How to cite:
Rahayu, V., et. al. (2021) The Success Of Corticosteroid Therapy For Visual Outcome and Choroidal
Tubercle Regression on Paradoxical Reaction In Tuberculous Lymphadenitis. Syntax Idea, 3(9),
https://doi.org/10.36418/syntax-idea.v3i9.1473
E-ISSN:
2684-883X
Published by:
Ridwan Institute
Syntax Idea: p–ISSN: 2684-6853 e-ISSN: 2684-883X
Vol. 3, No. 9, September 2021
THE SUCCESS OF CORTICOSTEROID THERAPY FOR VISUAL OUTCOME
AND CHOROIDAL TUBERCLE REGRESSION ON PARADOXICAL
REACTION IN TUBERCULOUS LYMPHADENITIS
Vita Rahayu, St. Soraya Taufik, Junaedi Sirajuddin, Hasnah Eka
Department of Ophthalmology, Hasanuddin University, Makassar, Indonesia
Abstract
Paradoxical reaction is worsening effect of pre-existing lesion or development new
lesion. Commonly occured in extrapulmonary tuberculosis, about 20-30% in
tuberculous lymphadenitis, showed by development of posterior uveitis like
choroidal tubercle. A 32-year-old man presented with sudden loss vision and central
scotoma on his left eye 1 day before admission. The patient got anti therapy
tuberculosis by pulmonologist in one month previously for his tuberculous
lymphadenitis. Our examinations revealed tuberculosis infection with swollen disc
and choroidal tubercle that affected the worsening of visual acuity until 2/60 in the
left eye. Based on clinical picture and history of treatment before, we decided the
patient had paradoxical reaction. Topical and oral corticosteroid therapy with
continuation of anti-tuberculosis therapy referred significant improvement toward
visual outcome untill 20/20 and posterior pole condition on 4 months. Paradoxical
reaction in tuberculous lymphadenitis is not well understood, it may caused by
bacterial spreading or hypersensitivity responses. Corticosteroid therapy with
continuation of anti-tuberculosis therapy recommended to help improvement visual
acuity by reducing inflammation and hypersensitivity response in patient tuberculous
lymphadenitis with paradoxical reaction. This is proved by improvement visual
acuity and choroidal tubercle regression in our patient. Intraocular lesion can be
caused by paradoxical reaction in tuberculous lymphadenitis. Early diagnosed and
early corticosteroid therapy may help to sight saving.
Keywords: choroidal tubercle; paradoxical reaction; tuberculous lymphadenitis
Received: 2021-08-22; Accepted: 2021-09-05; Published: 2021-09-20
Introduction
Tuberculosis is a chronic, infectious disease, caused by Mycobacterium
tuberculosis, which is characterized by necrotic granulation tissue in response to these
germs. The disease is transmitted quickly to vulnerable people and the body's endurance
is weak. It is estimated that a tuberculosis sufferer to 1 in 10 people around him.
Tuberculosis is a disease that disrupts human resources and generally affects people
with low socioeconomic groups (Nizar, 2017).
The Success of Corticosteroid Therapy for Visual Outcome and Choroidal Tubercle Regression
on Paradoxical Reaction In Tuberculous Lymphadenitis
Syntax Idea, Vol. 3, No. 9, September 2021 2231
Tuberculosis is one of the biggest health problems worldwide. The disease is also
the highest cause of death and morbidity in developing countries, such as Indonesia
(Perawat & Pasien, 2018).
Currently infectious diseases, tuberculosis (TB) is still a concern of the world and
no country is free of TB. The death and pain rate from the germ 'Mycobacterium
tuberculosis' is still high. In 2009, 1.7 million people died from TB, and one-third of the
world's population had contracted TB, most of whom were of productive age, 15–55
years old. Global Report 2009 (WHO) showed in 2008 Indonesia was ranked the 5th
most TB sufferers in the world after India, China, South Africa and Nigeria or decreased
from third after India and China in 2007 (Izza & Roosihermatie, 2013).
Tuberculosis (TB) is an airborne infectious disease that leading cause of mortality
and morbidity worldwide, including in Indonesia (Ghauri et al., 2019). Caused by
Mycobacterium Tuberculosis (MTb) which treated by anti tuberculosis therapy (ATT)
for certain period. However, in some patients who receiving ATT can occur paradoxical
reaction. Paradoxical reaction means worsening in pre-existing clinical or radiological
tuberculous lesion or new lesion was developed in patient who showed an initial
response or improvement with treatment (Ganesh, Abraham, & Sudharshan, 2019).
