|Year : 2022 | Volume
| Issue : 1 | Page : 1
Cytomegalovirus retinitis in Crohn's disease treated with anti-tumor necrosis factor-alpha antibody
Cristobal Andres Nazar1, José Antonio San Martín2, Rodolfo I Garretón1, Aldo Andres Muñoz3
1 Department of Ophthalmology, Pontificia Universidad Católica de Chile, Santiago, Chile
2 Fundación Oftalmológica Los Andes, Santiago, Chile
3 Department of Ophthalmology, Pontificia Universidad Católica de Chile, Santiago, Chile; Department of Ophthalmology, The University of Auckland, Auckland, New Zealand
|Date of Submission||01-Nov-2021|
|Date of Decision||14-Nov-2021|
|Date of Acceptance||15-Nov-2021|
|Date of Web Publication||13-Jan-2022|
Dr. Cristobal Andres Nazar
Department of Ophthalmology, Pontificia Universidad Católica de Chile, Santiago
Source of Support: None, Conflict of Interest: None
Cytomegalovirus (CMV) is a double-stranded DNA virus. It is an opportunistic infection that usually affects individuals with AIDS or with profound immunosuppression. CMV retinitis is the most frequent ocular manifestation. Infrequently, this pathology has been observed in patients undergoing immunosuppressive treatment due to autoimmune diseases. This article presents a case of Crohn's disease with systemic and ocular involvement by CMV after starting treatment with infliximab (anti-tumor necrosis factor-alpha antibody).
Keywords: Anti-tumor necrosis factor-alpha antibody, cytomegalovirus, cytomegalovirus retinitis, immunocompromised hosts, inflammatory bowel disease, infliximab
|How to cite this article:|
Nazar CA, San Martín JA, Garretón RI, Muñoz AA. Cytomegalovirus retinitis in Crohn's disease treated with anti-tumor necrosis factor-alpha antibody. Pan Am J Ophthalmol 2022;4:1
|How to cite this URL:|
Nazar CA, San Martín JA, Garretón RI, Muñoz AA. Cytomegalovirus retinitis in Crohn's disease treated with anti-tumor necrosis factor-alpha antibody. Pan Am J Ophthalmol [serial online] 2022 [cited 2022 Oct 1];4:1. Available from: https://www.thepajo.org/text.asp?2022/4/1/1/335852
| Introduction|| |
Cytomegalovirus (CMV) is a double-stranded DNA virus from the Herpesviridae family, it is ubiquitous, and its seropositivity in the adult population ranges from 40% to 100%. After the primary infection, which may or may not be symptomatic, CMV remains a latent infection in several organs. Viral reactivation is triggered by states of inflammation or immunosuppression and can severely affect multiple organs.
CMV retinitis is the most frequent ocular manifestation, causing progressive retinal damage and permanent visual deterioration in affected patients. It is an opportunistic infection that usually affects individuals with AIDS or with profound immunosuppression in the context of bone marrow or solid organ transplantation. Less commonly, this pathology has been observed in patients undergoing immunosuppressive treatment due to autoimmune diseases.
The administration of anti-tumor necrosis factor-alpha (anti-TNF-α) antibodies in patients with inflammatory bowel disease (IBD) refractory to other therapies has been shown to be effective. Therefore, its prescription is growing; nevertheless, its use could increase susceptibility to some opportunistic infections, such as CMV.
This article presents a case of Crohn's disease with systemic and ocular involvement by CMV after starting treatment with infliximab (anti-TNF-α antibody).
| Case Report|| |
Our patient is a 44-year-old Latino woman diagnosed with Crohn's disease, who started treatment with prednisone 40 mg/day and mesalazine 500 mg four times a day with a poor clinical response after 4 weeks under treatment. Given its resistance to steroids, infliximab 300 mg was started as induction according to the standard protocol and then maintained with infliximab 300 mg every 6 weeks (6,8 mg/kg), azathioprine 100 mg/day, and tapering prednisone up to 5 mg/day. After her fifth infliximab dose, our patient was admitted to the intensive care unit with hypotension, fever, and increased frequency of bloody stools, as well as decreased visual acuity in her left eye.
