[Midwives as influencers in skin care for newborns at risk of atopic diseases : Survey of midwives' current recommendations]. / Hebammen als Influencer bei der Hautpflege atopisch prädisponierter Neugeborener : Eine Umfrage zu den aktuellen Empfehlungen von Hebammen.

INTRODUCTION: The prevalence of atopic diseases remains high. Initial studies suggest that primary prevention with regular basic care may influence the incidence of atopic dermatitis in infants; however, data are unclear. Midwives play an important role in the care of women in the peripartum period and therefore also in providing advice on topics such as skin care, breastfeeding and nutrition of the newborn and young infant. The aim of this study was to determine the care recommendations for newborns by midwives. METHODS: We conducted a cross-sectional survey among German midwives using questionnaires on the topic of newborn skin care. RESULTS: A total of 128 questionnaires were analyzed. The most common recommendations were oil-based herbal topicals (34.9%) and plain water (34.0%). Approximately 70% of midwives reported recommending various options when there was a known family history of atopic diathesis. It was remarkable that most of the midwives' recommendations were identical regardless of the presence of an atopic diathesis. Essential care products are only used "when necessary". CONCLUSION: Training programs for midwives on the topic of "care and strengthening of the skin barrier", taking into account the current guidelines for allergy prevention, should be implemented.

[Immune-mediated inflammatory diseases in Germany : A cross-sectional analysis of comorbidities and pharmacotherapy]. / Chronische Entzündungserkrankungen in Deutschland : Eine Querschnittanalyse über Begleiterkrankungen und Arzneimitteleinsatz.

BACKGROUND: Immune-mediated inflammatory diseases (IMID) can lead to a substantial disease burden for those affected, in particular by the concomitant occurrence of other IMIDs or in the presence of comorbidities. The care of patients with IMIDs is complex and involves various medical disciplines. OBJECTIVE: To describe the burden of disease and the current routine drug treatment of patients with IMID. MATERIAL AND METHODS: The retrospective cross-sectional analysis was based on statutory health insurance claims data from the InGef database. Prevalent patients with psoriasis (Pso), psoriatic arthritis (PsA), spondylarthritis (SpA), rheumatoid arthritis (RA), Crohn's disease (MC), ulcerative colitis (CU), or connective tissue disease were identified among 3,988,695 insured patients in 2018. The concomitant occurrence of different IMIDs and the extent to which patients with IMID are affected by other comorbidities compared to a reference population were investigated. The current routine drug treatment was described based on the use of predefined forms of treatment. RESULTS: In the database 188,440 patients with IMID (4.7%) were identified. Compared to the reference population the prevalence of comorbidities, such as depressive episodes and cardiovascular risk factors was higher in patients with IMID. For MC, CU, RA, and PsA disease-modifying antirheumatic drugs (DMARD) and classical systemic forms of treatment were used most commonly. In Pso, SpA, and connective tissue disease nonsteroidal anti-inflammatory drugs (NSAID) were the most frequently used treatment often in combination with other drugs. CONCLUSION: A considerable number of patients with IMIDs (16.9-27.5%) suffer from different diseases of the IMID group. They are frequently affected by accompanying illnesses and require interdisciplinary medical treatment.

[Multidisciplinarity as the key to success : Cooperation between dermatology and rheumatology to optimize patient care]. / Multidisziplinarität als Schlüssel zum Erfolg : Zusammenarbeit zwischen Dermatologie und Rheumatologie zur Optimierung der Patientenversorgung.

