Paradoxical Psoriasiform Reactions Research Articles

Paradoxical psoriasiform reactions during treatment with adalimumab for hidradenitis suppurativa: Real-life experience and therapeutic response to other biological drugs.

Adalimumab is the only biological drug approved to date for the treatment of moderate and/or severe hidradenitis suppurativa. Adverse events reported during therapy include paradoxical psoriasiform reactions. No guidelines are currently available for the management of this clinical condition. The aim of this paper is to describe the incidence and clinical features of paradoxical psoriasiform eruptions occurring during treatment with adalimumab in patients with hidradenitis suppurativa and to report real-life experience in management and the possible role of other biologic agents for the treatment of both conditions.

Expression of microRNA-21 and TIMP-3 in paradoxical psoriasiform reactions during treatment with antitumor necrosis factor agents.

Expression of microRNA-21 (miR-21) is increased in psoriasis, leading to reduced levels of epidermal tissue inhibitor of matrix metalloproteinase 3 (TIMP-3), a highly potent inhibitor of the tumor necrosis factor alpha (TNFα) sheddase TACE (TNFα-converting enzyme)/ADAM17. We described the profile of miR-21 and TIMP-3 in paradoxical psoriasiform reactions induced by anti-TNFα drugs and in a control group to elucidate the pathogenesis of this reactions. We performed an analytic, cross-sectional, prospective, experimental case-control study. We compared our findings with those of non-induced psoriasis. We included 15 patients with a change of morphology (plaque to guttate psoriasis) and 10 patients with induced psoriasis (six palmoplantar pustulosis and four plaque psoriasis). Consecutive patients with different subtypes of non-induced, non-systemically treated psoriasis were included as a control group. We found that most cases with guttate psoriasis and with induced plaque psoriasis cases showed high expression of TIMP-3 expression and decreased or poorly increased levels of miR-21. The expression pattern was not homogeneous in the cases of induced palmoplantar pustulosis. These profiles differ from those of non-induced psoriasis. We conclude that various pro-inflammatory cytokine profiles are involved in the pathogenesis of paradoxical psoriasiform reactions and non-induced psoriasis.

DNA Copy Number Variation Associated with Anti-tumour Necrosis Factor Drug Response and Paradoxical Psoriasiform Reactions in Patients with Moderate-to-severe Psoriasis.

Biological drugs targeting tumour necrosis factor are effective for psoriasis. However, 30–50% of patients do not respond to these drugs and may even develop paradoxical psoriasiform reactions. This study searched for DNA copy number variations that could predict anti-tumour necrotic factor drug response or the appearance of antitumour necrotic factor induced psoriasiform reactions. Peripheral blood samples were collected from 70 patients with anti-tumour necrotic factor drug-treated moderate-to-severe plaque psoriasis. Samples were analysed with an Illumina 450K methylation microarray. Copy number variations were obtained from raw methylation data using conumee and Chip Analysis Methylation Pipeline (ChAMP) R packages. One copy number variation was found, harbouring one gene (CPM) that was significantly associated with adalimumab response (Bonferroni-adjusted p-value < 0.05). Moreover, one copy number variation was identified harbouring 3 genes (ARNT2, LOC101929586 and MIR5572) related to the development of paradoxical psoriasiform reactions. In conclusion, this study has identified DNA copy number variations that could be good candidate markers to predict response to adalimumab and the development of anti-tumour necrotic factor paradoxical psoriasiform reactions.

Experimental Methods for the Immunological Characterization of Paradoxical Psoriasis Reactions Induced by TNF-α Biologics.

Immunomodulation with anti-TNFα biologics is highly effective in the treatment of various immune-mediated inflammatory diseases, even though 2-5% of patients treated can develop paradoxical psoriasiform skin lesions. We recently analyzed three patients affected by severe hidradenite suppurativa (HS), and who developed paradoxical psoriasiform reactions following treatment with the TNF-α blockers. Psoriasiform skin reactions showed immunological and immunohistochemical features common to acute psoriasis, characterized by cellular players of innate immunity, such as plasmacytoid dendritic cells (pDC), neutrophils, mast cells, macrophages, and monocytes. In addition, IFN-β and IFN-α2a, two type I IFNs typical of early psoriasis, were highly expressed in paradoxical skin reactions. Concomitantly, the lymphotoxin (LT)-α and LT-β were overproduced. Detection of innate immunity cells was carried out on skin sections from HS patients, by immunohistochemistry (IHC) by using antibodies (Abs) against markers identifying specific leukocyte subpopulations. Anti-BDCA2, anti-CD15, anti-CD117, anti-CD68, anti-CD11c, and anti-CD3 Abs were employed to detect pDC, neutrophils, mast cells, macrophages, monocytes/dendritic cells, and T lymphocytes, respectively. In parallel, skin expression of the innate immunity soluble mediators IL-36γ, IFN-β, IFN-κ, LT-α and LT-β was also evaluated by IHC by using specific Abs. In this chapter, we describe the methods and protocols to detect the in situ expression and localization of innate immunity molecules and leukocyte subpopulations in skin lesions where inflammatory and psoriasiform reactions are evoked by anti-TNF- α biological therapy.

Paradoxical psoriasiform reactions by anti-TNF treated with Ustekinumab in patients with inflammatory bowel disease

Paradoxical psoriasiform reactions by anti-TNF treated with Ustekinumab in patients with inflammatory bowel disease

Paradoxical psoriasiform reactions of anti-tumour necrosis factor therapy in inflammatory bowel disease patients.

