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Drug Eruption Liangchun Wang Department of Dermatology, the Second Affiliated Hospital, Sun Yat-Sen University 09.3.20 What is drug eruptionWhat is drug eruption The adverse drug reactions of the skin Why do we have to know? Over 2 MILLION serious ADRs yearly 100,000 DEATHS yearly ADRs 4th leading cause of death ahead of pulmonary disease, diabetes, AIDS, pneumonia, accidents and automobile deaths Nursing home patients ADR rate350,000 yearly Why do we have to know? Gastrointestinal tract events 22.1% Electrolyte/renal 16.7% Hemorrhagic 12.7% Metabolic/endocrine 9.5% Dermatologic (skin) /allergic 7.9% Causes of drug eruption INGESTANTS: substances that enter the body by mouth INHALANTS: the allergen is breathed in through the nose or mouth CONTACT ALLERGIES: enter the body through the skin INJECTED: enter the body through puncture PathogenesisPathogenesis n n In most patterns pathogenesis is UNKOWN1!In most patterns pathogenesis is UNKOWN1! n n Possible mechanismsPossible mechanisms Immunologic mechanism - unpredictable Nonimmunologic mechanisms -sometimes predictable Idiosyncratic with a possible immunologic mechanism-unpredictable Immunologic mechanism - unpredictable Nonimmunologic mechanismsNonimmunologic mechanisms -sometimes -sometimes predictablepredictable Idiosyncratic with a possible immunologic Idiosyncratic with a possible immunologic mechanismmechanism-unpredictable-unpredictable Response by the patients to the drug or its metabolite Four types of hypersensitivity Type I hypersensitivity (1) Type I hypersensitivity (2) Systemic Anaphylaxis (Allergic shock) Anaphylactic shock ldrug allergy, e.g. penicillin ltoxin from bee, seafood Localized Anaphylaxis: lBreathe tract allergy: allergic rhinitis, allergic asthma lDigest tract allergy (food) lSkin allergy: urticaria, angioedema Type II hypersensitivity (1) Red cells: Penicillin, chloropromazine, phenacetin Granulocytes: Quinidine, amidopyrine Platelets: sulphonamides, thiazides Type II hypersensitivity (2) Infusion reaction Neonate hemolysis(Rh blood group antigen) Drug reactions hemolytic anemia, thrombocytopenic purpura , granulocytopenia Graves disease Type III hypersensitivity(1) z Initially described following administration of therapeutic horse serum for treatment of pneumococcal pneumonia z Now described following certain infections, administration of penicillin and other antibiotics, vaccines, and foreign proteins z Onset usually at 7-10 days following injection, coincides with switch to IgG, onset at 1-3 days with subsequent exposures Characterized by fever, chills, skin rash Type III hypersensitivity(2) Type IV hypersensitivity Nonimmunologic mechanismsNonimmunologic mechanisms -sometimes -sometimes predictablepredictable Idiosyncratic with a possible immunologic Idiosyncratic with a possible immunologic mechanismmechanism-unpredictable -unpredictable Immunologic mechanism - unpredictableImmunologic mechanism - unpredictable Over dose Cumulative toxicity Drug-drug interactions Exacerbation of disease Pharmacological side effects Idiosyncratic with a possible immunologic Idiosyncratic with a possible immunologic mechanismmechanism-unpredictable-unpredictable Immunologic mechanism - unpredictableImmunologic mechanism - unpredictable Nonimmunologic mechanisms -sometimes Nonimmunologic mechanisms -sometimes predictablepredictable DRESS TEN/SJS Drug reaction in the setting of HIV infection Drug induced lupus Clinical manifestation Clinical manifestation The most frequent cutaneous patterns: exanthemas urticarial eruptions/angioedema fixed drug eruptions Acneiform eruptions Photosensitivity Bullous drug reactions: Erythema multiforme SJS v. TEN (life threatening) n n Most common form of adverse cutaneous eruptionMost common form of adverse cutaneous eruption n n Lesions first appear proximally - especially groin and Lesions first appear proximally - especially groin and axilla, generalizing within 1-2 daysaxilla, generalizing within 1-2 days PruritusPruritus is usually prominent is usually prominent and is a distinguishing and is a distinguishing factor from a viral exanthemfactor from a viral exanthem Tend to occur within the first two weeks of txTend to occur within the first two weeks of tx but may occur later, even up to 10 days after tx but may occur later, even up to 10 days after tx n n Most common cause: Antibiotics, especially semi-Most common cause: Antibiotics, especially semi- synthetic penicillin consider untoward incidents Elicit history of allergies in patients with allergic
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