EuroGuiDerm Guideline on the systemic treatment of Psoriasis vulgaris - Part 2: specific clinical and comorbid situations.

This evidence- and consensus-based guideline on the treatment of psoriasis vulgaris was developed following the EuroGuiDerm Guideline and Consensus Statement Development Manual. The second part of the guideline provides guidance for specific clinical and comorbid situations such as treating psoriasis vulgaris patient with concomitant psoriatic arthritis, concomitant inflammatory bowel disease, a history of malignancies or a history of depression or suicidal ideation. It further holds recommendations for concomitant diabetes, viral hepatitis, disease affecting the heart or the kidneys as well as concomitant neurological disease. Advice on how to screen for tuberculosis and recommendations on how to manage patients with a positive tuberculosis test result are given. It further covers treatment for pregnant women or patients with a wish for a child in the near future. Information on vaccination, immunogenicity and systemic treatment during the COVID-19 pandemic is also provided.

EuroGuiDerm Guideline on the systemic treatment of Psoriasis vulgaris - Part 1: treatment and monitoring recommendations.

This evidence- and consensus-based guideline on the treatment of psoriasis vulgaris was developed following the EuroGuiDerm Guideline and Consensus Statement Development Manual. The first part of the guideline includes general information on the scope and purpose, health questions covered, target users and strength/limitations of the guideline. Suggestions for disease severity grading and treatment goals are provided. It presents the general treatment recommendations as well as detailed management and monitoring recommendations for the individual drugs. The treatment options discussed in this guideline are as follows: acitretin, ciclosporin, fumarates, methotrexate, adalimumab, apremilast, brodalumab, certolizumab pegol, etanercept, guselkumab, infliximab, ixekizumab, risankizumab, secukinumab, tildrakizumab and ustekinumab.

Genetic fuzzy system predicting contractile reactivity patterns of small arteries.

Monitoring of physiological surrogate end points in drug development generates dynamic time-domain data reflecting the state of the biological system. Conventional data analysis often reduces the information in these data by extracting specific data points, thereby discarding potentially useful information. We developed a genetic fuzzy system (GFS) algorithm that is capable of learning all information in time-domain physiological data. Data on isometric force development of isolated small arteries were used as a framework for developing and optimizing a GFS. GFS performance was improved by several strategies. Results show that optimized fuzzy systems (OFSs) predict contractile reactivity of arteries accurately. In addition, OFSs identified significant differences that were undetectable using conventional analysis in the responses of arteries between groups. We concluded that OFSs may be used in clustering or classification tasks as aids in the objective identification or prediction of dynamic physiological behavior.

How do children with a chronic or long-term illness perceive their school re-entry after a period of homebound instruction?

BACKGROUND: A considerable number of children are confronted with a chronic or long-term illness in their lives. For these children, absenteeism is problematic, because education plays a major role in stimulating their cognitive development and in promoting a sense of normalcy and psychosocial well-being. In the literature, a great deal of attention has been paid to school reintegration programmes, which try to counter the barriers that these children may face when they return to school. Another way of surmounting these barriers is through the use of homebound instruction, in which the educational process for the child is continued during the period of absence. Despite the growing awareness of the necessity of education for these children, there is still little empirical research available addressing programmes that facilitate school re-entry. METHODS: The major goal of this study is to investigate how parents and their children with a chronic or long-term illness perceive school re-entry after a period of homebound instruction, by using a descriptive-explorative, multi-informant research design. Participants were 60 children and their parents who filled in a self-constructed questionnaire. RESULTS: Both parents and children perceived the period of homebound instruction, as well as their school re-entry, predominantly positively. Most of the children stated that they had been able to keep up with their subjects, and that they had good contact with their peers when they returned to school. According to parents, homebound instruction made a positive contribution to the school re-entry of their child. CONCLUSIONS: The current study is one of the first to explore the school re-entry of children with a chronic or long-term illness. According to both parents and children, the school re-entry process passed off positively. However, more research is needed with regard to the quality of education and the programmes aimed at facilitating school re-entry.

