The review, conducted according to the PRISMA-ScR guidelines for scoping reviews, screened 1,936 records and ultimately included 27 studies that examined children and adolescents whose diagnosis was delayed, missed, or changed from one type of diabetes to another. The researchers used a population-concept-context framework to decide which studies qualified, focusing on three distinct scenarios: children whose type 1 diabetes diagnosis came late, children whose initial diagnosis was wrong at the first medical encounter, and children whose diabetes was initially classified as a different type altogether. This structure allowed the team to separate the different kinds of diagnostic failure that can occur on the long road from first symptoms to correct treatment.

The technical picture that emerges is one of striking heterogeneity. For newly diagnosed type 1 diabetes, the frequency of delayed diagnosis ranged from 14.1 to 46.6 percent in studies that did not stratify results by ketoacidosis status. When the analysis separated children by whether they had developed diabetic ketoacidosis, the most dangerous acute complication of the disease, the ranges diverged sharply: 55.0 to 58.7 percent among children without ketoacidosis, and a staggering 43.0 to 98.1 percent among those with it. In other words, children who ended up in the most life-threatening state were often those whose diagnosis had been missed the longest, allowing insulin deficiency to progress unchecked until the body began breaking down fat for fuel and accumulating acidic ketones in the blood.

Missed diagnosis at the first healthcare contact followed a similar pattern. Across studies without stratification by ketoacidosis status, 16.0 to 38.7 percent of children were sent home or otherwise misdiagnosed at their initial encounter. Among children who did not develop ketoacidosis, the range was 5.0 to 34.8 percent, while among those who did, it spanned from 0.6 to as high as 72.0 percent. The enormous variability, the authors stress, reflects real differences in populations, healthcare settings, definitions of delay, and the methods used to ascertain diagnostic error, rather than a single universal failure rate. A retrospective chart review in one country may count delay differently than a prospective cohort in another, which makes direct comparison difficult even when the underlying clinical problem is the same.

Beyond delays in recognizing type 1 diabetes itself, the review also quantified how often children are assigned the wrong type of diabetes. Misclassification between type 1 and type 2 diabetes occurred in 1.4 to 22.7 percent of cases across the included studies. This matters because the two diseases demand fundamentally different management: type 1 diabetes requires immediate and lifelong insulin replacement, while type 2 diabetes in adolescents may initially be managed with lifestyle changes and oral agents. A child with type 1 diabetes mistakenly treated as type 2 can deteriorate rapidly, and the review found that misdiagnosis was indeed associated with errors in management and an increased risk of adverse events.

The review also documented rarer but clinically important diagnostic revisions. In a population of patients with atypical presentations of type 1 diabetes, 11.6 percent were subsequently reclassified as having maturity-onset diabetes of the young, a monogenic form of diabetes caused by mutations in single genes that affect insulin-producing beta cells. In a cohort of patients initially diagnosed with type 1 diabetes, 4.58 percent were ultimately found to have Wolfram syndrome, a rare genetic disorder that combines diabetes with optic atrophy, deafness, and other neurological features. These figures underscore why the studies that addressed diabetes classification relied on diagnostic protocols and algorithms, and performed genetic testing, to arrive at the correct label. Monogenic diabetes, in particular, can masquerade as type 1 diabetes for years, and identifying it changes prognosis, family counseling, and sometimes treatment entirely.

So where do the errors actually happen? The review identified the most frequent mistakes made by healthcare professionals as the omission or misinterpretation of clinical symptoms and improper handling of laboratory examinations. The classic warning signs of type 1 diabetes in children, including excessive thirst, frequent urination, unexplained weight loss, and fatigue, can be subtle in their early stages and easily attributed to more benign causes such as urinary tract infections, viral illnesses, or behavioral changes. Laboratory findings can compound the confusion: a mildly elevated blood glucose may be dismissed as a laboratory artifact or a stress response, and glycosylated haemoglobin values may not yet reflect the rapid metabolic deterioration of new-onset disease.

The consequences of these errors are not abstract. Diabetic ketoacidosis at diagnosis is associated with longer hospital stays, admission to paediatric intensive care units, and potential long-term effects on the developing brain, since severe ketosis and cerebral edema can leave lasting neurological damage. Children who are misdiagnosed with type 2 diabetes and started on inappropriate therapy may experience worsening hyperglycemia and a more abrupt, more dangerous onset of insulin dependence. The review’s finding that misdiagnosis was linked to management errors and adverse events gives quantitative weight to what paediatric endocrinologists have long argued: the window between first symptoms and correct diagnosis is a critical period in which the entire trajectory of the disease can be shaped.

