Infliximab improves health-related quality of life in the presence of comorbidities among patients with moderate-to-severe psoriasis

Background  Psoriasis affects patients both physically and psychologically.
Objectives  To investigate the effect of comorbidities on health-related quality of life (HRQoL) and to determine whether infliximab improved HRQoL in the presence of these conditions.
Methods  In this multicentre, double-blind study, 835 patients with moderate-to-severe plaque psoriasis were randomized to receive infliximab 3 or 5 mg kg⁻¹ or placebo at weeks 0, 2 and 6. Infliximab-treated patients were re-randomized at week 14 to receive the same treatment every 8 weeks or as needed through week 46; placebo patients crossed over to infliximab 5 mg kg⁻¹ at week 16. Disease severity (Psoriasis Area and Severity Index, PASI) and HRQoL (Dermatology Life Quality Index, DLQI; 36-item Short-Form Health Survey, SF-36) were measured at various time points. The effect of patient comorbidities on baseline HRQoL was assessed using multiple regression models. The impact of key comorbidities on infliximab treatment effect was also assessed.
Results  Disease severity (PASI), depression and psoriatic arthritis (PsA) were predictors of poor baseline HRQoL. At week 10, infliximab 3 and 5 mg kg⁻¹ significantly improved physical and mental health dimensions of the SF-36 and the DLQI (all P  < 0·001). Consistent improvement in HRQoL with infliximab treatment was observed regardless of baseline patient characteristics or comorbidities. Through week 50, HRQoL and PASI scores were most improved with infliximab 5 mg kg⁻¹ administered every 8 weeks.
Conclusions  Disease severity, depression and PsA were significant predictors of poor HRQoL. Infliximab significantly improved HRQoL, regardless of these characteristics.     

Imiquimod 5% cream for external genital or perianal warts in human immunodeficiency virus-positive patients treated with highly active antiretroviral therapy: an open-label, noncomparative study

Background  Human immunodeficiency virus (HIV)+ patients have an increased risk of anogenital warts. High-risk (HR) human papillomaviruses (HPVs), especially types 16 and 18, are major risk factors for precancerous and cancerous lesions of the anogenital tract, while low-risk (LR) HPVs are associated with benign lesions. Cure of genital warts with ablative techniques, surgical excision, podophyllotoxin or trichloroacetic acid is frequently difficult. Treatment with imiquimod cream showed a total clearance of external genital or perianal warts in about 50% of immunocompetent subjects. However, total clearance was reduced in HIV+ subjects not treated with highly active antiretroviral therapy (HAART).
Objectives  To assess clinically and by monitoring HPV content the efficacy of 5% topical imiquimod to treat anogenital warts in HIV+ subjects with at least partially restored immune functions.
Methods  Fifty HIV+ patients successfully treated with HAART (total CD4+ cells ≥ 200 cells mm⁻³ and plasma HIV RNA load < 10⁴ copies mL⁻¹) with anogenital warts were included. Imiquimod 5% cream was applied on external genital or perianal warts three times weekly for up to 16 weeks. Warts were tested at entry and after treatment for human LR- and HR-HPV DNA.
Results  Total wart clearance was observed in 16 of 50 (32%) patients at week 16. At enrolment, HPV DNA was present in more than 90% of lesions with a majority of lesions co-infected by HR- and LR-HPV. At study end, the HPV load decreased or became undetectable in 40% of cases studied.
Conclusions  Imiquimod 5% cream did not show safety concerns and is suitable for use in HIV+ subjects with anogenital warts and successful HAART treatment.     

