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BRIEF COMMUNICATIONS
Year : 2017  |  Volume : 65  |  Issue : 8  |  Page : 761-764

Paradoxical worsening of a case of TB subretinal abscess with serpiginous-like choroiditis following the initiation of antitubercular therapy


Department of Uveitis, Medical Research Foundation, Sankara Nethralaya, Chennai, Tamilnadu, India

Date of Submission20-Mar-2017
Date of Acceptance23-May-2017
Date of Web Publication18-Aug-2017

Correspondence Address:
Sudha K Ganesh
Department of Uveitis, Medical Research Foundation, Sankara Nethralaya, No 18, College Road, Chennai - 600 006, Tamil Nadu
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/ijo.IJO_184_17

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  Abstract 


A 37-year-old immunocompetent male patient presented with the blurring of vision, both eyes for the past1 year. Fundus examination revealed bilateral multiple subretinal abscesses with areas of healed serpiginous-like choroiditis. Laboratory investigations showed positive tuberculin skin test, positive QuantiFERON TB-Gold Test, and high resolution computed tomography chest showed enlarged mediastinal lymph nodes. The aqueous sample revealed polymerase chain reaction (PCR) positive for Mycobacterium tuberculosis (MTB) (MPB64 genome). He was treated antitubercular therapy (ATT) along with oral steroids. Although he responded well initially, he had recurrent inflammation and paradoxical worsening. This was managed with a high dose of intravenous corticosteroids, immune suppressive and ATT. He also had a diagnostic vitreous biopsy which was also PCR positive for MTB (IS6110 gene). He subsequently continued ATT along with corticosteroids and immune suppressive and responded well. We present this case report for its unusual presentation.

Keywords: IS6110 gene, MPB64 genome, paradoxical worsening, subretinal abscess


How to cite this article:
Ganesh SK, Ali B S. Paradoxical worsening of a case of TB subretinal abscess with serpiginous-like choroiditis following the initiation of antitubercular therapy. Indian J Ophthalmol 2017;65:761-4

How to cite this URL:
Ganesh SK, Ali B S. Paradoxical worsening of a case of TB subretinal abscess with serpiginous-like choroiditis following the initiation of antitubercular therapy. Indian J Ophthalmol [serial online] 2017 [cited 2019 Nov 15];65:761-4. Available from: http://www.ijo.in/text.asp?2017/65/8/761/213226



Paradoxical reaction to anti-tubercular therapy has been observed in various forms of ocular tuberculosis (TB), including serpiginous-like choroiditis, intermediate uveitis, granulomatous anterior uveitis, retinal vasculitis, and panuveitis and has been documented frequently in extrapulmonary TB.[1],[2],[3] It is believed to be mediated by the host's immune system due to an enhanced delayed hypersensitivity of the host, decreased suppressor mechanisms, and as a response to mycobacterial antigens. We report, a case of bilateral paradoxical reaction in serpiginous-like choroiditis with multiple subretinal abscesses.


  Case Report Top


A 37-year-old male patient presented with the complaints of defective vision in both eyes associated with pain for the past 1 year. He was previously diagnosed and treated by his local ophthalmologist, as serpiginous choroiditis, with multiple courses of oral steroids. His previous investigations revealed a positive QuantiFERON TB-Gold Test, positive tuberculin skin test (10 mm × 10 mm induration with five tuberculin units), and high resolution computed tomography chest revealed subcarinal granulomatous lymph node enlargement with calcification. However, other investigations for syphilis, toxoplasmosis, HIV was negative.

