A rare case of eosinophilic granulomatosis with polyangiitis complicated with progressive pericardial effusion

Abstract

A 44-year-old woman had a 15-year history of asthma and had recently been treated for sinusitis and unidentified limb eruption. She had presented at a nearby clinic with inspiratory chest pain one week before hospitalization, and was diagnosed as having eosinophilic pneumonia based on peripheral blood eosinophilia and ground glass opacities in the right lung field, without pericardial effusion, as detected by chest computed tomography. She additionally presented with a feeling of chest tightness, and extensive pericardial effusion appeared within a week. She developed heart failure on admission, and we performed pericardiocentesis. We gave a clinical diagnosis of acute probable myopericarditis as the cause of pericardial effusion based on pleuritic chest pain, pericardial effusion, and elevation of cardiac enzymes, as well as eosinophilic granulomatosis with polyangiitis (EGPA) based on eosinophilia, her history of sinusitis, asthma, and migratory pulmonary opacities. We initiated oral prednisone 25 mg daily and pericardial effusion disappeared. In patients with EGPA, cardiac involvement is more serious than the involvement of other organs, and is associated with a poor prognosis. In this report we describe a rare case of EGPA complicated with progressive pericardial effusion and discuss the importance of the early diagnosis and treatment of EGPA.

<Learning objective: Eosinophilic granulomatosis with polyangiitis (EGPA), or Churg Strauss syndrome, is a multisystem disorder. It is important for patients with EGPA complicated with cardiac involvement to be diagnosed and treated early because cardiac involvement may lead to a fatal outcome.>

Introduction

Eosinophilic granulomatosis with polyangiitis (EGPA), or Churg Strauss syndrome, is a multisystem disorder that is characterized by allergic rhinitis, asthma, and prominent blood eosinophilia [1], [2], [3], [4], [5]. The prevalence of EGPA in Japan has been reported to be 17.8/1,000,000. The commonly involved organs are the peripheral nervous system and lungs, followed by the skin. However, EGPA can affect any organ system, including the cardiovascular, gastrointestinal, renal, and central nervous systems. In general, most patients with EGPA achieve remission with glucocorticoid therapy alone in the absence of factors associated with a poor prognosis, including cardiac, renal, and/or central nervous system involvement [6]. Cardiac involvement is more serious in patients with EGPA, and this case report highlights the importance of early diagnosis and treatment. We describe here a rare case of EGPA complicated with progressive pericardial effusion and discuss the importance of the early diagnosis and treatment of EGPA.