BACKGROUND: Treatment of patients with systemic autoimmune and/or autoinflammatory diseases (AI/AInf) often requires multidisciplinary collaboration of various medical specialties. OBJECTIVES: We evaluated whether the establishment of a multidisciplinary board, which we termed rheuma board (RB), can contribute to optimization of care for patients with psoriatic arthritis (PsA) or other AI/AInf. MATERIALS AND METHODS: A total of 272 patients were included in the study. Patients were divided into three groups-group 1: 41 patients with or with suspected PsA, initially assessed in the dermatology department and afterwards presented for consultation in the rheumatology department; group 2: 166 patients with or with suspected PsA presenting in the dermatology department and afterwards discussed by RB; group 3: 65 patients with other AI/AInf presenting in the dermatology department and afterwards discussed by RB. We evaluated the average duration from initial presentation to therapy initiation after completing evaluation and diagnostics by both specialties. In addition, diagnosis confirmation/verification and therapy continuation/optimization were analyzed for all three groups. RESULTS: The average duration from initial presentation until therapy initiation was 85 ± 42.24 (5-173) days in group 1, 15 ± 13.09 (0-78) days in group 2, and 20 ± 16.71 (1-75) days in group 3. In addition, in groups 2 and 3 confirmation of diagnosis was faster and waiting time for diagnosis and therapy initiation was significantly reduced. CONCLUSIONS: Establishment of a RB results in a significant reduction in the time duration between first presentation and initiation of therapy, and an improvement of care for patients with AI/AInf including confirmation of diagnosis and therapy optimization.

Pathobiology of Second-Generation Antihistamines Related to Sleep in Urticaria Patients.

Background: Standard treatment options for urticaria are second-generation antihistamines; however, their effect on sleep is uncertain. This study measures the influence of different antihistamines on the biologic sleep pattern of urticaria patients and the relevance of sleep in urticaria patients. Methods: Ten patients with chronic spontaneous urticaria (CSU) and uncontrolled symptoms under a single dose of second-generation antihistamines were included. Two nights were monitored: the first night after 5 days on single dosage and the second night after 5 days on fourfold dosage. Patient-rated questionnaires were used and sleep was monitored using polygraphy. Results: The patients' rated daytime sleepiness decreased (p = 0.0319), as did their insomnia severity (p = 0.0349). The urticaria control (UCT) improved (p = 0.0007), as did the quality of life (p < 0.0001). There was no significant change of nightly pruritus (p = 0.1173), but there was an improvement of daytime pruritus (p = 0.0120). A significant increase in rapid eye movement (REM) sleep was seen (p = 0.0002) (from a mean of 3.9% to 14.3%). The deep sleep state (N3) also improved (8.7% to 12.3%) (p = 0.1172). Conclusion: This study has demonstrated an improvement of the sleep pattern in CSU patients under up-dosed second-generation antihistamines, without increased daytime sleepiness, alongside an improvement of urticaria symptoms and quality of life.

TNF-α blockade may lead to improvement of vascular function in psoriasis patients.

Psoriasis is one of the most common chronic inflammatory skin diseases and at the same time a risk factor for cardiovascular disease. Interleukin-17A (IL-17A)-mediated inflammation in psoriasis may lead to vascular dysfunction. This study aimed at investigating whether anti-inflammatory treatment by tumor necrosis factor (TNF)-α blockade alters vascular function in psoriasis patients. A total of 11 patients with psoriasis who underwent treatment with either adalimumab (n = 8) or etanercept (n = 3), 10 healthy control individuals and 14 patients with coronary artery disease (CAD) were included in this study. Treatment response was assessed using the Psoriasis Area and Severity Index (PASI) score. Endothelial reactivity and resting endothelium-dependent vascular tone were assessed by ultrasound measurement of flow-mediated dilation (FMD) and low-flow-mediated constriction (l-FMC), respectively. FMD was slightly impaired in psoriasis patients compared to healthy controls. Anti-TNF-α treatment did not significantly change FMD levels. Psoriasis patients showed a trend towards increased baseline vascular activity compared to healthy controls. Anti-TNF-α treatment significantly improved l-FMC in psoriasis patients. Noteworthy, both FMD and l-FMC in psoriasis patients were comparable to those in patients with CAD; however, an important influence of age differences between the groups or co-existent classical cardiovascular risk factors on FMD and l-FMC cannot be ruled out by our small study. The results suggest that anti-inflammatory treatment with TNF-α blockade improves vascular function in patients with psoriasis, mainly by altering baseline vascular tone. Further studies will be necessary to establish the potentially protective impact of anti-inflammatory therapy on vascular function in patients with chronic inflammatory diseases.

Combination therapy of recalcitrant severe psoriasis with psoriatic arthritis, diabetes nephropathy, and liver cirrhosis.