Intraocular reaction on paradoxical reaction showed commonly as posterior
uveitis, like as choroidal tubercles, subretinal abscess or serpiginous-like choroiditis
(Goel, 2015), (Agarwal & Shrivastav, 2017). MTb is an obligate aerob acid
microorganism that affects high oxygen tension and high blood supply area like choroid
(uveal tract) in the eye (Goel, 2015), (Dalvin & Smith, 2017) . Different with intraocular
tuberculosis, visual complication in extraocular described rarely occur as a result of a
paradoxical reaction during ATT (Goel, 2015). This case report will describes a patient
with tuberculous lymphadenitis, showed development of choroidal tubercle in posterior
pole as part of a paradoxical reaction and have good visual outcomes after corticosteroid
therapy during anti-tuberculosis therapy.
Research Methods
This was an observational prospective study was conducted at Makassar, from
September 2019 to Mei 2020. The patient presented with complain of sudden loss of
vision and central scotoma on his left eye, then underwent detailed history, general
examination, anterior and posterior segment examination. The patient was administered
with corticosteroid oral (methylprednisolone) by ophthalmologist after diagnosed.
Clinical response, visual acuity and choroidal tubercle was assessed at 1, 2, 3 and 8
months followup. All data were collected and processed anonymously (Ata et al., 2020).
Results
A 32-year-old man presented with sudden loss vision and central scotoma on his
left eye 1 day before admission. On examination, his visual acuity (VA) was 20/20 in
the right eye and 2/60 in the left eye. Slitlamp examination for anterior segment
including intraocular pressure and pupils were within normal limits. Fundus
Vita Rahayu, St. Soraya Taufik, Junaedi Sirajuddin, Hasnah Eka
2232 Syntax Idea, Vol. 3, No. 9, September 2021
examination of right eye appeared normal, but in the left eye revealed a swollen disc
optic nerve and choroidal tubercle. (Figure 1).
Figure 1. Choroidal tubercle on first fundus examination
Figure 2. Optical coherence tomography scan showing subretinal fluid
Two month earlier, there was history of cough, dyspnea, recurrent middle-grade
fever, malaise, unexplained weight loss, and developed supraclavicular
lymphadenopathy which painless and tenderness, there was no history of other systemic
disease. Internist did physical examination to him, sputum examination, and chest X-
Ray, then he was diagnosed tuberculosis and referred to pulmonologist. Pulmonologist
did fine-needle aspiration biopsy to his gland, and diagnosed with tuberculous
lymphadenitis (Figure 3). He was started on standard four-regimen anti tuberculosis
therapy planned, consisting of rifampicin 600 mg once daily, isoniazid 450 mg once
daily, pyrazinamide 1.5 g once daily and ethambutol 800 mg once daily for one month
previously.
Figure 3. Swollen of supraclavicular gland
The Success of Corticosteroid Therapy for Visual Outcome and Choroidal Tubercle Regression
on Paradoxical Reaction In Tuberculous Lymphadenitis
Syntax Idea, Vol. 3, No. 9, September 2021 2233
Based on the clinical picture, evidence of confirmed active extra-pulmonary
tuberculosis, and history of tubercular treatment before, a diagnosis of left ocular
tuberculosis was made by ophthalmologist. The patient was diagnosed to have
paradoxical worsening following ATT based on complaints of visual worsening, no
ocular findings at the time of diagnosis but choroiditis tubercular developed on initial
ATT. Thus, the patient was administered with fluorometholon eye drops 5 times per
day, vitamin C 1 tablet per day and corticosteroid oral (methylprednisolone) starting
dose given was 1.0 mg/kg body weight then gradually tappered every week depending
on visual acuity improvement and decreasing of choroidal tubercle.
After 1 month treatment with corticosteroid, the BCVA on left eye was 20/150.
Fundus Examination of left eye result swollen disc of optic nerve and decreased of
choroidal tubercle size in perimacula.
