British Journal of Dermatology

Greaves, M.

doi: 10.1046/j.1365-2133.2000.03529.xpmid: 10848727

Piette, W.W.

doi: 10.1046/j.1365-2133.2000.03590.xpmid: 10848728

Cunliffe, W.J.; Holland, D.B.; Clark, S.M.; Stables, G.I.

doi: 10.1046/j.1365-2133.2000.03531.xpmid: 10848729

Hypercornification is an early feature of acne and precedes inflammation. It is associated with ductal hyperproliferation and there are many controlling factors such as androgens, retinoids and cytokines. Cycling of normal follicles and of comedones may explain the natural resolution of comedones and, in the longer term, resolution of the disease itself. There is a need to tailor treatment according to comedonal type. Suboptimal therapy can often result from inappropriate assessments of comedones, especially microcomedones, missed comedones, sandpaper comedones, submarine comedones and macrocomedones. Macrocomedones can produce devastating acne flares, particularly if patients are inappropriately prescribed oral isotretinoin. Gentle cautery under topical local anaesthesia is a useful therapy in the treatment of such lesions. The newer retinoids and new formulations of all‐trans‐retinoic acid show a better benefit/risk ratio. Evidence‐based studies are required to allow adequate comparisons.

Rumio, C.; Donetti, E.; Imberti, A.; Barajon, I.; Prosperi, E.; Brivio, M.F.; Boselli, A.; Lavezzari, E.; Veraldi, S.; Bignotto, M.; Castano, P.

doi: 10.1046/j.1365-2133.2000.03532.xpmid: 10848730

Kubo, Y.; Urano, Y.; Hida, Y.; Ikeuchi, T.; Nomoto, M.; Kunitomo, K.; Arase, S.

doi: 10.1046/j.1365-2133.2000.03533.xpmid: 10848731

Cowden disease (CD) is an autosomal dominant syndrome characterized by multiple hamartomatous lesions and an increased risk for malignancies. Recent evidence has indicated that the PTEN gene, encoding a protein tyrosine phosphatase, is the CD susceptibility gene. However, another line of evidence has suggested that CD might be genetically heterogeneous. Clinical features of CD are variable, and there are interfamilial differences in the expression of skin lesions. Therefore, information on PTEN mutations in CD patients should be accumulated to clarify the genotype–phenotype correlation. In the present study, we found heterozygous germline mutations of PTEN in all of three Japanese patients with CD examined, indicating no genetic heterogeneity among our patients. The mutations included two non‐sense mutations of R335X and R130X, and a mis‐sense mutation of C136R. To the best of our knowledge, the C136R mutation has not previously been reported in CD patients. This novel mutation was located outside the core motif of the phosphatase domain of PTEN protein, where most of the missense mutations previously reported in CD patients were clustered. Mucocutaneous manifestations were far fewer in the patient with this mutation than in the patients with nonsense mutations. Whether the phenotypic difference in mucocutaneous features was due to the different mutations remains unclear.

Kiekens, R.C.M.; Thepen, T.; Bihari, I.C.; Knol, E.F.; Van De Winkel, J.G.J.; Bruijnzeel‐Koomen, C.A.F.M.

doi: 10.1046/j.1365-2133.2000.03534.xpmid: 10848732

Atopic dermatitis is an allergic skin disease characterized by elevated total and antigen‐specific serum IgE and IgG4 levels. In acute and chronic cutaneous inflammation, large cellular infiltrates including T cells, dendritic cells and macrophages are found, especially in the dermis. These cells play an important part in the regulation of local inflammatory reactions. Receptors binding IgG (FcγR) are involved in dendritic cell and macrophage function. In this study, we examined the in vivo distribution and cellular expression of the three classes of leucocyte FcγR in human skin during acute and chronic cutaneous inflammation in atopic dermatitis. Atopy patch test skin was used as a model for acute inflammation in atopic dermatitis, while chronic lesional skin was used to investigate FcγR expression in chronically inflamed skin. In atopy patch test sites no increase in the number of CD1a+ dendritic cells and a slight increase in macrophages compared with non‐lesional skin was observed. Our results showed increased expression of FcγRI (CD64) and FcγRIII (CD16) in acutely inflamed skin as well as in chronically inflamed lesional skin, compared with healthy and non‐lesional atopic dermatitis skin. FcγRI was expressed by RFD1+, RFD7+ and CD68+, but not by CD1a+ dermal dendritic cells. RFD1+ dendritic cells and CD68+ macrophages were the main FcγRIII‐expressing cells during the acute inflammatory reaction. The significant increase in expression of FcγRIII (CD16) and FcγRI (CD64) probably results from upregulation of the receptors on resident cells. Insight into the presence of FcγR+ cells in human skin during inflammation is important both for our understanding of skin immune reactions and the development of new therapeutic concepts.

