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| CASE REPORT |
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| Ahead of print publication |
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Unilateral acute idiopathic maculopathy related to hand–foot–mouth disease: Case report and literature review
Chu-Yu Yen1, I-Mo Fang2
1 Department of Ophthalmology, Taipei City Hospital, Ren-Ai Branch, Taipei, Taiwan
2 Department of Ophthalmology, Taipei City Hospital, Ren-Ai Branch; Department of Ophthalmology, Taipei City Hospital, Zhongxiao Branch; Department of Ophthalmology, National Taiwan University Hospital; Department of Special Education, University of Taipei; Department of Medicine, Mackay Medical College, Taipei, Taiwan
| Date of Submission | 04-Oct-2022 |
| Date of Acceptance | 20-Nov-2022 |
| Date of Web Publication | 06-Jan-2023 |
Correspondence Address:
I-Mo Fang,
No. 87 Tonde Road, Nankang District, Taipei
Taiwan
 Source of Support: None, Conflict of Interest: None DOI: 10.4103/tjo.TJO-D-22-00139
Unilateral acute idiopathic maculopathy (UAIM) is a rare disease that may cause unilateral vision loss in young adults after a flu-like illness. Occasionally, it is associated with hand–foot–mouth disease (HFMD) and is often underdiagnosed. Herein, we report a case with characteristics of UAIM associated with HFMD with acute enteroviral infection. On the basis of the clinical findings using multimodality diagnostic imaging, including fundus image, optical coherence tomography, fluorescence angiography, and serological test for pan-enterovirus RNA polymerase chain reaction, we detailed the clinical course and postulated the pathogenesis of UAIM with choroiditis associated with HFMD. This study could remind every doctor of the potential visual loss caused by UAIM in HFMD, and referring patients to the ophthalmologic survey is important to eliminate potential visual impairment.
Keywords: Enterovirus infections, foot and mouth disease, hand, optical coherence tomography, polymerase chain reaction, unilateral acute idiopathic maculopathy
How to cite this URL:
Yen CY, Fang IM. Unilateral acute idiopathic maculopathy related to hand–foot–mouth disease: Case report and literature review. Taiwan J Ophthalmol [Epub ahead of print] [cited 2023 Jan 28]. Available from: https://www.e-tjo.org/preprintarticle.asp?id=367302 |
| Introduction | |  |
Unilateral acute idiopathic maculopathy (UAIM) is a rare disease that causes sudden, severe, and unilateral central vision loss in young adults after a flu-like illness.[1],[2] The reduced vision in these patients is due to an exudative neurosensory macular detachment with little or no vitreous inflammation and discoloration of the underlying retinal pigmented epithelium (RPE). It is often self-limited, spontaneously resolved without recurrence, and a “bull's-eye” appearance in the macula may persist.[1],[3],[4] UAIM, by definition, is not linked to an underlying disease process or known cause. However, several viral causes of UAIM have been reported. Ghazi et al. reported a 30-year-old female with bilateral UAIM that was associated with elevated coxsackievirus titers.[4] Dompieri et al. described a 59-year-old man with UAIM infected by yellow fever virus confirmed with reverse transcriptase polymerase chain reaction (PCR).[5] UAIM has also been associated with H1N1 vaccination in a 25-year-old Caucasian patient.[6] Our aim is to report a case of UAIM associated with hand–foot–mouth disease (HFMD) with acute enteroviral infection.
