Simultaneous clinical presentation of Vogt-Koyanagi-Harada disease and ocular tuberculosis: A diagnostic and therapeutic challenge

Raul E Ruiz-Lozano; I Jocelyn Rivera-Alvarado; Luis A Rodriguez-Gutierrez; Lucas A Garza-Garza; Alejandro Rodriguez-Garcia

doi:10.4103/pajo.pajo_45_22

CASE REPORT

Year : 2022 | Volume : 4 | Issue : 1 | Page : 54

Simultaneous clinical presentation of Vogt-Koyanagi-Harada disease and ocular tuberculosis: A diagnostic and therapeutic challenge

Raul E Ruiz-Lozano, I Jocelyn Rivera-Alvarado, Luis A Rodriguez-Gutierrez, Lucas A Garza-Garza, Alejandro Rodriguez-Garcia
Tecnologico de Monterrey, School of Medicine and Health Sciences, Institute of Ophthalmology and Visual Sciences, Monterrey, Mexico

Date of Submission	26-Aug-2022
Date of Decision	08-Sep-2022
Date of Acceptance	20-Sep-2022
Date of Web Publication	22-Nov-2022

Correspondence Address:
Alejandro Rodriguez-Garcia
Instituto De Oftalmologia Y Ciencias Visuales Centro Medico Zambrano Hellion, Av. Batallon De San Patricio No. 112. Col. Real De San Agustin, N.L. CP. 66278
Mexico

Source of Support: None, Conflict of Interest: None

DOI: 10.4103/pajo.pajo_45_22

Abstract

The simultaneous occurrence of an infectious and an autoimmune systemic disorder associated with bilateral panuveitis is always feasible but improbable. While Vogt-Koyanagi-Harada requires prompt systemic corticosteroids and immunosuppressives, ocular tuberculosis (TB) requires multiple antibiotic therapies, and to a certain extent, corticosteroids to avoid inflammatory damage to crucial intraocular structures. We report a patient with granulomatous bilateral panuveitis, in which VKH and ocular TB were diagnosed simultaneously. This case emphasizes the importance of ruling out TB in the presence of a granulomatous panuveitis, despite the lack of pulmonary manifestations, especially in an endemic country. The hindmost because both diseases require different treatments.

Keywords: Immunosuppressive therapy, ocular tuberculosis, panuveitis, Vogt-Koyanagi Harada disease

How to cite this article:
Ruiz-Lozano RE, Rivera-Alvarado I J, Rodriguez-Gutierrez LA, Garza-Garza LA, Rodriguez-Garcia A. Simultaneous clinical presentation of Vogt-Koyanagi-Harada disease and ocular tuberculosis: A diagnostic and therapeutic challenge. Pan Am J Ophthalmol 2022;4:54

How to cite this URL:
Ruiz-Lozano RE, Rivera-Alvarado I J, Rodriguez-Gutierrez LA, Garza-Garza LA, Rodriguez-Garcia A. Simultaneous clinical presentation of Vogt-Koyanagi-Harada disease and ocular tuberculosis: A diagnostic and therapeutic challenge. Pan Am J Ophthalmol [serial online] 2022 [cited 2023 Mar 28];4:54. Available from: https://www.thepajo.org/text.asp?2022/4/1/54/361715

Introduction

Ocular tuberculosis (TB) usually results from hematogenous spread from a distal focus of infection.^[1] The high oxygen tension due to high blood flow in the choroid promotes organism growth; thus, the most common ocular manifestation is choroidal granulomas, frequently accompanied by granulomatous panuveitis.^[2] Conversely, Vogt-Koyanagi-Harada (VKH) is an autoimmune inflammatory disorder affecting the skin, meninges, auditory system, and eyes.^[1] The pathogenic mechanism of VKH remains elusive; however, evidence suggests a T-cell-mediated autoimmune process directed against melanocytes.^[2] Clinical features include bilateral granulomatous panuveitis with serous retinal detachment (RD), meningismus, dysacusia, and skin changes. Patients with VKH typically require high-dose corticosteroids and immunosuppressive therapy (IMT).^[3] Unfortunately, such therapies may induce the reactivation of TB.^[3] There is evidence of TB reactivation after IMT of VKH, and the occurrence of VKH after Bacillus Calmette-Guérin (BCG) vaccination.^[2],[3],[4] To our knowledge, the simultaneous diagnosis of TB and VKH has not been reported.