Rukwied, R.; Lischetzki, G.; Mcglone, F.; Heyer, G.; Schmelz, M.

doi: 10.1046/j.1365-2133.2000.03535.xpmid: 10848733

While histamine is the crucial mediator of pruritus in type 1 allergic reactions, its role in atopic dermatitis (AD) is unclear. In this study, the role of mast cell mediators in protein extravasation and pruritus was evaluated using intradermal microdialysis. The microdialysis capillaries were used to apply the mast cell degranulating substance compound 48/80 (C48/80; 0·05%) or histamine (0·01%) and also to deliver H1‐blockers (cetirizine, 200 μg mL−1) in nine AD patients and nine controls. Large pore size membranes (3000 kDa) enabled simultaneous analysis of protein extravasation. Itch sensation was measured psychophysically and weal and flare reaction were evaluated planimetrically. Protein extravasation induced by histamine and C48/80 was significantly reduced in AD patients. Blockade of H1‐receptors by cetirizine significantly reduced C48/80‐induced protein extravasation in AD patients and controls to an identical level. C48/80‐induced pruritus was abolished by cetirizine in controls, whereas pruritus in AD patients was unchanged after H1 blockade. We conclude that mast cell mediators others than histamine are involved in C48/80‐induced pruritus in AD patients. Whether the reduced capacity of AD patients to induce protein extravasation is of pathophysiological relevance for pruritus remains to be established.

Westphal, G.A.; Reich, K.; Schulz, T.G.; Neumann, C.; Hallier, E.; Schnuch, A.

doi: 10.1046/j.1365-2133.2000.03536.xpmid: 10848734

Sensitization to arylamines such as p‐phenylenediamine is frequently diagnosed in patients with allergic contact dermatitis. Reactive metabolites of p‐phenylenediamine might be produced in the skin by O‐acetylation of N‐hydroxylamines catalysed by local N‐acetyltransferases (NATs). In this study, we tested whether genetic polymorphisms of NATs, which are known to affect enzyme activity, may influence the susceptibility to para‐substituted arylamine‐induced contact eczema. Using polymerase chain reaction and restriction enzyme analysis, the distribution of polymorphisms of NAT1 and NAT2 was investigated in 88 patients sensitized to para‐substituted aryl compounds and 123 healthy controls. NAT2 rapid acetylators, i.e. carriers of the NAT2*4 wild‐type allele, were more common in the contact allergy (44%) than in the healthy control group [30%; P = 0·042, odds ratio 1·9 (95% confidence interval, CI 1·05–3·27)]. Slow acetylators carrying the NAT2*5b/2*6a genotype were significantly less frequent among patients [13% vs. 38% in controls; P = 0·009, odds ratio 0·39 (95% CI 0·19–0·78)]. The carriage rate of the NAT1*10 allele, which is supposed to encode for a rapid NAT1 phenotype, was not significantly different between patients and controls [43% vs. 36%; odds ratio 1·5 (95% CI 0·88–2·68)]. Interactions between NAT2*4 and NAT1*10 were suggested by the increased frequency of the NAT2*4/NAT1*10 haplotype in patients (27%) compared with controls [15%; P = 0·039, odds ratio 2·1 (95% CI 1·04–4·04)]. As the NAT1 and NAT2 encoding genes are located in close proximity on chromosome 8p22, the latter finding could at least partly be due to genetic linkage. In fact, a linkage disequilibrium between NAT2*4 and NAT1*10 was observed in the contact allergy (P = 0·0025) and in the control group (P = 0·042). Our data indicate an association between the NAT2*4/NAT1*10 haplotype and contact sensitization to para‐substituted aryl compounds. Therefore, acetylation may either enhance contact sensitization or NAT2*4 and NAT1*10 might be linked to an unknown susceptibility factor.

