Joint Program in Nuclear Medicine
Susan Passalaqua, MD
Milos J. Janicek, MD PhD
October 3, 2000
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.
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.
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
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
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 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.
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.
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J. Anthony Parker, MD PhD, Tony_Parker@CareGroup.Harvard.edu