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Background Efalizumab (anti-CD11a), a humanized monoclonal antibody, blocks multiple T-cell-dependent functions implicated in the pathogenesis of psoriasis, including T-cell activation, migration to the skin, reactivation in psoriatic skin and interactions with keratinocytes. Objectives This multinational, randomized, double-blind, placebo-controlled, parallel-group trial was designed to evaluate the safety and efficacy of subcutaneous efalizumab 1·0 mg kg−1 once weekly for 12 weeks compared with placebo in a population that included high-need patients, defined as those for whom at least two systemic therapies were unsuitable because of lack of efficacy, intolerance or contraindication. Patients/methods Patients with moderate-to-severe plaque psoriasis [involvement of ≥ 10% of total body surface area and Psoriasis Area and Severity Index (PASI) ≥ 12·0 at screening] were randomized in a 2 : 1 ratio to receive efalizumab or placebo. The primary efficacy endpoint was the proportion of patients achieving ≥ 75% PASI improvement (PASI-75 response) at week 12 in the intention-to-treat population; secondary endpoints included changes in PASI, static Physician's Global Assessment, Physician's Global Assessment of change from baseline and percentage of body surface area affected. Results We enrolled 793 patients (529 received efalizumab and 264 placebo), including 526 high-need patients (342 received efalizumab and 184 placebo). Week 12 PASI-75 rates were 29·5% for efalizumab compared with 2·7% for placebo among high-need patients ( P < 0·0001) and 31·4% for efalizumab compared with 4·2% for placebo in the full study population ( P < 0·0001). Results for all secondary efficacy endpoints showed superiority of efalizumab over placebo in both the high-need and the full populations. Efalizumab demonstrated a favourable safety profile, without evidence of systemic toxicity, in both the high-need group and the overall study population. Conclusions The efficacy and safety of efalizumab therapy were comparable between high-need patients and the more general moderate-to-severe psoriasis patient population. In view of its demonstrated efficacy and safety profile, efalizumab represents a valuable option for the treatment of adult patients with moderate-to-severe plaque psoriasis, including high-need patients. [ABSTRACT FROM AUTHOR]

Background Lichen planus (LP) is a common inflammatory skin disease of unknown aetiology. Viral causes have been suggested. Objectives To find candidate viruses associated with LP. Methods Lesional and nonlesional skin samples, peripheral blood mononuclear cells and serum were obtained from patients with LP. Ultrastructural, viral DNA, immunohistochemical and serological analyses were performed, and comparisons were made with psoriatic and normal skin. Results Electron microscopy revealed typical 120–200-nm enveloped particles with a 100-nm nucleus resembling human herpesvirus (HHV) virions both in dermis and in epidermis of lesional LP tissue. HHV-7 DNA was found in 11 of 18 lesional LP samples, as opposed to only one of 11 nonlesional LP samples ( P =0·06), two of 11 lesional psoriasis samples ( P = 0·05) and none of four normal skin samples. No relation was found between LP skin and DNA of other known HHVs (HHV-1–6 and 8). With immunohistochemistry, significantly more HHV-7+ cells were found in lesional LP epidermis than in normal epidermis. Lesional LP dermis contained significantly more HHV-7+ cells than nonlesional LP, psoriatic or normal dermis. Moreover, LP skin contained overwhelmingly and consistently more plasmacytoid dendritic cells (upregulated in virally induced conditions) than nonlesional LP samples. Conclusions We conclude that HHV-7 replicates in LP lesions, but not in psoriasis, another inflammatory skin condition. HHV-7 is possibly involved in the pathogenesis of LP. These preliminary data make further research on this topic of interest. [ABSTRACT FROM AUTHOR]

