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 Table of Contents  
CASE REPORT
Year : 2022  |  Volume : 11  |  Issue : 1  |  Page : 126-129

A successful salvage story: Uveitis with nontuberculous mycobacterial infection in a patient on secukinumab


1 Department of Pulmonary Medicine, Rajagiri Hospital, Kochi, India
2 Dr. Tony Fernandez Eye Hospital, Aluva, Kerala, India

Date of Submission11-Nov-2021
Date of Decision30-Nov-2021
Date of Acceptance24-Dec-2021
Date of Web Publication12-Mar-2022

Correspondence Address:
Rajesh Venkitakrishnan
Department of Pulmonary Medicine, Rajagiri Hospital, Kochi, Kerala
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/ijmy.ijmy_226_21

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  Abstract 


The reported occurrence of ocular infections with nontuberculous mycobacterial (NTM) infections has been increasing in the past few decades. NTM are known to cause intraocular infections as well as infections of the ocular appendages and are often recalcitrant to medical therapy. Uveal involvement due to NTM is rare and most reported cases have predisposing factors such as cataract surgery or immunocompromised states. Diagnosis and treatment pose challenge due to difficulty in procuring sufficient clinical material to obtain microbial diagnosis and inadequate response to medical therapy. The clinical challenge is further heightened in the presence of an underlying rheumatologic disease that is known to cause uveitis. We share the case of a young gentleman with ankylosing spondylitis who was being treated with secukinumab with good response to joint symptoms. He developed sudden onset uveitis which was diagnosed to be due to NTM infection based on aqueous humor polymerase chain reaction studies. He had a good clinical response to an empirical anti-mycobacterial regime with the restoration of vision. This report narrates the first case of NTM uveitis secondary to secukinumab therapy.

Keywords: Ankylosing spondylitis, nontuberculous mycobacterial infection, secukinumab, uveitis


How to cite this article:
Venkitakrishnan R, George LS, Shahi A, Mani SL, Augustine J, Ramachandran D, Vija A. A successful salvage story: Uveitis with nontuberculous mycobacterial infection in a patient on secukinumab. Int J Mycobacteriol 2022;11:126-9

How to cite this URL:
Venkitakrishnan R, George LS, Shahi A, Mani SL, Augustine J, Ramachandran D, Vija A. A successful salvage story: Uveitis with nontuberculous mycobacterial infection in a patient on secukinumab. Int J Mycobacteriol [serial online] 2022 [cited 2022 Jul 6];11:126-9. Available from: https://www.ijmyco.org/text.asp?2022/11/1/126/339506




  Introduction Top


Nontuberculous mycobacteria (NTM) are aerobic, Gram-positive bacilli that commonly inhabit human macro environment including soil, dust, trees, and water. The source of NTM infection to the mankind can be from a contaminated environment source or nosocomial.[1] NTM have been divided into four groups (viz., – photo chromogens, scoto chromogens, nonchromogens, and rapid growers) by Runyon in 1959 based on speed of growth, pigment production and need for light exposure.[2] The Runyon Group IV (Rapid growers) includes three subgroups and is gaining increasing importance as human pathogens; the M. fortuitum group, the M. chelonae/abscessus group, and the M. smegmatis group. NTM ocular infection was first reported in 1965 after the removal of a corneal foreign body and the culprit organism was M. fortuitum. Since then, NTM has been increasingly isolated from periocular, conjunctival, scleral, corneal, orbital and intraocular infections.[3],[4] Rapid growers especially M. chelonae, M. fortuitum and M. abscessus are the most common causes of ocular infections and are generally associated with poor response to medical therapy with resultant poor visual outcomes.

Most cases of NTM uveitis and endophthalmitis occur due to an exogenous source of infections, typically occurring during or after an ocular surgery. A review of 112 cases of NTM endophthalmitis[5] revealed an exogenous source in 101 cases (87.8%). Causes of endogenous infection in this series included the impact of HIV, diabetes mellitus, therapy with immunosuppressive agents (for autoimmune disease, organ transplantations, or cancers), etc., Only one case occurred in a healthy host.

