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.

Miki Urushiyama ¹, Kunio Tarasawa ², Rintaro Moroi ¹, Hideya Iwaki ¹, Yusuke Hoshi ³, Hiroshi Nagai ¹, Yusuke Shimoyama ¹, Takeo Naito ¹, Fumihiko Kakuta ³, Hisashi Shiga ¹, Shin Hamada ¹, Yoichi Kakuta ¹, Kiyohide Fushimi ⁴, Yoshitaka Kinouchi ¹, Daiki Abukawa ³, Kenji Fujimori ², Atsushi Masamune ¹

JGH Open. . 2025 May 14;9(5):e70175. doi: 10.1002/jgh3.70175. eCollection 2025 May.

Aims: This study aimed to investigate the trends in pediatric inflammatory bowel diseases (IBD) management in Japan over the past decade.

Methods: We retrospectively analyzed data from Japan’s nationwide database from 2012 to 2022. Patients aged ≤ 15 years diagnosed with Crohn’s disease (CD) or ulcerative colitis (UC) were included. Trends in the use of biologics, capsule endoscopy, total parenteral nutrition (TPN), elemental diets, surgery, and granulocyte and monocyte apheresis (GMA) were examined using the Cochrane-Armitage and Jonckheere-Terpstra trend tests.

Results: Among the 8037 and 6153 pediatric UC and CD admissions, respectively, the use of biologics increased significantly (CD: from 46.0% to 53.6%; UC: from 15.0% to 33.0%, p < 0.0001). The use of capsule endoscopy in pediatric patients with CD increased markedly from 6.6% to 16.7% (p < 0.0001), whereas TPN use decreased from 8.4% to 3.0% (p < 0.0001). Surgery rates for patients with CD remained at approximately 5%, whereas those for patients with UC decreased (from 3.7% to 1.7%, p = 0.002). Elemental diets for pediatric patients with CD increased (from 54.4% to 66.2%, p < 0.0001). The use of GMA decreased significantly in patients with UC (from 12.1% to 2.7%, p < 0.0001).

Conclusion: The use of biologics and capsule endoscopy has increased in pediatric patients with IBD, whereas the use of more invasive treatments has decreased. These trends suggest a shift toward less invasive and more targeted therapeutic strategies in managing pediatric patients with IBD in Japan.

Siew Eng Choon ¹, Peter Anthony Foley ^2 3, Pravit Asawanonda ⁴, Hideki Fujita ⁵, Seong-Jin Jo ⁶, Yu-Ling Shi ^7 8, Colin Theng ⁹, Azura Mohd Affandi ¹⁰, Chul Hwan Bang ¹¹, Maria Lorna Frez ¹², Huang Yu Huei ^13 14, Doanh Le Huu ¹⁵, Tae-Gyun Kim ¹⁶, Akimichi Morita ¹⁷, Hazel H Oon ^18 19, Pablo Fernández-Peñas ^20 21, Natta Rajatanavin ²², Suganthy Robinson ¹⁰, Latha Selvarajah ²³, Tsen-Fang Tsai ²⁴

J Dermatol. 2024 Dec;51(12):1579-1595. doi: 10.1111/1346-8138.17471. Epub 2024 Oct 10.

Generalized pustular psoriasis (GPP) is a rare, chronic, heterogeneous, and potentially life-threatening disease characterized by primary, sterile, and macroscopically visible pustules with or without systemic symptoms. There are ethnic differences in the genetic mutations associated with GPP that might affect the clinical manifestations and treatment responses. Currently, there is limited evidence from the patient population in the Asia-Pacific (APAC) region, resulting in a general paucity of information on the effective management of patients with GPP in this region. This modified Delphi panel study aimed to identify current evidence and gain advanced insights to facilitate the development of a regionally tailored APAC consensus on the management of GPP. A systematic literature review (SLR) was conducted to identify published literature and develop consensus statements on (i) definition and clinical course, (ii) diagnosis of GPP, (iii) treatment outcomes, goals, and monitoring measures, and (iv) optimal management strategies and clinical practices. Statements were rated by a panel of dermatologists in two rounds, with the threshold for consensus at ≥80% agreement. Twenty experts from the APAC region reached consensus on 106 statements that were developed based on the SLR and experts’ collective expertise. The experts agreed that GPP is a rare, severe, and potentially life-threatening condition that is distinct from plaque psoriasis. This consensus emphasized the importance of a tailored treatment strategy taking into account the GPP flare severity and each patient’s unique clinical circumstances. The experts reached consensus on the severity classification of GPP flares and recommended first-line and maintenance treatment options for adult GPP, childhood GPP, and GPP in pregnancy. These consensus outcomes have been synthesized into treatment algorithms to guide dermatologists in the APAC region in their clinical decision-making processes.

Non-pharmacological treatments, such as GMA and IVIG, can be considered based on their availability in individual countries

Tomotaka Tanaka

Cureus 2023 Nov 16;15(11):e48913. doi: 10.7759/cureus.48913. eCollection 2023 Nov.