For more than five decades, topical corticosteroids and emollients have been the mainstay of therapy for atopic dermatitis. However, the potential for side-effects limits the clinical utility of corticosteroids in providing long-term disease control. With a unique mode of action that differs from that of corticosteroids, the steroid-free topical calcineurin inhibitors (TCIs), tacrolimus ointment and pimecrolimus cream, provide skin-selective treatment that targets key factors involved in the pathogenesis of this chronic disease. An extensive series of clinical trials involving more than 16 000 patients with predominately moderate to severe atopic dermatitis in tacrolimus studies and over 2000 patients with primarily mild to moderate disease in pimecrolimus studies has shown that both TCIs provide effective and well-tolerated treatment for atopic dermatitis. Randomized controlled trials have demonstrated that tacrolimus is superior to conventional hydrocortisone-based regimens and does not cause skin atrophy or other steroidal side-effects. Both tacrolimus and pimecrolimus prevent disease flares and provide progressive and sustained disease improvement with long-term therapy. These and other clinical benefits of TCIs are discussed, together with the safety profiles of tacrolimus and pimecrolimus and their use in clinical practice. In addition, this review summarizes findings from the many trials carried out with these agents and outlines how TCIs can provide long-term treatment and control of a chronic skin disease that may persist for years. [ABSTRACT FROM AUTHOR]

We report a 75-year-old man with a fulminant rosacea-like eruption, suggestive of demodicidosis. Multiple Demodex folliculorum mites were found in facial scales and pustules and, on histological examination, in the infundibulum of pilosebaceous follicles and in the dermis. Intradermal mites were surrounded either by polymorphonuclear granulocytes and histiocytes, or by a granulomatous infiltrate containing foreign-body giant cells, which had phagocytosed the parasites. Complete recovery, with disappearance of facial mites, was achieved by treatment with a combination of oral and topical metronidazole, although this drug is not known to be miticidal. [ABSTRACT FROM AUTHOR]

Although cyclosporin is effective in immunosuppression following organ transplantation and in the treatment of psoriasis, its use is limited by its side-effects, notably impaired renal function and hypertension. As SDZ IMM 125, a new derivative of the cyclosporin family, showed considerable immunosuppressive activity in experimental studies, with less effect on renal function, it was considered a potential successor to cyclosporin for both indications. In this multicentre, double-blind, placebo-controlled study, the efficacy and tolerability of 40, 100, 200 and 400 mg SDZ IMM 125 daily were studied in 59 patients with psoriasis. Patients were followed for a period of 5 weeks (4 weeks treatment, and 1 week post-treatment observation). A dose-dependent effect of SDZ IMM 125 was observed. A significant correlation was found between the dose of SDZ IMM 125 and changes in the sum of severity scores of three indicator plaques. There was a significant decrease in the body surface area affected by psoriasis in the 400-mg group (P ≤ 0.01), whereas a decrease of the global psoriasis severity was observed in the 200-mg (P ≤ 0.01) and the 400-mg groups (P ≤ 0.001). No serious adverse events occurred during the 4 weeks of treatment. Three patients discontinued treatment because of adverse events (one sore throat, two influenza). Clinical adverse events were similar to those reported with cyclosporin, the most frequent being gastrointestinal disturbances. Estimation of renal function indices showed that increases from baseline values were dose-dependent, and appeared to be similar to those seen with cyclosporin. Changes in liver function tests showed a clearcut dose-dependent increase of some liver enzymes, principally alanine aminotransferase (ALAT). SDZ IMM 125 is effective in clearing psoriasis. However, long-term studies comparing the efficacy and safety of SDZ IMM 125 and cyclosporin must be performed, to determine whether SDZ IMM 125 has a better risk-benefit ratio than cyclosporin. [ABSTRACT FROM AUTHOR]

Topical photochemotherapy with psoralen and its derivatives 4,5',8-trimethylpsoralen (TMP) and 8- methoxypsoralen (8-MOP), with UVA irradiation, was evaluated with regard to minimum phototoxic dose, concentration, timing of UVA irradiation and systemic and local side-effects, in healthy volunteers. Psoralen (0.005%) in aqueous gel was found to be superior to TMP and 8-MOP in aqueous gel. No hyperpigmentation was seen after topical PUVA treatment with psoralen in aqueous gel. Patients with plaque-type psoriasis (n = 7), palmoplantar psoriasis (n = 7) and hyperkeratotic eczema (n = 2) were treated. Topical PUVA therapy was effective in most psoriasis patients, without the occurrence of local or systemic side-effects. Moreover, hyperkeratotic eczema patients who did not respond to conventional therapy showed partial remission. These results indicate that topical PUVA therapy with psoralen in aqueous gel is a useful therapeutic modality for treatment of psoriasis patients, and patients with recalcitrant dermatoses such as palmoplantar psoriasis and hyperkeratotic eczema. [ABSTRACT FROM AUTHOR]