Case Report

A 60-year-old Mexican-mestizo male from Oaxaca, currently living in Nuevo Leon, presented with a 1 month history of malaise, neck stiffness, nausea, and bilateral progressive visual loss, which dramatically decreased the day before the consultation. The personal or familiar history of other ophthalmic and/or systemic diseases was denied. Best-corrected visual acuity (BCVA) was hand motion in both eyes (OU). An afferent pupillary defect in the left eye (OS) was noted, along with 1+ anterior chamber cells and medium-sized granulomatous keratic precipitates OU. Fundus examination disclosed bilateral optic disc edema, mainly in OS, with splinter hemorrhages in the peripapillary retinal nerve fiber layer OS. No vitreous inflammation was noted OU. Furthermore, retinal folds, subtle choroidal, and shallow exudative RDs involving the macula were seen OU [Figure 1]a and [Figure 1]b. Fluorescein angiography (FA) showed optic disc staining and leakage OU, and scattered hyperfluorescent spots, mainly in the right eye (OD), which tended to coalesce lately [Figure 1]c and [Figure 1]d. B-scan ultrasonography (US) confirmed an inferior RD in OD and choroidal thickening OU [Figure 2]a and [Figure 2]b. Macular TD-OCT revealed fluctuation of the internal limiting membrane and serous RD [Figure 2]c and [Figure 2]d. VKH was diagnosed based on the prodromal manifestations, the rapidity of bilateral visual loss, fundus appearance, and the multimodal imaging findings. Initial laboratory workup was negative for complete blood count, erythrocyte sedimentation rate, C-reactive protein, ANA, Chem-14, HIV enzyme-linked immunosorbent assay, fluorescent treponemal antibody absorption test (FTA-Abs), and chest X-ray. Hourly prednisolone acetate 1%, atropine 1% QD, and bromfenac 0.09% BID were initiated OU. A 40mg triamcinolone acetonide transseptal injection was applied OU, and prednisone 60 mg/day was initiated. After 72 h, BCVA improved to 20/60 OD and 20/80 OS. Purified protein derivative (PPD) test was positive (skin induration 22 mm) in the absence of BCG vaccination. Therefore, a new generation interferon-gamma release assay (IGRA), the QuantiFERON-TB Gold Plus (QFT-Plus), was ordered, resulting positive (0.45 UI/ml).^[5] The patient was referred to the infectious diseases department, and no other foci of TB, rather than the eye, were found. Antitubercular therapy (ATT) with isoniazid 300mg/day, rifampicin 600mg/day, ethambutol 15 mg/kg/day, and pyrazinamide 25 mg/kg/day was initiated.^[6] After 1 month, BCVA improved to 20/40 OU; thus, gradual tapering of corticosteroids was initiated. After 4 months, both eyes showed complete resolution of the optic disc swelling and macular edema [Figure 3]. At 18 months, the patient remains stable, and the IGRA turned negative (0.13 IU/ml) with no recurrences of inflammation and a BCVA of 20/25 OU.

Figure 1: (a) Fundus photograph of the right eye showing optic disc edema (360° blurred disc margins); venular tortuosity, and shallow serous retinal detachment of the posterior pole with radial macular folds (white arrow). (b) The left eye shows significant optic disc edema with splinter hemorrhages and shallow serous retinal detachment of the posterior pole with macular folds (white arrow). (c) Fluorescein angiography of the right eye at 5 min and 16 s shows leakage (red arrow) from the optic disc and multiple hyperfluorescent white dots in the posterior pole. (d) Fluorescein angiography of the left eye at 24 s also shows leakage (red arrow) from the optic disc and irregular choriocapillaris flush

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Figure 2: (a) B-scan ultrasound of the right eye showing an inferior serous retinal detachment (white arrow) and choroidal thickening. (b) Left eye B-scan ultrasound shows choroidal thickening. (c) Time-domain OCT of the right eye shows subretinal fluid centrally and nasally, and intraretinal fluid with a central macular thickness of 407mm. The findings are compatible with serous retinal detachment and macular edema. (d) OCT of the left eye shows subretinal fluid centrally and nasally, as well as intraretinal fluid with a central macular thickness of 405 mm. The findings are compatible with serous retinal detachment (red arrow) and macular edema. OCT: Ocular coherence tomography

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Figure 3: After 4 months on therapy. (a and b) The clinical picture of the right (a) and left (b) eyes showing complete resolution of the optic disc swelling and macular edema. BCVA of 20/25 OU. BCVA: Best-corrected visual acuity, OU: Both eyes

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Discussion

The incidence of VKH ranges from <1% in Europeans to 22.4% in Asians. Several studies have reported that 54%–58% of VKH patients have a Hispanic origin.^[1] Mexican-mestizo patients with VKH have a strong association with the HLA-DR4 allele, mainly the DRB1*0101 gene, which confers a strong susceptibility for disease development.^[7]

Ocular manifestations of VKH include granulomatous panuveitis, serous RD, optic disc swelling, diffuse multifocal chorioretinitis, and chronic pigmentary disturbances like the peripapillary sunset glow fundus. Typical FA findings include choroidal perfusion delay, late optic disc staining and leakage, and early hyperfluorescent spots that later coalesce into large pooling areas.^[1]

