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Delayed Hypersensitivity Reaction

Lisa Patel, MD and Andi Marmor, MD
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Lisa and Andi review common causes, clinical features, and treatment of delayed hypersensitivity reactions.

  • Drug hypersensitivity reactions can be divided based on timing of symptom onset as well as based on mode of action. 

  • Type I reactions are IgE-mediated and anaphylaxis is the most severe presentation of this type reaction. 

  • Type II reactions are uncommon and involve antibody-mediated cell destruction. Type II reactions may arise when drugs bind to surfaces of certain cell types and act as antigens.Goodpasture's syndrome , also known as anti-glomerular basement membrane disease, is a type II hypersensitivity that is caused by autoantibodies that attack the basement membrane of the pulmonary and renal blood vessels.

  • Type III reactions are mediated by antigen-antibody complexes and usually present as serum sickness, vasculitis, or drug fever.

  • Type IV reactions (also called delayed-type hypersensitivity) involve the activation and expansion of T cells.

    • There are four subtypes of type IV hypersensitivity mediated by either macrophages, eosinophils, T cell or neutrophils 

      •  Type IVa reactions involve Th1 immune reactions. An example of type IVa reactions is delayed swelling reaction to a tuberculin skin test.

      • Type IVb reactions involve a Th2 immune response. Th2 cells secrete the cytokines which promote an eosinophil response. Drug reaction with eosinophilia and systemic symptoms (DRESS) which is also known as drug induced hypersensitivity syndrome (DiHS) is a severe drug hypersensitivity reaction involving rash, fever and multiorgan failure. DRESS is mediated by type IVb T cell response.

      • It is postulated that a prior EBV infection primes an individual for this type of reaction. 

      • Type IVc reactions involve T cells functioning as cytotoxic effector cells. Some of the most severe cutaneous drug reactions, such as SJS and TEN, are believed to involve type IVc responses.

      • Type IVd reactions involve T cell-mediated neutrophilic inflammation. Acute-generalized exanthematous pustulosis (AGEP) is an example of this type of reaction in the skin. 

        • AGEP is characterized by pinhead-sized pustules on a background of edematous erythema with flexural accentuation. The rash resolves spontaneously once the offending drug is stopped. Aminopenicillins and fluconazole are common triggers of AGEP.

  • Contact dermatitis  is an example of type IVc reaction. Contact antigens are usually low-molecular-weight substances that penetrate the skin. The antigen is presented to T lymphocytes. These antigen-specific T lymphocytes undergo expansion that can generate an immune response upon re-exposure to the allergen. The dermatitis begins 12 to 24 hours after allergen exposure, peaks in three to five days, and may last three to four weeks if untreated

  • The most common plant contact allergen is urushiol, which is found in poison ivy and poison oak. 

    • Intact plants and stems are  less likely to irritate the skin. Urushiol is in the oils that are found in the broken twigs or crushed leaves. 

    • A contact dermatitis to poison ivy typically presents as erythema and edema with vesicles or bullae localized to the site where the allergen came into contact with the skin.

  • Other common contact allergens nickel and topical antimicrobials.

  • Topical corticosteroids are the mainstay of treatment of contact dermatitis. 

  • For more widespread or severe dermatitis, Dr. Marmor recommends using systemic steroids such as prednisone (1 to 2 mg/kg, up to a maximum dose of 60 mg) for 7 days followed by a taper over the next  several days. 

  • Patch testing can help make the diagnosis of contact dermatitis. This involves placement of the suspected allergen on the skin for about 48 hours. The patches are then removed and the skin is evaluated for positive reactions.

  • Exanthematous drug eruption, also called morbilliform or maculopapular drug eruption, is the most common type of drug hypersensitivity reaction. It is also an example of a type IVc reaction.

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Hippo Peds RAP April 2021 Written Summary 171 KB - PDF

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