Differences in binding and effector functions between classes of TNF antagonists.

There are currently two Food and Drug Administration-approved classes of biologic agents that target tumor necrosis factor-alpha (TNF-alpha): anti-TNF monoclonal antibodies (mAbs) (adalimumab and infliximab), and soluble TNF receptors (etanercept). This study examined the ability of the TNF antagonists to: (1) bind various polymorphic variants of cell surface-expressed Fc receptors (FcgammaRs) and the complement component C1q, and (2) mediate Ab-dependent cellular cytotoxicity (ADCC) and complement-mediated cytotoxicity (CDC) killing of cells expressing membrane-bound TNF (mTNF) in vitro. Both mAbs and the soluble TNF receptor demonstrated low-level binding to the activating receptors FcgammaRI, FcgammaRIIa, and FcgammaRIIIa, and the inhibitory receptor FcgammaRIIb, in the absence of exogenous TNF. However, upon addition of TNF, the mAbs, but not etanercept, showed significantly increased binding, in particular to the FcgammaRII and FcgammaRIII receptors. Infliximab and adalimumab induced ADCC much more potently than etanercept. In the presence of TNF, both mAbs bound C1q in in vitro assays, but etanercept did not bind C1q under any conditions. Infliximab and adalimumab also induced CDC in cells expressing mTNF more potently than etanercept. Differences in the ability to bind ligand and mediate cell death may account for the differences in efficacy and safety of TNF antagonists.

Topical application of green and white tea extracts provides protection from solar-simulated ultraviolet light in human skin.

BACKGROUND: Tea polyphenols have been found to exert beneficial effects on the skin via their antioxidant properties. AIMS: We sought to determine whether topical application of green tea or white tea extracts would prevent simulated solar radiation-induced oxidative damages to DNA and Langerhans cells that may lead to immune suppression and carcinogenesis. METHODS: Skin samples were analysed from volunteers or skin explants treated with white tea or green tea after UV irradiation. In another group of patients, the in vivo immune protective effects of green and white tea were evaluated using contact hypersensitivity to dinitrochlorobenzene. RESULTS: Topical application of green and white tea offered protection against detrimental effects of UV on cutaneous immunity. Such protection is not because of direct UV absorption or sunscreen effects as both products showed a sun protection factor of 1. There was no significant difference in the levels of protection afforded by the two agents. Hence, both green tea and white tea are potential photoprotective agents that may be used in conjunction with established methods of sun protection.

Patient-reported outcomes and health-care resource utilization in patients with psoriasis treated with etanercept: continuous versus interrupted treatment.

OBJECTIVE: The 24-week Etanercept Assessment of Safety and Effectiveness (EASE) study evaluated the effectiveness and tolerability of continuous versus interrupted etanercept treatment in patients with moderate to severe plaque psoriasis. The objective of this analysis was to assess patient-reported outcomes (PROs) and health-care resource utilization (HRU) data from the EASE study. METHODS: Patients received open-label etanercept 50 mg twice weekly for 12 weeks and then received either continued or interrupted (single round of discontinuation and re-treatment with etanercept) etanercept 50 mg once weekly for the second 12 weeks. PROs included the following: 1) the patient global assessments of psoriasis, joint pain, and itching scores; 2) the Dermatology Life Quality Index; 3) the Medical Outcomes Study Short Form 36 vitality domain; 4) the Beck Depression Inventory; 5) the European Quality-of-Life Group Feeling Thermometer; and 6) a patient satisfaction survey. HRU was evaluated using the Economic Implications of Psoriasis patient questionnaire. RESULTS: Continuous treatment with etanercept 50 mg twice weekly for 12 weeks followed by 50 mg once weekly for 12 weeks produced sustained and clinically important improvements in PROs and reductions in HRU. Reductions in some outcome measures after treatment discontinuation at week 12 were observed in the interrupted group; however, most changes did not revert to baseline levels, consistent with some residual clinical effect, and re-treatment produced improvements similar to week 12 levels. CONCLUSIONS: Continuous etanercept treatment provided greater sustained improvements in PROs than interrupted therapy; however, interrupting etanercept therapy, if needed, has predictable and manageable effects.

