of patients either had a nonfungal foot dermatitis or tinea pedis with false-negative cultures. CONCLUSIONS: This study demonstrates the need for fungal cultures when patients present with scaling feet as well as the importance of a broad differential diagnosis to ensure timely and appropriate therapy.

Arthrodermataceae↗
PubMed2004

Look beyond financial conflicts of interest in evaluating industry-academia collaborations in burden-of-illness and outcomes research studies in dermatology.

Financial relationships exist among industry, scientific investigators, and academic medical centers. These relationships can foster research in the basic sciences, clinical trials, health economics evaluations, and other outcomes assessment studies. To govern the conduct of burden-of-illness and outcomes research studies involving collaborations between industry and academia, we propose voluntary standards related to: 1) the development of and adherence to standards for research conduct and reporting; 2) disclosure, discussion, and management of potential impacts of financial conflicts of interest; and 3) transparency in research methods and open access to study results.

Academies and Institutes↗