Survival and Effectiveness of Tumour Necrosis Factor-alpha Inhibitors in the Treatment of Plaque Psoriasis under Daily Life Conditions: Report from the Psoriasis Registry Austria.

This retrospective multicentre analysis from the Psoriasis Registry Austria (PsoRA) was conducted to determine drug effectiveness and survival of anti-tumour necrosis factor alpha (anti-TNF-α) agents in patients with moderate-to-severe chronic plaque psoriasis over a 9-year period. Data on 1,019 treatment cycles with adalimumab (n = 460), etanercept (n = 501), and/or infliximab (n = 58) administered to 827 patients (272 women, 555 men) were available for analysis. Compared with etanercept, adalimumab and infliximab showed superior short-term effectiveness. Intention-to-treat-calculated median drug survivals for adalimumab (1,264 days) and etanercept (1,438 days) were similar to each other (p = 0.74), but significantly superior to that of infliximab (477 days) (p = 7.0e-07 vs. adalimumab and p=2.2e-07 vs. etanercept, respectively). Their drug survival rates at 36 months were 51.6%, 56.0%, and 22.6%, respectively. Survival rates correlated significantly with effectiveness for adalimumab and etanercept, but not for infliximab.

Thyroid screening in HIV-infected patients with antiretroviral therapy.

BACKGROUND: The literature reports an increased incidence of thyroid disorders in human immunodeficiency virus (HIV)-positive persons. We therefore retrospectively analyzed the strategy of collecting thyroid parameters on a routine basis. METHODS: Overall 410 patients (147 women, 263 men; age, 10-74 years; median age, 45 years) were included. For screening purposes, three parameters were determined; basal thyroid-stimulating hormone (TSH), free thyroxine (fT4), and free triiodothyronine (fT3). Descriptive and statistical analyses were performed in the patient groups with increased bTSH (> 4.0 µU/ml) and with decreased fT4 (< 8.9 pg/ml) to evaluate possible correlation with age, gender, duration of antiretroviral therapy (ART), substance classes of ART (nucleosidal reverse transcriptase inhibitors (NRTIs), nonnucleosidal reverse transcriptase inhibitors, and protease inhibitors (PIs)), Centers for Disease Control and Prevention (CDC) disease stage, lowest number of CD4 cells during course of disease, and coexistent hepatitis C. RESULTS: Elevated bTSH was found in 27 patients (median, 5.26 µU/ml), who also showed a correlation with ART duration and NRTI use. Decreased fT4 was seen in 53 persons, and a correlation with PI intake was observed. Of these patients, 31 exhibited normalization in follow-up. Decreased fT3 was observed in eight cases related to nonthyroid illness, and fT3 was elevated in ten patients. No overt hyperthyroidism was noticed; three cases of subclinical hyperthyroidism were transient. CONCLUSIONS: In the examined group of patients, the prevalence of abnormal thyroidal parameters was 23 %. Decreased fT4, which does not require therapy, was observed most frequently (12 %) and correlated with PI use. On the other hand, elevated bTSH (6 %) correlated with ART duration and NRTI use. In mild subclinical hypothyroidism as observed in this patient population, thyroxine medication is not indicated in principle. Annual TSH screening is probably sufficient in HIV-infected patients with no clinical symptoms suggestive for thyroid disease.

In vitro vs. in vivo tape stripping: validation of the porcine ear model and penetration assessment of novel sucrose stearate emulsions.

Porcine ear skin is frequently used as a substitute for human skin in dermatological research and is especially useful for tape stripping experiments where the penetration of active substances into the uppermost skin layers is investigated. However, certain differences between the surface properties of these skin types exist, and reports on the comparability of tape stripping data obtained in vitro using porcine ear skin and data obtained in vivo on human forearm skin are scarce. Thus, we performed comparative tape stripping experiments in which the skin penetration of curcumin and fluorescein sodium from conventional microemulsions and hydrogels was investigated. In this context, the skin penetration potential of novel semi-solid macroemulsions and fluid nanoemulsions based on sucrose stearate was evaluated as well. The removed corneocytes were quantified by NIR-densitometry using recent correlation data for human and porcine proteins. The trends observed for the skin penetration into porcine ear skin were highly representative for the in vivo situation on human skin, confirming that the porcine ear is an excellent in vitro model for tape stripping experiments. Moreover, the validity of the NIR-densitometric approach for the quantification of both human and porcine stratum corneum proteins was confirmed in this study for the first time.

Lymphocyte imbalance in vitiligo patients indicated by elevated CD4+/CD8+ T-cell ratio.

