IL-31 expression by inflammatory cells is preferentially elevated in atopic dermatitis

Interleukin-31 (IL-31) is a recently discovered cytokine expressed in many human tissues, and predominantly by activated CD4+ T cells. IL-31 signals through a heterodimeric receptor consisting of IL-31 receptor alpha (IL-31RA) and oncostatin M receptor beta (OSMR). Earlier studies have shown involvement of IL-31 and its receptor components IL-31RA and OSMR in atopic dermatitis, pruritus and Th2-weighted inflammation at the mRNA level. The aim of this study was to investigate IL-31 protein expression in skin of such conditions. Immunohisto-chemical staining for IL-31, IL-31RA and OSMR was performed in formalin-fixed paraffin-embedded biopsy specimens. IL-31 expression was increased in the inflammatory infiltrates from skin biopsies taken from subjects with atopic dermatitis, compared with controls (p ≤ 0.05). IL-31, IL-31RA and OSMR protein immunoreactivity was not increased in biopsies from subjects with other Th2-weighted and pruritic skin diseases. Our results confirm, at the protein level, the relationship between IL-31 expression and atopic dermatitis. Our results do not support a general relationship between expression of IL-31/IL-31R and pruritic or Th2-mediated diseases

A chemically modified antibody mediates complete eradication of tumours by selective disruption of tumour blood vessels

These results reinforce the concept that vascular shutdown can induce a curative avalanche of tumour cell death. Immuno-photodynamic therapy may be particularly indicated for squamous cell carcinoma of the skin, which we show to be strongly positive for markers of angiogenesis

Immune phenotype of peripheral blood cells and skin squamous cell carcinoma in organ transplant recipients

Evaluation of: Carroll RP, Segundo DS, Hollowood K et al. Immune phenotype predicts risk for posttransplantation squamous cell carcinoma. J. Am. Soc. Nephrol. 21, 713-722 (2010). Squamous cell carcinoma (SCC) of the skin is a common tumor in Caucasians, occurring on sun-damaged skin. The carcinogenesis of SCC is multifactorial and the most important risk factor is UV radiation. Interestingly, SCC is the most frequent malignancy following organ transplantation, with a 60-100-fold increased risk compared with the general population. Carroll et al. recently identified more than 35 FOXP3+ cells per microl and less than 100 natural killer cells per microl in peripheral blood and previous SCC as risk factors for SCC in renal transplant recipients. The ratio of CD8/FOXP3 cells was significantly lower in the microenvironment of SCC from kidney transplant recipients compared with immunocompetent patients. These findings provide hitherto unknown details about the potential influence of immunomodulation by drugs on the development of SCC in kidney transplant recipients. While this study population may not relate to all kidney transplant recipients, particularly those on other immunosuppressive regimens, Carroll et al. provide us with a tool to aid recognition of patients at a higher risk for SCC. Further studies will help to translate these findings into potentially useful tools for the dermatological management of kidney transplant recipients

Prevalence of Merkel cell polyomavirus among Swiss Merkel cell carcinoma patients

We detected viral DNA in 20 out of 30 cases of MCC and in 0 out of 19 control samples. The presence of viral DNA in 66.6% of our MCC tissue specimens confirms the high prevalence of MCPyV in MCC patients described in American, German, French and Hungarian patient collections

Multifactorial ERβ and NOTCH1 control of squamous differentiation and cancer.

Downmodulation or loss-of-function mutations of the gene encoding NOTCH1 are associated with dysfunctional squamous cell differentiation and development of squamous cell carcinoma (SCC) in skin and internal organs. While NOTCH1 receptor activation has been well characterized, little is known about how NOTCH1 gene transcription is regulated. Using bioinformatics and functional screening approaches, we identified several regulators of the NOTCH1 gene in keratinocytes, with the transcription factors DLX5 and EGR3 and estrogen receptor β (ERβ) directly controlling its expression in differentiation. DLX5 and ERG3 are required for RNA polymerase II (PolII) recruitment to the NOTCH1 locus, while ERβ controls NOTCH1 transcription through RNA PolII pause release. Expression of several identified NOTCH1 regulators, including ERβ, is frequently compromised in skin, head and neck, and lung SCCs and SCC-derived cell lines. Furthermore, a keratinocyte ERβ-dependent program of gene expression is subverted in SCCs from various body sites, and there are consistent differences in mutation and gene-expression signatures of head and neck and lung SCCs in female versus male patients. Experimentally increased ERβ expression or treatment with ERβ agonists inhibited proliferation of SCC cells and promoted NOTCH1 expression and squamous differentiation both in vitro and in mouse xenotransplants. Our data identify a link between transcriptional control of NOTCH1 expression and the estrogen response in keratinocytes, with implications for differentiation therapy of squamous cancer