On examination, we recorded a best-corrected visual acuity (BCVA) of 20/200 in the right eye and 20/40 in the left eye. Slit lamp examination of both eyes revealed a quiet anterior chamber. However, both eyes had plenty of vitreous cells in anterior vitreous. Fundus examination with indirect ophthalmoscopy, showed multiple subretinal abscesses with few areas of healed serpiginous-like choroiditis patches in both eyes [Figure 1]a. On B-scan ultrasonography, we noted a retinochoroidal elevation nasally with moderate surface and internal reflectivity in the right eye and inferiorly and temporally in left eye, respectively [Figure 1]b. Magnetic resonance imaging brain was found to be normal. The patient was referred to a chest physician, who initiated first-line antitibercular therapy (ATT) (isoniazid 300 mg rifampicin 450 mg, pyrazinamide 750 mg). Ethambutol was not added by the chest physician, probably due to its potential optic nerve toxicity. We started the patient on systemic steroids 1 mg/kg body weight/day which was tapered gradually. The patient was closely followed up every week. On the second visit at 3 weeks, his BCVA was 20/125 and 20/63 in the right and left eye, respectively. Fundus examination of both eyes showed resolution of the subretinal abscess noted earlier. However, we noted reactivation of serpiginous-like choroiditis lesions in the left eye [Figure 2]a and [Figure 2]b. Aqueous sample revealed polymerase chain reaction (PCR) positive for Mycobacterium tuberculosis (MTB) (MPB64 genome). Paradoxical reaction was suspected, ATT was continued, and the dose of oral steroid was stepped up. On the third visit at 4 weeks, his BCVA was 20/63 and 20/80 in the right and left eye, respectively. Fundus examination of both eyes revealed the progression of active lesions and appearance of new lesions in the left eye [Figure 2]c and [Figure 2]d. The patient was given 3 doses of 1 g intravenous methylprednisolone at this visit followed by of oral steroids 1 mg/kg body weight, and ATT was continued.
Figure 1: (a) At presentation, fundus photograph both eyes showing multiple subretinal abscesses with serpiginous-like choroiditis patches. (b) corresponding B scan ultrasonography showing retino choroidal elevations suggestive of multiple sub retinal abscesses in both eyes. Right eye measuring 10.1 mm × 9.1 mm × 5.1 mm, left eye measuring 10.6 mm × 5.8 mm × 4.1 mm, moderate internal reflectivity

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Figure 2: (a and b) Fundus photograph at 3 weeks, revealed resolving sub retinal abscess in both eyes, left eye had reactivation of serpiginous-like choroiditis, a paradoxical reaction, (c and d) fundus photograph at 4 weeks, showing formation of new lesions and progression of old lesions, (e and f) fundus photograph at 6 weeks, showing relentless progression of active lesions and appearance of new lesions, (g and h) fundus photograph at 10 weeks showing formation of the new active lesions in right eye involving fovea

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On the fourth visit at 6 weeks, his BCVA was 20/63 and 20/200 in the right and left eye, respectively. Fundus examination showed regressing lesions in the right eye and relentless progression of lesions in the left eye [Figure 2]e and [Figure 2]f. We added immunosuppressive azathioprine 50 mg thrice a day along with oral steroids and continued ATT. On the fifth visit at 10 weeks, his BCVA decreased to 20/200 and 20/400 in the right and left eye, respectively. Fundus examination showed few new active lesions in right eye threatening fovea, and left eye also showed active lesions [Figure 2]g and [Figure 2]h. Diagnostic vitrectomy was done and vitreous biopsy was also PCR positive for MTB (IS6110 gene); however, the culture did not show any growth. On the sixth visit at 12 weeks, his BCVA remained at 20/400 and 20/125 in the right and left eye, respectively [Table 1]. Fundus examination revealed regression of all abscesses and regression of serpiginous-like choroiditis in both eyes [Figure 3]a and [Figure 3]b. The patient presented at 4 months with his BCVA being 20/630 and 20/32 in the right and left eye, respectively, with fundus showing healed lesions in both eyes.
Figure 3: (a and b) Fundus photograph both eyes at 12 weeks showing resolution of the lesions with scarring over fovea in right eye

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Table 1: Best-corrected visual acuity both eyes corresponding to the fundus pictures in all six visits

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  Discussion Top


To summarize, we report a case of bilateral TB serpiginous-like choroiditis with multiple subretinal abscesses (PCR proven MTB) with paradoxical reaction on initiation of ATT that was managed with high doses of oral corticosteroids, intravenous methylprednisolone, and immunosuppressive agents. Hawkey et al. found that a higher bacillary load or a persistent antigenic stimulus that is poorly cleared from the diseased site may be responsible for the development of paradoxical worsening.[4] Our case presented as serpiginous-like choroiditis with multiple subretinal abscesses with a higher bacillary load that could have attributed to the paradoxical reaction. The other factor that could have contributed to the paradoxical reaction, was that our patient was on rifampicin, which is reported to reduce the bioavailability of corticosteroids.[5] Reports by Basu et al. and Gupta et al., on analysis of paradoxical reactions to ATT, describe paradoxical reactions in various forms, however, they have not reported any paradoxical reaction in cases of serpiginous-like choroiditis with associated subretinal abscess.[2],[6]

