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Saudi Journal of Kidney Diseases and Transplantation
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Table of Contents   
CASE REPORT  
Year : 2018  |  Volume : 29  |  Issue : 3  |  Page : 719-722
Multiple tuberculomas invading the central nervous system as a paradoxical reaction in a kidney transplantation recipient


1 Department of Internal Medicine, Keimyung University School of Medicine, Daegu, Korea
2 Department of Pathology, Keimyung University School of Medicine, Daegu, Korea
3 Department of Internal Medicine, Keimyung University School of Medicine, Keimyung University Kidney Institution, Daegu, Korea

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Date of Submission12-Dec-2016
Date of Decision30-Mar-2017
Date of Acceptance31-Mar-2017
Date of Web Publication28-Jun-2018
 

   Abstract 

A paradoxical reaction during anti-tuberculosis (anti-TB) therapy is commonly reported in patients with human immunodeficiency virus (HIV). However, a similar reaction to anti-TB therapy can also occur in patients without HIV, especially in patients who have undergone solid organ transplantation. A 65-year-old woman who underwent kidney transplantation six months prior presented to our emergency room with progressive paraparesis. She had been diagnosed with drug-susceptible miliary TB and had undergone two weeks of treatment with anti-TB medication. Magnetic resonance imaging showed a spinal intramedullary mass and multiple intracranial nodules. The etiology of the lesions was confirmed as Mycobacterium tuberculosis. We report a paradoxical reaction of spinal intramedullary and multiple intracranial tuberculomas in a patient with miliary TB who had received appropriate treatment for more than two weeks.

How to cite this article:
Kim Y, Kim SP, Han S. Multiple tuberculomas invading the central nervous system as a paradoxical reaction in a kidney transplantation recipient. Saudi J Kidney Dis Transpl 2018;29:719-22

How to cite this URL:
Kim Y, Kim SP, Han S. Multiple tuberculomas invading the central nervous system as a paradoxical reaction in a kidney transplantation recipient. Saudi J Kidney Dis Transpl [serial online] 2018 [cited 2019 Dec 6];29:719-22. Available from: http://www.sjkdt.org/text.asp?2018/29/3/719/235190

   Introduction Top


Tuberculosis (TB) is a global health problem. It can be a cause of graft failure and death in patients who have undergone transplantation. Furthermore, the diagnosis may be obscured by unusual manifestations, such as paradoxical reactions that are characterized by the worse-ning of preexisting disease or development of new lesions during TB treatment.[1],[2],[3] Although several reports have described the central nervous system (CNS) TB as a paradoxical reaction,[3],[4],[5] it has been reported rarely in transplant recipient. Herein, we report a case of coexisting spinal intramedullary and intra-cranial tuberculomas that developed as a paradoxical reaction in kidney transplantation (KT) recipient.


   Case Report Top


A 65-year-old woman presented to our emergency room with paraparesis in both legs. She had a 10-year history of hypertension and was a chronic hepatitis B virus carrier. She had received dialysis for 76 months due to chronic glomerulonephritis and had undergone KT from a deceased donor (a 33-year-old woman diagnosed with hypoxic brain damage) approximately six months before the presentation. Before KT, the patient did not have a previous history of TB. Moreover, her preoperative examination including chest radiograph showed normal findings. She and the donor had the same blood type (Rh+ A), there was zero mismatch for human leukocyte antigen, and panel reactive antigens class I and II were 0% at the time of transplantation. Thymoglobulin (7.5 mg/kg) was used for induction because the donor was compatible with marginal kidney donor; nonheart beating donor. Tacrolimus, mycophenolate mofetil, and prednisolone were used as maintenance immunosuppressants.

