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Biomedical subjects

T A Luger

Publications and source records attributed to T A Luger.

At least 19 recordsLinked to original sources

Mycosis fungoides: a dermatological masquerader.

Mycosis fungoides (MF), a low-grade lymphoproliferative disorder, is the most common type of cutaneous T-cell lymphoma. Typically, neoplastic T cells localize to the skin and produce patches, plaques, tumours or erythroderma. Diagnosis of MF can be difficult due to highly variable presentations and the sometimes nonspecific nature of histological findings. Molecular biology has improved the diagnostic accuracy. Nevertheless, clinical experience is of substantial importance as MF can resemble a wide variety of skin diseases. We performed a literature review and found that MF can mimic >50 different clinical entities. We present a structured framework of clinical variations of classical, unusual and distinct forms of MF. Distinct subforms such as ichthyotic MF, adnexotropic (including syringotropic and folliculotropic) MF, MF with follicular mucinosis, granulomatous MF with granulomatous slack skin and papuloerythroderma of Ofuji are delineated in more detail.

Diagnosis, Differential↗

Pimecrolimus cream 1% is effective in asteatotic eczema: results of a randomized, double-blind, vehicle-controlled study in 40 patients.

BACKGROUND AND OBJECTIVE: Pimecrolimus cream 1% is an effective treatment for atopic eczema. The aim was to investigate its efficacy in asteatotic eczema, a skin disease similar to atopic eczema and its associated dry skin and itching. METHODS: Single-centre, randomized, double-blind, vehicle controlled study in 40 patients with asteatotic eczema. Efficacy was assessed by eczema area and severity index (EASI), investigators global assessment (IGA), patient's self-assessment, and pruritus severity. RESULTS: After 4 weeks of treatment, EASI, the primary efficacy variable, was reduced by 62+/-7% from baseline in patients on pimecrolimus, compared to 21+/-14% in patients on vehicle (P=0.013). With pimecrolimus there was also a better control of pruritus (P=0.042) at week 4 whereas a better control of disease according to self-assessment could only be observed at weeks 2 (P=0.01) and week 3 (P=0.08). CONCLUSION: Pimecrolimus cream 1% is effective in patients with asteatotic eczema.

Adult↗

Non-pigmentary actions of alpha-melanocyte-stimulating hormone--lessons from the cutaneous melanocortin system.

In the last years the neuropeptide a-melanocyte-stimulating hormone has emerged as a regulator of various biological processes far beyond the initially described pigment-inducing action. Expression of melanocortin-receptors (MC-Rs), mainly MC-1R, has been identified in several non-pigmentary human skin cell types. Moreover, expression of MC-5R has been detected in sebocytes and skin mast cells while MC-4R has been reported in dermal papilla cells, a specialized myofibroblast cell type regulating hair follicle activity. In accordance with early observations in the rat preputial gland alpha-melanocyte-stimulating and related peptides have lipogenic activity in the human system. The immunomodulatory actions of alpha-melanocyte-stimulating include regulation of expression and secretion of chemokines, downregulation of proinflammatory signal-induced NF-kappaB activation and adhesion molecule expression, prostaglandin E2 synthesis, as well as induction of interleukin-10. Depending on the cell type studied and the experimental conditions alpha-melanocyte-stimulating however may also have weak proinflammatory actions. In dermal fibroblasts alpha-melanocyte-stimulating was further reported to modulate collagen metabolism via upregulating interstitial collagenase as well as by attenuating the inductive effect of transforming growth factor B on 1 collagen synthesis and fibrosis, the latter pointing towards a potential role of a-melanocyte-stimulating during chronic inflammatory skin responses. The immunomudulatory effects, the established melanotropic action and the recently identified cytoprotective activity of a-melanocyte-stimulating on UVB-induced apoptosis and DNA damage may be part of the body's host defence in which this neuropeptide--typically induced by proinflammatory signals--maintains tissue homeostasis and prevents genotoxicity during inflammatory responses.

Animals↗

Crucial role of the melanocortin receptor MC1R in experimental colitis.