After posterior uveitis, granulomatous panuveitis is the most common clinical presentation of ocular TB. The primary exogenous infection of the eye is exceedingly rare. Approximately 60% of the patients who have extrapulmonary TB do not have pulmonary disease.^[6] The latter, along with the myriad of clinical presentations, the lack of adequate diagnostic criteria, and poor access for choroidal tissue biopsy, renders TB an entity challenging to diagnose. In our patient, the diagnosis of ocular TB was based on the patient's high-risk related to the higher prevalence of TB in the country states he has lived in, the demographic and socioeconomic features, the ophthalmologic manifestations, and the positive IGRA and PPD test in the absence of BCG vaccination. In Mexico, the mean national rate of TB is 14.1 cases per 100,000 habitants. Oaxaca and Nuevo Leon, states where the patient has lived in, have a superior TB rate of 18.50 and 19.90.^[8]

Regarding diagnosis, the NICE guidelines suggest that the combination of PPD/IGRA can help diagnose extrapulmonary TB cases with no histopathologic proof. Unlike pulmonary TB, microbiology tests yield low sensitivity for ocular TB.^[9] Moreover, since ocular tissue availability is scanty, a positive PPD/IGRA supports the clinical diagnosis.^[9] Although there is limited evidence, some studies consider QFT-Plus a potential TB treatment monitoring tool. In our patient, there was a significant decrease in IGRA values after 18 months of ATT.^[10] Moreover, the NICE guidelines also suggest that testing for PPD or IGRA after the initial test is positive encourages compliance, which we thought was necessary given our patient's educational background.^[9]

Literature evidence of VKH and ocular TB coexistence is scant. Only two cases of ocular TB reactivation after the management of active VKH with steroids monotherapy,^[4] and in combination with azathioprine,^[3] have been reported. Dogan et al. reported a patient with bladder carcinoma who developed VKH after treatment with intravesical BCG.^[2] They also described a patient with prior TB history who, time after (not specified), developed VKH.^[2] Kalogeropoulos et al. described a patient with unilateral vision loss and pain who had the typical features of both ocular TB and VKH.^[6] After extensive workup, a diagnosis of pulmonary TB and tuberculous posterior sclerouveitis with features mimicking VKH was established.^[6]

Corticosteroids and IMT are the mainstay treatment for VKH disease. Nonetheless, this combined therapeutic strategy decreases the immune function, raising the risk of opportunistic infections. Almost one-third of the population worldwide have latent TB infection; of those, up to 10% will develop active TB.^[6] Poverty and immunosuppression are triggering factors.

This case is important because although VKH and TB may present a similar clinical picture, they require a different therapeutic approach. We decided to initiate aggressive steroid therapy based on the severe vision loss at presentation. However, when encountering a patient with intraocular inflammation in an endemic country, ocular TB must be assessed.

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 identity, but anonymity cannot be guaranteed.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

References

1.	Du L, Kijlstra A, Yang P. Vogt-Koyanagi-Harada disease: Novel insights into pathophysiology, diagnosis and treatment. Prog Retin Eye Res 2016;52:84-111.
2.	Dogan B, Erol MK, Cengiz A. Vogt-Koyanagi-Harada disease following BCG vaccination and tuberculosis. Springerplus 2016;5:603.
3.	Bajgai P, Sharma A, Singh R. Disseminated tubercular granulomas associated with the use of azathioprine. Ocul Immunol Inflamm 2021;29:906-10.
4.	Qian TW, Yu SQ, Xu X. A challenging case of tuberculosis-associated uveitis after corticosteroid treatment for Vogt-Koyanagi-Harada disease. Int J Ophthalmol 2018;11:1430-2.
5.	Mazurek GH, Jereb J, Vernon A, LoBue P, Goldberg S, Castro K, et al. Updated guidelines for using interferon gamma release assays to detect Mycobacterium tuberculosis infection-United States, 2010. MMWR Recomm Rep 2010;59:1-25.
6.	Kalogeropoulos D, Kitsos G, Konstantinidis A, Gartzonika C, Svarna E, Malamos K, et al. Tuberculous posterior sclero-uveitis with features of Vogt-Koyanagi-Harada uveitis: An unusual case. Am J Case Rep 2017;18:367-74.
7.	Alaez C, del Pilar Mora M, Arellanes L, Cano S, Perez-Luque E, Vazquez MN, et al. Strong association of HLA class II sequences in Mexicans with Vogt-Koyanagi-Harada's disease. Hum Immunol 1999;60:875-82.
8.	Cordova-Villalobos JA, Hernandez-Avila M, Ortiz-Dominguez ME, Martinez-Ampudia L, Sotelo-Gonzalez J, Fernandez-del Castillo BE, et al. Estándares para la atención de la tuberculosis en México. Report, Secretaria de Salud, Mexico; 2009.
9.	Llorenç V, González-Martin J, Keller J, Rey A, Pelegrín L, Mesquida M, et al. Indirect supportive evidence for diagnosis of tuberculosis-related uveitis: From the tuberculin skin test to the new interferon gamma release assays. Acta Ophthalmol 2013;91:e99-107.
10.	Kamada A, Amishima M. QuantiFERON-TB^® Gold Plus as a potential tuberculosis treatment monitoring tool. Eur Respir J 2017;49:1601976.