2 months under corticosteroid treatment, BCVA on the left eye more increased to
20/30 and central scotoma was dissolve. Fundus examination showed minimal tubercle
on perimacula (Figure 4A). 1 month later, BCVA showed very satisfying result, the
patient got 20/20 for both eyes. However on his fundus examination leaved minimal
scarred on perimacula (Figure 4B).
A
B
Figure 4.
(A) Funduscopy control on 2 months after corticosteroid theraphy showed minimal
tubercle on perimacula. (B) Scarred on perimacula showed regression of lesion on 3
months after corticosteroid theraphy
Vita Rahayu, St. Soraya Taufik, Junaedi Sirajuddin, Hasnah Eka
2234 Syntax Idea, Vol. 3, No. 9, September 2021
This clinical picture was maintained for 8 months with no recurrences marked
from stability of visual acuity and no worsening in fundus examination with
continuation of ATT. Altough, the treatment by ophthalmologist have been finished,
anti theraphy tuberculosis by pulmonologist have to continued up to 9 months to
maximized anti-tuberculosis therapy.
Discussions
Tuberculosis is a multi-organs disease caused by the obligate aerobic acid fast
bacilli Mycobacterium tuberculosis (MTb). Mainly, TB affects the lungs, but it may
have various extrapulmonary infection including ocular. Hematogenous and lymphatic
spread of MTb bacilli is mainly theory why extrapulmonary tuberculosis occurred 6.
Lymphadenitis is the most commonly form of extrapulmonary tuberculosis which has a
peak age of onset of 20-40 years (Dalvin & Smith, 2017), (Agarwal & Shrivastav,
2017).
Culturing MTb from a specimen obtained from the patient help a doctor to get
diagnosis. In superficial tuberculous lymphadenitis, fine-needle aspiration (FNA) biopsy
of affected lymph nodes is the first-line diagnostic technique. However, if the FNA
examination results are inconclusive, excisional biopsy may be useful because it has the
highest sensitivity and both sensitivities (82.4%–100%) till specificities (94%–100%)
were increased when fine needle aspiration (FNA) and PCR were combined in the
diagnosis of tuberculous lymphadenitis (Ramirez-Lapausa, Menendez-Saldana, &
Noguerado-Asensio, 2015),(Lee, 2015). In our patient, diagnosed was made by
pulmonologist from FNA that got purulen inflammation on microscopic examination,
suggestive tuberculous, therefore pulmonogist diagnosed the patient was suffered
tuberculous lymphadenitis and not did biopsy anymore. Tuberculin skin test (TST) was
not performed in this case because it has low sensitivity and specificity. Interpretation of
TST reactivity can be show false positive by cross-reactivity with previous BCG vac-
cination or latent tuberculosis infection in those living in endemic areas including in
Indonesia (Agarwal & Shrivastav, 2017).
A six-month to nine-month regimen (two months of isoniazid, rifampicin,
pyrazinamide, and ethambutol, followed by four to seven months of isoniazid and
rifampicin) is recommended as initial therapy for all forms of extrapulmonary
tuberculosis (Ghauri et al., 2019), (Agarwal & Shrivastav, 2017), (Golden & Vikram,
2005).
Paradoxical reaction (PR) in which worsening of existing disease or new lesions
developed, occur more frequently in extrapulmonary tuberculosis (20–30% with
tuberculous lymphadenitis) than pulmonary tuberculosis (Ganesh et al., 2019), (Goel,
2015), (Agarwal & Shrivastav, 2017), (Singh, Rahman, Kumar, & Anila, 2013). This
phenomenon is not well understood but it has been attributed to host immunologic
reactions, with possible mechanisms including delayed hypersensitivity response,
decrease immunosuppression mechanisms, and a response to MTb antigens (Agarwal &
Shrivastav, 2017), (Singh et al., 2013), (Chahed et al., 2017).
