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Liu* Reviewers: Mehul Gupta, Brian Rankin, Julia Chai, Stephen Williams Yan Yu* Laurie Parsons* *MD at time of publication Pathogenesis and clinical findings Genetic susceptibility Certain HLAs (e.g., HLA-B*58:01, HLA-B*57:01, and HLA-A*31:01) HLA alleles encode for MHC structure and may influence how specific drugs/drug metabolites interact with T cell receptors and MHC proteins on antigen-presenting cells Exposure to offending drug E.g., Aromatic anticonvulsants (lamotrigine, carbamazepine, and phenytoin), allopurinol, and sulfonamides Drug-specific CD4+ and CD8+ T cells produce tumor necrosis factor-alpha and interferon gamma activated T-cells 2-6 weeks after drug exposure Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS) Latent Viral infection Latent viruses (HHV-6, HHV- 7, CMV, and EBV) concealed in regulatory T-cells Reactivation of latent viruses may be contributory or secondary to T cell activation by drugs Eosinophilia +/- atypical lymphocytes T helper type 2 cells recruit and activate eosinophils by releasing cytokines Activated leukocytes create a humoral immune and allergic response Dysfunction of regulatory T cells, resulting in failure to control unwanted immune responses against self Autoimmune processes with single- or multi-organ involvement CMV- Cytomegalovirus EBV- Epstein-Barr Virus HHV- Human Herpesvirus HLA- Human Leukocyte Antigens MHC Major Histo- compatibility Complex Endocrine system mechanism of dysfunction unclear but may be linked to autoreactive T cells Autoimmune Type 1 thyroiditis diabetes Lymphadenopathy Fever Facial edema Liver lobular inflammation, dispersed foci of necrotic hepatocytes, granulomatous infiltrates consisting of eosinophils Hepatitis Kidney Interstitial edema and infiltrates of lymphocytes, histiocytes, eosinophils, and plasma cells Acute interstitial nephritis Lung increased pulmonary infiltrate and edema Morbilliform Skin Eruption Spongiosis Epidermal layer Dermal- Epidermal Junction Dermal layer Interface dermatitis Skin eruption (morbilliform to diffuse erythema with follicular accentuation) Interstitial pneumonitis Pleural effusion Eosinophilic infiltration Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Published October 19, 2021 on www.thecalgaryguide.com