Secukinumab is a humanized, monoclonal antibody to interleukin-17 A (IL-17A), and is US-Food and Drug Administration approved for the treatment of moderate to severe plaque psoriasis, active psoriatic arthritis, and ankylosing spondylitis. The efficacy and adverse effect profile of secukinumab has been extensively reviewed.[6] It has shown superiority in clinical trials to other biologic agents used for treating these conditions like etanercept and ustekinumab, with a favorable safety profile. A pooled safety analysis of 10 clinical studies was performed by van de Kerkhof and colleagues[7] who examined data on 2725 subject-years of exposure to secukinumab. Infection rate requiring antimicrobial treatment were comparable between various doses of secukinumab and etanercept but numerically higher than placebo. No incidents of disseminated herpes or reactivation of latent tuberculosis (TB) were noticed although numerically higher occurrence of nonserious candidiasis infections was reported for secukinumab than etanercept.


  Case Report Top


A 33-year-old man, a software employee by profession, presented with progressive deterioration of vision and redness in the left eye for 2 weeks. His past history was remarkable with a diagnosis of ankylosing spondylitis for the last 12 years. He had taken sulfasalazine for the past 10 years and had progressively inadequate response to this drug with worsening joint (sacroiliac joint and spine) manifestations. He was switched to biological agents and took 10 doses of secukinumab for the same. The last dose was taken 1½ months before the onset of ophthalmic symptoms. He had no other medical comorbid illnesses and denied usage of tobacco products, ethanol, or substance abuse. He did not have fever, cough, loss of appetite, or weight loss. He had no allergic manifestations. He had been diagnosed with anterior uveitis elsewhere and had undergone a series of preliminary investigations. His Mantoux Test was negative (maximum transverse diameter of induration of 3 mm) and serum angiotensin converting enzyme level was within normal limit. On examination, the best-corrected visual acuity (BCVA) was 6/36 in left eye and 6/6 in the right eye. Slit-lamp examination of the left eye revealed a clear cornea, with 1+ cells in anterior chamber and 4+ vitreous cells [Figure 1]a. The right eye showed a clear cornea with quiet anterior chamber and vitreous. Fundus examination revealed grade 4 vitritis with a hazy view of fundus. B scan also confirmed vitritis [Figure 1]b. Fundus examination of the right eye was unremarkable. A possibility of nongranulomatous uveitis secondary to ankylosing spondylitis was entertained, but in view of recent therapeutic immunosuppression, aqueous aspirate was done and sent for multiplex polymerase chain reaction (PCR) uveitis panel (targeting Mycobacterium TB, Toxoplasma gondii, fungal and herpes virus genomes). The reverse transcription–PCR for NTM was positive, whereas M. TB complex was negative. Ziehl–Neelsen staining and mycobacterial culture could not be carried out because of small quantity of the sample obtained through the paracentesis. Chest X-ray and high resolution computerized tomography of the chest [Figure 2] were within normal limits and showed no pulmonary parenchymal or mediastinal involvement with mycobacterial disease. Bronchoscopy with BAL was negative for bacterial and mycobacterial isolates. Serology for HIV infection was negative.
Figure 1: (a) Fundus examination of the left eye showing at presentation hazy fundus due to vitritis (b) scan of the eye at presentation showing

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Figure 2: Normal high-resolution computerized tomography thorax – representative image at presentation

