Idiopathic Psoriasis Research Articles

Paradoxical psoriasis: The flip side of idiopathic psoriasis or an autocephalous reversible drug reaction?

Psoriasis is a common, chronic skin disease that results mainly from the complex interplay between T cells, dendritic cells, and inflammatory cytokines including TNF-α, IL-17, IL-12, and IL-23. Successful therapy with anti-cytokine antibodies has proved the importance of these key cytokines, especially TNF-α. During the anti-TNF-α treatment of classical idiopathic psoriasis, a small portion of patients develop new psoriasiform lesions. This contradictory phenomenon was named paradoxical psoriasis which resembles idiopathic psoriasis clinically but presents overlapped histological patterns and distinct immunological processes. In this review, we discuss the differences between idiopathic psoriasis and paradoxical psoriasis with an emphasis on their innate immunity, as it is predominant in paradoxical psoriasis which exhibits type I IFN-mediated immunity without the activation of autoreactive T cells and memory T cells. We also put up an instructive algorithm for the management of paradoxical psoriasis. The decision on drug discontinuation or switching of biologics should be made based on the condition of underlying diseases and the severity of lesions.

Treatment of immune checkpoint inhibitor–mediated psoriasis: A systematic review

Immune checkpoint inhibitors (ICIs) have revolutionized the treatment of advanced/metastatic cancers.1 Because ICIs augment Th1/Th17 cell activity and interleukin (IL) 17A secretion, ICI-induced de novo psoriasis and exacerbations of pre-existing psoriasis of diverse phenotypes have been widely reported.1,2 Although many efficacious treatments exist for idiopathic psoriasis, recommendations for managing ICI-mediated psoriasis are insufficient and notably absent from the National Comprehensive Cancer Network guidelines for treating immune-related adverse events.

Histologic comparison of tumor necrosis factor-α inhibitor–induced psoriasis and psoriasis vulgaris

Tumornecrosis factor-α inhibitor (TNFi)-induced psoriasis is a paradoxic reaction characterized by the development of a psoriasiform rash that mimics idiopathic psoriasis subtypes both clinically and histologically. Few studies have investigated the histologic features of TNFi-induced psoriasis skin lesions, and most of these are limited by inclusion of few specimens. We aimed to characterize histologic features of TNFi-induced psoriasis and identify histologic differences between TNFi-induced psoriasis and idiopathic psoriasis. We characterized 60 biopsy specimens obtained from 47 unique patients at a single tertiary care referral center between 2004 and 2016 who developed TNFi-induced psoriasis, and we compared histologic features to those of 85 biopsy specimens from a control group of 85 patients with idiopathic psoriasis. The most common histologic reaction pattern in TNFi-induced psoriasis biopsy specimens was psoriasiform (80.0%). Five histologic parameters were significantly different in TNFi-induced psoriasis biopsy specimens compared with idiopathic psoriasis biopsy specimens: at least 3 dermal eosinophils per histologic section, neutrophils in the stratum corneum, neutrophils in the epidermis, papillary plate thinning, and absence of parakeratosis. Inability to exclude lesion selection bias as a potential reason for some significant histologic differences. This study supports the idea that histologic differences exist between TNFi-induced psoriasis and idiopathic psoriasis may help distinguish between these conditions, especially for dermal eosinophil counts of 3 or greater.

Psoriasis precipitated by timolol eye drops. A series of eight cases.

Induction of psoriasis following administration of beta blocker containing eye drops has rarely been documented. We report eight cases of psoriasis triggered by timolol eye drops. Since the clinical and histopathological features of this drug reaction are indistinguishable from those of idiopathic psoriasis, a thorough drug history should be taken in all patients, especially elderly ones, with recent onset of psoriasis.

067 Comparison of histologic features in biopsies of patients with tumor necrosis factor-α-induced psoriasiform reactions and psoriasis vulgaris

One of the most intriguing adverse reactions of TNF-α inhibitors (TNFis) is occurrence of de novo psoriasiform eruptions (TNF-psoriasis). Although well-accepted as a relatively common reaction of this medication class, many aspects of this side effect remain poorly characterized. Specifically, few studies have evaluated histologic features of TNF-psoriasis skin lesions, and most are limited by inclusion of few specimens. We comprehensively evaluated histologic features of 57 TNF-psoriasis biopsies from 50 unique patients seen at a single, tertiary care center dermatology department, and additionally compared histologic features of these biopsies to those of 85 biopsies from control patients with idiopathic psoriasis. The dominant reaction pattern in TNF-psoriasis biopsies was psoriasiform (80.7%), followed by spongiotic and pustular. Papillary plate thinning (p=0.03574) and neutrophils in the stratum corneum (p=8.89x10-7) were significantly more likely in histologic sections of idiopathic psoriasis compared to TNF-psoriasis. Alternatively, lack of parakeratosis (p=0.01983), neutrophils in the epidermis (p=0.01654), and eosinophils in the dermis (p=2.23x10-6) were significantly more likely in histologic sections of TNF-psoriasis compared to idiopathic psoriasis. Whereas eosinophils were present in the minority of idiopathic psoriasis specimens (17.6%) and no section had more than 3 eosinophils (n=1), 52.6% of TNF-psoriasis specimens displayed dermal eosinophils and 21.1% (n=12) had >3 eosinophils. There was no statistical difference in histological characteristics between the TNF-psoriasis cohort who responded to topicals compared to the cohort requiring more aggressive therapies. We believe consideration of these 5 contrasting histologic features can help dermatologists and pathologists confidently assess biopsies of psoriasiform lesions in patients treated with TNFis, and help drive more appropriate and effective treatment recommendations.

