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The levels of soluble CD30 in 79 patients with atopic Elevated plasma levels of soluble CD30 (sCD30) have been found in patients with AD but not in those with dermatitis were compared with those found in 54 patients with psoriasis and 36 control individuals (no psoriasis, no psoriasis (5). The 120kD protein CD30 (Ki-1) is a member of the tumour necrosis factor receptor family atopic dermatitis). In relation to the control group, patients with atopic dermatitis were found to exhibit an and is mainly expressed by Th0 and Th2 T-helper cell clones (6). Specie c activation of CD30 positive cells increased concentration of sCD30 of at least 1.5-fold (p

Summary Psoriasis is a chronic inflammatory skin disease with a strong genetic component. Linkage studies have identified several susceptibility loci for psoriasis including a region on chromosome 1q21 termed the ‘epidermal differentiation complex’. At least 20 genes involved in epidermal differentiation and proliferation have been mapped to this region including S100A2, a gene known to be over-expressed in psoriasis lesions. In the course of cloning and sequencing several S100A2 cDNAs, we identified an A/G (Asn62Ser) polymorphism at nucleotide 185 of the S100A2 coding region. To determine whether this polymorphism is associated with psoriasis, we tested DNA from 38 unrelated normal and 40 unrelated psoriatic individuals. The 185G allele was present in 148 of the 156 chromosomes analysed, giving an allele frequency of 94.9%. All of the remaining chromosomes carried 185A. There was no significant difference in the allele distribution between normal and psoriatic individuals (normals 72G, 4A; psoriatics 76G, 4A; Pa 1.00 by Fisher’s exact test). Our data explain conflicting results in the literature regarding the sequence of S100A2 but provide no support for a direct causal role for S100A2 in psoriasis.

The possible interference of neighbouring allergic patch-test reactions is still an open question. In this study, we investigated whether there is a distance-related mutual modification of neighbouring allergic patch-test reactions to nickel sulfate and potassium dichromate. We used a double-blind multicentre study design with randomized attachment of special TRUE Tests with 1, 3 and 7 cm distance between nickel sulfate and potassium dichromate patches. 589 patients with a history of nickel allergy (523 female, 66 male) were tested, with a mean age of 35 years. A log-linear modelling approach was used for statistical assessment of the relation between the distance separating neighbouring patch tests with nickel and dichromate and the reactions to the allergens. Non-reproducibility coefficients were compared by the generalized version of Fisher's exact test for arbitrary 2-dimensional contingency tables. For the left side of the back, virtually no differences (p=0.70) were found in the reaction patterns obtained for the 3 distances separating nickel and dichromate patch tests. On the right side of the back, the number of reactions to dichromate patches with only 1 cm distance from moderate/strong nickel reactions was lower than the number of positive dichromate tests at larger distances from nickel tests (on the border of statistical significance: p= 0.05). Corresponding side-related results were obtained for subgroups of patients with and without a history of atopic dermatitis. The non-reproducibility of reactions to dichromate was not significantly related to the distance between neighbouring tests. Our data argue against a "spillover" effect of strong/moderate nickel reactions, but indicate that such reactions may, under certain conditions, attenuate adjacent reactions to an unrelated allergen. In the case of future verification, this will have implications for the interpretation of patch tests.

The analysis of population-specific human leukocyte antigen (HLA) haplotypes has provided evidence that susceptibility to psoriasis is linked to the class I and II major histo-compatibility complex on human chromosome 6. In addition, these studies show that psoriasis consists of two distinct disease subtypes (type I and type II), which differ in age of onset and in the frequency of HLA. In type I (early-onset) psoriasis, Cw6, B57, and DR7 are strongly increased, whereas in type II (late-onset) psoriasis, HLA-Cw2 is overrepresented. It has also been proposed that HLA haplotypes extended by class III play a role in the genetics of this disease. Moreover, studies of affected families indicate that other disease susceptibility loci may also be involved. Likely candidates for additional susceptibility genes are located at chromosomes 1, 6, and 17, and microsatellite markers over the whole genome have been used to identify susceptibility genes. Two years ago linkage to the distal part of chromosome 17 was published. However, this linkage could not be confirmed by other groups with comparable or enlarged numbers of psoriatic family members investigated. Recently, an investigation presenting an area of chromosome 4 as a susceptibility locus for psoriasis was published. According to our knowledge today, psoriasis is a polygenetically inherited disease. Furthermore from twin studies it is known that environmental factors play a significant role in the onset or recurrence of the disease.