The Success of Corticosteroid Therapy for Visual Outcome and Choroidal Tubercle Regression
on Paradoxical Reaction In Tuberculous Lymphadenitis
Syntax Idea, Vol. 3, No. 9, September 2021 2235
In this case, the patient came with sudden blurred vision up to 2/60 and central
scotoma in his left eye. This case represent a paradoxical reaction in a month with
tuberculous lymphadenitis, presenting with posterior uveitis, specifically choroidal
tubercle. Choroidal tubercle presenting as yellowish lesions, discrete with ill-defined
borders, may occur from liquefaction necrosis within a caseating granuloma that may
contain acid-fast bacilli and can develop in patients with disseminated tuberculosis
(Agarwal & Shrivastav, 2017), (Dalvin & Smith, 2017). Bacteria-laden macrophages
appeared when a caseous lesion erodes into the blood vessels or the lymphatic channels
then carrying the bacteria to the eye, where the organisms may persist and initiate an
immune-mediated response (Ganesh et al., 2019), (Sharma, Thapa, & Lavaju, 2011). If
it seen in a tuberculosis of endemic area should raise a strong suspicion of ocular
tuberculosis associated uveitis (Agarwal & Shrivastav, 2017).
Altough, intraocular disease in this case may caused by secondary hematogenous
or lymphatogenous spread, direct local extension and hypersensitivity responses from
existing infection in the body can also result in intraocular findings (Dalvin & Smith,
2017). Optic neuropathy may also develop due to a hypersensitivity response to antigen.
The manifestations of involvement of the optic nerve may be papillitis, optic neuritis, or
papilledema as like occurs in this patient (Agarwal & Shrivastav, 2017).
Steroids are recommended in other forms of extrapulmonary tuberculosis. This
patient got steroid treatment that expected help to limiting the damage of the ocular
tissues, resulting more rapid improvement to reducing inflammation and also preventing
a delayed hypersensitivity response to the tubercular antigen (Agarwal & Shrivastav,
2017), (Chahed et al., 2017). Methylprednisolone was given in a dose of 1.0 mg/kg
given for 1 week, then tappered off every week, according to the response to the
treatment. The result of adding corticosteroid for 4 months during continuation of anti-
tuberculosis therapy, got a maximal visual outcomes untill 20/20 and showed regression
of choroidal tubercle. Serial fundus photographs help documenting appearance of new
lesions as well as studying the regression of lesions. The healed lesions show scarred
areas with chances of good visual recovery (Sharma et al., 2011).
The diagnosis of a paradoxical reaction was made, based on the exclusion of other
diseases, adequate adherence to anti-tuberculosis therapy (intraocular disease
progressivity was noted on anti-tuberculosis therapy alone), and the dramatic response
to corticosteroids. On the other hand, if this is not a paradoxical reaction but treatment
failure, steroids would exaggerate the infection further (Goel, 2015), (Gogia, Venkatesh,
Garg, Takkar, & Sheemar, 2019). Early time institution of therapy can lead to
restoration of vision and may prevent irreversible vision loss (Alvarez, Roth, & Hodge,
2009).
Conclusion
Paradoxical reaction occur more frequently in extrapulmonary tuberculosis that
can affected to intraocular lesions. The mechanisms is not too unclear, but it is thought
Vita Rahayu, St. Soraya Taufik, Junaedi Sirajuddin, Hasnah Eka
2236 Syntax Idea, Vol. 3, No. 9, September 2021
to result from host immunologic reactions, with possible mechanisms including delayed
hypersensitivity response, decrease immunosuppression mechanisms, and a response to
mycobacterial antigens. Steroids are recommended to solve paradoxical reaction to help
limiting the damage of the tissues, resulting more rapid improvement to reducing
inflammation and also preventing a delayed hypersensitivity response to the tubercular
antigen. Timely treatment of therapy, anti-tuberculosis therapy and corticosteroid also
can lead sight saving for the patient.
The Success of Corticosteroid Therapy for Visual Outcome and Choroidal Tubercle Regression
on Paradoxical Reaction In Tuberculous Lymphadenitis
Syntax Idea, Vol. 3, No. 9, September 2021 2237
BIBLIOGRAFI
Agarwal, M., & Shrivastav, A. (2017). An update on tubercular uveitis. J Clin Exp
Ophthalmol, 8(676), 2.Google Scholar
Alvarez, Gonzalo G., Roth, Virginia R., & Hodge, William. (2009). Ocular tuberculosis:
diagnostic and treatment challenges. International Journal of Infectious Diseases,
13(4), 432–435. Google Scholar
Ata, Fateen, Bilal, Ammara Bint I., Javed, Saad, Chaudhry, Hammad Shabir, Sharma,
Rohit, Malik, Rubab Fatima, Choudry, Hassan, & Kartha, Anand Bhaskaran.
