Novel Presentation of Terminal Ileitis Associated with Secukinumab Therapy

Inflammatory bowel disease (IBD) and psoriasis are chronic inflammatory immune-mediated diseases. The interleukin-23- (IL23-) T helper (Th)17 pathway has been implicated in their pathogenesis, with multiple biologic therapies targeting this pathway. IL-17, the main proinflammatory cytokine produced by (TH)17, has been targeted by antibodies and IL-17 receptor blockers with favorable outcomes in treating psoriasis and psoriatic arthritis. However, their role in IBD is unpredictable as studies reported worsening of IBD with agents targeting IL-17 and rare case reports with new-onset IBD. We present a case of Crohn's-like severe terminal ileitis and worsening diverticulitis complicated by intestinal perforation requiring total parenteral nutrition shortly after being started on secukinumab.

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PARADOXICAL CROHN’S DISEASE – MYTH OR REALITY?

Romanian Journal of Rheumatology ◽

10.37897/rjr.2017.1.9 ◽

2017 ◽

Vol 26 (1) ◽

pp. 45-49

Author(s):

Cristina Pomirleanu ◽

◽

Catalina Mihai ◽

Codrina Ancuta ◽

◽

...

Keyword(s):

Crohn’S Disease ◽

Crohn's Disease ◽

Fecal Calprotectin ◽

Positive Outcomes ◽

Drug Induced ◽

Immune Mediated ◽

Histopathologic Evaluation ◽

Inflammatory Bowel ◽

Optimal Treatment Strategy ◽

New Onset

We report the clinical case of an emergent Crohn’s disease (CD) as a paradoxical effect after 24 months of successfully treatment with etanercept for active ankylosing spondylitis in a young women. Despite rapid and sustained response of articular disease (remission achieved as soon as three months and maintained through the entire period of administration), new onset intestinal manifestations developed during biological therapy. A complex assessment comprising clinical, endoscopic and histopathologic evaluation, associated with high levels of fecal calprotectin confirmed drug-induced inflammatory bowel disease (IBD) compatible with CD. Although optimal treatment strategy is not yet validated, discontinuation of putative etanercept and cycling to a monoclonal anti-TNF antibody (adalimumab) demonstrated positive outcomes for both articular and IBD. New onset CD may be considered as an immune-mediated injury induced etanercept and should be considered in any patient with spondylarthritis in whom IBD develops with a clear temporal relationship with TNF inhibitors, especially etanercept.

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IL-23/Th17 Axis: A Potential Therapeutic Target of Psoriasis

Current Drug Research Reviews ◽

10.2174/2589977513666210707114520 ◽

2021 ◽

Vol 13 ◽

Author(s):

Amit Sharma ◽

Deepak Kumar Upadhyay ◽

Ghanshyam Das Gupta ◽

Raj Kumar Narang ◽

Vineet Kumar Rai

Keyword(s):

Therapeutic Target ◽

T Helper Cells ◽

T Helper ◽

Potential Therapeutic Target ◽

Immune Mediated ◽

Th 17 ◽

Tnf Α ◽

Different Types ◽

Th 1

: Psoriasis is an immune-mediated skin disease that leads to the initiation of abnormal production of inflammatory mediators and keratinocytes hyper-proliferation. Th-1 cell expressing cytokines such as IL-1β and TNF-α have been the important hallmarks in the management of psoriasis. However, investigations carried out in the previous few years underline the involvement of another subset of T helper cells, i.e. Th-17 in psoriasis exacerbation, and hence become the point of focus now. The immunopathogenesis of Th-17 is the result of the IL-23/Th-17 axis. It involves the release of IL-17 and IL-22 in response to the activated NF-kβ dependent activation of IL-23. The function of human Th-17 cells as well as the crucial role of IL-23/Th-17 axis in the exacerbation of psoriasis and treatment have been well explored. Therefore, considering IL-23/Th17 axis as a pertinent therapeutic target in immune driven disorders, extensive investigations are now highlighting the utility of biopharmaceuticals and/or biological agents acting on these targets. Here, we review the IL-23/Th-17 axis based therapeutic targets, different types of active moieties based on their source of availability and most useful USFDA approved Mabs targeting the IL-23/Th17 axis in psoriasis for a better understanding of the future possibilities in this area.