Psoriasis is one of a number of autoimmune diseases that display significant HLA associations. In particular, individuals with onset of disease prior to 40 years of age display striking associations with HLA-Cw6 and are much more likely to have a positive family for psoriasis. However, only about 10% of Cw6-positive individuals develop disease, suggesting that other genetic and/or environmental factors must be involved. Several compelling lines of epidemiologic evidence indicate that psoriasis susceptibility is inherited, albeit not in a simple monogenic fashion, and that genetic, rather than environmental, factors are primarily responsible for the variability in inheritance of psoriasis. Taken together, these observations suggest that one or more loci in addition to HLA are necessary for the development of psoriasis. The number of additional loci is likely to be small, because i) the disease is very common ii) substantial excess risk of psoriasis is observed in first degree relatives, and iii) nevoid variants of psoriasis have been reported, suggestive of somatic mutation of a single gene during development. The substantial homogeneity of the psoriatic phenotype and the clear evidence for increased HLA association and heritability in juvenile onset disease indicate that despite its complexity, psoriasis is a common disease whose etiology is amenable to elucidation through the techniques of modern molecular genetics. J Invest Dermatol 103:150S-153S, 1994

Background: The efficiency and reproducibility of patch tests remain controversial. Objective: Our purpose was to determine the efficiency and reproducibility of patch tests and to identify factors influencing these features. Methods: We double-tested 1285 patients concomitantly with 10 standard allergens by manually filled test chambers. Additional information was obtained from all patients with a standardized protocol. Results: Patch test efficiency was good (≥0.94) with all 10 allergens. In contrast, nonreproducibility of patch tests was strongly allergen dependent, ranging from 0.2 for nickel sulfate to 0.6 for formaldehyde. The likelihood of nonreproducible allergic reactions increased when more than four positive reactions were seen at the same time, and with another positive reaction located in close proximity to an allergic reaction. Sex and age of patients, atopy, dermatitis at distant sites, sleeping habits, and the time of allergen exposure (24 or 48 hours) did not affect the rate of nonreproducible results. Conclusion: To increase patch test reproducibility, specific preparations of patch test allergens need to be improved, Furthermore, amplification effects by synchronous neighboring positive reactions should be excluded.

commercially available, highly standardized, ready-to-use test withnickel sulfate andpotassiumdichromate patchtests attached synchronously to both sides of the back of patients with a history system (TRUE-testâ ) with randomized location of the allergens. Using a double-blind study design 589 patients with a of nickel allergy, conducted with a highly standardized randomized test system (TRUE-testâ ). Out of 589 patients tested, a history of nickel allergy were tested with 2 of the most common standard allergens that have a diŒerent potential to elicit total of 388 had responded with allergic reactions to nickel sulfate and 130 to potassium dichromate. The reproducibility of allergic, questionable and irritant reactions, i.e. nickel sulfate and potassium dichromate. positive nickel (dichromate) patch tests was 99.2% (90.8%). The reaction index was also calculated, which relates the number of allergic reactions obtained with a test preparation to the number MATERIAL AND METHODS of questionable and irritant reactions; the reaction index can range from ‐1 (questionable and irritant reactions only occur) Thirteen centres of the German Contact Dermatitis Research Group contributed data from a double-blind study approved by the local to 1 (allergic reactions only occur). For nickel sulfate the Ethical Committees. Patch-test patients older than 17 years with a reaction index was 0.91, but it was only 0.23 for potassium history of nickel allergy (reported eczematous reactions to skin contact dichromate, as a result of considerably more questionable reac- with metal likely to contain nickel or positive nickel patch test) were tions. In conclusion, a highly synchronous reproducibility of enrolled after giving their informed consent. Exclusion criteria were results can be achieved by using a well-standardized patch-test as follows: any kind of immunosuppressive medication, treatment of the back with ultraviolet (UV) light or corticosteroids within 4 weeks system, especially withnickel sulfate. However, distinct allergens prior to testing, ineammatory dermatoses of the back, any major

Background This study investigates four measures of disease severity in patients with psoriasis, both before and after therapy. Methods Data records were analyzed from 33 patients with moderate-to-severe chronic plaque psoriasis who were treated with efalizumab, 1 mg/kg/week subcutaneously, for 12 weeks. Four measures of disease severity were used: body surface area (BSA), psoriasis area and severity index (PASI), psoriasis log-based area and severity index (PLASI) and self-administered PASI (SAPASI). Results At the end of the 12-week therapy, the mean percent improvement shown by each measure varied considerably, ranging from 48.6% (PASI) to 70.6% (SAPASI). PASI and PLASI were the most comparable (67.3% and 66.5%). These differences were smaller when a dermatologist's opinion about the improvement was taken into account, for example “very good improvement” ranged from mean percent improvement of 63.8% (BSA) to 83.8% (PASI). The correlation between all measures revealed a high level of significance (P≤ 10−5). Conclusions Comparing the slopes and intercepts of the regression lines revealed PLASI as the most reliable measure for the severity and therapeutic improvement in patients with moderate-to-severe chronic plaque psoriasis. PLASI proved to be a marginally more accurate than PASI, and much more accurate than SAPASI and BSA. The superiority of PLASI may be a result of the logarithmic scale of the affected skin surface.

