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.

Alopecia areata is a common cause of non-scaring autoimmune hair loss, associated with substantial psychosocial burden. Alopecia areata is an autoimmune disease in which loss of immune privilege in hair follicles leads to local hair follicle-associated inflammation. A chronic disease with uncertain course that is estimated to affect 2% of people over their lifetime, alopecia areata can present with a range of clinical features, from a single small round patch of hair loss to full scalp and body hair loss, and is associated with atopic, autoimmune and psychological comorbidities. Alopecia areata also has a major negative impact on quality of life, with a greater mental burden than physical burden. Since the 2010s, advances in understanding of disease pathogenesis have led to the identification of inflammatory pathways that can be successfully inhibited to produce substantial clinical responses. The therapeutic landscape has been transformed, with FDA approval of the first treatment for adults with severe alopecia areata in 2022 and for adolescents with severe alopecia areata in 2023, with multiple investigational treatments currently in phase II and phase III clinical trials.

The appendix is a small, worm-like diverticulum of the caecum, potentially having a role in regulating intestinal microbiota and immunology. Inflammation of the appendix, acute appendicitis, is one of the most common reasons for acute abdominal pain in children and adults and surgical emergency visits worldwide. The pathophysiology of appendicitis is still poorly understood. During the past decade, evidence has overturned the long-lasting dogma that all appendicitis cases have a clinical course inevitably progressing to perforation and life-threatening peritonitis unless operated upon in a timely manner. Instead, this natural course occurs only in a smaller proportion of patients, for whom emergency appendectomy remains mandatory. Advances in diagnostic accuracy following utilization of clinical scoring systems and imaging has enabled more accurate pre-interventional assessment of appendicitis disease severity. While some patients still require urgent surgery, the majority can be treated successfully with antibiotics, and in some the disease has even been shown to resolve spontaneously. This has confirmed the notion of at least two different forms of appendicitis: non-perforating and perforating, often referred to as uncomplicated and complicated appendicitis. Unified definitions of these forms are still undergoing rigorous research and debate, hampering both comparison of different studies and the establishment of unified treatment guidelines. The current knowledge on the safe and effective outcomes of non-operative treatment alternatives has further underlined the need for standardized uniform definitions of appendicitis severity and assessment of the success of two fundamentally different treatment options.

Leishmaniasis is an endemic disease in Asia, Africa, the Americas and Southern Europe caused by Leishmania parasites and transmitted through the bite of female sandflies, resulting in Leishmania replication in macrophages. The condition manifests either as visceral leishmaniasis, a potentially fatal systemic disease that causes persistent fever, enlargement of the liver and spleen (hepatosplenomegaly), and a reduction in almost all blood cells (pancytopenia), or as cutaneous leishmaniasis, characterized by ulcerative or non-ulcerative skin lesions. Disease manifestation and severity are determined by parasite, host and vector characteristics, with a complex immunological interplay. The rK39 rapid diagnostic test is the primary diagnostic method for visceral leishmaniasis, while cutaneous leishmaniasis is commonly diagnosed by microscopy of skin samples. Visceral leishmaniasis and severe forms of cutaneous leishmaniasis are managed by systemic treatment. For localized cutaneous leishmaniasis, treatment involves topical therapies, including cryotherapy, thermotherapy and/or intralesional injections with antimonials. The WHO 2021-2030 roadmap of neglected tropical diseases aims to eliminate visceral leishmaniasis as a public health problem and to achieve enhanced control of cutaneous leishmaniasis. In South Asia, a regional visceral leishmaniasis programme has dramatically reduced the caseload. Eastern Africa has recently launched a similar initiative. Sustainable progress in the control and elimination of leishmaniasis will require better diagnostics, treatment and vector control interventions as well as progress in vaccine development, political commitment, improved surveillance and healthcare services.

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.

