Journal of Clinical and Aesthetic Dermatology

Updates on Psoriasis & Cutaneou Oncology

An evidence-based, peer-reviewed journal for practicing clinicians in the field of dermatology

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S22 P r o c e e D i n G s JCAD jOUrnAl Of ClInICAl And AEsthEtIC dErMAtOlOgy september 2017 • volume 10 • number 9 • supplement indeed, the pathogenic axes of certain cutaneous diseases are distinct and defned by a type of polar axis (table 5). CEllUlAr And MOlECUlAr PrOfIlIng Of MIld PsOrIAsIs Psoriasis occurs in all populations around the world, but frequencies vary. the disease is less prevalent in asia than in the united states, and in the united states it is more common in caucasians than african-americans. there are also diderent subtypes of psoriasis. 109,110 asian populations are more likely to develop small plaque psoriasis compared to severe psoriasis, which is more widespread in the West. in a study of 51 patients with biopsy-confrmed psoriasis, plaque size was measured (<2cm = small plaque) and disease severity assessed by Pasi. Genomic and histologic studies were done to defne psoriasis subtypes. a gene set variation analysis was conducted to determine which genes were expressed in the population. these results validated that asian small and intermediate psoriasis were phenotypes and shared a common psoriasis transcriptome and histology with Western psoriasis (psoriasis vulgaris). Disease progression was then evaluated. Psoriasis spreads by vertical growth and radial expansion. However, asian small plaque psoriasis revealed limited spreading but with great expression of proingammatory cytokines regulated by il-17a and il-17. 109 in Western psoriasis, il-17a- and il-17-mediated cytokines were lower, but Western patients had many more t-cells and dendritic cells in their psoriatic skin areas. Both groups had diminished presence of negative immune regulators (cD69 and fas), and both groups had incidences of arthritis and obesity, correlating with psoriasis severity. Based on this comparison, it seems that the dysregulation of t-cell expansion allows for the down-regulation of immune-negative regulators in large plaque psoriasis. 109 Psoriasis is a t-cell mediated condition and autoimmune disorder, but the mechanisms by which autoantigens trigger t-cells in psoriasis continue to be elucidated. 111 Dendritic cells (Dcs) stimulate autoimmune t-cells, and an antimicrobial peptide (aMP), specifcally ll37, is present at high levels in psoriatic lesions and has been implicated in this process. 112–115 a cationic peptide, ll37 may oder antimicrobial protection to the skin, and a recent study found that ll37 could be considered an autoantigen. ll37- specifc t-cells produce pathogenic cytokines, including il-17. this may be the frst example of an aMP that stimulates both the body's innate 112–114 and adaptive immune cells in the setting of autoimmune disease. 111 about two- thirds of patients with moderate-to-severe plaque psoriasis have cD4(+) and/or cD8(+) t- cells specifc for ll37. 111 the risk gene for psoriasis is Hla-c*0.6:02 on locus Psor1 (6p21.33). 115 it has been observed that epidermal cD8(+) cells must be present for skin psoriasis to develop. 116 Melanocytes have been identifed as targets of the psoriatic t-cell response. 116 Melanocytes are the only epidermal cells that express aDaMtsl5, an aDaMts-like protein that acts as a melanocytic autoantigen. aDaMtsl5 stimulation also induces cytokine, il-17a, and cD8(+) t-cells, but only in patients with psoriasis, which suggests it is a psoriatic autoantigen. 1 16 thus, il-17 directly or indirectly regulates autoantigens in psoriasis. the emerging hypotheses are that there are type 17 t-cell clones in psoriatic lesions, probably tissue-resident memory (trm) phenotypes. at some point, tolerance to self- antigens would be broken. it is expected that regulating functions on t-cells in patients with moderate-to-severe psoriasis is partial at most. t-cells may potentially be restrained to some degree by the expression of negative immune regulatory pathways in a process known as "checkpoint inhibition." in a collaborative project by clark, 117 psoriasis lesions were treated to resolution with etanercept. the lesions were then subjected to t-cell antigen receptor (tcr) sequencing, because it was thought that pathogenic trm t-cells would remain in the skin at their previous lesional location. vβ-2, -13, and -16 clones were identifed, which indicated that diderent clones shared the same cDr3 sequence, suggesting that they share reactivity to the same antigen. antigens, constitutive in normal skin, are up- regulated either directly or indirectly by il-17 in keratinocytes or melanocytes. trm t-cells may be reactive cells and will probably remain lifelong at their location and serve as memory for psoriasis antigens. ccl20, a substance induced by il-17, triggers dendritic cell infltration (both tiP-Dcs and mature Dcs) with potential for strong stimulation of t-cells in the skin. note that ccl20 is also chemotactic for th-17. there are a number of negative immune regulators associated with psoriasis, including tAblE 5. Polar ingammatory cutaneous diseases I nflAMMAtOry dIsEAsE d OMInAtEd by C OMACtIVAtIng d rIVEn by Psoriasis vulgaris il-17 (th17) th1, th22 il-23 produced by tiP- D cs (cD11c + Dc) atopic dermatitis il-4/il-13 (th2) th1, th22 tslP-receptor+, fcεr+Dc (cD11c + Dc) cutaneous lupus interferon innate interferon producing cells Myeloid and plasmacytoid Dc il: interleukin; th: t helper cells; cD: cluster diderentiation; Dc: dendritic cell

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