Cord colitis syndrome

Overview

Cord colitis syndrome is a rare and recently described gastrointestinal condition that occurs in patients who have undergone umbilical cord blood stem cell transplantation. It is characterized by persistent, non-infectious diarrhea and colonic inflammation that mimics infectious or graft-versus-host disease (GVHD) colitis but does not respond to standard antibiotics or steroids. The syndrome appears unique to cord blood transplant recipients and often improves with specific antibiotic therapy, suggesting a distinct underlying pathophysiology.

Causes

The exact cause of cord colitis syndrome is not fully understood. It is believed to be related to an altered immune response or dysbiosis of the gut microbiota following umbilical cord blood transplantation. Unlike GVHD or infectious colitis, cord colitis does not show typical histological markers of either. Some theories suggest that a previously unrecognized microbial agent or a specific immune-mediated response related to cord blood engraftment may play a role. Importantly, this syndrome is not caused by standard pathogens typically found in post-transplant infections.

Symptoms

The hallmark symptoms of cord colitis syndrome include:

• Chronic watery diarrhea: Persistent, non-bloody, and unresponsive to conventional treatments

• Abdominal pain or cramping

• Low-grade fever: In some patients

• Weight loss and dehydration

• Fatigue and general malaise

These symptoms usually begin weeks to months after cord blood transplantation, often during the engraftment or early post-engraftment period.

Diagnosis

Diagnosis of cord colitis syndrome involves ruling out other causes of post-transplant diarrhea and recognizing its distinct features. Diagnostic steps include:

• Stool studies: Negative for common infectious organisms such as Clostridioides difficile, cytomegalovirus (CMV), or bacterial pathogens

• Colonoscopy: May reveal mild inflammation, mucosal erythema, or ulceration

• Biopsy of colonic tissue: Shows nonspecific inflammation without features typical of GVHD or infections

• Exclusion of GVHD: Important to distinguish, as treatment approaches differ

• Clinical response to antibiotics: Particularly metronidazole and ciprofloxacin, is considered diagnostic in some cases

Treatment

The most effective treatment for cord colitis syndrome is a combination of antibiotics, despite the absence of detectable pathogens. Recommended treatments include:

• Metronidazole: Often used as monotherapy or in combination

• Ciprofloxacin: Commonly combined with metronidazole for improved response

• Supportive care: Including hydration, electrolyte replacement, and nutritional support

• Avoidance of steroids: Since the condition is not typically responsive to immunosuppressive therapy used for GVHD

Most patients respond well to antibiotics within days to weeks, and relapses are uncommon if treated promptly.

Prognosis

The prognosis for patients with cord colitis syndrome is generally favorable if the condition is recognized and treated early with appropriate antibiotics. Misdiagnosis as GVHD or infection can lead to ineffective treatment and prolonged illness. Once correctly identified, most patients experience complete resolution of symptoms without recurrence. However, close monitoring is necessary, especially in immunocompromised individuals, to ensure proper recovery and to rule out overlapping complications.