Erdheim–Chester disease: The role of video-assisted thoracoscopic surgery in diagnosing and treating cardiac involvement

Abstract

INTRODUCTION

Erdheim–Chester disease is a rare, non-Langerhans histiocytosis in which pericardial involvement is diagnosed with increasing frequency and is associated with high mortality rates.

PRESENTATION OF CASE

A 53-year-old woman presented with progressive exertional dyspnea and pericardial effusion was discovered. Further investigations revealed the presence of a diffuse, infiltrating process and a diagnosis of Erdheim–Chester disease was made. An emergent pericardiocentesis by subxiphoid approach was completed but recurrent drainage obviated removal of the pigtail catheter. A pleuro-pericardial window was placed using video-assisted thoracoscopic surgery (VATS) and analysis of the resected specimen confirmed pericardial involvement.

DISCUSSION

In this case, high pericardial fluid output demanded definitive treatment of the pericardial effusion. Traditionally this would be completed via thoracotomy. VATS is a minimally invasive alternative which permits exploration of the thoracic cavity and the creation of a pleuropericardial window.

CONCLUSION

We describe, for the first time, the successful use of VATS for both diagnostic confirmation and therapeutic relief of recurrent pericardial fluid drainage due to pericardial involvement by Erdheim–Chester disease.

1. Background

Erdheim–Chester disease (ECD) is a rare, non-Langerhans histiocytosis with multisystem involvement. These foamy histiocytes are characterized by CD68 positivity and CD1a negativity on immunohistochemical staining. As CD68 is a histiocyte marker and CD1a is a marker for Langerhans cells, this finding distinguishes ECD from Langerhans cell histiocytosis.¹ The most common presentation is that of bone pain due to xanthomatous tissue infiltration,² however protean manifestations including disease of the hypothalamic–pituitary axis, eyes, heart, lungs, retroperitoneum, and skin and heart has been described.^3–5

Cardiovascular manifestations are frequently present (75% of patients) but underdiagnosed clinically. Nonetheless, cardiac involvement portends a poor prognosis and ultimately causes death in 31% of all cases.²

Interferon-alpha is considered first line therapy and shows a variable response depending on organs involved.^6,7 However, treatment is not standardized and varies according to clinician preference.

More recently, pericardial involvement has been diagnosed with increasing frequency and ranges from pericardial effusion more commonly to pericardial constriction (24–44%).^2,3 Video-assisted thoracoscopic surgery (VATS) has potential for diagnosing cardiac involvement and managing recurrent pericardial effusion in ECD. VATS is a novel but attractive option because of its feasibility and low morbidity in a variety of cardiac and thoracic condititions.^8–12 The VATS procedure has real utility both as a diagnostic and therapeutic procedure in the management of pericardial disease. We report a case of ECD that highlights the role of VATS in obtaining a biopsy to prove cardiac involvement and subsequently creating a pericardial window to treat recurrent pericardial effusion.

2. Case report

A 53-year-old woman presented with progressive dyspnea on exertion and lower extremity edema over a period of 1 year. Physical exam revealed heart rate 100/min, blood pressure 100/70 mmHg with a pulsus paradoxus, elevated neck veins and a positive Kussmauls sign. Cardiac sounds were distant and significant lower extremity edema was noted.

Initial laboratory results included an erythrocyte sedimentation rate of 5 mm/h and a C-reactive protein concentration of 18.2 mg/L (normal range <8 mg/L) and a normal complete blood count and metabolic panel. Chest X-ray showed an enlarged cardiac silhouette and subsequent echocardiogram revealed a circumferential pericardial effusion with evidence of tamponade. ECG showed low voltage in the limb leads with evidence of electrical alternans. An emergent pericardiocentesis by subxiphoid approach yielded 1700 mL of serous fluid. A pigtail catheter was left in place to assist with further drainage. Cultures of the pericardial fluid were negative for bacteria, fungus and acid fast bacilli, while cytology revealed no malignant cells.