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Alopecia Diffusa while Using Interleukin-17 Inhibitors against Psoriasis Vulgaris

Case Reports in Dermatology ◽

10.1159/000499030 ◽

2019 ◽

Vol 11 (1) ◽

pp. 82-85 ◽

Cited By ~ 3

Author(s):

Makiko Yajima ◽

Tomoko Akeda ◽

Makoto Kondo ◽

Koji Habe ◽

Keiichi Yamanaka

Keyword(s):

Hair Follicle ◽

Psoriasis Vulgaris ◽

Skin Diseases ◽

Interleukin 17 ◽

Th1 Cells ◽

T Helper ◽

Immune Mediated ◽

Th 17 ◽

Chronic Skin ◽

Chronic Skin Diseases

We report two cases of alopecia diffusa during the treatment of psoriasis vulgaris with interleukin (IL)-17 inhibitors. Psoriasis is one of the most common immune-mediated chronic skin diseases, strongly associated with IL-17A. Clinically, the monoclonal antibodies to IL-17A or its receptor, IL-17R, show a dramatic effect against psoriasis. Alopecia is also an IL-17-mediated autoimmune disease, and IL-17 inhibitors have been expected to be the gold standard for the treatment of alopecia; therefore, the complication of alopecia while using IL-17 may be regarded as an unexpected “paradoxical reaction.” T helper (Th)17 cells are not cytotoxic enough by themselves to undermine the hair follicle under normal circumstances, they need the coexistence of CD8+ cytotoxic Th1 cells. Th17 cells may be the initiator of the damage of the hair follicle, but CD8 T cells or more powerful Th1 cells are required as followers. The Th17/Th1 axis might convert into a Th1-dominant immune status using IL-17 inhibitors, and the destruction of the hair follicle might result in alopecia. An accumulation of cases is to be expected.

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Prevalence and Outcomes of COVID-19 Among Patients With Inflammatory Bowel Disease—A Danish Prospective Population-based Cohort Study

Journal of Crohn s and Colitis ◽

10.1093/ecco-jcc/jjaa205 ◽

2020 ◽

Author(s):

Mohamed Attauabi ◽

Anja Poulsen ◽

Klaus Theede ◽

Natalia Pedersen ◽

Lone Larsen ◽

...

Keyword(s):

Inflammatory Diseases ◽

Population Based ◽

Disease Course ◽

Biologic Therapies ◽

Population Based Study ◽

Immune Mediated ◽

Related Hospitalisation ◽

Bowel Diseases ◽

National Cohort ◽

Inflammatory Bowel

Abstract Background and Aims As no population-based study has investigated the susceptibility and disease course of COVID-19 among patients with inflammatory bowel diseases [IBD], we aimed to investigate this topic in a population-based setting. Methods Two cohorts were investigated. First, a nationwide cohort of all IBD patients diagnosed with COVID-19 was prospectively followed to investigate the disease courses of both diseases. Second, within a population-based cohort of 2.6 million Danish citizens, we identified all individuals tested for SARS-CoV-2 to determine the occurrence of COVID-19 among patients with and without IBD and other immune-mediated inflammatory diseases [IMIDs]. Results Between January 28, 2020 and June 2, 2020, a total of 76 IBD patients with COVID-19 were identified in the national cohort and prospectively followed for 35 days (interquartile range [IQR]: 25–51). A large proportion [n = 19: 25%] required a COVID-19-related hospitalisation for 7 days [IQR: 2–8.5] which was associated with being 65 years or older (odds ratio [OR] = 23].80, 95% confidence interval [CI] 6.32–89.63, p <0.01) and presence of any non-IMID comorbidity [OR = 8.12, 95% CI 2.55–25.87, p <0.01], but not use of immunomodulators [p = 0.52] or biologic therapies [p = 0.14]. In the population-based study, 8476 of 231 601 [3.7%] residents tested positive for SARS-CoV-2; however, the occurrence was significantly lower among patients with IBD [62 of the 2486 patients = 2.5%, p <0.01] and other IMIDs [531 of 16 492 patients = 3.2%, p <0.01] as compared with patients without IMIDs. Conclusions Patients with IMIDs, including IBD, had a significantly lower susceptibility to COVID-19 than patients without IMIDs, and neither immunosuppressive therapies nor IBD activity were associated with the disease course of COVID-19.

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The Significance of IL-36 Hyperactivation and IL-36R Targeting in Psoriasis

International Journal of Molecular Sciences ◽

10.3390/ijms20133318 ◽

2019 ◽

Vol 20 (13) ◽

pp. 3318 ◽

Cited By ~ 16

Author(s):

Madonna ◽

Girolomoni ◽

Dinarello ◽

Albanesi

Keyword(s):

