Колониальная ишемия без мезентерического оккулирования: случай, имплицитирующий интерферон-β.

INTRODUCTION

Ischemic colitis is the most common form of intestinal ischemia. It is typically caused by reduction in colonic blood flow from systemic hypoperfusion, vascular occlusion, vasoconstriction, or microvascular dysfunction. 1 Medications are often recognized as causes of ischemic complications through mechanisms that induce vasospasm or endothelial dysfunction, leading to hypercoagulability. 2

Type I interferons, including interferon-α (IFN-α) and interferon-β (IFN-β), have historically been used in the treatment of chronic viral hepatitis and remain United States Food and Drug Administration (FDA)–approved for relapsing forms of multiple sclerosis, respectively. While IFN-α has been associated with ischemic colitis in several reports, cases linked to IFN-β are rare. 3 – 5 It is thought that type I interferons cause endothelial dysfunction, increased vascular tone, platelet activation, and microvascular ischemia. 5 We present a case of isolated right-sided colonic ischemia (IRCI) with biopsy-proven ischemic colitis in a patient receiving long-term IFN-β-1a therapy with clinical and radiographic resolution after drug discontinuation.

CASE REPORT

A 66-year-old woman presented with acute right-sided abdominal pain and a 2-day history of watery diarrhea. She rated as 7/10 in severity and denied hematochezia, melena, fever, recent medication changes, nonsteroidal anti-inflammatory drug use, or systemic signs of infection. Medical history was notable for multiple sclerosis treated with IFN-β-1a 44 mcg subcutaneously 3 times weekly for more than 7 years, methylenetetrahydrofolate reductase (MTHFR) gene mutation with prior deep vein thrombosis, hypertension, and gastroesophageal reflux disease. Home medications included aspirin 81 mg daily, bisoprolol-hydrochlorothiazide, metformin, tirzepatide, pravastatin, verapamil, and pantoprazole. The patient was not receiving anticoagulation at presentation. She denied tobacco use or other identifiable precipitating factors.

On presentation, the patient remained hemodynamically stable without hypotension or vasopressor requirement. Physical examination demonstrated diffuse abdominal tenderness greatest in the right lower quadrant, without guarding, or peritoneal signs and active bowel sounds. Laboratory testing demonstrated leukocytosis of 38.2 K/μL, elevated C-reactive protein of 54.4 mg/L, and normal serum lactate of 1.4 mmol/L. Computed tomography (CT) of the abdomen and pelvis with intravenous contrast demonstrated isolated right-sided colonic involvement with circumferential wall thickening at the cecum and ascending colon, cecal pneumatosis, and a small focus of portal venous gas within the right hepatic lobe (Figure 1 ). Infectious evaluation, including Clostridioides difficile toxin, and multiplex gastrointestinal pathogen testing were negative. Empiric antimicrobial therapy with azithromycin 500 mg orally was administered on presentation while infectious etiologies were being excluded.

Axial contrast-enhanced computed tomography abdomen demonstrating circumferential wall thickening and inflammatory changes involving the cecum and ascending colon with associated pneumatosis (white arrows). The affected bowel segment demonstrates mural stratification with mucosal hyperenhancement and submucosal edema. Pericolic fat stranding can be seen in the surrounding mesentery (red arrow). Findings consistent with an acute colitis pattern with pneumatosis raising concern for compromised bowel wall integrity.

Colonoscopy performed on hospital day 2 demonstrated confluent ulceration and pale mucosa involving the cecum with patchy ulcerations in the ascending colon and hepatic flexure (Figure 2 ). Histologic analysis strongly supported the diagnosis of ischemic colitis showing architectural distortion with mucosal hemorrhage and necrosis (Figure 3 ). Given the patient's hypercoagulable history, CT angiography was performed and demonstrated patent mesenteric vasculature without evidence of mesenteric venous thrombosis or arterial occlusion.

Colonoscopy images demonstrating confluent ulceration and pale, edematous mucosa in the cecum (black arrows) with patchy ulcerations extending into the ascending colon (white arrows) and hepatic flexure. The affected mucosa exhibits friability, erythema and exudate overlying denuded mucosal surfaces. The lower right panel shows a yellow-green material suggestive of purulent exudate within the involved colonic segment.

Histopathologic analysis demonstrating, (A) H&E image at 10× of colonic mucosa displaying features of ischemic colitis including mild crypt damage, mucosal ulceration, and hemorrhage. The ulcerated area on the right side of the fragment coincides with underlying fibrosis and crypt dropout. (B) H&E image at 20× demonstrating acute inflammation in the stroma, along with subtle lamina propria hyalinization. (C) H&E image at 20× showing vascular congestion with hyalinization of the lamina propria beneath the crypts. (D) H&E image at 20× showing vascular congestion and lymphoplasmacytosis. H&E, hematoxylin and eosin.

