Eytan Wine, Marina Aloi, Stephanie Van Biervliet, Jiri Bronsky, Javier Martín di Carpi, Marco Gasparetto, Laura Gianolio, Hannah Gordon, Iva Hojsak, Alexandra S. Hudson, Séamus Hussey, Johan van Limbergen, Erasmo Miele, Lorenzo Norsa, Ola Olén, Gianluca Pellino, Patrick van Rheenen, Lissy de Ridder, Richard K. Russell, Dror S. Shouval, Eunice Trindade, Dan Turner, David C. Wilson, Anat Yerushalmy Feler, Amit Assa

J Pediatr Gastroenterol Nutr. 2025; 1-51. doi:10.1002/jpn3.70097

Objectives

Despite advances in the management of ambulatory paediatric ulcerative colitis (UC), challenges remain as many patients are refractory to therapy and some require colectomy. The aim of these guidelines is to provide an update on optimal care for UC through detailed recommendations and practice points.

Methods

These guidelines are an update to those published in 2018 and are a joint effort of the Paediatric IBD Porto group of European Society of Paediatric Gastroenterology, Hepatology and Nutrition and the European Crohn’s and Colitis Organisation. An extensive literature search with subsequent evidence appraisal using the Oxford methodology was performed, followed by three online voting sessions and a consensus face-to-face meeting. Thirty-nine recommendations and 77 practice points were endorsed by the 25 experts with at least an 84% consensus rate.

Results

Robust evidence-based recommendations and detailed practice points are provided. In addition to reemphasising and updating the role of more ‘traditional’ UC therapies, these guidelines outline optimising the use of antitumour necrosis factor therapies and integrating newer biologics and small molecules, as well as supportive therapy, to improve outcomes and provide an updated management algorithm. Measurement and monitoring tools and decision aids are provided, and additional aspects, including nutritional support, extraintestinal manifestations, pouchitis, inflammatory bowel disease-unclassified and patient support, are discussed. Some aspects, including surgery and thromboprophylaxis, are covered in the acute severe UC guidelines.

GMA has a good safety profile, especially in difficult-to-treat and paediatric settings^. GMA also requires central venous access but may still be considered in children with UC who do not respond or lose response to conventional treatments, but more studies are needed before formal recommendations can be made.

Conclusions

These guidelines serve as an aid in managing children with UC through a combination of evidence-based recommendations and more practical practice points in the ambulatory setting.

Anas Zaher ¹, Maria Julia Moura Nascimento Santos ², Hassan Elsaygh ³, Stephen J Peterson ¹, Carolina Colli Cruz ², Anusha Shirwaikar Thomas ², Yinghong Wang ²

Expert Opin Drug Saf. 2025 Apr 21:1-10. doi: 10.1080/14740338.2025.2496431. Online ahead of print.

Introduction: This review discusses the epidemiology, pathophysiology, and factors associated with refractory immune-mediated diarrhea and colitis (r-IMDC), emphasizing tailored treatment strategies.

Areas covered: The current literature on r-IMDC was reviewed using PubMed (2015-2025), focusing on clinical trials, meta-analyses, and case reports relevant to its management.

Expert opinion: Effectively managing r-IMDC is crucial for balancing toxicities and antitumor response. Available second and third-line management options for r-IMDC cases must be carefully evaluated. Future perspectives include development of standardized protocols beyond second-line therapies and predictive biomarkers to enable personalized treatment.

• ICIs are essential in cancer therapy but often cause IMDC, with up to 41% of patients developing steroid-refractory cases.
• Current guideline-recommended second-line therapies, such as infliximab and vedolizumab, fail in 11% of IMDC cases, underscoring the need for third-line interventions.
• Emerging therapies, including Janus kinase inhibitors, fecal microbiota transplantation, and interleukin-targeting agents, show promise for r-IMDC management. Also gma, IVIG.
• Personalized management strategies, incorporating gut microbiota modulation and targeted immune suppression, could improve outcomes in refractory colitis.
• Effective management of r-IMDC is critical for reducing prolonged immunosuppression, minimizing cancer treatment interruptions, and improving patient quality of life.