(2020). Optic neuropathy as a presenting feature of vitamin B–12 deficiency: A
systematic review of literature and a case report. Annals of Medicine and Surgery.
Google Scholar
Chahed, Houda, Hachicha, Hela, Berriche, Aida, Abdelmalek, Rim, Mediouni, Azza,
Kilani, Badreddine, Amor, Mohamed Ben, Benaissa, Hanene Tiouiri, & Besbes,
Ghazi. (2017). Paradoxical reaction associated with cervical lymph node
tuberculosis: predictive factors and therapeutic management. International Journal
of Infectious Diseases, 54, 4–7. Google Scholar
Dalvin, Lauren A., & Smith, Wendy M. (2017). Intraocular manifestations of
mycobacterium tuberculosis: a review of the literature. Journal of Clinical
Tuberculosis and Other Mycobacterial Diseases, 7, 13–21. Google Scholar
Ganesh, Sudha K., Abraham, Sharanya, & Sudharshan, Sridharan. (2019). Paradoxical
reactions in ocular tuberculosis. Journal of Ophthalmic Inflammation and
Infection, 9(1), 1–10. Google Scholar
Ghauri, Muhammad Ishaq, Iqbal, Nousheen, Riaz, Syeda Urooj, Irfan, Muhammad,
Kumar, Ajeet, & Mukarram, Muhamad Shariq. (2019). Visual and treatment
outcomes of tubercular uveitis: a prospective case series from a referral hospital in
Pakistan. BMC Research Notes, 12(1), 1–4. Google Scholar
Goel, Neha. (2015). Paradoxical response to anti‐tuberculous therapy presenting as
choroiditis. Clinical and Experimental Optometry, 98(2), 183–185. Google Scholar
Gogia, Varun, Venkatesh, Pradeep, Garg, Sat Pal, Takkar, Brijesh, & Sheemar,
Abhishek. (2019). Patterns of uveitis in patients with proven systemic (pulmonary
and extrapulmonary) tuberculosis. International Ophthalmology, 39(8), 1665–
1667. Google Scholar
Golden, Marjorie P., & Vikram, Holenarasipur R. (2005). Extrapulmonary tuberculosis:
an overview. American Family Physician, 72(9), 1761–1768. Google Scholar
Izza, Nailul, & Roosihermatie, Betty. (2013). Peningkatan Tuberkulosis di Puskesmas
Pacarkeling, Surabaya Tahun 2009–2011. Buletin Penelitian Sistem Kesehatan,
16(1), 21372. Google Scholar
Vita Rahayu, St. Soraya Taufik, Junaedi Sirajuddin, Hasnah Eka
2238 Syntax Idea, Vol. 3, No. 9, September 2021
Lee, Ji Yeon. (2015). Diagnosis and treatment of extrapulmonary tuberculosis.
Tuberculosis and Respiratory Diseases, 78(2), 47–55. Google Scholar
Nizar, Muhamad. (2017). Pemberantas dan Penanggulangan Tuberkulosis. Google
Scholar
Perawat, Diagnosa Keperawatan Yang Sering Ditegakkan, & Pasien, Pada. (2018).
Tuberkulosis Paru Di Rumah Sakit. Jurnal Kepemimpinan Dan Manajemen
Keperawatan, 1(2), 1–8. Google Scholar
Ramirez-Lapausa, M., Menendez-Saldana, A., & Noguerado-Asensio, A. (2015).
Extrapulmonary tuberculosis: an overview. Rev Esp Sanid Penit, 17(1), 3–11.
Google Scholar
Sharma, A., Thapa, B., & Lavaju, P. (2011). Ocular tuberculosis: an update. Nepalese
Journal of Ophthalmology, 3(1), 52–67. Google Scholar
Singh, Anil, Rahman, Habibur, Kumar, Viki, & Anila, Fnu. (2013). An unusual case of
paradoxical enlargement of lymph nodes during treatment of tuberculous
lymphadenitis in immunocompetent patient and literature review. The American
Journal of Case Reports, 14, 201. Google Scholar
Copyright holder:
Vita Rahayu, St. Soraya Taufik, Junaedi Sirajuddin, Hasnah Eka (2021)
First publication right:
Syntax Idea
This article is licensed under:
