Abstract
More than 90% of people worldwide are seropositive for herpes simplex virus (HSV) by the fourth decade of their lives. HSV is usually asymptomatic or follows a mild, self-limited course in healthy individuals. In severely immunocompromised hosts or in patients with underlying inflammatory bowel disease (IBD) treated with immunomodulators, HSV can cause significant morbidity and mortality, including mucocutaneous ulcerations, esophagitis, hepatitis, and encephalitis. This is a rare case of HSV-2 causing necrotizing ischemic colitis, toxic megacolon, and necroinflammation of the liver in the absence of transaminitis in a patient who received steroids for drug rash with eosinophilia and systemic symptoms (DRESS) syndrome.
Case Presentation
A seventy-year-old African American female with a past medical history of essential hypertension, type two diabetes mellitus, gout, and osteoarthritis presented to the hospital with complaints of pruritic skin rash around the eyes, diarrhea, and weakness. The patient was started on allopurinol a few weeks prior to presentation after an acute gout flare in the right foot. Patient had an oral temperature of 103 ˝F, a maculopapular rash of the face, eyelids, torso, and extremities, and diffuse tenderness with palpation of the abdomen.
| Initial Blood Work and Diagnostic Workup | |
|---|---|
| White Blood Cell Count | 14.3 K/UL with 21% bands |
| Eosinophils | 16% |
| Hemoglobin | 6.8 g/dl |
| Blood Urea Nitrogen | 38 mg/dl |
| Creatinine | 2.0 mg/dl |
| Aspartate Aminotransferase | 79 IU/L |
| Alanine Aminotransferase | 44 IU/L |
| Alkaline Phosphatase | 173 IU/L |
| Total Bilirubin | 1.9 mg/dl |
| Lactate Dehydrogenase | 505 IU/L |
| Haptoglobin | less than 15 |
| Direct Coombs test | Positive |
| HIV Antigen and Antibodies | Negative |
An esophagogastroduodenoscopy revealed reflux esophagitis and an erythematous duodenum (Figure 1). A colonoscopy showed congested mucosa in the ascending colon and diverticulosis in the sigmoid and descending colon (Figure 2). The histopathology of colon biopsies revealed extensive crypt dropout and crypt epithelial apoptosis, suggestive of a drug reaction. The viral immunostains were negative.
The patient was diagnosed with DRESS syndrome and autoimmune hemolytic anemia secondary to allopurinol. She was started on IV solumedrol and topical triamcinolone cream. On day ten of admission, the patient became hypotensive with a blood pressure of 79/61 mmHg and was complaining of persistent diarrhea. A computed tomography (CT) scan of the abdomen and pelvis showed severe dilatation of the small bowel, suggestive of severe ileus, and free fluid surrounding the liver and spleen.
| Day Ten Diagnostic Workup | |
|---|---|
| White Blood Cell Count | 13.6 K/UL with 21% bands |
| Hemoglobin | 7.8 g/dl |
| Eosinophils | 1% |
| Blood Urea Nitrogen | 102 mg/dl |
| Creatinine | 1.7 mg/dl |
| Aspartate Aminotransferase | 18 IU/L |
A repeat colonoscopy reported evidence of segmental ischemic colitis in the descending and sigmoid colon as well as erythema and punctate hemorrhage in the rest of the colon, with suspicion of small bowel involvement (Figure 3).
The patient underwent an exploratory laparotomy, and a toxic megacolon and segmental ileal ischemia were found. A left hemicolectomy, a segmental ileal resection, an end colostomy, and a takedown of the splenic flexure were performed. On day fourteen of admission, the patient was experiencing severe abdominal pain, and the ostomy site was noted to be dusky. A repeat colonoscopy revealed a continuous area of non-bleeding ulcerated mucosa in the descending colon and ulcerated ischemic changes in the colostomy and right colonic mucosa which were not present before surgery (Figure 4).
The patient was taken back to the operating room. Nodular tissue in the liver and patchy, dusky areas in the right colon concerning for severe ischemic colitis were noted. A liver biopsy was performed, and she underwent a right hemicolectomy with resection of the distal ileum. The pathology from the colon and ileum biopsies showed submucosal necrosis, transmural inflammation, and multiple cells exhibiting an HSV viral cytopathic effect, which was confirmed via HSV immunostaining. A liver biopsy showed subcapsular necroinflammation and focal cells exhibiting an HSV viral cytopathic effect, which was confirmed via HSV immunostaining. A qualitative HSV PCR in the serum came back positive for HSV-2 and negative for HSV-1. The patient was started on intravenous acyclovir and significantly clinically improved.
Discussion
This is a case of a patient with HSV-2 infection presenting with toxic megacolon, ischemic colitis, and necroinflammation of the liver in the absence of transaminitis. Classically, HSV tends to infect squamous epithelial cells rather than columnar epithelial cells. In the literature review, disseminated gastrointestinal HSV infection can occur in immunocompromised hosts, particularly those on steroids or in IBD patients treated with immunomodulators [1–3]. Cytomegalovirus has been described to cause toxic megacolon and ischemic colitis in patients with underlying IBD [2–3]. HSV is known to cause mucocutaneous ulcerations and esophagitis when reactivated in immunocompromised hosts, but it does not typically cause ischemic colitis [4]. There are rare case reports of HSV causing ischemic colitis in patients with IBD on immunomodulators [2–3]. This patient was different than other prior case reports of HSV causing ischemic colitis because she was not on any immunomodulators. This is also the first known reported case of HSV causing toxic megacolon. In patients who present with fulminant HSV hepatitis, one of the hallmark signs is markedly elevated transaminases. This patient was noted to have visible intraoperative nodular changes to her liver, and a liver biopsy showed necroinflammation secondary to HSV despite the normal aspartate aminotransferase and alanine transaminase at the time of her surgery. To our knowledge, this is the first case of a patient presenting with toxic megacolon, ischemic colitis, and hepatitis (in the absence of transaminitis) secondary to disseminated HSV-2 following steroid use
Funding
This research received no external funding.
Conflicts of Interest
The authors declare no conflict of interest.
References
- Chevaux, J.B.; Peyrin-Biroulet, L. Herpes Simplex Virus Colitis Complicating the Course of a Patient with Crohns Disease and Cirrhosis: An Underestimated Association? Gastroenterol. Hepatol. 2010, 6, 122–124
- Schunter, M.O.; Walles, T.; Fritz, P.; Meyding-Lamadé, U.; Thon, K.-P.; Fellermann, K.; Stange, E.F.; Lamadé, W. Herpes simplex virus colitis complicating ulcerative colitis: A case report and brief review on superinfections. J. Crohns Colitis 2007, 1, 41–46. [CrossRef] [PubMed]
- Phadke, V.K.; Friedman-Moraco, R.J.; Quigley, B.C.; Farris, A.B.; Norvell, J.P. Concomitant Herpes Simplex Virus Colitis and Hepatitis in a Man with Ulcerative Colitis: Case Report and Review of the Literature. Medicine 2016, 95, e5082. [CrossRef] [PubMed]
- Colemont, L.J.; Pen, J.H.; Pelckmans, P.A.; Degryse, H.R.; Pattyn, S.R.; Van Maercke, Y.M. Herpes Simplex Virus Type 1 Colitis: An Unusual Cause of Diarrhea. Am. J. Gastroenterol. 1990, 85, 1182–1185. [PubMed]