Chisato Tawada ¹, Yoko Ueda ², Yoko Mizutani ¹, Xiaoyu Zang ¹, Kayoko Tanaka ¹, Hiroaki Iwata ¹

Exp Dermatol. 2025 Mar;34(3):e70076. doi: 10.1111/exd.70076.

Reactive oxygen species (ROS) are involved in the pathogenesis of generalised pustular psoriasis (GPP), but this involvement has not been fully elucidated. We performed the diacron-reactive oxygen metabolite (d-ROM) test and the biological antioxidant potential (BAP) test on sera from nine patients with active GPP who were hospitalised and treated at our hospital, (6/9 with GMA) including three patients with pustular psoriasis of pregnancy (PPP). The serum d-ROM and BAP levels were evaluated before treatment and at 1 month of treatment. We also performed immunostaining of 4-hydroxy-2-nonenal (4-HNE) in skin tissues. In the GPP patients, the average d-ROM levels were significantly reduced at 1 month of treatment (reduced to 343.0 ± 82.1 U.Carr from 423.2 ± 95.0 U.Carr, p = 0.005). The Generalised Pustular Psoriasis Area and Severity Index (GPPASI) score correlated with d-ROM levels (r = 0.57, p = 0.10), suggesting that those levels reflect the disease severity. In normal pregnancy, d-ROM values are known to increase from mid-term to late-term. The d-ROM values increased when GPP worsened in the case of PPP. Immunohistochemical staining of 4-HNE was positive for subcorneal pustules, neutrophils, and for the cytoplasm of epidermal keratinocytes, especially in upper epidermal layers. Our findings indicate that 4-HNE may play an important role in GPP and PPP.

Mary Grace Hash¹, Guang Orestes², Camile Delva³, Bailey Patrick⁴, Donna Pham⁵, Olivia Biddle⁶, Teonna Sharpe⁷, Kaitlyn Miner⁸, Kelly Frasier^9,*

Dermis. 5(1):28.

Psoriasis treatment demonstrates significant racial disparities, with Black patients and other individuals with skin of color experiencing higher disease severity yet receiving less access to advanced therapies compared to White patients. This review examines existing literature on differences in prescription patterns, treatment modalities, and clinical outcomes for psoriasis in White versus Black populations. Focus is placed on biologics, systemic non-biologic therapies, phototherapy, and topical treatments, highlighting inequities in treatment access, clinician decision-making, and infrastructure availability. Black patients are consistently underprescribed advanced therapies, such as IL-17 and IL-23 inhibitors, despite evidence supporting their efficacy in severe plaque-dominant phenotypes. Instead, systemic corticosteroids and methotrexate are disproportionately prescribed, even though they are associated with suboptimal outcomes and higher side-effect profiles. Phototherapy, while effective for darker skin types, is less frequently recommended due to barriers including access and clinician unfamiliarity with tailoring treatment for skin of color. Emerging data suggests that the specialty of the prescribing clinician plays a role in these disparities, with non-dermatologists being less likely to initiate biologic therapies and more likely to prescribe older systemic treatments. Additionally, structural barriers, including limited access to dermatologists and phototherapy centers equipped for darker skin tones, exacerbate inequities. This review identifies key gaps in understanding, including the impact of implicit bias on treatment decisions, differences in adherence and patient-reported outcomes by race, and the role of systemic factors such as insurance coverage and geographic access to care. Strategies to address these disparities include expanding education for non-dermatologist providers, improving infrastructure for phototherapy, and incorporating culturally sensitive approaches into patient education and clinician training.

Tomotaka Tanaka ¹, Daiki Hirano ¹, Syohei Ishimaru ¹, Keiko Arataki ¹

Cureus 2025 Jan 18;17(1):e77641. doi: 10.7759/cureus.77641. eCollection 2025 Jan.

