British Journal of DermatologyVolume 144, Issue 5 p. 1094-1095 Scarring molluscum contagiosum in patients with severe atopic dermatitis: report of two cases H.S. Ghura, H.S. Ghura Department of Dermatology, Leicester Royal Infirmary, Infirmary Square, Leicester LE1 5WW, U.K.Search for more papers by this authorR.D.R. Camp, R.D.R. Camp Department of Dermatology, Leicester Royal Infirmary, Infirmary Square, Leicester LE1 5WW, U.K.Search for more papers by this author H.S. Ghura, H.S. Ghura Department of Dermatology, Leicester Royal Infirmary, Infirmary Square, Leicester LE1 5WW, U.K.Search for more papers by this authorR.D.R. Camp, R.D.R. Camp Department of Dermatology, Leicester Royal Infirmary, Infirmary Square, Leicester LE1 5WW, U.K.Search for more papers by this author First published: 23 January 2002 https://doi.org/10.1046/j.1365-2133.2001.04211.xCitations: 12Read the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinked InRedditWechat Citing Literature Volume144, Issue5May 2001Pages 1094-1095 RelatedInformation

Purified, resting peripheral blood T lymphocytes were previously reported to undergo beta (1) integrin-dependent activation when cultured with anti-CD3 mAb coimmobilized with fibronectin, but not type I collagen. However, the extravascular T cells that encounter immobilized extracellular matrix proteins and are involved in disease pathogenesis have different properties from resting peripheral blood cells, In this study, we confirm that resting CD4(+) and CD8(+) T cells from peripheral blood are costimulated by immobilized fibronectin, but not type I collagen. In contrast, Ag- or mitogen-stimulated CD4(+) and CD8(+) T cell lines, used as models of the effector cells involved in disease, are more potently costimulated by type I collagen than fibronectin. The collagen-induced effects are similar in assays with serum-free medium and in more physiological assays in which anti-CD3 mAb is replaced by a threshold concentration of Ag and irradiated autologous PBMC as APC. The responses are beta (1) integrin dependent and mediated largely by very late Ag (VLA) 1 and 2, as shown by their up-regulation on the T cell lines as compared with freshly purified resting PBL, and by the effects of blocking mAb, Reversed phase HPLC located the major costimulatory sequence(s) in the alpha1 chain of type I collagen, the structure of which was confirmed by amino acid sequencing, The results demonstrate the potential importance of type I collagen, an abundant extracellular matrix protein, in enhancing the activation of extravascular effector T cells in inflammatory disease, and point to a new immunotherapeutic target.

As part of a search for T cell autoantigens in inflammatory skin diseases, we have demonstrated proteinase K sensitive, denaturation stable, T cell stimulatory material with antigenic properties in aqueous extracts of stratum corneum from normal human skin. Activity was also demonstrable in extracts of whole epidermis. A combination of preparative, analytical, and microbore reversed phase high performance liquid chromatography, chromatofocusing, and denaturing preparative sodium dodecylsulfate-polyacrylamide gel electrophoresis indicated limited structural diversity. Five components were separated, with Mr values from 5 to 18 kDa and apparent PI values from 4.5 to 10. Three components were purified to near homogeneity and showed molecular weights of 5, 13.5, and 18 kDa. Their potency was shown by the ability to induce stimulation indices of 20-89 with peripheral blood mononuclear cells and >500 with T cell lines. Use of inhibitors indicated that the active materials were not generated by the in vitro actions of proteases during extraction. The five partially purified components induced a time course of peripheral blood mononuclear cell proliferation compatible with the effects of antigen rather than superantigen. The 5 kDa component was rigorously bulk purified to yield a fraction that induced potent T cell activation but contained minimal detectable protein, a further indication of its biologic potency. Normal stratum corneum thus contains previously undescribed T cell antigens of high potency but limited structural diversity. The present data form a basis for determining their structure, cellular origin, and pathogenic relevance.

