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"Medical Journeys" is a set of clinical resources reviewed by physicians, meant for the medical team as well as the patients they serve. Each episode of this journey through a disease state contains both a physician guide and a downloadable/printable patient resource. "Medical Journeys" chart a path each step of the way for physicians and patients and provide continual resources and support, as the caregiver team navigates the course of a disease.

This month: A noteworthy case study

What was the cause of the severe bloody diarrhea that developed in a 60-year-old woman shortly after she returned from a 2-week vacation in East Africa? As Marionna Cathomas, MD, of Cantonal Hospital Baselland in Liestal, Switzerland, and colleagues detailed in the , clinicians in the emergency department (ED) where she presented learned that she had been living with left-sided ulcerative colitis since she was 40.

During most of that time, the patient's symptoms of abdominal pain and diarrhea had been sporadic and relatively mild, and she had managed them with alternative medicine. Her gut pain had worsened during her vacation, however, she said, and she was experiencing up to 10 episodes of diarrhea each day. At that point, she began using budesonide rectal foam and over-the-counter ciprofloxacin.

On physical examination, clinicians noted tenderness of the lower abdominal but no signs of peritonitis. Laboratory results showed that her C-reactive protein was 166 mg/l.

The patient declined hospital admission, and so was prescribed outpatient treatment with oral prednisone 60 mg/day, along with 5-aminosalicylic acid administered orally and rectally.

Two days later, she returned to the ED because her symptoms had not been relieved; at that point, she was hospitalized.

Multiplex polymerase chain reaction (PCR) testing of stool samples showed no microbial infection. Cathomas and co-authors noted that sigmoidoscopy showed the colon to be severely inflamed with evidence of deep-reaching ulcers and necrotic lesions on the colon wall. Clinicians took biopsies from the rectum and distal colon, which also confirmed severe inflammation and necrosis. Immunohistochemistry (IHC) test results were negative for cytomegalovirus (CMV).

Clinicians changed the patient's treatment regimen to intravenous methylprednisolone 50 mg/day and metronidazole/ciprofloxacin. The patient underwent a CT scan of the abdomen, which showed thickening of the left-sided colonic wall, with free intra-abdominal air, the team noted.

They performed an emergency laparoscopy, which revealed inflammation and infection of the peritoneum, and the descending colon had sustained a perforation. The patient told clinicians she would prefer to avoid subtotal colectomy. Given that the right colon showed no inflammation, the team performed Hartmann's procedure – i.e., a laparoscopic left hemicolectomy with formation of an end colostomy.

After surgery, the patient quickly improved. She was started on a biologic, infliximab, 2 days after surgery, to relieve the severe proctitis and any inflammation that persisted in the remnant colon. "Gross specimen examination showed a severe diffuse necrotizing colitis, and histology revealed an extensive ulcerating colitis with pseudomembranous character with patchy, transmural necrosis and perforation in the proximal descending colon," the case authors wrote.

Inflammation of the mucosa disappeared abruptly next to the perforation, and the oral resection margin showed normal mucosa, whereas the aboral margin was heavily inflamed and partially necrotic.

On day 3 after surgery, clinicians observed a marked increase in the patient's hepatic enzymes. Hypodense liver lesions were evident on an abdominal CT scan which they suspected might be caused by hepatic necrosis. Over the next 24 hours, her liver function continued to deteriorate, and she became encephalopathic. The team transferred the patient to a transplant center to be assessed for an urgent liver transplant.

Additional blood tests were positive for herpes simplex virus (HSV)-1 + 2 immunoglobulin G and M, and a liver biopsy showed that the patient had HSV hepatitis. Test results showed HSV viremia with 60 million copies/ml, which the case authors noted likely indicated systemic HSV infection.

Clinical examination showed erosive genital lesions; histology findings were positive for HSV-2. IHC of the colonic tissue confirmed HSV infection in the ulcers and necrotic areas, and further molecular analysis of the colonic tissue by type-specific PCR revealed HSV-2.

The patient received antiviral treatment and extensive critical care management, but unfortunately developed multiple organ failure, which led to her death 16 days after her initial presentation.

Discussion

"This case report describes an HSV-2-positive vulvar lesion [that] indicates a potentially primary florid HSV infection at the time of clinical exacerbation. The clinical course of inflammatory bowel disease (IBD) can be complicated by viral reactivation or superinfection," Cathomas and colleagues explained. They added that because opportunistic infections carry significant safety risks for IBD patients, they should be excluded during clinical workup.

The authors noted that cytomegalovirus is the most prevalent of these, affecting about one-third of IBD patients, and is known to be associated with "significant morbidity and poor outcome." In contrast, are rare and unexpected causes of deterioration in IBD patients, the team said.

In the general population, the prevalence of HSV-1 is as high as 98%, while HSV-2 is much rarer, occurring in about 20% of the population. These infections generally cause self-limiting, localized lesions in immunocompetent individuals. In patients who are however, HSV infection may result in severe local or systemic infection with potentially significant morbidity and mortality. Proctitis due to HSV-2 infection, for example, the case report authors noted, is seen frequently in men who have sex with men, whereas in individuals who are not immunocompromised, "the infection rarely extends above 15 cm of the anal verge."

Since the current patient had never been affected by "conventional immunosuppression," and had only taken rectal budesonide and high-dose oral prednisone for 4 days prior to surgery, the authors suggested that she already had significant HSV colitis at her first visit, which the systemic corticosteroids then aggravated.

"Despite the high seroprevalence of HSV worldwide, HSV colitis is a rarity," Cathomas and co-authors said. They found only seven reports of HSV colitis in patients with IBD, all of which presented with symptoms that suggested acute severe ulcerative colitis and involved initial corticosteroid treatment, followed by either cyclosporine, anti-tumor necrosis factor-inhibitors, or concomitant treatment with tacrolimus and azathioprine.

The diagnosis of HSV colitis was made by biopsy in one of those cases; diagnosis was delayed in three others, when surgery was required after bowel perforation. HSV-2 was found in three patients, and the remaining cases did not identify the genotype.

The authors concluded that while severe colitis due to HSV infection is a rare complication in IBD, physicians treating IBD patients need to be aware of the potential risk of severe HSV colitis following immunosuppressive therapy.

The team also pointed out that the most recent (2021) recommend asking all patients about their history of recurrent or florid HSV infection prior to starting immunosuppressive treatment. In those with a positive history, clinicians should consider preventive use of antivirals. "A thorough medical history and clinical examination can lead to rapid diagnosis and early initiation of antiviral treatment," the case authors concluded.

Read previous installments in this Medical Journeys series:

Part 1: UC: Understanding the Epidemiology and Pathophysiology

Part 2: UC: Symptoms, Exams, Diagnosis

Part 3: UC: How and Why Does It Arise?

Part 4: Case Study: Why Is This Teen's Ulcerative Colitis So Severe, So Resistant?

Part 5: UC: Initial Treatments and Response Monitoring

Part 6: UC: Dietary and Lifestyle Interventions

Part 7: Ulcerative Colitis: Second-Line Treatments