We report the case of a 37-year-old male patient diagnosed with moderate left-sided ulcerative colitis (UC). Initial therapy with 5-aminosalicylic acid (5-ASA) was terminated within days due to exacerbation of symptoms, leading to a diagnosis of 5-ASA intolerance. Although induction of remission was achieved with prednisolone, the patient developed steroid dependency. Treatment with vedolizumab and ustekinumab subsequently failed to achieve clinical or endoscopic improvement. Intensive granulocyte and monocyte apheresis (GMA) was introduced, successfully inducing remission. However, during maintenance therapy with GMA, the patient experienced a relapse. Initiation of golimumab yielded suboptimal results, necessitating a combination therapy involving prednisolone and reintensified intensive GMA. This multimodal approach successfully achieved remission induction and maintenance. This case highlights the potential utility of intensive GMA in combination with golimumab and prednisolone for the management of refractory UC, particularly in patients with 5-ASA intolerance and failure of multiple biologic agents. A brief review of the relevant literature is included.

M Hupé , G Bouguen , A Buisson , C Landman , M Uzzan , S Nancey , C Guillaume , G Cyrielle , M Charkaoui , M Serrero , A Wampach , M Collins , R Altwegg , F Cholet , A Amiot

Journal of Crohn’s and Colitis, Volume 19, Issue Supplement_1, January 2025, Page i1338, https://doi.org/10.1093/ecco-jcc/jjae190.0858

Background: Granulocyte and monocyte adsorptive apheresis (GMA) with ADACOLUMN® (JIMRO Takasaki Japan) is an effective and safe therapeutic option for patients with mild to moderate inflammatory bowel disease (IBD) refractory to pharmacological therapy, especially ulcerative colitis (UC). The aim of this study was to report effectiveness of GMA in patients with IBD.

Methods: All consecutive active, non-operated UC patients and Crohn’s disease (CD) patients treated with GMA in 15 French tertiary-care centres from 2007 to september 2024 were assessed. Patients received 4 to 8 weekly sessions of GMA alone or in combination with previously failing advanced therapy. Patients were assessed for effectiveness at week 14 and at week 54 for those continuing GMA as maintenance therapy and at every visit for safety. Clinical remission, steroid-free clinical remission, clinical response, colectomy as well as safety were ascertained.

Results: One hundred and twenty-nine patients with IBD (75 males, median age: 40.9 IQR[29.3-58.1] years, 102 with UC, IBD duration: 7.0 [2.9-13.1] years) were included. One hundred patients (77.5%) were previously treated with immunosuppressants and 97 (72.2%) with at least one anti-TNF. In patients with UC, baseline median total Mayo score was 7 [6-12] and mean CRP level was 23.3 ± 86.0 mg/L. In patients with CD, baseline median Harvey-Bradshaw index was 9 [7.25-10.75] and mean CRP level was 21.9 ± 27.3 mg/L. In patients with UC, week 14 clinical remission, steroid-free clinical remission and response rates were 33.3%, 27.5% and 52.0%, respectively. In patients with CD, week 14 clinical remission, steroid-free clinical remission and response rates were 33.3%, 29.6% and 66.7%, respectively. At week 14, nine patients with UC and 3 patients with CD required emergent surgery. At week 14, adverse events were reported in 26 (20.2%) and were mainly related to flare of IBD in 16 (12.4%). Other adverse events which were never classified as serious included headache in 3, arthromyalgia in 3 and abdominal pain, diarrhea, grade-1 increase in liver enzymes and mild hypotension in one. At week 54, 48 patients were still treated with maintenance GMA therapy including 13 with CD and 35 with UC. At week 54, steroid-free clinical remission rates were 38.5% (5/13) in patients with CD and 60% (21/35) in patients with UC.

Conclusion: In this real world cohort of patients with refractory IBD, GMA induced steroid-free clinical remission in one third of patients with CD and UC at W14. In patients continuing GMA maintenance therapy, steroid-free clinical remission was observed in one third of patients with CD and two thirds of patients with UC. Safety profile was favourable mostly related to relapse of IBD.