T cell mediated autoimmunity may be important in inflammatory skin disease, but target autoantigens have not previously been described. In studies aimed at defining T cell epitopes, aqueous extracts of normal facial and plantar stratum corneum have consistently been found to induce potent proliferation of peripheral blood mononuclear cells from normal donors and patients with inflammatory skin disease, giving stimulation indices up to 80. Potent stimulation was seen with both autologous and allogeneic stratum corneum extracts. Because of the presence of inhibitory material, demonstration of the stimulatory activity was critically dependent on extract concentration, and was facilitated by short-term pulsing of cultures with extract. The proliferation of cells purified from peripheral blood mononuclear cells by immunomagnetic beads and immunophenotyping of cell lines generated from peripheral blood mononuclear cells, confirmed the T cell nature of the response to stratum corneum extracts. The activity was inhibited by HLA-DR monoclonal antibody, indicating the presence of antigen or superantigen. Tetanus toxoid reactive clones and a purified protein derivative reactive line failed to respond to the stratum corneum extracts, indicating that the active material is not a nonspecific T cell stimulant such as a cytokine or mitogen. This and the failure of recombinant interleukin-1alpha to stimulate peripheral blood mononuclear cells in concentrations up to 1000 U per ml, indicate that the activity is not due to interleukin-1. We propose the hypothesis that antigenic or superantigenic material is normally sequestered from the immune system in the epidermis, but induces T cell activation when released following wounding and in disease, and that this represents an important and previously unrecognized pathogenic mechanism.

To the Editor: Study of T cell receptor (TCR) expression by lymphocytes in psoriatic lesions may provide evidence for the occurrence of specific cellular immune events and indicate the possibility of selective, TCR directed immunotherapy; however, results to date have not been consistent. Three groups have analyzed biopsies and peripheral blood either by labeling with panels of monoclonal antibodies directed against TCR β chain variable (V) region families, or by polymerase chain reaction based molecular techniques employing multiple BV family specific primers. These groups have reported highly skewed lesional TCR expression, particularly involving BV2 and BV6 families (Lewis et al., 1993Lewis H.M. Baker B.S. Bokth S. Powles A.V. Garioch J.J. Valdimarsson H. Fry L. Restricted cell receptor Vβ gene usage in the skin of patients with guttate and chronic plaque psoriasis.Br J Dermatol. 1993; 129: 514-520Crossref PubMed Scopus (117) Google Scholar; Leung et al., 1995Leung D.Y.M. Travers J.B. Giorno R. et al.Evidence for a streptococcal superantigen-driven process in acute guttate psoriasis.J Clin Invest. 1995; 96: 2106-2112Crossref PubMed Scopus (235) Google Scholar; Menssen et al., 1995Menssen A. Trommler P. Vollmer S. et al.Evidence for an antigen-specific cellular immune response in skin lesions of patients with psoriasis vulgaris.J Immunol. 1995; 155: 4078-4083PubMed Google Scholar). The findings were interpreted as compatible either with the local effects of superantigen (Lewis et al., 1993Lewis H.M. Baker B.S. Bokth S. Powles A.V. Garioch J.J. Valdimarsson H. Fry L. Restricted cell receptor Vβ gene usage in the skin of patients with guttate and chronic plaque psoriasis.Br J Dermatol. 1993; 129: 514-520Crossref PubMed Scopus (117) Google Scholar; Leung et al., 1995Leung D.Y.M. Travers J.B. Giorno R. et al.Evidence for a streptococcal superantigen-driven process in acute guttate psoriasis.J Clin Invest. 1995; 96: 2106-2112Crossref PubMed Scopus (235) Google Scholar) or with conventional antigen (Menssen et al., 1995Menssen A. Trommler P. Vollmer S. et al.Evidence for an antigen-specific cellular immune response in skin lesions of patients with psoriasis vulgaris.J Immunol. 1995; 155: 4078-4083PubMed Google Scholar). A further study found no evidence for increased expression of selected BV species in psoriasis lesions (Boehncke et al., 1995Boehncke W.-H. Dressel D. Manfras B. Zollner T.M. Wettstein A. Bohm B.O. Sterry W. T-cell-receptor repertoire in chronic plaque-stage psoriasis is restricted and lacks enrichment of superantigen-associated Vb regions.J Invest Dermatol. 