Computerized axial tomography (Siemens Somatom Sensation 64, Malvern, Pennsylvania) of the thorax, abdomen and pelvis showed an infiltrative process primarily encasing the kidneys and retroperitoneal structures (Fig. 1). A CT guided needle biopsy of the abnormal tissue in the left periaortic retroperitoneum revealed fibrosis with chronic inflammation including foamy macrophages, which were CD68+ and reactive with antibodies to S100 protein (Fig. 2). A subsequent skeletal survey was normal. A technetium whole body scan revealed tracer uptake at the mandible diffusely, mid and distal sternum, proximal humeri, distal femurs and distal tibia bilaterally. MRI head demonstrated bilateral intraconal masses, approximately 1.5 cm in diameter, centered between the optic nerve and lateral rectus muscle.

Fig. 1.

CT reveals an extensive infiltrating process primarily affecting the kidneys and retroperitoneal area (region of white arrows).

Fig. 2.

Pericardium. It is greatly thickened by dense eosinophilic connective tissue and inflammation (a). The cellular infiltrate is comprised of macrophages, some of which have eosinophilic and others of which have foamy cytoplasm (b).

Persistent drainage of pericardial fluid (>100 mL daily) obviated removal of the catheter. To facilitate drainage a pericardial window was placed. Under general anesthesia, the patient was placed in the left lateral decubitus position and three ports were inserted between the fourth and sixth intercostal spaces in the right hemithorax (Fig. 3). Following dissection of adhesions between lung, chest wall and pericardium, a large segment of pericardium measuring 5.5 cm × 3.7 cm × 0.2 cm was removed freeing completely the right atrium and a portion of the upper right ventricle. This resection formed the pericardial window. Pathology confirmed a mild chronic fibrosing pericarditis associated with an infiltrate of foamy and eosinophilic histiocytes. These histiocytes were CD68+, and had negative antibody reactivity to S100 protein and CD1a. A diagnosis of ECD with cardiac involvement was established.

Fig. 3.

Positioning of ports intraoperatively. The patient is draped and in the left lateral decubitus position. Three ports are in situ between the fourth and sixth intercostal spaces in the right hemithorax.

There were no surgical complications and the patient was discharged on post operative day 4. At four months follow-up there was no recurrence of the pericardial effusion.

3. Discussion

William Chester a cardiology fellow working under the pathologist Jakob Erdheim in Vienna, first described 2 cases of ‘lipoid granulomatosis’ in 1930.¹³ This disease later became known as Erdheim–Chester disease (ECD).¹⁴ Biopsy is required for definitive diagnosis, with pathology showing CD68+/CD1a− non-Langerhans histiocytes. There is variable reactivity for S100 protein, a marker also present in other disorders of histiocytes.¹ Infiltration of the bones and other organs by these foamy histiocytes lead to a variety of clinical presentations. Typically, bone pain is the most frequent symptom,^2,5,15 with underlying cortical osteosclerosis of long bones and abnormally increased labeling in the long bones of the lower limbs on technetium-99 bone scans.^5,15,16 Half of patients however have extra-skeletal manifestations including exophthalmos, interstitial lung disease, diabetes insipidus, and xanthelasma.^3,5,17

Interferon-alpha is generally used as first line therapy for ECD, but given the variable response, treatment is individualized depending on extent and severity of organ involved.^6,7 A multitude of treatments for ECD have been proposed including various cytotoxic agents, steroids, radiation therapy and stem cell transplantation.^5,18,19 Analysis of the various therapies is difficult as response is often not stated and followup periods are short (Table 1).

Table 1.

Selection of treatments previously used for ECD and outcomes.

