Related Experiment Videos
Paradoxical inflammatory switches during biologic therapy: a mechanistic framework, clinical algorithm, and pediatric
Małgorzata Kowacka1, Michał Dec1, Hubert Arasiewicz1
1Clinical Department of Pediatric Dermatology and Vascular Anomalies, Faculty of Medical Sciences in Katowice, Medical University of Silesia, John Paul II Children's and Family Health Center, Sosnowiec, Poland.
Frontiers in Pediatrics
|June 5, 2026
Summary
Paradoxical inflammatory reactions, or flip-flop phenomena, during biologic therapy can arise from immune pathway shifts. This review synthesizes evidence and offers a clinical algorithm for managing these complex immune responses in pediatric patients.
Area of Science:
- Immunology
- Dermatology
- Pediatrics
Background:
- Biologic therapies targeting specific immune pathways can paradoxically trigger inflammatory reactions, termed flip-flop phenomena.
- These reactions involve new inflammatory phenotypes or disease exacerbation despite prior treatment success.
- A unified mechanistic framework and clinical approach are lacking, especially in pediatric populations.
Purpose of the Study:
- To synthesize evidence on the immunopathogenesis of flip-flop reactions.
- To propose a mechanistic framework for paradoxical inflammation during biologic therapy.
- To introduce a practical diagnostic and therapeutic algorithm for managing these reactions.
Main Methods:
- Narrative review of current evidence on flip-flop reactions.
- Focus on interactions between Th1/Th17, Th2, and interferon-JAK/STAT immune axes.
- Presentation of five pediatric cases illustrating distinct paradoxical inflammatory phenotypes.
Main Results:
- Paradoxical inflammation may result from selective immune pressure, leading to immune rebalancing.
- Distinct pathways contribute to eczematous, psoriasiform, and interferon-driven phenotypes.
- A diagnostic and therapeutic algorithm for early recognition and management was developed.
Conclusions:
- Paradoxical inflammatory reactions during biologic therapy are mechanistically consistent events.
- Immune rebalancing is a key therapeutic goal for managing these reactions.
- The proposed algorithm aids in the rational treatment selection and improved outcomes for patients receiving biologic agents.
Related Concept Videos
01:29Inflammatory Bowel Disease IV: Pharmacological Management
Upon diagnosis, managing Inflammatory Bowel Disease (IBD) involves addressing several crucial aspects. The primary goals include resting the bowel, correcting malnutrition, and providing symptomatic relief. Resting the bowel may consist of medications to reduce inflammation and promote healing. Correcting malnutrition is essential, often requiring dietary adjustments and nutritional supplements. Symptomatic relief aims to ease pain, diarrhea, and other discomforts in IBD.
Pharmacologic...
Pharmacologic...
01:20Inflammatory Bowel Disease IV: Clinical Manifestations
Inflammatory bowel disease (IBD) encompasses two major chronic disorders—ulcerative colitis and Crohn’s disease—each characterized by relapsing episodes of gastrointestinal inflammation. Although they share certain clinical features, their patterns of involvement and manifestations differ in ways that aid diagnosis and guide management.Ulcerative ColitisUlcerative colitis is limited to the colon and rectum and involves continuous inflammation of the mucosal layer. The disease course is marked...
01:28Inflammatory Response
An inflammatory response is a localized, nonspecific immune reaction that occurs when a tissue is injured. It is characterized by redness, swelling, heat, and pain, which are commonly called the cardinal signs and symptoms of inflammation. Inflammation can sometimes result in a loss of function.
Inflammation can be triggered by various stimuli, such as impact, abrasion, chemical irritation, infections, and extreme hot or cold temperatures. These can damage cells and connective tissue fibers,...
Inflammation can be triggered by various stimuli, such as impact, abrasion, chemical irritation, infections, and extreme hot or cold temperatures. These can damage cells and connective tissue fibers,...
01:26Inflammatory Bowel Disease I: Introduction
Inflammatory bowel disease is a group of chronic disorders marked by recurrent inflammation of the gastrointestinal tract due to an abnormal immune response against gut microflora. This leads to tissue damage. The two main forms are Crohn’s disease and ulcerative colitis.Crohn’s DiseaseCrohn’s disease is a relapsing inflammatory disorder that can affect any part of the GI tract, from the mouth to the anus. It involves all layers of the bowel wall (transmural) and shows “skip lesions” in which...
01:20Asthma: Pathogenesis and Management
Asthma is a chronic pulmonary condition involving inflammation of the airways, hyper-reactivity, and reversible obstruction of the airways. This condition can significantly impact a person's quality of life, making breathing difficult and leading to distressing symptoms.
Asthma is classified as allergic and non-allergic. Allergens such as dust mites, pollen, and pet dander trigger allergic asthma, while factors like cold air, intense emotions, or exercise can induce non-allergic asthma.
Asthma is classified as allergic and non-allergic. Allergens such as dust mites, pollen, and pet dander trigger allergic asthma, while factors like cold air, intense emotions, or exercise can induce non-allergic asthma.
01:20The JAK-STAT Signaling Pathway
Several cytokine receptors have tightly bound Janus kinase or JAK proteins attached at their cytosolic tail. Small signaling molecules such as cytokines, growth hormones, or prolactins bind to the cytokine receptors and initiate their dimerization. The dimerization brings the cytosolic JAKs together that trans-phosphorylate and activates each other. The activated JAKs now phosphorylate cytosolic tails of the cytokine receptors, which serve as binding sites for adaptor proteins such as SH2...