Restless-Legs-Syndrom

SummaryRestless legs syndrome (RLS) is characterised by an uncontrollable urge to move, in particular the lower limbs, often accompanied by discomfort or a painful sensation that occurs typically at night. It is categorized under the ICD-Classification of extrapyramidal and movement disorders. As patients often suffer from insomnia due to the involuntary nocturnal leg movements and irritable sensations in the legs, RLS is also classified as a sleep-related movement disorder. The incidence of a mild form of RLS is frequent, although it often remains undiagnosed.After the exclusion of other diseases by differential diagnosis, RLS is diagnosed on the basis of a clinical test administering a single dose of levodopa. There are two forms of RLS: idiopathic and secondary. The secondary form is encountered in an astonishing number of diseases, including renal insufficiency, diabetes, chronic obstructive pulmonary disease (COPD) and iron deficiency. The treatment of RLS is complex and the benefits and risks of pharmacotherapy should be considered carefully. Non-ergoline dopamine agonists (e.g. ropinirole, pramipexole) are the first-line treatment in severe cases of RLS. Transdermal rotigotine is also a promising treatment option. Opioids in combination with naloxone are recommended for patients suffering from severe pain. In mild cases of RLS, patients benefit from a balanced lifestyle with gentle physical activity and avoiding the excessive consumption of caffeine or alcohol.</jats:p

Komplexes regionales Schmerzsyndrom (CRPS)

Einleitung: Das komplexe regionale Schmerzsyndrom (CRPS) ist eine relativ seltene, jedoch für die Betroffenen äußerst gravierende Erkrankung, welche meist distal einer Extremitätenverletzung auftritt. Die klinischen Symptome sowie die Schmerzen stehen in keinem Verhältnis zum auslösenden Ereignis. Bei etwa 10% der Patienten liegt gar kein auslösendes Ereignis vor. Bei ungefähr der Hälfte der Patienten führt CRPS zu dauerhafter Arbeitsunfähigkeit und hohen Behandlungs- und Folgekosten. Klinik: Es werden zwei Formen unterschieden. Beim CRPS 1 lässt sich keine Nervenläsion nachweisen, wohingegen es beim CRPS 2 zu einer Verletzung eines Nerven oder Nervenhauptstamms gekommen ist. Im klinischen Verlauf gibt es jedoch keinen Unterschied zwischen den beiden Formen. In ca. 90 % aller Fälle handelt es sich um ein CRPS 1, früher als „Morbus Sudeck“ bekannt. Das Leitsymptom sind Schmerzen. Zudem können auch trophische Störungen wie Schwelllungen, lokale Verfärbungen der Haut oder asymmetrische Hauttemperaturen auftreten. Häufig finden sich auch eine eingeschränkte Beweglichkeit und Funktionseinbuße der betroffenen Extremität, welche sehr schwer zu therapieren sind. Diagnostik: Initial kann die Unterscheidung eines CRPS von einem normalen posttraumatischen Verlauf schwierig sein. Im weiteren Verlauf stehen die gravierenden Symptome in keinem Verhältnis mehr zum auslösenden Ereignis. Die Diagnose eines CRPS wird primär klinisch gestellt. Die Budapest-Kriterien helfen, die Diagnose zu sichern. Therapie: Eine frühe und interdisziplinäre Rehabilitation ist zentral in der Therapie des CRPS. Ergo- und physiotherapeutische Maßnahmen werden ergänzt mit einer guten medikamentösen Schmerzeinstellung sowie gegebenenfalls auch psychologischer Unterstützung. Medikamentös kommt das analgetische Stufenschema der WHO zum Einsatz, bei starken Hyperalgesien zeigte Methadon gute Erfolge, bei therapieresistenten Schmerzen auch Gabapentin oder Pregabalin. Biphosphonate zeigten einen guten analgetischen Effekt, insbesondere bei nachgewiesenen ossären Läsionen. Die chronischen Ödeme und Entzündungen können einen vorübergehenden Einsatz von Steroiden erfordern. Weiter gilt es, Folgeschäden wie Osteoporose zu verhindern. Patienten, bei welchen der Verdacht auf ein CRPS geäußert wird, sollten durch ein multidisziplinäres Behandlungsteam mit möglicher großer Erfahrung in der Betreuung dieses Krankheitsbildes überwiesen werden. Ein Arzt sollte die Betreuung des Patienten koordinieren. Je früher die Behandlung begonnen wird, desto besser ist die Prognose

Wundschmerz

SummaryIn acute and chronic wounds, pain represents a common and central medical problem. Wound pain can be caused by multiple factors, such as macro- or microvascular as well as inflammatory processes.The basic concept of pain management is based on the WHO pain ladder. Often this concept of pain therapy remains insufficient. Apart from the conventionally used anal-getics, there are not yet established guidelines for the use of alternative substances.Ultimately the adequate wound pain therapy must be adjusted to each patient and his comorbidities.</jats:p