Atopic Dermatitis

• Skin


  Also known as the cutaneous membrane or integument, covers the external surface of the body and is the largest organ of the body in terms of surface area and weight
• Skin


  • Composed of two main parts; the outer epithelial tissue called the epidermis and the thicker connective tissue part called the dermis
  • Under the dermis is the subcutaneous layer of fatty adipose tissue
• Epidermis


  Contains no blood vessels and relies on diffusion of oxygen and nutrients from the blood vessels in the dermis
• Dermis


  • Composed of strong connective tissue made up of collagen and elastin, which gives skin its elasticity
  • Blood vessels, nerves, glands and hair follicles are embedded in the dermis
• Glands in the dermis

  • Sweat glands (eccrine and apocrine)
  • Sebaceous glands
• Sweat glands


  Eccrine glands produce watery sweat for thermoregulation, apocrine glands produce a protein rich secretion during emotional sweating
• Apocrine sweat glands


  Responsible for body odour when the components of the sweat, lipids and proteins, are metabolised by bacteria on the surface of the skin
• Sebaceous glands


  Produce an oil to prevent dehydration of skin and hair
• Dermis


  • Phagocytic macrophages are found in the dermis to protect this layer from microbes
• Cells of the epidermis

  • Keratinocytes (90%)
  • Melanocytes (8%)
  • Langerhans cells
  • Merkel cells
• Keratinocytes


  Produce keratin and lamellar granules containing ceramide
• Melanocytes


  Produce melanin for keratinocytes
• Langerhans cells


  Antigen presenting cells of the skin
• Merkel cells


  Contact sensory neurones and detect touch
• Layers of the epidermis

  • Stratum basale
  • Stratum spinosum
  • Stratum granulosum
  • Stratum lucidum (in thick skin)
  • Stratum corneum
• Stratum basale


  • Single layer of cuboidal or columnar keratinocytes containing intermediate filaments that are the precursor of keratin
  • Melanocytes and Merkel cells are found in this layer
• Stratum spinosum


  • Keratinocytes have spiny projections of filaments that tightly join the cells together, to give strength and flexibility
  • Langerhans cells and projections from melanocytes are found in this layer
• Stratum granulosum


  • Keratinocytes undergoing apoptosis and producing keratin
  • Lamellar granules release lipids to fill the spaces between the cells in the epidermis
  • As these cells die they become the dead cells of the stratum lucidum and the stratum corneum
• Stratum corneum


  • Consists of 25-30 layers of flattened dead cells called corneocytes
  • Filaggrin aggregates the keratin cytoskeleton, causing the cell to collapse and flatten in the outermost cell layer
  • Filaggrin is important for normal hydration of the epidermal layer
• Extracellular matrix of stratum corneum

  • Contains anti-bacterial lipids such as ceramide and sphingosine, which protect the underlying layers from bacteria
• Cells move from the metabolically active stratum basale to the dead layers of the stratum corneum over a period of 4 weeks
• Normal innate skin defences against infection

  • Cornified outer layer of skin (keratin + filaggrin), an impermeable barrier
  • Physical barrier-interlocking keratinocytes
  • Extracellular anti-microbial lipids, eg ceramide and sphingosine
  • Anti-microbial peptide defensins eg LL-37 , HBD2
  • Acid pH of sweat retards growth of some microbes
  • Defensins in sweat eg dermicidin
  • Anti-bacterial effect of oil from sebaceous glands
• Atopic dermatitis


  A common chronic inflammatory disease apparent in young children
• 80% of patients with atopic dermatitis have high levels of IgE to common environmental or food allergens
• 50% of patients with atopic dermatitis will develop asthma/allergies by their third birthday
• Symptoms of atopic dermatitis


  Itch (pruritis), dry, red, flaky skin
• Epidermal barrier defects in atopic dermatitis

  • Decreased expression of filaggrin
  • Decreased levels of ceramide and sphingosine in the stratum corneum
  • Decreased production of antimicrobial peptides
  • Physiological stress increases endogenous glucocorticosteroids which suppress lipid production
• Filaggrin


  • Contributes to the cornified cell envelope and to normal hydration of the cell layer
  • Filaggrin is a natural moisturising factor that is deficient in atopic dermatitis, due to mutations in the filaggrin gene or the inhibitory effect of Th2 cell-derived cytokines
• Decreased ceramide and sphingosine in stratum corneum


  Decreased anti-microbial function, increased water loss
• Decreased antimicrobial peptides


  Due to the inhibitory effects of Th2 cytokines on their synthesis
• Stress


  • Increases corticotropin releasing hormone (CRH), adrenocorticotropic hormone (ACTH), cortisol
  • Decreases IL-18, IL-1β, ceramide and sphingosine
• Th2 cell cytokines


  • Decrease antimicrobial peptides and filaggrin
  • Increase IgE
• Role of IgE in atopic dermatitis

  • 80% of patients have high levels of IgE in the blood
  • Specific IgE antibodies directed to staphylococcal superantigens, food antigens, aeroallergens
  • These antigens cross-link IgE bound to mast cells to induce histamine release and the itch-scratch cycle
  • IgE on dendritic cells can bind allergen and enhance antigen presentation to T-cells
  • Th2 cells stimulate immunoglobulin isotype class switching and synthesis of IgE
• Treatments for mild atopic dermatitis

  • Emollients
  • Antiseptic wash and shampoos
  • Topical antibiotics
  • Topical corticosteroids
• Immunosuppressant drugs for atopic dermatitis

  • Calcineurin inhibitors (topical tacrolimus, oral/IV cyclosporine)
  • Mycophenolate
  • Methotrexate
  • Anti-histamines