Long-term maintenance treatment of moderate-to-severe plaque psoriasis with infliximab in combination with methotrexate or azathioprine in a retrospective cohort

Background  Effective, fast-acting and safe therapies are needed for long-term maintenance treatment of psoriasis. In October 2005, infliximab was approved for the treatment of moderate-to-severe plaque psoriasis, but long-term data are limited.
Objective  To evaluate the effectiveness of infliximab, used in combination with methotrexate or azathioprine, in maintaining clinical benefit in patients with moderate-to-severe psoriasis.
Methods  The medical charts of 23 patients treated with infliximab from August 2001 to February 2007 were retrospectively reviewed. Most patients received either infliximab 3 mg/kg (17 of 23) or 5 mg/kg (1 of 23) in combination with methotrexate, while 5 of 23 patients received infliximab 5 mg/kg in combination with azathioprine. Psoriasis Area Severity Index (PASI) score and adverse events were recorded at every infliximab infusion visit at the hospital.
Results  Patient data were available for a minimum of 4 weeks and up to 5 years and 5 months. At week 14, 91.3% achieved PASI 50, 69.6% achieved PASI 75, and 39.1% achieved PASI 90. Only two patients discontinued therapy due to loss of response: one after 15 months and one after 3 years. All other patients displayed a good clinical response (≥ PASI 50) and were still receiving this regimen at last observation. Combination regimens of infliximab with methotrexate or azathioprine were well tolerated, and only one patient discontinued therapy because of an adverse event (lung embolism) after two infusions with infliximab.
Conclusions  Long-term (> 1 year) maintenance therapy of infliximab combined with methotrexate or azathioprine is effective and well tolerated for moderate-to-severe plaque-type psoriasis.

Conflicts of interest

None declared     

Adalimumab for psoriasis patients who are non-responders to etanercept: open-label prospective evaluation

Background  Targeted biologic therapies have made a significant impact on the treatment for moderate to severe psoriasis. In the United Kingdom, the National Institute for Health and Clinical Excellence recommends etanercept, a human recombinant tumour necrosis factor (TNF) receptor fusion protein, for moderate to severe psoriasis patients who have failed conventional therapies. There is, however, no data available on the role of other TNF antagonists for patients who have failed etanercept. Adalimumab, a fully human, anti-TNF monoclonal antibody, is approved for treatment of moderate to severe psoriasis.
Objectives  To assess the efficacy and safety of adalimumab (40 mg weekly) in psoriasis patients who were non-responders to high-dosage etanercept (50 mg twice weekly).
Methods  All patients attending a tertiary referral service for severe psoriasis who were non-responders to high-dosage etanercept [i.e. failed to achieve ≥ 50% improvement in Psoriasis Area and Severity Index (PASI 50) after 12 weeks of treatment] were considered for open-label adalimumab therapy for 12 weeks. Details on clinical course, PASI, Dermatology Life Quality Index (DLQI) and adverse events were recorded at baseline and weeks 2, 4, 8, and 12.
Results  Four of five patients in this study had reached at least PASI 50 by week 12. Of these, two patients achieved a 75% improvement in PASI (PASI 75). No serious adverse events were reported.
Conclusions  Initial data from this open-label prospective evaluation suggests that weekly adalimumab therapy is an effective treatment for patients with severe psoriasis who had failed to respond to at least 3 months of high-dosage etanercept.     

Open-label, single-center, safety dose escalation trial of alefacept for the treatment of moderate to severe chronic plaque psoriasis