[The strategy of prevention and early detection of cutaneous melanoma]. / La stratégie de prévention et de dépistage du mélanome cutané.

Dermatology, and more specifically cutaneous oncology, has evolved from a descriptive science concept towards multifaceted medico-surgical medicine which is nowadays based not only on observation. In this view, the importance of prevention and early detection of skin cancers including cutaneous melanoma has been recognized and has created a new challenge. Thanks to this proactive approach, the improvement in the prognosis of newly diagnosed melanomas has been demonstrated, but many efforts have to be brought to reduce the incidence and the mortality of this potentially aggressive tumor.

Desloratadine 5 mg once daily improves the quality of life of patients with chronic idiopathic urticaria.

BACKGROUND: Chronic urticaria is known to debilitate a person's quality of life via sleep disruption, itching lesions, fatigue, social isolation, energy loss and emotional/sexual difficulties. Once-daily desloratadine significantly improved the signs and symptoms of CIU. OBJECTIVE: Assess the effect of desloratadine 5 mg once daily on the quality of life of patients suffering of chronic idiopathic urticaria (CIU). Study population One-hundred twenty-one consecutive patients with CIU present for at least 6 weeks prior to inclusion and with a current flare of at least 3 weeks, were included in the study in 24 Belgian centres. RESULTS: The mean dermatology life quality index (DLQI) significantly decreased from baseline to day 7 and further to day 42. Sixty per cent and 77% of patients had a clinically significant change (i.e. a decrease of at least 2 points) at day 7 or day 42, respectively, as compared with that of day 0. Change in pruritus and size of the hives significantly correlated with the change in the score of the quality of life. One-third of patients experienced complete relief whereas in 1 of 10 patients no effect was experienced. CONCLUSIONS: Desloratadine significantly improves the quality of life of patients with chronic idiopathic urticaria as reflected by the dermatology life quality index (DLQI).

Mesenteric small artery changes after vasoconstrictor infusion in young rats.

We evaluated whether chronic alpha 1-adrenergic stimulation, angiotensin II (AII), or increased blood pressure (BP) alters resistance arterial structure and function. Structural parameters and wall tension were recorded in mesenteric small arteries (MrA) isolated from 6-week-old normotensive Wistar Kyoto rats that had been infused for 4 days with saline (WKY), 2 mg/kg/day phenylephrine (WKY + PHE), or 0.3 mg/kg/day AII (WKY + AII) and from saline-infused spontaneously hypertensive rats (SHR). During the experimental period, systolic BP (SBP) did not change in WKY but increased in WKY + PHE, WKY + AII, and SHR. Relative cardiac mass did not differ between SHR and WKY, but was increased in WKY + PHE and WKY + AII. Stiffness and optimal lumen diameter of MrA did not differ between WKY and SHR and were not altered in WKY + PHE or WKY + AII. Maximal contractile responses and sensitivities for vasconstrictors and calcium in vessels of WKY + AII and SHR did not differ from those in WKY. In vessels of WKY + PHE, maximal responses to vasoconstrictors and sensitivities for norepinephrine (NE) and PHE were reduced. Relaxing responses to isoproterenol (ISO) and Na-nitroprusside did not differ between SHR and WKY and were not altered in WKY + PHE and WKY + AII. Those to acetylcholine (ACh) were reduced in WKY + PHE. Media cross-sectional area and media thickness were significantly larger in WKY + AII and SHR as compared with WKY but were not altered in WKY + PHE. These data indicate that in young rats AII leads to small artery hypertrophy and that neither increased BP or increased vasconstriction appear to be involved therein. Chronic alpha 1-adrenergic stimulation, on the other hand, did not modify small artery structure but resulted in nonselective reduction of arterial smooth muscle contractile reactivity.

Force, membrane potential, and [Ca2+]i during activation of rat mesenteric small arteries with norepinephrine, potassium, aluminum fluoride, and phorbol ester. Effects of changes in pHi.

