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 Table of Contents  
CASE REPORTS
Year : 2021  |  Volume : 4  |  Issue : 1  |  Page : 138-141

Infliximab-related tubercular spinal epidural abscess without osseous involvement in a patient with Crohn’s disease: A case report


1 Institute of Advanced Spine Sciences, Chennai, Tamil Nadu, India
2 Department of Gastroenterology, Gleneagles Global Health City, Chennai, Tamil Nadu, India
3 Department of Infectious diseases, Gleneagles Global Health City, Chennai, Tamil Nadu, India

Date of Submission29-Jan-2020
Date of Decision10-Feb-2020
Date of Acceptance23-Mar-2020
Date of Web Publication01-Oct-2020

Correspondence Address:
Phani Kiran Surapuraju
Gleneagles Global Health City, #439, Cheran Nagar, Sholinganallur, Medavakkam Road, Perumbakkam, Chennai 600100, Tamil Nadu.
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/ISJ.ISJ_7_20

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  Abstract 

Tubercular spinal epidural abscess without osseous involvement is an extremely rare presentation of spinal tuberculosis. We report a case of perianal Crohn’s disease, who developed a tubercular epidural abscess in lumbosacral spine without osseous involvement, secondary to infliximab administration, despite being on 6 months of antituberculous therapy for perianal tuberculosis even as the primary focus healed well. This is probably the first case of infliximab-related tubercular spinal epidural abscess without osseous involvement. A combination of surgical treatment and antitubercular therapy gives a good outcome. This case highlights the rare and atypical nature of presentation of spinal tuberculosis in this scenario and emphasizes the importance of vigilant follow-up to prevent delayed diagnosis, due to atypical presentations following anti-tumor necrosis factor therapy.

Keywords: Crohn’s disease, epidural abscess, extrapulmonary tuberculosis, infliximab, paradoxical response, tuberculosis


How to cite this article:
Surapuraju PK, M. S, Swaminathan S. Infliximab-related tubercular spinal epidural abscess without osseous involvement in a patient with Crohn’s disease: A case report. Indian Spine J 2021;4:138-41

How to cite this URL:
Surapuraju PK, M. S, Swaminathan S. Infliximab-related tubercular spinal epidural abscess without osseous involvement in a patient with Crohn’s disease: A case report. Indian Spine J [serial online] 2021 [cited 2021 May 12];4:138-41. Available from: https://www.isjonline.com/text.asp?2021/4/1/138/308215




  Introduction Top


Primary tubercular spinal epidural abscess without osseous involvement is extremely rare, and there are only six such cases reported so far in the English literature. Infliximab is a chimeric monoclonal antibody that acts against tumor necrosis factor-alpha (TNF-α), and is used to treat inflammatory diseases, such as rheumatoid arthritis, ankylosing spondylosis, and inflammatory bowel diseases. It is a known fact that there is a risk of reactivation of latent tuberculosis in patients receiving infliximab, usually seen as extrapulmonary disease.[1],[2] This is most probably the first case report of infliximab-related tubercular epidural abscess without osseous involvement.


  Case History Top


A 58-year-old man presented with complaints of progressive weakness and numbness in both lower limbs, affecting his walking balance over a period of 4 months. He also had pain in both the thighs, associated with paresthesias in the left thigh. There was no history of bladder or bowel incontinence, fever, weight loss, or anorexia.

He had a past history of biopsy-proven diagnosis of Crohn’s disease and an active perianal fistula. As the disease remained active, despite prolonged course of antibiotics and 2.5 mg/kg/day of azathioprine, he had received infliximab (Remicade) infusion at 5 mg/kg (three doses: 0, 2, and 6 weeks) after appropriate counseling and screening for various latent infections, including tuberculosis (normal chest X-ray and negative QuantiFERON gold test on two occasions, 6 months apart). As the patient had a biopsy-proven Crohn’s disease and as the routine screening tests were negative for latent tuberculosis, a separate biopsy of the perianal fistula was not done before infliximab administration.

After good response initially for the first two doses, the third infusion of infliximab was followed in a week by high fever and perianal discharge. A subsequent biopsy from the perianal fistula showed granulomas, acid-fast bacilli, and a positive GeneXpert for Mycobacterium tuberculosis with no rifampicin resistance. He was treated with standard 6-month antitubercular therapy (ATT) (Isoniazid (H), Rifampicin (R), Pyrazinamide (Z), Ethamutol (E) 3 months + HR 3 months) with good healing of the perianal fistula and remission of fever.

It was after being on 6 months of ATT, while his perianal disease had healed that he started developing the lower limb pain and weakness. He did not have any other comorbidities or risk factors making him susceptible for a tubercular infection.

