What is the etiology and pathophysiology of chronic skin inflammation like psoriasis or atopic dermatitis?

Etiology and Pathophysiology of Chronic Skin Inflammation: Psoriasis and Atopic Dermatitis

Chronic skin inflammation in conditions like psoriasis and atopic dermatitis stems from complex interactions between genetic predisposition, immune dysregulation, and environmental triggers that disrupt normal skin barrier function and immune homeostasis.

Atopic Dermatitis Pathophysiology

Atopic dermatitis (AD) is a chronic, pruritic inflammatory skin disease characterized by:

• Genetic Basis:

  • Associated with elevated serum immunoglobulin E (IgE) levels 1
  • Personal or family history of type I allergies, allergic rhinitis, and asthma 1

• Immune Dysregulation:

  • Abnormal T-helper cell responses
  • Disrupted skin barrier function
  • Circadian rhythm abnormalities contributing to nocturnal exacerbations 1

• Nocturnal Factors Worsening AD:

  • Cortisol nadir during night hours
  • Increased skin temperature and poor barrier function
  • Increased transepidermal water loss (TEWL)
  • Neuropeptide-induced sensitivity
  • Susceptibility to infections
  • Itch exacerbation by bacterial products (staphylococcal superantigens)
  • Diurnally mediated chemokine gradients 1

• Inflammatory Profile:

  • TH1, TH2, and TH22 cellular infiltrate
  • Circadian variation in pruritogenic inflammatory cytokines (IL-2, IL-31) 1

Psoriasis Pathophysiology

Psoriasis is defined as a genetic, systemic, inflammatory, chronic disorder with the following characteristics:

• Genetic and Systemic Nature:

  • Genetic predisposition with environmental triggers
  • Systemic inflammatory condition affecting multiple body systems 1

• Associated Conditions:

  • Psoriatic arthritis (seronegative spondyloarthropathy)
  • Inflammatory bowel disease
  • Components of metabolic syndrome (diabetes)
  • Cardiovascular disease
  • Lymphoma 1

• Clinical Manifestations:

  • Disfiguring, scaling, and erythematous plaques
  • Often painful or severely pruritic
  • Chronic disease that waxes and wanes throughout life 1

Comparative Pathophysiology

Both conditions represent different ends of the inflammatory spectrum:

• Immune Pathway Differences:

  • AD: Predominantly TH2-driven in acute phase, with TH1 involvement in chronic phase
  • Psoriasis: Predominantly TH1/TH17-driven inflammatory pathway 2

• Barrier Function:

  • Both conditions involve disruption of epidermal barrier
  • AD: Primary barrier dysfunction with secondary immune activation
  • Psoriasis: Primary immune dysregulation with secondary barrier disruption 3

• Microenvironmental Factors:

  • Vitamins A and D metabolites influence both innate and adaptive immune responses
  • These factors can suppress inflammation and lymphocyte infiltration 4

Clinical Implications of Pathophysiology

Understanding the pathophysiological mechanisms has led to targeted therapeutic approaches:

• Treatment Targets:

  • Topical therapies addressing barrier dysfunction and inflammation
  • Phototherapy targeting immune cell proliferation
  • Systemic immunomodulatory agents for severe disease 1

• Emerging Approaches:

  • Biologic therapies targeting specific molecular pathways
  • Potential for disease modification beyond symptom control 5
  • In rare cases of concurrent AD and psoriasis, dual biologic therapy may be necessary 6

Key Differences in Clinical Presentation

• Atopic Dermatitis:

  • Typically begins in childhood
  • Characterized by intense pruritus
  • Flexural distribution in children and adults
  • Associated with other atopic conditions 7

• Psoriasis:

  • Can begin at any age
  • Multiple clinical variants (plaque, guttate, pustular, inverse, erythrodermic)
  • Well-demarcated, erythematous plaques with silvery scale
  • Often involves extensor surfaces 1

Understanding the complex pathophysiology of these chronic inflammatory skin conditions is essential for developing targeted therapies that address the underlying mechanisms rather than just managing symptoms.