Paradoxical Psoriasis Research Articles

S3909 Paradoxical Psoriasis and Alopecia Areata After the Use of Anti-TNF in a Patient With Crohn's Cisease

S3909 Paradoxical Psoriasis and Alopecia Areata After the Use of Anti-TNF in a Patient With Crohn's Cisease

Unintended Consequences of Immune Therapy for Immune-Mediated Diseases: Paradoxical Psoriasis and Dupilumab-Associated Musculoskeletal Syndrome.

Two presentations at the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA) 2023 annual meeting focused on unintended consequences of immunomodulatory therapy for psoriasis (PsO). Dr. Elizabeth Wallace presented on unintended consequences of tumor necrosis factor inhibitors for treating PsO and other inflammatory disorders. These consequences include paradoxical PsO, which is defined as unexpected new PsO cases or worsening PsO symptoms seemingly induced by treatment. Dr. Bruce Kirkham focused on unintended consequences of dupilumab treatment, which can include a musculoskeletal syndrome similar to psoriatic arthritis.

Adalimumab induced psoriasis in a Crohn’s disease patient: a case report

Adalimumab is a human monoclonal antibody that selectively targets tumour necrosis factor-alpha (TNF- Alpha), a cytokine involved in the pathogenesis of various inflammatory and autoimmune disorders. Adalimumab has been approved worldwide for the treatment of several chronic immune-mediated diseases, including rheumatoid arthritis, psoriasis, psoriatic arthritis, ankylosing spondylitis, Crohn's disease, ulcerative colitis, and juvenile idiopathic arthritis. One of the adverse reactions caused by Adalimumab is psoriasis. This study reports the case of a 37-year-old male with palmoplantar psoriasis triggered by adalimumab for treatment of Crohn’s disease. This eruption resisted complete clearance with various potent corticosteroids. The patient was referred back to the treating rheumatologist to possibly change adalimumab to another type of therapy. Keywords: Adalimumab, psoriasis, Crohn’s disease, paradoxical psoriasis.

Paradoxical Psoriasis in Patients Receiving Therapy with Tumor Necrosis Factor Inhibitors: Potential Pathogenic Mechanisms and the Role of Genetic Factors.

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 with IL-17 inhibitors.

Paradoxical psoriasis with IL-17 inhibitors.

Paradoxical psoriasis induced by IL-17 antagonists.

Background The paradoxical occurrence of psoriasis triggered by Interleukin-17 (IL-17) inhibitors is notable due to its prominent symptoms and the therapeutic dilemma it presents for follow-up care. Objective To describe cases in our clinic, perform an in-depth literature review, and suggest the most probable mechanisms of action. Method We conducted a literature review on published cases of IL-17 inhibitor-induced psoriasis. Results We found 22 articles reporting 30 cases of IL-17 inhibitor-induced paradoxical psoriasis, primarily observed in patients with a previous psoriasis history. Almost 60% of cases showed a change in lesion morphology, with the plaque or pustular type being prevalent. About 73.3% of patients had to discontinue the implicated drug, leading to partial or complete symptom resolution. The mechanism behind this response seemed to involve IL-17 inhibitors downregulating Tumour Necrosis Factor alpha (TNF-α), subsequently upregulating plasmacytoid dendritic cells and triggering unopposed IFN-alpha (IFN-α) production. Limitation Data are confined to case reports and case series. Conclusion More assertive measures are recommended for treating paradoxical psoriasis induced by IL-17 inhibitors than those caused by TNF-α inhibitors. Reintroducing an IL-17 inhibitor is not advised, as patients did not show improvement.

Not Your Typical Ulcerative Colitis Patient

Background: Extraintestinal manifestations (EIMs) of inflammatory bowel diseases (IBDs) are a common and debilitating feature of disease, occurring in up to 40% of patients with IBD. Despite the huge therapeutic progress of the last decade, one must not forget about the side effects that currently available medications might have and the challenges to both patient and physician. Case presentation: We present the case of a 33-year-old woman, that initially was admitted for diffuse abdominal pain, nausea and bloating. After careful investigation she was diagnosed with a drug induced acute pancreatitis, caused by sulfamethoxazole/trimethoprim taken for UTI. Further investigations established a diagnosis of ulcerative colitis. Initial treatment with mesalamine resulted in another acute pancreatitis event that required hospitalization. An anti-TNF therapy with infliximab was started with initial clinical remission but then she developed another adverse reaction, this time paradoxical psoriasis, while having an IBD flare. So, this begged the question, how do we treat a patient that had an adverse reaction to every prior treatment? Conclusion: Developing newer and newer therapies will bring also different possible adverse events that should be carefully diagnosed and managed.

