Type 2 inflammation (T2I) plays a crucial role in several allergic and inflammatory diseases, including asthma, atopic dermatitis (AD), chronic rhinosinusitis with nasal polyps (CRSwNP), eosinophilic esophagitis (EoE), prurigo nodularis (PN), bullous pemphigoid (BP), chronic spontaneous urticaria (CSU), and chronic obstructive pulmonary disease (COPD).1
Comorbid presentation of type 2 inflammatory diseases is common and is associated with a greater clinical and quality-of-life burden. Patients should be assessed for comorbid diseases.2 Better understanding the contribution of T2I to these diseases is critical to providing a patient-centered approach to diagnosis and individualized treatment and, thus, to improving patient outcomes.
Asthma represents the most studied type 2 inflammatory disease, with roughly 84% of asthma patients exhibiting T2I characterized by increased blood or sputum eosinophils whose counts correlate with disease severity.4 Infiltrating tissue eosinophils are a source of potent type 2 proinflammatory signals (including type 2 cytokines IL-4, IL-5 and IL-13) that facilitate lung tissue remodeling leading to airway thickening and fibrosis. Impaired lung function over time further leads to exacerbations and poor asthma control, highlighting the importance of early identification for optimal control.5,6
Atopic dermatitis (AD) is a common, chronic, inflammatory skin disease characterized by intense itch, recurring eczematous skin lesions, and greatly reduced quality of life for patients and their caregivers. Type 2 inflammation plays a significant role in AD pathophysiology, with key type 2 cytokines implicated including IL- 4, IL-5, IL-13 and IL-31.9
T2I leads to multiple clinical features associated with eczematous lesions, including intense itch, barrier dysfunction, and increased risk of skin infections. Up to 80% of atopic dermatitis patients present with other type 2 inflammatory diseases.1
Chronic rhinosinusitis with nasal polyps (CRSwNP) is a chronic inflammatory disease marked by grape-like projections of inflammatory polyps within the nasal cavity leading to a myriad of persistent symptoms including nasal congestion, post-nasal drip, facial pressure or pain, rhinorrhea, and loss of smell, all of which negatively affect the patient’s health-related quality of life.11-13 Asthma commonly co-occurs with CRSwNP, and symptoms for both diseases are often exacerbated in these patients.14
Approximately 80% of CRwNP cases present with T2I characterized by an increase in IL-4, IL-5, and IL-13 production by TH2 and ILC2 cells.15-18
T2I is present in up to 40% of patients with COPD and is associated with an increased risk of exacerbations.20 Cytokines commonly elevated in these patients include IL-4, IL-5, IL-13, with ILC2 and TH2 cells also elevated. These changes can cause raised eosinophil counts in sputum, bronchial tissue, and blood, and/or elevated levels of fractional exhaled nitric oxide.21
Eosinophilic esophagitis is a chronic, allergen-driven, type 2 inflammatory disease of the esophagus. Persistent T2I in untreated EoE leads to stricture formation, magnifying the clinical sequelae of dysphagia, food impactions, and a markedly diminished quality of life.23 A dysregulated feed-forward cycle that develops between an abnormal esophageal epithelium and the immune system is central to EoE pathophysiology. The esophageal epithelium with impaired barrier function stimulates allergen-induced type 2-biased immune activation. Characteristic Th2 cytokines include interleukin IL-33, TSLP, IL-4, IL-5, and IL-13.24
Prurigo nodularis (PN) is a highly burdensome condition that presents with pruritic nodules on the skin of extremities and the trunk and is characterized by an intractable itch-scratch cycle, severely impacting patient quality of life. Its pathogenesis is associated with immune dysregulation mediated by cytokines, including IL-4, IL-13, IL-17, IL-22 and IL-31, indicating a role for type 2 inflammation alongside Th17 and Th22-mediated inflammation.26
Bullous pemphigoid (BP) is an autoimmune blistering disease that mainly occurs in the elderly. T2I plays a central role in the pathogenesis of BP, beginning when autoantibodies target two proteins in the skin’s basement membrane zone: BP180 and BP230. This activates Th2 cells and ILC2s, which produce inflammatory cytokines including IL-4, IL-5, and IL-13.27,28
IL-4 promotes Th2 cell differentiation and drives B cells to produce IgE antibodies—a hallmark of BP found in 70%-85% of patients. IL-5 supports eosinophil development and survival, explaining why eosinophilia is common in BP and correlates with disease severity. IL-13 works synergistically with IL-4 to enhance IgE production and is associated with itch severity. The presence of elevated IgE leads to mast cell and basophil activation, causing the release of inflammatory mediators that contribute to tissue damage and blister formation.27,28
Chronic spontaneous urticaria (CSU) is an autoimmune condition characterized by the recurrent appearance of itchy wheals and/or angioedema that persists for several months or years. There are two main types:31,32
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