Extensive Colonic Pseudopolyposis Leading to Protein-Losing Enteropathy and Severe Hypoalbuminemia With Refractory Ulcerative Colitis

ABSTRACT

Extensive pseudopolyposis in ulcerative colitis (UC) is rare and can lead to protein-losing enteropathy (PLE) with severe hypoalbuminemia. We report an 18-year-old male with steroid-dependent UC complicated by extensive colonic pseudopolyposis causing PLE. This represents one of the few reported cases of PLE secondary to extensive colonic pseudopolyposis in UC. He presented with profound hypoalbuminemia reaching a nadir of 1.0–1.5 g/dL, malnutrition, iron-deficiency anemia, and deep-vein thrombosis. Colonoscopy and imaging revealed dense pseudopolyps from the proximal sigmoid to the cecum, with minimal inflammation. Renal and hepatic causes of protein loss were excluded through routine urinalysis, the absence of proteinuria, normal creatinine levels, normal liver enzymes, and unremarkable renal and hepatic imaging. Although formal quantitative PLE testing, such as α-1 antitrypsin clearance, was unavailable at our center, the persistent severe hypoalbuminemia, minimal inflammatory activity, and exclusion of alternative etiologies strongly supported a diagnosis of pseudopolyposis-associated PLE. Management included multiple biologics, steroid tapering, total parenteral nutrition, and anticoagulation; colectomy was declined. Clinicians should maintain a high index of suspicion for PLE in UC patients with extensive pseudopolyposis and hypoalbuminemia disproportionate to the degree of inflammation.

INTRODUCTION

Ulcerative colitis (UC) is an inflammatory bowel disease (IBD) characterized by continuous mucosal inflammation of the colon. Recurrent cycles of ulceration and healing may result in pseudopolyps or post-inflammatory polyps. Although usually benign, extensive pseudopolyposis is uncommon and can cause complications such as severe anemia, obstruction, diagnostic difficulty with dysplasia, and, rarely, protein-losing enteropathy (PLE).^1,2

PLE results from excessive loss of serum proteins into the gastrointestinal lumen, leading to hypoproteinemia and hypoalbuminemia.³ Mechanisms include increased mucosal permeability, erosions, ulcerations, and lymphatic dysfunction.³ In UC, PLE attributable to pseudopolyposis is exceedingly rare, with fewer than 10 cases reported, making this an exceptionally uncommon and under-recognized complication.

In this report, we describe a biologic-refractory UC patient with extensive pseudopolyposis leading to severe hypoalbuminemia after renal and hepatic causes of protein loss were thoroughly excluded. His course was complicated by malnutrition, adrenal insufficiency, and thromboembolic events. Colectomy was declined by the patient, necessitating prolonged nonsurgical management. This case adds to the limited literature and emphasizes the need for early recognition and timely intervention when pseudopolyposis-associated PLE is suspected. This case highlights an exceptionally rare presentation of pseudopolyposis-associated PLE and outlines medical management considerations in a patient who do not undergo colectomy.

CASE REPORT

An 18-year-old male with no family history of IBD was diagnosed with UC at age 17 following 1 month of bloody diarrhea (Figure 1). Colonoscopy demonstrated pancolitis with a normal terminal ileum, and histology confirmed severe chronic active colitis. Serum albumin at diagnosis was normal (4.3 g/dL), and no extraintestinal manifestations were present.

Figure 1.

Clinical timeline of the case relative to index presentation.

Initial therapy with oral mesalamine and systemic corticosteroids resulted in partial clinical improvement; however, attempts to taper prednisone below moderate doses led to symptom recurrence. Two months after diagnosis, adalimumab was initiated while albumin remained normal. Despite therapeutic drug exposure, approximately 4 months later the patient experienced a significant clinical flare, prompting discontinuation of adalimumab and escalation to infliximab at intensified dosing. During this flare, serum albumin declined to 2.7 g/dL. The clinical course was complicated by Clostridioides difficile infection, which resolved with oral vancomycin; however, the patient remained steroid-dependent.

Four months later, he developed severe iron-deficiency anemia requiring intravenous iron replacement. Therapeutic drug monitoring at that time demonstrated therapeutic infliximab trough levels without detectable anti-drug antibodies, consistent with adequate biologic exposure.

Upon transition to adult gastroenterology care, the patient presented with fatigue, diarrhea, and hypotension. Evaluation revealed adrenal insufficiency secondary to chronic corticosteroid exposure, and hydrocortisone replacement therapy was initiated. During this admission, a persistent pattern of profound hypoalbuminemia was noted, with levels ranging from 1.0 to 1.5 g/dL for several months despite clinical and biochemical improvement of colitis.

