Case Presentation: An 81-year-old man with a history of coronary artery disease (CAD) and pulmonary tuberculosis (TB) presented with acute chest discomfort and rash. One month ago, the patient was admitted for evaluation of a pleural effusion. He was diagnosed with TB and began therapy with rifampin, isoniazid, pyrazinamide, and ethambutol. Two days prior to presentation, the patient developed the acute onset of a diffuse, erythematous, pruritic rash, with associated fever, dyspnea, and chest discomfort. He reported these symptoms to the infectious disease clinic and was instructed to hold his TB medications until further advised. While the patient’s rash improved, his chest discomfort worsened, prompting hospital presentation. On presentation, vital signs were notable for a fever of 101.5 F. Physical examination was normal. Laboratory data showed no eosinophilia, though serial troponin levels obtained over the course of eight hours were 1126, 2578, and 5642 ng/L. There were acute ST changes on electrocardiogram that did not meet criteria for ST-elevation myocardial infarction (MI). The patient was admitted to the cardiac care unit, where he was treated with heparin and dual antiplatelet therapy for a presumed Type I non-ST elevation MI, with plans for outpatient cardiac catheterization. The patient was then transferred to the hospital medicine service with infectious disease consultation for stepwise reintroduction of his TB therapy. He tolerated reintroduction of isoniazid, pyrazinamide, and ethambutol; however, following a dose of rifampin, he developed an urticarial rash, hypotension, chest discomfort, and dyspnea. Notably, the patient described these symptoms as identical to those on initial presentation, suggesting a link between rifampin and his MI. He had marked eosinophilia, and his troponin levels were elevated, though lower than on admission. He was treated for anaphylaxis. Rifampin was discontinued, and moxifloxacin was started as TB therapy instead (1). Cardiac catheterization later revealed severe multi-vessel obstructive CAD.
Discussion: This case highlights a unique concurrent presentation of two rare entities: anaphylaxis due to rifampin and Kounis syndrome. There are limited documented cases of anaphylaxis to rifampin, in which repeat exposures to the medication are thought to increase the risk of anaphylaxis through IgE-mediated sensitization and subsequent immune cell mediator release (2,3). Kounis syndrome is a rare, but well-described, cause of acute coronary syndrome due to an allergic reaction, where mast cell activation and degranulation result in a pro-inflammatory environment that causes destabilization of atherosclerotic plaque (4). The diagnosis is primarily clinical, and no specific laboratory data are required (4). In this patient’s case, repeated exposures likely sensitized him to rifampin, ultimately leading to an allergic reaction that caused mast cell-mediated plaque rupture and MI in the context of pre-existing CAD.
Conclusions: To our knowledge, this is the first reported case of Kounis syndrome secondary to an allergic reaction to rifampin. Because the diagnosis of Kounis syndrome is largely clinical, clinicians should be mindful of this syndrome as a cause of chest pain and MI, especially in patients presenting with allergic symptoms and a new exposure. Moreover, this case underscores the integrative diagnostic role that hospital medicine plays across multiple medicine subspecialities.