Erdheim-Chester Disease: A Case Report and Review of the Literature

INTRODUCTION

The first case of Erdheim-Chester disease (ECD) was described in 1930 by Jakob Erdheim, an Austrian pathologist, and William Chester, an American pathologist.^[1] It is a rare, systemic form of non-Langerhans’ cell histiocytosis and is of unknown etiology.^[2] It primarily affects adults between their 5^th and 7^th decades of life but patients between the ages of 7 and 84 years have been diagnosed.^[3] There is a slight male predominance with some studies suggesting an earlier diagnosis in female compared to male patients.^[4] ECD may be asymptomatic or present as a multi-systemic disease with life-threatening manifestations affecting the skeleton, central nervous system, respiratory, cardiovascular and renal systems, as well as the retroperitoneum and skin. In symptomatic patients, bone pain is the most common initial presentation. Extra-skeletal manifestations are seen in up to 50% of cases.^[3]

ECD is characterized by xanthogranulomatous infiltration of foamy histiocytes surrounded by fibrosis.^[5-8] They lack Birbeck granules (a characteristic intracellular organelle found in Langerhans’ cells) and immunohistochemical staining is positive for CD68 and negative for CD1a.^[9] The World Health Organization has proposed a classification system for histiocytic disorders; Class I is Langerhans’ cell histiocytosis (LCH) and Class II are the non-Langerhans’ histiocytoses and include juvenile xanthogranuloma (JXG), Rosai-Dorfman disease, and ECD.^[10] LCH encompasses the conditions previously known as Hand-Schüller-Christian disease, Letterer-Siwe disease, and eosinophilic granuloma.^[3] Class III includes the malignant histiocytic disorders.^[10] LCH and ECD share common properties and overlap can occur in up to 12% of ECD cases.^[11-15] However, ECD differs from LCH in the immunohistochemical and microscopic characteristics in that the histiocytes only in the latter stain positive for S100 protein and electron microscopy of their cytoplasm demonstrates Birbeck granules in more than 20% of cells.^[16]

CASE PRESENTATION

A 69-year-old gentleman presented with recurrent episodes of left arm and leg weakness over 1 week, which was diagnosed as crescendo transient ischemic attacks (TIA). His only medical history was previous alcohol excess, which he had overcome. On admission, the chest radiograph reported bilateral interstitial coarse reticulation, predominantly in the right mid zone. Incidental note was made of coarsening of the trabecular pattern and ill-defined sclerosis of the proximal humeri. Computed tomography (CT) of the head, performed for the TIAs, reported no acute intracranial abnormality, mild chronic ischemic small vessel disease, and an incidental sphenoid sinus mucous retention cyst. The skull bones were normal.

The blood results during admission revealed a microcytic anemia with a hemoglobin of 100 g/L and a mean corpuscular volume of 76.9 femtoliter. The white cell count, renal function tests, and liver function tests, including alkaline phosphatase (ALP), were normal (apart from low albumin, 22 g/L). The coagulation screen, total cholesterol, glucose, and prostate- specific antigen were also all within normal limits.

Due to the microcytic anemia and humeral findings on the chest radiograph, in addition to some weight loss, a CT scan of the chest, abdomen, and pelvis were requested to rule out malignancy. As demonstrated in Figure 1, the findings within the chest were a combination of interlobular septal thickening and patchy ground glass opacification, producing a crazy paving pattern, with two ill-defined small solid nodules in the right upper and left lower lobes, respectively. Both kidneys showed diffuse perinephric soft tissue with further soft tissue within both renal pelvices and mild dilatation of the intrarenal collecting system. Bony appearances revealed coarsening of the trabeculae and a mixed pattern of sclerosis and lucency within the proximal humeri, scapulae, proximal femora, and acetabulae bilaterally. The case was forwarded to the neuroradiology multidisciplinary team meeting and on discussion of the findings; a diagnosis of ECD was made by the radiologist. It was felt that the patient’s neurological symptoms were unrelated to the incidental radiological findings of ECD and he was referred on to a consultant neurologist at a specialist center.

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Figure 1:

69-year-old male patient who presented with left sided weakness secondary to a TIA. A history of weight loss and anaemia triggered further imaging investigation with a whole body CT, which subsequently lead to the diagnosis of Erdheim-Chest Disease. (a) An AP chest radiograph taken on admission, showing bilateral fine reticular and reticulonodular opacification, predominantly in the upper zones with areas of peripheral ground glass opacification, (black arrows). In addition, there are sclerotic changes in the humeri (red box). (b) Contrast enhanced, coronal CT of the chest, in bony window, shows further evidence of the sclerotic changes in both humeri (red boxes). (c) Contrast enhanced axial image of the chest, in lung window, shows interlobular septal thickening (black arrows) and patchy ground glass opacification in both upper lobes in a crazy paving-type pattern (red boxes). (d) Contrast enhanced axial view of the chest, in mediastinal window, showing a pericardial effusion (black arrows). (e) and (f) Contrast enhanced coronal (e) and axial (f) CT images through the abdomen, in soft tissue window, demonstrating diffuse perinephric soft tissue around both kidneys (black arrows) with additional soft tissue within the region of both renal pelvises and mild dilatation of the intrarenal collecting system (white arrows). (g) Contrast enhanced coronal abdominal CT image, in soft tissue window, demonstrating circumferential periaortic fibrosis, giving a ‘coated aorta’ appearance (black arrows). The perinephric soft tissue thickening is again demonstrated on this coronal image (white arrows). (h) Contrast enhanced coronal image of the pelvis and proximal femora, in bony window, demonstrating coarsened trabeculae with a mixed pattern of dense sclerosis and lucency.

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DISCUSSION

ECD is a rare, xanthogranulomatous form of non- Langerhans’ cell histiocytosis, characterized by infiltration of foamy histiocytes and surrounding fibrosis. Diagnosis relies on established radiological and histological criteria, as described below.

CONCLUSION

ECD is a form of non-Langerhans’ cell histiocytosis characterized by xanthogranulomatous infiltration of foamy histiocytes surrounded by fibrosis. Its rarity and multi-systemic involvement can make diagnosis challenging and it therefore requires a multidisciplinary approach. To add to the diagnostic dilemma, patients with ECD may be asymptomatic despite the multi-systemic involvement, as in this case. However, recognition of the characteristic radiological features, with diagnostic skeletal, pulmonary, cardiac, renal, and retroperitoneal manifestations, can help to clinch the diagnosis of this rare condition, without histological confirmation.