UV protective effects of DNA repair enzymes and RNA lotion.

Solar UV radiation is known to cause immune suppression, believed to be a critical factor in cutaneous carcinogenesis. Although the mechanism is not entirely understood, DNA damage is clearly involved. Sunscreens function by attenuating the UV radiation that reaches the epidermis. However, once DNA damage ensues, repair mechanisms become essential for prevention of malignant transformation. DNA repair enzymes have shown efficacy in reducing cutaneous neoplasms among xeroderma pigmentosum patients. In vitro studies suggest that RNA fragments increase the resistance of human keratinocytes to UVB damage and enhance DNA repair but in vivo data are lacking. This study aimed to determine the effect of topical formulations containing either DNA repair enzymes (Micrococcus luteus) or RNA fragments (UVC-irradiated rabbit globin mRNA) on UV-induced local contact hypersensitivity (CHS) suppression in humans as measured in vivo using the contact allergen dinitrochlorobenzene. Immunohistochemistry was also employed in skin biopsies to evaluate the level of thymine dimers after UV. Eighty volunteers completed the CHS portion. A single 0.75 minimum erythema dose (MED) simulated solar radiation exposure resulted in 64% CHS suppression in unprotected subjects compared with unirradiated sensitized controls. In contrast, UV-induced CHS suppression was reduced to 19% with DNA repair enzymes, and 7% with RNA fragments. Sun protection factor (SPF) testing revealed an SPF of 1 for both formulations, indicating that the observed immune protection cannot be attributed to sunscreen effects. Biopsies from an additional nine volunteers showed an 18% decrease in thymine dimers by both DNA repair enzymes and RNA fragments, relative to unprotected UV-irradiated skin. These results suggest that RNA fragments may be useful as a photoprotective agent with in vivo effects comparable to DNA repair enzymes.

Apoptosis mechanisms related to the increased sensitivity of Jurkat T-cells vs A431 epidermoid cells to photodynamic therapy with the phthalocyanine Pc 4.

To examine the clinical applicability of Pc 4, a promising second-generation photosensitizer, for the photodynamic treatment of lymphocyte-mediated skin diseases, we studied the A431 and Jurkat cell lines, commonly used as surrogates for human keratinocyte-derived carcinomas and lymphocytes, respectively. As revealed by ethyl acetate extraction and absorption spectrophotometry, uptake of Pc 4 into the two cell lines was linear with Pc 4 concentration and similar on a per cell basis but greater in Jurkat cells on a per mass basis. Flow cytometry showed that uptake was linear at low doses; variations in the dose-response for uptake measured by fluorescence supported differential aggregation of Pc 4 in the two cell types. As detected by confocal microscopy, Pc 4 localized to mitochondria and endoplasmic reticulum in both cell lines. Jurkat cells were much more sensitive to the lethal effects of phthalocyanine photodynamic therapy (Pc 4-PDT) than were A431 cells, as measured by a tetrazolium dye reduction assay, and more readily underwent morphological apoptosis. In a search for molecular factors to explain the greater photosensitivity of Jurkat cells, the fate of important Bcl-2 family members was monitored. Jurkat cells were more sensitive to the induction of immediate photodamage to Bcl-2, but the difference was insufficient to account fully for their greater sensitivity. The antiapoptotic protein Mcl-1 was extensively cleaved in a dose- and caspase-dependent manner in Jurkat, but not in A431, cells exposed to Pc 4-PDT. Thus, the greater killing by Pc 4-PDT in Jurkat compared with A431 cells correlated with greater Bcl-2 photodamage and more strongly to the more extensive Mcl-1 degradation. Pc 4-PDT may offer therapeutic advantages in targeting inflammatory cells over normal keratinocytes in the treatment of T-cell-mediated skin diseases, such as cutaneous lymphomas, dermatitis, lichenoid tissue reactions and psoriasis, and it will be instructive to evaluate the role of Bcl-2 family proteins, especially Mcl-1, in the therapeutic response.