| Case Report | | |
A 23-year-old male without ophthalmic disease presented with a central scotoma in the left eye for 5 days. In addition, he had a fever, sore throat, and skin rash on the palmoplantar and perioral regions for 7 days [Figure 1]. The intraocular pressure in the left eye was 19 mmHg. The best-corrected visual acuity (BCVA) according to the Snellen chart was 0.9. Dilated fundus examination revealed a grayish-white patch at the superior-temporal macula [Figure 2]a. Optical coherence tomography (OCT) examination revealed abnormal heterogeneous hyperreflective thickening at the level of the outer retina and RPE in the foveal region with a central subfield thickness of 318 μm. There was evident ellipsoid zone (EZ) loss in the outer retina. The choroidal thickness was increased, and the connective interstitial tissue was less reflective [Figure 2]b. Fluorescence angiography (FA) examination showed irregular hyperfluorescence at the level of the retinal pigment epithelial lesion, followed by complete staining in the late phase of the study [Figure 2]c. There was no pinpoint leakage on FA or any signs of central serous chorioretinopathy on OCT. Serum laboratory data revealed unremarkable complete blood count, mycoplasma pneumonia immunoglobulin (Ig) M, and serological test for syphilis-rapid plasma. However, a positive result was shown in pan-enterovirus RNA PCR. | Figure 2: (a) A grayish-white patch at the superior-temporal macula. Circle: corresponding area in OCT; (b) Horizontal cross-sectional OCT of the left eye revealed abnormal heterogeneous hyperreflective thickening at the level of the outer retina and RPE in the foveal region. The choroidal thickness was increased, and the connective interstitial tissue was less reflective. Arrows: EZ loss in the outer retina; and (c) FA examination revealed irregular hyperfluorescence at the level of the retinal pigment epithelial lesion. OCT: Optical coherence tomography, RPE: Retinal pigmented epithelium, FA: Fluorescence angiography, EZ: Ellipsoid zone
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Under the impression of HFMD-related UAIM in the left eye, oral acetaminophen 500 mg four times a day was given for 7 days for general discomfort relief. One week later, the BCVA was 0.9, and the symptoms decreased gradually. An OCT examination revealed decreased thickening of the macula. In addition, there is focal EZ and interdigitation zone (IDZ) loss, as well as hyporeflective material in the subretinal space and focal choroiditis (the choriocapillaris layer is not clearly seen) on OCT [Figure 3]a. The follow-up examination showed BCVA 1.0 4 weeks later. There is recovery of the choriocapillaris layer, more prominent EZ and IDZ lines, and a more prominent Sattler's layer. However, the Haller's layer is still thickened [Figure 3]b. The EZ line is recovered and fully continuous 2 months later, but there are still irregularities in the IDZ lines. The choroiditis is fully recovered [Figure 3]c. | Figure 3: (a) Fundus photograph and OCT of the left eye revealed decreased thickening of the macula 1 week later. In addition, there is focal EZ and IDZ loss, as well as hyporeflective material in the subretinal space and focal choroiditis (the choriocapillaris layer is not clearly seen) on OCT. Right upper image: a vertical cross-section; right lower image: a horizontal cross-section. Circle: corresponding area in OCT, (b) Fundus photograph and OCT of the left eye revealed the macula lesion had completely subsided 4 weeks later. There is recovery of the choriocapillaris layer, more prominent EZ and IDZ lines, and a more prominent Sattler's layer. However, the Haller's layer is still thickened; (c) The EZ line is recovered and fully continuous 2 months later, but there are still irregularities in the IDZ lines. The choroiditis has fully recovered. OCT: Optical coherence tomography, EZ: Ellipsoid zone, IDZ: Interdigitation zone
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The patient provided written informed consent to the publication of her case report and any accompanying images.
| Discussion | | |
HFMD is a common contagious viral infection mostly caused by the Enterovirus family. Coxsackievirus A16, coxsackievirus A6, and enterovirus 71 are the most common causes of HFMD.[7] It is mainly in children under 10 years old and rarely in adults.[8] The most distinguished features are fever, oral ulcers, and skin manifestations affecting the palms, soles, and buttocks, with symptoms usually lasting <1 week.[9] Molecular biology tests for coxsackievirus-specific IgM or viral RNA positive by PCR are the recommended standard diagnostic tests for HFMD.[10] HFMD is self-limited and often recovers in 7–10 days.[11]
Enterovirus has been reported in several ocular diseases, especially in coxsackievirus groups. They include acute hemorrhagic conjunctivitis (coxsackievirus A24 variant), corneal endotheliitis (coxsackievirus A24 variant), UAIM, idiopathic retinal vasculitis (coxsackievirus A4), panuveitis (coxsackievirus B4), and chorioretinitis (coxsackievirus B4).[12] Duman et al. reviewed 11 cases of HFMD-related UAIM, and the following characteristics of these cases have been identified: young adults (19–38 years old); males predominate (female/male = 4/7); initial presentation: acute vision loss, 2 cases with scotoma; duration of visual symptoms: most within 1–2 weeks (one lasting 5 months); no treatment was given (only one oral corticosteroid); some residual pigmentary and scarring changes after disease; prognosis: complete recovery with some mild visual loss.[13]
The exact mechanism of HFMD-related UAIM is still under investigation. However, several hypotheses have been suggested. Coxsackievirus B3 has been proven to directly infect RPE in vitro.[14] Furthermore, coxsackievirus proteins may activate the host immune response, and molecular mimicry may make it difficult for autoreactive T-cells to distinguish between nonself (i.e., coxsackievirus) and self-antigen (e.g., choroidal, RPE, or outer retina).[15] Therefore, either direct hematogenous spread to RPE in viremia or immune-mediated damage may participate in this process.
