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SAPHO syndrome is a systemic inflammatory disease characterized by skin lesions and inflammatory changes in the bones and joints. There is no consensus on the treatment strategy of SAPHO syndrome. For patients with refractory SAPHO syndrome, biological agents can be considered. We report three patients who responded poorly to conventional therapy, all of whom had paradoxical recurrence of pustulosis after receiving secukinumab, and whose paradoxical pustulosis resolved after adjustment to tofacitinib. We reviewed the literature and concluded that secukinumab may be potentially risky for the treatment of SAPHO syndrome. This paradoxical aggravation of the rash may be related to paradoxical psoriasis. The specific pathogenesis is not clear, and tofacitinib may be a remedy for this situation.

Chronic plaque psoriasis is a common debilitating skin disease. The identification of the pathogenic role of the TNF/IL-23/T 17 pathway has enabled the development of targeted therapies used in the clinic today. Particularly, TNF inhibitors have become a benchmark for the treatment of numerous chronic inflammatory diseases such as psoriasis. Although being highly effective in psoriasis treatment, anti-TNFs can themselves induce psoriasis-like skin lesions, a side effect called paradoxical psoriasis. In this review, we provide a comprehensive look at the different cellular and molecular players involved in classical plaque psoriasis and contrast its pathogenesis to paradoxical psoriasis, which is clinically similar but immunologically distinct. Classical psoriasis is a T-cell mediated autoimmune disease driven by TNF, characterised by T-cells memory, and a relapsing disease course. In contrast, paradoxical psoriasis is caused by the absence of TNF and represents an ongoing type-I interferon-driven innate inflammation that fails to elicit T-cell autoimmunity and lacks memory T cell-mediated relapses.

Following the market authorization of interleukin (IL)-17 inhibitors, a growing number of cases of IL-17 inhibitor-induced paradoxical psoriasis (PsO) have been reported. Our objectives were to present two cases of IL-17 inhibitor-induced paradoxical PsO and to systematically review the literature for similar cases, summarizing and presenting the relevant data. A systematic literature review of previously presented cases of paradoxical PsO induced by IL-17 inhibitors was conducted. We presented two patients with axial spondyloarthritis (axSpA) and paradoxical PsO induced by secukinumab (SEC). One patient’s psoriatic lesions responded well to adjuvant topical treatment, while the other patient required a combination of topical treatment and cyclosporine Α for successful treatment. SEC was continued in both cases. We also identified 35 patients with IL-17 inhibitor-induced paradoxical PsO in the literature review. The most frequent types of paradoxical PsO were palmoplantar pustular and plaque PsO, while the median latency period was 11 weeks. Approximately one-third of patients continued IL-17 inhibitor treatment with adjunctive therapy, primarily topical, which produced satisfactory results in most patients. Almost two-thirds of the patients discontinued the IL-17 inhibitor, with the majority of patients switching to another biological agent with a different mechanism of action or initiating other systemic antipsoriatic treatments, resulting in mainly satisfactory outcomes. Therefore, paradoxical PsO induced by IL-17 inhibitors appears to respond well in both patients who continue IL-17 inhibitors with adjunctive treatment and those who discontinue IL-17 inhibitors while switching to a different class of biological agent or initiating other systemic antipsoriatic treatments.

TNF inhibitors (TNFi) have revolutionized the therapeutic management of various chronic immune-mediated inflammatory diseases. Despite their known benefits, these therapies are related to paradoxical adverse effects (PAEs), including paradoxical psoriasis (PP). Although the underlying mechanism remains somewhat unclear, some theories suggest that genetic factors, particularly certain single-nucleotide polymorphisms (SNPs), may play an important role. The present review aimed to research and analyze recent findings regarding the pathomechanisms involved in the appearance of PP and the association between various genetic factors and PP in individuals treated with TNFi. We performed a literature search and found that certain genes (IL23R, TNF, FBXL19, CTLA4, SLC12A8, TAP1) are strongly associated with the occurrence of PP in pediatric and adult patients during therapy with TNFi. The identification of the specific SNPs involved in the appearance of PP and other PAEs in patients treated with TNFi for various diseases and in different populations may later favor the recognition of those patients at a high risk of developing such adverse effects and could guide personalized therapeutic strategies in future years.

Paradoxical psoriasis (PP) may occur during treatment with anti-tumor necrosis factor-alpha (TNF-α) drugs in various chronic immune-mediated diseases, mainly inflammatory bowel diseases (IBD) and psoriasis. In this study, clinical and genetic characteristics of PP arising in IBD and psoriatic patients were investigated to identify disease-specific markers of the paradoxical effect. A total of 161 IBD and psoriatic patients treated with anti-TNF-α drugs were included in the study. Of these patients, 39 developed PP. All patients were characterized for the main clinical–pathologic characteristics and genotyped for six candidate single nucleotide polymorphisms (SNPs) selected for their possible role in PP susceptibility. In IBD patients, the onset of PP was associated with female sex, presence of comorbidities, and use of adalimumab. IBD patients with PP had a higher frequency of the TNF-α rs1799964 rare allele (p = 0.006) compared with cases without the paradoxical effect, and a lower frequency of the human leucocyte antigen (HLA)-Cw06 rs10484554 rare allele (p = 0.03) compared with psoriatic patients with PP. Overall, these findings point to specific clinical and genetic characteristics of IBD patients with PP and provide data showing that genetic variability may be related to the paradoxical effect of anti-TNF-α drugs with possible implications into clinical practice.

