Cardiac Involvement in Eosinophilic Granulomatosis with Polyangiitis (Churg-Strauss Syndrome)

Ritu Agarwal MD^{1, 2} and Milind Srivastava MD²

¹Eternal Heart Care Center, Jaipur, India
²Santokba Durlabhji Memorial Hospital, Jaipur, India

Clinical History:

A 48 year old male with known history of bronchial asthma and hypertension presented to the emergency department with chest pain, progressive difficulty in breathing and weakness and pain in bilateral upper limbs. The possibility of acute coronary syndrome (ACS) was considered, with electrocardiogram (ECG) showing non-ST elevation myocardial infarction (NSTEMI). Echocardiography revealed global hypokinesis with LVEF 35%, with pericardial effusion. Laboratory analysis was significant for elevated troponin I 5.5 ng/mL (normal <0.05). Catheter coronary angiogram was done, which showed non-obstructive coronaries with aberrant origin of right coronary artery from the left sinus.

Chest X-ray showed bilateral pleural effusions. CT chest showed bilateral pleural effusion, pulmonary edema, and moderately enlarged mediastinal lymph nodes (Figure 1).

Figure 1. CT chest (left panel) with contrast showed bilateral pleural effusion, pulmonary edema, and moderately enlarged mediastinal lymph nodes. Anomalous origin of the right coronary artery from the left sinus of Valsalva is demonstrated (right panel, orange arrow).

Cardiac size was unremarkable (except for mild left atrial enlargement); however, few faint subendocardial hypodense areas were seen on post contrast images in LV (Figure 2). The significance of these lesions was not understood at the
time of reporting.

Figure 2. Heterogenous hypoattenuation of the myocardium noted on post-contrast CT images (orange arrows).

Laboratory analysis was significant for a white blood cell count of 19,200 WBC/uL (normal 4500–10,000) with 29% eosinophils (normal 0.4–7.5%), increased IgE 156 IU/ml (normal 1.5-144 IU/mL). The C-reactive protein (CRP) level was 62.8 mg/L (normal 0–10), erythrocyte sedimentation rate 38 mm/ hour and the rheumatoid factor was 20 IU/mL (normal 0–15). The patient’s cANCA/pANCA panel were negative.

Given the history of bronchial asthma, ACS- NSTEMI and neuropathy (proximal muscle weakness & pain), hypereosinophillia, increased IgE, increased CRP, increased ESR and positive rheumatoid factor, a diagnosis of Eosinophilic Granulomatosis with Polyangiitis (Churg-Strauss Syndrome) was made.

CMR was done to evaluate further and to rule out cardiac involvement.

CMR Findings:

CMR imaging (3T Signa Pioneer, multiplanar cine steady state free precession, T2 double inversion recovery imaging with and without fat saturation and multi-planar late gadolinium enhancement PSIR imaging) was carried out.CMR showed bi-atrial enlargement, dilated LV (LVEDV 185ml, normal range 115-180 ml), with moderate to severely reduced global systolic function (LEVF 26%, normal 55-75%). RV was dilated (RVEDV 166ml, normal 113-160 ml) with moderately reduced global systolic function ( RVEF 24%, normal 50-70%) (Movie 1).

On perfusion imaging small subendocardial hypointense areas were noted, in non-coronary artery distribution (which corresponded to subendocardial hypodensities on CT), also involving anterior and posterior papillary muscles (Movie 2).

Late gadolinium enhancement shows diffuse subendocardial delayed enhancement involving the LV and RV with small non enhancing left apical thrombus. Mild circumferential pericardial enhancement is also seen. (Figure 3).

Figure 3. First pass perfusion (left panel) demonstrating small regions of hypo-perfusion in non-coronary distribution that corresponded to hypoattenuation on CT and hypo-perfusion of the papillary muscles (orange arrow, left panel). Late gadolinium enhancement images in short axis (left) and 4 chamber (right) view demonstrate diffuse subendocardial enhancement (orange arrows) involving the LV and RV with small non enhancing left ventricular apical thrombus (red arrows). Mild circumferential pericardial enhancement is also seen (yellow arrows).

Additional findings of bilateral pleural effusions with sub segmental atelectasis, patchy areas of signal abnormality in bilateral lungs and small circumferential pericardial effusion were also noted.

Conclusion:

These findings of myocarditis with subendocardial scar in LV and RV, LV apical thrombus, mild pericarditis & lung involvement in a suspected Churg–Strauss vasculitis with cANCA/pANCA negative status; all suggested cardiac involvement in Churg–Strauss vasculitis.

Patient was started on immunosuppressive therapy with oral steroids, and showed significant improvement, and was discharged with steroid tapering. Endocardial biopsy was not performed.

