SJS

• Initially presents with a prodome of nausea, vomiting, sore throat, cough, fever, myalgias, arthralgias
• Blistering of the mucous membranes (mouth, eyes, nasal cavity, vagina) and patchy rashes over most of the body

TEN

• Widespread blister formation in the epidermis and mucous membranes; preceded by SJS
• Large areas of skin may peel off

Symptoms

• Angioedema
• Facial flushing
• Wheezing
• Chest tightness
• Laryngeal edema
• Stridor
• Feeling of impending doom

Signs

• Hypotension
• Cardiac arrhythmias

• Asymmetric, circumscribed erythematous popular lesions
• Lesions have raised borders and areas of central clearing
• Pruritus

Formation of a complete antigen

• To be recognized as a complete antigen, drugs (haptens) must bind to high molecular weight carrier proteins
• Parent drug rarely has the ability to bind and serve as a hapten -- usually a reactive metabolite

Processing of the complete antigen by antigen presenting cells

• APCs help the hapten-protein complex to be recognized
• APCs break down complex and the hapten-peptide fragments bind to MHC class I or II
• T lymphocytes recognize hapten-MHC complex on APC

Recognition of antigenic determinant by T lymphocytes

• 3 signals are needed to activate T-helper cells
• Signal 1 occurs when Hapten-MHC complex interacts with antigen receptor on T-helper cells
• Signal 2 involves interaction between APC and T-helper cell resuling in release of cytokines by T-helper cells -- does not always occur so immune reaction will be blunted
• Signal 3 activates CD4+ T cells and causes them to differentiate into T-helper type 1 (Th1) or Th2 cells

Generation of drug-specific antibody or sensitized T cells

• Immune responses lead to generation of either antibodies (if Th2) or sensitized T cells (if Th1)
• Memory cells are produced during this stage to allow for a faster response upon re-exposure

Elicitation of clinical immune response

May take 5-21 days of continued therapy

Anaphylactic

• Timing: within 30 min
• Antibody: IgE
• Targeted Cell: Basophils, Mast cells
• Clinical presentation

Anaphylaxis

Isolated urticaria

Angioedema

Bronchospasm

Respiratory distress

Abdominal cramping

Cardiovascular collapse

Arrhythmias

Eosinophilia

Cytotoxic

• Timing: 5-12 hrs
• Antibody: IgG, IgM
• Targeted Cell: Blood cells
• Clinical presentation

Hemolytic anemia

Thrombocytopenia

Neutropenias

Vasculitis

Immune Complex

• Timing: 3-8 hrs
• Antibody: IgG, IgM
• Targeted Cell: Skin, blood vessel walls, joint tissue, kidney, liver
• Clinical presentation

Serum sickness-like illness

Vasculities

Morbilliform rash

Maculopapular rash

Urticaria

Glomerulonephritis

Interstitial nephritis

Erythema multiformes

SJS

Anaphylactic

• Timing: 24-48 hrs
• Antibody: Sensitized T Lymphocyte
• Targeted Cell: Skin, liver, kidney, lungs
• Clinical presentation

Contact dermatitis

Maculopapular rash

Bullous or pustular eruptions

SJS

TEN

Interstitial pneumonitis

Granulomatous hepatitis