Herpes simplex virus ileitis

Case report

A 30-year old immuno-compromised male presented with abdominal distension and loss of appetite for two months, abdominal pain for five days and fever for the last two days. He was known to have HIV infection with pulmonary tuberculosis, currently on anti-retroviral therapy (ART) and anti-tubercular therapy (ATT).

On clinical examination, he was conscious and oriented. His body temperature was 38°C, blood pressure was 90/60 mmHg, pulse rate was 110 beats/min with oxygen saturation (SpO₂) of 87% on room air. He had a distended abdomen with guarding and diffuse tenderness.

Blood investigations revealed anaemia (Hb = 83 g/L) with leucocytosis (total leucocyte count = 16.1 × 10⁹/L) with increased liver enzymes. The CD4 count was 165 cells/µL. Chest radiography revealed multiple subdiaphragmatic air fluid levels with patchy consolidation in the upper lobe of the left lung. Peritonitis was suspected, and an exploratory laparotomy revealed a perforated ileal segment that was identified and resected, with a protective end ileostomy.

Grossly, the intestinal segment measured 110 cm in length with multiple perforations identified throughout, ranging in size from 0.5 to 1.5 cm in diameter (Fig. 1(a)). Microscopic sections revealed extensive ulceration of the lining epithelium (Fig. 1(b)) with multiple ill-defined epithelioid cell granulomas with areas of necrosis (Fig. 1(c)). There was the presence of intranuclear inclusions resembling herpes simplex virus (HSV) in the mucosal lining, ulcer bed and stromal cells together with the characteristic nuclear changes, including margination of chromatin and multinucleation (Fig. 1(d) and (e)). The viral inclusions were small pink deposits with a clear halo seen within the nucleus, similar to Cowdry Type A inclusions. On immunohistochemistry, these cells were highlighted by anti-HSV-1 monoclonal antibody (Fig. 1(f)). The stain for acid-fast bacilli was strongly positive. The diagnosis of HSV was further confirmed on serology (Western blot).

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Figure 1.

(a) Gross specimen showing perforation in the ileal segment, (b) HE ×100: section from the perforation sites shows extensive ulceration of the lining epithelium, (c) HE ×100: ill-defined epithelioid cell granulomas with areas of necrosis, (d) HE ×100: intranuclear inclusions of HSV in the ulcer bed and stromal cells, (e) HE ×400: higher magnification showing intranuclear inclusions of HSV along with the characteristic nuclear changes including margination of chromatin and multinucleation, (f) IHC ×400: the cells with inclusions highlighted by anti-HSV-1 monoclonal antibody.

A final diagnosis of dual infection (HSV-1 and tubercular ileitis) in a known case of pulmonary tuberculosis and HIV was made. Our patient was started on antiviral therapy, and the ATT and ART were continued; however, he succumbed and died shortly after surgery.

Discussion

HSV is a double-stranded DNA virus of the herpesviridae family, comprising two species: HSV-1 and HSV-2. ¹ Their estimated prevalence in the United States is approximately 50% and 15%, respectively. ² HSV-1 infection has a wide variety of presentations, including orolabial herpes, herpetic sycosis (HSV folliculitis), herpes gladiatorum, herpetic whitlow, ocular HSV infection, herpes encephalitis, Kaposi varicelliform eruption (eczema herpeticum), and severe or chronic HSV infection. HSV-2 more commonly presents with genital lesions. HSV is generally spread via direct contact with bodily secretions. The virus's ability to establish latency within a sensory ganglion after primary infection can lead to subsequent reactivation. ¹

Infection of the gastro-intestinal tract by HSV is very rare, the commonest site being the oesophagus. Herpes simplex oesophagitis is usually found in immuno-suppressed individuals. ³ HSV colitis may also occur, especially in patients with inflammatory bowel disease receiving systemic steroids and antimetabolites. ⁴

An extensive literature search has shown <10 reported cases of HSV duodenitis, and only one reported case of ileal involvement (ileo-colitis) in a post-chemotherapy immuno-compromised individual. ⁵ It is possible for HSV-1 and tubercular infection to occur concurrently, especially in individuals with weakened immune systems, as in our case; the mechanisms of pathogenesis are completely distinct. ¹

The gold standard for diagnosing HSV-1 infection is HSV-1 serology (antibody detection via Western blot). HSV detection by polymerase chain reaction and immunohistochemistry using monoclonal antibodies against HSV-1/2 antigens has shown good sensitivity and specificity in diagnosis. ⁶ Antiviral therapy, such as Acyclovir in combination with ART, is effective in the treatment of such cases. By reducing HSV replication, Acyclovir can indirectly help manage HIV by decreasing HIV viral load and potentially improving survival in HIV-infected individuals. ⁷