Cytomegalovirus Keratitis in Acute Myeloblastic Leukemia Report of a Case

Objectives: Here, we report a rare case of acute myeloblastic leukemia (AML) developed a bilateral dendritic epithelial keratitis without retinitis Case presentation: A 58-year-old woman presented to the emergency department of Baqiyatallah Hospital in Tehran due to dyspnea and dry cough along with weakness, lethargy and weight loss resulting from acute myeloblastic leukemia. She was treated for systemic problem. In a while after developing pain, burning, redness of the eyes and ocular mucopurulent discharge, ocular symptoms began. The patient was initially treated with oral acyclovir with a possible diagnosis of Herpes simplex virus Keratitis. Polymerase Chain Reaction (PCR) was performed on ocular discharge specimens collected by soft-tipped applicators reported as CMV. Then, acyclovir was discontinued and bilateral CMV keratitis treated with IV Ganciclovir and her epithelial lesions gradually disappeared. Conclusions: CMV is capable of generating corneal epithelial engagement without corneal endothelium and retina involvement and demonstrated that CMV keratitis can be a rare cause but an emergent problem of acute myeloblastic leukemia (AML). Therefore, in any cases with bilateral corneal herpes keratitis, the patient should be evaluated for immune system deciency.


Introduction
As a herpes virus, the human cytomegalovirus contracts via close personal exposure and causes a subclinical, self-recovering disease in healthy individuals. In immunocompetent individuals, systemic and ocular disorders are rare, meanwhile presenting a mononucleosis like syndrome with acute conjunctivitis is not rare. [1]Acquired immunode ciency syndrome (AIDS), Newborns, transplant recipients, and other patients with weaken immune system are prone to disseminated infectious agents that contain the retinal pigment epithelium as well as sensory retina. CMV infection also causes anterior segment manifestations, which are hardly identi ed. In the present study, a rare case with acute myeloblastic leukemia who developed bilateral CMV keratitis approved by Polymerase Chain Reaction is reported.

Case Report
A 58-year-old Iranian woman was referred to the emergency department of Baqiyatallah Hospital in Tehran with a diagnosis of in uenza due to dyspnea and dry cough along with weakness, lethargy and weight loss. She was treated with Levo oxacin 500 mg twice daily, N-acetylcysteine 600 mg twice daily, Bisoprolol 5 mg twice daily and Losartan 25 mg twice daily for systemic problem.
In a while after developing pain, burning, redness of the eyes and ocular mucopurulent discharge, ocular symptoms began. In ophthalmological examinations, the visual acuity of both eyes was 8/10 decimal.
Both eyes had mild conjunctival hyperemia. The corneal sensation was decreased. A dendritic epithelial defect was detected at paracentral and corneal periphery of both eyes (Fig. 1). Both lesions comprised swollen epithelial cells. The basic stroma was well identi ed. We could not nd iritis. Moreover, ophthalmic exam revealed no retinal lesion. Treatment with oral acyclovir, 400 mg 5 times per day was initiated for presumed herpes simplex virus epithelial keratitis, however, bilateral lesions suggested that the patient may have some form of immunode ciency.
Simultaneously computed tomography (CT) of the lung was done that revealed a ground glass opacity. Then, a PCR test from Bronchioalveolar Lavage was requested that reported positive for CMV. Three days later, Bone Marrow Aspiration test was done that reported M3-Non type acute myeloblastic leukemia (AML).
Due to the bilateral ocular manifestation's lesions, the patient's dendritic epithelium was sampled with an applicator under sterile conditions and tested for PCR for CMV, EBV and HSV. The PCR test of ocular epithelial sample reported as CMV.
Consequently, acyclovir was discontinued and the patient was treated with Ganciclovir 30mg/ kg/ IV for Bilateral CMV keratitis. The patient followed -up closely every 3 days and her epithelial lesions gradually disappeared.

Discussion
Cytomegalovirus disease of external eye is rare and its anterior segment presentations are extraordinary. Cytomegalovirus can be latent without manifestation in immunocompromised patients and CMVinduced retinitis is an important cause of blindness in this group. One previously described an adult suffering from CMV keratitis with a history of cardiac transplant recipient suffering from acquired CMV infection due to transpalation. [2] Positive corneal culture results indicated the presence of the disease, and unilateral dendritic epithelial keratitis resolved after super cial debridement. Also, CMV epithelialithis along with endotheliitis has been reported in patients with AIDS without retinitis. [3] Likewise, intravitreal inoculation of CMV in healthy mice showed that CMV caused a self-limiting and temporary affecting anterior segment of the eye. In contrast, in mice with suppressed immunity, necrotizing retinitis occurred. [ 4] In our patient, CMV manifested only as dendritic epithelial lesions (see Fig. 1) akin to formerly described case who mimicked the epithelial keratitis due to herpes zoster. [ 5]. The linear lesion did not develop terminal bulbs or epithelial ulceration. PCR test of the sample taken with the applicator from dendritic epithelial lesions of both eyes con rmed CMV infection of the corneal epithelium.
Dendritic epithelial lesions can be caused by the HSV virus, and HSV-induced keratitis is also often unilateral, but in this patient bilateral dendritic manifestations was appeared. Varicella Zoster Virus can also cause these manifestations but epithelial keratitis of dendritic type is unusual, however is common in HZO. [6] In HZO, the branched and Medusa-like lesions plaques are prominent. These lesions do not have central ulcers and have minimal staining with uorescein. Meanwhile, the bulbous end is not seen.
[7] Nevertheless, in this patient the dendritic lesions were different from those of HZO including painful skin lesions, with no distributed dermatome.
We could not identify how the patient was infected. Still, no investigational model of CMV keratitis is developed by topical challenge 8 although occasional intravitreal inoculation caused corneal in ltrates. 9 In most cases, CMV does not manifest in the corneal of AML patients, viral reactivation at a non-ocular site may extend to the anterior segment. Moreover, Viremia with conjunctival or limbal contamination and lacrimal gland involvement are probable mechanisms that the corneal epithelium can be infected throughout a systemic CMV contamination.
In this case peripheral involvement of the cornea shows a systemic CMV infection that most probably has arisen from the limbus. In other words, diminishing immune activity presumably permits infection of the ocular surface. During primary infection, CMV infects myeloid precursors CD34 +. Such cells are capable of differentiating into macrophages and dendritic cells as a whole and the body allows the virus to spread. [4] Therefore, redistribution of the virus leads to a range of CMV-induced diseases, including asymptomatic diseases in patients without immunode ciency to severe multisystem diseases and even loss of life in patients with weak immune system as well as infants.
Ocular presentations of CMV contain conjunctivitis, microphthalmos, cataract, optic nerve abnormalities, eye in ammation, retinitis and in ammation of the cornea. While CMV keratitis is rare, but its manifestation is growing. [4] Delayed diagnosis of CMV keratitis often causes serious problems including stromal keratitis and endothelialitis [10] In summary, although, herpes simplex virus and varicella-zoster virus are usual origins of corneal infection during immunode ciency and CMV-induced keratitis often involve endothelium, bilateral corneal epithelial keratitis manifestations will be con rmed as a newly identi ed consequence of AML. Therefore, investigating risk factors of the host and viral genomics can pave the way for further intuition regarding the pathogenesis of CMV keratitis in otherwise immunocompetent individuals.