Type III hypersensitivity drug reactions

Hypersensitivity vasculitis induced by drags is another manifestation of a type III response. Drags involved include some p-lactams, particularly, amoxicillin and cephalexin, cotrimoxazole, NSAIDs, monoclonal antibodies, and chemotherapeutic drags such as tamoxifen and erlotinib. A proportion of small-vessel vasculitis patients have anti-neutrophil cytoplasmic antibodies. Although there is evidence of a pathogenic role for these antibodies and they are used as a diagnostic marker, operative mechanisms underlying this hypersensitivity state are still far from established. 

Hypersensitivity reactions are one of a number of different mechanisms producing drug-induced lung disease. These reactions result from interaction of drag with the immune system and 

Cysteinyl leukotrienes are generated de novo from arachidonic acid by phospholipase A2 with the initial participation of 5-lipoxygenase-activating protein and the enzyme 5-lipoxygenase. 

l-0-alkyl-2-acetyl-5n-glycero-3-phospho-choline, a phospholipid of relatively simple but unique structure, produces both the signs and symptoms of anaphylaxis. PAF is also an important mediator in asthma and septic shock. Recent findings in the mouse identified a second pathway of anaphylaxis involving the IgG receptor FcyRIH and the release of PAF as the major mediator. 

Recruitment of the Syk kinase and subsequent phosphorylation activation steps involving Lyn lead to mast cell activation demonstrating the importance of protein tyrosine kinases in the pathways that result in allergic inflammation and anaphylaxis. 

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