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CASE BASED REVIEW
Ahead of print publication  

Successful treatment of cardiac tamponade with systemic lupus erythematosus using belimumab and hydroxychloroquine


 Okinawa Prefectural Nanbu Medical Center, Children's Medical Center, Arakawa, Okinawa, Japan

Date of Submission21-Apr-2022
Date of Acceptance20-May-2022
Date of Web Publication18-Aug-2022

Correspondence Address:
Tomoo Kise,
Okinawa Prefectural Nanbu Medical Center, Children's Medical Center, Arakawa, Okinawa
Japan
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/injr.injr_83_22

  Abstract 


Cardiac tamponade with systemic lupus erythematosus (SLE) is a rare but fatal complication. Although cardiac tamponade is typically managed with pericardiocentesis and medication, there is no definitive treatment for this condition. Herein, we report a case of cardiac tamponade with SLE in a 15-year-old girl. The patient had fever, chest pain, and fatigue for 1 month. She was diagnosed with SLE, and hence, prednisolone treatment was initiated. Her symptoms had alleviated on the 4th day of treatment; however, the following day, she was admitted to our hospital with fever and vomiting. The patient did not show chest pain or dyspnea. She developed hypotension, chest pain, and dyspnea the day after admission. She was diagnosed with cardiac tamponade using echocardiography. After pericardiocentesis, she was administered belimumab and hydroxychloroquine following intravenous methylprednisolone pulses and was maintained with complete remission for 2 years after the discontinuation of prednisolone and mycophenolate mofetil. This case highlights the potential for successful treatment of lupus cardiac tamponade with intravenous methylprednisolone pulses followed by administration of belimumab and hydroxychloroquine.

Keywords: Complete remission, intravenous methylprednisolone pulses, pericardiocentesis



How to cite this URL:
Kise T, Fukuyama S, Uehara M. Successful treatment of cardiac tamponade with systemic lupus erythematosus using belimumab and hydroxychloroquine. Indian J Rheumatol [Epub ahead of print] [cited 2022 Oct 3]. Available from: https://www.indianjrheumatol.com/preprintarticle.asp?id=353997




  Introduction Top


Systemic lupus erythematosus (SLE) is an autoimmune disease with various manifestations. Pericarditis is the most common cardiac manifestation of SLE, with an incidence of 9%–54%.[1] In contrast, cardiac tamponade is rare, with an incidence of <2.5% in patients with SLE,[1] and it is a potentially fatal complication if not treated promptly. Treatment of cardiac tamponade involves prompt pericardiocentesis and medication; however, there is no definitive medication for this complication. Herein, we report a patient with SLE and cardiac tamponade who received belimumab and hydroxychloroquine following intravenous methylprednisolone pulses; the patient has maintained complete remission for 2 years after the discontinuation of prednisolone and mycophenolate mofetil (MMF).


  Case Report Top


A 15-year-old girl presented to the emergency department of our hospital with fever and frequent vomiting that had started the previous night. She had the following three symptoms for 1 month: fever, chest pain, and fatigue. She was diagnosed with SLE based on a butterfly rash, mouth ulcer, antinuclear antibody positivity (1:1280; normal range, <1:40), and antidouble-strand DNA antibody positivity (58 IU/mL; normal range, <10 IU/mL) at our hospital 5 days before admission. At the time of diagnosis, the C-reactive protein (CRP) level (7.80; normal range, 0–0.14 mg/dL) and erythrocyte sedimentation rate (ESR; 72 mm/h; normal range, 3–15 mm/h) were elevated. Microhematuria and urine sediments, but no proteinuria, were observed. Chest computed tomography (CT) at the onset of chest pain confirmed no pleural effusion or pericardial fluid [Figure 1]. The patient's family had no history of collagen diseases.
Figure 1: Chest computed tomography confirmed no pleural effusion or pericardial fluid. RV: Right ventricle, LV: Left ventricle

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Prednisolone treatment (20 mg/day) was initiated on the day of diagnosis. Four days after the initiation of prednisolone treatment (i.e., the day before emergency department consultation), her symptoms (fever, chest pain, and fatigue) were alleviated completely. Electrocardiography yielded normal results.

At the time of admission, the patient weighed 45.4 kg (unchanged from the previous day), and her body mass index was 18.1. She had a regular heart rate of 135 beats/min without any murmurs, respiratory rate of 28 breaths/min, and oxygen saturation of 99% without O2 administration. Her blood pressure was 104/60 mmHg, and her body temperature was 38.7°C. Her breath sounds were clear, and her limbs showed no edema or chill. Laboratory data showed renal dysfunction, leukocytosis, increased hemoglobin and hematocrit levels, decreased serum C4 level, microhematuria, and proteinuria [Table 1].
Table 1: Laboratory data of the patient at diagnosis, at admission, before pericardiocentesis, at re-admission, and 2 years after discontinuation of prednisolone treatment

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The patient was diagnosed with dehydration due to fever and vomiting, and fluid replacement was initiated. She was infused with 1200 mL of extracellular fluid infusion over 12 h before the onset of cardiac tamponade. After 24 h, she weighed 47.6 kg and had a blood pressure of 86/40 mmHg, heart rate of 132 beats/min, and oxygen saturation of 97% at room air. Laboratory data showed improved renal function and hemoglobin and hematocrit levels but unimproved leukocytosis. Unlike that on the previous day, the CRP level was elevated [Table 1]. She complained of left shoulder pain, left chest pain, and dyspnea. Jugular venous distension was evident, and her heart sounds were diminished. Her pulse was weak; however, pulsus paradoxus had not yet been confirmed. Chest radiography revealed an enlarged cardiac silhouette (cardiothoracic ratio 68.5%) [Figure 2]. Transthoracic echocardiography confirmed pericardial effusion around the circumference [Figure 3]. Systolic collapse of right atrium or diastolic collapse of right ventricle was not observed. A diagnosis of cardiac tamponade was made.
Figure 2: Chest radiograph before pericardiocentesis displaying an enlarged cardiac silhouette (cardiothoracic ratio 68.5%)

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Figure 3: Transthoracic echocardiogram (apical four-chamber view) showing massive PE. PE: Pericardial effusion, LV: Left ventricle

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Echocardiography-guided pericardiocentesis and drain placement were performed, and 500 mL of pericardial fluid was drained. After drainage, her shoulder and chest pain disappeared, the blood pressure was 100/60 mmHg, and the heart rate was 86 beats/min. The next day, 25 mL of pericardial fluid was drained. The drain catheter was removed because there was no drainage for the next 2 days. The pericardial fluid was classified as exudative based on Light's criteria (pericardial fluid: serum protein ratio 2.1 ≥ 0.5; pericardial fluid: serum lactate dehydrogenase 3.6 ≥ 0.6; pericardial fluid: lactate dehydrogenase 1321 ≥ 200 IU/L).[2] Pericardial fluid cytology showed an inflammatory response in the cells with no evidence of malignancy. No microorganisms were detected in the pericardial fluid cultures.

The patient then received intravenous methylprednisolone pulses (1 g/dose) nine times, followed by oral prednisolone (30 mg). MMF was initiated at a dose of 500 mg/day, which was increased to 1 g/day from the 6th day after initiation.

Three days after reducing the prednisolone dose to 20 mg, the patient was readmitted with pain in both knees. There was no redness, swelling, or warmth in either knee. Laboratory data showed leukocytosis and a decreased serum C4 level [Table 1]. Magnetic resonance imaging revealed nonspecific bilateral knee arthritis, right biceps femoris myositis, and right patellar myositis. Echocardiography revealed no pericardial fluid. Acetaminophen, ibuprofen, and pentazocine treatments were ineffective, but increasing the prednisolone dose from 20 to 45 mg/day was effective. Consequently, arthritis and myositis were determined to be due to SLE. The patient and her family did not consent to the use of cyclophosphamide and azathioprine. Belimumab treatment was initiated to enable a prednisolone dose reduction without SLE recurrence. One month later, hydroxychloroquine was administered. Two months after increasing the MMF dose to 1 g/day, it was reduced to 500 mg owing to nausea. However, nausea continued even after lowering the MMF dose, and thus, MMF was discontinued 2 months after reducing the dosage. Seven months after initiating belimumab treatment, prednisolone treatment was discontinued. Two years after prednisolone discontinuation, SLE did not recur. After pericardiocentesis, renal function and urinary findings improved, and renal biopsy was not performed at the request of her family.


  Discussion Top


The clinical course of this patient suggests two important clinical findings. First, cardiac tamponade with SLE was successfully treated with intravenous methylprednisolone pulses in the acute phase and with belimumab and hydroxychloroquine without prednisolone or immunosuppressants in the maintenance phase. Second, early diagnosis of pericarditis was difficult.