In activated rat mesenteric small arteries, the effect of pHi on force, membrane potential, and free cytosolic calcium ([Ca2+]i) was assessed. Arteries were mounted in a myograph for isometric force development, and [Ca2+]i, pHi, or membrane potential was measured simultaneously with force. During activation with norepinephrine, potassium, aluminum fluoride (AlF-4), and phorbol 12-myristate 13-acetate (PMA, a phorbol ester), the vessels depolarized and [Ca2+]i increased, although the ratio of force to [Ca2+]i was less during potassium activation than with the other types of activation. Changes in pHi, with a constant pHo, were induced with NH4Cl or by changing PCO2. In resting vessels, the effects of the changes in pHi on tension, membrane potential, and [Ca2+]i were negligible. In vessels activated with norepinephrine or AlF-4, alkalinization caused an acute decrease of tone, which could be explained by a decrease in [Ca2+]i consequent to repolarization of the membrane. In vessels activated with potassium or PMA, the effects of alkalinization were smaller. This is consistent with acute alkalinization, affecting steps proximal in the excitation-contraction coupling distal to activation of G proteins. Acidification caused a transient increase in tone and [Ca2+]i, irrespective of the mode of stimulation, without affecting the membrane potential. Ryanodine did not abolish the transient increase in tone and [Ca2+]i. Thus, acute intracellular acidification may induce tone by release of an intracellular ryanodine-insensitive calcium pool or by affecting transmembranal calcium flux although in a membrane potential-independent way.

Effects of a phorbol ester and staurosporine on electro- and pharmacomechanical coupling in a resistance artery.

We examined the role of protein kinase-C in contractile responses of small arteries of the rat by stimulating and inhibiting protein kinase-C with phorbol myristate acetate and staurosporine, respectively. The experiments were performed in isolated mesenteric resistance arteries that had been sympathectomized and mounted for recording of isometric force development. Phorbol myristate acetate (i) at concentrations lower than 3 nM increased sensitivity for the contractile effect of potassium, but not for the effect of noradrenaline or BAY-K8644, (ii) at concentrations higher than 30 nM increased the sensitivity of depolarized vessels to extracellular calcium and (iii) at concentrations higher than 30 nM induced a contractile effect that depended on the presence of extracellular calcium and that was reduced by the calcium antagonist felodipine. Neither the phorbol ester nor staurosporine affected contractile responses to caffeine in calcium-free solution. Staurosporine (10 nM) reduced the response of resistance arteries to potassium but not to noradrenaline. These results are in agreement with direct observations by others that protein kinase-C plays a role in the activation of voltage-operated calcium channels. Protein kinase-C could participate in this way in electro-mechanical coupling in resistance arterial smooth muscle and, when strongly activated, sensitize the contractile apparatus to calcium.

In vivo DNA synthesis is not uniformly increased in arterial smooth muscle of young spontaneously hypertensive rats.

We compared the distribution of DNA synthesis over the arterial tree of young normotensive Wistar-Kyoto (WKY) rats and spontaneously hypertensive rats (SHR) with marginally elevated blood pressure. Six-week-old male SHR and WKY rats were therefore infused with 5-bromo-2'-deoxyuridine (BrdUrd) for 2 days and the nuclear incorporation of the thymidine analogue in the media of various arteries was determined by immunohistochemistry. In WKY rats, 2.5% of the arterial smooth muscle nuclei in elastic, muscular and resistance arteries incorporated BrdUrd. In SHR, DNA synthesis was more marked in large arteries than in resistance arteries. It was in addition significantly larger in the aorta, superior mesenteric, renal and femoral arteries of the SHR than in those of the WKY rats. However, nuclear incorporation of BrdUrd in vivo did not differ between SHR and WKY rats in aortic endothelium, carotid arterial smooth muscle, nor in mesenteric or renal resistance arteries. Between 6 and 20 weeks of age, the number of nuclear profiles per media cross-section did not increase in large arteries of WKY rats and SHR. During this period of time, however, carotid artery and thoracic aorta weight and DNA content increased. SHR large arteries gained more DNA than those of WKY rats. These data indicate that DNA synthesis is uniformly distributed over the arterial system in young WKY rats and that DNA synthesis is elevated in the smooth muscle of large arteries of 6-week-old SHR but not in their resistance arteries.