Psoriasis treatment patterns: results of a cross-sectional survey of dermatologists.

OBJECTIVE: The study evaluated community physician prescribing patterns for patients with psoriasis. METHODS: US dermatologists actively practicing general dermatology and treating 10 or more patients with psoriasis/mo were interviewed (n = 90) in April and June 2006 and they recruited 8 to 10 consecutive patients for record review (n = 895, mean age = 46 years, 51% men). Proportion of patients treated with systemic, biologic, or topical therapy as reported by the dermatologist and recorded in the records was assessed by psoriasis severity. RESULTS: Among patients with severe psoriasis (body surface area affected > 10%), 56% to 63% received systemic therapy (including biologics) or phototherapy and 37% to 44% received topical therapy only. Dermatologists reported prescribing biologics to 41% of patients with severe disease compared with patient records where 27% to 34% of body surface area = 11% to 40% and 36% of body surface area greater than 40% patients received biologics. LIMITATIONS: Because of the small sample, eligibility criteria, and voluntary interview, selection bias may have occurred. CONCLUSIONS: Some dermatologists are prescribing systemic therapy for the majority of their patients with severe psoriasis but a gap in treatment remains for about 40% who received topical therapy alone.

Utilization of narrow-band ultraviolet light B therapy and etanercept for the treatment of psoriasis (UNITE): efficacy, safety, and patient-reported outcomes.

BACKGROUND: Moderate to severe psoriasis is a significant inflammatory disease that frequently requires systemic therapies to effectively treat the underlying disorder. Etanercept and narrow-band ultraviolet light B (NB-UVB) are widely used to treat this disease. OBJECTIVE: To evaluate the effectiveness, tolerability, and patient-reported outcomes of combination etanercept plus NB-UVB phototherapy in moderate to severe plaque psoriasis. METHODS: This 12-week, single-arm, open-label study evaluated the combination of etanercept 50 mg twice weekly and NB-UVB thrice weekly in 86 patients. The primary outcome measure was > or =75% improvement from baseline in the Psoriasis Area and Severity Index (PASI 75). Other measures included PASI 90, PASI 100, and the Dermatology Life Quality Index (DLQI). RESULTS: At week 12, 26.0% achieved PASI 100, 58.1% achieved PASI 90, and 84.9% of patients achieved PASI 75. Mean improvement from baseline in DLQI was 84.4%. No unexpected, untoward adverse events were noted. CONCLUSIONS: A 12-week course of etanercept plus NB-UVB phototherapy was well tolerated and produced clinically meaningful improvements in signs and symptoms of moderate to severe plaque psoriasis and in patient-reported outcomes. Further investigation of the safety and efficacy of the use of such combination for this indication in controlled clinical trials would be of interest.

A randomized, open-label trial of continuous versus interrupted etanercept therapy in the treatment of psoriasis.

BACKGROUND: Although etanercept is used as a continuous therapy for moderate to severe plaque psoriasis, intermittent use may be necessary in some instances. OBJECTIVE: In this randomized, open-label study, we evaluated the effectiveness and safety of continuous versus interrupted etanercept therapy. METHODS: All patients received uninterrupted etanercept 50 mg twice weekly during the first 12 weeks, followed by either continuous (n = 1272) or interrupted (n = 1274) etanercept 50 mg once weekly in the next 12 weeks. The primary effectiveness end point was the proportion of responders (those who achieved a Physician's Global Assessment [PGA] score

Immunohistochemical staining for CD45R isoforms in paraffin sections to diagnose mycosis fungoides-type cutaneous T-cell lymphoma.