Anti-tumour necrosis factor (TNF) agents have demonstrated efficacy in inflammatory bowel disease (IBD). Cutaneous reactions such as new onset psoriasis or psoriasiform-like reactions are among the most common adverse reactions. We retrospectively identified cases of anti-TNF-induced psoriasis or psoriasiform manifestations in IBD patients at a tertiary centre in Australia. A total of 10 (six females) of 270 (3.7%) IBD patients treated with anti-TNF therapy developed drug-induced psoriatic or psoriasiform-like reactions: five patients were treated with infliximab and five with adalimumab; nine had Crohn disease. The time from initiation of anti-TNF agent to onset of rash was 7.5 months on average. The most frequent distributions were the scalp (7/10) and extremities (6/10). Three patients discontinued anti-TNF treatment with resolution of the rash. Topical treatment of the lesions allowed continued use of biological agent in the majority. Paradoxical psoriatic lesions are recognised adverse events associated with anti-TNF therapy, but discontinuation of therapy due to dermatological complications is required only rarely, even in patients with psoriasiform lesions.

Inflammatory Bowel Disease: Joint Management in Gastroenterology and Dermatology

Inflammatory bowel disease (IBD) is a complex entity that includes Crohn disease and ulcerative colitis. It is characterized by a chronic proinflammatory state of varying intensity that often leads to considerable morbidity. In the last decade, several therapeutic targets have been identified that are susceptible to the use of biological agents, including anti-tumor necrosis factor alpha antibodies, which are associated with paradoxical psoriasiform reactions in 5% of patients. Decision-making in the management of these cases requires close collaboration between the dermatologist and gastroenterologist. Inflammatory bowel disease is also associated with various other dermatologic and rheumatologic manifestations, and presents a genetic and pathogenic association with psoriasis that justifies both the interdisciplinary approach to these patients and the present review.

Enfermedad inflamatoria intestinal: abordaje conjunto digestivo-dermatológico

Inflammatory bowel disease (IBD) is a complex entity that includes Crohn disease and ulcerative colitis. It is characterized by a chronic proinflammatory state of varying intensity that often leads to considerable morbidity. In the last decade, several therapeutic targets have been identified that are susceptible to the use of biological agents, including anti-tumor necrosis factor alpha antibodies, which are associated with paradoxical psoriasiform reactions in 5% of patients. Decision-making in the management of these cases requires close collaboration between the dermatologist and gastroenterologist. Inflammatory bowel disease is also associated with various other dermatologic and rheumatologic manifestations, and presents a genetic and pathogenic association with psoriasis that justifies both the interdisciplinary approach to these patients and the present review.

Paradoxical psoriasiform reactions to anti-TNFα drugs are associated with genetic polymorphisms in patients with psoriasis.

Paradoxical psoriasiform reactions to anti-tumor necrosis factor α (TNFα) agents have been described. We aimed to study the association between these reactions and polymorphisms in genes previously associated with psoriasis or other autoimmune diseases. A total of 161 patients with plaque-type psoriasis treated with anti-TNFα drugs were genotyped for 173 single-nucleotide polymorphisms (SNPs) using the Illumina Veracode genotyping platform. Among the 161 patients, 25 patients developed a paradoxical psoriasiform reaction consisting of a change in morphology, mostly to guttate psoriasis (88%). These lesions developed 9.20±13.52 months after initiating treatment, mainly with etanercept (72%). Psoriasis type and a Psoriasis Area and Severity Index (PASI) 75 response to treatment were not associated with lesions. Multivariate logistic regression revealed that five SNPs (rs11209026 in IL23R, rs10782001 in FBXL19, rs3087243 in CTLA4, rs651630 in SLC12A8 and rs1800453 in TAP1) were associated with paradoxical reactions. This is the first study to show an association between genetic polymorphisms and paradoxical reactions in patients with psoriasis treated with anti-TNFα drugs.The Pharmacogenomics Journal advance online publication, 21 July 2015; doi:10.1038/tpj.2015.53.

Clinical Management of Paradoxical Psoriasiform Reactions During TNF-α Therapy

There have been reports of paradoxical induction or worsening of psoriasis during treatment with tumor necrosis factor (TNF) α agents (infliximab, etanercept, adalimumab, and certolizumab). It has been hypothesized that an imbalance between TNF-α and interferon α might have a role in the etiology and pathogenesis of these reactions. Paradoxical psoriasiform reactions can be divided clinically into de novo psoriasis and exacerbation of preexisting psoriasis. The first, which is more common and more extensively described in the literature, occurs in patients without a history of psoriasis who are receiving TNF-α therapy for another inflammatory disorder. The second can occur with or without changes in the morphology of the lesions. In this article, we review the literature on the clinical and histologic features of paradoxical psoriasiform reactions, analyze their clinical course and treatment, and propose a clinical management model for use in routine practice.

Reacciones psoriasiformes paradójicas durante el tratamiento con terapia anti-factor de necrosis tumoral. Manejo clínico

There have been reports of paradoxical induction or worsening of psoriasis during treatment with tumor necrosis factor (TNF) α agents (infliximab, etanercept, adalimumab, and certolizumab). It has been hypothesized that an imbalance between TNF-α and interferon α might have a role in the etiology and pathogenesis of these reactions. Paradoxical psoriasiform reactions can be divided clinically into de novo psoriasis and exacerbation of preexisting psoriasis. The first, which is more common and more extensively described in the literature, occurs in patients without a history of psoriasis who are receiving TNF-α therapy for another inflammatory disorder. The second can occur with or without changes in the morphology of the lesions. In this article, we review the literature on the clinical and histologic features of paradoxical psoriasiform reactions, analyze their clinical course and treatment, and propose a clinical management model for use in routine practice.