BACKGROUND AND AIMS: alpha-Melanocyte stimulating hormone (alpha MSH) is known to exert anti-inflammatory effects, for example in murine DSS (dextran sodium sulphate induced) colitis. The anti-inflammatory functions of alpha MSH are mediated by the melanocortin1-receptor (MC1R) in an autoregulatory loop. The aim of this study was therefore to determine whether a breakdown of the alpha MSH-MC1R pathway leads to worsening of disease. METHODS: Experimental colitis was induced in mice with a frameshift mutation in the MC1R gene (MC1Re/e), C57BL/6 wild type mice, and MC1Re/e-C57BL/6 bone marrow chimeras. The course of inflammation was monitored by weight loss, histological changes in the colon, and myeloperoxidase activity. In addition, MC1R expression was analysed in intestinal epithelial cells. RESULTS: While the colon of untreated MC1Re/e appeared normal, the course of DSS-colitis in MC1Re/e mice was dramatically aggravated, with a significantly higher weight loss and marked histological changes compared to C57BL/6WT. The inflammation eventually led to death in all MC1Re/e, while all C57BL/6WT survived. Similar observations were detected in a transmissible murine colitis model induced by Citrobacter rodentium. Infected MC1Re/e showed delayed clearance of infection. To determine whether missing haematopoietic cell expressed MC1R was responsible, DSS colitis was induced in MC1Re/e-C57BL/6 bone marrow chimeras. MC1Re/e mice receiving MC1R+ bone marrow showed a similar course of inflammation to non-transplanted MC1Re/e. Likewise, transplantation of MC1R bone marrow into C57BL/6WT mice did not lead to any worsening of disease. CONCLUSIONS: This is the first study to show a functional role of MC1R in intestinal inflammation. The data suggest a pivotal role of non-haematopoietic cell expressed MC1R in the host's response to pathogenic stimuli.

Animals↗

[Topical cannabinoid agonists. An effective new possibility for treating chronic pruritus].

BACKGROUND: Chronic, therapy-resistant pruritus often fails to respond to standard measures so new therapeutic approaches are needed. Recently, the expression of cannabinoid receptors on cutaneous sensory nerve fibers was described, so cannabinoid agonists seem a rational therapeutic option for pruritus. PATIENTS: In an open application observation 22 patients with prurigo, lichen simplex and pruritus applied an emollient cream containing N-palmitoyl ethanolamine (PEA). RESULTS: In 14/22 patients a good antipruritic effect could be documented. The average reduction in itch was 86.4%. The therapy was well-tolerated by all patients; neither burning burn nor contact dermatitis was observed. CONCLUSIONS: Topical cannabinoid agonists represent an new effective and well-tolerated therapy for refractory itching of various origins. Creams with a higher concentration may be even more effective with broader indications.

Administration, Topical↗

Psychological factors in prurigo nodularis in comparison with psoriasis vulgaris: results of a case-control study.

BACKGROUND: It has been suggested that psychological factors such as repressing anger and altruistic interpersonal behaviour may play a role in the aetiology of chronic itching in prurigo nodularis (PN). Whether these issues are specific for PN or are also common in other chronic skin diseases, e.g. psoriasis, has not been investigated until now. OBJECTIVES: To investigate psychosomatic problem areas and psychiatric comorbidity in patients with PN in comparison with patients with psoriasis. METHODS: Ninety-four patients with PN and 91 patients with psoriasis were administered the Hospital Anxiety and Depression Scale, Toronto Alexithymia Scale, State-Trait Anger Expression Inventory, Inventory of Interpersonal Problems, Screening for Somatoform Disorders and the Whiteley Index for hypochondriasis. RESULTS: After Bonferroni post hoc adjustment, the metrical scales demonstrated no significant differences between patients with PN and those with psoriasis. There was only a tendency to less 'anger-out' and to less autocratic/dominant and more insecure/submissive behaviour in the patients with PN. Patients with PN were, in general, comparable with those with psoriasis with regard to alexithymia, somatization symptoms, hypochondriasis, anxiety and depression, with 18% cases of anxiety and 22% cases of depression. CONCLUSIONS: The hypotheses formulated in the literature on the specific aetiology of PN could not be proven for the majority of patients with PN in our study. Concerning their psychopathology, patients with PN were comparable with those with psoriasis. Therefore the clinical management of PN should include psychosomatic assessment.

Adult↗

Update on the use of ciclosporin in immune-mediated dermatoses.

Immune-mediated dermatoses, such as psoriasis and atopic dermatitis, affect a significant proportion of the population. Although most cases are not life threatening, these diseases can have a profound effect on the sufferer's quality of life and that of their family. Systemic therapy, such as ciclosporin, is often indicated for severe or recalcitrant disease. The efficacy of ciclosporin in the treatment of psoriasis and atopic dermatitis has been established and clinical data also demonstrate its efficacy in treating less common but equally challenging conditions such as pyoderma gangrenosum, lichen planus, autoimmune bullous disease, recalcitrant chronic idiopathic urticaria and chronic dermatitis of the hands and feet. The risk of potential adverse events associated with ciclosporin is greatly reduced if current treatment and monitoring guidelines are followed.

Arthritis, Psoriatic↗

Psychosomatic cofactors and psychiatric comorbidity in patients with chronic itch.