Paradoxical Psoriasis: From its Many Faces to Possible Shared Therapeutic Targets

Paradoxical Psoriasis: From its Many Faces to Possible Shared Therapeutic Targets

Identification of immunological patterns characterizing immune-related psoriasis reactions in oncological patients in therapy with anti-PD-1 checkpoint inhibitors.

Immunotherapy with biologics targeting programmed cell death protein-1 (PD-1) is highly effective in the treatment of various malignancies. Nevertheless, it is frequently responsible for unexpected cutaneous manifestations, including psoriasis-like dermatitis. The pathogenesis of anti-PD-1-induced psoriasis has yet to be clarified, even though it is plausible that some innate and adaptive immunity processes are in common with canonical psoriasis. The genetic predisposition to psoriasis of patients could also be a contributing factor. Here, we investigated the immunological and genetic profiles of two patients with metastatic melanoma and one patient affected by lung cancer, who developed severe psoriasis after receiving anti-PD-1 nivolumab therapy. The immune patterns of the three patients were compared with those detectable in classical, chronic plaque-type psoriasis or paradoxical psoriasis induced by anti-TNF-α therapy, mostly sustained by adaptive and innate immunity processes, respectively. Therefore, immunohistochemistry and mRNA analyses of innate and adaptive immunity molecules were conducted on skin biopsy of patients. Genetic analysis of polymorphisms predisposing to psoriasis was carried out by NGS technology. We found that anti-PD-1-induced psoriasis showed immunological features similar to chronic psoriasis, characterized by the presence of cellular players of adaptive immunity, with abundant CD3+, CD8+ T cells and CD11c+ dendritic cells infiltrating skin lesions, and producing IL-23, IL-6, TNF-α, IFN-γ and IL-17. On the contrary, a lower number of innate immunity cells (BDCA2+ plasmacytoid dendritic cells, CD15+ neutrophils, CD117+ mast cells) and reduced IFN-α/β, lymphotoxin (LT)-α/β, were observed in anti-PD-1-induced psoriasis lesions, as compared with anti-TNF-α-induced paradoxical psoriasis. Importantly, the disintegrin and metalloprotease domain containing thrombospondin type 1 motif-like 5 (ADAMTSL5) psoriasis autoantigen was significantly upregulated in psoriasis lesions of anti-PD-1-treated patients, at levels comparable with chronic plaque-type psoriasis. Finally, NGS analysis revealed that all patients carried several allelic variants in psoriasis susceptibility genes, such as HLA-C, ERAP1 and other genes of the major psoriasis susceptibility PSORS1 locus. Our study showed that adaptive immunity predominates over innate immunity in anti-PD-1-induced psoriasis lesions, consistently with the local ADAMTSL5 overexpression. The presence of numerous SNPs in psoriasis susceptibility genes of the three patients also suggested their strong predisposition to the disease.

A249 PARADOXICAL PSORIASIS FOLLOWING ANTI-TNFΑ THERAPY IN INFLAMMATORY BOWEL DISEASE AND ASSOCIATION WITH AN IL-23 RECEPTOR VARIANT: A PRELIMINARY REPORT

Abstract Background Patients with inflammatory bowel disease (IBD) who receive anti-tumor necrosis factor (TNF) α therapy are at risk of developing drug-related psoriatic skin lesions known as paradoxical psoriasis (PP). This is a severe unpredictable adverse drug event that often leads to discontinuation of anti-TNFα therapy. To date, there are no tools for identifying high-risk individuals. Variation in the IL-23 receptor (IL23R) gene has been linked to psoriasis onset and may be implicated in PP. Aims To evaluate the frequency of the IL23R variant (IL23R1142Gampersand:003EA) in anti-TNFα exposed IBD patients who develop PP versus those who do not. Clinical variables associated with PP development will also be assessed. Methods A case-control study is ongoing, including anti-TNFα-exposed adult IBD patients. Participants are divided based on the development of PP (cases n=11; controls n=48, identified to date, 500 additional patients will be screened). All participants were retrospectively genotyped for the occurrence of the IL23R1142Gampersand:003EA variant. Clinical variables and outcomes were assessed from the time of anti-TNFα exposure for at least one year of follow-up or to the time of anti-TNFα discontinuation. Results To date, we have included 59 adult IBD patients treated with infliximab or adalimumab. Eleven patients developed PP after a median duration of treatment of three months with anti-TNFα therapy. The most common presentations were guttate, plaque, and pustular psoriasis. Six patients had PP that involved 50% or more of their body surface area (BSA). Nine participants discontinued their anti-TNFα therapy due to PP. None of the cases had a personal or family history of psoriasis. PP patients were similar to controls with respect to age, sex, ethnicity, IBD type, disease duration, and concurrent immunomodulator use. The variant genotype occurred more frequently in PP patients compared to controls (54.5% vs. 4.2%, OR 27.6, 95%CI 4.3-145.4). Those with the variant genotype also had more extensive psoriasis compared to wildtypes (mean BSA 61% vs. 25%, p=0.045). Conclusions In this preliminary analysis, there was an increased frequency of the IL23R1142Gampersand:003EA variant in patients who developed PP compared to those who did not after anti-TNFα exposure. We did not identify any other clinical variables associated with development of PP. Interpretation of these results is limited by the small sample size. Completion of this study may help clarify the association between PP and the IL23R gene as well as other clinical risk factors implicated in PP development. Funding Agencies None

A multidisciplinary dermatology-gastroenterology-rheumatology (DER.RE.GA) unit for the care of patients with immune-mediated inflammatory diseases: analysis of the first 5 years from the dermatologist’s perspective

Immune-mediated inflammatory diseases (IMIDs) constitute a heterogenous group of chronic and highly disabling conditions. The clinical challenges they often pose led to formation of numerous dermo-rheumatological interdisciplinary units around the world, which are reported to benefit their patients in various ways. The present paper describes our experience with a multidisciplinary dermatology-rheumatology-gastroenterology unit DERREGA at the IRCCS Foundation Policlinico San Matteo of Pavia over a period of 5 years of its activity (2017–2022). A digital database was created, containing the medical records of 146 patients referred to the dermatology unit only by rheumatologists or gastroenterologists belonging to the multidisciplinary unit DERREGA. Then, aspects such as demographics, initial basis of referral and final diagnosis among the patients were analyzed retrospectively. Patients were classified as either gastroenterological or rheumatological, and then categorized according to the specific basis of referral. Most of the gastroenterological patients (97%) were affected by inflammatory bowel diseases (IBDs). Rheumatological patients were divided in three subgroups, including patients referred with vasculitis, arthropathies (undifferentiated arthritis, psoriatic arthritis and other arthritis) and other rheumatological diseases. Then, final diagnoses were evaluated in each group. Almost a third of IBD patients received a diagnosis of paradoxical psoriasis. Dermatological examination allowed diagnosis of minimal psoriasis based on Caspar criteria in over 70% of the patients admitted with undifferentiated arthritis. A multidisciplinary approach is suggested to provide more effective management of IMIDs and, specifically, from a dermatological perspective, allows for the diagnosis of minimal manifestations of psoriasis in patients with a provisional diagnosis of undifferentiated arthritis.

TNF-α Inhibitor-Induced Psoriasis and Psoriatic Alopecia in Adolescent with Ulcerative Colitis: Clinical Case

Background. Genetically engineered biological therapy has revolutionized the treatment of many chronic inflammatory diseases. It often allows to achieve significant clinical effect and improve the patient's quality of life. However, sometimes it leads to adverse events, and physicians encounter them more often. One of such side effects is paradoxical psoriasis (PP) that can be revealed during the therapy with tumor necrosis factor alpha (TNF-α) inhibitors. PP is the debut or exacerbation of pre-existing psoriasis.Clinical case description. Patient A., 17 years old, has suffered from ulcerative colitis since 2020; biological therapy with infliximab has been initiated in March 2022. Numerous rashes were revealed, as well as development of confluent alopecia foci on the background of scalp psoriatic damage, during the next hospitalization in December 2022. The patient was examined by dermatologist; diagnosis of PP was established according to the clinical picture and medical history. Skin rashes progressed and ulcerative colitis worsened (diarrheal syndrome, fecal calprotectin levels increased up to 526 μg/g) after cessation of infliximab therapy. Biological therapy with the inhibitor IL-12/23 (ustekinumab) was initiated due to the aggressive cutaneous pathological process and the aggravation of inflammatory bowel disease (IBD) symptoms. The gradual regression of rashes with the restoration of scalp hair growth and ulcerative colitis clinical and laboratory remission were noted during the treatment.Conclusion. PP is a rare complication that develops during therapy with TNF-α inhibitors, and it is most often observed in patients with IBD. In our case there was aggressive course of psoriasis with severe scalp lesion and hair loss (it is specific type of lesion in such patients). The ustekinumab, inhibitor IL-12/23, treatment efficacy correlates with the literature data on this drug successful use in both nosologies. Ustekinumab can be a first-line therapy in such pediatric patients. This clinical case is the first case in the Russian literature on effective management of PP and ulcerative colitis with ustekinumab in children.

