Anti-tumor necrosis factor (TNF) agents have revolutionized the treatment of several immune-mediated inflammatory diseases, including Crohn’s disease and ulcerative colitis. Although greatly effective, theses biologics put the patients at increased risk for developing serious and opportunistic infections and some types of cancer as lymphomas, the latter one especially when on combination of anti-TNF and thiopurines. Here we report a male who developed an atypical presentation of a severe opportunistic infection when using anti-TNF agent for Crohn’s disease treatment.