BACKGROUND: Alefacept (Amevive) is a fully human LFA-3/IgG1 fusion protein with a dual mechanism of action inhibiting T-cell activation and selectively reducing memory T cells. Alefacept is currently approved as a 12-week course of weekly 15 mg intramuscular (IM) injections for the treatment of adults with moderate to severe chronic plaque psoriasis. In clinical trials using the currently approved dosing regimen, 33% and 57% of patients achieved a 75% or greater or 50% or greater reduction in Psoriasis Area and Severity Index score (PASI 75 and PASI 50), respectively, after one course of alefacept. OBJECTIVE: To evaluate the tolerability and efficacy of alefacept 15 mg IM weekly for 6 weeks followed by alefacept 30 mg IM weekly for 6 weeks. DESIGN: Open-label, single-center, dose escalation study of alefacept. PATIENTS: Adult patients with chronic plaque psoriasis involving a minimum body surface area of 10% and with a minimum PASI of 12. INTERVENTION: Patients were treated with alefacept 15 mg IM for 6 weeks followed by alefacept 30 mg IM for an additional 6 weeks; doses were held for CD4 counts < 200 cells/mm(3) or evidence of a clinically significant infection. MAIN OUTCOME MEASURE: Efficacy was evaluated by PASI and Physician Global Assessment (PGA) at baseline, week 7, and 2, 6, 12, and 24 weeks post-treatment. RESULTS: Sixteen patients were enrolled; at 6 weeks post-treatment, the PASI mean reduction was 39%, with continued improvement to 46% at 12 weeks post-treatment. The PASI 90, PASI 75, and PASI 50 responses at 12 weeks post-treatment were 6% (1 of 16), 13% (2 of 16), and 38% (6 of 16), respectively; 12% (2 of 16) of patients achieved a PGA of clear to almost clear at 12 weeks post-treatment. The overall PASI 75 and PASI 50 responses were 19% (3 of 16) and 38% (6 of 16), respectively. CONCLUSION: The treatment regimen of alefacept 15 mg IM for 6 weeks followed by alefacept 30 mg IM for 6 weeks was well tolerated by our patients. There was no increased incidence of infections when patients were treated with alefacept 30 mg compared with the 15 mg dose. The increased dose of alefacept 30 mg for the last 6 weeks of a 12-week course did not appear to yield a higher efficacy rate compared with historical controls.     

CD28 T-cell costimulatory molecule expression in pemphigus vulgaris

Background  CD28 superfamily of immune costimulatory molecules could play an important role in autotolerance control. CD28 costimulation seems to be necessary for regulatory T cell (Treg) activation and successive suppressive activities involved in autoimmunity protection. This study investigates CD28 expression, especially inducible costimulator fraction, on T lymphocytes in pemphigus vulgaris (PV) patients.
Methods  CD28 expression on T lymphocytes was assessed in 16 PV patients during acute attack. All patients and 10 healthy control subjects were tested for lymphocyte populations, T-cell subpopulations (T-CD4⁺, T-CD8⁺), Treg and CD28 expression on T-cell subpopulations.
Results  T, B and natural killer cells average values in PV patients were close to the control group values. Compared with control group, PV values showed lower Treg (2.2% compared with 4.7%), slightly decreased CD4⁺ CD28⁺ T cells (91% compared with 95%), higher CD4⁺ CD28⁻ T cells (9% compared with 5%), decreased CD8⁺ CD28⁺ T cells (57% and 73%, respectively) and significantly enhanced CD8⁺ CD28⁻ T cells (43% compared with 27%).
Conclusions  These data suggest that Treg-mediated suppressor T-cell effects could be diminished in PV, together with an abnormal or ineffective subsequent helper T-cell suppression. CD28 high expression on helper T cells and low expression on suppressor T cells are arguments for a potential CD28 role in PV autoimmune response mechanism.

Conflicts of interest

None declared     

Systematic administration of chloroquine in discoid lupus erythematosus reduces skin lesions via inhibition of angiogenesis

Background.  Discoid lupus erythematosus (DLE) is a chronic cutaneous form of lupus erythematosus, characterized by inflammation and scarring skin lesions, with lymphocyte infiltration and vasodilation. Antimalarial drugs have beneficial therapeutic effects in DLE, partially resulting from their immunomodulating and photoprotective properties. The possible influence of these drugs on angiogenesis has not been previously evaluated.
Aims.  To investigate the impact of chloroquine (CQ) treatment on the expression of vascular endothelial growth factor (VEGF, a major regulator of angiogenesis) and CD34 (a transmembrane glycoprotein expressed on endothelial cells and involved in tethering lymphocytes) in patients with DLE.
Methods.  A 3-mm skin biopsy was taken from typical skin lesions in 10 people with DLE. Another biopsy was taken from the same area after 3 months of treatment with CQ (250 mg/day). Skin sections were stained with monoclonal antibodies directed against VEGF and CD34. The intensity of epidermal VEGF expression, and the number and area of CD34-positive dermal blood vessels were assessed.
Results.  CQ treatment induced a reduction in epidermal VEGF expression. It also resulted in a significant decrease in the median number of CD34+ dermal blood vessels (from 219 to 125 vessels per mm²). Furthermore the median vessel area was significantly lowered from 9.76 × 10⁶ to 6.92 × 10⁶ mm² per mm² of the dermis.
Conclusions.  These results indicate that one beneficial effect of CQ treatment in DLE may be due to its antiangiogenic properties.     