OBJECTIVE: Treatment of recalcitrant moderate-to-severe psoriasis can be challenging. Combination therapy of biologics and immunosuppressive agents can be a new strategy for treating therapy-resistant cases with comorbidities, where many systemic medications are contraindicated. CASE PRESENTATION: We report a case of a 62-year-old diabetic man with a 30-year history of severe plaque psoriasis and psoriatic arthritis with cirrhosis and diabetic nephropathy that was treated successfully in combination with apremilast and etanercept after multiple previous unsuccessful treatment attempts. CONCLUSION: There are no data supporting the combination of apremilast and etanercept in the management of recalcitrant cases of moderate-to-severe psoriasis and multiple comorbidities including psoriatic arthritis, diabetic nephropathy, and cirrhosis. In patients who do not respond to multiple approaches for the treatment of psoriasis, combination therapy with biologic agents and new systemic medications may lead to dramatic disease control.

Skin Sodium Accumulates in Psoriasis and Reflects Disease Severity.

Sodium can accumulate in the skin at concentrations exceeding serum levels. A high sodium environment can lead to pathogenic T helper 17 cell expansion. Psoriasis is a chronic inflammatory skin disease in which IL-17‒producing T helper 17 cells play a crucial role. In an observational study, we measured skin sodium content in patients with psoriasis and in age-matched healthy controls by Sodium-23 magnetic resonance imaging. Patients with PASI > 5 showed significantly higher sodium and water content in the skin but not in other tissues than those with lower PASI or healthy controls. Skin sodium concentrations measured by Sodium-23 spectroscopy or by atomic absorption spectrometry in ashed-skin biopsies verified the findings with Sodium-23 magnetic resonance imaging. In vitro T helper 17 cell differentiation of naive CD4+ cells from patients with psoriasis markedly induced IL-17A expression under increased sodium chloride concentrations. The imiquimod-induced psoriasis mouse model replicated the human findings. Extracellular tracer Chromium-51-EDTA measurements in imiquimod- and sham-treated skin showed similar extracellular volumes, rendering excessive water of intracellular origin. Chronic genetic IL-17A‒driven psoriasis mouse models underlined the role of IL-17A in dermal sodium accumulation and inflammation. Our data describe skin sodium as a pathophysiological feature of psoriasis, which could open new avenues for its treatment.

Immunohistochemical markers for histopathological diagnosis and differentiation of acute cutaneous graft-versus-host disease.

Graft-versus-host disease (GvHD) is a major complication following stem-cell or solid-organ transplantation. Accurate diagnosis of cutaneous GvHD is challenging, given that drug eruptions and viral rashes may present with similar clinical/histological manifestations. Specific markers are not available. We performed the histological examination of biopsy samples from acute GvHD (aGvHD; n = 54), Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN; n = 27), maculopapular drug eruption (MDE; n = 26) and healthy controls (n = 26). Samples of aGvHD showed a decrease in Langerhans cells (LC, p = 0.0001) and an increase in macrophages (MΦ, p = 0.0001) compared to healthy skin. Compared to SJS/TEN, MDE and healthy skin, aGvHD biopsies contained greater numbers of CD4+ and CD8+ T cells. The majority of CD4+ T-helper cells were localized in the upper dermis, whereas cytotoxic CD8+ T cells were found in the epidermis. Increased numbers of CD56+ natural killer (NK) cells in the upper dermis of aGvHD skin (p = 0.007) were not observed in controls or SJS/TEN and MDE. There were no differences in elafin staining between aGvHD and the latter two conditions. Acute GvHD appears to have a distinct inflammatory cell profile (T cells/NK cells) that may aid establishing in a more accurate diagnosis, especially when used to rule out differential diagnoses such as SJS/TEN or MDE.

Aestivation motifs explain hypertension and muscle mass loss in mice with psoriatic skin barrier defect.

