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Unusual manifestation of Erdheim-Chester disease
© Pan et al; licensee BioMed Central Ltd. 2011
Received: 21 March 2011
Accepted: 22 June 2011
Published: 22 June 2011
Erdheim-Chester disease (ECD) is a rare multisystem non-Langerhans cell histiocytosis that is characterized histologically by xanthogranulomatous infiltrates and radiologically by symmetrical sclerosis of long bones. The xanthomatous process is characterized by prominent foamy histiocytes staining positive for CD68, occasionally for PS100 and negative for S100 and CD1a. Gastroenterological involvement is exceedingly rare.
This case report describes the case of a 69-year-old man who presented otherwise well to the gastroenterology department with unspecific abdominal symptoms, nausea, vomiting and weight loss. ECD involving the gastrointestinal tract was confirmed clinically, radiologically and histologically.
Gastroenterological manifestation of ECD is rare but should be considered in the differential diagnosis in patients presenting with evidence of multi-organ disease and typical radiological features of Erdheim-Chester disease elsewhere.
Erdheim-Chester Disease (ECD) is a rare multisystem histiocytosis characterized by the xanthomatous or xanthogranulomatous infiltration of tissues with histiocytes, surrounded by fibrosis. The disease can affect multiple organs systems, but gastrointestinal involvement, is exceedingly rare. We describe here the case of a 69-year old man with ECD who presented to the gastroenterology department with unspecific abdominal symptoms, nausea, vomiting and weight loss.
A previously fit and well 69-year-old man was admitted to the gastroenterology department with a short one month history of lethargy, decreased appetite, persistent vomiting, significant weight loss of six kilograms over 1 month and a dry cough. He denied abdominal pain, haematemesis, dysphagia and a change in bowel habit and described no cardiac, respiratory, neurological symptoms or bone pain. His past medical history includes appendectomy and total hip joint replacement. At the time of admission, he was not on any regular medication.
Erdheim-Chester Disease (ECD) is a rare multisystem non-Langerhans cell histiocytosis first described by Jakob Erdheim and William Chester in 1930  and since then approximately 400 cases have been reported . It is characterized by the xanthomatous or xanthogranulomatous infiltration of tissues with foamy histiocytes, surrounded by fibrosis. The aetiology of the disease remains unknown. The disease can affect multiple organs systems, including musculoskeletal, central nervous, cardiac, pulmonary and renal systems. Gastrointestinal involvement, despite being seen more often in other histiocytoses , is exceedingly rare and to our knowledge there are 2 case reports regarding involvement of the liver and biliary system [4, 8].
Two criteria, of which one should be fulfilled, were proposed by Veyssier-Belot  in 1996 as a requirement for the diagnosis of ECD. (1) Typical histological findings with foamy histiocytes nested among polymorphic granuloma and fibrosis or xanthogranulomatosis with CD68-positive and CD1a-negative immunohistochemical staining. (2) Typical skeletal findings with a) radiographs showing bilateral and symmetric osteosclerosis of the diaphyseal and metaphyseal regions in the bones and/or b) symmetric and abnormally increased labeling of the distal ends of the long bones of the lower limbs, and sometimes the upper limbs, on 99Tc bone scintigraphies.
There are typical radiological and pathological features which can lead to the diagnosis, but the clinical spectrum shows a broad variation, ranging from asymptomatic tissue infiltration to fulminant multisystem organ failure.
Bone pain is the most common presenting symptom of ECD mainly affecting the legs, especially knees and ankles and has been reported in 47-86% of patients with ECD [1, 9–12]. About half of all patients have extra-skeletal manifestations including retroperitoneal fibrosis, orbital infiltration, interstitial lung disease [2, 13], bilateral adrenal involvement , testis infiltration , breast, central nervous [9, 16, 17] and/or cardiovascular system . Other general symptoms such as fever, weight loss and weakness can also occur.
Retroperitoneal involvement is secondary to infiltration of the fat and surrounding structures by histiocytes and associated fibrosis. This process can lead to peri-renal and/or ureteral obstruction causing renal impairment. This is reported to occur in 29-59% of patients with ECD [1, 19]. Erdheim-Chester infiltration is distinguished from retroperitoneal fibrosis principally by its many foamy histiocytes, lack of plasma cells, and lack of vasculitis .