Accumulating evidence indicates that psoriasis is a multifactorial disorder caused by the concerted action of multiple disease genes in a single individual, triggered by environmental factors. Some of these genes control the severity of multiple diseases by regulating inflammation and immunity (severity genes), whereas others are unique to psoriasis. Various combinations of these genes can occur even within a single family, accounting in large measure for the many clinical manifestations of psoriasis. The disease-causing variants (alleles) of these genes probably arose early in the history of modern humans. As a result, psoriasis disease alleles are common in the general population, have a worldwide distribution, and often share the same ancestral chromosome with neutral alleles at adjacent loci. This phenomenon, called linkage disequilibrium, explains why psoriasis is strongly associated with HLA-Cw6 worldwide, although HLA-Cw6 is unlikely to be the disease allele. Many unaffected individuals carry 1 or more disease alleles, but lack other genetic and/or environmental factors necessary to produce disease. This explains why psoriasis develops in only about 10% of HLA-Cw6-positive individuals, and why genome-wide linkage scans for psoriasis and other multifactorial genetic disorders have not been uniformly successful. The Human Genome Project is rapidly generating a catalog of human DNA sequence variations. This resource has already allowed precise linkage disequilibrium mapping of the major histocompatibility complex psoriasis gene to just beyond HLA-C, toward HLA-A. This gene is likely to be identified soon. Further development and use of linkage disequilibrium resources will provide a powerful tool for the identification of the remaining psoriasis genes.

Non-pustular psoriasis consists of two disease subtypes, type I and type II, which demonstrate distinct characteristics. Firstly the disease presents in different decades of life, in type I before the age of 40 years and later in type II. Secondly, contrasting frequencies of HLA alleles are found: type I patients express predominantly HLA-Cw6, -B57, and -DR7, whereas in type II patients HLA-Cw2 is overrepresented. Finally, familial inheritance is found in type I but not in type II psoriasis. The study of concomitant diseases in psoriasis contributes to deciphering the distinct patterns of the disease. Defence against invading microorganisms seems better developed in psoriatics than in controls. This evolutionary benefit may have caused the overall high incidence of psoriasis of 2%. Psoriasis is a multifactorial and heterogenetically inherited disease. The heterogeneity is evident by the diversity of genetically linked markers. The multifactorial component results from the observation of external trigger mechanisms, such as the Koebner phenomenon, stress and the intake of certain drugs. Twin studies have shown that environmental factors contribute to the onset of the disease. In type I psoriasis, special extended haplotypes such as EH57.1 (HLA-Cw6-B57-DRB1*0701-DQA1*0201-DQB1*0303) and EH65.1 (HLA-Cw8-B65-DRB1*0102-DQB1*0501) have been found to be increased. The application of microsatellite techniques has identified distinct positions on several chromosomes at which putative psoriasis genes may be located. Disease susceptibility genes are thought to be present on chromosomes 4q, 6p, 16q, 17q and 20p. Moreover, on chromosome 1q, genes regulating epidermal differentiation have been identified. Linkage to this area has been proposed. Furthermore, psoriasis gene loci on chromosomes 2, 8 and 20 have been suggested.

Background : Psoriasis is a multifactorial disease of unknown origin. Objective : Our purpose was to determine the frequency of skin disorders concomitantly seen in patients with psoriasis. Methods : We analyzed data from more than 40,000 patients and calculated sex- and age-adjusted ratios of expected and observed incidence rates of associated disorders. Results : The results demonstrate that, compared with age-matched control patients without psoriasis, cutaneous immune disorders such as allergic contact dermatitis, atopic dermatitis, and urticaria are underrepresented in patients with psoriasis. In contrast, certain systemic disorders such as diabetes, heart insufficiency, and obesity occur significantly more often in patients with psoriasis than in control subjects. Increased resistance to cutaneous bacterial infections was noted only in patients with early-onset psoriasis. Conclusion : Our observations show that a distinct pattern of associated diseases exists in patients with psoriasis. Although systemic disorders such as obesity, diabetes, and heart disease may be related to dietary habits and nutritional status, the relative resistance to cutaneous infections together with decreased immune responsiveness suggest a genetically determined selection.