The definitive diagnosis of mycosis fungoides (MF)-type cutaneous T-cell lymphoma (CTCL) is difficult because a cumulative set of information is typically required: clinical features, histopathology, and special diagnostic tests (typically immunophenotyping and T-cell receptor gamma [TCRgamma] gene rearrangement). Fresh tissue is not always available for the special tests. We report a simple and readily available procedure evaluating the staining pattern on formalin-fixed, paraffin-embedded skin that can help with the diagnosis of patch/plaque stage MF. We reviewed 92 cases of MF or probable MF that had clinical information, immunophenotyping and TCRgamma gene rearrangement studies and that had been evaluated in our multidisciplinary lymphoma conference. We used antibodies to the isoforms of CD45, CD45RO for mature T cells and CD45RB for subsets of T cells. When atypical CD45RB-positive/CD45RO-negative cells were seen in nonspongiotic epidermis, the individuals had a high cumulative clinical and histologic score for MF. In contrast, 15 cases of known contact dermatitis showed a reactive pattern of both CD45RB- and CD45RO-positive cells in spongiotic epidermis. We compared the epidermal CD45RB-positive/CD45RO-negative staining pattern with CD7 deficiency by immunophenotyping and TCRgamma gene rearrangement, two commonly used methods in the diagnosis of MF. The epidermal CD45RB-positive/CD45RO-negative staining pattern is comparable and may be better in equivocal cases of possible MF. Therefore immunostaining for CD45RB and CD45RO on paraffin sections is a simple, reliable, and convenient modality in the diagnosis of MF.

Reductions in healthcare resource utilization in psoriatic arthritis patients receiving etanercept therapy: results from the educate trial.

The Experience Diagnosing, Understanding Care, and Treatment with Enbrel (EDUCATE) trial is a phase IV, 24-week, multicenter, open-label study of etanercept 50 mg weekly in the treatment of psoriatic arthritis (PsA) in community dermatology clinics. In this study, patients with active PsA and moderate to severe plaque psoriasis have measurable uses of healthcare resources at baseline, reflecting a burden of illness. Etanercept significantly reduced healthcare resource utilization, absenteeism, and caregiver assistance in PsA patients after 24 weeks of treatment. These results could translate into savings on both direct and indirect costs and improvements in health-related quality of life for patients with PsA.

Etanercept improves psoriatic arthritis patient-reported outcomes: results from EDUCATE.

Experience Diagnosing, Understanding Care, and Treatment With Etanercept (EDUCATE) is a multicenter, phase 4, 24-week, open-label study of the safety and efficacy of etanercept therapy in patients with psoriatic arthritis (PsA) in routine dermatologic practice. We present data on patient-reported outcomes (PROs) from EDUCATE, which demonstrate that subjects with PsA achieved clinically meaningful improvements in both skin- and joint-related PROs after 24 weeks of treatment.

What have we learned in dermatology from the biologic therapies?

Recent advances in our basic understanding of immunology, specifically the roles of various cell types involved in immune response and the action of cytokines they produce, has radically changed our understanding of the origin of inflammatory dermatoses, and other autoimmune diseases. Broadened comprehension of the immune response on a molecular level has facilitated the development of biologic therapeutics for the treatment of psoriasis, atopic dermatosis, and other inflammatory conditions. However, despite major advances in development and use of targeted biologics for controlling autoimmune disease, effective cures for these conditions remain to be developed and genetic determinants of predisposition to such diseases remain to be identified. Here, we review the history of our understanding of inflammatory dermatoses, traditional and new treatment approaches, and future directions for research and therapy in this area.

Etanercept for the treatment of psoriasis in the elderly.

This study's objective was to analyze the effect of etanercept on Psoriasis Area and Severity Index (PASI) 50, PASI 75, and Dermatology Life Quality Index in geriatric and nongeriatric populations. We conducted a post hoc analysis of two large phase III randomized placebo trials of etanercept. There were no statistically significant differences between the elderly and young with regard to the number of patients reaching a PASI 50 or PASI 75 at any of the 3 dosing regimens. Baseline Dermatology Life Quality Index scores were not statistically significant between both groups and both the elderly and young had similar changes in Dermatology Life Quality Index with therapy. A limitation of the study was the small number of patients in the elderly group. In conclusion, psoriasis and its treatment has a similar impact on quality of life in the elderly as it does in the young.

