Eosinophilic Myocarditis as a Paraneoplastic Phenomenon Dr Enrico Ammirati,a MD; Miriam Stucchi,a MD, Michela Brambatti,a MD, Francesca Spanò,a MD, Edgardo Bonacina,a MD, Fabio Recalcati,a MD, Giulio Cerea,b MD, Angelo Vanzulli,c MD, Maria Frigerio,a MD, and Dr Fabrizio Olivaa MD.
a “Angelo De Gasperis” Cardiothoracic and Vascular Department, Niguarda Ca' Granda Hospital, Milan, Italy b Falck Division of Medical Oncology, Niguarda Cancer Center, Niguarda Ca' Granda Hospital, Milan, Italy c Radiology Department, Niguarda Ca' Granda Hospital, Milan, Italy Word Count: 600 (text)
Correspondence to: Dr. Enrico Ammirati, MD, “Angelo De Gasperis” Cardiothoracic and Vascular Department; Azienda Ospedaliera Ospedale Niguarda Ca' Granda; Piazza Ospedale Maggiore 3, 20162 Milan, Italy. Phone: +39 02644 2569; Email:
[email protected]
In September 2014, a 55-year-old woman presented to our emergency department with a 2month history of worsening dyspnoea. She was a smoker with no other risk factors for pulmonary or cardiovascular disease. Her vital signs were blood pressure 90/60 mmHg, heart rate 130 per minute and oxygen saturation 92% on room air. She had jugular venous distension and diminished 1
breath sounds bilaterally but no pitting edema of lower extremities. Laboratory testing revealed an increase leukocyte count (18.9x10^9/L) with neutrophilia (79%) and normal eosinophils, with elevated C-reactive protein (36mg/L), and troponin T (354 ng/L). ECG showed sinus tachycardia with low voltage pattern. Chest radiograph revealed cardiomegaly and bilateral pleural effusions. Echocardiography showed a severe circumferential pericardial effusion, with signs of cardiac tamponade. Evacuative pericardiocentesis was immediately performed and 650 ml of serosanguineous pericardial fluid was drained. Post-pericardiocentesis, echocardiography revealed a left ventricle (LV) with normal dimension, and severe systolic dysfunction (LV ejection fraction– LVEF- 25%). Right ventricle (RV) was severely dilated and hypokinetic with normal pulmonary artery systolic pressure. CT scan confirmed large bilateral pleural effusions and showed a 40mm hypodense lesion surrounding the right main bronchus (Figure 1A). The patient progressively developed cardiogenic shock with acute respiratory failure. She underwent evacuative thoracentesis (1 litre of serous pleural fluid was drained) and coronary angiography, which ruled out artery stenosis. Intra-aortic balloon pump (IABP) was positioned, and vasopressor inotropes (dopamine 4 µg*kg-1*min-1 and adrenaline 0.1 µg*kg-1min-1), intravenous (iv) furosemide and tracheal mechanical ventilation were administered. RV endomyocardial biopsies were urgently performed and histology revealed an acute eosinophilic myocarditis (EM, Figure 1B). Treatment with iv methylprednisolone (1 g*daily) was initiated for three days followed by oral prednisone at 50 mg*daily. Cardiogenic shock quickly resolved. After 5 days IABP was removed and she was extubated one day later. LVEF improved up to 45% 12 days after the admission and normalized 2 weeks later. The analysis of pericardial fluid revealed the presence of adenocarcinoma-like cells, whereas no malignant cells were found in the pleural fluid. Further investigations confirmed the lung as the primary site of the malignancy and a final diagnosis of stage IV lung adenocarcinoma with a cerebral metastasis was made. She continued oral steroid (dexamethasone 4mg) as brain metastasis and myocarditis treatment and began chemotherapy with cisplatin and pemetrexed. In March 2015, LVEF was 59% and the pulmonary and brain lesions were reduced. 2
EM, a rare form of myocardial inflammation, is a life-threating condition with a variable presentation,1 characterised by eosinophilic infiltration and associated with systemic disorders like parasitic infection, hypersensitivity reaction to drugs, eosinophilic granulomatosis with polyangiitis, hypereosinophilic syndrome and malignancies.2 EM as a paraneoplastic phenomenon is extremely rare.2 The pathogenesis is unclear; one plausible explanation may be the bone marrow stimulation via interleukin-5 (IL-5) secreted by the tumour itself, associated with peripheral hypereosinophilia as the putative factor. IL-5 can be produced by eosinophils also at the site of myocardial tissue playing a role in both chemoattraction and degranulation, potentially explaining a local injury without peripheral hypereosinophilia.3 In our case, the EM did not have a standard clinical presentation. It could be suspected by cardiac symptoms, elevated cardiac enzymes and severe cardiac dysfunction in the setting of normal coronary angiography, but the echocardiography showed an uncommon enlarged RV and no peripheral
hypereosinophilia
was
observed.4
Definitive
diagnosis
was
established
by
endomyocardial biopsy and the early start of steroid therapy was crucial to restore cardiac contractility allowing subsequent chemotherapy. Finally, as our case shows, the clinical condition associated with EM influences the treatment and prognosis, warranting further investigation.
Contributors All authors managed the patient. EA, MS, MB, MF and FO wrote the report.
References 1.
Sagar S, Liu PP, Cooper LT, Jr. Myocarditis. Lancet 2012; 379(9817): 738-47.
2.
Baandrup U. Eosinophilic myocarditis. Herz 2012; 37(8): 849-52. 3
3.
Desreumaux P, Janin A, Dubucquoi S, et al. Synthesis of interleukin-5 by activated
eosinophils in patients with eosinophilic heart diseases. Blood 1993; 82(5): 1553-60. 4.
Fozing T, Zouri N, Tost A, et al. Management of a patient with eosinophilic myocarditis and
normal peripheral eosinophil count: case report and literature review. Circulation Heart failure 2014; 7(4): 692-4.
4
Figure Legend A) Axial CT scan during contrast agent injection (Iopamidolo 370; 90 ml) at the level of the right medium lobe bronchus. Bilateral pleural and pericardial effusion are present. Solid mass of about 4 cm is evident involving both the medial and lateral segmental bronchi (white arrow).
B) Endomyocardial biopsy specimen highlighting the eosinophilic infiltration into the myocardial interstitium characteristic of the eosinophilic myocarditis. Hematoxylin and Eosin staining, x200
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