Anti-tumor necrosis factor (TNF) antibodies have become an indispensable part in the therapeutic landscape of treating inflammatory bowel disease (IBD) patients. Nevertheless, they can be associated with the occurrence of severe systemic side effects. Here, we report the case of a 23-year-old patient with ileocolonic Crohn's disease in endoscopic remission under ongoing anti-TNF infliximab therapy with occurrence of novel generalized arthralgia, pleuritic chest pain, and dyspnea. Clinical, laboratory, and imaging diagnostic workup in an extended clinical routine setting at the University Hospital of Erlangen, Germany, was used by a multidisciplinary team consisting of gastroenterologists, radiologists, cardiologists, and rheumatologists to investigate the underlying cause of the clinical symptoms in the patient. The results received using the aforementioned diagnostic setup led to the diagnosis of severe constrictive perimyocarditis due to infliximab-induced lupus-like syndrome with distinct ANA reactivity and elevated anti-dsDNA levels. Furthermore, pronounced ischemic hepatitis was diagnosed. Infliximab treatment was immediately stopped, and initiated corticosteroid pulse therapy only led to partial response as it had to be reduced due to pronounced psychiatric side effects. Persistent signs of pericarditis required additional ibuprofen therapy, which led to subsequent resolution of cardial symptoms. Formerly elevated liver enzymes returned to normal, and there were no clinical signs of recurrence of Crohn's disease activity over 18 months of follow-up. The patient was subsequently switched to ustekinumab therapy for further treatment of underlying Crohn's disease. This case report describes for the first time severe infliximab-induced lupus-like syndrome in an IBD patient, concurrently mimicking ST-elevation myocardial infarction with MRI visualization of pericarditis, occurrence of ischemic hepatitis, and pronounced signs of systemic inflammation.