Androgenetic alopecia (AGA) is a condition of scalp hair growth characterized by progressive miniaturization of hair follicles and a reduction in the number of active follicles. In general, frontal, mid-scalp and crown hair follicles in postpubescent men and in postmenopausal women are susceptible to AGA. In rare cases, premenopausal women and prepubescent individuals are affected. In men, AGA is hypothesized to be caused by increased androgen signalling within susceptible hair follicles, altering the levels of locally produced signalling factors that sustain hair growth, whereas the molecular basis of AGA in women remains undetermined. AGA displays variability in its time of onset, severity and distribution patterns, and genome-wide association studies have uncovered more than 380 genomic loci associated with AGA, including genes involved in androgen and WNT pathways. Furthermore, epidemiological studies support substantial ancestral variation in AGA. Effective therapies for AGA include autologous transplantation of androgen-resistant occipital hair follicles, oral finasteride and topical minoxidil. Not all individuals with AGA respond to these therapies or comply with daily use of medicines, creating a need for new approaches. Emerging therapies for AGA include hair follicle-activating peptides, mRNA-containing liposomes, as well as bioengineering of new hair follicles. AGA has a negative socioemotional effect on affected individuals, and its prompt diagnosis and treatment can improve self-reported quality of life.

Listeriosis is a serious food-borne bacterial infection caused by Listeria monocytogenes. L. monocytogenes is a facultative intracellular bacterial species that can replicate inside human cells, as well as thrive in a variety of environments, including soil, decaying vegetation, animal intestines and foods such as unpasteurized dairy products, soft cheese, raw meat, fish, seafood, vegetables and fruits. Clinically, L. monocytogenes can cause gastroenteritis in healthy individuals or serious invasive infections in at-risk populations. For example, maternal-fetal infections during pregnancy can lead to adverse pregnancy outcomes. In the elderly and immunosuppressed, listeriosis can cause septicaemia and central nervous system infections (also known as neurolisteriosis) with high mortality and risk of long-term sequelae. Genomic studies have identified four lineages of L. monocytogenes, with lineage I comprising the most virulent strains. The pathogenicity of L. monocytogenes reflects its ability to resist gastric and bile acids, colonize the intestinal lumen, cross the intestinal barrier, survive intracellularly in the bloodstream, evade immune responses, and cross the placental and blood-brain barriers. Diagnosis of listeriosis (septicaemia, neurolisteriosis, maternal-neonatal listeriosis or focal listeriosis) involves clinical observations and microbiological testing based on bacterial culture or DNA detection in individuals with prior antimicrobial therapy. Treatment typically involves aminopenicillins and aminoglycosides, with no evidence of clinically meaningful acquired antimicrobial resistance. Although listeriosis is a well-studied infection, a clearer picture of its global burden, its pathophysiology, the dynamics of the L. monocytogenes population and transmission routes is needed. On the host side, new risk factors, including genetics, and new treatment regimens to improve patient outcomes need to be identified.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a respiratory pathogen that emerged in December 2019 and caused a global pandemic by March 2020, with >7 million deaths due to coronavirus disease 2019 (COVID-19) globally as of September 2025. The clinical syndrome of COVID-19 ranges from asymptomatic infection to severe disease with pneumonia and death. SARS-CoV-2 variant type, inoculum, previous exposure and host factors influence the clinical trajectory. Identification of key structural proteins of SARS-CoV-2 and insights into the pathophysiology of the immune response to infection led to the development of effective preventive (vaccines and monoclonal antibodies) and therapeutic (antivirals and immunomodulatory agents) agents. Antiviral agents, such as remdesivir and nirmatrelvir-ritonavir, inhibit viral replication and immunomodulatory agents, such as tocilizumab and baricitinib, act to reduce a dysregulated immune response to SARS-CoV-2. The pandemic had economic and socio-cultural consequences that affected the quality of life and overall life expectancy of individuals. As the emergency phase of the pandemic concludes, robust monitoring and surveillance systems must be sustained and research to improve vaccines and therapeutics must continue to maintain control of SARS-CoV-2 in the population and be prepared for emerging pathogens with pandemic potential.