BACKGROUND: While psychosomatic factors may be involved in eliciting as well as coping with chronic itch, psychiatric comorbidity often goes unrecognized in dermatological patients. AIM: To record psychiatric illness, psychiatric and psychotherapeutic pretreatment, and psychotherapy indication in dermatology inpatients with pruritus. METHODS: A consecutive sample of 109 dermatology inpatients with the symptom of pruritus were examined by interviews with consecutive ratings by experts (using psychiatric ICD-10 diagnoses, the Global Assessment of Functioning Scale and the Impairment Score) and self-assessment using the the Eppendorf Itch Questionnaire. RESULTS: In > 70% of the pruritus patients, 1-6 psychiatric diagnoses could be demonstrated. In > 60%, psychotherapeutic or psychiatric treatment was recommended. In contrast, almost 90% of the patients had had no previous psychotherapeutic experience. CONCLUSION: As psychiatric comorbidity in dermatology inpatients suffering from chronic itch is high, dermatology departments should aim for an improvement of their psychosomatic consultation and liaison services.

Adult↗

Diagnosis and treatment of atopic dermatitis in children and adults: European Academy of Allergology and Clinical Immunology/American Academy of Allergy, Asthma and Immunology/PRACTALL Consensus Report.

There are remarkable differences in the diagnostic and therapeutic management of atopic dermatitis practiced by dermatologists and pediatricians in different countries. Therefore, the European Academy of Allergy and Clinical Immunology and the American Academy of Allergy, Asthma and Immunology nominated expert teams who were given the task of finding a consensus to serve as a guideline for clinical practice in Europe as well as in North America. The consensus report is part of the PRACTALL initiative, which is endorsed by both academies.

Adult↗

[Pruritus in pregnancy. A frequent diagnostic and therapeutic challenge].

Pruritus is the leading dermatological symptom during pregnancy. Besides preexisting or acquired dermatoses, there are a number of pregnancy-specific dermatological diseases such as PEP (polymorphic eruption of pregnancy, previously named PUPPP), pemphigoid (herpes) gestationis, and pruritus gravidarum that are accompanied by severe itching and scratching. Because of potential effects on the fetus, the treatment of pruritus in pregnancy requires prudent consideration. The use of topical and systemic treatments depends on the underlying aetiology of pruritus and the stage and status of the skin. In general, emollients, topical anti-pruritics and topical corticosteroids appear to be the safest options for localised forms of pruritus in pregnancy whereas systemic treatments and/or UV phototherapy are adequate for generalized pruritus. Systemic corticosteroids and a restricted number of antihistamines may be administered in severe cases. This paper highlights the major aetiologies of pruritus during pregnancy and points out the cornerstones of antipruritic therapy in recognition of our own clinical experiences and the current literature.

Administration, Topical↗

Confetti-like lesions with hyperkeratosis: a novel ultraviolet-induced hypomelanotic disorder?

Confetti leucoderma can occur in a variety of unrelated skin disorders and is often a diagnostic challenge. We describe a 33-year-old man with a history of mycosis fungoides and vitiligo. He developed disseminated 1-2-mm round-shaped leucodermic lesions 6 months after psoralen photochemotherapy and 12 months after systemic therapy with interferon. The skin lesions had a discrete hyperkeratotic scale. Multiple skin biopsies and immunohistochemical studies showed lamellar orthohyperkeratosis, papillomatosis, hypomelanotic keratinocytes but a normal number of melanocytes. Langerhans cells, in contrast, were reduced in lesional skin. Electron microscopy disclosed only a few type I and II melanosomes in lesional melanocytes, while keratinocytes were largely devoid of any melanosomes. This constellation of clinical, immunohistochemical and ultrastructural findings has not been reported before and distinguishes our case from leucoderma punctatum, idiopathic guttate hypomelanosis and disseminated hypopigmented keratoses. We suggest that the skin lesions observed in our patient represent an unusual response to ultraviolet damage to melanocytes followed by reactive epidermal hyperkeratosis.

Adult↗

Case mix measures and diagnosis-related groups: opportunities and threats for inpatient dermatology.

OBJECTIVE: The changing healthcare environment world-wide is leading to extensive use of per case payment systems based on diagnosis-related groups (DRG). The aim of this study was to examine the impact of application of different DRG systems used in the German healthcare system. METHODS: We retrospectively analysed 2334 clinical data sets of inpatients discharged from an academic dermatological inpatient unit in 2003. Data were regarded as providing high coding quality in compliance with the diagnosis and procedure classifications as well as coding standards. The application of the Australian AR-DRG version 4.1, the German G-DRG version 1.0, and the German G-DRG version 2004 was considered in detail. To evaluate more specific aspects, data were broken down into 11 groups based on the principle diagnosis. MAIN OUTCOME MEASURE: DRG cost weights and case mix index were used to compare coverage of inpatient dermatological services. Economic impacts were illustrated by case mix volumes and calculation of DRG payments. RESULTS: Case mix index results and the pending prospective revenues vary tremendously from the application of one or another of the DRG systems. The G-DRG version 2004 provides increased levels of case mix index that encourages, in particular, medical dermatology. CONCLUSIONS: The AR-DRG version 4.1 and the first German DRG version 1.0 appear to be less suitable to adequately cover inpatient dermatology. The G-DRG version 2004 has been greatly improved, probably due to proceeding calculation standards and DRG adjustments. The future of inpatient dermatology is subject to appropriate depiction of well-established treatment standards.