Oral prednisolone is often used for cardiac tamponade treatment.[3],[4],[5],[6] However, Rosenbaum et al.[7] reported that six out of nine patients required a pericardial window even with high-dose prednisolone (at least 50 mg/day). Goswami et al.[1] recommended high-dose immunosuppression (intravenous methylprednisolone and pulse cyclophosphamide) to reduce surgical intervention. Moreover, intravenous methylprednisolone pulses have an immediate therapeutic effect and facilitate the reduction of dosage.[8] We administered intravenous methylprednisolone pulses (1 g/dose) nine times considering the complications of lupus nephritis because of renal dysfunction, proteinuria, and hematuria at admission. Pediatric lupus nephritis cases are more severe than adult cases; therefore, we routinely administer nine doses of 1 g methylprednisolone pulse for III or IV lupus nephritis.[9] We treated this case similarly. However, the 2019 EULAR recommendations for the management[10] of lupus nephritis state that total intravenous methylprednisolone dose should range from 500 to 2500 mg; therefore, we believe that the dose of intravenous methylprednisolone could have been reduced.

Belimumab is a human, immunoglobulin-G1 λ monoclonal antibody that inhibits the soluble B-lymphocyte stimulator cytokine,[11] and its use should be considered in the treatment of extrarenal diseases when it is difficult to taper the prednisolone dose.[8] There have been no reports on the use of belimumab for cardiac tamponade with SLE. However, in our case, disease recurrence was suppressed for 2 years after prednisolone discontinuation using only belimumab and hydroxychloroquine. High-dose immunosuppression with intravenous methylprednisolone pulses at the onset of cardiac tamponade and the use of belimumab and hydroxychloroquine following intravenous methylprednisolone pulses may substitute the use of prednisolone and immunosuppressants during the maintenance phase. The benefits of discontinuing prednisolone and immunosuppressants to reduce the adverse effects of the drugs are significant.

Early diagnosis of pericarditis is difficult. The diagnosis of acute pericarditis requires two or more of the following criteria to be met: chest pain, pericardial friction rub, electrocardiographic changes, and pericardial effusion.[12] Typical symptoms at the onset of cardiac tamponade are dyspnea, chest pain, orthopnea, pulsus paradoxus, and hypotension.[13] In our case, no abnormality was detected in the chest CT performed owing to chest pain 1 month before pericardiocentesis. The patient exhibited chest pain, dyspnea, and hypotension the day after being admitted with fever and vomiting. Pericarditis may have started 1 month before admission, and pericardial fluid gradually accumulated after the chest CT, resulting in cardiac tamponade the day after admission. In addition, 1 month before pericardiocentesis, prednisolone treatment led to a reduction in chest pain; consequently, the diagnosis of cardiac tamponade was delayed. In a previous study, the patient had no chest pain or respiratory symptoms at the time of cardiac tamponade diagnosis, and the chief complaints were abdominal pain, vomiting, and bloody stools. The patient had chest pain 10 days before admission.[14] Thus, if patients with SLE have a history of chest pain, a chest imaging examination should be performed even if the patient did not have chest pain at the time of treatment.

Rosenbaum et al.[7] reported decreased serum C4 level, female sex, concurrent renal disease, hemolytic anemia, and pleurisy, and Goswami et al.[1] reported pleuritis, antinucleosome antibody, and size of the pericardial effusion as the predictive factors of cardiac tamponade with SLE. Moreover, serositis is one of the few manifestations of SLE that elevates both the CRP level and ESR.[3] In our case, of all these factors, only female sex is applicable. Renal dysfunction was prerenal, hemolytic anemia was absent, pleurisy and pericardial effusion were not present in the chest CT images at the time of SLE diagnosis, and antinucleosome antibodies were not measured. ESR was not evaluated as a predictor of cardiac tamponade because it was not measured at admission or before pericardiocentesis. The serum C4 level decreased at admission and re-admission and was within the normal range at the time of SLE diagnosis. Changes in the serum C4 level were not consistent with cardiac tamponade expression. The CRP level was elevated at diagnosis and before pericardiocentesis but was within the normal range at admission (the day before pericardiocentesis). Thus, neither parameter was useful as a predictor of cardiac tamponade. Pereira et al.[15] suggested that patients with SLE onset before 16 years of age should be routinely screened for C4 gene copy number, and those with low total C4 or C4A gene copy numbers should be carefully monitored for pericarditis. Although we suggest implementing antinucleosome antibody and C4 gene copy number as predictors of cardiac tamponade with SLE, these predictors cannot be easily measured in general hospitals. Currently, no laboratory findings can predict cardiac tamponade, and echocardiography is essential in the case of chest pain, dyspnea, or hypotension in patients with SLE.


  Conclusion Top


The treatment of lupus cardiac tamponade with intravenous methylprednisolone pulses in combination with belimumab and hydroxychloroquine was successful. However, the study of additional cases and long-term follow-up are required to better understand the effectiveness of this treatment.