The major phenotypes of inflammatory bowel disease (IBD) include ulcerative colitis (UC) and Crohn’s disease (CD), which cause debilitating symptoms, including bloody diarrhea, abdominal discomfort, and fever. Patients require life-long immunosuppressive medications, which cause adverse side effects as additional morbidity factors. However, IBD is initiated and perpetuated by inflammatory cytokines, and given that in patients with IBD myeloid lineage leukocytes are elevated with activation behavior and release inflammatory cytokines, selective depletion of elevated granulocytes and monocytes by granulomonocytapheresis is a relevant therapeutic option for IBD patients. Therefore, a column filled with specially designed beads as granulomonocytapheresis carriers for selective adsorption of myeloid lineage leukocytes (Adacolumn) has been applied to treat patients with active IBD. Patients receive up to 10 granulomonocytapheresis sessions at one or two sessions per week. During each session, the carriers adsorb up to 60% of the myeloid leukocytes from the blood that passes through the granulomonocytapheresis column. Efficacy rates in the UC setting have been as high as 85% in steroid-naïve patients, and 100% in drug-naïve, first-episode cases, but patients with a long duration of active IBD and extensive colonic lesions that have become refractory to pharmacological treatment have not responded well. However, granulomonocytapheresis has a favorable safety profile. Given that immunosuppressive medications used to treat IBD potentially may increase the risk of severe viral infection, non-drug granulomonocytapheresis should be a favorable treatment strategy. Further, by targeting granulomonocytapheresis to patients with background features and identifying a patient as a likely responder, futile use of medical resources is avoided.

Therapeutic Granulomonocytapheresis as a Non-pharmacologic Treatment Option for Inflammatory Bowel Disease: Efficacy Reports on a Wide Age Range and Disease Profile – PubMed (nih.gov)

Therapeutic Granulomonocytapheresis as a Non-pharmacologic Treatment Option for Inflammatory Bowel Disease: Efficacy Reports on a Wide Age Range and Disease Profile – PMC (nih.gov)

Chiamaka L Okorie ¹, Krithika Nayudu ², Vinod E Nambudiri ^3 4

Exp Dermatol. 2024 Jan;33(1):e14934. doi: 10.1111/exd.14934. Epub 2023 Sep 19.

Deficiency of the interleukin-36 receptor antagonist (DITRA) is a rare autoinflammatory disorder caused by mutations in the IL36RN gene. This mutation leads to a lack of functional interleukin-36 receptor antagonists (IL-36Ra), which results in an overactive immune system and chronic inflammation. Despite its rarity, numerous case series and individual reports in the literature emphasize the importance of recognizing and managing DITRA. Early identification of the cutaneous signs of DITRA is crucial for accurate diagnosis and timely administration of appropriate treatment. This review article provides a comprehensive overview of the current understanding of the cutaneous, non-cutaneous and histopathological manifestations of DITRA, with a focus on reported treatments. The disease typically presents in early childhood, although the age of onset can vary. Patients with DITRA exhibit recurrent episodes of skin inflammation, often with a pustular or pustular psoriasis-like appearance. Additionally, non-cutaneous manifestations are common, with recurrent fevers and elevated acute-phase reactants being the most prevalent. The exact prevalence of DITRA is unknown. Some cases of loss-of-function mutations in the IL36RN gene, considered a hallmark for diagnosis, have been identified in patients with familial generalized pustular psoriasis (GPP). Biological therapies with inhibition of IL-12/23 and IL-17 are promising treatment options; paediatric patients with DITRA have shown complete response with mild relapses. New and emerging biologic therapeutics targeting the IL-36 pathway are also of interest in the management of this rare autoinflammatory disorder.

5.3 Granulocyte and monocyte apheresis (GMA) The use of GMA warrants further exploration.

Giorgos Bamias ¹, Evanthia Zampeli ², Eugeni Domènech ³ Expert Rev Gastroenterol Hepatol  2022 Jul 19;1-15. doi: 10.1080/17474124.2022.2100759.

Introduction: Inflammatory bowel disease (IBD) is a chronic immune-mediated disease of the gastrointestinal tract comprising Crohn’s disease (CD) and ulcerative colitis (UC). While any part of the digestive tract can be affected in CD, mucosal inflammation in UC is limited to the colon. Differences and similarities between the two conditions are reflected by their pathophysiology. Areas covered: An overview of immunological aspects, pharmacological management, and biomarkers of IBD is provided. The role of adsorptive granulocyte and monocyte apheresis (GMA) is reviewed including its primary and secondary effects on the immune system, as well as clinical studies in IBD (mainly UC), and potential biomarkers for adsorptive GMA. Expert opinion: In UC, adsorptive GMA with Adacolumn (Adacolumn®, JIMRO Co., Ltd. Takasaki, Gunma, Japan) selectively depletes elevated myeloid lineage leukocytes and has a range of beneficial secondary immune effects. Adsorptive GMA is a safe and effective non-pharmacological treatment option for UC. Pilot studies have reported promising results for adsorptive GMA in combination with biological agents, although larger studies are required. Fecal calprotectin concentrations, neutrophil counts in histological samples and/or the neutrophil/lymphocyte ratio in peripheral blood may prove to be useful biomarkers for predicting GMA effectiveness in the future.

