Severe Mpox-Associated Proctocolitis Mimicking Opportunistic Colitis in a Liver Transplant Recipient

Abstract

Mpox infection increasingly manifests with anorectal disease during the recent global outbreak. Severe ulcerative proctocolitis in solid-organ transplant recipients remains rarely described. We report a 37-year-old liver transplant recipient with well-controlled HIV infection (CD4 count 661 cells/µL [35%] and HIV RNA <20 copies/mL) presenting with severe watery diarrhea, rectal pain, disseminated vesiculopustular lesions, and inflammatory proctocolitis on imaging and endoscopy. Histopathology demonstrated ulceration and cryptitis without viral inclusions, while extensive infectious evaluation was negative. Polymerase chain reaction testing of a cutaneous lesion was positive for mpox virus. Symptoms improved with supportive care and reduction of immunosuppression. This case highlights mpox as an important diagnostic consideration in immunocompromised patients presenting with severe ulcerative proctocolitis, including patients with preserved CD4 immunity and virologically suppressed HIV infection.

INTRODUCTION

Mpox is a zoonotic infection caused by the monkeypox virus that gained global attention during the 2022 outbreak. The resurgence of mpox has led to increasing recognition of atypical clinical presentations beyond the classic febrile vesiculopustular illness. Gastrointestinal manifestations—including anorectal pain, rectal ulceration, and proctitis—have emerged as important features of the disease during the outbreak.^1–6

Recent reports have highlighted anorectal involvement as a frequent presentation, particularly among immunocompromised individuals and patients with HIV infection.^2–5 However, mpox-associated severe ulcerative proctocolitis in solid-organ transplant recipients remains rarely described. We present a case of mpox-associated severe proctocolitis in a liver transplant recipient whose presentation closely mimicked opportunistic colitis.

CASE REPORT

A 37-year-old man with alcohol-associated cirrhosis who underwent orthotopic liver transplantation on December 30, 2022, presented approximately 35 months after transplantation with 2 weeks of worsening gastrointestinal symptoms. The donor was HIV-negative; therefore, the transplant was not performed under an HIV-positive donor HIV Organ Policy Equity Act protocol. His post-transplant course was notable only for a transient episode of neutropenia that resolved. Maintenance immunosuppression consisted of tacrolimus and mycophenolate mofetil. He also had HIV infection managed with bictegravir/emtricitabine/tenofovir alafenamide (Biktarvy) and reported excellent adherence. His most recent CD4 count was 661 cells/µL (35%) in May 2025, and HIV RNA was <20 copies/mL on November 10, 2025, 3 days before admission, consistent with well-controlled HIV infection.

The patient reported explosive nonbloody watery diarrhea, severe rectal pain, lower abdominal pain, nausea, and nonbloody emesis. One week before presentation, he developed a disseminated vesiculopustular rash initially involving the knee and subsequently spreading to the face, trunk, extremities, hands, perianal region, and penis. He reported sexual activity with male and female partners, including new partners within the preceding month and both insertive and receptive anal intercourse, with consistent barrier protection. He reported no known contact with a person with confirmed or suspected mpox.

Laboratory evaluation revealed leukocytosis (10.4 ×10³/µL), mild transaminitis, and an international normalized ratio of 1.49. Cross-sectional imaging with abdominal and pelvic computed tomography demonstrated marked rectal and distal colonic wall thickening with associated perirectal lymphadenopathy consistent with severe inflammatory proctocolitis.

Given the patient's immunosuppressed state, the differential diagnosis included opportunistic infections such as cytomegalovirus colitis as well as parasitic infections including Cryptosporidium, Cyclospora cayetanensis, and Cystoisospora belli.

Initial infectious evaluation with stool studies including Clostridioides difficile and screening for sexually transmitted infection was negative. Mycophenolate mofetil was held while tacrolimus therapy was continued for reduction in immunosuppression due to suspected infection.

Flexible sigmoidoscopy demonstrated severe ulceration, mucosal friability, and diffuse erythema involving the rectum and distal sigmoid colon (Figure 1). The mucosal pattern consisted of confluent ulcerations with surrounding edema and contact bleeding, a pattern that may mimic opportunistic infections such as cytomegalovirus colitis or severe inflammatory bowel disease. Endoscopic findings were consistent with severe inflammatory proctocolitis.

Figure 1.