Cell Activation ◽

Psoriatic Skin ◽

T Helper ◽

Endothelial Cell Activation ◽

Pathological Angiogenesis ◽

Immune Mediated ◽

Th 17 ◽

Tnf Α ◽

Inflammatory Processes ◽

Novel Therapeutic Strategies

Psoriasis is an immune-mediated inflammatory skin disease that involves mainly T helper (Th)17, Th1 and Th22 lymphocytes, which cause hyper-proliferation of the epidermis with aberrant differentiation of keratinocytes, and local production of chemokines and cytokines. These fuel a self-amplifying loop where these products act on T cells to perpetuate cutaneous inflammatory processes. Among the various inflammatory mediators involved, interleukin (IL)-36 cytokines are important for the recruitment and activation of neutrophils and Th17 cells in psoriatic skin. In particular, IL-36s induce chemokines and cytokines interfere with differentiation/cornification programs in the epidermis, as well as promote pathological angiogenesis and endothelial cell activation. IL-36 cytokines belong to the IL-1 family, and comprise IL-36α, IL-36β, and IL-36γ agonists as well as IL-36 receptor antagonist and IL-38 antagonists. IL-36 cytokines are up-regulated in psoriatic epidermis, and their expression is strongly induced by TNF-α and IL-17. Contrarily, IL-38 antagonist is downregulated, and its impaired expression may be relevant to the dysregulated inflammatory processes induced by IL-36. Here, we discuss on the pathogenic mechanisms leading to the altered balance of IL-36 agonists/antagonists and the significance of this dysregulation in psoriasis. Collection of the information will provide a theoretical basis for the development of novel therapeutic strategies based on IL-36 agonist/antagonist manipulation in psoriasis.

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Interferon-β Intensifies Interleukin-23-Driven Pathogenicity of T Helper Cells in Neuroinflammatory Disease

Cells ◽

10.3390/cells10082139 ◽

2021 ◽

Vol 10 (8) ◽

pp. 2139

Author(s):

Agnieshka Agasing ◽

James L. Quinn ◽

Gaurav Kumar ◽

Robert C. Axtell

Keyword(s):

T Helper Cells ◽

Th17 Cells ◽

T Helper ◽

Interferon Β ◽

Gm Csf ◽

Neuroinflammatory Disease ◽

Th 17 ◽

Th17 Differentiation ◽

Interleukin 23 ◽

And Function

Interferon (IFN)-β is a popular therapy for multiple sclerosis (MS). However, 25–40% of patients are nonresponsive to this therapy, and it worsens neuromyelitis optica (NMO), another neuroinflammatory disease. We previously identified, in both NMO patients and in mice, that IFN-β treatment had inflammatory effects in T Helper (TH) 17-induced disease through the production of the inflammatory cytokine IL-6. However, other studies have shown that IFN-β inhibits the differentiation and function of TH17 cells. In this manuscript, we identified that IFN-β had differential effects on discrete stages of TH17 development. During early TH17 development, IFN-β inhibits IL-17 production. Conversely, during late TH17 differentiation, IFN-β synergizes with IL-23 to promote a pathogenic T cell that has both TH1 and TH17 characteristics and expresses elevated levels of the potent inflammatory cytokines IL-6 and GM-CSF and the transcription factor BLIMP. Together, these findings help resolve a paradox surrounding IFN-β and TH17-induced disease and illuminate the pathways responsible for the pathophysiology of NMO and MS patients who are IFN-β nonresponders.

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Ustekinumab in Psoriasis Immunopathology with Emphasis on the Th17-IL23 Axis: A Primer

Journal of Biomedicine and Biotechnology ◽

10.1155/2012/147413 ◽

2012 ◽

Vol 2012 ◽

pp. 1-5 ◽

Cited By ~ 7

Author(s):

Pascale Quatresooz ◽

Trinh Hermanns-Lê ◽

Gérald E. Piérard ◽

Philippe Humbert ◽

Philippe Delvenne ◽

...

Keyword(s):

Monoclonal Antibody ◽

Inflammatory Bowel Diseases ◽

T Helper Cells ◽

Th17 Cells ◽

Human Monoclonal Antibody ◽

Biologic Therapies ◽

T Helper ◽

Bowel Diseases ◽

Inflammatory Bowel ◽

Th 1

Psoriasis is a chronic relapsing immunoinflammatory dermatosis that is commonly associated with systemic comorbidities. The pathogenic importance of interleukin (IL)-12 and IL-23 is beyond doubt, as well as the involvement of T helper cells (Th)1 and Th17 cells. There is upregulation of the p40 subunit shared by IL-12 and IL-23 and of the IL-23 p19 subunit, but not an increased expression of the IL-12 p35 subunit. This indicates that IL-23 appears more involved than IL-12 in the pathogenesis of psoriatic plaques. Ustekinumab is a fully human monoclonal antibody of the immunoglobulin (Ig) G1 class targeting the p40 subunit common to both IL-12 and IL-23, thus inhibiting both IL-12 and IL-23 receptor-mediated signalling. Ustekinumab is part of the recent biologic therapies active in psoriasis, autoimmune arthritides, and inflammatory bowel diseases.