Autoimmune encephalitis (AE) is a treatable neuro-inflammatory disorder that is increasing in incidence. AE can be associated with malignancy (paraneoplastic), but in many patients no tumour is present. The disease presentation of AE can be heterogeneous depending on the type of antibody involved. AE is often caused by neuronal antibodies that bind to extracellular autoantigens (that is, N-methyl-D-aspartate receptor (NMDAR) and LGI1). Binding of these antibodies causes dysfunction of synaptic receptors, which leads to neurological symptoms. In these patients, treatment with immunosuppressive therapies is believed to decrease inflammation and deplete antibodies, and is essential for recovery. AE can also occur in patients with antibodies against intracellular antigens (such as Hu and Ri), often in the setting of malignancy. In these patients, tumour treatment is essential for stabilization or improvement. The most frequent symptoms of AE are cognitive problems, behavioural changes and seizures. Rapid recognition of AE syndromes is essential as earlier treatment of AE leads to better outcomes. For a definite diagnosis, the identification of an autoantibody is essential; however, some patients have seronegative AE. Most patients are severely affected during the acute disease stage, but long-term functional recovery is often good, particularly for patients without cancer. Nevertheless, residual anxiety, fatigue and cognitive problems can considerably affect quality of life. Research focuses on improving the understanding of pathophysiological processes, establishing patient-tailored outcome measures, optimizing treatment prediction models and studying different therapeutic regimens, all aiming to improve treatment and long-term outcomes.

Peripheral artery disease (PAD) is characterized by blockage of the arteries that supply the lower extremities, often occurring as a result of atherosclerosis and thrombosis. PAD affects approximately 230 million people worldwide, with a growing prevalence owing to population ageing and concomitant cardiovascular risk factors, including smoking, diabetes mellitus, hypertension and dyslipidaemia. Patients with PAD have an increased risk of major cardiovascular and limb events, and substantially poorer walking performance compared with those without PAD. The screening and identification of PAD involves clinical and imaging assessments of disease extent and severity and stratification of individual risk to ensure appropriate management. Patients with PAD should be treated with guideline-directed medical therapy (GDMT), including antithrombotic, lipid-lowering, glucose-lowering and anti-hypertensive therapies, and exercise therapies that aim to improve function as well as cardiovascular and limb outcomes. For patients with compromised limb viability, such as acute and chronic limb-threatening ischaemia, or severe functional impairment that does not improve with exercise training, lower extremity revascularization is recommended. Given the complexity of PAD management, a multidisciplinary vascular team is required to achieve the best individualized treatment. Further research efforts should focus on reducing ischaemic events and health disparities and on optimizing the implementation of GDMT and exercise therapy, as well as improving the quality of life in patients with PAD.

Lupus nephritis (LN) is a type of glomerulonephritis and one of the most serious complications of systemic lupus erythematosus (SLE). LN affects 25-60% of patients with SLE, with incidence and prevalence varying by age, sex, ethnicity and socioeconomic factors. LN predominantly develops within 5 years of an SLE diagnosis and, for many patients, it is the initial manifestation that leads to the recognition of SLE. In some patients, LN may develop late in the disease course, highlighting the importance of persistent awareness of its symptoms and signs. Despite an increasing understanding of disease biology and more effective treatment options, LN remains a substantial cause of morbidity and mortality as it can lead to irreversible kidney failure and associated complications. Risk factors for progression to kidney failure include persistent proteinuria, low glomerular filtration rate, hypertension at diagnosis and frequent disease flares. LN pathogenesis involves complex immune dysregulation, with key pathways including type I interferon signalling, calcineurin activation, and B and T cell dysfunction. Several immunomodulatory drugs are used for the management of LN, and treatment paradigms are increasingly shifting towards multi-agent regimens. Along with appropriate pharmacotherapy, multidisciplinary care tailored to the patient's individual needs, involving rheumatologists, nephrologists, social workers and other health professionals, is crucial for holistically addressing both the immune and non-immune risk factors for progressive kidney function loss and for maximizing kidney lifespan in LN.