Ethical approval

All procedures were performed in accordance with the ethical standards of the Okinawa Prefectural Nanbu Medical Center, Children's Medical Center Ethics Committee, and adhered to the 1964 Declaration of Helsinki and its later amendments. The study protocol was approved by the Okinawa Prefectural Nanbu Medical Center, Children's Medical Center Ethics Committee (document submission number: 128; date of approval: February 28, 2022).

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form, the patient's parents have given consent for images and other clinical information to be reported in the journal. The patient's parents understand that the names and initials will not be published and due efforts will be made to conceal identity, but anonymity cannot be guarantee.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
  References Top

1.
Goswami RP, Sircar G, Ghosh A, Ghosh P. Cardiac tamponade in systemic lupus erythematosus. QJM 2018;111:83-7.  Back to cited text no. 1
    
2.
Light RW. Clinical practice. Pleural effusion. N Engl J Med 2002;346:1971-7.  Back to cited text no. 2
    
3.
Maharaj SS, Chang SM. Cardiac tamponade as the initial presentation of systemic lupus erythematosus: A case report and review of the literature. Pediatr Rheumatol Online J 2015;13:9.  Back to cited text no. 3
    
4.
Swinkels BM, Scheffer RC, Tahapary GJ, Jaarsma W, Plokker HW, Mast EG, et al. Cardiac tamponade as the initial manifestation of systemic lupus erythematosus in a young female patient. Neth Heart J 2007;15:71.  Back to cited text no. 4
    
5.
Shimizu T, Murata M, Tomizawa H, Mitsuhashi T, Katsuki T, Shimada K. Systemic lupus erythematosus initially manifesting as acute pericarditis complicating with cardiac tamponade: A case report. J Cardiol 2007;49:273-6.  Back to cited text no. 5
    
6.
Zhang X, Wu W. Cardiac tamponade as the initial symptom due to systemic lupus erythematosus in a young man: A case report. Medicine (Baltimore) 2018;97:e13708.  Back to cited text no. 6
    
7.
Rosenbaum E, Krebs E, Cohen M, Tiliakos A, Derk CT. The spectrum of clinical manifestations, outcome and treatment of pericardial tamponade in patients with systemic lupus erythematosus: A retrospective study and literature review. Lupus 2009;18:608-12.  Back to cited text no. 7
    
8.
Fanouriakis A, Kostopoulou M, Alunno A, Aringer M, Bajema I, Boletis JN, et al. 2019 update of the EULAR recommendations for the management of systemic lupus erythematosus. Ann Rheum Dis 2019;78:736-45.  Back to cited text no. 8
    
9.
Kise T, Yoshimura H, Fukuyama S, Uehara M. Evaluation of the long-term outcome of treatment with corticosteroids and mycophenolate mofetil in juvenile onset severe lupus nephritis – A single center experience. Ann Paediatr Rheum 2017;6:41-7.  Back to cited text no. 9
    
10.
Fanouriakis A, Kostopoulou M, Cheema K, Anders HJ, Aringer M, Bajema I, et al. 2019 Update of the Joint European League Against Rheumatism and European Renal Association-European Dialysis and Transplant Association (EULAR/ERA-EDTA) recommendations for the management of lupus nephritis. Ann Rheum Dis 2020;79:713-23.  Back to cited text no. 10
    
11.
Strand V, Levy RA, Cervera R, Petri MA, Birch H, Freimuth WW, et al. Improvements in health-related quality of life with belimumab, a B-lymphocyte stimulator-specific inhibitor, in patients with autoantibody-positive systemic lupus erythematosus from the randomised controlled BLISS trials. Ann Rheum Dis 2014;73:838-44.  Back to cited text no. 11
    
12.
Imazio M, Gaita F, LeWinter M. Evaluation and treatment of pericarditis: A systematic review. JAMA 2015;314:1498-506.  Back to cited text no. 12
    
13.
Jawaid A, Almas A. Cardiac tamponade as initial presentation in systemic lupus erythematosus. J Coll Physicians Surg Pak 2014;24 Suppl 2:S138-40.  Back to cited text no. 13
    
14.
Larson NP, Frawley TC, Long B. Cardiac tamponade in an 18-year-old male with undiagnosed systemic lupus erythematosus. Cureus 2019;11:e5186.  Back to cited text no. 14
    
15.
Pereira KM, Faria AG, Liphaus BL, Jesus AA, Silva CA, Carneiro-Sampaio M, et al. Low C4, C4A and C4B gene copy numbers are stronger risk factors for juvenile-onset than for adult-onset systemic lupus erythematosus. Rheumatology (Oxford) 2016;55:869-73.  Back to cited text no. 15
    


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