Case Management↗

Agonists of proteinase-activated receptor-2 modulate human neutrophil cytokine secretion, expression of cell adhesion molecules, and migration within 3-D collagen lattices.

Proteinase-activated receptor-2 (PAR2) belongs to a novel subfamily of G-protein-coupled receptors with seven-transmembrane domains. PAR2 can be activated by serine proteases such as trypsin, mast cell tryptase, and allergic or bacterial proteases. This receptor is expressed by various cells and seems to be crucially involved during inflammation and the immune response. As previously reported, human neutrophils express functional PAR2. However, the precise physiological role of PAR2 on human neutrophils and its implication in human diseases remain unclear. We demonstrate that PAR2 agonist-stimulated human neutrophils show significantly enhanced migration in 3-D collagen lattices. PAR2 agonist stimulation also induced down-regulation of L-selectin display and up-regulation of membrane-activated complex-1 very late antigen-4 integrin expression on the neutrophil cell surface. Moreover, PAR2 stimulation results in an increased secretion of the cytokines interleukin (IL)-1beta, IL-8, and IL-6 by human neutrophils. These data indicate that PAR2 plays an important role in human neutrophil activation and may affect key neutrophil functions by regulating cell motility in the extracellular matrix, selectin shedding, and up-regulation of integrin expression and by stimulating the secretion of inflammatory mediators. Thus, PAR2 may represent a potential therapeutic target for the treatment of diseases involving activated neutrophils.

Calcium↗

[Imiquimod, pegylated interferon-alpha-2b and interleukin-2 in the treatment of cutaneous melanoma metastases].

The immune system plays an important role in the defense against malignant melanoma. Interferon-alpha (IFN-alpha) and interleukin-2 (IL-2) are therapeutically used for unspecific stimulation of the immune system. After intralesional injections of these cytokines into cutaneous melanoma metastases, regression has been observed. In view of its immunomodulating effects, imiquimod appears as an additional promising therapeutic option for treatment of malignant tumors. In a case report, we present combined therapy with intralesional IL-2, pegylated IFN-alpha-2b and topical imiquimod 5% cream for disseminated cutaneous metastatic malignant melanoma stage IIIa. This therapy achieved an almost complete remission. In a treatment period of eight months, side effects remained tolerable. Histologically, both fibrosis and inflammation were found in the regressing lesions. After the end of therapy, no disease progression occurred during 11 months follow-up.

Adjuvants, Immunologic↗

[Alpha-melanocyte-stimulating hormone. Its current significance for dermatology].

Alpha-melanocyte-stimulating hormone (alpha-MSH) is a tridecapeptide that was originally characterized as a neuropeptide derived from the pituitary gland. alpha-MSH is synthesized from pro-opiomelanocortin (POMC) by the action of specific prohormone convertases which cleave POMC into alpha-MSH, adrenocorticotropin and beta-endorphin. The various effects of alpha-MSH are mediated via melanocortin receptors. The skin as well as the majority of cutaneous cell types express POMC. Proinflammatory stimuli such as ultraviolet (UV) light induce POMC expression and alpha-MSH secretion. Receptors for alpha-MSH are not only expressed by melanocytes, where they mediate melanogenesis and proliferation, but also by virtually every cutaneous cell type. Accordingly, alpha-MSH elicits a plethora of biological actions in these cell types including immunomodulation, protection from oxidative stress and UV-induced apoptosis, modulation of secretory epithelial function and regulation of extracellular matrix composition. These actions may be exploited in future by using super potent and truncated MSH peptides for the treatment of various skin disorders including inflammatory dermatoses.

Adjuvants, Immunologic↗

[Ambulatory procedures to replace inpatient care. Background and applications].

Since January 2004, German hospitals and specialists in private practice have equal rights to provide and to charge for ambulatory surgeries according to paragraph 115b, 5th Code of Social Law. The current agreement between the German self-governing bodies replaces the existing contracts from 1993. In contrast to the previous version, the revised catalogue contains additional non-operative procedures. Some procedures may be provided either in an ambulatory or inpatient setting. However, for the hospitals it is of particular importance that some specified procedures should be performed on an ambulatory basis. If these particular services are delivered in an inpatient setting at least one stipulated criteria of exception has to be fulfilled. From the perspective of dermatology, not only opportunities but also obligations for ambulatory care arise from the new conditions. The critical facts and aspects with special relevance to dermatology are reviewed in detail.

Ambulatory Surgical Procedures↗