Comparison of phototherapy with near vs. far erythemogenic doses of narrow-band ultraviolet B in patients with psoriasis

The therapeutic effectiveness of radiation from a 311 nm ultravoilet B (UVB) lamp (Philips TL-01) in a near vs. far erythemogenic therapy regimen was investigated in 13 patients with widespread, symmetrically distributed psoriasis. The patients received UV therapy starting with 70% of the 311 nm minimal erythema dose (MED) on one randomly chosen half of the body and 35% of the 311 nm MED on the other half. Therapy was given three to five times a week, and the UVB dose in both regimens was increased simultaneously in the same relation. For the 11 patients completing the study, the mean psoriasis area and severity index (PASI) score for the near vs. far erythemogenic treatment side was 21.2 vs. 18.5 before therapy (Wilcoxon's test, not significant), 11.8 vs. 14.4 at week 1 ( P  = 0.003), 8.2 vs. 12.0 at week 2 ( P  = 0.004), and 6.6 vs. 15.6 at week 3 ( P  = 0.005). After 3 weeks, a satisfactory response (i.e. improvement of the initial PASI score by more than 75%) was observed in six of 11 patients on the near erythemogenic treatment side vs. three of 11 patients on the far erythemogenic side. However, the definitive median total number of treatments needed to achieve a satisfactory therapy response on the near vs. far erythemogenic sides was 12 vs. 16 ( P  = 0.022), whereas the definitive median cumulative UV dose was 14.0 vs. 9.1 J/cm² ( P  = 0.088), respectively. These results suggest that near erythemogenic 311 nm UVB therapy may clear psoriasis faster than far erythemogenic therapy but that the latter regimen may be equally effective as it requires slightly more treatment sessions at a lower (and possibly less carcinogenic) cumulative UV dose.     

CD30+ lymphoproliferative disorders: histopathology, differential diagnosis, new variants, and simulators

Summary:  CD30⁺ lymphoproliferative disorders of the skin (CD30⁺ LPD) represent a well-defined spectrum of primary cutaneous T-cell lymphomas which have been recognized as distinct entities in recent lymphoma classifications. Lymphomatoid papulosis and anaplastic large-cell lymphoma share the expression of CD30 antigen as a common phenotypic hallmark but differ in regard to their clinical and histologic features as well as their biologic behavior. This article summarizes the histologic features of CD30⁺ LPD and presents recently identified new clinicopathologic variants of CD30⁺ LPD. There is an increasing number of reactive inflammatory disorders and neoplastic diseases which are composed of or contain a significant number of CD30⁺ cells and mimic LyP or anaplastic large cell lymphoma clinically or histologically. Differential diagnostic considerations focus on other lymphoproliferative processes with CD30⁺ tumor cells as well as non-lymphoid neoplasms and inflammatory simulators. The term CD30⁺ pseudolymphoma is proposed to designate inflammatory processes with CD30⁺ T cells. The final diagnosis of CD30⁺ LPD is based on a synthesis of clinical, histologic, phenotypic, and molecular genetic findings.     