DNA synthesis in isolated arteries. Kinetics and structural consequences.

We evaluated changes in DNA synthesis, structure, and mechanical activity in isolated arteries during exposure to growth factors. Renal arteries were isolated from rats, sympathectomized, denuded of endothelium, and maintained in tissue culture. Up to 4 days of culture did not affect maximal contractile responses to depolarization. From the results of nuclear incorporation of the thymidine analogue 5-bromo-2-deoxyuridine (BrdUrd), culture stimulated DNA synthesis. In the media, incorporation of BrdUrd was maximal after 3 days but fell precipitously thereafter. Culture of arterial segments did not, however, increase the cross-sectional area of the media, the ploidy of the arterial nuclei, or the number of medial cells. In contrast, new layers of cells, part of which displayed smooth musclelike properties, developed at the border of the segments. The outermost edge of this newly formed layer continued to incorporate BrdUrd for at least 2 wk. These data demonstrate that stimulation of DNA synthesis by continuous exposure of the arterial wall to exogenous growth factors is 1) transient in the media; 2) does not, at least initially, compromise contractile reactivity; 3) does not alter gross medial structure; but 4) leads to proliferation of smooth musclelike cells outside the media. These findings suggest that the number of smooth muscle cells in the arterial media is maintained constant in the presence of even strong mitogenic stimuli.

Growth responses in isolated elastic, muscular and resistance-sized arterial segments of the rat.

To evaluate whether intravascular phenomena contribute to local differences in growth responses of the arterial wall, we evaluated responses to organoid culture in a broad variety of arterial preparations. Arterial segments were isolated from adult, normotensive rats, sympathectomized, denuded from endothelium, and suspended in medium supplemented with serum. As judged from the nuclear incorporation of the thymidine analogue 5-bromo-2'-deoxyuridine (BrdUrd), this induced a transient stimulation of DNA synthesis in only a fraction of the arterial smooth muscle cells in all types of arteries. This intramedial DNA synthesis was more marked in renal arteries than in carotid arteries or aortae and was least pronounced in main pulmonary, femoral, and superior mesenteric artery and in mesenteric resistance-sized arteries. Organoid culture of isolated arteries did not increase the cross-sectional area of the media or the number of medial cells. It rather resulted in proliferation of smooth-muscle-like cells outside the media. In addition, smooth-muscle-like cells migrated out of the isolated arterial segments during culture. The rate of proliferation of these isolated cells did not differ between large arteries of different anatomical origin. However, isolated cells derived from mesenteric resistance arteries proliferated at a rate that was 4 times slower than that of large artery cells. The presence of endothelium significantly reduced medial DNA synthesis in carotid and renal artery segments, but not in mesenteric resistance-sized preparations. These data indicate that growth responses of the arterial wall differ quantitatively with the anatomical location and branching order of the vascular segment. In addition to the regional heterogeneity of endothelial effects on mitogenic responses of arterial smooth muscle, this seems to be due to regional differences in the susceptibility of arterial smooth muscle to exogenous growth factors. In this respect, we speculate that subsets of growth-resistant and growth-prone arterial smooth muscle cells could be heterogeneously distributed over the arterial tree.

[Effect of treatment with salt from the Dead Sea (Tomesa therapy) on epidermal Langerhans cells--a clinical study]. / Der Einfluss einer Behandlung mit Salz des Toten Meeres (Tomesa-Therapie) auf epidermale Langerhanszellen--Eine klinische Studie.