1995; 104: 725-728Crossref PubMed Scopus (34) Google Scholar). Recently, we have developed a highly reproducible anchored polymerase chain reaction method in which all TCR B chain species are amplified with the same primer pair, and products quantitated by dot blot hybridization with BV family specific oligonucleotide probes (Vekony et al., 1997Vekony M.A. Holder J.E. Lee A.J. Horrocks C. Eperon I.C. Camp R.D.R. Selective amplification of T cell receptor variable region species is demonstrable but not essential in early lesions of psoriasis vulgaris: analysis by anchored polymerase chain reaction and hypervariable region size spectratyping.J Invest Dermatol. 1997; 109: 5-13Abstract Full Text PDF PubMed Scopus (32) Google Scholar). Our results suggested that selective accumulation of T cells expressing certain BV species may occur in early lesions of psoriasis vulgaris, but that the BV species varied between samples and that skewing was modest. Furthermore, no BV skewing was seen in a third of the biopsies analyzed (Vekony et al., 1997Vekony M.A. Holder J.E. Lee A.J. Horrocks C. Eperon I.C. Camp R.D.R. Selective amplification of T cell receptor variable region species is demonstrable but not essential in early lesions of psoriasis vulgaris: analysis by anchored polymerase chain reaction and hypervariable region size spectratyping.J Invest Dermatol. 1997; 109: 5-13Abstract Full Text PDF PubMed Scopus (32) Google Scholar). Our results were supported by an additional recent study employing polymerase chain reaction and multiple validated BV family specific primers (Moss et al., 1997Moss P. Charmley P. Mulvihill E. et al.The repertoire of T cell antigen receptor β-chain variable regions associated with psoriasis vulgaris.J Invest Dermatol. 1997; 109: 14-19Abstract Full Text PDF PubMed Scopus (22) Google Scholar). In the latter study, preliminary work with several sets of published BV family specific primer panels showed the different primers to have an uneven ability to amplify the same BV cDNA. This finding suggests that the variable results reported to date may arise at least in part from methodologic differences, in addition to immunogenetic differences between patients and the state of the psoriasis lesions at the time of biopsy. A further study has suggested markedly increased expression of BV3 and/or BV13.1 families by lesional CD8+ T cells in psoriasis, indicative of clonal expansion of this subset, but found no evidence for clonality amongst CD4+ cells (Chang et al., 1994Chang J.C.C. Smith L.R. Froning K.J. et al.CD8+ T cells in psoriatic lesions preferentially use T-cell receptor Vβ3 and/or Vβ13.1 genes.Proc Natl Acad Science. 1994; 91: 9282-9286Crossref PubMed Scopus (210) Google Scholar). In this study, keratotome slices of lesional skin were enzymatically dissociated and fractionated by fluorescence-activated cell sorting prior to analysis of T cell subset extracts by polymerase chain reaction with multiple BV family specific primers. These findings point to a role for CD8+ T cells in the pathogenesis of psoriasis. The findings are supported by the evidence that CD8+ cells are the predominant T cell subset in lesional epidermis (Baker et al., 1984Baker B.S. Swain A.F. Fry L. Valdimarsson H. Epidermal T lymphocytes and HLA-DR expression in psoriasis.Br J Dermatol. 1984; 110: 555-564Crossref PubMed Scopus (240) Google Scholar; Jones et al., 1994Jones L.J. Berth-Jones J. Fletcher A. Hutchinson P.E. Assessment of epidermal dendritic cell markers and T-lymphocytes in psoriasis.J Pathol. 1994; 174: 77-82Crossref PubMed Scopus (23) Google Scholar), by the reported deterioration of psoriasis in patients with progressive AIDS (Duvic et al., 1987Duvic M. Johnson T.M. Rapini R.P. et al.Acquired immunodeficiency syndrome-associated psoriasis and Reiter’s syndrome.Arch Dermatol. 1987; 123: 1622-1632Crossref PubMed Scopus (219) Google Scholar), and, as antigens are presented to CD8+ T cells by major histocompatibility complex class I molecules, by the major histocompatibility complex class I association of psoriasis in epidemiologic (Elder et al., 1994Elder J.T. Nair R.P. Guo S.-W. Chr Henseler T. istophers E. Voorhees J.J. The genetics of psoriasis.Arch Dermatol. 1994; 216: 224-229Google Scholar) and genetic (Trembath et al., 1997Trembath R.C. Clough R.L. Rosbotham J.L. et al.Identification of a major susceptibility locus on chromosome 6p and evidence for further disease loci revealed by a two stage genome-wide search in psoriasis.Human Molec Genet. 