A randomized,double-blind,placebo-controlled phase III study evaluating efficacy and tolerability of 2 courses of alefacept in patients with chronic plaque psoriasis

BACKGROUND: In previous phase II studies, alefacept significantly improved psoriasis and was well tolerated. The clinical response to alefacept was durable. OBJECTIVE: Our purpose was to further evaluate efficacy and tolerability of alefacept in a phase III study of patients (n = 553) with chronic plaque psoriasis. METHODS: Two 12-week courses of once-weekly intravenous alefacept 7.5 mg or placebo were given in a randomized double-blind study; patients were followed up for 12 weeks after each course. RESULTS: During treatment and follow-up of course 1, a 75% or greater reduction in the Psoriasis Area Severity Index (PASI) was achieved by 28% of alefacept-treated and 8% of placebo-treated patients (P <.001). Patients who received a single course of alefacept and achieved a 75% or greater reduction from baseline PASI during or after treatment, without the use of phototherapy or systemic therapies, maintained a 50% or greater reduction in PASI for a median duration of more than 7 months. Among patients who received 2 courses of alefacept, 40% and 71% of patients achieved a 75% or greater and 50% or greater reduction in PASI, respectively, during the study period. Alefacept was well tolerated over both courses. In course 1, the incidence of transient chills was higher in the alefacept group compared with the placebo group; more than 90% of cases occurred within 24 hours after the first few doses. CONCLUSION: Alefacept significantly improved psoriasis and produced durable clinical improvements among patients who responded. A second course of alefacept increased efficacy and was equally well tolerated.     

Prevention of psoriasis-like lesions development in fsn/fsn mice by helminth glycans

Abstract:  The helminth glycan LNFPIII is an immunomodulatory molecule, driving CD4⁺ Th2-type biasing as well as immune suppression. Psoriasis is an autoimmune disease where the immune mechanisms as well as the antigens responsible for development of immune autoreactivity are still not known. In the absence of defined immunological mechanisms, we asked whether LNFPIII would function as novel therapy for psoriasis. We tested the therapeutic efficacy of LNFPIII using the flaky skin (fsn)/fsn mutant mouse model of psoriasis-like lesion development. We found that treatment of mice with LNFPIII prevented the appearance of psoriatic skin lesions on fsn/fsn mice. Examination of the skin 2 weeks after treatment demonstrated that prevention of skin lesions was associated with maintenance of normal epidermis thickness in LNFPIII-treated mice as compared with a significantly thickened epidermis in control treated and diseased mice. In addition, cells from skin of LNFPIII-treated mice produced lower amounts of interferon-γ as compared with cells from skin of control treated diseased mice. Examination of macrophages and T cells from peripheral lymph nodes of control and LNFPIII-treated fsn/fsn mice showed that glycan treatment reduced the numbers of Gr1⁺F4/80⁺ macrophages and the numbers of CD8⁺ T cells, restoring the numbers of these two cell populations as well as the CD4 : CD8 ratio to near normal levels. Overall, the results from this study suggest that the helminth immunomodulatory glycan LNFPIII functions to prevent development of psoriatic-like skin lesions in fsn/fsn mice.     

An international,randomized, double-blind,placebo-controlled phase 3 trial of intramuscular alefacept in patients with chronic plaque psoriasis

BACKGROUND: Alefacept, human lymphocyte function-associated antigen 3/immunoglobulin 1 fusion protein, binds to CD2 molecules on the surface of activated T cells, selectively targeting memory-effector (CD45RO+) T cells, which comprise more than 75% of T cells in psoriatic plaques. OBJECTIVE: To examine the efficacy and tolerability of intramuscular alefacept. DESIGN: International, randomized, double-blind, placebo-controlled, parallel-group trial. PATIENTS: A total of 507 patients with chronic plaque psoriasis. INTERVENTION: Placebo, 10 mg of alefacept, or 15 mg of alefacept administered once weekly for 12 weeks followed by 12 weeks of observation. MAIN OUTCOME MEASURE: Psoriasis Area Severity Index (PASI). RESULTS: Alefacept treatment was associated with dose-related significant improvements in PASI from baseline. Throughout the study, a greater percentage of patients in the 15-mg group than in the placebo group achieved a significant reduction in PASI. Of patients in the 15-mg group who achieved at least 75% PASI reduction 2 weeks after the last dose, 71% maintained at least 50% improvement in PASI throughout the 12-week follow-up. There were no opportunistic infections and no cases of disease rebound. CONCLUSION: Intramuscular administration of alefacept was a well-tolerated and effective therapy for chronic plaque psoriasis and thus represents a convenient alternative to intravenous dosing.     