The authors are careful about the limits of their evidence. Because the included studies differed so widely in populations, settings, definitions, and ascertainment methods, the reported frequencies of missed recognition, diagnostic delay, and misclassification vary markedly, and no single figure can be treated as a universal benchmark. A scoping review, by design, maps the breadth of existing literature rather than pooling it into a single estimate, and the 27 included studies represent a heterogeneous mix of prospective cohorts, retrospective cohorts, and cross-sectional designs from different healthcare systems. What the review does establish is that these diagnostic failures are not rare curiosities but recurring features of paediatric diabetes care across multiple countries and settings.

The practical implications are clear. Raising awareness of the classic symptom cluster among primary care providers, parents, and school health staff could shorten the delay between first symptoms and first test. Simple protocols, such as checking blood glucose in any child presenting with unexplained thirst, urination, or weight loss, could catch cases before ketoacidosis develops. And for children whose diabetes does not behave as expected, structured diagnostic algorithms and access to genetic testing for monogenic forms such as maturity-onset diabetes of the young and Wolfram syndrome could prevent years of misdirected treatment. As the incidence of type 1 diabetes in children continues to rise worldwide, the review serves as both a warning and a roadmap: the tools for earlier, more accurate diagnosis already exist, and the evidence now shows exactly how much is at stake when they are not used.

Subject of Research: Delayed diagnosis and misdiagnosis of type 1 diabetes in children and adolescents

Article Title: Delayed diagnosis and misdiagnosis of type 1 diabetes in children and adolescents: a scoping review

Article References: Giza, S., Fedi, L., Schierloh, U., Fagherazzi, G., de Beaufort, C., & Aguayo, G. A. (2026). Delayed diagnosis and misdiagnosis of type 1 diabetes in children and adolescents: a scoping review. BMC Pediatrics. https://doi.org/10.1186/s12887-026-07808-0

Image Credits: AI Generated

DOI: 10.1186/s12887-026-07808-0

Keywords: type 1 diabetes, children, adolescents, delayed diagnosis, misdiagnosis, diabetic ketoacidosis, misclassification, MODY, Wolfram syndrome, scoping review, paediatric care, diagnostic errors

The technology at the heart of this effort, chimeric antigen receptor T-cell therapy, involves extracting a patient’s own T lymphocytes and genetically engineering them to express an artificial receptor that recognises a specific molecular target. In oncology, the most common target is CD19, a protein displayed by many B-cell malignancies, but the same target has proved decisive in autoimmunity for a different reason: pathogenic B cells drive diseases such as systemic lupus erythematosus, myositis and systemic sclerosis. When engineered CAR T cells encounter CD19-expressing B cells, they eliminate them with a depth that conventional immunosuppressive drugs rarely achieve, and in doing so they can interrupt the autoimmune cascade at its source. Early clinical reports have described patients with severe, treatment-refractory disease entering drug-free remission after a single infusion, an outcome that would have seemed implausible only a few years ago.

Yet the expert panel is emphatic that enthusiasm must be tempered by caution. CAR T-cell therapy remains an evolving discipline in autoimmunity, with most evidence derived from small, single-arm studies rather than large randomised trials. Because high-level evidence is still emerging, the recommendations were constructed using the EBMT’s structured practice harmonisation methodology, a formal consensus process designed precisely for situations where clinical practice is racing ahead of definitive data. The result is not a rigid protocol but a shared framework: a set of expectations about who should be treated, where, by whom, and with what degree of monitoring before and after the cells are infused.

The cornerstone of the framework is patient selection. The consensus recommends considering CAR T-cell therapy only for patients with severe autoimmune disease that remains active or progressive despite appropriate standard treatment, meaning that conventional therapies must have been given a genuine opportunity to work before the cellular option is pursued. Whenever possible, the experts say, treatment should be delivered within the controlled environment of a clinical trial, where systematic data collection can accelerate the field’s understanding of efficacy and risk. When trial participation is not feasible, the decision to proceed should be documented through a multidisciplinary assessment involving both autoimmune disease specialists and haematology or cellular therapy experts, ensuring that perspectives from both sides of this unusual therapeutic border are represented before an irreversible step is taken.