Paradoxical psoriasis is a rare but increasingly recognized adverse effect of anti-tumor necrosis factor-α (TNF-α) therapy, characterized by the onset or exacerbation of psoriatic lesions in patients treated for other immune-mediated conditions. We report the case of a 47-year-old woman with chronic plaque psoriasis who developed severe generalized pustular psoriasis (GPP) after six months of treatment with an adalimumab biosimilar. Given the extent and severity of the eruption and following inadequate response to previous conventional therapies, the patient was treated with brodalumab, an interleukin-17 receptor A (IL-17RA) inhibitor. Rapid and complete remission of both pustular and plaque psoriasis was achieved and maintained for over 60 weeks. This case supports the efficacy of IL-17 pathway blockade in managing paradoxical GPP and highlights the importance of prompt recognition and appropriate therapeutic switching in severe biologic-induced psoriasis.

Psoriasis is a chronic, autoinflammatory skin disease. Tumor necrosis factor-alpha inhibitors are commonly used for the treatment of moderate-to-severe psoriasis; however, paradoxical psoriatic eruptions are a well-recognized adverse effect. There are no validated guidelines to manage this. We present the case of a 48-year-old woman with severe pustular psoriasis who developed acute paradoxical reactions after her first two infusions of infliximab, requiring hospitalization. She achieved disease control after transitioning to secukinumab, an interleukin-17 inhibitor. This case highlights the importance of early monitoring for paradoxical reactions in patients with severe psoriasis after initiating tumor necrosis factor-alpha inhibitor therapy and the value of transitioning to an alternative biologic class for effective management.

Paradoxical psoriasis (PPs) is new-onset psoriatic skin lesions or worsening of the existing psoriatic skin lesions during anti-TNF therapy. PPs occurs in 2-5% of patients using anti TNF drugs (1). It is a class effect of anti-TNF agents rather than a drug effect and has been observed with all diseases for which TNF-a inhibitors are indicated (2). The time between the starting treatment and the appearance of lesions can range from a few days to years. Discontinuation of anti-TNF therapy, replacement of biological agents, or continued adjuvant therapy are among the treatment options. Inhibition of IL17 can lead to a decrease in PPs and rheumatic disease activity. We aimed to discuss the treatment process and secukinumab in three cases in PPs and to discuss the remission with IL-17 inhibition.

Immunomodulation with anti‐TNF‐α is highly effective in the treatment of various immune‐mediated inflammatory diseases, including hidradenitis suppurativa (HS). However, this may be responsible for unexpected paradoxical psoriasiform reactions. The pathogenic mechanisms underlying the induction of these events are not clear, even though the involvement of innate immune responses driven by plasmacytoid dendritic cells (pDC) has been described. In addition, the genetic predisposition to psoriasis of patients could be determinant. In this study, we investigated the immunological and genetic profiles of three HS patients without psoriasis who developed paradoxical psoriasiform reactions following anti‐TNF‐α therapy with adalimumab. We found that paradoxical psoriasiform skin reactions show immunological features common to the early phases of psoriasis development, characterized by cellular players of innate immunity, such as 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, other innate immunity molecules, such as the catheledicin LL37 and lymphotoxin (LT)‐α and LT‐β were overproduced. Interestingly, these innate immunity molecules were abundantly expressed by keratinocytes, in addition to the inflammatory infiltrate. In contrast to classical psoriasis, psoriasiform lesions of HS patients showed a reduced number of IFN‐γ and TNF‐α‐releasing T lymphocytes. On the contrary, IL‐22 immunoreactivity was significantly augmented together with the IL‐36γ staining in leukocytes infiltrating the dermis. Finally, we found that all HS patients with paradoxical reactions carried allelic variants in genes predisposing to psoriasis. Among them, SNPs in ERAP1, NFKBIZ, and TNFAIP genes and in the HLA‐C genomic region were found.

Anti-TNFα drugs have been shown to be effective for maintaining stable remission in patients with Crohn's disease. However, some problems have been identified during clinical use of this class of drugs, such as secondary treatment failure, in which the drugs become progressively less effective with time, and the development of paradoxical reactions such as psoriatic skin symptoms. Thus, while anti-TNFα drugs are used to treat psoriasis, they can sometimes also cause paradoxical psoriasis, characterized by the appearance of psoriasis-like eruptions, which has recently begun to attract attention. Furthermore, inflammatory bowel disease is not only associated with intestinal lesions, but also with a variety of extraintestinal manifestations, of which arthritis is relatively common. We encountered a case of Crohn's disease with arthritis, as an extraintestinal manifestation, and paradoxical psoriasis caused by infliximab treatment, in which ustekinumab proved extremely effective, not only for alleviating the arthritis, but also against the skin manifestations. To the best of our knowledge, this is the first reported case of the efficacy of ustekinumab against paradoxical psoriasis and arthritis in a patient with Crohn's disease.