In 2002, the National Rosacea Society assembled an expert committee to develop the first standard classification of rosacea. This original classification was intended to be updated as scientific knowledge and clinical experience increased. Over the last 15 years, significant new insights into rosacea's pathogenesis and pathophysiology have emerged, and the disorder is now widely addressed in clinical practice. Growing knowledge of rosacea's pathophysiology has established that a consistent multivariate disease process underlies the various clinical manifestations of this disorder, and the clinical significance of each of these elements is increasing as more is understood. This review proposes an updated standard classification of rosacea that is based on phenotypes linked to our increased understanding of disease pathophysiology. This updated classification is intended to provide clearer parameters to conduct investigations, guide diagnosis, and improve treatment.

Several observations suggest interactions between the immune and nervous systems. Psoriasis and atopic dermatitis may worsen with anxiety and have been associated with anomalous neuropeptide regulation. Neurotransmitters affect lymphocyte function and lymphoid organs are innervated. Calcitonin gene-related peptide (CGRP) is a neuropeptide and vasodilator that modulates some macrophage functions, including antigen presentation in vitro. CGRP is associated with Langerhans cells (LC) in oesophageal mucosa, particularly during inflammation, is present in epidermal nerves and is associated with Merkel cells. We examined the ability of CGRP to modulate LC antigen-presenting function and asked if CGRP-containing nerves impinge on LC. We report here that CGRP-containing nerve fibres are intimately associated with LC in human epidermis and CGRP is found at the surface of some LC. In three functional assays CGRP inhibited LC antigen presentation. These findings indicate that CGRP may have immunomodulatory effects in vivo and suggest a locus of interaction between the nervous system and immunological function.

Despite clear exacerbation of several skin disorders by stress, the effect of psychologic or exertional stress on human skin has not been well studied. We investigated the effect of three different stressors, psychologic interview stress, sleep deprivation, and exercise, on several dermatologic measures: transepidermal water loss, recovery of skin barrier function after tape stripping, and stratum corneum water content (skin conductance). We simultaneously measured the effects of stress on plasma levels of several stress-response hormones and cytokines, natural killer cell activity, and absolute numbers of peripheral blood leukocytes. Twenty-five women participated in a laboratory psychologic interview stress, 11 women participated in one night of sleep deprivation, and 10 women participated in a 3 d exercise protocol. The interview stress caused a delay in the recovery of skin barrier function, as well as increases in plasma cortisol, norepinephrine, interleukin-1beta and interleukin-10, tumor necrosis factor-alpha, and an increase in circulating natural killer cell activity and natural killer cell number. Sleep deprivation also decreased skin barrier function recovery and increased plasma interleukin-1beta, tumor necrosis factor-alpha, and natural killer cell activity. The exercise stress did not affect skin barrier function recovery, but caused an increase in natural killer cell activity and circulating numbers of both cytolytic T lymphocytes and helper T cells. In addition, cytokine responses to the interview stress were inversely correlated with changes in barrier function recovery. These results suggest that acute psychosocial and sleep deprivation stress disrupts skin barrier function homeostasis in women, and that this disruption may be related to stress-induced changes in cytokine secretion.

Dendritic cells (DCs) are potent antigen-presenting cells that play a critical role in the initiation of antitumor immune responses. In this study, we show that genetic modifications of a murine epidermis-derived DC line and primary bone marrow–derived DCs to express a model antigen β-galactosidase (βgal) can be achieved through the use of a replication-deficient, recombinant adenovirus vector, and that the modified DCs are capable of eliciting antigen-specific, MHC-restricted CTL responses. Importantly, using a murine metastatic lung tumor model with syngeneic colon carcinoma cells expressing βgal, we show that immunization of mice with the genetically modified DC line or bone marrow DCs confers potent protection against a lethal tumor challenge, as well as suppression of preestablished tumors, resulting in a significant survival advantage. We conclude that genetic modification of DCs to express antigens that are also expressed in tumors can lead to antigen-specific, antitumor killer cells, with a concomitant resistance to tumor challenge and a decrease in the size of existing tumors.