ADAMTSL5 is upregulated in melanoma tissues in patients with idiopathic psoriasis vulgaris induced by nivolumab

ADAMTSL5 is upregulated in melanoma tissues in patients with idiopathic psoriasis vulgaris induced by nivolumab

Genetic basis of TNF-α antagonist associated psoriasis in inflammatory bowel diseases: a genotype-phenotype analysis.

Anti-tumour necrosis factor (anti-TNF) biologic associated psoriasis has been reported in inflammatory bowel disease (IBD) patients. However, little is known regarding its pathogenesis. To identify potential genetic predispositions to anti-TNF associated psoriasis in IBD patients. This retrospective chart review included IBD patients enrolled in a prospective registry. Cases of anti-TNF associated psoriasis and idiopathic psoriasis unrelated to anti-TNF exposure were confirmed by an expert dermatologist. All patients were genotyped on the Illumina Immunochip. A weighted genetic risk score ascertaining genetic pre-disposition towards psoriasis was calculated and overall genetic pre-disposition as well as differential distribution of individual polymorphisms was compared across the three groups. Our study included 724 IBD patients who initiated anti-TNF therapy and did not develop psoriasis, 35 patients with anti-TNF associated psoriasis, and 38 patients with idiopathic psoriasis. Anti-TNF users who developed psoriasis had a modest but statistically significantly greater psoriasis genetic risk score than anti-TNF controls (mean 0.64 vs. 0.61, P = 0.04), and had a similar genetic risk score as those with idiopathic psoriasis (0.64 vs. 0.62, P = 0.22). Two loci associated with NOS2 and ETS1 genes achieved P < 0.05 when comparing anti-TNF associated psoriasis to anti-TNF controls. Three loci were significantly different between anti-TNF associated psoriasis and idiopathic psoriasis including a polymorphism near NOS2 encoding for inducible nitric oxide synthase that is produced by dendritic cells in skin lesions in psoriasis. Patients with anti-TNF associated psoriasis had a modestly greater genetic pre-disposition towards psoriasis but no single causative polymorphism was identified.

P547 Biological agents for moderately-to-severely active ulcerative colitis in adults: a network meta-analysis of randomized controlled trials

for psoriasis, such as hands, feet, scalp and groin region. Half of the cases had a familiar history of idiopathic psoriasis: these were the most severe and invalidating forms and required definitive interruption of the therapy. Conclusions: This study shows that long-term treatment with IFX and ADA was safe and well tolerated in most cases. Considering the remarkable benefits of this new form of medical therapy for IBD in pediatric age, the decision to use an anti-TNFalpha agent should be individualized and based upon specific clinical features and unique risk profile of a given patient.

Allelic Variants of Drug Metabolizing Enzymes as Risk Factors in Psoriasis

The onset or exacerbation of psoriasis, a T-cell-dependent skin disease with autoimmune features, can be triggered by drugs such as antimalarials and beta-blockers. Xenobiotics may also play a role in idiopathic psoriasis. It has been hypothesized that different metabolic efficiencies caused by variant alleles of xenobiotic metabolizing enzymes could lead to the accumulation of xenobiotics or their reactive metabolites in target organs. Subsequently, neoantigens or cryptic peptides could be presented and initiate an aggressive T cell response. In this context, we analyzed a broad array of xenobiotic metabolizing enzymes in up to 327 Caucasian psoriasis patients and compared them to 235 control persons. Alleles tested include four phase I and three phase II enzymes. Significantly more carriers of the variant alleles of CYP1A1 (alleles *2A and *2C) were found in healthy controls than in patients, suggesting a protective role for these alleles. No significant difference between patients and controls could be found, however, for the other phase I alleles 1B1*1 and 1B1 *3, 2C19*1A and 2C19*2A, and 2E1*1A and 2E1*5B. Of the variant alleles coding for phase II enzymes only GSTM1, but not GSTT1 or NQOR, correlated with a risk to contract psoriasis. Some combinations of phase I and phase II enzymes suggested protective or risk-associated effects. Interestingly, heterozygosity for CYP2C19 alleles *1A and *2A was associated with increased risk for "late onset" psoriasis, whereas this genotype was protective for psoriatic arthritis. This is the first large-scale study on these enzymes and the results obtained support the concept that different activities of metabolizing enzymes can contribute to disease etiology and progression.