Renal and hepatic causes of protein loss were excluded based on routine urinalysis without proteinuria, preserved renal function, normal liver enzymes, liver synthetic markers, and unremarkable renal and hepatic ultrasound. In the absence of active systemic inflammation, PLE became the leading diagnostic consideration, although the structural source of protein loss remained unclear.

Approximately 14 months after the index presentation, colonoscopy revealed extensive colonic pseudopolyposis extending proximally from 60 cm to the cecum, with minimal active inflammation (Figure 2). Targeted biopsies demonstrated chronic mild colitis without dysplasia. Abdominal computed tomography imaging confirmed dense pseudopolyposis throughout the proximal colon (Figure 3). Although α-1 antitrypsin clearance testing was unavailable, the combination of persistent severe hypoalbuminemia, minimal inflammatory activity, temporal association with pseudopolyposis development, and exclusion of renal and hepatic etiologies strongly supported a diagnosis of pseudopolyposis-associated PLE.

Figure 2.

Colonoscopy showing extensive pseudopolyposis from the sigmoid colon to the cecum, with preserved mucosal architecture and minimal active inflammation (A-D).

Figure 3.

Contrast-enhanced computed tomography of the abdomen and pelvis demonstrating extensive pseudopolyposis extending from the proximal sigmoid colon to the cecum with preserved colonic wall thickness (A-B).

Several weeks later, the patient was hospitalized with progressive malnutrition and weakness. Total parenteral nutrition was initiated, though serum albumin remained persistently low. The hospital course was complicated by a peripherally inserted central catheter–associated deep vein thrombosis, transfusion-dependent anemia due to rectal bleeding, adrenal crisis, and low-titer cytomegalovirus (CMV) viremia. Flexible sigmoidoscopy excluded CMV colitis and demonstrated mild patchy erythema and granularity with multiple pseudopolyps, consistent with mild endoscopic disease activity.

Overall, the clinical picture was consistent with refractory pancolitis complicated by extensive pseudopolyposis-associated PLE, profound hypoalbuminemia, malnutrition, chronic steroid dependence with adrenal insufficiency, thromboembolic disease, and low-titer CMV viremia.

Management included continuation of infliximab with corticosteroid tapering, therapeutic anticoagulation, and nutritional support. Low-titer CMV viremia was not treated following multidisciplinary discussion. Subtotal colectomy was considered following repeated surgical consultations; however, surgical management was deferred after shared decision-making with the patient and family. In the setting of persistent steroid dependence and re-emergence of endoscopic disease activity, infliximab was discontinued and risankizumab was initiated. Infliximab trough levels were therapeutic with no detectable anti-drug antibodies, indicating loss of response not attributable to pharmacokinetic failure. The decision to transition therapy was made in the context of ongoing disease activity requiring continued medical management and after discussion of all available advanced biologic and small-molecule treatment options with the patient.

At the most recent follow-up, laboratory evaluation demonstrated anemia (hemoglobin 9.3 g/dL), low ferritin (21.1 ng/mL), elevated inflammatory markers (C-reactive protein 7.75 mg/L), and persistent severe hypoalbuminemia (2.7 g/dL following nutritional support, subsequently declining to 1.9 g/dL), with preserved renal and hepatic function.

DISCUSSION

Pseudopolyps arise from repeated cycles of mucosal injury and regeneration in UC.^1,4 While often asymptomatic, extensive pseudopolyposis may signal a more severe disease course and predispose to rare complications such as PLE.^2,5,6 PLE results from excessive protein loss across disrupted intestinal mucosa, leading to hypoproteinemia and, as demonstrated in this case, profound hypoalbuminemia.^3,7 In pseudopolyposis-associated PLE, several mechanisms may contribute to protein loss, including widespread microerosions, increased epithelial permeability, and inflammatory exudation across a broad polyp-laden surface. Additional contributors include mechanical trauma to friable pseudopolyps during peristalsis and impaired lymphatic drainage within chronically inflamed mucosa. Together, these processes can result in significant protein loss even when endoscopic inflammation appears minimal.

Only a small number of published reports describe pseudopolyposis-induced PLE, underscoring its rarity. Ungaro et al confirmed PLE using α-1 antitrypsin clearance, with hypoalbuminemia resolving following colectomy.⁵ Anderson et al reported a case of giant pseudopolyposis complicated by PLE and massive pulmonary embolism, highlighting the systemic risks of severe protein depletion.⁸ Watanabe et al similarly described a young adult with extensive polyposis coli and PLE requiring surgical management.⁶ These cases share key features with our patient, including long-standing pancolitis, extensive pseudopolyposis, disproportionate hypoalbuminemia, malnutrition, and heightened thromboembolic risk, further supporting a pathophysiologic link between dense pseudopolyposis and clinically significant protein loss. In UC, pseudopolyposis-associated PLE should be considered when patients present with profound, unexplained hypoalbuminemia disproportionate to the degree of clinical, biochemical, or endoscopic inflammation.^3,5,7 A structured diagnostic approach begins with exclusion of alternative sources of protein loss. In this case, renal etiologies were excluded by the absence of proteinuria and preserved renal function, and hepatic causes were ruled out based on normal synthetic liver markers, normal liver enzymes, and unremarkable abdominal imaging. When hypoalbuminemia remains severe (1.0–1.5 g/dL) and persistent despite minimal active inflammation, exclusion of renal and hepatic causes and demonstration of a temporal relationship between the extent of pseudopolyposis and albumin decline strongly support pseudopolyposis-associated PLE. Although confirmatory testing, such as α-1 antitrypsin clearance or radionuclide scintigraphy, is ideal, these modalities are not universally available, and diagnosis may therefore rely on clinicopathologic correlation supported by endoscopic and radiologic evidence of extensive pseudopolyposis.