S3239 Paradoxical Pustular Psoriasis Secondary to TNF Alpha Inhibitor Use in Ulcerative Colitis

S3239 Paradoxical Pustular Psoriasis Secondary to TNF Alpha Inhibitor Use in Ulcerative Colitis

Paradoxical Pustular Psoriasis Following Treatment of Chronic Plaque Psoriasis with Ustekinumab

A 51-year-old female with red plaques and scales for 20 years, aggravated with pustules for more than 10 days.Physical examination: scattered red patches, silver-white scales, thin film, Auspitz sign (+) can be seen on the head and face.The trunk and limbs were scattered in large erythema and erythema, on which were dense pustules of the size of chestnut. The central color of local pustules was brown, presenting target-shaped lesions, and some pustules fused into pus lake.Vulvar mucosa scattered in pustules, erosion surface.Nail clipping thimble changes, deck thickening changes.Histopathology: Hyperkeratosis, fusion keratosis, thinning or disappearance of granular layer, epidermal psoriatic hyperplasia, munro and Kogoj microabscess, dermal papilloma, vascular dilatation, perivascular lymphocyte infiltration.Diagnosis: pustular psoriasis.

Paradoxical pustular psoriasis in a patient with spondyloarthritis treated with secukinumab

AbstractSecukinumab is a monoclonal antibody used to specifically inhibit pathologic interleukin‐17 and therefore effectively manage conditions like plaque psoriasis, psoriatic arthritis and ankylosing spondylitis. Although we know that antitumor necrosis factor molecules can cause paradoxical pustular psoriasis, a few case reports noted this reaction in patients treated with secukinumab. We report a case of a paradoxical drug reaction consisting of palmar pustular psoriasis in a female patient treated with secukinumab for spondyloarthritis.

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.

O10 Cohort study of paradoxical psoriasis in an adolescent population receiving anti-tumour necrosis factor-α for inflammatory bowel disease in a large teaching hospital with specialist dermatology and paediatric gastroenterology services

Abstract Paradoxical psoriasis is well recognized in adults receiving anti-tumour necrosis factor-(TNF)-α therapy for inflammatory bowel disease (IBD) [Bucalo A, Rega F, Zangrilli A et al. Paradoxical psoriasis induced by anti-TNFα treatment: evaluation of disease-specific clinical genetic markers. Int J Mol Sci 2020; 21: 7873. https://doi.org/10.3390/ijms21217873]. Biologics are increasingly being initiated earlier in the treatment ladder for IBD in the paediatric population, who are also vulnerable to paradoxical psoriasis. This observational study aimed to describe the clinical features and management in this group, as there are limited data on how paradoxical psoriasis differs in children. Eight patients with paradoxical psoriasis were referred between 2019 and 2022: five females and three males; age range 12–19 years (mean 15.4 years). They all had Crohn disease and were receiving infliximab (7/8 patients) or adalimumab (1/8). The onset of symptoms following anti-TNF-α initiation was 3 months to 3 years (mean 12.75 months). Involvement included scalp (7), flexural areas (3), trunk (4) limb (3) and face (1). In adults, palmoplantar and pustular forms were commonly reported whereas our cohort demonstrated eczematous forms requiring antibacterial agents, rarely seen in adults. Management included switching from infliximab to ustekinumab in three patients; and the addition of methotrexate (two). Topical treatments alone were sufficient in three patients. There were florid presentations in our cohort and the scalp was predominantly affected (7/8). Five of eight patients required a switch of their anti-TNF-α therapy or an additional systemic treatment. It is crucial for physicians to be aware of this phenomenon and work collaboratively to recognize this early to optimize patients’ symptoms and quality of life [Bucalo et al.].