Narrowband UV-B phototherapy, alefacept, and clearance of psoriasis

OBJECTIVE: To determine whether the addition of 311-nm narrowband UV-B (NB UV-B) phototherapy accelerates and improves the therapeutic efficacy of alefacept, a biological antipsoriatic drug approved for the treatment of moderate to severe psoriasis. DESIGN: Randomized half-body comparison study. SETTING: Ambulatory section of a university hospital photodermatology unit. PATIENTS: Fourteen patients with moderate to severe psoriasis. INTERVENTIONS: All patients were treated with 7.5 mg of intravenous alefacept once weekly for 12 weeks. Three times each week, a randomly selected body half (left or right) was treated with NB UV-B light until complete remission, defined as a reduction in the Psoriasis Area Severity Index (PASI) to 3 or lower, was achieved on the irradiated body half. MAIN OUTCOME MEASURES: Modified PASI, self-assessed visual analogue scale rating of skin lesions, and self-assessed therapeutic efficacy. RESULTS: After 12 weeks of treatment, the mean PASIs on UV-irradiated and nonirradiated body halves were significantly reduced by 81% and 62%, respectively (P < .001). From week 3 to week 12, the mean PASI was significantly lower on UV-irradiated body halves than on nonirradiated body halves (P < .001). At week 12, PASI reductions of greater than 75% had been achieved significantly more often on UV-irradiated body halves (86%, 12 of 14) than on nonirradiated body halves (43%, 6 of 14), and complete remission had been achieved significantly more often on UV-irradiated body halves (43%, 6 of 14) than on nonirradiated body halves (0 of 14) (McNemar test P = .03). CONCLUSIONS: In this randomized half-side comparison of alefacept with and without phototherapy for psoriasis, alefacept with NB UV-B phototherapy accelerated and improved the clearance of psoriasis. This suggests a promising future for this combination as antipsoriatic therapy.     

Adalimumab treatment for severe recalcitrant chronic plaque psoriasis

Aim.  To assess the efficacy and safety profile of adalimumab in patients with severe, recalcitrant chronic plaque psoriasis, and to assess short-term overlapping of other systemic treatment with adalimumab to prevent flaring of disease.
Methods.  This was a retrospective study comprising 39 patients with chronic plaque psoriasis treated with adalimumab between October 2005 and January 2008. All had failed treatment with other systemic agents, including biological therapies in 59% of patients. Patients were started on adalimumab 40 mg weekly or fortnightly, as clinically indicated. Severity of psoriasis was assessed by the Psoriasis Area and Severity Index (PASI). Therapeutic response was assessed by 75% improvement on PASI (PASI 75). All adverse events were recorded.
Results.  Results were analysed separately for those treated with adalimumab only and those on combination treatment. PASI 75 was achieved in 38% (8 of 21 patients at week 16), 62% (13 of 21 patients) at week 24, 69% (9 of 13 patients) at week 48% and 71% (5 of 7 patients) at week 72 in the adalimumab-only group, compared with 56% (5 of 9 patients) at week 16, 50% (4 of 8 patients) at week 24, 80% (4 of 5 patients) at week 48% and 67% (2 of 3 patients) at week 72 in the combined group. Of the 39 patients, 15 (38%) achieved a PASI of 0 at some point in their treatment. Adalimumab was well tolerated; 38% of patients experienced side-effects, which were generally mild.
Conclusion.  Adalimumab was effective in a group of patients with psoriasis refractory to other systemic therapies, including biological treatments, and was well tolerated.     