Management of pseudopolyposis-associated PLE requires multidisciplinary coordination among gastroenterology, colorectal surgery, nutrition support, and internal medicine teams. Prior reports demonstrate that colectomy represents definitive therapy when pseudopolyposis is the structural driver of protein loss.^5,6,9 When surgical intervention is deferred, as in this case, prolonged medical optimization may be pursued but is often insufficient, as biologic therapies do not address the structural source of protein leakage.

Earlier recognition of pseudopolyposis-associated PLE may have facilitated surgical discussions before the development of chronic steroid dependence and subsequent adrenal insufficiency, a recognized complication of prolonged glucocorticoid exposure in IBD.¹⁰

With respect to biologic therapy, risankizumab was selected for its selective interleukin-23 inhibition, favorable safety profile, and demonstrated efficacy in biologic-exposed patients, including those with prior anti–tumor necrosis factor failure. Janus kinase inhibitors were avoided considering the patient's thromboembolic history, and vedolizumab was considered a less optimal option in the context of anti–tumor necrosis factor nonresponse. Although risankizumab represented a reasonable therapeutic choice, limited follow-up precludes conclusions regarding its effectiveness in reversing pseudopolyposis-associated PLE.

Ultimately, ongoing deferral of colectomy significantly constrained management options, resulting in medical therapy serving primarily as a temporizing rather than definitive strategy.

This report is limited by the absence of quantitative confirmation of PLE, as α-1 antitrypsin clearance testing and nuclear scintigraphy were unavailable. In addition, the lack of long-term follow-up after initiation of risankizumab limits assessment of sustained therapeutic benefit. Surgical outcomes could not be evaluated because colectomy was deferred, precluding comparison between medical and surgical management strategies. As a single case report, generalizability is inherently limited.

Future studies should focus on defining clinical thresholds for prioritizing colectomy over continued biologic escalation in patients with pseudopolyposis-associated PLE. Further research is also needed to determine whether interleukin-23 inhibition or other advanced therapies can meaningfully reduce protein loss when pseudopolyposis, rather than active ulceration, is the predominant driver. Development of standardized diagnostic algorithms, including guidance on the use of α-1 antitrypsin clearance and radionuclide imaging, may further improve diagnostic consistency and accuracy.

Extensive pseudopolyposis in UC is an uncommon but clinically significant cause of PLE, capable of producing profound hypoalbuminemia and systemic complications, including malnutrition, thromboembolic events, and immunodeficiency. Early recognition is essential because medical therapy is often insufficient and remains understudied in this setting, whereas colectomy remains the definitive treatment once PLE develops. Clinicians should maintain a high index of suspicion for this complication in UC patients whose hypoalbuminemia is unexplained or disproportionate to the degree of clinical or endoscopic inflammation. This case reinforces that when renal and hepatic causes of protein loss have been thoroughly excluded, severe hypoalbuminemia in otherwise minimally active UC should prompt evaluation for structural contributors, such as extensive pseudopolyposis, to guide timely and appropriate management.

DISCLOSURES

Author contributions: H. Nadeem: Data collection, literature review, drafting of the manuscript, and critical revisions. M. Alsaeid: Data collection, literature review, and drafting of the manuscript. A. Bitton: Critical review of the manuscript for important intellectual content and supervision. H. Nadeem: Data collection, manuscript editing. PL Lakatos: Conception of the case report, data collection, data interpretation, critical manuscript revisions, and supervision of the study. All authors meet the ICMJE authorship criteria, have contributed, reviewed and approved the final version. PL Lakatos is the article guarantor.

Financial disclosure: The authors received no financial support or grant funding for this case report. The authors declare no conflicts of interest related to this manuscript.

Informed consent was obtained for this case report.

ABBREVIATIONS:

CMV

cytomegalovirus

CRP

C reactive protein

CT

computed tomography

IBD

inflammatory bowel disease

IL

interleukin

PLE

to protein-losing enteropathy

UC

ulcerative colitis