Ultraviolet (UV) irradiation of trans-urocanic acid (UCA). a major UV absorbing component of the epidermis, leads to the formation of cis-UCA, which mediates immunosuppressive effects. In this study, the net yield of cis-UCA was measured after the photoisomerization of urocanic acid by narrow UV wavebands (spectral range 295-405 nm), with the irradiation doses related to solar irradiance at sea level. The formation of cis-UCA in Caucasian skin (in vivo), as well as in aqueous solution (in vitro), was determined by HPLC analysis. The same irradiation conditions were met in both components of the study. The in vivo experiments showed high efficiency of cis-UCA formation in the spectral region of 305-341 nm, whereas high efficiency in vitro was found at 305 and 326 nm. At 350 and 563 nm, cis-UCA was formed in vivo, but not in vitro. At longer lest wavelengths up to 405 nm. no significant formation of cis-UCA was detectable. The established partition between UVB and UVA at 320 nm is not relevant for the isomerization pattern of UCA. Additional studies revealed substantial cis-UCA formation in human skin by UVA phototherapy lamps. Furthermore, raised levels of 295 nm irradiation doses, a possible effect of stratospheric ozone depletion, were found to increase the cis-UCA yield. Our results demonstrate that the formation of cis-UCA in the skin with common exposures takes place over a broad spectrum range of UVB and UVA, up to at least 363 nm. These findings emphasize the potency of UVA to isomerize UCA. and they they contribute to further elucidation of the effects of phototherapy and sunbathing. [ABSTRACT FROM AUTHOR]

We report a comparative study of the patch-test results obtained with a corticosteroid series, added to the standard series, in two centres, one in Belgium and the other in the Netherlands. The frequencies of positive reactions to the corticosteroids differed considerably between the two centres, and we suggest several reasons for this. [ABSTRACT FROM AUTHOR]

We report the case of a boy with severe combined immunodeficiency (SCID) and serious skin problems. The level of purine 5′-nudeotidase was greatly reduced in the lymphocytes of this patient. To our knowledge, no patients with SCID and this enzyme deficiency have been described previously. The relationship between reduced levels of this enzyme and the immunodeficiency is unclear. This case is also unusual because of the presence of large numbers of T lymphocytes expressing TCR1 (γ/δ) in the skin. Moreover, the presence of so many TCK1-positive cells was not consistent with the low numbers of these cells in the peripheral blood. These cells were not present in skin biopsies taken at a later stage during the course of the disease. An oligoclonal lymphocytosis developed during follow-up, and a monoclonal antibody reactive with these clones was found, indicating that these lymphocytes were present in the skin. This case report illustrates the benefit of the use of monoclonal antibodies in identifying the cells involved in the cutaneous inflammation in SCID, in order to gain a better insight into the characteristics of these cells. [ABSTRACT FROM AUTHOR]

The side-effects of long-term cyclosporin A (CyA) treatment in 26 patients with severe psoriasis were evaluated. These patients had a mean PASI score of 302 and were treated with CyA for between 7 and p months (mean 195 months). There were three groups according to the dose of CyA, <2 mg/kg per day, 2-3 mg/kg per day and > 3 mg/kg per day. In all three groups, CyA was found to be equally effective. Treatment with CyA was discontinued in 12 of the 26 patients because of nephrotoxicity and/or development of hypertension. One was in the <2 mg/kg per day group, three were in the 2-3 mg/kg per day group and eight in the > 3 mg/kg per day group. There was no hepatotoxicity with CyA treatment. One patient developed two squamous cell carcinomas of the skin. [ABSTRACT FROM AUTHOR]

A questionnaire was sent to 16 carriers of the X-linked cytochrome-b558 negative variant of chronic granulomatous disease (CGD). Of the 15 who answered the questionnaire and from data of one additional case, 70% reported recurrent aphthous stomatitis and 63% had recurrent skin eruptions. Five of the carriers (31%) had clinically discoid lupus erythematosus (DLE), although the histopathology was not typical and the immunofluorescence findings were negative. The infiltrate in the lesional skin of three of these patients was analysed using monoclonal antibodies against CD3, CD4, CD8, CD1a, HLA-DR, CD1c, interdigitating cells, B lymphocytes and cells of the monocyte/macrophage lineage. The immunophenotype of the infiltrating cells resembled that found in discoid lupus erythematosus. [ABSTRACT FROM AUTHOR]