Clinical-scale generation of strongly CD83-expressing dendritic cells using extracorporeal photopheresis

Background: Many strategies are currently being pursued in order to generate mature dendritic cells (DC) to be used for immunotherapy. A potent anti-tumour influence by extracorporeal photopheresis has been documented for cutaneous T-cell lymphoma, and a major mechanism of action has been suggested to be generation of DC presenting tumour antigens.
Purpose: To determine the potential of a simple clinical photopheresis protocol for large-scale development of mature DC.
Methods: A standard monocyte-enriched leukapheresis preparation of 10⁹–10¹⁰ cells was derived during each of five consecutive treatment sessions of a patient with cutaneous T-cell lymphoma. The cells were incubated overnight in autologous plasma with no addition of growth medium. Cell surface lymphocyte, monocyte and DC markers were determined using multi-colour flow cytometry.
Results: We find signs of activation of the CD14+ monocytes, as well as the appearance of a minor population of mature DC negative for CD14 but with strong CD83 expression.
Conclusions: With a procedure appropriate for routine clinical use, a total number of 10⁶–10⁷ DC ready for patient reinfusion can be prepared within 24 h. Our findings indicate the need to further explore the capacity of photopheresis to stimulate cancer patients' anti-tumour defence reaction.     

Colorimetry provides a rapid objective measurement of de novo hair growth rate in mice

Background: Depilated mice have been used as a test platform for hair growth-regulating agents. However, currently available assessment tools for hair growth in mice are less than ideal.
Methods: Tristimulus colorimetry of the fur color of depilated agouti, albino, and black mice with L ^*, a ^*, and b ^* values were performed daily until the full growth of pelage. Using light-emitting diode (LED) irradiation (650 and 890 nm) with a daily dose of 3.5 J/cm² as hair growth regulators, the hair growth rates observed by the global assessment were compared with those derived from colorimetry.
Results: In contrast to a ^* and b ^* values, L ^* values changed more drastically over time in the anagen phase regardless of fur color. Unlike the inhibitory effect of 650 nm irradiation, LED of 890 nm promoted de novo hair regrowth in mice. The difference in hair growth rates detected by colorimetry paralleled the observation made by the global assessment.
Conclusion: The L ^* value of fur color obtained by tristimulus colorimetry was a sensitive yet quantitative indicator of de novo hair growth, and could be used to project the hair growth rate in mice.     

Mycosis fungoides skin lesions contain CD8+ tumor-infiltrating lymphocytes expressing an activated, MHC-restricted cytotoxic T-lymphocyte phenotype

In prior studies, we showed that most CD8⁺ cells infiltrating skin lesions of CD3⁺CD4⁺ mycosis fungoides were CD3⁺ T-line-age tumor-infiltrating lymphocytes (TIL) whose overall phenotype was suggestive of MHC-restricted cytotoxic T lymphocytes (CTL). However, their lack of cytotoxic-associated granzyme A mRNA suggested that they might be inactivated CTL precursors. In this study, we used single- and double-label immunohistologic techniques to assess the expression of TlA-1-reactive protein and HLA-DR by these CD8⁺TIL. Monoclonal antibody TIA-1 recognises a novel family of proteins expressed preferentially by cytotoxic cells, including some that lack grauzyme A. HLA-DR is a marker of T-cell activation. Single-label studies of 32 cases showed that CD8⁺TIL and TIA-1⁺ cells constituted a variable minority of the total cellular infiltrate and had a similar distribution. Double-label studies of 14 cases showed that in most instances the aggregate phenotype of the majority of CD8⁺TIL was CD3⁺TIA-1⁺HLA-DR⁺CD56⁻CD57⁻. These findings suggest that many of the CD8⁺TIL within skin lesions of CD3⁺CD4⁺ mycosis fungoides are activated, MHC-restricted CTL.     