Ludovica Franceschin ¹, Alessia Guidotti ¹, Roberto Mazzetto ¹, Jacopo Tartaglia ¹, Christian Ciolfi ¹, Mauro Alaibac ¹, Alvise Sernicola ¹

Biomolecules. 2024 Nov 27;14(12):1515. doi: 10.3390/biom14121515.

Neutrophil-mediated inflammation is a key feature of immune-mediated chronic skin disorders, but the mechanistic understanding of neutrophil involvement in these conditions remains incomplete. Dapsone, colchicine, and tetracyclines are established drugs within the dermatologist’s therapeutic armamentarium that are credited with potent anti-neutrophilic effects. Anti-neutrophilic drugs have established themselves as versatile agents in the treatment of a wide range of dermatological conditions. Some of these agents are approved for the management of specific dermatologic conditions, but most of their current uses are off-label and only supported by isolated reports or case series. Their anti-inflammatory and immunomodulatory properties make them particularly valuable in managing auto-immune bullous diseases, neutrophilic dermatoses, eosinophilic dermatoses, interface dermatitis, and granulomatous diseases that are the focus of this review. By inhibiting inflammatory pathways, reducing cytokine production, and modulating immune responses, they contribute significantly to the treatment and management of these complex skin conditions. Their use continues to evolve as our understanding of these diseases deepens, and they remain a cornerstone of dermatological therapy.

GMA is a promising alternative in patients who have failed conventional therapies for generalized pustular psoriasis, pyoderma gangrenosum, Behçet’s disease, and hidradenitis suppurativa. The strengths of GMA lie in its favorable tolerability and peculiar mode of action that is able to deplete inflammation without causing immunodeficiency.

Francisco José Fernández-Pérez ¹, Nuria Fernández-Moreno ², Estela Soria-López ², Francisco Javier Rodriguez-González ², Francisco José Fernández-Galeote ³, Ana Lifante-Oliva ⁴, Concepción Ruíz-Hernández ⁴, Elisabeth Escalante-Quijaite ⁴, Francisco Rivas-Ruiz ⁵

Gastroenterol Hepatol. 2024 Nov;47(9):502196. doi: 10.1016/j.gastrohep.2024.502196. Epub 2024 May 6. (Article in Spanish)

Introduction: Granulocyte and monocyte adsorptive apheresis (GMA) removes neutrophils and monocytes from peripheral blood, preventing their incorporation into the inflamed tissue also influencing cytokine balance. Published therapeutic efficacy in ulcerative colitis (UC) is more consistent than in Crohn’s disease (CD). We assessed clinical efficacy of GMA in UC and CD 4 weeks after last induction session, at 3 and 12 months, sustained remission and corticosteroid-free remission.

Patients and method: Retrospective observational study of UC and CD patients treated with GMA. Partial Disease Activity Index-DAIp in UC and Harvey-Bradshaw Index-HBI in CD assessed efficacy of Adacolumn® with induction and optional maintenance sessions.

Results: We treated 87 patients (CD-25, UC-62), 87.3% corticosteroid-dependent (CSD), 42.5% refractory/intolerant to immunomodulators. In UC, remission and response were 32.2% and 19.3% after induction, 35.5% and 6.5% at 12 weeks and 29% and 6.5% at 52 weeks. In CD, remission rates were 60%, 52% and 40% respectively. In corticosteroid-dependent and refractory or intolerant to INM patients (UC-41, CD-14), 68.3% of UC achieved remission or response after induction, 51.2% at 12 weeks and 46.3% at 52 weeks, and 62.3%, 64.3% and 42.9% in CD. Maintained remission was achieved by 66.6% in CD and 53.1% in UC. Up to 74.5% of patients required corticosteroids at some timepoint. Corticosteroid-free response/remission was 17.7% in UC and 24% in CD.

