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 Table of Contents  
CASE REPORT
Year : 2021  |  Volume : 10  |  Issue : 1  |  Page : 82-84

Immune reconstitution inflammatory syndrome in Mycobacterium chimaera mediastinitis: When clinical judgment trumps imaging


1 Department of Internal Medicine, Lankenau Medical Center, Wynnewood, PA, USA
2 Division of Infectious Diseases, Lankenau Medical Center, Wynnewood, PA, USA
3 Division of Pulmonary and Critical Care, Lankenau Medical Center, Wynnewood, PA, USA

Date of Submission21-Dec-2020
Date of Acceptance13-Jan-2021
Date of Web Publication28-Feb-2021

Correspondence Address:
Ralph Tayyar
Stanford Health Care, 300 Pasteur Dr, Stanford, CA 94305
USA
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/ijmy.ijmy_242_20

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  Abstract 


Mycobacterium chimaera has been described in postoperative cardiovascular procedures in patients after an outbreak of contaminated 3T heater–cooler units. Immune reconstitution inflammatory syndrome (IRIS) has been mostly reported in immunocompromised patients, especially HIV after starting therapy. Our case is a 52-year-old immunocompetent male who was diagnosed with M. chimaera mediastinitis a year after Type A dissection repair and was started on quadruple antimicrobial therapy. He clinically improved but 8 months into therapy he presented with a declining kidney function, pancytopenia, and hypercalcemia which after bone marrow and kidney biopsies were attributed to IRIS. Our patient's diagnosis spared him subsequent surgery. IRIS during the treatment of nontuberculous mycobacteria must be suspected even in immunocompetent patients as reaching the diagnosis is very helpful in preventing additional diagnostic and therapeutic measures.

Keywords: Immune reconstitution inflammatory syndrome, mediastinitis, Mycobacterium chimaera, nontuberculous mycobacterium, postoperative cardiovascular infections


How to cite this article:
Haddad S, Tayyar R, Jr LL, Lande L, Santoro J. Immune reconstitution inflammatory syndrome in Mycobacterium chimaera mediastinitis: When clinical judgment trumps imaging. Int J Mycobacteriol 2021;10:82-4

How to cite this URL:
Haddad S, Tayyar R, Jr LL, Lande L, Santoro J. Immune reconstitution inflammatory syndrome in Mycobacterium chimaera mediastinitis: When clinical judgment trumps imaging. Int J Mycobacteriol [serial online] 2021 [cited 2021 Apr 20];10:82-4. Available from: https://www.ijmyco.org/text.asp?2021/10/1/82/310513

Sara Haddad and Ralph Tayyar contributed equally to the manuscript





  Introduction Top


Since 2013, there have been hundreds of localized and disseminated cases of Mycobacterium chimaera postoperative cardiovascular infections associated with contaminated 3T heater–cooler units used in cardiac surgeries.[1],[2]

Immune reconstitution inflammatory syndrome (IRIS) is an exaggerated immune response to a variety of pathogens following therapy and recovery of the immune system.[3] It has been particularly reported in patients with HIV in response to highly active antiretroviral therapy (HAART) or in patients with primary immunodeficiencies undergoing hematopoietic cell transplantation.[4] The resulting clinical manifestations can include lymphadenitis, relapse of symptoms of the prior infection in addition to noninfectious features[5] such as renal failure and hyperkalcemia.[6]

We present an initially unrecognized case of IRIS after the treatment for M. chimaera mediastinitis following cardiac surgery in an immunocompetent patient.


  Case Report Top


The patient is a 52-year-old male with a history of Type A aortic dissection repair 1 year before presentation with utilization of a 3T heater–cooler unit. Surgery was complicated by postoperative bleeding and re-exploration. He presented to our hospital for the first time with fatigue, weight loss, and drenching night sweats along with drainage from the sternal wound. He was found to have a collection around his aortic aneurysm repair site and underwent surgical debridement and washout. Intraoperative fluid cultures grew M. chimaera, and he was started on azithromycin, ethambutol, rifabutin, and amikacin with close follow-up with the infectious diseases and pulmonary services.

A repeat computed tomography scan during week 5 of antimicrobials did not show any new collections around the aorta. After 6 weeks of therapy, the patient was switched from amikacin to Clofamizine based on in vitro sensitivity studies as his renal function deteriorated with a creatinine level reaching 2.4 mg/dL (reference range 0.8–1.3 mg/dL). After switching the antimicrobial regimen, his kidney function improved and the creatinine gradually decreased to 1.1 mg/dL. His overall condition progressively improved with reported weight gain, increased energy, and appetite. At week 22, he reported experiencing visual difficulties. Retinal examination was consistent with ethambutol toxicity, and the drug was discontinued with subsequent restoration of vision.