1997; 6: 813-820Crossref PubMed Scopus (440) Google Scholar) studies. We have therefore re-investigated the TCR BV expression by CD4+ and CD8+ T cells in psoriatic lesions, by using our anchored polymerase chain reaction method, particularly in view of the variable results that have been obtained in recent studies, and the fact that there are no other reports of the analysis of BV expression by T cell subsets in psoriasis. Following ethical committee approval, six volunteers (age 32–59 y; five male, one female; PASI scores 10–20) with chronic plaque psoriasis that had not received treatment apart from bland emollients for at least a week, each provided venous blood samples and two punch biopsies (4–5 mm diameter) under local anesthesia with lignocaine and adrenaline. Biopsies were taken either from the edge and center of the same lesion or from adjacent small plaque lesions, rinsed free of blood in cold phosphate buffered saline, placed in ice-cold RPMI-1640 medium containing 1% fetal calf serum, and subjected to further processing within 60–90 min. Subcutaneous fat and deep dermis were trimmed away and the remaining sample cut into small pieces. These were incubated for 30 min at 37°C in RPMI-1640 medium containing 1% fetal calf serum, 0.5 mM CaCl2, and 0.3% collagenase (type 1A, Sigma, Poole, U.K.). The pieces were then mechanically disaggregated in a Medimachine (Dako, High Wycombe, U.K.) according to the manufacturer’s instructions and the cell suspensions separated into CD4+ and CD8+ fractions with anti-CD8 conjugated immunomagnetic beads (Dynabeads M-450; Dynal, Wirral, U.K.). Briefly, cells were incubated with a large excess of the beads with continuous rocking for 60 min at 4°C. CD8+ cells were recovered by magnet and washed, and the unbound cells taken as the CD4+ fraction. Peripheral blood mononuclear cells (PBMC) were obtained from venous blood by density gradient centrifugation, and 107 cells separated with a 3-fold excess of immunomagnetic beads. RNA was isolated from CD4+ and CD8+ fractions (the latter without detachment from beads), contaminating DNA removed by incubation with RNase-free DNase, and residual RNA quantitated spectrophotometrically (Vekony et al., 1997Vekony M.A. Holder J.E. Lee A.J. Horrocks C. Eperon I.C. Camp R.D.R. Selective amplification of T cell receptor variable region species is demonstrable but not essential in early lesions of psoriasis vulgaris: analysis by anchored polymerase chain reaction and hypervariable region size spectratyping.J Invest Dermatol. 1997; 109: 5-13Abstract Full Text PDF PubMed Scopus (32) Google Scholar). TCR β-chain cDNA was synthesized from 20 ng (CD8+ fractions) or 100 ng (CD4+ fractions) total RNA, tailed with poly (A), and amplified by two-step, seminested, anchored polymerase chain reaction. Following clean-up and spectrophotometric quantitation, second round polymerase chain reaction products were separated into 25,100 ng aliquots, and subjected to dot blot hybridization with 25 [32P]-labeled, BV family specific oligonucleotide probes, bound probes being quantitated by PhosphoImager (Vekony et al., 1997Vekony M.A. Holder J.E. Lee A.J. Horrocks C. Eperon I.C. Camp R.D.R. Selective amplification of T cell receptor variable region species is demonstrable but not essential in early lesions of psoriasis vulgaris: analysis by anchored polymerase chain reaction and hypervariable region size spectratyping.J Invest Dermatol. 1997; 109: 5-13Abstract Full Text PDF PubMed Scopus (32) Google Scholar). The amount of each bound probe was expressed as a percentage of the sum of all bound probes for each sample. Sufficient RNA for complete assay of CD4+ and CD8+ fractions from both skin biopsies and PBMC was obtained in four of the six patients. If significant lesional expansion of a specific BV family is defined as an approximately 2-fold or greater mean increase in lesional versus PBMC BV expression, with mean lesional expression of the specific BV family representing at least 5% of the total, then significant expansion amongst CD8+ cells was seen in three of the four patients and amongst CD4+ cells in two of four patients. The BV families involved and the percentage expression in PBMC and both lesional biopsies are shown in Table 1. Among lesional CD8+ cells, increased expression of BV6 was seen in one patient, of BV13 in another, and of BV18 in a third. Among lesional CD4+ cells, an increase of BV5 was seen in one patient and of BV7 and BV9 in another. In contrast with the previous report (Chang et al., 1994Chang J.C.C. Smith L.R. Froning K.J. et al.CD8+ T cells in psoriatic lesions preferentially use T-cell receptor Vβ3 and/or Vβ13.1 genes.Proc Natl Acad Science. 