Case report

A 44-year-old woman presented at a nearby clinic with inspiratory chest pain one week before hospitalization. She had a 15-year history of bronchial asthma (with allergic rhinitis) which was well-controlled by inhaled corticosteroid. She was treated for sinusitis which was diagnosed based on fever, purulent nasal drainage, and facial pain 7 months before hospitalization, and was also treated with steroid ointment for unidentified limb eruption with itching, painfulness, and partial purulence 4 months previously. At the clinic, she had peripheral blood eosinophilia (eosinophil 1029/μL) and ground glass opacities (GGO) in the right upper lobe lung field, without pericardial effusion, by chest computed tomography (CT) (Fig. 1A and B). She was diagnosed as having eosinophilic pneumonia. She additionally complained of a feeling of chest tightness, and when she returned to the clinic, cardiomegaly and extensive pericardial effusion, as detected by chest radiography and echocardiogram, respectively, had developed. She was referred to our hospital for the treatment of extensive pericardial effusion. On admission, her level of consciousness was clear, blood pressure was 96/65 mmHg, pulse rate was 103 beats per minute, temperature was 37.8 °C, respiratory rate was 22 breaths per minute, and oxygen saturation (measured by pulse oximetry) was 94% while breathing room air. In the physical examination, distended jugular veins, distant heart sounds, and bilateral leg edema were present. Additionally, crusted eruptions which were treated with steroid ointment 4 months previously were seen on the dorsal side of the hands (Fig. 2A). The electrocardiogram showed flat T wave in the inferior (II, III, and aVf) and lateral walls (I, aVL, and V5-6) (Fig. 2B). Chest radiography showed cardiomegaly (cardiothoracic ratio 59%) and left pleural effusion (Fig. 3A). Transthoracic echocardiogram showed extensive pericardial effusion (front of the right ventricle: 17.8 mm, back of the left ventricle: 29.6 mm, at systole, respectively) which developed progressively within one week and dilatation of the inferior vena cava without asynergic motion, left ventricular hypertrophy, or valvular disease (Fig. 3B and C). With regard to biochemical parameters in blood, the creatine phosphokinase level, the creatine phosphokinase MB isoenzyme and renal, coagulative, and thyrogenic functions were all within the normal range, whereas the eosinophil count (2079/μL, 33% of the differential blood count), C-reactive protein (CRP) level (2.5 mg/dL), transaminase levels (aspartate aminotransferase 42 IU/L, alanine aminotransferase 75 IU/L), troponin-I level (101.1 pg/mL), and brain natriuretic peptide (143 pg/mL) were elevated. We considered that she was in a state of heart failure due to extensive pericardial effusion, and performed pericardiocentesis. The pericardial effusion was dark red and contained red blood cells. In the fluid examination, the cell count was 1575/μL (differential count: neutrophil 315/μL, lymphocyte 882/μL, eosinophil 157/μL), the protein level was 4.8 g/dL (fluid to protein ratio 0.68), the glucose level was 65 mg/dL (fluid to serum glucose ratio 0.73), and lactate dehydrogenase (LDH) was 1707 U/L (fluid to serum LDH ratio 7.58), which were classified as exudates. We initially suspected malignancy or tuberculosis because of the bloody pericardial effusion, but these possibilities could be excluded because the cytology and bacterial culture were both negative and the adenosine deaminase value (34.8 IU/L) in effusion was within the normal range. Aortic dissection was excluded by enhanced chest CT, and we gave a clinical diagnosis of acute myopericarditis as the cause of pericardial effusion based on findings including pleuritic chest pain, pericardial effusion, and elevated cardiac enzyme according to diagnostic criteria [7]. We placed a drainage tube into the pericardial cavity and drained approximately 500 mL on the first day; the tube was removed on the fifth day when the volume of drainage was less than 25 mL/day. Her heart failure improved after drainage, but pleuritic chest pain persisted. She had also been febrile (37–38 °C) after admission, but a septic condition was unlikely because the physical examination did not reveal a source of infection and two blood cultures were both negative. The GGO that had previously been observed in the right upper lobe lung field disappeared under repeated chest CT and a new GGO developed in the left upper lobe lung field, suggesting that pulmonary opacity was migratory　(Fig. 4A and B). Although antineutrophil cytoplasmic antibodies (ANCA) were negative and there was no accumulation of eosinophils in a skin biopsy of crusted eruption at right fifth finger because of local steroid therapy, we gave a diagnosis of EGPA based on findings including a history of asthma and sinusitis, peripheral blood eosinophilia, and migratory pulmonary opacities detected radiographically, which fulfilled the American College of Rheumatology criteria. The severity of vasculitis was 1 point (cardiac involvement) on the revised five-factors score (FFS), and we initiated oral prednisone 25 mg daily first after consultation with rheumatologists. After the initiation of prednisone, she became afebrile and pleuritic chest pain was relieved. Peripheral blood eosinophil and CRP levels became normal and pericardial effusion did not reaccumulate. She was discharged after 22 days of hospitalization. The dose of prednisone was tapered in the outpatient department. There has been no recurrence of pericardial effusion, and the abnormal findings by electrocardiogram have become normal (Fig. 5).

Fig. 1.

Ground glass opacities in the right upper lobe lung field (A) and without pericardial effusion (B).

Fig. 2.

