IBD-related hypercoagulability is a rare and underdiagnosed condition that can present with multifocal strokes and systemic inflammation, often mimicking lymphoma or primary CNS vasculitis.

We present a 47-year-old immunocompetent Nigerian man with uncontrolled diabetes, hypertension, and CKD who developed unintentional weight loss and progressive bilateral necrotic leg ulcers concerning for pyoderma gangrenosum over 3–4 months. He presented with encephalopathy, dyspnea, new heart failure, bilateral pulmonary emboli, and sepsis.

MRI brain revealed multifocal acute infarcts consistent with an embolic or hypercoagulable pattern. Stroke work-up including CTA, CTP, TTE, TEE, and malignancy screening showed no large-artery disease or embolic source. CSF cultures were repeatedly negative for infection but demonstrated inflammatory activation (IL-6, IL-10, IL-2R). Cytology and flow cytometry were repeatedly negative. ESR and CRP were elevated throughout the hospital course. Additionally, IBD-associated markers were abnormal, with elevated anti-Saccharomyces cerevisiae IgG (62.9) and increased total IgA. Despite extensive hypercoagulability and autoimmune work-up, no clear diagnosis emerged. Repeat MRI demonstrated additional acute multifocal strokes raising concern for primary vasculitis or systemic inflammatory hypercoagulability. Cerebral angiography showed no vasculopathy. Initial dermatopathology of the ulcers showed reactive fibrosis. He received two days of empiric high-dose steroids and demonstrated initial, but not sustained, improvement. Repeat deep skin biopsy and initial brain biopsy obtained after steroids were negative for vasculitis or malignancy although no vessels were isolated from the specimens. Brain biopsy cultures grew Staphylococcus aureus and Alcaligenes xylosoxidans (a species associated with IBD microbiome alterations), which were organisms initially isolated from the skin; however, blood and CSF cultures were persistently negative.

The constellation of necrotic ulcers, multifocal strokes, disseminated infection without bacteremia, and serologic evidence of gut-associated immune activation suggests IBD-related systemic hypercoagulability as the unifying diagnosis. Early biopsy and integration of inflammatory and microbiologic data are essential to distinguish inflammatory hypercoagulable syndromes from other mimics.