Where the therapy is delivered matters as much as who receives it. The recommendations call for treatment in experienced centres, preferably those accredited by FACT or JACIE for immune effector cell therapies, because accreditation signals consistent quality and safety standards in cell processing, manufacturing oversight and toxicity management. The panel also stresses that autoimmune diseases differ enormously from one another in organ involvement, comorbidity burden and prior treatment exposure, so disease-specific assessment and monitoring remain essential even within a common framework. A patient with refractory lupus nephritis, a patient with severe multiple sclerosis and a child with juvenile dermatomyositis present distinct anatomical and immunological challenges, and the guidance explicitly resists the temptation to impose a one-size-fits-all pathway on this heterogeneity.

Raffaella Greco of San Raffaele Hospital in Milan and Dominique Farge of St-Louis Hospital in Paris, who coordinated the consensus process, framed the initiative as a balance between promise and prudence. CAR T-cell therapy, they noted, is emerging as an important new therapeutic approach for patients with severe and refractory autoimmune diseases, but the field is evolving rapidly, and careful patient selection, multidisciplinary management and long-term follow-up are essential. Their stated aim is a shared framework that supports patient safety and greater consistency in clinical practice while the evidence base continues to be built, a formulation that captures the panel’s central tension: how to standardise care without freezing a science that is still moving.

A substantial portion of the guidance concerns what happens around the infusion itself. The recommendations place strong emphasis on activities before and after CAR T-cell administration, including diagnostic assessment, treatment planning, immune monitoring and the management of treatment-related toxicities. One of the most clinically demanding challenges highlighted is the need to distinguish inflammatory complications caused by the therapy, such as cytokine release syndrome or immune effector cell-associated neurotoxicity, from a flare or progression of the underlying autoimmune disease. These entities can overlap in presentation, and misattributing one for the other can lead to harmful treatment decisions. The panel therefore calls for close collaboration between haematology, cellular therapy and autoimmune disease teams, so that the interpretation of fevers, neurological changes or serological shifts is informed by expertise on both sides.

Long-term follow-up and systematic data collection emerge as the panel’s most urgent priorities. The experts strongly recommend reporting every patient treated with CAR T-cell therapies to the EBMT Registry, a step intended to build understanding of long-term outcomes, durability of response and late toxicities. This emphasis echoes recent statements from both the United States Food and Drug Administration and the European Medicines Agency, which have underscored the need for extended surveillance of patients receiving these genetically modified cells. Because CAR T cells can persist in the body for years and deplete B-cell lineages for prolonged periods, questions about hypogammaglobulinaemia, infection risk, secondary malignancy and immune reconstitution cannot be answered without registry-scale data. The EBMT Registry has accordingly been expanded to support structured follow-up of patients with autoimmune diseases across participating centres, converting scattered clinical anecdotes into a coherent evidence base.

Children and adolescents receive dedicated attention in the update, reflecting both the particular vulnerability of younger patients and the relative scarcity of paediatric evidence. The recommendations call for multidisciplinary assessment that weighs disease severity and previous treatments against factors unique to growing patients: organ damage accumulated during development, fertility preservation, quality of life and the long-term consequences of chronic immunosuppression, which in young patients can span decades. The calculus of offering a single potentially curative infusion to a teenager instead of a lifetime of steroid and immunosuppressant exposure is compelling, but the panel insists that the limited paediatric data demand heightened deliberation rather than reduced scrutiny.

Looking forward, the authors identify priorities that will shape the next phase of research: larger controlled clinical trials to establish efficacy beyond single-arm cohorts, biomarkers capable of predicting which patients will respond and which will suffer toxicity, novel CAR targets that might extend the approach beyond B-cell-driven disease, and strategies to improve treatment access so that the therapy does not remain confined to a handful of specialised centres. The 2026 recommendations are explicitly conceived as living guidance under the auspices of EBMT, ISCT and JACIE, and they will continue to evolve as new evidence and clinical experience emerge. For now, they represent the most comprehensive attempt yet to impose scientific discipline on one of the most exciting developments in modern immunology, ensuring that as CAR T cells march from the oncology ward into the rheumatology clinic, they do so under conditions designed to protect the very patients they are meant to help.

Subject of Research: Consensus recommendations for CAR T-cell therapy in severe autoimmune diseases

Article Title: International consensus sets updated framework for CAR T-cell therapy in severe autoimmune diseases

Article References: International consensus sets updated framework for CAR T-cell therapy in severe autoimmune diseases. (n.d.). Original publication

Image Credits: AI Generated

DOI: Not provided

Keywords: CAR T-cell therapy, autoimmune diseases, EBMT, ISCT, JACIE, The Lancet Rheumatology, patient selection, immune monitoring, long-term follow-up, clinical trials, paediatric care, registry data