AIM: Recent evidence suggests that arterial hypertension could be alternatively explained as a physiological adaptation response to water shortage, termed aestivation, which relies on complex multi-organ metabolic adjustments to prevent dehydration. Here, we tested the hypothesis that chronic water loss across diseased skin leads to similar adaptive water conservation responses as observed in experimental renal failure or high salt diet. METHODS: We studied mice with keratinocyte-specific overexpression of IL-17A which develop severe psoriasis-like skin disease. We measured transepidermal water loss and solute and water excretion in the urine. We quantified glomerular filtration rate (GFR) by intravital microscopy, and energy and nitrogen pathways by metabolomics. We measured skin blood flow and transepidermal water loss (TEWL) in conjunction with renal resistive indices and arterial blood pressure. RESULTS: Psoriatic animals lost large amounts of water across their defective cutaneous epithelial barrier. Metabolic adaptive water conservation included mobilization of nitrogen and energy from muscle to increase organic osmolyte production, solute-driven maximal anti-diuresis at normal GFR, increased metanephrine and angiotensin 2 levels, and cutaneous vasoconstriction to limit TEWL. Heat exposure led to cutaneous vasodilation and blood pressure normalization without parallel changes in renal resistive index, albeit at the expense of further increased TEWL. CONCLUSION: Severe cutaneous water loss predisposes psoriatic mice to lethal dehydration. In response to this dehydration stress, the mice activate aestivation-like water conservation motifs to maintain their body hydration status. The circulatory water conservation response explains their arterial hypertension. The nitrogen-dependency of the metabolic water conservation response explains their catabolic muscle wasting.

Combined treatment of hidradenitis suppurativa with intense pulsed light (IPL) and radiofrequency (RF).

BACKGROUND: Hidradenitis suppurativa is a chronic inflammatory disease with high burden. Treatment options are often unsatisfactory. We assessed the effect of a combination therapy of intense pulsed light (IPL) and radiofrequency (RF). METHODS: The explorative study included 47 patients and was performed as a prospective, monocentric, randomized, three-arm parallel-group design trial with a prior 12 weeks observation period. Treatment arms were IPL and RF monotherapies or IPL + RF combination therapy. After 12 weeks, all patients received IPL + RF for additional 12 weeks (cross-over). Primary endpoint was the change in active lesion numbers, secondary endpoint the change in Dermatology Quality of Life Index (DLQI). RESULTS: After 12 weeks, active lesion counts of the IPL + RF group decreased more than in the IPL group (p = .044); the decrease in DLQI was significantly higher in the IPL + RF and RF groups compared to IPL. Prolonged 24-week treatment with IPL + RF obtained better results as 12 weeks. Overall, disease burden after 24 weeks of treatment compared to disease fluctuation during the observation period was significantly lower (change in active lesions -3.6, p = .001; in DLQI -5.2, p = .003). CONCLUSIONS: IPL + RF treatment appears to represent a promising therapeutic option that leads to reduction of disease activity without severe side effects.

Impact of Psoriasis on Mortality Rate and Outcome in Myocardial Infarction.

Background Psoriasis is a frequent chronic inflammatory cytokine-mediated skin disease and was identified to be an independent risk factor for the occurrence of myocardial infarction (MI). However, data about the impact of psoriasis on mortality and other in-hospital adverse events in the setting of MI are sparse and inconsistent. Methods and Results The nationwide German inpatient sample of the years 2005 to 2016 was used for statistical analysis. Hospitalized patients with MI were stratified for the presence of psoriasis and the impact of psoriasis on in-hospital events was investigated. Overall, 3 307 703 patients with MI (37.6% females, 56.8% aged ≥70 years) were treated in Germany (2005-2016); among them 9028 (0.3%) were diagnosed with psoriasis. Patients with MI with psoriasis were significantly younger (68.0 [58.0-76.0] versus 73.0 [62.0-81.0] years; P<0.001) and showed significant lower in-hospital case-fatality rate (7.1% versus 12.4%; P<0.001), confirmed in the regression (odds ratio, 0.68; 95% CI, 0.63-0.74; P<0.001) adjusted for age, sex, and comorbidities. They more frequently revealed cardiovascular risk factors such as arterial hypertension (58.9% versus 55.0%; P<0.001), hyperlipidemia (44.4% versus 38.6%; P<0.001), smoking (14.3% versus 7.4%; P<0.001), diabetes mellitus (34.8% versus 30.4%; P<0.001) or obesity (17.9% versus 9.3%; P<0.001). While the rate of percutaneous coronary intervention (41.4 versus 42.0%; P=0.223) was comparable between both groups, coronary bypass surgery was more often performed in patients with MI with psoriasis (7.7% versus 4.7%; P<0.001). Conclusions Overall, only 0.3% of all MI cases were diagnosed with psoriasis, and patients with MI with psoriasis were in median 5 years younger than patients with MI without psoriasis. Psoriasis seems to enhance the prevalence of classical cardiovascular risk factors and might therefore explain the earlier time point for MI. Our data also showed in turn a lower in-hospital mortality rate in patients with MI with psoriasis, presumably driven by younger age.