Perspective:

Churg-Strauss vasculitis (also called Eosinophilic granulomatosis with polyangiitis) is characterized by necrotizing vasculitis of small and medium-sized systemic blood vessels described in 1951 by Drs. Jacob Churg and Lotte Strauss [1]. The 1990 American College of Rheumatology criteria for the classification of Churg-Strauss Syndrome requires at least four of the following six criteria: asthma, eosinophilia >10%, mononeuritis or polyneuritis, non-fixed pulmonary infiltrates, paranasal sinus abnormality and extravascular eosinophils. [2]

Estimated prevalence of the disease is 10.7 to 14 per million adults worldwide. The mean age of onset, is between 38 to 54 years, with a median of 40. There is no gender difference in incidence. [3]

Two phenotypes of the disease have been recognized – those with ANCA positive have a vasculitis phenotype and present with myalgia, migrating polyarthralgia, weight loss, mononeuritis multiplex, and renal involvement; however, those who are ANCA negative have an eosinophilic phenotype with a higher incidence of myocarditis.

Churg-Strauss vasculitis is a rare disease, but there is a possibility of misdiagnosis and missed diagnoses. However, cardiac involvement is present in more than 50% of patients with EGPA, which is the major cause of morbidity and mortality [4]. Cardiac involvement is caused by both mediators released from activated eosinophils as well as from coronary arteries vasculitis. Myocarditis (in acute phase), leads to post-inflammatory fibrosis and restrictive cardiomyopathy, followed by congestive cardiac failure. Cardiac involvement is associated with a poor prognosis, and therefore early diagnosis and institution of treatment is imperative.

Endocardial biopsy is the gold standard for myocarditis, however is invasive and not easily available. Additionally, due to the focal nature of involvement the sensitivity is low (approximately 50%). [5]

In a recent article by Pakbaz et al [6], they collected the clinical data of 62 patients suffering from EGPA with cardiac involvement from the literature. CMR was done for 29 (46.8%) patients, and it was abnormal in all; thus, it is probably the most sensitive method for detecting cardiac involvement in patients with EGPA. Furthermore, any part of the heart can be involved by EGPA; therefore CMR will provide a more comprehensive evaluation of the pericardium as the myocardium, will detect early myocardial inflammation, myocardial fibrosis as well ventricular thrombi. Additionally, CMR can demonstrate myocardial involvement when echocardiography is not diagnostic and biopsy is negative. [7]Therefore, CMR is the considered the gold standard noninvasive diagnostic test for early diagnosis and rapid institution of therapy. This case highlights the importance of CMR in early diagnosis of cardiomyopathy, and subclassify the exact etiology of non-ischemic pattern of cardiac involvement, albeit in appropriate clinical context.

Click here to view the Cardiac MRI Images for the case on CloudCMR

Click here to view the Cardiac CT Angiography images for the case on CloudCMR

References:

1. Allergic granulomatosis, allergic angiitis, and periarteritis nodosa. CHURG J, STRAUSS L. Am J Pathol. 1951 Mar-Apr; 27(2):277-301.
2. The American College of Rheumatology 1990 criteria for the classification of Churg-Strauss syndrome (allergic granulomatosis and angiitis). Masi AT, Hunder GG, Lie JT, Michel BA, Bloch DA, Arend WP, Calabrese LH, Edworthy SM, Fauci AS, Leavitt RY Arthritis Rheum. 1990 Aug; 33(8):1094-100.
3. Harrold LR, Andrade SE, Go AS, Buist AS, Eisner M, Vollmer WM, Chan KA, Frazier EA, Weller PF, Wechsler ME, Yood RA, Davis KJ, Platt R. Incidence of Churg-Strauss syndrome in asthma drug users: a population-based perspective. J Rheumatol. 2005 Jun;32(6):1076-80.
4. Nadeau PL, Kumar A, O’Connor K, et al. Usefulness of cardiac resonance imaging in Churg-Strauss syndrome. J Cardiovasc Med (Hagerstown) 2016;17(Suppl 2):e233–e234
5. A.P. Burke, J. Saenger, F. Mullick, R. Virmani Hypersensitivity myocarditis. Arch. Pathol. Lab Med., 115 (1991), pp. 764-769].
6. Pakbaz M, Pakbaz M. Cardiac Involvement in Eosinophilic Granulomatosis with Polyangiitis: A Meta-Analysis of 62 Case Reports. J Teh Univ Heart Ctr 2020;15(1):18-26.
7. Dahiya A, Chao C, Younger J, et al. Society for Cardiovascular Magnetic Resonance 2019 Case of the Week series. J Cardiovasc Magn Reson. 2021 Apr 1;23(1):44.

Case prepared by:
Eddie Hulten, MD, MPH, FACC, FACP, FSCMR, FSCCT, FASNC
Editorial Team Cases of SCMR
Lifespan Cardiovascular Institute, Rhode Island, the Miriam and Newport Hospitals
Warren Alpert Medical School, Brown University
Uniformed Services University, Bethesda, MD