Among the therapeutical modes of psoriasis, sea-water baths with salts from the Dead Sea in combination with ultraviolet light (Tomesa therapy) play an important part. In a previous paper, we showed that treatment of isolated murine skin with Tomesa salt solutions resulted in an irreversible decrease of ATPase-positive epidermal Langerhans' cells. Our present study is concerned with the treatment of healthy persons and psoriasis patients with baths containing Tomesa salts, which lead to reduced amounts of detectable Langerhans' cells in the epidermis, as well. Baths containing sodium chloride in comparable concentrations, however, were without effect at all. Our findings demonstrate that the antipsoriatic activity of Tomesa therapy is not only due to physical effects but may also be the result of definable pharmacological actions of the salts on skin cells.

G-proteins are involved in contractile responses of isolated mesenteric resistance arteries to agonists.

We evaluated whether GTP-binding regulatory proteins (G-proteins) are involved in responses of resistance arterial smooth muscle to contractile agonists. We therefore pretreated isolated sympathectomized mesenteric resistance arteries of the rat with pertussis toxin (PTX) and recorded their contractile responses to aluminium fluoride, endothelin, high potassium, phenylephrine, phorbol myristate acetate, serotonin and vasopressin. PTX reduced contractile responses to agonists with the following order of potency: phenylephrine = serotonin greater than vasopressin = endothelin. The toxin reduced responses to phenylephrine in both the presence and absence of extracellular Ca2+. In Ca2(+)-depleted vessels that were exposed to phenylephrine, PTX virtually abolished responses to Ca2+ while hardly affecting responses to Ca2+ in the presence of endothelin. Also aluminium fluoride and phorbol myristate acetate induced contractions. These were dependent on extracellular Ca2+ and inhibited by felodipine. PTX reduced responses to aluminium fluoride but not those to phorbol myristate acetate. These data indicate that PTX sensitive G-proteins are involved in both influx of Ca2+ and release of intracellular Ca2+ following alpha 1-adrenergic and serotonergic stimulation of resistance arteries. The role of G-proteins in stimulated Ca2+ influx could involve a direct effect on calcium channels although an indirect effect through protein kinase-C can not be entirely excluded. The persistance of contractile responses to vasopressin and endothelin following PTX suggests that these agonists engage different pathways to induce contraction or have a higher efficacy in activating similar G-proteins.

[Squamous cell carcinoma of the lower lip in discoid lupus erythematosus associated with hereditary deficiency of complement 2]. / Plattenepithelkarzinom (P) der Unterlippe auf diskoidem Lupus erythematodes bei hereditärer Defizienz der 2. Komplementkomponente (C2).

We report on a 48-year-old female patient suffering from lupus erythematosus associated with C2 deficiency, who developed squamous cell carcinoma on a discoid lesion of her lower lip. Vermilionectomy (Langenbec-v. Bruns' technique) resulted in a good cosmetic and functional outcome.

Increased calcium sensitivity in isolated resistance arteries from spontaneously hypertensive rats: effects of dihydropyridines.

We recorded the contractile responses to calcium in mesenteric resistance arteries of Wistar Kyoto (WKY) and spontaneously hypertensive rats (SHR) during depolarization or stimulation with noradrenaline. The effects of Bay-K8644 and nimodipine on these responses were evaluated. Calcium sensitivity was greater in noradrenaline-stimulated than in depolarized vessels. Nimodipine decreased and Bay-K8644 increased calcium sensitivity. Both substances were more potent in the presence of potassium than in the presence of noradrenaline. Calcium sensitivity was greater in SHR than in WKY vessels only during stimulation with noradrenaline. The rhythmic responses of SHR vessels during stimulation with noradrenaline were abolished by nimodipine. Rhythmicity could be induced in WKY vessels by Bay-K8644. Modulation of calcium sensitivity by dihydropyridines during electrochemical as well as pharmacological stimulation suggests that, in resistance arterial smooth muscle, the function of potential-operated calcium channels can be modulated by noradrenaline. This modulation could differ quantitatively between mesenteric resistance arteries of SHR and WKY.