Effective treatment of disseminated superficial actinic porokeratosis with chemical peels - customary treatment for a rare disease.

Background: Disseminated superficial actinic porokeratosis (DSAP) is a rare dermatologic disorder of the epidermis. Often misdiagnosed as chronic UV-damage or actinic keratoses, patients are treated for years with different therapeutic options with little success. Current treatment options include imiquimod, ingenol mebutate, cryosurgery, photodynamic therapy and topical or systemic therapy with retinoids. Since those approaches show only little success or come along with major side effects, therapeutic alternatives are strongly requested. Methods: We report a series of five female patients with history of DSAP that were successfully treated with chemical peels. Results: All patients suffered from the disease for 14.4 years on average and all were refractory to at least two therapeutic options, mostly imiquimod and topical tretinoin. Patients were treated with glycolic acid 50% and salicylic acid 25% in a two-layer-technique. After a mean of three cycles every 6 weeks a clear reduction in lesion was assessed by physicians. Patients were highly satisfied with outcome and rare occurrence of side effects as assessed by TSQM questionnaire. Conclusion: Chemical peels are safe and well tolerated treatment options for patients with refractory porokeratosis. As characteristic for chronic diseases, frequent repetition of treatment is needed in order to control disease activity.

Platelets Aggregate With Neutrophils and Promote Skin Pathology in Psoriasis.

Psoriasis is a frequent systemic inflammatory autoimmune disease characterized primarily by skin lesions with massive infiltration of leukocytes, but frequently also presents with cardiovascular comorbidities. Especially polymorphonuclear neutrophils (PMNs) abundantly infiltrate psoriatic skin but the cues that prompt PMNs to home to the skin are not well-defined. To identify PMN surface receptors that may explain PMN skin homing in psoriasis patients, we screened 332 surface antigens on primary human blood PMNs from healthy donors and psoriasis patients. We identified platelet surface antigens as a defining feature of psoriasis PMNs, due to a significantly increased aggregation of neutrophils and platelets in the blood of psoriasis patients. Similarly, in the imiquimod-induced experimental in vivo mouse model of psoriasis, disease induction promoted PMN-platelet aggregate formation. In psoriasis patients, disease incidence directly correlated with blood platelet counts and platelets were detected in direct contact with PMNs in psoriatic but not healthy skin. Importantly, depletion of circulating platelets in mice in vivo ameliorated disease severity significantly, indicating that both PMNs and platelets may be relevant for psoriasis pathology and disease severity.

Humanized mice in cutaneous leishmaniasis-Suitability analysis of human PBMC transfer into immunodeficient mice.

Humanized mice represent a suitable preclinical test system for example therapeutic interventions in various disease settings, including infections. Here, we intended to establish such system for cutaneous leishmaniasis by infecting T, B and NK cell-deficient mice adoptively transferred with human peripheral blood mononuclear cells (PBMC). L major infection led to the establishment of parasite lesions harbouring viable parasites and human T cells, but parasite elimination was not seen due to a species-specific activity of T cell-derived human IFNγ. In addition, up to 50% of infected mice succumbed to severe graft-versus-host disease. In summary, even though long-term disease outcome assessments are impossible, this model of humanized mice can be used for studying lesion development and generation of oligoclonal anti-parasite human T cell responses in vivo.