Rajendra Karki, Mihai G Netea, Caroline Diorio, Thirumala-Devi Kanneganti
{"title":"Cytokine storm.","authors":"Rajendra Karki, Mihai G Netea, Caroline Diorio, Thirumala-Devi Kanneganti","doi":"10.1038/s41572-025-00677-4","DOIUrl":"10.1038/s41572-025-00677-4","url":null,"abstract":"<p><p>Cytokine storm describes a spectrum of clinical manifestations that feature increased cytokine levels in circulation owing to overactivated immune responses. These increased concentrations of cytokines can cause tissue and organ damage, potentially leading to lethality. Cytokine storm can be induced by a variety of underlying clinical conditions, including infection, auto-inflammatory and autoimmune conditions, monogenic causes, or therapeutic intervention, which often makes diagnosis and treatment difficult. However, studies have identified conserved molecular mechanisms that inform therapeutic strategies. Cytokine storm is initiated by cytokine production and exacerbated by a self-amplifying positive feedback loop between cytokines and inflammatory cell death (PANoptosis). The process begins when cells detect triggers and undergo inflammatory signalling to produce and release cytokines via canonical secretion pathways or through lytic cell death such as pyroptosis and PANoptosis. This release of inflammatory cytokines, and potentially of other damage-associated molecules, can then drive inflammation and cell death in neighbouring cells through paracrine PANoptosis, resulting in further cytokine release and the amplification of the cycle. Improved understanding of the molecular and cellular mechanisms driving cytokine storm is critical for developing effective therapeutic strategies and improving clinical outcomes.</p>","PeriodicalId":18910,"journal":{"name":"Nature Reviews Disease Primers","volume":"12 1","pages":"1"},"PeriodicalIF":79.8,"publicationDate":"2026-01-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145985137","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Jo Ellen Wilson, Deepti Gurdasani, Raimund Helbok, Serefnur Ozturk, Douglas D Fraser, Saša R Filipović, Michael J Peluso, Akiko Iwasaki, Clarissa Lin Yasuda, Tommaso Bocci, Alberto Priori, Daniel Altmann, Nisreen A Alwan, E Wesley Ely
{"title":"COVID-19-associated neurological and psychological manifestations.","authors":"Jo Ellen Wilson, Deepti Gurdasani, Raimund Helbok, Serefnur Ozturk, Douglas D Fraser, Saša R Filipović, Michael J Peluso, Akiko Iwasaki, Clarissa Lin Yasuda, Tommaso Bocci, Alberto Priori, Daniel Altmann, Nisreen A Alwan, E Wesley Ely","doi":"10.1038/s41572-025-00674-7","DOIUrl":"10.1038/s41572-025-00674-7","url":null,"abstract":"<p><p>Long COVID is an infection-associated chronic condition that typically occurs within 3 months of acute COVID-19 infection in which symptoms are intermittently or continuously present for at least 3 months. Long COVID is estimated to affect between 80 and 400 million people globally, with an incidence of 5-20% in the community and up to 50% among hospitalized patients following acute SARS-CoV-2 infection. Common neuropsychiatric and mental health symptoms of long COVID include memory deficits, executive dysfunction, anxiety, depression, recurring headaches, sleep disturbances, neuropathies, problems with taste and smell, and dizziness that accompanies erratic heart rates and severe post-exertional malaise. Underlying pathophysiological mechanisms includes SARS-CoV-2 viral persistence, herpesvirus reactivation, microbiota dysbiosis, autoimmunity, clotting and endothelial abnormalities, and chronic immune activation. Owing to the variability in the clinical presentation, management must be tailored based on a patient's presenting symptoms.</p>","PeriodicalId":18910,"journal":{"name":"Nature Reviews Disease Primers","volume":"11 1","pages":"91"},"PeriodicalIF":76.9,"publicationDate":"2025-12-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145827997","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Rie R Yotsu, Rachel E Simmonds, Dziedzom K de Souza, Richard Odame Phillips, Yaw Ampem Amoako, Shashikant Srivastava, Kingsley Asiedu, Sara Eyangoh, Paul D R Johnson, Gerd Pluschke
{"title":"Buruli ulcer.","authors":"Rie R Yotsu, Rachel E Simmonds, Dziedzom K de Souza, Richard Odame Phillips, Yaw Ampem Amoako, Shashikant Srivastava, Kingsley Asiedu, Sara Eyangoh, Paul D R Johnson, Gerd Pluschke","doi":"10.1038/s41572-025-00672-9","DOIUrl":"10.1038/s41572-025-00672-9","url":null,"abstract":"<p><p>Buruli ulcer is a slowly progressive necrotizing disease of the skin caused by Mycobacterium ulcerans, recognized by WHO as a neglected tropical disease. Around 2,000 cases are reported annually, but underdiagnosis and under-reporting probably obscure the true burden. A major advance in the understanding of Buruli ulcer pathogenesis was the discovery that mycolactone, a lipid-like exotoxin secreted by M. ulcerans, inhibits the Sec61 translocon, driving tissue destruction and immune suppression. M. ulcerans is an opportunistic environmental pathogen; however, its mechanisms of transmission remain unclear in most regions. PCR is the current gold standard for diagnosis, but its cost and technical demands limit use in resource-limited settings. Treatment is available with an oral regimen of rifampicin plus clarithromycin for 8 weeks, but further research is in progress to explore alternative drugs, optimized dosing and duration, and improved affordability. Adjunctive wound care, management of paradoxical reactions and rehabilitation, including physiotherapy and psychosocial support, are essential components of Buruli ulcer management. Future efforts should focus on elucidating transmission pathways to inform prevention, developing rapid diagnostics, refining and adapting drug regimens for diverse clinical presentations and patient groups, and advancing wound care. Strengthening healthcare worker training and integrating Buruli ulcer control with that of other skin diseases will enhance accessibility to early diagnosis and treatment, prevent disabilities and deformities, and reduce stigma, ultimately ensuring better quality of life for affected individuals worldwide.</p>","PeriodicalId":18910,"journal":{"name":"Nature Reviews Disease Primers","volume":"11 1","pages":"89"},"PeriodicalIF":79.8,"publicationDate":"2025-12-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145781534","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Paola Romagnani, Sydney C W Tang, Astrid Weins, Tobias B Huber, Charlotte Osafo, Hans-Joachim Anders
{"title":"Podocytopathies.","authors":"Paola Romagnani, Sydney C W Tang, Astrid Weins, Tobias B Huber, Charlotte Osafo, Hans-Joachim Anders","doi":"10.1038/s41572-025-00671-w","DOIUrl":"https://doi.org/10.1038/s41572-025-00671-w","url":null,"abstract":"<p><p>Podocytopathies are glomerular diseases caused by initial podocyte injury or dysfunction that lead to proteinuria and often nephrotic syndrome. The term encompasses characteristic histological patterns, most commonly focal segmental glomerulosclerosis, minimal changes, membranous nephropathy, diffuse mesangial sclerosis and collapsing glomerulopathy. However, proteinuria of glomerular origin is frequently managed without biopsy; importantly, when the protein loss is mostly albumin, it is a direct readout of podocyte injury and a strong predictor of cardiovascular events, kidney failure and reduced survival. Patients present with oedema and volume disturbances and are at risk of thromboembolism, serious infections and progressive kidney dysfunction. Aetiologically, podocytopathies arise from autoimmune, genetic, mechanical (hyperfiltration), infectious, toxic or monoclonal mechanisms, which may coexist and vary by age; this unifying, mechanism-based view bridges the historically divergent paediatric (response-based) and adult (histology-based) classifications. Diagnosis integrates clinical features with emerging serology for podocyte-directed autoantibodies, targeted genetic testing and kidney biopsy when required. Diagnostic workup has to delineate the causes of podocyte dysfunction. Management combines supportive care with aetiology-guided therapy aimed at minimizing steroid exposure and preventing relapses. Current advances in the field and their effects on diagnostic and therapeutic algorithms open the path towards personalized use of traditional treatments and newly available drugs, which should improve outcomes and quality of life for patients with podocytopathies.</p>","PeriodicalId":18910,"journal":{"name":"Nature Reviews Disease Primers","volume":"11 1","pages":"87"},"PeriodicalIF":76.9,"publicationDate":"2025-12-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145743360","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Julien Seneschal, Jung Min Bae, Khaled Ezzedine, Iltefat Hamzavi, John E Harris, Barbara Bellei, Davinder Parsad, Thierry Passeron, Nanja van Geel, Katia Boniface, Mauro Picardo