[The effect of Tomesa therapy on epidermal Langerhans cells in experimental animals]. / Die Wirkung der Tomesa-Therapie auf epidermale Langerhanszellen im Experiment.

In the last years a new therapy of psoriasis was developed, which consists in a treatment with salt solutions, resembling the water of the Dead Sea, and ultraviolet light (Tomesa-therapy). We studied the influence of the used salt on ATPase positive epidermal Langerhans cells in murine ear skin. An irreversible partial reduction of the Langerhans cell ATPase was found after salt treatment of separated epidermis or of full skin preparations. These results may have implications for the optimization and broader application of this therapy.

Effects of tertatolol on the responsiveness of isolated femoral, mesenteric, and renal resistance arteries to adrenergic stimuli.

We evaluated effects of the beta-adrenoceptor antagonist tertatolol on responses of resistance arteries to isoproterenol and phenylephrine and compared them with those of propranolol. The experiments were performed in femoral, mesenteric, and renal resistance arteries that had been isolated from adult Wistar-Kyoto rats, chemically sympathectomized and mounted for recording of contractile reactivity in vitro. In renal resistance arteries that had been pretreated with phenoxybenzamine, isoproterenol did not affect contractile responses to potassium. Under these conditions, isoproterenol induced relaxation in mesenteric resistance arteries. Low concentrations of both SR-tertatolol and SR-propranolol shifted concentration-response curves for isoproterenol to the right. Affinity for competitive beta-adrenergic antagonism did not differ between both agents. Unlike SR-propranolol, SR-tertatolol reduced maximal relaxing responses to isoproterenol. As compared with R-tertatolol, S-tertatolol was 100 times less potent as a competitive beta-adrenergic antagonist and failed to affect maximal relaxing responses to isoproterenol. In femoral, mesenteric, and renal resistance arteries preconstricted by phenylephrine, concentrations of SR-tertatolol greater than 1 microM induced relaxation. This relaxing effect did not differ between SR-tertatolol and SR-propranolol or between S-tertatolol and R-tertatolol. These data indicate that in resistance arteries tertatolol is a stereoselective beta-adrenoceptor antagonist that exhibits both a competitive and a noncompetitive mechanism of action. In addition, high concentrations of tertatolol relax resistance arterial smooth muscle. This effect was neither stereoselective nor selective for the renal vascular bed and was also observed with propranolol.

Acute and long-term effects of tissue culture on contractile reactivity in renal arteries of the rat.

To evaluate long-term effects of contractile and mitogenic stimuli on the contractile reactivity of arterial smooth muscle, we measured the incorporation of the thymidine analogue 5-bromo-2'-deoxyuridine (BrdUrd) and mechanical responses in arterial segments that had been maintained in tissue culture. The experiments were performed on renal arteries that had been isolated from adult rats, chemically sympathectomized, mechanically denuded from endothelium and mounted under distension. Exposure of arterial segments for up to 3 weeks to culture medium supplemented with fetal calf serum resulted in the following consecutive changes: a strong acute contraction, selective pharmacological changes that included decreased contractile responses to phenylephrine and vasopressin and increased relaxing responses to isoproterenol, increased incorporation of BrdUrd, a progressive fall in contractile responses to all vasoconstrictor stimuli, and an increase in excitability. Serum-free medium resulted in a much smaller acute arterial contraction, induced less incorporation of BrdUrd, accelerated the occurrence of hyperexcitability, but did not affect early pharmacological changes or the subsequent fall in overall arterial contractility with tissue culture. Dialysis of the serum or addition of ketanserin abolished the contractile effect of serum but did not affect the incorporation of BrdUrd or the loss of contractility with tissue culture. Addition of serotonin to serum-free culture medium mimicked the contractile response to serum but not the stimulation of BrdUrd incorporation. These data indicate that tissue culture alters the properties of the arterial wall, that contraction does not underlie the proliferative response of arterial smooth muscle to serum-derived mitogens in vitro, and that stimulation of DNA synthesis does in itself not lead to selective changes in arterial contractility.