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High Intestinal and Systemic Levels of Interleukin-23/T-Helper 17 Pathway in Chinese Patients with Inflammatory Bowel Disease

Mediators of Inflammation ◽

10.1155/2013/425915 ◽

2013 ◽

Vol 2013 ◽

pp. 1-10 ◽

Cited By ~ 21

Author(s):

Lu Song ◽

Rui Zhou ◽

Sha Huang ◽

Feng Zhou ◽

Shufang Xu ◽

...

Keyword(s):

Inflammatory Bowel Disease ◽

Bowel Disease ◽

Chinese Population ◽

Janus Kinase ◽

Chinese Patients ◽

Mrna Levels ◽

T Helper ◽

T Helper 17 ◽

Inflammatory Bowel ◽

Interleukin 23

Interleukin-23/T-helper 17 (IL-23/Th17) pathway plays a key role in the pathogenesis of inflammatory bowel disease (IBD), but little is known about its expression in Chinese population. In this study, we investigated the mRNA and protein levels of IL-12p40, tumor necrosis factor-like cytokine 1A (TL1A), Janus kinase 2 (JAK2), and IL-23R both locally and systemically in Chinese IBD patients. Our results indicated that the mRNA levels of IL-12p40 and TL1A were increased in ulcerative colitis (UC) patients. Furthermore, serum IL-12p40 and TL1A levels were higher in active UC patients, especially in patients with disease course less than 1.25 years or initial onset. No correlation was found between the genotype and serum levels of IL-12p40 or TL1A in UC patients. Additionally, the mRNA and protein expression of JAK2 and IL-23R were increased in UC and Crohn’s disease (CD) patients. Taken together, our results provided evidence that IL-23/Th17 pathway genes may represent important biomarkers of active stage of IBD and serve as novel therapeutic targets for IBD in Chinese population.

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Adverse Events Following SARS-CoV-2 mRNA Vaccination Among Patients with Inflammatory Bowel Disease

10.1101/2021.03.30.21254607 ◽

2021 ◽

Author(s):

Gregory J. Botwin ◽

Dalin Li ◽

Jane Figueiredo ◽

Susan Cheng ◽

Jonathan Braun ◽

...

Keyword(s):

Inflammatory Bowel Disease ◽

General Population ◽

Adverse Events ◽

Bowel Disease ◽

Biologic Therapy ◽

Inflammatory Diseases ◽

Biologic Therapies ◽

Vaccine Trials ◽

Immune Mediated ◽

Inflammatory Bowel

AbstractPatients with immune-mediated inflammatory diseases (IMID) such as inflammatory bowel disease (IBD) on immunosuppressive and biologic therapies were largely excluded from SARS-CoV-2 mRNA vaccine trials. We thus evaluated post-mRNA vaccination adverse events (AE) in 246 vaccinated adults with IBD participating in a longitudinal vaccine registry. In general, AE frequency was similar to that reported in the general population. As in the general population, AE were more common among younger patients, and those with prior COVID-19. We additionally found that AE were less common in individuals receiving biologic therapy. Those with IBD and other IMID on these commonly prescribed therapies can be reassured that the AE risk is likely not increased, and may be reduced, while on biologics.

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Immune Thrombocytopenic Purpura (ITP) as an Uncommon Extraintestinal Complication of Crohn’s Disease: Case Vignette and Systematic Literature Review

Case Reports in Hematology ◽

10.1155/2020/4785759 ◽

2020 ◽

Vol 2020 ◽

pp. 1-6

Author(s):

Raisa Epistola ◽

Tiffanie Do ◽

Ritika Vankina ◽

Daniel Wu ◽

James Yeh ◽

...

Keyword(s):

Crohn’S Disease ◽

Crohn's Disease ◽

Immune Thrombocytopenic Purpura ◽

Case Reports ◽

Case Vignette ◽

Mucosal Permeability ◽

Extraintestinal Manifestation ◽

Thrombocytopenic Purpura ◽

Disease Case ◽

Inflammatory Bowel

While the association of immune thrombocytopenic purpura (ITP) and inflammatory bowel disease (IBD) has been described in a few case reports, management of ITP as an extraintestinal manifestation of Crohn’s disease (CD) is less studied. There are approximately a dozen cases describing the management of patients dually diagnosed with CD/ITP. Previous reports postulated that the mechanism of ITP in CD was through the presence of circulating immune complexes in the serum and antigenic mimicry due to increased mucosal permeability in active colitis, versus increased mucosal production of TH1-type proinflammatory cytokines during CD flares, which may account for remission of ITP with surgery for CD. We present a case of a 27-year-old man who presented with medically refractory CD and ITP who responded to surgical management with colectomy and splenectomy, along with a systematic review of the literature. These cases suggest that colectomy should be considered in the treatment of medically refractory ITP among patients with concomitant CD.

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