Examination revealed weakness in bilateral hip abduction, ankle dorsiflexion, and toe extension (Medical Research Council grade 3/5). The straight leg raising test was positive at 60° on both sides, and both ankle jerks were absent. Lumbosacral spine movements were normal and pain free and no spinal tenderness was reported. Hemoglobin was 11.2 gm%, total leukocyte count was 4700/mL, erythrocyte sedimentation rate (ESR) was 94 mm at 1h, and C-reactive protein (CRP) was 40.3 mg/L.

A magnetic resonance imaging (MRI) of the lumbosacral spine revealed an epidural abscess L4 to S2 in the ventral epidural space, causing severe cauda equina compression [Figure 1]A–C. A computed tomography (CT) scan of the spine did not reveal any osseous involvement [Figure 2]. MRI scan of pelvis and CT scan of abdomen with contrast were done to evaluate his perianal disease, and they did not show any evidence of direct communication of the epidural abscess to the perianal/pelvic region. As he had progressive neurological deficit and severe spinal canal compromise due to the abscess, a prior CT-guided biopsy was not considered, and an L4 to S2 left side hemilaminectomy and drainage of epidural abscess was performed. Caseous pus and granulation tissue was excised, decompressing the dural sac and roots adequately. The histopathology was confirmative of tubercular infection [Figure 3], and GeneXpert was positive for M. tuberculosis, not resistant to rifampicin. As he was already on two-drug ATT, the same (isoniazid and rifampin) was continued for an additional 9 months (total of 15 months of ATT). His lower limb pain and muscle power started improving within 4 weeks. His recovery was monitored with clinical evaluation of pain and neurological examination at 4 weeks, 8 weeks, 12 weeks, and at 12 months after surgery. His ESR was normal at 8 weeks after surgery. The pain was completely relieved, and lower limb muscle power was normal at 12 months after surgery. He was disease free at follow-up of 18 months after completion of ATT.
Figure 1: (A) Sagittal T2-weighted (T2W) magnetic resonance imaging (MRI) of lumbosacral spine. (B) Sagittal T1-weighted MRI of lumbosacral spine. (C) Axial T2W MRI image at L5-S1 level showing the epidural abscess

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Figure 2: Sagittal computed tomography scan image of lumbosacral spine

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Figure 3: Histopathology from epidural abscess - suggestive of tubercular infection

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  Discussion Top


Primary tubercular spinal epidural abscess without osseous involvement is extremely rare, and there are only six such cases reported so far in the English literature.[3],[4],[5],[6],[7] TNF-α is an important inflammatory mediator that regulates cell-mediated immunity against infections, such as tuberculosis. Reactivation of latent tuberculosis or an exogenous tubercular infection and other bacterial infections are a known risk of administering TNF-α antagonists.[1],[8],[9] Although, Smith et al.[8] have previously reported a case of infliximab-related staphylococcal spinal epidural abscess, this is the first case of tubercular epidural abscess without osseous involvement after infliximab therapy, to be reported, to the best of our knowledge.

Anti-TNF-α therapy hampers macrophage activity, crucial in control of tubercular infection.[1],[2] In a review of adverse effect reporting system of Food and Drug Administration (FDA), it was found that tuberculosis that develops after infliximab administration is most commonly extrapulmonary (56%) or disseminated (24%).[1] Our case emphasizes the fact that spinal tuberculosis after infliximab administration is often atypical. Our patient had a subacute onset and course of the disease and did not have the typical features suggestive of an active infection or an acute epidural abscess clinically.

This case highlights several interesting points. The tuberculosis was not triggered by maximum dose of azathioprine administered for about a year before infliximab therapy. Despite being screened thoroughly for latent tuberculosis before administration of infliximab, he developed florid tubercular infection in the perianal fistula after infliximab therapy. It is possible, in hindsight, that the perianal disease was tubercular in nature but not obvious due to its paucibacillary latent nature. The diagnosis became clear with TNF suppression resulting in rapid multiplication of the tubercular bacilli and subsequent definitive diagnosis from biopsy at the perianal fistula site. Despite completing 6 months of ATT and resolution of the primary pathology site, that is, perianal fistula, he developed the spinal epidural abscess. Such a paradoxical response (immune reconstitution syndrome) to ATT has been reported to happen after stopping anti-TNF-α agents in the literature.[10]

Paradoxical response represents worsening of preexisting tuberculous lesion or appearance of new site of tubercular infection not attributable to the normal course of the disease, after a period of initial positive response after starting ATT, in patients who have received anti-TNF-α agents. The paradoxical response typically occurs after a minimum latent period of 4 weeks after starting the ATT after stopping anti-TNF-α agents. It occurs due to a combination of immune reconstitution after stopping the anti-TNF-α agents and increased exposure to the tubercular antigens after the start of ATT. There is no need to discontinue or change the ATT when there is a paradoxical response. Additional use of corticosteroids and reintroduction of anti-TNF-α agents could be considered based on individual case.[11]

The spread of tuberculosis infection to epidural space could have been through hematogenous route or through the venous plexus between the pelvic organs and the epidural veins.