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The exact etiological agent responsible for the NTM uveitis could not be settled in the absence of mycobacterial culture. The patient denied the suggestion for a repeat aspiration of aqueous for securing microbial etiology up to the species level and opted for an empirical medical treatment regimen. A multidisciplinary meeting was conveyed with the pulmonologist, infectious diseases specialist, ophthalmologist, and rheumatologist. Uncertainties regarding the therapeutic regimen and potential failure of treatment were conveyed to the patient. Based on a consensus of the multidisciplinary team, the patient was started on an anti-mycobacterial regimen including ethambutol, clarithromycin, and ciprofloxacin. Subsequently, he was also started on oral steroids under this anti mycobacterial cover. A gradual reduction in vitritis was seen within the next 1–2 months and symptomatic improvement was evident within 2 weeks. His BCVA improved to 6/6 following the treatment. He continued the antimicrobial treatment for 8 months and there was a remarkable recovery of vision. Almost complete clearance of vitritis was noticed on fundus examination at the end of treatment [Figure 3]. Subsequently, the patient was restarted on secukinumab for his rheumatologic disease. He is on follow-up for the last 10 months after stoppage of anti-mycobacterial therapy and has no recurrence of the uveitis till date.
Figure 3: Fundus examination at the end of treatment showing significant clearance of vitritis and almost normal fundus

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  Discussion Top


Although the disease caused by M. TB is still the major mycobacterial disease across the globe, the prevalence of nontuberculous mycobacteria (NTM) has been on the increase in both developed and developing countries. NTM infection is clinically indistinguishable from TB and poses significant challenges to drug therapy. The sputum smear microscopy, a widely used diagnostic test for diagnosing TB, fails to detect up to half of the TB cases and is unable to differentiate between mycobacterial species. The World Health Organization recommends the use of Xpert MTB/RIF (Xpert) assay; however, Xpert is less sensitive than sputum culture and does not detect NTM infections.[8] The identification and differentiation of NTM from MTB complex is crucial as treatment regimens for these diseases are different. The varying pattern of susceptibility toward anti-TB drugs imposes the need of different treatment strategies even among various NTM species. Thus, species-specific identification of NTM is crucial for proper treatment and appropriate patient management. NTM species are identified by phenotypic methods which are very cumbersome and time taking. The development of multiplex PCR-based assays[9] has allowed for rapid detection and speciation in NTM infections. Unfortunately, in our case, we employed a uveitis syndrome evaluation system focused multiplex PCR panel (igenetic diagnostics) which detected NTM but could not speciate the same. Since procuring a second sample of aqueous humor was challenging and the patient opted out of the same, we had to proceed with an empirical regimen with a macrolide, quinolone, and ethambutol. We were fortunate to have an excellent clinical response with this empirical regimen.

An extensive review of ocular NTM infections[3] identified 9 reported cases of uveitis caused by NTM in the literature. Choroiditis was seen in 6 cases, iridocyclitis in one and granulomatous panuveitis in two cases. Predisposing factors included an intervention of cataract with PPV in one case, treatment with steroids in 3 cases. Five patients were immunocompromised patients, all of whom had HIV/AIDS. Three patients had a disseminated NTM infection or localized infection elsewhere in the body. The diagnosis was secured by mycobacterial culture of ocular samples in 3 cases and PCR-based molecular techniques in three cases. NTM was not retrieved in 2 cases, and the diagnosis was made in the light of consistent ocular findings, presence of systemic NTM infections, and response to empirical therapy. Microbial analysis was carried out on vitreous samples in 5 cases and on a corneal biopsy in one patient having iris root abscess. Medical management was successful in 4 cases and surgical treatment resulting in loss of vision was required in three cases.

Extensive clinical and preclinical investigations with secukinumab have found no evidence of increased M. TB or NTM infections. A study[10] assessed the effect of secukinumab on the occurrence of acute TB and reactivation of latent TB infection in pooled safety data from five randomized, double-blind, placebo-controlled, phase 3 clinical trials in subjects with moderate-to-severe plaque psoriasis. No cases of TB were observed after 1 year. Importantly, in subjects with a history of pulmonary TB (but negative for interferon-γ release and receiving no anti-TB medication) or positive for latent TB (screened by interferon-γ release assay and receiving anti-TB medication), no cases of active TB were reported. Our case is the first one to report an association with secukinumab use and NTM uveitis. After completion of antimycobacterial chemotherapy, our patient has been re-initiated on the secukinumab for the last 10 months with no evidence of ocular or systemic relapse.