Crusted eruption on the dorsal side of the hands (A) and electrocardiogram (B) on admission.

Fig. 3.

Chest radiography (A) and transthoracic echocardiogram (B and C) on admission. Ejection fraction was 67%, the thickness of interventricular septum and left ventricular posterior wall was 8.6 mm and 8.6 mm, respectively, and the dimension of left ventricular end-diastole and end-systole was 44.6 mm and 28.2 mm, respectively.

Fig. 4.

Migratory pulmonary opacities before admission (A) and on admission (B).

Fig. 5.

Electrocardiogram before discharge.

Discussion

Patients with EGPA, which is a form of systemic vasculitis that affects medium-sized arteries, generally achieve remission with glucocorticoid therapy alone. However, patients with poor prognostic factors, including cardiac involvement, often have a more serious course. The present case emphasizes two important considerations. First, it is difficult to differentiate EGPA from eosinophilic pneumonia, and an episode of eosinophilic pneumonia may precede other manifestations of EGPA, as in this case. These two diseases differ in that eosinophilic pneumonia usually lacks granulomas on biopsy and generally does not involve organs other than the lung [8], [9]. In this case, since extrapulmonary involvement appeared in addition to pulmonary involvement, we eventually gave a diagnosis of EGPA. Patients who present with eosinophilic pneumonia should be closely monitored for evidence of additional organ involvement that would secure a diagnosis of EGPA. Second, cardiac involvement is one of the more serious manifestations of EGPA, and accounts for approximately one-half of deaths attributable to EGPA [10], [11]. Neumann et al., who investigated the prevalence and clinical impact of cardiac involvement in EGPA patients in a multicenter, cross-sectional analysis, reported that cardiac involvement occurred in 22 (45%) of 49 patients, and 9 of these (41%) showed pericardial effusions [10]. The characteristics of patients with cardiac involvement include a negative ANCA test (0% vs. 25.9%, respectively, p < 0.05), much higher eosinophil counts (9947 vs. 3657/μL, respectively, p = 0.001), and a higher FFS (FFS 2 or more) (22.7% vs. 0%, respectively, p < 0.001) compared to patients without cardiac involvement. Although this patient did not have a particularly high eosinophil count and high FFS, she was ANCA-negative, which was consistent with the above finding. As for treatment, because it was reported that the high FFS was associated with high mortality rate [12], the addition of cyclophosphamide not only systemic glucocorticoids alone is considered in patients with FFS of 2 or FFS of 1 who particularly have cardiac or central nervous system involvement. In this case, who had FFS of 1 and cardiac involvement, we hesitated to treat with systemic glucocorticoids alone or the addition of cyclophosphamide to systemic glucocorticoids. After discussion with rheumatologists, we planned to initiate systemic glucocorticoids alone at first, and add cyclophosphamide if systemic glucocorticoids alone did not achieve remission or disease relapse under follow-up. A good course was achieved by systemic glucocorticoids alone currently, and the dose of glucocorticoids is tapered. Endomyocarditis detected by cardiac magnetic resonance imaging (MRI), cardiac thrombus formation, and endomyocardial biopsy has been reported to be associated with impaired cardiac function and a fatal outcome due to heart failure. In this case, we did not perform cardiac MRI or endomyocardial biopsy since left ventricular function was preserved. However, in cases complicated with left ventricular dysfunction, these tools may be useful for the detection of endomyocarditis, which would require further aggressive treatment. In conclusion, it is important for patients with EGPA complicated with cardiac involvement to be diagnosed and treated early because cardiac involvement may lead to a fatal outcome.

Conflict(s) of interest/disclosure(s)

K.S. is a Chief Director and S.M. is a Director of NPO Clinical and Applied Science, Fukuoka, Japan. K.S. has an Endowed “Department of Molecular Cardiovascular Therapeutics” supported by MSD, Co. LTD. S.M. belongs to the Department of Molecular Cardiovascular Therapeutics supported by MSD, Co. LTD.