Endoscopic findings of mpox-associated proctocolitis. (A)–(D) Flexible sigmoidoscopy demonstrating diffuse rectal ulceration, mucosal edema, erythema, and contact bleeding involving the rectum and distal sigmoid colon consistent with severe inflammatory proctocolitis.

Colonic biopsies revealed mucosal ulceration, cryptitis, crypt abscesses, architectural distortion, and mixed acute and chronic inflammatory infiltrates without viral inclusions or viral cytopathic changes. Further infectious workup including blood cytomegalovirus polymerase chain reaction (PCR), herpes simplex virus PCR, varicella zoster virus PCR, and serum cryptococcal antigen was negative. HIV RNA remained suppressed, with a level <20 copies/mL 3 days before admission.

Given the presence of disseminated cutaneous lesions and severe proctitis, mpox PCR testing of a swab obtained from a cutaneous lesion returned positive. The patient was managed with supportive care and reduction of immunosuppression. His diarrhea, rectal pain, and cutaneous lesions gradually improved without antiviral therapy.

DISCUSSION

Mpox infection has increasingly been associated with anorectal disease during the recent global outbreak. Gastrointestinal manifestations including proctitis, rectal ulceration, and severe anorectal pain have been described in affected patients.^1–6 In immunocompromised individuals, including those with advanced HIV infection or receiving immunosuppressive therapy after solid-organ transplantation, these manifestations may be more severe.^7,8

Recent studies describing the 2022 outbreak have reported high rates of anorectal symptoms including proctitis, rectal pain, and mucosal ulceration, often requiring endoscopic evaluation.^2–4 These presentations may closely mimic other infectious or inflammatory etiologies of colitis.

To our knowledge, severe mpox-associated proctocolitis in a liver transplant recipient has rarely been reported, particularly with endoscopic findings mimicking opportunistic colitis.

In this case, the patient's presentation closely resembled opportunistic infections such as cytomegalovirus colitis. Endoscopic findings demonstrated severe ulceration and mucosal friability, while histopathology revealed nonspecific inflammatory changes without viral inclusions. These findings highlight the diagnostic challenge posed by mpox-associated gastrointestinal disease in immunosuppressed patients.

Importantly, this patient's HIV infection was virologically suppressed, with a preserved CD4 count of 661 cells/µL (35%), arguing against advanced HIV-associated immunodeficiency as the sole driver of severe disease. In a global series of people with advanced HIV and mpox, severe complications were concentrated at lower CD4 counts, and all deaths occurred in patients with CD4 counts below 200 cells/µL.⁷ Significant mpox morbidity has also been reported among solid-organ transplant recipients, including high rates of hospitalization and proctitis,⁸ and severe systemic mpox has been reported in a non-HIV-infected kidney transplant recipient.⁹ These observations support transplant-related immunosuppression as a plausible contributor in our patient, although the independent contributions of HIV infection and chronic transplant immunosuppression cannot be definitively separated.

The precise source of infection could not be established. The patient reported new sexual partners during the preceding month and both insertive and receptive anal intercourse, making recent intimate or sexual contact a plausible exposure; however, no partner was known to have confirmed or suspected mpox.

This case highlights the importance of considering mpox infection in the differential diagnosis of ulcerative proctocolitis in immunocompromised patients, particularly when cutaneous lesions are present, as it may closely mimic opportunistic infections such as cytomegalovirus colitis or inflammatory bowel disease.

Recognition of mpox-associated proctitis or proctocolitis is important because early identification can guide infection-control precautions and mpox-specific management in immunocompromised patients¹⁰ and may prevent unnecessary treatment of alternative etiologies.

DISCLOSURES

Author contributions: F. Deepali: conceptualization, data collection, manuscript drafting, literature review, and manuscript revision. K. Bhatia: endoscopic evaluation, clinical supervision and manuscript revision. A. Rembalsky: data collection and manuscript revision. J. Akinwuntan: literature review and manuscript revision. MN Jara-Tantoco: clinical care of patient and manuscript revision. G Ezaz: gastroenterology supervision, and manuscript revision. All authors approved the final manuscript. F. Deepali is the article guarantor.

Financial disclosure: None to report.

Conflicts of interest: The authors declare no conflicts of interest related to this manuscript.

Previous presentation: This case was presented at Digestive Disease Week, May 2–5, 2026; Chicago, IL.

Informed consent was obtained for this case report.

ABBREVIATIONS:

CMV

cytomegalovirus

HIV

human immunodeficiency virus

VZV

varicella zoster virus