The pathophysiology of UAIM shares similar features as other serous retinal detachments, as the integrity of the blood–retina barrier is disrupted and causes fluid leakage that enlarges the subretinal space and separates the sensory retina from the RPE.[16] UAIM was reported to be a consequence of choroidal inflammation, and indocyanine green angiography examination showed dilated choroidal vessels and neighboring “moth-eaten” appearing choroid vasculature, suggesting active choroiditis. In addition, OCT images revealed that the serous retinal detachment may result from underlying choroidal vasculitis or choroidal congestion and resultant RPE injury.[15] It is reasonable that the choroidal structure is the primary site of damage in UAIM secondary to viremia, as the immune-mediated inflammatory damage of the eyes is most likely to involve the uvea tissue, as in several of the auto-inflammatory disorders.[17]
The clinical presentation of UAIM in the fundus included irregular neurosensory retinal detachment overlying a smaller, grayish thickening at the level of the RPE, intraretinal hemorrhages, and inflammatory cells in the posterior vitreous. Other findings may include papillitis and eccentric macular lesions.[3] OCT scanning revealed hyperreflective debris on the apical side of the RPE, disruption of the ellipsoid layer, and the formation of subretinal fluid.[18],[19] FA showed early mottled or irregular hyperfluorescence and hypofluorescence, followed by late staining, pooling, or leakage.[15] Choroidal neovascularization (CNV) can also be seen as a complication of acute idiopathic maculopathy.[20]
The differential diagnosis of UAIM included central serous chorioretinopathy, Harada's disease, serpiginous choroidopathy, posterior scleritis, idiopathic CNV, acute posterior multifocal placoid pigment epitheliopathy (APMPPE), and placoid syphilitic retinitis. UAIM and APMPPE have been categorized as highly related due to the rapid resolution of symptoms following a flu-like illness in young adults.[1],[21] The rapid clinical course and epidemiology can help distinguish UAIM from other diseases.
Up till now, there has been no proven effective treatment for UAIM. Anti-vascular endothelial growth factor therapy may be beneficial if choroidal neovascularization occurs.[21] Conservative treatment and viral serology tests may be needed to identify the pathogen. As in our case, the etiology was confirmed by the clinical presentation of HFMD and pan-enterovirus RNA PCR.
This report demonstrated a case of HFMD-related UAIM in a community hospital using multimodality diagnostic imaging. The visual prognosis is fine without treatment, and no residual pigmentary or scarring changes, or CNV occurred after this episode. This study could remind every doctor of the potential visual loss caused by UAIM in HFMD. The correct diagnosis could avoid unnecessary or erroneous treatment, and referring patients to the ophthalmologic survey is important to eliminate potential visual impairment.
| Conclusion | | |
HFMD-related UAIM is a rare disease only in adults and always unilateral. It is associated with the inflammation of the outer retina, RPE, and inner choroid. The course is self-limited, and most of the patients complete visual recovery within weeks. Using multimodality diagnostic imaging, including fundus image, OCT, and FA, is the most reliable in diagnosis and follow-up.
Declaration of patient consent
The authors certify that they have obtained all appropriate patient consent forms. In the form, the patient has given his consent for his 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 his identity, but anonymity cannot be guaranteed.
Financial support and sponsorship
Nil.
Conflicts of interest
The authors declare that there are no conflicts of interest of this paper.
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[Figure 1], [Figure 2], [Figure 3]
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