  Summary Top


We share the first case report narrating NTM uveitis in a patient with ankylosing spondylitis receiving secukinumab treatment. The case is noteworthy on multiple accounts. NTM uveitis is a rare entity with only a handful of cases reported this far, and the occurrence in the absence of profound immunosuppression or intraocular procedures is virtually unheard of. As previously mentioned, secukinumab usage has not been linked with an increased risk of mycobacterial disease till date. Since we had the diagnosis of NTM uveitis from a syndrome-based multiplex PCR panel, we could not further speciate the pathogen and had to institute an empirical regimen covering all relevant potential NTM species. We had a successful outcome (excellent restoration of vision to normalcy) with medical therapy, thus obviating the need for surgical interventions. Since our patient was dependent on secukinumab for control of his axial disease (ankylosing spondylitis), we were able to resume treatment with this drug after successful completion of anti-mycobacterial chemotherapy.

Ethical clearance

Ethical clearance was obtained from hospital ethical committee (RHEC – RAJH 2021).

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
  References Top

1.
Paulose RM, Joseph J, Narayanan R, Sharma S. Clinical and microbiological profile of non-tuberculous mycobacterial endophthalmitis-experience in a tertiary eye care centre in Southern India. J Ophthalmic Inflamm Infect 2016;6:27.  Back to cited text no. 1
    
2.
Runyon EH. Anonymous mycobacteria in pulmonary disease. Med Clin North Am 1959;43:273-90.  Back to cited text no. 2
    
3.
Kheir WJ, Sheheitli H, Abdul Fattah M, Hamam RN. Nontuberculous mycobacterial ocular infections: A systematic review of the literature. Biomed Res Int 2015;2015:164989.  Back to cited text no. 3
    
4.
Moorthy RS, Valluri S, Rao NA. Nontuberculous mycobacterial ocular and adnexal infections. Surv Ophthalmol 2012;57:202-35.  Back to cited text no. 4
    
5.
Pinitpuwadol W, Tesavibul N, Boonsopon S, Sakiyalak D, Sarunket S, Choopong P. Nontuberculous mycobacterial endophthalmitis: Case series and review of literature. BMC Infect Dis 2020;20:877.  Back to cited text no. 5
    
6.
Frieder J, Kivelevitch D, Menter A. Secukinumab: A review of the anti-IL-17A biologic for the treatment of psoriasis. Ther Adv Chronic Dis 2018;9:5-21.  Back to cited text no. 6
    
7.
van de Kerkhof PC, Griffiths CE, Reich K, Leonardi CL, Blauvelt A, Tsai TF, et al. Secukinumab long-term safety experience: A pooled analysis of 10 phase II and III clinical studies in patients with moderate to severe plaque psoriasis. J Am Acad Dermatol 2016;75:83-98.e4.  Back to cited text no. 7
    
8.
Steingart KR, Schiller I, Horne DJ, Pai M, Boehme CC, Dendukuri N. Xpert® MTB/RIF assay for pulmonary tuberculosis and rifampicin resistance in adults. Cochrane Database Syst Rev 2014;2014:CD009593.  Back to cited text no. 8
    
9.
Sarro YD, Butzler MA, Sanogo F, Kodio O, Tolofoudie M, Goumane MS, et al. Development and clinical evaluation of a new multiplex PCR assay for a simultaneous diagnosis of tuberculous and nontuberculous mycobacteria. EBioMedicine 2021;70:103527.  Back to cited text no. 9
    
10.
Kammüller M, Tsai TF, Griffiths CE, Kapoor N, Kolattukudy PE, Brees D, et al. Inhibition of IL-17A by secukinumab shows no evidence of increased Mycobacterium tuberculosis infections. Clin Transl Immunology 2017;6:e152.  Back to cited text no. 10
    


    Figures

  [Figure 1], [Figure 2], [Figure 3]



 

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