Erdheim-Chester Disease (ECD)

Systemic non-Langerhans cell histiocytic disorder characterized by development of lipoid granulomas in many organs and tissues of the body. Clinical manifestations range from asymptomatic to fatal multisystem involvement.

Lipid Granulomatosis; Polyostotic Sclerosing Histiocytosis.

First described by the American pathologist William Chester in 1930. Credit was later also given to Chester's mentor during his time in Vienna, the Austrian pathologist Jakob Erdheim, although he was not an author on the paper.

Fewer than 100 cases have been described in the medical literature. Erdheim-Chester disease (ECD) has a male predilection and most often affects adults older than 40 years, although the reported age range is wide.

Etiology is unknown. No genetic basis has been described.

ECD results from infiltration of the bones and other tissues by foamy histiocytes. These histiocytes are derived from monocytes/macrophages, lack intracytoplasmic granules (Birbeck granules), and do not stain positive for S-100 protein, which makes them histologically distinguishable from histiocytes derived from Langerhans cells. (However, researchers now have found extensive S-100-positive staining in some ECD histiocytes, so further evaluation seems necessary.) ECD characteristically affects the long bones symmetrically.

Based on clinical and histopathologic findings. Symmetrical long bone osteosclerosis is the characteristic radiologic finding. However, histologic confirmation is required for the final diagnosis, preferentially from specimens from bone or retrobulbar tissue.

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.

Pulmonary involvement must be assessed by clinical examination, chest radiograph, and pulmonary function tests (including arterial blood gas analysis) often revealing moderate restrictive lung disease and reduced carbon monoxide diffusion capacity. Cardiac/pericardial involvement should be evaluated by echocardiography. Look for cor pulmonale in patients with significant pulmonary symptoms. Urine analysis and serum levels of electrolytes, creatinine, and urea should be checked in the presence of suspected renal disease. In addition, plasma and urine osmolality should be checked preoperatively to exclude diabetes insipidus, because it may cause electrolyte abnormalities and water depletion, if left untreated. Therapy with vasopressin is usually successful. A complete blood count is recommended, because medullary sclerosis could theoretically affect hemopoiesis. Assess dental status for vulnerability during direct laryngoscopy.

The choice of anesthetic technique is guided by the degree of organ compromise from the disease. A urinary catheter may be helpful to diagnose diabetes insipidus and follow-up of the effect of vasopressin. Attention should be paid to protecting the eyes in the presence of exophthalmos. Depending on the chemotherapy drugs that have been used, high oxygen concentrations may not be appropriate (in order to prevent pulmonary oxygen toxicity).

These patients may be on oral steroid therapy, and perioperative stress coverage may be required. Careful dosage (titration) of predominantly renally excreted drugs in the presence of decreased kidney function is recommended.

Histiocytosis: Group of disorders characterized by infiltration and accumulation of histiocytes in various tissues, such as the skin, bones, brain, lungs, spleen, and liver. Despite nonmalignant growth, the prognosis is poor.

Gaucher Disease: Most common inherited lipid storage disease, particularly common in Ashkenazi Jewish people (Eastern European ancestry). Accumulation of glucocerebrosides (derived from red blood cells) in many tissues, especially the macrophages in the bone marrow (the normal functions of which are impaired). Significant-to-major anesthetic implications.

Niemann-Pick Disease: Group of rare inherited disorders of fat metabolism. Lysosomal storage disorder caused by a defect in sphingolipid metabolism and involving brain and/or viscera. Clinical features include jaundice, progressive loss of motor skills, feeding difficulties, learning disabilities, and hepatosplenomegaly.