An 18-year-old man is evaluated for recurrent episodes of shortness of breath, wheezing, runny nose, and watery eyes. The patient reports that his symptoms have recently worsened since he started training outdoors for an upcoming marathon. He does not use tobacco, alcohol, or illicit drugs. Skin testing is performed to determine symptom triggers. A pricking device is used to apply allergen extract underneath the skin. After 15 minutes, the patient develops raised, erythematous plaques with surrounding erythema at the application site. Which of the following mediators is the first to be released during the pathogenesis of this patient's skin findings?

Question

An 18-year-old man is evaluated for recurrent episodes of shortness of breath, wheezing, runny nose, and watery eyes.  The patient reports that his symptoms have recently worsened since he started training outdoors for an upcoming marathon.  He does not use tobacco, alcohol, or illicit drugs.  Skin testing is performed to determine symptom triggers.  A pricking device is used to apply allergen extract underneath the skin.  After 15 minutes, the patient develops raised, erythematous plaques with surrounding erythema at the application site.  Which of the following mediators is the first to be released during the pathogenesis of this patient's skin findings?

Quizplus · Accepted Answer

11ec160b_3b4e_95fd_9249_cf7fc829ee0d_MD0001_00 This patient's shortness of breath and wheezing are suggestive of asthma, and his rhinorrhea and watery eyes are suggestive of allergic rhinitis. Both of these conditions are examples of type I hypersensitivity, which involves the triggering of an allergic response via the binding of previously recognized antigen to IgE antibodies on mast cells. Many type I hypersensitivity reactions are composed of both an early and late phase. Histamine is housed in preformed granules of unactivated mast cells and plays an important role in the early phase of type I hypersensitivity. Upon activation, mast cells rapidly release histamine via degranulation, making histamine the first chemical mediator to take effect. Once released, histamine triggers smooth muscle contraction leading to bronchoconstriction, increases vascular permeability leading to edema, and increases mucus secretion from glandular tissue. (Choice B) Leukotriene D4, along with the other cysteinyl leukotrienes (C4 and E4), are not preformed but require synthesis via the 5-lipoxygenase pathway of arachidonic acid metabolism. Therefore, these mediators are released by mast cells later than histamine. Once released, the cysteinyl leukotrienes are potent mediators of vasoconstriction, bronchoconstriction, and increased vascular permeability. (Choice C) Major basic protein is released from eosinophils in the late stage of a type I hypersensitivity reaction and causes localized tissue damage. (Choice D) Platelet-activating factor is a secondary inflammatory mediator that must be synthesized from phospholipid prior to being released from activated mast cells and basophils. Once released, it stimulates bronchospasm and increased vascular permeability. (Choice E) Prostaglandin D2 is synthesized via the cyclooxygenase pathway of arachidonic acid metabolism prior to being released from mast cells. Once released, it causes bronchospasm and vasodilation. Educational objective: Type I hypersensitivity reactions are an allergic response triggered by the binding of previously recognized antigen to IgE antibodies on mast cells. In the early phase of the response, histamine, already stored in preformed granules in mast cells, is the first chemical mediator released. Once released, histamine stimulates smooth muscle contraction (bronchoconstriction), increases vascular permeability (edema), and increases mucus secretion. __________ References: The development of allergic inflammation. (http://www.ncbi.nlm.nih.gov/pubmed/18650915)

An 18-Year-Old Man Is Evaluated for Recurrent Episodes of Shortness