Approximately six months after the KT, the patient presented with a two-week history of coughing. Chest radiography and computed tomography showed multifocal patchy consolidation in both lung fields [Figure 1]. The patient was diagnosed with miliary TB based on a positive acid-fast bacilli (AFB) culture from bronchial alveolar lavage specimens. Anti-TB medications were initiated with daily doses of isoniazid (300 mg), rifampin (600 mg), ethambutol (800 mg), and pyrazinamide (1500 mg); the cultured organism revealed sensitivity to all four drugs. Two weeks later, the patient returned with rapidly progressive paraparesis.
Figure 1: (a) Chest radiograph showing numerous small nodules in both lung fields with some coalescence. (b) Chest computed tomography scan revealing bronchial thickening and multiple nodules of varying sizes with a centrilobular distribution.

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The patient's mental status was clear, and physical examination revealed sensory loss below the level of T10 and marked motor weakness in both legs. In particular, there were trace flexion/extension movements from hip to toe (1/5, 1/5), and the anal tone was decreased. Magnetic resonance imaging (MRI) of the spine and brain showed an intramedullary enhancing mass at the T9-T10 level, extensive spinal cord edema from T5 to L1, and multiple ring-enhancing masses in the cerebral subcortical area [Figure 2]. To treat the progressive symptoms, surgical resection of the spinal mass was performed. Microscopic findings showed noncaseating granulomatous inflammation, and the acid-fast stain showed a few AFB in the granulomas [Figure 3].
Figure 2: (a) T1-weighted spinal magnetic resonance imaging scan showing a round, well-enhanced intramedullary mass lesion at T9–T10 level. (b) Brain magnetic resonance imaging showing a ring- enhancing mass lesion in the left cerebral hemisphere.

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Figure 3: Microscopic findings of intra-spinal mass showing noncaseating granulomatous inflammation (hematoxylin and eosin stain, original magnification ×200).

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After the diagnosis of paradoxical reactions of TB, mycophenolate mofetil was discontinued, and anti-TB medication was continued for one year without a change in regimen. One year after completing the treatment for disseminated TB, the patient showed no clinical evidence of TB recurrence. The chest radiograph was clear after treatment completion, and repeat MRI showed that the lesions decreased in size, with no new mass lesions in the spine or brain. The patient's kidney function was good before and after the TB treatment. The symptoms of paraparesis also improved: the motor grade of the lower extremities was 3/5 and the patient could walk with the use of walking aids.


   Discussion Top


Deterioration during anti-TB treatment referred to as a paradoxical reaction, has been recognized for many years; it generally occurs several weeks to months after initiating treatment.[1] Patients may present with unexpected clinical manifestations, which can lead to additional laboratory tests and often to unnecessary changes in appropriate drugs. The mechanism underlying paradoxical reactions has not been clearly identified; however, in human immunodeficiency virus (HlV)-infected patients on antiretroviral therapy, it is related to an exacerbation of the inflammatory response, referred to as immune reconstitution inflammatory syndrome.[6] In this case, although the patient was diagnosed with infection caused by Mycobacterium tuberculosis that was sensitive to all anti-TB drugs in in vitro studies, she experienced new onset paraparesis after taking anti-TB drugs for more than two weeks.

The basis of treatment for paradoxical TB reactions is the continuation of anti-TB medications. Although corticosteroids appear to be safe and helpful in patients with CNS involvement,[7],[8] their use in the treatment of paradoxical reactions has not yet been revealed. In the present case, we continued the initial anti-TB medication for 12 months, with concomitant use of prednisolone. Eventually, the TB infection resolved.

Even when patients with TB are immediately taken prompt treatment, infection involving the CNS is associated with significantly higher morbidity and mortality rates.[9] Moreover, transplant recipients, in particular, can be exposed to a number of infections, including TB. Thus, physicians should be vigilant for any unusual manifestations, such as paradoxical reactions.

Furthermore, assertive actions should be taken to prevent infections in patients after KT. Screening for latent TB is standard practice in patients undergoing solid organ transplantation because reactivation of TB commonly occurs after transplantation.[10] A previous study showed that 20%-25% of patients who develop TB after KT had positive tuberculin reactions before transplantation.[11] Patients who received prophylactic anti-TB medication were 65% less likely to develop TB than those who did not take prophylactic drugs.[12] The guideline for latent TB in Korea recommends prophylactic administration of isoniazid to patients who are taking immunosuppressants after transplantation.[13] However, physicians are often hesitant to prescribe prophylactic drugs for KT recipients due to potential interactions between immunosuppressants and anti-TB drugs, as well as the side effects of anti-TB drugs, such as liver dysfunction.

