Pemphigus vulgaris (PV) is a rare life-threatening condition of the pemphigus group of autoimmune blistering diseases. Systemic glucocorticoids are the cornerstone of management for PV, but complications can arise from their long-term use. We report a case of recurrence of a well-controlled case of PV that could not be alleviated by a combination of steroids, mycophenolate mofetil, and high-dose intravenous immune proteins. The patient had developed numerous complications during previous glucocorticoid therapy, including hypertension, diabetes, glaucoma, cataracts, optic nerve atrophy, aseptic necrosis of the femoral head, osteoporosis, and pulmonary tuberculosis. We determined that recurrence of PV and treatment resistance were consequences of the interaction between the antitubercular agent rifampicin that the patient was taking and corticosteroids. Pemphigus vulgaris was quickly controlled after the rifampicin was discontinued.