In the absence of mesenteric occlusion, multifactorial nonocclusive ischemia with IFN-β as a potential precipitating contributor was considered the most likely etiology. After multidisciplinary discussion with the patient's neurologist, IFN-β therapy was discontinued. The patient remained hemodynamically stable throughout admission and symptoms improved with supportive care. At the 2-week follow up, she reported complete resolution of abdominal pain and diarrhea. Repeat CT imaging demonstrated near-complete resolution of prior inflammatory changes (Figure 4 ). She was transitioned to glatiramer acetate by her outpatient neurologist and has remained without recurrent gastrointestinal symptoms on subsequent follow-ups with her primary care provider at 5 and 9 months.

Axial contrast-enhanced computed tomography abdomen 2 weeks after discontinuation of IFN-β, demonstrating near-complete resolution of previously identified circumferential wall thickening, pneumatosis intestinalis and pericolic inflammatory changes involving the cecum and ascending colon. The marked interval improvement in colonic wall thickening and surrounding inflammation following cessation of IFN-β provides support for a drug-induced etiology. IFN-β, interferon-β.

DISCUSSION

Ischemic colitis results from colonic hypoperfusion and can frequently occur without radiographic evidence of large-vessel occlusion. Nonocclusive ischemia is often multifactorial, involving transient hypoperfusion, vasoconstriction, or microvascular dysfunction. Drug-induced ischemia has become increasingly recognized as a cause of nonocclusive ischemia, particularly in drugs that alter vascular or endothelial structure. 1 , 2

Type I interferons have been associated with vascular adverse events through mechanisms involving endothelial injury, increased vascular tone, platelet activation, and impaired microvascular perfusion. 5 Although IFN-α-associated ischemic colitis has been described in multiple published case reports, reports involving IFN-β remain exceedingly rare. 3 – 5 In a pharmacovigilance review of the FDA Adverse Event Reporting System, Salk et al identified 39 reported cases of IFN-β-associated ischemic colitis in patients with multiple sclerosis, of which 19 were categorized as probable adverse drug reactions using the Naranjo probability scale. 5 However, no individual case reports describing an association between IFN-β and IRCI were identified in the literature, and the anatomic distribution of colonic involvement was not reported in the FDA Adverse Event Reporting System analysis. Prior published interferon-associated ischemic colitis cases involving IFN-α have predominantly described left-sided colonic disease. 6 , 7

The present case is notable for IRCI with associated pneumatosis and portal venous gas occurring after more than 7 years of IFN-β therapy. IRCI represents a less common but clinically important subtype of ischemic colitis, accounting for approximately 20%–25% of cases and associated with increased morbidity and mortality compared to left-sided disease. 1 The right colon is believed to be particularly susceptible to ischemia because of relatively limited collateral circulation and increased vulnerability to low-flow states or microvascular compromise. 1 Unlike classic IRCI, which is more commonly associated with systemic hypoperfusion, atrial fibrillation, coronary artery disease, or hemodynamic instability, this patient remained hemodynamically stable without evidence of embolic disease or flow-limiting mesenteric occlusion. 1

The patient's history of MTHFR mutation, prior deep vein thrombosis, diabetes mellitus, hypertension, and mild underlying atherosclerotic disease likely contributed to increased susceptibility to vascular dysfunction and ischemia. Although homocysteine levels were not obtained during admission and outside neurologic laboratory records were unavailable for review, hyperhomocysteinemia associated with certain MTHFR variants has been linked to endothelial dysfunction and prothrombotic states. In this setting, IFN-β may have acted synergistically through endothelial injury, vasoconstriction, and microvascular dysfunction to precipitate a nonocclusive ischemic event.

The delayed onset of ischemic colitis after years of previously uneventful IFN-β exposure suggests that cumulative endothelial injury or age-related decline in microvascular reserve may have contributed to disease development. No alternative precipitating trigger, including hypotension, infection, medication change, or dehydration, was identified.

Although causality cannot be definitively established, the temporal association with IFN-β exposure, exclusion of alternative etiologies, and complete clinical and radiographic resolution following drug discontinuation support IFN-β as a likely contributing factor. Clinicians should recognize ischemic colitis as a rare but potentially serious complication of IFN-β therapy, particularly in patients with underlying vascular or hypercoagulable risk factors presenting with acute abdominal symptoms.

DISCLOSURES

Author contributions: A. Siegel drafted the manuscript, performed literature review and is article guarantor. KM Tun helps with endoscopic image interpretation. J. Gamache assisted with obtaining histologic images and writing captions. R. Kizer revised the manuscript for accuracy. All authors approved the final manuscript.

Financial disclosure: None to report.

Previous presentation: Case presented at the American College of Gastroenterology Annual Scientific Meeting, October 24–29, 2025; Phoenix, Arizona.

Informed consent was obtained for this case report.