Herein, we report a rare case of coexisting spinal intramedullary and multiple CNS tuber-culomas presenting as a paradoxical reaction in a KT recipient. Although not all patients with positive TB screening results experience TB reactivation, the development of TB can be complicated and fatal for KT recipients. Therefore, physicians caring for such patients should perform a screening test before KT. Physicians also should consider the use of prophylactic isoniazid for patients with a positive screening test, even for patients without definite signs of a previous TB infection.

Conflict of interest: None declared.

 
   References Top

1.
Immune reactions in tuberculosis. Lancet 1984;2:204.  Back to cited text no. 1
    
2.
Smith H. Paradoxical responses during the chemotherapy of tuberculosis. J Infect 1987; 15:1-3.  Back to cited text no. 2
[PUBMED]    
3.
Cheng VC, Ho PL, Lee RA, et al. Clinical spectrum of paradoxical deterioration during antituberculosis therapy in non-HIV-infected patients. Eur J Clin Microbiol Infect Dis 2002; 21:803-9.  Back to cited text no. 3
[PUBMED]    
4.
Rao GP, Nadh BR, Hemaratnan A, Srinivas TV, Reddy PK. Paradoxical progression of tuberculous lesions during chemotherapy of central nervous system tuberculosis. Report of four cases. J Neurosurg 1995;83:359-62.  Back to cited text no. 4
    
5.
Thrush DC, Barwick DD. Three patients with intracranial tuberculomas with unusual features. J Neurol Neurosurg Psychiatry 1974;37: 566-9.  Back to cited text no. 5
    
6.
Shelburne SA 3rd, Hamill RJ, Rodriguez-Barradas MC, et al. Immune reconstitution inflammatory syndrome: Emergence of a unique syndrome during highly active antiretroviral therapy. Medicine (Baltimore) 2002;81:213-27.  Back to cited text no. 6
    
7.
Murdoch DM, Venter WD, Van Rie A, Feldman C. Immune reconstitution inflammatory syndrome (IRIS): Review of common infectious manifestations and treatment options. AIDS Res Ther 2007;4:9.  Back to cited text no. 7
[PUBMED]    
8.
Sun HY, Singh N. Immune reconstitution inflammatory syndrome in non-HIV immunocompromised patients. Curr Opin Infect Dis 2009;22:394-402.  Back to cited text no. 8
[PUBMED]    
9.
Li H, Liu W, You C. Central nervous system tuberculoma. J Clin Neurosci 2012;19:691-5.  Back to cited text no. 9
[PUBMED]    
10.
Muñoz P, Rodríguez C, Bouza E. Mycobacterium tuberculosis infection in recipients of solid organ transplants. Clin Infect Dis 2005; 40:581-7.  Back to cited text no. 10
    
11.
Klote MM, Agodoa LY, Abbott K. Mycobacterium tuberculosis infection incidence in hospitalized renal transplant patients in the United States, 1998-2000. Am J Transplant 2004;4:1523-8.  Back to cited text no. 11
[PUBMED]    
12.
Adamu B, Abdu A, Abba AA, Borodo MM, Tleyjeh IM. Antibiotic prophylaxis for preventing post solid organ transplant tuberculosis. Cochrane Database Syst Rev 2014;3:CD008597.  Back to cited text no. 12
    
13.
Shim TS. Diagnosis and treatment of latent tuberculosis infection. Korean J Med 2012 ;82: 284-90.  Back to cited text no. 13
    

Top
Correspondence Address:
Dr. Seungyeup Han
Department of Internal Medicine, Keimyung University School of Medicine, Keimyung University Kidney Institute, Jung-gu, Daegu 41931
Korea
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DOI: 10.4103/1319-2442.235190

PMID: 29970752

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