J.P. Ortonne

European S3‐Guidelines on the systemic treatment of psoriasis vulgaris

Of the 131 studies on monotherapy or combination therapy assessed, 56 studies on the different forms of phototherapy fulfilled the criteria for inclusion in the guidelines. Approximately three-quarters of all patients treated with phototherapy attained at least a PASI 75 response after 4 to 6 weeks, and clearance was frequently achieved (levels of evidence 2 and 3). Phototherapy represents a safe and very effective treatment option for moderate to severe forms of psoriasis vulgaris. The onset of clinical effects occurs within 2 weeks. Of the unwanted side effects, UV erythema from overexposure is by far the most common and is observed frequently. With repeated or long-term use, the consequences of high, cumulative UV doses (such as premature aging of the skin) must be taken into consideration. In addition, carcinogenic risk is associated with oral PUVA and is probable for local PUVA and UVB. The practicability of the therapy is limited by spatial, financial, human, and time constraints on the part of the physician, as well as by the amount of time required by the patient. From the perspective of the cost-bearing institution, phototherapy has a good cost-benefit ratio. However, the potentially significant costs for, and time required of, the patient must be considered.

Efficacy and safety of infliximab vs. methotrexate in patients with moderate-to-severe plaque psoriasis: results of an open-label, active-controlled, randomized trial (RESTORE1).

Background  Infliximab is indicated for treatment of moderate‐to‐severe plaque psoriasis in adults whose disease cannot be controlled with other systemic therapies, including methotrexate (MTX). To date, no studies have directly compared the efficacy and safety of infliximab and MTX.

Porphyria cutanea tarda and antibodies to hepatitis C virus

We have studied the prevalence of hepatitis C virus antibodies (anti‐HCV) in 13 patients suffering from sporadic porphyria cutanea tarda. The sera were tested by Abbott second‐generation enzyme immunoassay; seropositivity was confirmed by Ortho second‐generation recombinant immunoblot assay. Ten cases (76.1%) were anti‐HCV positive; one patient was also seropositive for HIV. This preliminary study suggests that HCV could be a frequent triggering factor for sporadic porphyria cutanea tarda.

Diagnostic and neural analysis of skin cancer (DANAOS). A multicentre study for collection and computer-aided analysis of data from pigmented skin lesions using digital dermoscopy

Background  Early detection of melanomas by means of diverse screening campaigns is an important step towards a reduction in mortality. Computer‐aided analysis of digital images obtained by dermoscopy has been reported to be an accurate, practical and time‐saving tool for the evaluation of pigmented skin lesions (PSLs). A prototype for the computer‐aided diagnosis of PSLs using artificial neural networks (NNs) has recently been developed: diagnostic and neural analysis of skin cancer (DANAOS).

Corrective gene transfer of keratinocytes from patients with junctional epidermolysis bullosa restores assembly of hemidesmosomes in reconstructed epithelia.

Herlitz junctional epidermolysis bullosa (H-JEB) provides a promising model for somatic gene therapy of heritable mechano-bullous disorders. This genodermatosis is caused by the lack of laminin-5 that results in absence of hemidesmosomes (HD) and defective adhesion of squamous epithelia. To establish whether re-expression of laminin-5 can restore assembly of the dermal-epidermal attachment structures lacking in the H-JEB skin, we corrected the genetic mutation hindering expression of the β3 chain of laminin-5 in human H-JEB keratinocytes by transfer of a laminin β3 transgene. The transduced keratinocytes synthesized a recombinant β3 polypeptide that assembled with the endogenous laminin α3 and γ2 chains into a biologically active laminin-5 that was secreted, processed and deposited into the extracellular matrix. Re-expression of laminin-5 induced cell spreading, nucleation of hemidesmosomal-like structures and enhanced adhesion to the culture substrate. Organotypic cultures performed with the transduced keratinocytes, reconstituted epidermis closely adhering to the mesenchyme and presenting mature hemidesmosomes, bridging the cytoplasmic intermediate filaments of the basal cells to the anchoring filaments of the basement membrane. Our results provide the first evidence of phenotypic reversion of JEB keratinocytes by somatic gene therapy and demonstrate that genetic treatment of the mild forms of skin blistering diseases and other inherited extracellular matrix pathologies is a realistic goal.

Abnormal binding of an anti-amnion antibody to epidermal basement membrane provides a novel diagnostic probe for junctional epidermolysis bullosa

AA3 is a novel antibody raised against human amnion, which reacts with the basement membrane of various epithelia of ectodermal origin. We use AA3 to examine the epidermal basement membrane zone in normal skin and different genetically determined types of epidermolysis bullosa (EB), by indirect immunofluorescence. AA3 staining was normal in dystrophic and simplex EB, but was markedly reduced in lesional and non‐blistered skin in severe forms of junctional EB. In non‐lethal junctional EB, the intensity of staining was variable and appeared to be inversely associated with disease severity, but did not correlate with demonstrable abnormalities of hemidesmosomes. AA3 binding was not reduced in pemphigoid lesions or normal suction blisters. It appeared to localize to the lamina lucida, but with different characteristics compared with antibodies to laminin and bullous pemphigoid antigen. These findings suggest that AA3 recognizes an antigen (or antigens) which may be involved in a primary biochemical defect in junctional EB. Moreover, this antibody may act as a new probe for this potentially lethal mechano‐bullous disease.

A phase IIIb, multicentre, randomized, double-blind, vehicle-controlled study of the efficacy and safety of adalimumab with and without calcipotriol/betamethasone topical treatment in patients with moderate to severe psoriasis: the BELIEVE study

Background  Data are lacking on the use of topical therapies in combination with tumour necrosis factor blockers for the treatment of psoriasis.

Successful treatment of moderate to severe plaque psoriasis with the PEGylated Fab′ certolizumab pegol: results of a phase II randomized, placebo-controlled trial with a re-treatment extension

Background  Certolizumab pegol (CZP) is a PEGylated antitumour necrosis factor agent.

Anatomical mapping of Merkel cells in normal human adult epidermis

Summary The destribution of Merkel cells (MCs) in normal human skin and mucosa was studied using the mouse monoclonal antibody Troma‐1, reacting specifically with component 8 of the moll cytokeratin catalogue. The specificily of this antibody for MCs in human skin was assesed by double indirect immunofluorescence (IIF) and immunoelectron microscopy. Two‐hundred and thirty 6‐mm punch biopsies were obtained from 44 different sites from six human cadavers Within 48 h post‐mortem. IIF was performed with Troma‐1 on EDTA‐split epithelial sheets and the MCs were counted and the mean values per mm2 calculated for each site. regions with >50MC/mm2 were the lips, hard palate, palms, finger pads, proximal nail fold, and dorsum of the feet. Three different patterns were observed in the epidermis or mucosa: MCs grouped in clumps, linear and arciform arrangements, and scattered MCs. In the hair follicles grouped MCs were observed in the bulb and scattered MCs were seen in the outer root sheath.

Improvements in patient-reported outcomes in moderate-to-severe psoriasis patients receiving continuous or paused etanercept treatment over 54 weeks: the CRYSTEL study.

Objective  To assess patient‐reported outcomes (PRO) in patients with moderate‐to‐severe plaque psoriasis receiving continuous or paused etanercept treatment.