Clinical characteristics of psoriatic arthritis and psoriasis in dermatologists' offices.

OBJECTIVE: To describe the skin and joint disease of patients with psoriatic arthritis being treated in dermatology clinics. METHODS: A total of 1122 patients who had active psoriatic arthritis were enrolled in a Phase 4, non-randomized, open-label, single-arm, 24-week study. They were treated at 108 community and 17 academic dermatology centers. These patients experienced clinically stable, plaque psoriasis involving > or =10% body surface area and joint disease (either > or = two swollen and > or = two tender/painful joints for > or =3 months, or > or = one joint with sacroiliitis or spondylitis). RESULTS: In general, patient demographics and disease characteristics did not appear to differ between academic and community dermatology sites. Based on patient-reported assessments, patients rated the severity of their baseline joint symptoms lower than the severity of their skin disease. Baseline skin and joint disease measures were not correlated. Psoriatic arthritis was newly diagnosed in 23% of the patients. Most had received prior therapy for psoriasis, but only half had received systemic therapy for psoriatic arthritis. CONCLUSION: Assessment for joint disease in psoriasis patients being treated at dermatology clinics may facilitate earlier psoriatic arthritis diagnosis and treatment initiation, which may prevent disability and other negative impacts.

Use of etanercept for psoriatic arthritis in the dermatology clinic: the Experience Diagnosing, Understanding Care, and Treatment with Etanercept (EDUCATE) study.

OBJECTIVE: To assess the efficacy and tolerability of etanercept to treat psoriatic arthritis. MATERIALS AND METHODS: A total of 1,122 patients who had active psoriatic arthritis were enrolled in a Phase 4, non-randomized, open-label, single-arm, 24-week study. These patients had clinically stable, plaque psoriasis involving >or=10% body surface area and joint disease (either >or=two swollen and >or=two tender/painful joints for >or=3 months, or >or=one joint with sacroiliitis or spondylitis). They received etanercept therapy 50 mg subcutaneously once weekly for 24 weeks. RESULTS: After 24 weeks of treatment, 865 patients (77.1%; 95% CI: 74.64-79.55%) achieved a 'mild or better' score on the physician global assessment of psoriasis and were improved from baseline. Mean improvement in body surface area involvement was 16.9 percentage points (15.89-17.91). Patient global assessment of psoriasis, joint pain, and joint disease scores were improved by means of 2.2 (2.15-2.34), 2.7 (2.53-2.84), and 1.5 (1.39-1.55), respectively. Thirty-five patients (3.1%) experienced at least one serious adverse event. No patient died during the study. CONCLUSIONS: These results support the effectiveness and tolerability of etanercept treatment in patients with psoriatic arthritis being treated at dermatology clinics.

High ultraviolet A protection affords greater immune protection confirming that ultraviolet A contributes to photoimmunosuppression in humans.

Solar radiation causes immunosuppression that contributes to skin cancer growth. Photoprotective strategies initially focused on the more erythemogenic ultraviolet B. More recently, the relationship of ultraviolet A and skin cancer has received increased attention. We hypothesized that if ultraviolet A contributes significantly to human ultraviolet-induced immune suppression, then increased ultraviolet A filtration by a sunscreen would better protect the immune system during ultraviolet exposure. Two hundred and eleven volunteers were randomized into study groups and received solar-simulated radiation, ranging from 0 to 2 minimum erythema dose, on gluteal skin, with or without sunscreen, 48 h prior to sensitization with dinitrochlorobenzene. Contact hypersensitivity response was evaluated by measuring the increase in skin fold thickness of five graded dinitrochlorobenzene challenge sites on the arm, 2 wk after sensitization. Clinical scoring using the North American Contact Dermatitis Group method was also performed. Solar-simulated radiation dose-response curves were generated and immune protection factor was calculated using a nonlinear regression model. Significance of immune protection between study groups was determined with the Mann-Whitney-Wilcoxon exact test. The sunscreen with high ultraviolet A absorption (ultraviolet A protection factor of 10, based on the in vivo persistent pigment darkening method) and a labeled sun protection factor of 15 demonstrated better immune protection than the product that had a low ultraviolet A absorption (ultraviolet A protection factor of 2) and a labeled sun protection factor of 15. Nonlinear regression analysis based on skin fold thickness increase revealed that the high ultraviolet A protection factor sunscreen had an immune protection factor of 50, more than three times its sun protection factor, whereas the low ultraviolet A protection factor sunscreen had an immune protection factor of 15, which was equal to its labeled sun protection factor. This study demonstrates that ultraviolet A contributes greatly to human immune suppression and that a broad-spectrum sunscreen with high ultraviolet A filtering capacity results in immune protection that exceeds erythema protection. These results show that high ultraviolet A protection is required to protect against ultraviolet-induced damage to cutaneous immunity.