Computerized quantification of psoriasis lesions with colour calibration: preliminary results

An evaluation was made of a fully automated index of psoriasis, termed Computer-assisted Area and Severity Index (CASI). This method requires taking digital photographs of the target skin area(s) with a colour reference marker, Casmatch^®. The CASI evaluates the severity of the psoriasis from the size and redness of the lesion(s). In five patients with mild psoriasis vulgaris mainly observed on their trunk, 18 photographs of the trunk were taken every 2 weeks. Three of the five patients [Psoriasis Area and Severity Index (PASI) of 3.0, 3.6 and 10.1, respectively] were treated with oral ciclosporin 3 mg/kg/day for 4 weeks. The mean ± SD area of lesion selected by a dermatologist was 2.3 ± 1.3% of the total skin area. This method achieved extraction performance for psoriasis of 72.1 ± 19.4% for sensitivity and 97.4 ± 2.0% for specificity. CASI correlated strongly with PASI ( r  = 0.92), but not with Skindex16^® ( r  = 0.35). Although only erythema was evaluated, our preliminary results indicate that this method is capable of quantifying psoriasis lesions.     

Characterization of the mechanical properties of a dermal equivalent compared with human skin in vivo by indentation and static friction tests

Background/aims: The study of changes in skin structure with age is becoming all the more important with the increase in life. The atrophy that occurs during aging is accompanied by more profound changes, with a loss of organization within the elastic collagen network and alterations in the basal elements. The aim of this study is to present a method to determine the mechanical properties of total human skin in vivo compared with dermal equivalents (DEs) using indentation and static friction tests.
Methods: A new bio-tribometer working at a low contact pressure for the characterization the mechanical properties of the skin has been developed. This device, based on indentation and static friction tests, also allows to characterize the skin in vivo and reconstructed DEs in a wide range of light contact forces, stress and strain.
Results: This original bio-tribometer shows the ability to assess the skin elasticity and friction force in a wide range of light normal load (0.5–2 g) and low contact pressure (0.5–2 kPa). The results obtained by this approach show identical values of the Young's modulus E ^* and the shear modulus G ^* of six DEs obtained from a 62-year-old subject ( E ^*=8.5±1.74 kPa and G ^*=3.3±0.46 kPa) and in vivo total skin of 20 subjects aged 55 to 70 years ( E ^*=8.3±2.1 kPa, G ^*=2.8±0.8 kpa).     

In vivo depletion of CD8+ T cells restores hair growth in the DEBR model for alopecia areata

Summary Alopecia areata (AA) is a putative autoimmune disease in which anagen hair follicles are the target of immune cell attack. While both CD4⁺ and CD8⁺ T lymphocytes are prominent in the infiltrate, their respective roles in the pathogenesis of AA remain unknown. Here we directly investigated the activity of CD8⁺ cells in the inhibition of hair growth using the Dundee experimental bald rat (DEBR) model for AA. Eight lesional DEBRs were fully depleted of their CD8⁺ cells by intraperitoneal injection of OX-8 monoclonal antibody (MoAb) specific for these cells over a 15-day therapy course. A control group of eight lesional rats was injected with the irrelevant MoAb OX-21. Sequential blood samples were analysed by flow cytometry to observe changes in the CD8⁺ cell population and macropliotography used to record changes in hair growth activity.
All eight CD8⁺ depleted rats started to regrow hair within 29 days from the start of treatment, the tinal response ranging from sparse regrowth to a near normal coal. While two rats maintained their new pelage, the remainder lost hair as the CD8⁺ population in peripheral blood increased. Two of the control rats also showed hair regrowth over the experimental period of 156 days. These results suggest that CD8⁺ cells play an active part in the pathogenesis of AA. As hair production did not fully recover in all animals, immune mechanisms other than CD8⁺ cells may be involved in effecting hair loss. However, analysis of CD8⁺ cell levels in the skin of CD8⁺ depleted rats may help resolve their full importance in AA.