ECD is a systemic, xanthogranulomatous,
proliferative, infiltrative disease with foamy (lipid-laden)
macrophages/histiocytes of unknown etiology. The signs and symptoms are
unspecific and mainly result from the histiocytic infiltration of different
tissues. The bones most often affected are the femora, tibiae, and fibulae;
humeri, ulnae, and radius are less often involved. The axial skeleton is
usually spared. The diaphyses and metaphyses of the long bones are
characterized by a diffuse or patchy increase in density, coarsening of the
trabecular pattern, medullary sclerosis, and cortical thickening. The
epiphyses usually are not affected. The most common presenting features
include lower limb pain (knees, ankles), exophthalmos, diabetes insipidus,
and general symptoms such as fever and weight loss. Retroperitoneal
involvement with paraaortic and perirenal infiltration may cause postrenal
obstructive uropathy. Pulmonary interstitial involvement is seen in
approximately 35% of cases, with the upper parts of the lungs usually
being more severely affected. Pulmonary lesions are characterized by
interstitial accumulations of histiocytes and fibrosis in a mainly
perilymphangitic and subpleural pattern. Computed tomographic scanning may
demonstrate centrilobular nodularity and thickening of the interlobular
septa and the visceral pleura. Other nonbony sites affected may include skin
(pruritic rash, xanthelasma, periorbital xanthomata), retroorbital tissue
(resulting in exophthalmos and rarely blindness), and central nervous system
(dural and falcine masses possibly compressing the brain, seizures,
dysarthria, cerebellar symptoms such as nystagmus, hypermetric saccades,
negative suppression of the vestibuloocular reflex, dysmetria and ataxia,
and diabetes insipidus with polyuria and polydipsia from infiltration of the
pituitary gland). Pericardial effusion and hepatosplenomegaly have been
described. Jaw infiltration (mandibula and maxilla) resulting in
periodontitis and loss of teeth has been reported in a small number of
patients. The clinical course is quite variable. Steroids, chemotherapy
(vincristine, vinblastine, cyclophosphamide, doxorubicin), radiotherapy,
immunotherapy (cyclosporin, interferon-α-2A), and surgery have all
been used with various success in the treatment of this disease. Reports
about response to therapy and overall survival are limited and highly
variable; however, survival after diagnosis in the largest study was
approximately 32 months, with pulmonary fibrosis, respiratory distress,
and/or heart failure the most common causes of death.