[|In view of the recent publication by Zenz et al. (Psoriasis-like skin
disease and arthritis caused by inducible epidermal deletion of Jun
proteins. Nature. 2005 Sep 15;437(7057):369-75.) the abrogation of
JunB/activator protein 1 (AP-1) in keratinocytes may trigger
chemokine/cytokine expression, which recruits neutrophils and
macrophages to the epidermis thereby contributing to the phenotypic
changes observed in psoriasis. These data do support the hypothesis
that epidermal alterations are sufficient to initiate both skin lesions
and arthritis in psoriasis.|auteur192]
[|Here I agree – psoriasis is maintained by T cells!|auteur195]
[|While the immunopathogenesis of psoriasis is driving new drug development with antigen presenting cells (APC)-T-cell interaction with a host of cytokines, particularly TNF-? and IL 12/23 implicated, what I believe the next focus of our research needs to be is antigen presentation. This is well-discussed in #6, ie activation of certain subpopulations of T lymphocytes. In addition to antigens, super antigens, or ultra antigens mentioned, I do believe the role of drugs in triggering psoriasis, ie beta-blockers, lithium, could be proved to be a fruitful line of investigation. Certainly, laboratories exist in the world, ie here in Dallas under the supervision of Jacques Banchereau, PhD, a Frenchman and world leader in antigen presenting cells, which could pave the way for better understanding of this complex disease.|auteur215]
Whether a basic defect does exist at the level of skin cells and possibly fibroblasts, it has been perfectly demonstrated that the T lymphocytes play a major role in maintaining the disease (photo 1). This is based on three main lines of argument:
- triggering of psoriasis in a non-psoriatic person after bone-marrow grafting taken from a subject suffering from psoriasis;
- triggering of a clinical and histological psoriatic lesion after grafting on the immuno-tolerant mouse of a non involved psoriatic skin, followed by an injection of activated psoriatic T lymphocytes;
- the efficacy of numerous immunosuppressive drugs inhibiting T lymphocyte activation in psoriasis treatment. This argument is more flimsy because, although it is true that cyclosporine is remarkably effective, other immunosuppressants are less efficient. Moreover, cyclosporine has various cellular targets and, in addition to its action on T lymphocytes, it might conceivably be capable of inhibiting the secretion of certain cytokines by the skin cells. Its action on fibroblast activation has not been specifically studied.
The field of immunological research remains thus wide open in the sphere of psoriasis. Research is currently expanding to identify, in functional terms, the T lymphocytes migrating into a psoriasis plaque. There is a need to identify the molecules attracting and activating these lymphocytes in the skin, to identify the cytokines released by these lymphocytes and to understand how they maintain proliferation and epidermal inflammation. In particular, there is a need to research the antigens, superantigens and/or autoantigens that might be initiating this torrent of activation. Amongst these antigens, research is currently turning towards bacterial and viral antigens. Part of the HPV 5 genome has been found in many psoriatic lesions. Moreover, the incidence of psoriasis is higher in HIV-positive subjects. Similarly, antigens of streptococcal and staphylococcal origin might shoulder some responsibility for the lymphocytic activation of the psoriatic plaque.
Whatever the interest in such research might be, it should not end in some conceptual abuse, the most frequent being to classify psoriasis among the autoimmune disorders, when it is nothing like it. Immunosuppressants are not effective in all the patients. This immunological research should not slow down research on the anomalies present in the structural cells of the skin.
One of the most interesting fields of research at the moment relates to the study of innate defence mechanisms. These mechanisms are expressed not only by adaptive immunity cells but also by keratinocytes, macrophages and neutrophils. They may even be more important for psoriasis than adaptive immunity.
A different research pathway consists of studying the interactions between lymphocytes and skin cells. Recently, we have observed that psoriatic fibroblasts activate CD4 lymphocytes more effectively than normal fibroblasts, and that CD4 lymphocytes stemming from psoriatics activate fibroblasts more effectively than non-psoriatic CD4 lymphocytes.