Author, year	No. patients	Treatment	Anatomical involvement	Outcome
Haroche et al., 20057	8	Interferon alpha: 3–9 × 106 units 3 times weekly for median of 23 months	Multisystem including: bone, renal, cardiovascular, CNS.	Efficacious in 6 patients: xanthelasma disappeared in 2; hydronephrosis regressed in 2, papilledema disappeared in 1, exophthalmos disappeared in 2, variable regression of coated aorta. 2/5 with CV involvement died.
Myra et al., 200423	1	Cladribine: 0.14 mg/kg/day for 5 consecutive days every 4 weeks. 6 courses	Orbital, cardiac, bone and lung	Regression of bone, lung and orbital disease at two years
Miller et al., 200618	9	Radiotherapy (for palliation purposes):	Osseous sites × 6; brain sites × 2, retroorbital × 1	Osseous sites: pain scores improved at 1 year post therapy
		10–24 Gy (median, 16 Gy) in 5–12 fractions (median, 8) at 1.8–2.0 Gy/d (median, 2.0 Gy/d)		Brain: initial improvement in symptoms but progression by 4 months post therapy
				Retro-orbital: pain free at 1 year with decrease in size of mass
Haroche et al., 200824	6	Imatinib mesylate (for severe/resistant disease):	Multisystem including: CNS, cardiovascular, bone	CNS involvement worsened in 75% cases, cardiovascular disease remained stable in 80%, bone involvement worsened.
		Initially 100 mg/day, increasing according to tolerence + efficacy
Boissel et al., 200118	1	Double autologous hematopoietic stem cell transplant (conditioning with etoposide and melphalan; post conditioning with carmustine)	Renal, facial bones and retroorbital involvement	Improvement in retroorbital disease, facial tumor and kidney tumor. Improvement stable at 2 years

We describe a patient with multisystem involvement by ECD. Two biopsies from different anatomical sites exhibited the typical CD68+/CD1a− histiocytes, and different reactivity to S100 protein. Our patient presented with life-threatening pericardial effusion with tamponade apparent on physical exam and echocardiography.

Cardiac involvement by ECD is common and is associated with high mortality rates.² In our patient, pericardiocentesis was therapeutic initially but persistent high pericardial fluid output demanded definitive treatment of the pericardial effusion with pericardiotomy or ‘window’ insertion. Traditionally, this would be completed via thoracotomy. Currently, subxiphoid pericardiotomy and video-assisted thoracoscopic surgery are the most commonly employed techniques for management of recurrent pericardial effusions.

VATS is a minimally invasive alternative which permits exploration of the thoracic cavity and the creation of a pleuro-pericardial window.²⁰ It is an appealing new option for the management of many cardiothoracic diseases.^8–11,20 It combines the advantages of subxiphoid pericardiotomy and thoracotomy.²⁰

Compared with thoracotomy, the VATS procedure is being used increasingly for management of recurrent pericardial effusions, as it has less post-operative pain and less effect on pulmonary dysfunction.¹¹ Patients in whom collection of a biopsy specimen is important, VATS when compared to subxiphoid approaches offers an increased area of exposure at lower risk to allow for pericardial biopsy.^20–22 VATS is also associated with a lower rate of effusion recurrence when compared with subxiphoid approaches (Table 1). The choice of procedure, depends significantly on local expertise.

In our case, VATS provided a viable option for both diagnostic confirmation and therapeutic relief of recurrent pericardial fluid drainage.

To our knowledge, this is the first reported case of the successful use of VATS to diagnose cardiac involvement in Erdheim–Chester disease and to treat recurrent pericardial effusion through formation of a pericardial window.

4. Conclusion

ECD disease is a rare entity with a large proportion of cases having cardiac involvement, specifically pericardial disease. VATS is a novel and appealing way both to diagnose and to manage recurrent pericardial effusions in ECD. VATS is associated with a lower morbidity and mortality than traditional thoracotomy or subxiphoid pericardial window procedures.

Conflict of interest statement

None declared.

Funding

None.

Ethical approval

Written informed consent was obtained from the patient for publication of this case report and accompanying images. A copy of the written consent is available for review by the Editor-in-Chief of this journal on request.

Author contributions

Aoife Egan collected the data regarding the case, drafted the manuscript.

Dan Sorajja modified the manuscript, completed literature review.

Dawn Jaroszewski modified the manuscript, provided images.

Farouk Mookadam supervised the project, designed the format, modified the manuscript.