Vitiligo is a disorder of pigmentation associated with an autoimmune-mediated loss of melanocytes from the epidermis. Humoral immunity and the involvement of cellular immunity have been investigated in the pathogenesis of vitiligo. We evaluated the role of pro-inflammatory cytokines and lymphocyte fractions in peripheral blood in a cohort of Austrian patients with vitiligo. Morning blood samples from 40 patients with vitiligo were collected. Twenty-one patients had active and 19 had stable vitiligo disease. All patients were suffering from non-segmental vitiligo at different stages of the disease. Sixteen persons presented with an additional autoimmune thyroid disease. To evaluate a possible involvement of proinflammatory cytokines in vitiligo we measured sTNF-RI (soluble tumour necrosis factor receptor I), IL-6 and additionally CIC (circulating immune complexes). We compared these findings to the data from matched normal persons. To investigate the mechanisms of cellular immunity, peripheral blood cell count and lymphocyte subtype analysis by flow cytometry were done. sTNF-RI, IL-6 and CIC serum levels were in the normal range. In the patient group median sTNF-RI level was 1.5 ng/ml and median CIC level was 35.2 microg/ml, and no statistically significant differences to the control group were observed. Median IL-6 level in vitiligo patients was 2.7 pg/ml and in the normal range-but higher than the median level of 0.5 pg/ml observed in normal persons (p < 0.001). Absolute and relative counts of lymphocyte subtypes were normal. The ratio of CD4+/CD8+ T-cells had an elevated median value of 2.6 [quartiles 2.0; 3.1]. 61% of the vitiligo patients had a ratio higher than 2.4, which was the normal cut-off point. In most vitiligo patients the balance of cytotoxic/suppressor and helper/inducer T-cells in peripheral blood is disturbed which might lead to a predominance of T-cell subtypes in the intracutaneous site of autoimmune melanocyte loss.

Vitiligo patients present lower plasma levels of alpha-melanotropin immunoreactivities.

Vitiligo is a depigmenting disorder characterized by the development of white patches with evidence in favour of an autoimmune mechanism. We investigated the role of melanotropins and the plasma levels of alpha-melanotropin and ACTH-like immunoreactivities in 40 vitiligo patients with the aim of detecting a possible influence of neuropeptide regulation of immunity. Twenty-one patients had active and 19 had stable vitiligo disease, 16 persons presented with an additional autoimmune thyroid disease. Median alpha-MSH levels in vitiligo patients were 6.4p mol/l [5.2;11.3] and significantly lower than in control persons with 11.4 pmol/l [8.6;13.4]. Median ACTH levels of the affected patient group were 17 pg/ml [10.5;28] and appeared statistically higher than 12 pg/ml [7;17] measured in the control group. Measured morning cortisol levels in both groups were not significantly different. Reduced cutaneous alpha-MSH immunoreactivities have been related to the development of autoimmune-induced depigmenting disorders. Our data present lower alpha-MSH plasma levels in vitiligo patients which may be associated with the development of vitiligo depigmentation and may indicate a condition of impaired peripheral tolerance in this autoimmune disorder.

Adolf Jarisch (1850-1902): an important contributor to Austrian dermatology.

Adolf Jarisch was born on the 15th of February 1850 in the city of Vienna, where he also studied medicine. He soon pursued a career in dermatology and venereology and, thus, joined the clinic of von Hebra, one of the founders of the famous new Vienna School of Medicine. After temporarily replacing von Hebra, Jarisch became the chief of the Department of Dermatology at the University of Innsbruck (1887). Although Adolf Jarisch was appointed chief of the dermatologic department at the University of Graz 5 years later (1892), his biggest dream, to become successor of his former teacher Ferdinand von Hebra and head the dermatological department of the Wiener Allgemeines Krankenhaus (Vienna General Hospital) did not come true. Although Adolf Jarisch is mainly known for his observations on skin reactions and a profound worsening of symptoms in syphilitic patients immediately following treatment with mercury (Jarisch-Herxheimer reaction), he authored more than 25 scientific articles and wrote a book, "Hautkrankheiten", which was considered as the most important in German-speaking literature at the beginning of the twentieth century. The purpose of this historical article is to discuss Jarisch's achievements in the field of dermatology based on a detailed analysis of his scientific work.

Hypoplastic thyroid, growth hormone deficiency, corneal opacities, cataract and hyperkeratotic skin disease: a possible new ichthyosis syndrome associated with endocrinopathies.

A 56 year old man presented with ichthyosis vulgaris since early childhood, clinically characterised by fine scaling of the trunk and hyperkeratotic scales on the exterior surfaces of the upper and lower extremities. The patient also showed hypothyroidism due to hypoplastic thyroid, cataract, hypercholesterinemia with concommitant arcus cornealis and biliary concrements. Renal lithiasis caused by calcio-oxalate was additionally present. Endocrinological screening revealed growth hormone deficiency in the 1.55 m tall man-(secondary) osteoporosis was observed. The clinical symptomatology indicates that this case cannot be considered as a subtype of the inherited ichthyosis group, but suggests a new syndrome as a separate nosologic entity.

Plasma levels of alpha-melanotropin and ACTH-like immunoreactivities do not vary by season or skin type in women from southern and central Europe.

Melanotropins (MSH) are involved in tanning by stimulating melanocytes via the activation of the melanocortin-1 receptor to melanin production. Its main site of production is the pituitary gland, but alpha-MSH and related ACTH peptides are produced at other sites, including the skin. It has been hypothesized that systemic levels of alpha-MSH are controlled by a varying UV radiation (UVR) exposure. A seasonal rhythm of plasma levels has been proposed by some authors. We investigated healthy females in southern Spain and central Austria in summer and winter. The alpha-MSH and ACTH-like immunoreactivity plasma levels did not present marked differences between the groups of Malaga and Linz, dark and light skin and between seasons. An association of alpha-MSH to ACTH or cortisol levels could not be observed. Individual values of alpha-MSH were shown to be relatively constant at both times of measurement (p<0.05 by rank correlation) indicating an independent personal disposition for individual systemic alpha-MSH immunoreactivity levels. Our data do not support the concept of a marked involvement of melanotropins of pituitary origin in tanning, and no seasonal rhythm was observed.