Tilo Henseler

Psoriasis of early and late onset: Characterization of two types of psoriasis vulgaris

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.

Disease concomitance in psoriasis

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.

The genetics of psoriasis

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.

ORAL 8-METHOXYPSORALEN PHOTOCHEMOTHERAPY OF PSORIASIS: The European PUVA Study: a Cooperative Study among 18 European Centres

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/cm2 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.

Skin tumors in the European PUVA Study: Eight-year follow-up of 1,643 patients treated with PUVA for psoriasis

In the continuation of the European PUVA Study, 1,643 patients of the original cohort of 3,175 patients enrolled in this prospective study were reevaluated for skin tumors after an average observation period of 96 months. Thirty-six patients with a total of seventy-one tumors (forty squamous cell carcinomas, twenty-three basal cell carcinomas) were observed. In contrast to the U.S. sixteen-center study, we were unable to demonstrate a clinically relevant increase in the risk of tumors induced by psoralens with ultraviolet A (PUVA), and we also failed to show a clear relationship between PUVA exposure and tumor development. Almost all patients with tumors had been exposed to various carcinogens before the initiation of PUVA. No tumors were detected in patients without such prior treatment, although 10% of the patients had received more than 3,000 joules/cm 2 total cumulative phototoxic PUVA dose during the observation period. The discrepancy between the results of the U.S. study and our findings may partly be explained by a variety of factors such as a different treatment approach, a different attitude toward sun exposure, and the overall lower incidence of skin cancer in the European population.

Reproducibility of patch tests: A multicenter study of synchronous left- versus right-sided patch tests by the German Contact Dermatitis Research Group

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 (> or = 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.

Contrasting disease patterns in psoriasis and atopic dermatitis

SummaryIn 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 sporiatics. 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.

Genetics of psoriasis.

Abstract 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-DQBl*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.

The reaction index: a parameter to assess the quality of patch test preparations.

Allergic contact dermatitis might have been caused by epoxy resin 6360, the non-bisphenol-A-type epoxy resin. The hardener GY-051 and HD-electrician specialized filling powder might also have been allergens. But many of the skin and lip lesions might have been due to the other epoxy resin and to additives. These would have been mild chronic irritant reactions, such as the nail changes. It has already been reported that contact dermatitis from epoxy Contact Dermatitis 1992: 27: 203

Scanning Chromosome 17 for Psoriasis Susceptibility: Lack of Evidence for a Distal 17q Locus

Evidence for a genetically heterogeneous psoriasis susceptibility locus on distal human chromosome 17q has recently been reported [Science 1994;264:1141]. Making use of an independently ascertained collection of 24 multiplex psoriasis kindreds, we have performed a genotyping scan of chromosome 17 using 12 microsatellite markers and analyzed the data using parametric (lod score) as well as novel nonparametric methods. Pairwise lod scores revealed no evidence for linkage to the previously implicated marker D17S784 under any of eight models varying in mode of inheritance, penetrance, and sporadic cases. Homogeneous linkage to D17S784 could be excluded under all four autosomal dominant models tested (Z < - 5.8 at theta = 0.05), and there was no evidence for genetic heterogeneity. All other chromosome 17 markers tested also failed to detect evidence for linkage in any of the kindreds under either a dominant or a recessive model. Although further analysis using affected sib pair methods provided no statistically significant evidence for linkage to any chromosome 17 marker, a cluster of three distal 17q loci displayed a trend towards greater than expected allele-sharing values (observed/expected = 1.10-1.14). These results do not formally confirm the existence of a psoriasis susceptibility locus on the distal long arm of human chromosome 17, but are suggestive of its possible involvement under a polygenic model, warranting its further investigation in familial psoriasis.