Therefore, the most likely scenario is that CD4 lymphocytes accumulated in the dermis after any cutaneous aggression powerfully activate psoriatic fibroblasts and these activated fibroblasts activate the CD4 lymphocytes in return. This self-activating loop ends in the release of cytokines responsible for epidermal proliferation. Furthermore, the same hyperreactivity is likely to be expressed at keratinocyte level. All genetic and environmental events resulting in an increase of the pro-inflammatory cytokine production by the epidermis and by the inflammatory cells would thus be capable of triggering the appearance of psoriasis. These events vary and some of them are beginning to be identified: release of neurotransmitters at times of stress, presence of viral antigens, existence of varied genotypes leading, via the activation of various transduction pathways, to a cytokinic response heightened in response to stress. If this hypothesis is confirmed, psoriasis is certainly a syndrome, and a variety of different physiopathological pathways can result in this same clinical and histological expression.
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Recent publications on Psoriasis and Atopic Dermatitis
JAK-inhibitors in dermatology: current evidence and future applications.
J Dermatolog Treat. 2019 Nov , 30, (7):648-658.
The Janus kinase (JAK) and signal transducer and activator of transcription (STAT) pathway is a ubiquitous intracellular signaling network. Selective JAK-inhibitors have anti-inflammatory properties and have been approved in many countries for the treatment of rheumatoid arthritis (tofacitinib, baricitinib) and myelofibrosis or polycythemia vera (ruxolitinib). The aim of the publication was to summarize and critically analyze the efficacy and safety of JAK-inhibitors in skin diseases, such (...)see on pubmed
Patient preferences for attributes of topical anti-psoriatic medicines.
J Dermatolog Treat. 2019 Nov , 30, (7):659-663.
Patient preferences should be considered when prescribing topical treatments to drive up adherence and improve clinical outcomes. The aim of this work was to identify the most important attributes of topical medicines for psoriasis treatment in the patients' view, and explore the sociodemographic and clinical determinants of these preferences. A questionnaire for the evaluation of the relevancy given to specific attributes of topical medicines used for psoriasis treatment was developed (...)see on pubmed
Salidroside inhibits MAPK, NF-κB, and STAT3 pathways in psoriasis-associated oxidative stress via SIRT1 activation.
Redox Rep.. 2019 Dec , 24, (1):70-74.
To unveil the role of SIRT1 in limiting oxidative stress in psoriasis and to further discuss the therapeutic prospects of salidroside in psoriasis. Literature from 2002 to 2019 was searched with "psoriasis", "oxidative stress", "SIRT1", "salidroside" as the key words. Then, Oxidative stress in psoriasis and the role of SIRT1 were summarized and the potential role of salidroside in the disease was speculated. Oxidative stress might contribute to the pathogenesis of psoriasis. High levels (...)see on pubmed
A case of infective endocarditis associated with atopic dermatitis perioperatively treated with dupilumab.
J Dermatolog Treat. 2019 Nov , 30, (7):674-676.
Several case reports and reviews support a relationship between atopic dermatitis (AD) and infective endocarditis (IE). Here, we present a case of severe AD suspected of causing IE. A 21-year-old man with severe AD was admitted to our hospital due to unidentified fever, syncope, and headache. He was diagnosed with IE with cerebral embolism and mitral regurgitation. Before elective cardiac surgery, he was subcutaneously administered dupilumab for 2 months to control AD. Dupilumab improved (...)see on pubmed
Effect of cinnamamides on atopic dermatitis through regulation of IL-4 in CD4 cells.
J Enzyme Inhib Med Chem. 2019 Dec , 34, (1):613-619.
This study aimed to evaluate the effects of cinnamamides on atopic dermatitis (AD) and the mechanisms underlying these effects. To this end, the actions of two cinnamamides, (E)-3-(4-hydroxyphenyl)-N-phenylethyl acrylamide (NCT) and N-trans-coumaroyltyramine (NCPA), were determined on AD by orally administering them to mice. Oral administration of the cinnamamides ameliorated the increase in epidermal and dermal thickness as well as mast cell infiltration. Cinnamamides suppressed serum (...)see on pubmed
Sublingual immunotherapy of atopic dermatitis in mite-sensitized patients: a multi-centre, randomized, double-blind, placebo-controlled study.
Artif Cells Nanomed Biotechnol. 2019 Dec , 47, (1):3540-3547.
Allergen-specific immunotherapy is widely used for allergic rhinitis and asthma treatment worldwide. This study explored the efficacy and safety of sublingual immunotherapy (SLIT) with the extracts of ( Drops) on house dust mites (HDM)-induced atopic dermatitis (AD). 239 patients with HDM-induced AD were recruited and exposure to a multi-centre, randomized, double-blind, and placebo-controlled clinical trials for 36 weeks, which were randomly divided into placebo and sublingual Drops (...)see on pubmed