The cardiovascular manifestations of ECD have been known to exist since the disease was first described; this occurs in about 40% of the patients with peri-aortic "fibrosis" as the most frequent cardiovascular involvement. Other manifestations include heart failure, valvular dysfunction, reno-vascular hypertension and pericarditis . It was previously thought that only about 20% of patients have lung involvement however, a recent study reported clinical and/or radiological pulmonary involvement in up to 59% of patients . Usually patients present with dyspnea or a dry cough . Most patients have mediastinal infiltration, diffuse interstitial infiltrates and pleural and/or interlobar septal thickening best seen on high-resolution CT . Characteristic lung histopathology includes the accumulation of histiocytes with variable amounts of fibrosis and a variable lymphoplasmacytic infiltrate in a lymphangitic distribution .
The involvement of liver, pancreas, mesentery and gastrointestinal tract is extremely rare [8, 4]. The diagnosis of ECD in our patient was challenging as he presented with unspecific symptoms such as a decrease in appetite, persistent vomiting, weight loss and fever. He had features of malnutrition with cachexia, peripheral oedema secondary to hypoalbuminaemia. Evidence of both hepatic and mesenteric involvement of ECD was present, with operative findings of liver, omentum and small bowel mesentery infiltration. Liver biopsy showed xanthomatous infiltration with prominent foamy histiocytes positive for CD68 and negative for S100 and CD1a. Biopsies also confirmed the involvement of mesenteric lymph nodes and the omentum. It was interesting to see that a normal liver function test does not preclude the involvement of the liver by histiocytic infiltration in ECD. Our patient also showed features consistent with skeletal involvement with MRI demonstrating increased marrow signal in the distal femur and proximal tibia. Although bone pain is the most common presenting of ECD, he remained asymptomatic from his skeletal lesions. Other features of ECD demonstrated in our patient include retroperitoneal, cardiovascular and respiratory involvement.
Various therapies for ECD have been proposed, including corticosteroids , multiple chemotherapeutic regimes including vinblastine, vincristine, cyclosphosphamide, doxorubicin , cladribine [1, 21–23], radiotherapy [19, 24], cyclosporine and alpha interferon . The latter treatment has gained some attention recently with the initial report of a durable response in three patients . This was followed by a series report of treatment with interferon-alpha in eight patients with variable response. While treatment with interferon-alpha is promising, mechanisms of action are still largely unkown . Prognosis of the disease depends largely on the extent and distribution of the extra-skeletal, in particular cardio-vascular  and central nervous system  involvement. Based on these results it was suggested by the authors that interferon-alpha is considered as a first-line treatment for patients with ECD but a 40% mortality in the first 40 months after diagnosis has still to be accepted .
In summary, we describe the case of a 69-year-old man who presented to the gastroenterological department with unspecific symptoms of fever, fatigue, decreased appetite, persistent vomiting and weight loss. He had clinical, radiological and histological features consistent with gastrointestinal involvement of ECD. He also demonstrated the involvement of skeletal, retroperitoneal, cardiovascular, and respiratory system. He fulfilled the two criteria proposed by Veyssier-Belot1 in 1996 for the diagnosis of Erdheim-Chester disease. Although a bone scan was not performed, the MRI STIR showed an increased marrow signal in the distal femur and proximal tibia. Even though bone pain is the most commonly presenting symptom in ECD, apart from general unspecific symptoms, our patient did not show any evidence of bone pain. Despite the multiple extra-skeletal manifestations seen radiologically, gastroenterological manifestation of ECD is rare but should be considered in the differential diagnosis in patients presenting with evidence of multi-organ disease and typical radiological features of Erdheim-Chester disease elsewhere.
Dr Pan is an advanced trainee in gastroenterology and general medicine at the Dunedin Hospital, Southern District Health Board, New Zealand.
Written consent was obtained from the patient for publication of study. Special thanks to Dr Michael Lau, Pathologist, Southern Community Laboratories, Dunedin for his provision of histology slides.
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