Cherry, N.; Meyer, J.D.; Adisesh, A.; Brooke, R.; Owen‐Smith, V.; Swales, C.; Beck, M.H.

doi: 10.1046/j.1365-2133.2000.03537.xpmid: 10848735

Consultant dermatologists in the U.K. have been reporting to EPIDERM, a voluntary surveillance scheme for occupational skin disease, since February 1993; reporting by occupational physicians to the scheme began in May 1994 and was superseded in January 1996 by OPRA (Occupational Physicians Reporting Activity). Currently 244 dermatologists and 790 occupational physicians report incident cases to these schemes. During the 6 years to January 1999 a total of 12,574 new cases of occupational skin disease was estimated from reports by consultant dermatologists and 10,136 cases estimated from occupational physicians (since May 1994). The annual incidence of occupational contact dermatitis using data from both schemes was 12·9 per 100,000 workers. The incidence of contact dermatitis per 100,000 workers increased with age in men from 4·9 (age 16–29 years) to 6·6 (age 45–60 years); in women a higher rate (9·5) was apparent in the younger age group, with lower rates in older female workers. High rates in young workers were associated with wet work and in older workers with exposure to oils. For men, high rates of contact dermatitis were seen in reports from both schemes for chemical operatives, machine tool setters and operatives, coach and spray painters and metal workers. For women, high rates were found for hairdressers, biological scientists and laboratory workers, nurses and those working in catering. The most frequent agents for contact dermatitis were rubber chemicals and materials (14·1% of cases reported by dermatologists), soaps and cleaners (12·7%), nickel (11·9%), wet work (11·1%), personal protective equipment (6·2%), petroleum products (6·3%), cutting oils and coolants (5·6%), and epoxy and other resins (6·1%). In the 1608 estimated cases of skin cancer all but 4% were attributed to ultraviolet radiation. Cases of contact urticaria attributed to latex peaked in 1996, with a decline in cases since that time.

Harman, K.E.; Gratian, M.J.; Bhogal, B.S.; Challacombe, S.J.; Black, M.M.

doi: 10.1046/j.1365-2133.2000.03538.xpmid: 10848736

The aim of this study was to re‐evaluate indirect immunofluorescence (IIF) comparing two substrates, normal human skin (HS) and monkey oesophagus (MO) using serum from 29 pemphigus patients classified according to the presence of serum autoantibodies to either desmoglein (Dsg) 1 or Dsg3 detected by enzyme‐linked immunosorbent assay (ELISA). Overall, the sensitivity of IIF was 83% on HS and 90% on MO. When data from both substrates were combined, the sensitivity increased to 100%. When sera from pemphigus foliaceus (PF) patients were studied, which contained Dsg1 antibodies only, the sensitivity of IIF was greatest on HS and titres were on average 4·8 doubling dilutions higher than on MO. In contrast, when sera containing autoantibodies only to Dsg3 from pemphigus vulgaris (PV) patients was studied, the sensitivity was greatest on MO and titres were on average 4·4 doubling dilutions higher than on HS. There was a significant correlation between Dsg1 antibody levels and IIF titres on HS and between Dsg3 antibody levels and IIF titres on MO. The investigation of immunobullous disorders in the future is likely to move towards antigen‐specific techniques such as the Dsg ELISAs used in this study. However, in laboratories which currently rely on IIF for detecting pemphigus autoantibodies, the data presented in this study strongly suggest that two substrates should be used for IIF screening: one rich in Dsg1, such as HS, and the other rich in Dsg3, such as MO. This combination of substrates should not only increase the sensitivity of detecting pemphigus antibodies, but will aid in the differentiation of PV from PF. It is also possible that the data might be more useful for disease monitoring.