Cutaneous lymphoid hyperplasia: a lymphoproliferative continuum with lymphomatous potential.

Cutaneous lymphoid hyperplasia (CLH) has been proposed to be the benign end of a continuum of lymphoproliferative disorders with cutaneous lymphoma at its malignant extreme. An intermediate condition, known as "clonal CLH," was first recognized by us and shown to be a transitional state capable of eventuating in overt lymphoma. To better determine the prevalence of dominant clonality and risk of lymphoma among CLH cases, we studied the immunohistology and clonality of fresh-frozen samples from 44 CLH patients referred to a multidisciplinary cutaneous lymphoproliferative disorders program. Using a large panel of lymphoid markers, the cases were divided into 38 typical mixed B-cell/T-cell type CLH and 6 T-cell-rich type (T-CLH), the latter containing > 90% T cells. Of the 44 patients, 38 had solitary or localized lesions (4 cases of T-CLH), and 6 had regional/generalized lesions (2 cases of T-CLH). Forty cases were of idiopathic etiology. Suspected etiologies among 4 other cases included mercuric tattoo pigment, doxepin, clozapine, and bacterial infection. Immunoglobulin heavy chain (IgH) and T-cell receptor (TCR)-gamma gene rearrangements (GR) were studied using polymerase chain reaction assays, which are approximately 80% sensitive. Overall, 27 cases (61%) showed clonal CLH: 12 IgH+ (27%; 3 cases of T-CLH); 13 TCR+ (30%; 1 case of T-CLH); and 2 IgH+/TCR+ (4%; neither case was T-CLH). Two cases (4%; 1 case of T-CLH) progressed to cutaneous B-cell lymphoma. Both of these patients presented with regional lesions. Our findings indicate that clonal overgrowth is common in CLH, links CLH to lymphoma, and probably involves both B- and T-cell lineages (although TCR GR by B cells and vice versa could not be ruled out). The high prevalence of dominant clonality in our series may have resulted from the sensitivity of our PCR assays as well as patient selection.

Circulating CD4+CD7- lymphocyte burden and rapidity of response: predictors of outcome in the treatment of Sézary syndrome and erythrodermic mycosis fungoides with extracorporeal photopheresis.

BACKGROUND: Extracorporeal photopheresis (ECP) is an effective treatment for cutaneous T-cell lymphoma. Controversy has arisen regarding its ability to improve survival rates in Sézary syndrome (SS). We describe our experience with ECP in the treatment of SS and erythrodermic mycosis fungoides, with particular emphasis on early predictors of long-term outcome. OBSERVATIONS: We included 17 patients (15 with SS and 2 with erythrodermic mycosis fungoides) who received ECP as initial treatment. Four of these patients were moribund on presentation (Eastern Cooperative Oncology Group Performance Status score, 4) and underwent only 1 to 2 cycles of ECP. The median survival was 56 months for the 11 patients with SS and an Eastern Cooperative Oncology Group Performance Status score of less than 4. If all 15 patients with SS are considered, median survival was 34 months. Response after 5 months of ECP correlated with long-term survival. A low number (<6.0 x10(3)/ micro L) of circulating CD4(+)CD7(-) lymphocytes correlated with response after 5 months of ECP. CONCLUSIONS: Extracorporeal photopheresis is a safe, effective, and well-tolerated treatment for erythrodermic mycosis fungoides and SS. Low numbers of CD4(+)CD7(-) cells in the circulation and a positive response after 5 months of therapy predicted long-term survival. Moribund patients are much less likely to benefit from ECP.