After hemodynamic stabilization, a colonoscopy was performed. Biopsies of the distal ileum and colon were sampled, reporting findings consistent with ulcerative type colitis and cytopathic abnormalities suggestive of CMV infection. CMV immunohistochemical study was positive [Figure 1], and quantitative real-time polymerase chain reaction (PCR) identified more than 9,000,000 IU/mL. HIV infection was ruled out.
|Figure 1: Granulation tissue from the ulcer of an active inflammatory intestinal disease in a colon endoscopic sample HE ×10 (a). Cytomegalic cells containing basophilic intranuclear inclusion bodies (Cowdry bodies) ×40 HE (b). Positive stain for cytomegalovirus by immunohistochemistry in the stromal and endothelial cell of the granulation tissue ×10 (c) and ×40 (d)|
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At the initial ophthalmological examination, our patient presented normal pupillary reflexes, anterior segment examination was unremarkable, and intraocular pressure was within the physiological range. Visual acuity in the right eye was 1.0, but in the left eye, it was counting fingers associated with an evident central scotoma. Examination of the fundus revealed an area of hemorrhagic retinal necrosis extending from the optic nerve to the upper sector of the macula, following the superior branch retinal vessels distribution. The retinal periphery showed no other similar lesions [Figure 2].
|Figure 2: Initial fundus. Necrohemorrhagic retinitis from the superotemporal margin of the optic disc, extending through the superotemporal vascular arcade to the superior macular area, with foveal involvement|
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Given these findings, the diagnosis of systemic CMV disease was made, and ganciclovir IV was started. She evolved unfavorably both from the gastroenterological and retinal point of view, so it was decided to perform a total colectomy and start intravitreal ganciclovir (2.5 mg/0.05 mL). After three intravitreal injections and completion of antiviral treatment with valganciclovir 900 mg/day, visual acuity in the left eye had improved to 20/400, but a positive central scotoma was still present, the rest of her ophthalmological examination remained unchanged after 1 year [Figure 3].
|Figure 3: Evolution under treatment. Significant regression after intravitreal ganciclovir. Retinitis in Frank resolution after three doses of intravitreal ganciclovir, with atrophic retinal areas|
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| Discussion|| |
IBD, including Ulcerative Colitis and Crohn's Disease, is a group of chronic conditions characterized by highly disabling periods of remission and relapse, affecting approximately 1.3% of the United States population.
The current IBD treatment is based on the progressive use of 5-aminosalicylic acid, corticosteroids, immunomodulators, and biological agents. TNF-α inhibitors are especially useful in cortico-refractory people. However, a large part of these drugs have been associated with an increased risk of opportunistic infections.
Regarding CMV, colonic infection is observed more frequently in cases of IBD refractory to corticosteroids or in treatment with immunomodulators. Despite the above, its pathogenic role in immunosuppressed patients with IBD is still unclear. Matsuoka et al. published a series of 69 patients with ulcerative colitis with moderate to severe activity. CMV-positive serology (IgG) was detected in 48 patients. About 52.2% of those seropositive patients had a subclinical systemic infection defined by positivity for CMV in plasma by PCR. Most of the patients with positive plasma PCR for CMV presented a spontaneous resolution of subclinical infection (negative PCR) in weeks to months. On the other hand, there is evidence showing that CMV infection is significantly associated with a higher frequency of colectomy and reactivations of IBD.
There are only a few reports in the literature of systemic CMV infection with extra-digestive organs involvement in immunosuppressed patients with IBD. In relation to the use of anti-TNF-α agents in IBD, there are approximately six reports of opportunistic CMV infection, but none of them mention retinal involvement., However, Haerter et al. described the only one report in literature of CMV retinitis secondary to immunosuppressive treatment with anti-TNFα antibody (infliximab) in a rheumatoid arthritis patient. Five weeks after cessation of antiviral maintenance therapy with valganciclovir, CMV retinitis occurred in the contralateral eye.
Regarding ophthalmological reports, Ammari and Berriche published a case of CMV retinitis in a patient with ulcerative colitis treated with azathioprine. In most case reports about CMV infection associated with the use of anti-TNF-α, patients have been exposed to multiple immunosuppressive drugs simultaneously. This is also valid for this case since our patient received infliximab, prednisone, and azathioprine. In view of the above, it is difficult to know with absolute certainty whether the use of anti-TNF-α is causally linked to the development of CMV disease. However, it seems possible that TNF-α inhibition was a predominant risk factor.
This case exemplifies that systemic CMV infection in immunosuppressed patients with IBD can have severe clinical consequences. To the best of our knowledge, the case presented here constitutes the first report in the literature of CMV retinitis in an individual treated with anti-TNF-α in Crohn's disease.
Although it is true that in a significant percentage of CMV cases in immunosuppressed patients with IBD, the infection is subclinical, its potentially pathogenic role should not be minimized. This emphasis should be maximized in patients undergoing treatment with multiple immunosuppressive drugs. Thus, in any patient treated with anti-TNF-α antibodies who complained about visual disturbances, a presumed ocular involvement due to CMV should be considered. Specialists who handle immunosuppressive drugs must be aware of a possible CMV retinal infection and should educate patients to consult promptly when visual symptoms appear.
Declaration of patient consent
The authors certify that they have obtained all appropriate patient consent forms. In the form, the patient has given her consent for her images and other clinical information to be reported in the journal. The patient understands that name and initials will not be published and due efforts will be made to conceal identity, but anonymity cannot be guaranteed.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
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[Figure 1], [Figure 2], [Figure 3]