There are reports of tuberculosis occurring despite negative screening before therapy, usually within 12 weeks of infliximab therapy.[1],[12] Prophylactic ATT has been recommended in those with prior positive history and those considered at high risk of reactivation of tuberculosis.[1],[2]

A combination of surgical treatment and ATT has been shown to be very effective in treating patients with spinal epidural abscess with or without osseous involvement.[3],[4],[5],[6],[7]


  Conclusion Top


Spinal tuberculosis can occur with atypical features in patients on infliximab therapy and a high index of suspicion is essential to identify the infection early and possibility of a paradoxical response after ATT should also be kept in mind. Tubercular infection can occur despite negative screening before infliximab administration. The treating clinicians should be aware of occurrence of paradoxical response due to immune reconstitution in such clinical scenario. Possibility of occurrence of spinal epidural abscess with a subacute clinical picture, without osseous involvement, should be considered and an MRI should be done as soon as any neurological symptoms arise in this group of patients.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
  References Top

1.
Keane J, Gershon S, Wise RP, Mirabile-Levens E, Kasznica J, Schwieterman WD, et al. Tuberculosis associated with infliximab, a tumor necrosis factor alpha-neutralizing agent. N Engl J Med 2001;345:1098-104.  Back to cited text no. 1
    
2.
Solovic I, Sester M, Gomez-Reino JJ, Rieder HL, Ehlers S, Milburn HJ, et al. The risk of tuberculosis related to tumour necrosis factor antagonist therapies: A TBNET consensus statement. Eur Respir J 2010;36:1185-206.  Back to cited text no. 2
    
3.
Arora S, Kumar R Tubercular spinal epidural abscess involving the dorsal-lumbar-sacral region without osseous involvement. J Infect Dev Ctries 2011;5:544-9.  Back to cited text no. 3
    
4.
Zhang Q, Koga H Tubercular spinal epidural abscess of the lumbosacral region without osseous involvement: Comparison of spinal MRI and pathological findings of the resected tissue. Intern Med 2016;55:695-8.  Back to cited text no. 4
    
5.
Baallal H, El Mostarchid B Multisegmental tubercular spinal epidural abscess. Pan Afr Med J 2013;14:2.  Back to cited text no. 5
    
6.
Kumar A, Singh AK, Badole CM, Patond KR Tubercular epidural abscess in children: Report of two cases. Indian J Tuberc 2009;56:217-9.  Back to cited text no. 6
    
7.
Hasan GA, Kani SM, Alqatub A Tuberculous lumbar spinal epidural abscess in a young adult (case report). SICOT J 2018; 4:5.  Back to cited text no. 7
    
8.
Smith AP, Musacchio MJ, O’Toole JE Spinal epidural abscess associated with infliximab treatment for psoriatic arthritis. Case report. J Neurosurg Spine 2008;9:261-4.  Back to cited text no. 8
    
9.
Wallis RS, Broder MS, Wong JY, Hanson ME, Beenhouwer DO Granulomatous infectious diseases associated with tumor necrosis factor antagonists. Clin Infect Dis 2004;38:1261-5.  Back to cited text no. 9
    
10.
Watanabe S, Kaneko Y, Kawamoto H, Maehara T, Baba Y, Fujisaki I, et al. Paradoxical response with increased tumor necrosis factor-α levels to anti-tuberculosis treatment in a patient with disseminated tuberculosis. Respir Med Case Rep 2017;20: 201-4.  Back to cited text no. 10
    
11.
Vidal CG, Fernandez SR, Lacasa JM, Salavert M, Vidal R, Carballeira MR, et al. Paradoxical response to antituberculous therapy in infliximab-treated patients with disseminated tuberculosis. Clin Infect Dis 2005;40:756-9.  Back to cited text no. 11
    
12.
Parita S, Vivek K, Stephan K, William P, Yizhak K Infliximab therapy leading to pulmonary tuberculosis in a patient with negative interferon γ release assay (IGRA)-based quantiferon gold test. J Investig Med High Impact Case Rep 2017;5: 2324709617717540.  Back to cited text no. 12
    


    Figures

  [Figure 1], [Figure 2], [Figure 3]



 

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