Quantifying skin disease burden in mycosis fungoides-type cutaneous T-cell lymphomas: the severity-weighted assessment tool (SWAT).

OBJECTIVE: To develop a quantitative tool to assess severity of mycosis fungoides. DESIGN: Prospective analysis of a cohort. SETTING: University department of dermatology-based cutaneous lymphoma clinic. PATIENTS: From 1984 to 1995, 1186 visits from 323 referred patients seen in a multidisciplinary cutaneous lymphoma program. MAIN OUTCOME MEASURES: Severity-weighted assessment tool (SWAT) scores were obtained for patients at each visit. This score represents the product of the percentage total body surface area (%TBSA) involvement of each lesion type (patch, plaque, and tumor or ulceration), multiplied by a weighting factor: SWAT = (patch %TBSA x 1) + (plaque %TBSA x 2) + (tumor or ulcer %TBSA x 3). In addition, the standard measurements of TBSA involvement and physician global assessments were recorded for comparison. RESULTS: The SWAT score correlated well with %TBSA (r = 0.95, P<.001), physician global assessment (r = 0.60, P<.001), and time to complete remission during psoralen-UV-A therapy (r = 0.80, P<.001), therefore indicating validity against standard measures. Analysis of individual and subsets of patients demonstrated that the SWAT score more accurately quantified changes in skin disease burden, including mixed responses to treatment, than did %TBSA alone. CONCLUSIONS: The SWAT score is a useful clinical measurement for mycosis fungoides. The SWAT score captures overall physician impressions of disease status on a continuous dimensionless numerical scale, therefore providing a defined, objective, and sensitive quantitative measure. This tool is suitable for individual patient assessment, clinical trials, and outcome comparisons.

Laser-assisted penetration of topical anesthetic in adults.

OBJECTIVE: To determine whether pretreatment of skin with erbium:YAG (Er:YAG) laser-assisted delivery facilitates the penetration of lidocaine cream to provide anesthesia suitable for needlesticks after just 5 minutes. DESIGN: Trial 1 was a double-blind randomized controlled trial, whereas trial 2 was a nonblinded randomized controlled trial. SETTING: The study was conducted in 2 facilities, an academic and a private clinical research unit. PARTICIPANTS: A total of 320 healthy volunteers, aged 18 to 65 years and of any Fitzpatrick skin phototype. INTERVENTIONS: Trial 1 involved an Er:YAG laser pretreatment to disrupt the stratum corneum followed by an application of 4% lidocaine cream on one arm, and a laser pretreatment plus placebo on the other arm. Trial 2 involved an application of 4% lidocaine cream alone on one arm, and a laser pretreatment followed by an application of 4% lidocaine cream on the other arm. MAIN OUTCOME MEASURE: Self-reported pain perception on a 100-mm visual analog scale after quick insertion and removal of a 25-gauge hypodermic needle on the treatment sites. RESULTS: Data from the 2 trials showed that there was a 62% pain reduction with laser pretreatment plus lidocaine compared with laser pretreatment plus placebo, and a 61% pain reduction with laser pretreatment plus lidocaine, compared with lidocaine alone. The decrease in pain in both trials was statistically significant (P<.001). Adverse events reported 48 hours after treatment were few and mild. CONCLUSION: Treatment with the Er:YAG laser followed by lidocaine cream is a safe, effective, and efficient means of inducing skin anesthesia that significantly reduces the pain of hypodermic needle insertion.