We report the case of a 39-year-old woman who presented with generalized malaise; lymphadenopathy; arthritis; dactylitis; ecchymosis; acute onycholysis; and a red, nonpruritic, nonscaly, mottled rash on the right breast 24 hours after the first injections of ixekizumab for psoriasis and psoriatic arthritis. Ixekizumab is a humanized IgG4 monoclonal antibody that binds to IL-17A. Adverse events of ixeki-zumab include infection, inflammatory bowel disease, candidiasis and tinea infections, severe injection-site reactions, arthralgia, headache, infections, neutropenia, and thrombocytopenia. Other biologics, specifically tumor necrosis factor (TNF) inhibitors, have been reported to cause onycholysis attributed to immune dysregulation. We propose that ixekizumab alters the inflammatory cascade that underlies the induction of acute onycholysis and arthritis.