Atopic dermatitis (AD) is a common and chronic, pruritic inflammatory skin condition that can affect all age groups. This evidence-based guideline addresses important clinical questions that arise in its management. In this second of four sections, treatment of AD with non-pharmacological interventions and pharmacological topical therapies are reviewed. Where possible, suggestions on dosing and monitoring are given based on available evidence.
Multiple sclerosis (MS) is a T cell-mediated autoimmune demyelinating disease, which may be initiated by a virus infection. Theiler's murine encephalomyelitis virus (TMEV), a natural mouse pathogen, is a picornavirus that induces a chronic, CD4+ T cell-mediated demyelinating disease with a clinical course and histopathology similar to that of chronic progressive MS (ref. 3). Demyelination in TMEV-infected mice is initiated by a mononuclear inflammatory response mediated by virus-specific CD4+ T cells targeting virus, which chronically persists in the CNS (ref. 4-6). We show that beginning 3-4 weeks after disease onset, T-cell responses to multiple myelin autoepitopes arise in an ordered progression and may play a pathologic role in chronic disease. Kinetic and functional studies show that T-cell responses to the immunodominant myelin proteolipid protein epitope (PLP139-151) did not arise because of cross-reactivity between TMEV and self epitopes (that is, molecular mimicry), but because of de novo priming of self-reactive T cells to sequestered autoantigens released secondary to virus-specific T cell-mediated demyelination (that is, epitope spreading). Epitope spreading is an important alternate mechanism to explain the etiology of virus-induced organ-specific autoimmune diseases.
Atopic dermatitis (AD) is a chronic, pruritic inflammatory dermatosis that affects up to 25% of children and 2–3% of adults. This guideline addresses important clinical questions that arise in AD management and care, providing updated and expanded recommendations based on the available evidence. In this first of four sections, methods for diagnosis and monitoring of disease, outcomes measures for assessment and common clinical associations that affect patients with AD are discussed. Known risk factors for the development of disease are also reviewed.
The immunologic privilege of the central nervous system (CNS) makes it crucial that CNS resident cells be capable of responding rapidly to infection. Astrocytes have been reported to express Toll-like receptors (TLRs), hallmark pattern recognition receptors of the innate immune system, and respond to their ligation with cytokine production. Astrocytes have also been reported to respond to cytokines of the adaptive immune system with the induction of antigen presentation functions. Here we have compared the ability of TLR stimuli and the adaptive immune cytokines interferon-gamma (IFN-gamma) and tumor necrosis factor-alpha (TNF-alpha) to induce a variety of immunologic functions of astrocytes. We show that innate signals LPS- and poly I:C lead to stronger upregulation of TLRs and production of the cytokines IL-6 and TNF-alpha as well as innate immune effector molecules IFN-alpha4, IFN-beta, and iNOS compared with cytokine-stimulated astrocytes. Both innate stimulation and adaptive stimulation induce similar expression of the chemokines CCL2, CCL3, and CCL5, as well as similar enhancement of adhesion molecule ICAM-1 and VCAM-1 expression by astrocytes. Stimulation with adaptive immune cytokines, however, was unique in its ability to induce upregulation of MHC II and the functional ability of astrocytes to activate CD4(+) T cells. These results indicate potentially important and changing roles for astrocytes during the progression of CNS infection.
Since the publication of the last US national burden of skin disease report in 2006, there have been substantial changes in the practice of dermatology and the US health care system. These include the development of new treatment modalities, marked increases in the cost of medications, increasingly complex payer rules and regulations, and an aging of the US population. Recognizing the need for up-to-date data to inform researchers, policy makers, public stakeholders, and health care providers about the impact of skin disease on patients and US society, the American Academy of Dermatology produced a new national burden of skin disease report. Using 2013 claims data from private and governmental insurance providers, this report analyzed the prevalence, cost, and mortality attributable to 24 skin disease categories in the US population. In this first of 3 articles, the presented data demonstrate that nearly 85 million Americans were seen by a physician for at least 1 skin disease in 2013. This led to an estimated direct health care cost of $75 billion and an indirect lost opportunity cost of $11 billion. Further, mortality was noted in half of the 24 skin disease categories.
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