Eight months into treatment, declining renal function, mild pancytopenia, and hypercalcemia developed are shown in [Table 1]. These changes raised concern for a possible relapse of the underlying M. chimaera infection. The patient instructed to follow a low calcium diet and an extensive workup was performed; parathyroid hormone was 2.7 pg/mL and Vitamin D was 31 ng/mL. Positron emission tomography (PET) scan demonstrated hypermetabolic activity associated with the prosthetic aortic valve, aortic root, ascending aorta, proximal aortic arch, and venous graft to the right coronary artery [Figure 1]. The observed degree of hypermetabolic activity was greater than would be expected 9 months postoperatively and supported a possible relapse of infection or an inflammatory/granulomatous process. The need for possible repeat surgery for graft excision was entertained. Paradoxically, despite the alarming laboratory and imaging findings, the patient continued to clinically improve and feel better.
Figure 1: Coronal positron emission tomography computed tomography showing hypermetabolic activity associated with the aorta and aortic valve and root

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Table 1: Laboratory workup

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Further studies were undertaken before committing to repeat surgery which included bone marrow and renal biopsies [Figure 2] revealing noncaseating nonnecrotizing granulomas with negative acid-fast bacilli smears and cultures. The diagnosis of IRIS in the setting of recovery from severe M. chimaera infection was confirmed. Surgery was deferred, and the patient was maintained on his antimicrobial regimen and continued to do well with spontaneous normalization of hyperkalcemia, pancytopenia, and renal function.
Figure 2: Kidney biopsy showing diffuse subacute interstitial nephritis with granulomatous noncaseating features

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  Discussion Top


IRIS has been reported in HIV patients with Mycobacterium avium complex infections[4] or with underlying tuberculosis.[7] These patients develop exacerbating symptoms and radiological manifestations of their underlying infection that are not due to relapse or recurrence. These reactions in HIV patients are likely secondary to the HAART-related reconstitution of immunity.[7] However, this case is notable in that IRIS was developed in a patient with M. chimaera with no known HIV background and was heralded by the onset of hypercalcemia in the face of generalized improvement suggesting the onset of granuloma formation. In fact, hypercalcemia is a well-known complication of the latter.[8]Studies looking at time of onset of Mycobacterium associated IRIS noted that the first signs of the syndrome occurred between 6 and 20 weeks after therapeutic interventions.[9] However, in our case, the timing of the development of IRIS was 8 months after surgical debridement and initiation of oral therapy. This made the diagnosis even more challenging as it was not reflective of the usual timeline reported in the literature and as our patient did not have typical symptoms. One might expect a variety of divergent and puzzling symptoms of IRIS in individuals like our patient. It is known that the organism becomes dispersed in every organ in the body with noted localizing symptoms such as renal failure, visual disturbances, and bone marrow failure occurring once the immune system is reconstituted.[10] PET scan findings in this case which likely represented the formation of new granulomas leading to hyperkalcemia and renal failure could have been misinterpreted leading to unnecessary surgical intervention.

IRIS should be considered in patients with nontuberculous mycobacteria infections when any constellation of the described symptoms occurs during antimicrobial therapy. Despite not fitting the typical picture for IRIS development, our patient had spontaneous improvement in both clinical well-being and laboratory parameters with no further need for surgical intervention or change in the therapeutic management. He continues to do well.

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.
Hasse B, Hannan MM, Keller PM, Maurer FP, Sommerstein R, Mertz D, et al. International society of cardiovascular infectious diseases guidelines for the diagnosis, treatment and prevention of disseminated mycobacterium chimaera infection following cardiac surgery with cardiopulmonary bypass. J Hosp Infect 2020;104:214-35.  Back to cited text no. 1
    
2.
Lecorche E, Pean de Ponfilly G, Mougari F, Benmansour H, Poisnel E, Janvier F, et al. Disseminated Mycobacterium chimaera following open-heart surgery, the heater-cooler unit worldwide outbreak: Case report and minireview. Front Med (Lausanne) 2020;7:243.  Back to cited text no. 2
    
3.
Gopal R, Rapaka RR, Kolls JK. Immune reconstitution inflammatory syndrome associated with pulmonary pathogens. Eur Respir Rev 2017;26:160042.  Back to cited text no. 3
    
4.
Manion M, Dimitrova D, Pei L, Gea-Banacloche J, Zelazny A, Lisco A, et al. Immune reconstitution inflammatory syndrome as a posttransplantation complication in primary immunodeficiency with disseminated Mycobacterium avium. Clin Infect Dis 2020;70:676-9.  Back to cited text no. 4
    
5.
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. 5
    
6.
Ferrand RA, Elgalib A, Newsholme W, Childerhouse A, Edwards SG, Miller RF. Hypercalcaemia complicating immune reconstitution in an HIV-infected patient with disseminated tuberculosis. Int J STD AIDS 2006;17:349-50.  Back to cited text no. 6
    
7.
Michailidis C, Pozniak AL, Mandalia S, Basnayake S, Nelson MR, Gazzard BG. Clinical characteristics of IRIS syndrome in patients with HIV and tuberculosis. Antivir Ther 2005;10:417-22.  Back to cited text no. 7
    
8.
Sharma OP. Hypercalcemia in granulomatous disorders: A clinical review. Curr Opin Pulm Med 2000;6:442-7.  Back to cited text no. 8
    
9.
Phillips P, Kwiatkowski MB, Copland M, Craib K, Montaner J. Mycobacterial lymphadenitis associated with the initiation of combination antiretroviral therapy. J Acquir Immune Defic Syndr Hum Retrovirol 1999;20:122-8.  Back to cited text no. 9
    
10.
Kasperbauer SH, Daley CL. Mycobacterium chimaera infections related to the heater-cooler unit outbreak: A guide to diagnosis and management. Clin Infect Dis 2019;68:1244-50.  Back to cited text no. 10
    


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