Background and Design: Psoriasis is a member of a class of common, HLA-associated conditions in which disease susceptibility appears to be heritable. However, the mode of inheritance of these diseases has been difficult to define in simple mendelian terms. Psoriasis displays one of the strongest HLA associations of this class of diseases. However, only a small fraction of those who carry the implicated HLA susceptibility alleles develop disease, and it has proven difficult to demonstrate that the HLA associations observed are due to formal genetic linkage between the disease and the HLA locus. Although the role of environmenta factors in psoriasis and these other diseases cannot be denied, the participation of additional genes, not necessarily linked to HLA, has long been suspected. Observations: Epidemiologic and immunogenetic data are reviewed and analyzed, which demonstrate that a predisposition to psoriasis is heritable, and which implicate genes of the HLA locus as necessary but not sufficient determinants of psoriasis. Recent developments in human genome research are described, which make possible a systematic search for additional genetic determinants of psoriasis, including those unlinked to HLA. Conclusions: As one of the most common, most heritable, and most highly HLA-associated examples of this class of HLA-associated diseases, psoriasis represents an ideal target for the application of this emerging genomic technology. (Arch Dermatol. 1994;130:216-224)

In this report we investigate the simultaneous occurrence of psoriasis and atopic dermatitis (AD) as well as the association with infectious skin diseases. Among 29,159 patients hospitalized between 1953 and 1983, 8.5% (2,467 patients) were treated for psoriasis, while 1.6% (470 patients) were hospitalized for AD treatment. On the basis of incidence rates for both diseases, 36 patients (0.14%) with both psoriasis and AD were expected to be seen. However, the two conditions were simultaneously present in 2 patients only. Approximately 30% of the AD patients were suffering from either bacterial or viral infection, while this complication occurred in 6.7% of psoriatics. In addition, among 48 patients hospitalized for eczema herpeticatum 39 were atopics and none was psoriatic. The data demonstrate that the occurrence of psoriasis and AD in one and the same patient is quite rare and this may be related to conflicting immune defense patterns. Thus, increased sensitization against foreign protein together with high susceptibility to cutaneous infection present in AD is in contrast to high phagocyte responsiveness in psoriasis, where concurrent infections are rare.

In a multicentre study in eighteen European cities 3175 patients were treated with photochemotherapy (PUVA) for severe psoriasis and data obtained during a period of 39 months were analysed. A response better than marked improvement was obtained in 88·8% of patients; twenty exposures and a total cumulative UVA dose of 96 J/cm 2 were required for clearing, the duration of the clearing phase being 5·3 weeks. A comparison of the results of this study with those of a similar multicentre study in the United States on 1300 patients and using a different treatment protocol, revealed that while treatment results and the number of individual treatment sessions were similar the European protocol requires only half the time and less than half the total cumulative UVA dose for clearing of psoriasis. When patients in the European study who received continuous maintenance treatment were compared with patients who received no maintenance treatment the probability that a patient would remain in remission for a period of 80 weeks was the same, irrespective of whether patients received maintenance treatment or not. This study confirms the dramatic efficacy of PUVA in clearing psoriasis and contains two important messages for the reduction of possible long-term hazards of this treatment. Firstly, the total UVA energy requirements for clearing psoriasis strongly depend on the treatment schedule and can be kept low if an individual approach aimed at rapid clearing of psoriasis is used. Secondly, maintenance therapy may not significantly prevent recurrences for prolonged periods of time and may thus not be necessary in most patients.

In 2,147 patients suffering from psoriasis, evaluation of the age of onset revealed two peaks, one occurring at the age of 16 years (female) or 22 years (males) and a second peak at the age of 60 years (female) or 57 years (males). Human lymphocyte antigen (HLA) tissue typing in 112 randomly assigned patients showed that HLA-Cw6, known to be at disequilibrium in psoriasis, is present in 85.3% of patients with early onset. In contrast, 14.7% patients with late onset showed this marker. Parents (father or mother) were affected in approximately half of the patients with early onset and in none belonging to the group with late onset. Furthermore, psoriasis in patients with early onset follows an irregular course and shows a strong tendency to become generalized. On the basis of clearly defined criteria (e.g., age of onset, heritability, and clinical course of disease), nonpustular psoriasis shows two distinct forms, one of which is hereditary, with early onset, and the other is sporadic and occurs in older age.