Conclusions: GMA is a good therapeutic tool for both in UC and CD patients. In corticosteroid-dependent and refractory or intolerant to INM patients it avoids biological therapy or surgery in up to 40% of them in one year.

Sneha Annie Sebastian ¹, Oroshay Kaiwan ², Edzel L Co ³, Meghana Mehendale ⁴, Babu P Mohan

Spartan Med Res J. 2024 Sep 9;9(3):123397. doi: 10.51894/001c.123397. eCollection 2024.

Introduction: Ulcerative colitis (UC) is a chronic inflammatory bowel disorder (IBD) with periods of relapse and remission. Current advancements in clinical research have led to the development of more refined and effective medical therapy for UC.

Summary of the evidence: Traditional therapeutic agents such as 5-aminosalicylates (5-ASAs), sulfasalazine (SASP), corticosteroids, and immunomodulatory drugs have remained the gold standard for decades. However, their novel formulations and dosage regimens have changed their sequences in the medical management of UC. Several other novel drugs are in the final phases of clinical development or have recently received regulatory approval designed to target specific mechanisms involved in the inflammatory cascade for UC.

GMA has shown its efficacy in mild to moderate UC and refractory UC (steroid-dependent UC or biologic/immunologic resistant UC or lost their response to biologics) for remission induction.

Conclusions: This narrative review sought to provide a comprehensive knowledge of the potential benefits of standard and emerging therapies, including novel formulations, new chemical entities, and novel therapeutic approaches in managing UC. Keywords: Ulcerative colitis, 5- Aminosalicylic acid, sulfasalazine, corticosteroids, biologics, immunomodulators, novel formulations.

Walter Jauregui ¹, Yozahandy A Abarca ², Yasmin Ahmadi ³, Vaishnavi B Menon ⁴, Daniela A Zumárraga ⁵, Maria Camila Rojas Gomez ⁶, Aleeza Basri ⁷, Rohitha S Madala ⁸, Peter Girgis ⁹, Zahra Nazir ¹⁰

Cureus. 2024 Sep 3;16(9):e68569. doi: 10.7759/cureus.68569. eCollection 2024 Sep.

Psoriasis (PS) and inflammatory bowel disease (IBD) are immune-mediated chronic conditions that share pathophysiological processes, including immune system dysfunction, microbiome dysbiosis, and inflammatory pathways. These pathways result in increased turnover of epithelial cells and compromised barrier function. The assessment of the literature suggests that immunopathogenic mechanisms, such as tumor necrosis factor (TNF)-α signaling and IL-23/IL-17 axis dysregulation, are shared by PS and IBD. Clinical characteristics and diagnostic approaches overlap significantly, and advances in biomarker identification benefit both conditions. Current treatments, namely biologics that target TNF-α, IL-17, and IL-23, show promising results in decreasing inflammation and controlling symptoms. Precision medicine approaches are prioritized in prospective therapeutic procedures to tailor pharmaceuticals based on specific biomarkers, perhaps improving outcomes and minimizing side effects. This study thoroughly examines and evaluates the body of research on PS and IBD. Several papers were examined to compile data on clinical features, diagnosis, therapies, pathophysiology, epidemiology, and potential future therapeutic developments. The selection of articles was based on three methodological qualities: relevance and addition to the knowledge of IBD and PS. The retrieved data were combined to provide a coherent summary of the state of the knowledge and to spot new trends. The overview of the latest studies demonstrates that both PS and IBD share pathophysiological foundations and therapeutic approaches. With a spotlight on particular biomarkers, advances in precision medicine provide a promising path toward enhancing therapeutic effectiveness and minimizing side effects.

in CD Moderate to severe Oral corticosteroids. Consider enteral nutritional therapy. TNF inhibitors are recommended to be considered for steroid-dependent or refractory patients. If pharmacotherapy or nutrition therapy is ineffective or unable to adapt, the combination with granulocyte monocyte apheresis (GMA) can be considered.