Our case of bilateral TB serpiginous-like choroiditis with multiple subretinal abscesses was PCR positive for MTB in the aqueous sample as well as the vitreous biopsy. However, we found two different genome sequences by PCR in aqueous (MPB64) and vitreous samples (IS6110), respectively, which is unique to this case. The probable reason for the positivity of IS6110 in vitreous and presence of MPB64 in aqueous aspirate could be due to variation in the initial load of MTB-DNA in vitreous and aqueous samples.[7]

When our patient had relentless, recurrent paradoxical reactivation of inflammation, we did not consider intravitreal methotrexate as suggested by Julian et al.[8] as our patient probably had a higher bacillary load in the eye, indicated by the presence of subretinal abscesses. We started oral steroids concomitantly with anti-tubercular therapy and not later as suggested by Siantar et al.[5] Intravenous methylprednisolone was given on the third visit and immunosupressives were used in the fourth visit, when the paradoxical reaction appeared to be relentless and recurrent. Gupta et al. in her case series had used Azathioprine as a second-line immunosuppressive in cases not controlled with corticosteroids.[6] Esen et al.[9] had reported paradoxical reaction in serpiginous-like choroiditis, who later developed macular edema and serous macular detachment. However, our patient developed a macular scar in the right eye that was responsible for poor visual recovery.

Our case is unique, as we report, the bilateral paradoxical reaction in PCR proven serpiginous-like choroiditis with multiple subretinal abscesses, that was successfully managed with ATT, oral and intravenous steroids and immunosuppressives.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
  References Top

1.
Gupta V, Gupta A, Arora S, Bambery P, Dogra MR, Agarwal A. Presumed tubercular serpiginouslike choroiditis: Clinical presentations and management. Ophthalmology 2003;110:1744-9.  Back to cited text no. 1
[PUBMED]    
2.
Basu S, Nayak S, Padhi TR, Das T. Progressive ocular inflammation following anti-tubercular therapy for presumed ocular tuberculosis in a high-endemic setting. Eye (Lond) 2013;27:657-62.  Back to cited text no. 2
[PUBMED]    
3.
Gupta M, Bajaj BK, Khwaja G. Paradoxical response in patients with CNS tuberculosis. J Assoc Physicians India 2003;51:257-60.  Back to cited text no. 3
[PUBMED]    
4.
Hawkey CR, Yap T, Pereira J, Moore DA, Davidson RN, Pasvol G, et al. Characterization and management of paradoxical upgrading reactions in HIV-uninfected patients with lymph node tuberculosis. Clin Infect Dis 2005;40:1368-71.  Back to cited text no. 4
[PUBMED]    
5.
Siantar RG, Ho SL, Agrawal R. Paradoxical worsening of tuberculous chorioretinitis in a Chinese gentleman. J Ophthalmic Inflamm Infect 2015;5:21.  Back to cited text no. 5
[PUBMED]    
6.
Gupta V, Bansal R, Gupta A. Continuous progression of tubercular serpiginous-like choroiditis after initiating antituberculosis treatment. Am J Ophthalmol 2011;152:857-63.e2.  Back to cited text no. 6
    
7.
Sharma K, Gupta V, Bansal R, Sharma A, Sharma M, Gupta A. Novel multi-targeted polymerase chain reaction for diagnosis of presumed tubercular uveitis. J Ophthalmic Inflamm Infect 2013;3:25.  Back to cited text no. 7
[PUBMED]    
8.
Julian K, Langner-Wegscheider BJ, Haas A, De Smet MD. Intravitreal methotrexate in the management of presumed tuberculous serpiginous-like choroiditis. Retina 2013;33:1943-8.  Back to cited text no. 8
[PUBMED]    
9.
Esen E, Sizmaz S, Kunt Z, Demircan N. Paradoxical worsening of tubercular serpiginous-like choroiditis after initiation of antitubercular therapy. Turk J Ophthalmol 2016;46:186-9.  Back to cited text no. 9
    


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