Perceived stress in patients with inflammatory and non-inflammatory skin conditions. An observational controlled study among 255 Norwegian dermatological outpatients.

Background: Inflammation may increase stress, while stress may promote inflammation. Most dermatological conditions are chronic and inflammatory, while some, such as cancer, naevi and tumours are non-inflammatory, but may cause stress because of the fear of malignancy and the necessity for surgical and other invasive treatments. Stress among patients with skin diseases is little explored. Objectives: To assess perceived stress in patients with inflammatory and non-inflammatory skin conditions compared to healthy controls. Methods: Observational cross-sectional study. Consecutive outpatients (N = 255) visiting the Department of Dermatology, Stavanger University Hospital, Norway and 148 skin-healthy controls contributed by answering questionnaires on sociodemographics, stressful life events, economic difficulties, self-rated health and perceived stress. The validated Perceived Stress Scale10 was used to evaluate stress. A dermatologist examined patients and registered their diagnoses and comorbidities. Controls included in this study were not examined by a dermatologist and self-reported their comorbidities. Results: Patients with an inflammatory skin disease or psoriasis have a tripled risk of reporting moderate to high stress compared with controls when adjusted for relevant confounders, including having experienced a stressful life event recently or having a comorbidity. Patients with a purely non-inflammatory skin disease perceived stress no differently than controls. Conclusion: Patients with inflammatory skin disease perceived higher stress than controls and patients with non-inflammatory skin conditions. Dermatologists may play a role in awareness of the importance of stress in skin disease.

Modelling pulmonary microthrombosis coupled to metastasis: distinct effects of thrombogenesis on tumorigenesis.

Thrombosis can cause localized ischemia and tissue hypoxia, and both of these are linked to cancer metastasis. Vascular micro-occlusion can occur as a result of arrest of circulating tumour cells in small capillaries, giving rise to microthrombotic events that affect flow, creating localized hypoxic regions. To better understand the association between metastasis and thrombotic events, we generated an experimental strategy whereby we modelled the effect of microvascular occlusion in metastatic efficiency by using inert microbeads to obstruct lung microvasculature before, during and after intravenous tumour cell injection. We found that controlled induction of a specific number of these microthrombotic insults in the lungs caused an increase in expression of the hypoxia-inducible transcription factors (HIFs), a pro-angiogenic and pro-tumorigenic environment, as well as an increase in myeloid cell infiltration. Induction of pulmonary microthrombosis prior to introduction of tumour cells to the lungs had no effect on tumorigenic success, but thrombosis at the time of tumour cell seeding increased number and size of tumours in the lung, and this effect was strikingly more pronounced when the micro-occlusion occurred on the day following introduction of tumour cells. The tumorigenic effect of microbead treatment was seen even when thrombosis was induced five days after tumour cell injection. We also found positive correlations between thrombotic factors and expression of HIF2α in human tumours. The model system described here demonstrates the importance of thrombotic insult in metastatic success and can be used to improve understanding of thrombosis-associated tumorigenesis and its treatment.