Joint Program in Nuclear Medicine

Erdheim-Chester Disease

Susan Passalaqua, MD
Milos J. Janicek, MD PhD

October 3, 2000

Presentation

A forty-four year old man presented with an eight-month history of lightheadedness and dysarthria. Significant past medical history included hyperlipidemia, heroin and cocaine addiction. Various radiological studies were obtained.

Imaging Findings

MRI: Axial T1 weighted and sagital T1 weighted MRI images showed bilateral retrobulbar intraconal masses (shown by arrows on axial and on sagital images). Axial T2 weighted MRI images showed abnormal increased signal in the pons (shown by arrow).
Bone Scintigraphy: Tc-99m MDP bone scintigraphy showed uptake within the tibial shafts bilaterally with relative sparing of the epiphyses (shown by arrows). Radiotracer accumulation is also present within the distal radial metadiaphyses, the distal left femur, the mandible and region of the paranasal sinuses (shown by arrowheads).
Plain Radiography: Radiographs of the left femur showed ill defined sclerosis of the distal femur extending to the epiphysis of the medial femoral condyle (shown by arrows) and sparing the lateral condyle (arrowhead). The sclerosis corresponds to the scintigraphic abnormality.
CT: A CT of the abdomen showed perinephric stranding (shown by arrow).

Discussion

Erdheim-Chester disease (ECD) is a rare non-Langerhans cell histiocytosis first described by Jakob Erdheim and William Chester in 1930. They described two patients who had a distinctive lipidosis with associated bone changes. In 1972, Jaffe reported a third patient and coined the term "Erdheim-Chester disease". Jaffe described the disease as a rare histiocytic disorder of adults characterized by an infiltrate of lipid-laden macrophages, multinucleated giant cells, inflammatory infiltrate of lymphocytes and histiocytes in the bone marrow and a generalized sclerosis of the long bones sparing the epiphysis. Approximately 80 cases have been reported in the literature.

Erdheim-Chester Disease versus Langerhans Cell Histiocytosis

ECD is very similar to Langerhans cell histiocytosis (LCH) in its histopathology and distribution and was thought to represent the same disease process. ECD differs from LCH in its age distribution, immunochemical characteristics and radiologic characteristics.

LCH is a disease of childhood. The average age at presentation for ECD is 53 years.
The Langerhans cell histiocytes stain positively for S-100 antigen and have Birbeck granules on electron microscopy. The histiocytes in ECD do not share these characteristics.
The bony lesions in ECD are typically symmetric and sclerotic and involve the long bones in the region of the metadiaphyses. The lesions of LCH are typically lytic and involve the axial skeleton.

Skeletal Manifestations

Bone pain is the most common presenting symptom of ECD. Other common symptoms and signs include fever, weight loss, exopthalmos, dyspnea and neurologic signs. The typical findings on bone scintigraphy are bilateral symmetric uptake of bone seeking radiopharmaceutical within the metadiaphyses of the appendicular skeleton. Plain radiographs of the involved bones demonstrate ostesclerosis of the diaphyses and the metaphyses with sparing of the epiphyses. This pattern is considered to be pathognomonic of ECD.

Nonosseous disease is well recognized and includes hypothalamic / pituitary involvement with resultant diabetes insipidus, renal and retroperitoneal infiltration, eyelid and cutaneous xanthomas, intra and extra axial cerebral infiltration, pericardial infiltration and pulmonary fibrosis. The clinical course of ECD depends on the extent and distribution of the extraosseous disease.

Neurologic Manifestations

The most common neurologic manifestation is central diabetes insipidus. Next in frequency is cerebellar symptoms, usually ataxia of gait. MRI of the brain in patients with neurologic symptoms demonstrates intra-axial lesions with T2 hyperintensity and often intense gadolinium enhancement. The lesions occur most often in the cerebellum and pons. The MRI findings mimic a demyelinating process and are often confused with multiple sclerosis. The MRI findings in patients with diabetes insipidus vary. Often no structural changes are seen. Loss of the normal T1 hyperintensity of the posterior pituitary, pituitary enhancement and enlargement of the infundibulum have been described.

Obital Manifestations

Orbital manifestations in ECD range from infiltration of the retroconal fat and optic nerve sheath to large retrobulbar, intraconal masses. The clinical differential diagnosis in orbital involvement includes thyroid orbitopathy, pseudotumor, lymphoma and metastatic carcinoma.

Retroperitoneal Manifestations

Retroperitoneal involvement in ECD is secondary to infiltration of the fat and surrounding structures by histiocytes and associated fibrosis. CT findings range from fat stranding in the retroperitoneum to soft tissue masses in the retroperitoneum. This may result in hydronephrosis leading to renal failure and hypertension. Periaortic fibrosis has been described and has been shown to involve the entire aorta and its branches causing lower extremity claudications.

Pulmonary Manifestations

The most common pulmonary symptom is progressive dyspnea. Chest radiographs demonstrate diffuse interstitial prominence and pleural thickening. CT typically shows interlobular septal and pleural thickening. Other findings include patchy centrilobular ground glass opacities.

Prognosis and Therapy

The prognosis for ECD is related to the extent of visceral involvement. Most patients die within two to three years after diagnosis due to congestive heart failure, lung fibrosis or renal insufficiency. Treatment options include corticosteriods, radiotherapy, chemotherapy and immunotherapy or combination therapy. None have been highly effective and the disease is typically relentless in its course.

References

Veyssier-Belot C, Cacoub P, Caparros-Lefebvre D, Wechsler J, Brun B, Remy M et al. Erdheim-Chester disease. Clinical and radiologic characteristics of 59 cases. Medicine 1996; 75(3):157-69.
Wright R A, Hermann R, Parisi J. Neurological manifestations of Erdheim-Chester disease, J Neurol Neurosug Psychiatry 1999(66):72-75.
Valmaggia C, Neuweiler J, Fretz C, Gottlob I. A Case of Erdheim-Chester disease with orbital involvement. Arch Opthalmol;115, 1467-68.
Serratrice J, Granel B, De Roux C, Pellissier J, Swiader L, Bartoli J et al. "Coated Aorta": A new sign of Erdheim-Chester disease, Journal of Rheumatology 2000;27(6)1550-53.
Franzius C, Sciuk J, Bremer C, Kempkes M, Schober O. Determination of extent and activity with radionuclide imaging in Erdheim-Chester disease. Clinical Nuclear Medicine 1999, 24(4), 252-55.

Click here to go to Joint Program in Nuclear Medicine home page and Copyright notice.

J. Anthony Parker, MD PhD, Tony_Parker@CareGroup.Harvard.edu