1994; 91: 9282-9286Crossref PubMed Scopus (210) Google Scholar), we found no evidence for lesional expansion of CD8+ T cells expressing the BV3 family, and increased BV13 was seen in only one of four patients.Table 1BV expression by CD4+ and CD8+ cells in PBMC and lesional biopsiesCD4PBMCCD4biopsy ACD4biopsy BCD8PBMCCD8biopsy ACD8biopsy BPatient 1BV5BaTwo probes, designated 5A and 5B, were required to allow detection of all BV5 family members (Vekonyet al,1997).2%7.5%4.2%BV180.5%5%4.9%Patient 3bThere was no significantly skewed BV expression by either CD4+or CD8+cells in the two lesional biopsies of patient 2. In patient 3, there was no skewing of BV expression by lesional CD4+cells.BV136.1%11.6%14.7%Patient 4BV67.5%15.8%12.4%BV72.3%4.5%6.2%BV91.6%6.1%4.5%a Two probes, designated 5A and 5B, were required to allow detection of all BV5 family members (Vekony et al,1997).b There was no significantly skewed BV expression by either CD4+or CD8+cells in the two lesional biopsies of patient 2. In patient 3, there was no skewing of BV expression by lesional CD4+cells. Open table in a new tab In our work, full thickness punch biopsies of skin, trimmed of subcutaneous fat and deeper dermis, were subjected to analysis; however, we do not believe that this fact explains the differences between the present and previously reported work, in which “epidermal” samples were obtained by keratotome (Chang et al., 1994Chang J.C.C. Smith L.R. Froning K.J. et al.CD8+ T cells in psoriatic lesions preferentially use T-cell receptor Vβ3 and/or Vβ13.1 genes.Proc Natl Acad Science. 1994; 91: 9282-9286Crossref PubMed Scopus (210) Google Scholar). As previously argued (Vekony et al., 1997Vekony M.A. Holder J.E. Lee A.J. Horrocks C. Eperon I.C. Camp R.D.R. Selective amplification of T cell receptor variable region species is demonstrable but not essential in early lesions of psoriasis vulgaris: analysis by anchored polymerase chain reaction and hypervariable region size spectratyping.J Invest Dermatol. 1997; 109: 5-13Abstract Full Text PDF PubMed Scopus (32) Google Scholar), keratotome biopsies of psoriatic lesions are likely to include superficial dermis, which contains the major portion of lesional T cell infiltrates. More precise molecular analysis of the clonality of intraepidermal CD8+ T cells in psoriatic lesions requires recovery of epidermis uncontaminated with dermis, a procedure fraught with difficulty in view of the highly irregular epidermal hyperplasia and suprapapillary epidermal thinning characteristic of psoriatic lesions (Camp, 1992Camp R.D.R. Psoriasis. In. Champion RH, Burton JL, Ebling FJG (eds).Textbook of Dermatology. Blackwell, Oxford1992: 1391-1457Google Scholar). This work is compatible with the possibility that clonal expansion of CD8+ T cells occurs in some psoriatic skin lesions; however, our findings suggest that skewing of BV expression by lesional CD8+ cells versus PBMC is relatively modest and more variable than previously reported (Chang et al., 1994Chang J.C.C. Smith L.R. Froning K.J. et al.CD8+ T cells in psoriatic lesions preferentially use T-cell receptor Vβ3 and/or Vβ13.1 genes.Proc Natl Acad Science. 1994; 91: 9282-9286Crossref PubMed Scopus (210) Google Scholar), and that any TCR directed therapy for psoriasis should be customised for each patient. This work was supported by grants from the Wellcome Trust (037395/Z/92/Z and 039375/Z/93/Z) and the Psoriasis Association.

The pathogenesis of psoriasis appears to depend on T cells, which have been proposed to mediate the disease through an autoimmune process. To test this hypothesis we have propagated four T-cell lines from biopsies of psoriatic skin lesions by antigen-independent methods. Flow cytometric immunophenotyping showed the lines to be composed mainly of CD4-positive, alpha beta T-cell receptor (TCR)-positive cells, which secreted a cytokine profile suggestive of predominant T-helper type 1 (Th1) status. Analysis of TCR variable region (V beta) usage revealed two- to eight-fold increases in the expression of certain V beta species in lesional lines as compared with autologous peripheral blood mononuclear cells (PBMC), with the increased V beta species being expressed on more than 5% of cells in two of the lines. Lines were also used to test for responses to a range of epidermal antigen preparations in the presence of irradiated autologous PBMC as antigen-presenting cells. The lines failed--to proliferate in response to psoriatic lesional stratum corneum extracts, dispase-separated normal human epidermal extracts, and an epidermal keratin preparation before and after trypsinization, in spite of good proliferative responses to anti-CD3 which indicated that the lines were not anergic. In addition, the lines and PBMC from normal volunteers and the patients with psoriasis gave little or no response to recombinant streptococcal M protein. Thus, in spite of accumulating evidence for selective expansion of certain V beta-expressing T cells in psoriatic lesions, epidermal autoantigens have not been identified by using a bioassay which depended largely on the proliferation of lesional CD4-positive cells. The role of streptococcal M protein, which bears some homology with epidermal keratin is also open to question, at least in chronic plaque psoriasis. Further work is therefore required to obtain direct evidence that autoimmune processes are important in the pathogenesis of chronic plaque psoriasis.