Adalimumab-Induced Paradoxical Psoriasis Treated with Biologics Targeting the IL-17/IL-23 Axis in Patients with Hidradenitis Suppurativa

Background: Paradoxical psoriasis (PP) has been mainly described in patients receiving tumor necrosis factor-α (TNFα) inhibitors for inflammatory bowel disease or psoriasis vulgaris, while such data in the context of hidradenitis suppurativa (HS) are scarce. The purpose of this study was to demonstrate the course of PP and the underlying HS upon switching from adalimumab to a biologic agent targeting the interleukin (IL)-17/IL-23 axis. Methods: The electronic medical database of the outpatient department for HS of a tertiary hospital for skin diseases was searched to identify patients with moderate-to-severe HS under treatment with adalimumab, who developed PP and were switched to biological therapy with an IL-17 or IL-23 inhibitor between February 2016 and January 2022. Disease assessment scores were evaluated at baseline, at time of PP development, as well as six and 12 months thereafter. Results: Among the 83 patients who received adalimumab for the treatment of HS between February 2016 and January 2022, 10 patients (12%) developed paradoxical psoriasiform skin reactions after a median time of seven (range, 2–48) months. There were four females (40%) and six males (60%) with a median age of 42.5 (range, 33–56) years. Five patients presented with plaque psoriasis and five with palmoplantar pustulosis, while four had intertriginous and three nail involvement. In most of the patients, HS responded well to adalimumab at onset of PP. Eight patients were changed to secukinumab, one to ustekinumab, and one to risankizumab. HS further improved in all but 2 patients, one receiving secukinumab and one receiving risankizumab. In addition, all patients achieved improvement of PP. Conclusion: Despite the small number of patients, this study provides support that patients with adalimumab-induced PP may benefit from biologics targeting the IL-17/IL-23 axis. Further studies are needed to establish the optimal therapeutic strategy of the anti-TNFα-induced PP in the context of HS.

Paradoxical Tumor Necrosis Factor-Alpha (TNF-α) Inhibitor-Induced Psoriasis: A Systematic Review of Pathogenesis, Clinical Presentation, and Treatment.

Tumor necrosis factor-alpha (TNF-α) inhibitors have been shown to be well tolerated among patients with rheumatoid arthritis, inflammatory bowel disease, and psoriasis. Meanwhile, more recently, clinical practice and research efforts have uncovered increasing cases of psoriatic lesion development tied to initiating treatment with a TNF-α inhibitor. The underlying mechanisms associated with this occurrence have yet to be fully elucidated. A review and analysis of cases of paradoxical psoriasis currently published in the literature is warranted. In addition, exploring possible mechanisms of action and potential treatment options associated with favorable outcomes is much needed. A systematic literature review was performed utilizing PubMed and Google Scholar databases (1992-present), in which 106 cases of paradoxical psoriasis were reviewed. The most common morphology developed was plaque psoriasis vulgaris. There was a female predominance (61.3%), and the most common underlying autoimmune disease was rheumatoid arthritis (45.3%). In addition, the most commonly associated drug with the onset of psoriatic lesions was infliximab (62.3%). Furthermore, the findings suggest that the most well-supported mechanism of action involves the uncontrolled release of interferon-alpha (IFN-α) from plasmacytoid dendritic cells (pDCs) after TNF-α inhibition. While TNF-α inhibitors have been shown to have great benefits to patients with rheumatologic diseases, cases of paradoxical psoriasis demonstrate the importance of close monitoring of patients on TNF-α inhibitors to allow for early recognition, treatment, and potentially change to a different mechanism of action of the medication used to prevent further progression of the inflammatory lesions.

Psoriasis in children and adolescents

Psoriasis is nowadays regarded as amultifactorial, inflammatory, immune-mediated systemic condition with predominant involvement of the skin. It starts in about one third of cases in childhood and adolescence and is often accompanied by marked impairment of the quality of life of sufferers and their parents. Aside from genetic disposition, trigger factors such as streptococcal infections are notably involved in manifestation and in exacerbations. The harmful role of comorbidities even in the young, particularly of obesity, has been well documented. Treatment options have considerably improved following the approval of five biologic agents in childhood but are still insufficiently used. The present article gives ashort overview of current knowledge and the recommendations of the updated German guideline. Besides frequent types, unusual presentations such as pustular psoriasis, psoriasis dermatitis, and paradoxical psoriasis induced by tumor necrosis factor alpha (TNF-α) inhibitors are addressed.