{"title":"Vitiligo.","authors":"Julien Seneschal, Jung Min Bae, Khaled Ezzedine, Iltefat Hamzavi, John E Harris, Barbara Bellei, Davinder Parsad, Thierry Passeron, Nanja van Geel, Katia Boniface, Mauro Picardo","doi":"10.1038/s41572-025-00670-x","DOIUrl":"10.1038/s41572-025-00670-x","url":null,"abstract":"<p><p>Vitiligo is an acquired autoimmune depigmenting disorder that affects approximately 0.36% of the global population and presents in three forms based on lesion distribution: non-segmental, segmental and mixed vitiligo. Beyond its visible impact on the skin, vitiligo deeply affects mental well-being and quality of life. The pathogenesis of non-segmental vitiligo is influenced by genetic polymorphisms that are linked to immune response and melanogenesis pathways, whereas environmental factors contribute to disease onset. Diagnosis is generally clinical, with laboratory tests or biopsies rarely required. Melanocyte loss involves mechanisms, such as cellular stress, innate immune activation and adaptive immune responses, that specifically target melanocytes, with a central role for tissue-resident memory T cells. This cascade ultimately leads to the depletion of epidermal melanocytes and impairs melanocyte stem cell regeneration. Clinical management emphasizes shared decision-making with three primary objectives: halting depigmentation, initiating repigmentation and sustaining pigment restoration. Signs of active disease help clinicians to identify patients in need of intervention. Treatments approved in the past 2 years offer potential for reversing disease progression, and emerging therapies targeting key pathways to modulate immune activation and stimulate melanocyte regeneration and differentiation are being tested in clinical trials.</p>","PeriodicalId":18910,"journal":{"name":"Nature Reviews Disease Primers","volume":"11 1","pages":"85"},"PeriodicalIF":76.9,"publicationDate":"2025-12-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145678215","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Stefan Leucht, Spyridon Siafis, John J McGrath, Patrick McGorry, Oliver D Howes, Carol Tamminga, Richard Carr, Irene Bighelli, Johannes Schneider-Thoma, Josef Priller, John M Davis
{"title":"Schizophrenia.","authors":"Stefan Leucht, Spyridon Siafis, John J McGrath, Patrick McGorry, Oliver D Howes, Carol Tamminga, Richard Carr, Irene Bighelli, Johannes Schneider-Thoma, Josef Priller, John M Davis","doi":"10.1038/s41572-025-00667-6","DOIUrl":"https://doi.org/10.1038/s41572-025-00667-6","url":null,"abstract":"<p><p>Schizophrenia is a challenging and diverse mental health condition with a lifetime prevalence of 0.4%. Schizophrenia usually manifests in late adolescence or early adulthood and is associated with high disability and a reduced life expectancy. Risk factors include genetic predisposition, prenatal and birth complications, infections and immune dysfunction, and cannabis use as well as psychosocial factors such as childhood trauma or migration. The first psychotic episode is often preceded by a long prodromal phase that can last for several years. No markers are yet available for clinical use that allow prediction of disease development or a diagnosis to be established. A leading theory postulates that excitatory-inhibitory (that is, glutamate-GABA) imbalance in the cortex ultimately leads to dysfunction of the dopaminergic system. Schizophrenia is a heterogeneous disease with different manifestations, including psychotic symptoms as well as negative symptoms and global cognitive deficit, that do not respond to antipsychotic drugs, making management very difficult. Pharmacological treatment coupled with psychotherapeutic interventions, such as cognitive behavioural therapy, cognitive remediation and psychoeducation, remains the mainstay of treatment; however, treatment resistance is frequent. The first medication that targets neurotransmitter systems other than dopamine has been approved for use. Current attempts to use virtual reality and avatars to improve psychotic symptoms and smartphone applications to prevent relapses seem promising.</p>","PeriodicalId":18910,"journal":{"name":"Nature Reviews Disease Primers","volume":"11 1","pages":"83"},"PeriodicalIF":76.9,"publicationDate":"2025-11-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145636245","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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