https://pubmed.ncbi.nlm.nih.gov/35833363/

https://www.tandfonline.com/doi/epub/10.1080/17474124.2022.2100759?needAccess=true

Gerardo Prieto Bozano an. pedatr. contin.2012;10(5):286-9

• Existen 2 dispositivos de granulocitoféresis: Cellsorba^® (fibras de poliéster no tejidas), que fija granulocitos y linfocitos, y Adacolumn^® (acetato de celulosa) que fija selectivamente granulocitos y monocitos.
• Además de retirar leucocitos activados, la aféresis produce incremento del número de granulocitos CD10-negativos (inmaduros), disminución de citocinas proinflamatorias (factor de necrosis tumoral alfa [TNF-α], interleucina [IL-6],IL-8 e IL-1β) e incremento de citocinas inhibitorias (IL-1, IL-10)
• La granulocitoféresis es un método razonablemente eficaz y seguro para obtener la remisión en niños con colitis ulcerosa corticodependiente o resistente, sobre todo en pacientes en el primer episodio, en enfermedad de corta evolución y en aquellos que no han recibido esteroides
• El procedimiento requiere 2 accesos venosos de buen flujo. La pauta más habitual de tratamiento consiste en 1–2 sesiones semanales de 60min a un flujo de 30ml/min, hasta un total de 5–10 sesiones

https://www.elsevier.es/es-revista-anales-pediatria-continuada-51-articulo-granulocitoferesis-colitis-ulcerosa-S1696281812701002

Víctor López Baez, Pedro Arango Sancho, Yolanda Calzada Baños, Elena Codina Sampera, Ana Vinuesa Jaca, Lina Hernández Zúñiga, Álvaro Madrid Aris, Nephrology Dialysis Transplantation, Volume 35, Issue Supplement_3

The apheresis techniques in pediatrics had been presented with few complications in our center, none derived from vascular access, anticoagulation, infections or adverse effects due to use of replacement fluid. The training of medical and nursing staff is essential to identify risk situations. The use of protocols and international guidelines ensure safety in pediatrics.

https://academic.oup.com/ndt/article/35/Supplement_3/gfaa140.MO079/5853667

OP-NDTJ_Perlims 1..15 (silverchair.com)

Nina Worel ¹, Behrouz Mansouri Taleghani ², Erwin Strasser ³ Transfus Med Hemother 2019 Dec;46(6):394-406. doi: 10.1159/000503937. Epub 2019 Nov 6.

The section «Preparative and Therapeutic Hemapheresis» of the German Society for Transfusion Medicine and Immunohematology (DGTI) has reviewed the actual literature and updated techniques and indications for evidence-based use of therapeutic apheresis in human disease. The recommendations are mostly in line with the «Guidelines on the Use of Therapeutic Apheresis in Clinical Practice» published by the Writing Committee of the American Society for Apheresis (ASFA) and have been conducted by experts from the DACH (Germany, Austria, Switzerland) region.

https://pubmed.ncbi.nlm.nih.gov/31933569/

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6944925/

Mariko Sawada

poster at ISFA 2019 pag 164-165

Ensuring reliable vascular access (VA) and maintaining stable extracorporeal circulation are the most basic aspects of blood purification therapy (BPT). In children and neonates, specific tips could be helpful for BPT.
VA guidelines were published in 2011 and management methods have been unified. To ensure VA, it is necessary to determine a suitable placement site and catheter size (diameter and length), adjust the catheter tip position, and manage the catheters appropriately. It is common to use dialysis catheters for BPT, placing them in the central and peripheral veins. In neonates, the umbilical vein could also be one of the options, and central venous catheters and peripheral vein catheters could be used for BPT. In order to maintain stable extracorporeal circulation, it is necessary to maintain sufficient intravascular volume and blood pressure, set appropriate blood flow rates, and adjust the type and amount of anticoagulant. In children who cannot cooperate,
sedation management and catheter fixation should be performed to stabilize extracorporeal circulation.
There are also tips specialized for each disease state. In neonates, there is a high risk of intracranial hemorrhage and nafamostat mesylate is often used as an anticoagulant. In addition, it is necessary to increase the dose of anticoagulant or administer it from two places in the circuits. In patients with severe inflammatory bowel diseases, intestinal bleeding continues despite increased clotting function and hypovolemia is common. Heparin and nafamostat mesylate are chosen as anticoagulants. During BPT, monitoring activated clotting time, administering minimal anticoagulants, and administering transfusion and fluid load are useful methods to maintain stable extracorporeal circulation. BPT might be a powerful therapeutic tool for children as well as adults, ensuring reliable VA and maintaining stable extracorporeal circulation.

http://www.atalacia.com/isfa/data/abstract.pdf