A prospective, open, multicentre study was performed to investigate the efficacy and safety of long-term treatment with cyclosporin in adults with severe atopic dermatitis. Subjects were treated for a maximum of 48 weeks. For the first 8 weeks, cyclosporin was administered at 2.5 mg/kg per day. The dose was then adjusted according to response. Disease activity was monitored using the six-area, six-sign score and the proportion of skin involved. Pruritus and sleep disturbance were assessed using four-point scales. Response was further evaluated on a five-point scale. Adverse events, blood pressure and serum biochemistry were monitored. Tolerability was assessed on a five-point scale. One hundred subjects were enrolled and 65 completed 48 weeks of treatment. Withdrawals occurred due to remission (three), inadequate response (seven), protocol violations (11) and adverse events (14, of which seven were probably treatment related). Cyclosporin produced rapid and highly significant improvements in all indices of disease activity. Sixty-five subjects considered that they had shown a considerable improvement or complete clearance of disease. Most patients relapsed after cessation of treatment, but neither signs nor symptoms had returned to baseline severity 8 weeks later. Blood pressure and serum creatinine levels increased slightly, and in one subject renal impairment was a major factor contributing to withdrawal of the drug. Overall, 85 subjects rated the tolerability of cyclosporin as good or very good. The results indicate that cyclosporin has a place in the long-term treatment of severe atopic dermatitis provided that appropriate patients are selected and careful monitoring is performed.

Several groups have investigated the role of T cells in the pathogenesis of psoriasis by determination of T-cell receptor (TCR) B-chain variable (V) region usage, both in chronic plaque (psoriasis vulgaris) and guttate forms, with various results. Because there are no data on TCR expression in early psoriasis vulgaris, when specific cellular immune events may be expected to be most pronounced, we have analyzed early lesions (less than 3 wk old) of ten patients, with highly reproducible results. We have developed a highly controlled anchored polymerase chain reaction (PCR) method in which TCR beta chain species are all amplified with the same primer pair and products are quantified by dot blot hybridization with BV family-specific oligonucleotide probes. Overexpression of certain TCR BV genes was observed in the majority of lesional biopsies, but in samples in which the expanded BV family formed more than 10% of total lesional BV (half of the samples analyzed), BV2 and BV6 predominated. The consistency of overexpression of these BV species between patients was much less than in previous studies of TCRBV usage in established chronic plaque psoriasis lesions. Complementarity-determining region 3 (CDR3) size spectratyping demonstrated evidence for selective clonal T cell accumulation in less than half of the lesional samples showing BV expansion. These results indicate that selective amplification of TCRBV species occurs in early psoriasis vulgaris but is not essential to the pathogenic process and may be more important in the maintenance or expansion of chronic lesions.

A 67-year-old woman presented with a scaly, erythematous plaque, for which a clinical diagnosis of Bowen's disease was made. However, incisional biopsy established the diagnosis of amelanotic superficial spreading malignant melanoma. Biopsy thus avoided the use of inappropriate destructive therapy, such as cryotherapy or cautery. This case illustrates the importance of obtaining a histological diagnosis, prior to treatment, in suspected cases of Bowen's disease.

Background: Severe atopic dermatitis (AD) remains difficult to treat. Cyclosporine is effective in adults but has not previously been investigated in children with AD. Objective: The aims were to investigate the efficacy, safety, and tolerability of cyclosporine in severe refractory childhood AD. Methods: Subjects 2 to 16 years of age were treated for 6 weeks with cyclosporine, 5 mg/kg per day, in an open study. Disease activity was monitored every 2 weeks by means of sign scores, visual analogue scales for symptoms, and quality-of-life questionnaires. Adverse events were monitored. Efficacy and tolerability were assessed with five-point scales. Results: Twenty-seven children were treated. Significant improvements were seen in all measures of disease activity. Twenty-two showed marked improvement or total clearing. Quality of life improved for both the children and their families. Tolerability was considered good or very good in 25 subjects. Conclusion: Cyclosporine may offer an effective, safe, and well-tolerated short-term treatment option for children with severe AD.