Causes of Eczema
Eczema occurs primarily due to an interplay between genetic, immunological, and environmental factors that lead to skin barrier dysfunction and immune system dysregulation. 1
Pathophysiological Mechanisms
Skin Barrier Dysfunction
- Genetic factors: Abnormalities in filaggrin and other stratum corneum constituents compromise the skin barrier 2
- Tight junction defects: Disruption in epidermal tight junctions further impairs barrier function 2
- Vicious cycle: Skin inflammation deteriorates barrier function by downregulating essential barrier-maintaining molecules 2
Immunological Factors
- Dendritic cell involvement: Multiple dendritic cell subtypes play key roles in eczema development:
- Langerhans cells
- Inflammatory dendritic epidermal cells
- Plasmacytoid dendritic cells 3
- T-cell responses: Various T-cell subsets contribute to inflammation:
- Th1/Tc1 or Th2/Tc2 cells
- Th17, Th22, and/or Tc22 cells infiltrate the upper dermis 4
- Innate lymphoid cells: These cells are involved in eczema formation 4
Inflammatory Process
- Acute phase: Characterized by:
- Spongiosis associated with hyaluronic acid overproduction
- Secretion of self-protective galectin-7
- Decreased expression of E-cadherin 4
- Chronic phase: Features include:
- Periostin contribution to inflammatory skin remodeling
- Dermal fibrosis
- Epidermal melanogenesis and dermal pigment deposition leading to hyperpigmentation 4
Environmental Triggers
External Factors
- Allergens: Common allergens can trigger or worsen eczema 3
- Microbial factors: Bacterial and viral stimuli influence the course and severity of eczema 3
- Irritants: Various substances can act as irritants:
- "Wet" irritants: detergents, organic solvents, soaps, weak acids and alkalis
- "Dry" irritants: low humidity air, heat, powders and dusts 1
Contact Mechanisms
Eczema can develop through different contact mechanisms:
- Irritant contact: Direct damage to the skin barrier without immune involvement
- Allergic contact: T cell-mediated immune response to specific allergens
- Phototoxic/photoallergic: Reactions triggered or worsened by light exposure 1
Pruritus (Itching) Mechanisms
- Neurological factors: Hyperinnervation of the epidermis contributes to intense itching
- Chemical mediators: Increased pruritogens in the skin
- Central sensitization: Heightened sensitivity to itch signals in the central nervous system
- Vicious cycle: Scratching damages skin, promoting further inflammation and itching 2
Clinical Manifestations
- Acute eczema: Characterized by erythema, papules, seropapules, vesicles, pustules, scales, and crusts
- Chronic eczema: Features lichenification, hyperpigmentation, and sometimes hypopigmentation
- Common symptoms: Multiple pinpoint lesions, polymorphic appearance, and intense itching 4
Comorbidities
Eczematous diseases are associated with increased risk of:
- Other allergic conditions (asthma, rhinoconjunctivitis, food allergies)
- Coronary heart disease
- Mental health issues such as depression 4, 5
Understanding these complex pathophysiological mechanisms has led to the development of targeted therapies for eczema, particularly for severe cases that don't respond to conventional treatments 5.