
==== Front
Radiol Case Rep
Radiol Case Rep
Radiology Case Reports
1930-0433
Elsevier

S1930-0433(24)00826-4
10.1016/j.radcr.2024.08.043
Case Report
A rare case of Erdheim Chester disease
Oualladi Feryal El MD eloualladi.feryal@gmail.com
⁎
Labied Mohamed MD
Hassani Rabab MD
Mountassir Chorouk MD
Lembarki Ghizlane MD
Sabiri Mouna PhD
Lezar Samira PhD
Central Unit of Radiology, University Hospital Center Ibn Rochd, School of Medicine and Pharmacy of Casablanca, Hassan II University, Casablanca, Morocco
⁎ Corresponding author. eloualladi.feryal@gmail.com
07 9 2024
12 2024
07 9 2024
19 12 56195623
13 7 2024
8 8 2024
10 8 2024
© 2024 The Authors. Published by Elsevier Inc. on behalf of University of Washington.
2024

https://creativecommons.org/licenses/by-nc-nd/4.0/ This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
Erdheim-Chester disease (ECD) is a rare form of non-Langerhans cell histiocytosis. There are few documented cases in the medical literature. Here, we present an infrequent case of a 53-year-old patient who presented with cutaneous xanthelasma and a gradual decline in general health characterized by asthenia, anorexia, and chronic dyspnea over the last 5 years. Chest, abdominal, and pelvic CT scans revealed distinct findings suggestive of ECD, including peri-renal fat infiltration resulting in the “hairy kidney” sign, hepatosplenomegaly, renal artery ostial stenosis, pneumopericardium thickening, interstitial lung parenchymal involvement, metaphyseal-diaphyseal osteosclerosis affecting long bones, and sinus osteosclerosis. A biopsy confirmed the diagnosis. This case highlights the importance of radiologists being familiar with the characteristic radiologic signs of ECD to avoid unnecessary repeat examinations, delays in diagnosis, or misdiagnosis.

Keywords

Erdheim-Chester disease
Non-Langerhans histiocytosis
Radiologic findings
Hairy kidney sign
Coated aorta sign
Sinus osteosclerosis
Osteosclerosis of long bones
==== Body
pmcKey points

- Erdheim-Chester disease has distinct radiologic features that are critical for diagnosis.

- Radiologic imaging plays a unique role in diagnosing, managing, and monitoring Erdheim-Chester disease.

- Recognizable pathognomonic signs include the hairy kidney sign, coated aorta, symmetrical bilateral osteosclerosis of the long bones, intra- and extraconal masses in the orbits with exophthalmos, and masses in the right atrioventricular groove.

Introduction

Erdheim-Chester disease (ECD) is a sporadic form of non-Langerhans histiocytosis with multisystem involvement that is under-recognized and contributes to significant diagnostic delays. It most commonly affects middle-aged individuals. The clinical presentation is highly variable. Imaging plays a central role in the diagnosis. Bone involvement is the most common finding. Retroperitoneal involvement mainly involves perirenal tissue. Pathognomonic imaging findings include symmetric diaphyseal osteosclerosis of long bones, retroperitoneal infiltration (“hairy kidney”), and periaortic sheathing (“coated aorta”). Cardiac, neurological, and pulmonary involvement contribute to the severity of the disease. The differential diagnosis depends on the organs involved. The diagnosis is based on histopathologic evidence in a clinically and radiologically suggestive context.

Case report

We present the case of a 53-year-old patient, a carpenter by profession, who presented with a 3-year history of chronic dyspnea at rest, bone pain in both legs and chronic intermittent abdominal pain, all in the context of an altered general condition consisting of asthenia and anorexia.

Physical examination revealed cutaneous xanthelasma and abdominal tenderness of both flanks without other systemic abnormalities.

The patient initially underwent an abdominal CT scan, which showed peri-renal fat infiltration with the pathognomonic “hairy kidney” sign typical of the disease (Fig. 1), hepatosplenomegaly, peri-aortic infiltration, stenosis of the renal artery ostia (Fig. 2), and mesenteric lymphadenopathies.Fig. 1 A 53-year-old male patient with Erdheim Chester disease. Abdominal CT scan after contrast injection showing thickening and infiltration of peri-renal fat producing the “hairy kidney” sign (black arrow) responsible for the more pronounced bilateral hydronephrosis on the left side (white arrow).

Fig 1:

Fig. 2 A 53-year-old male patient with Erdheim Chester disease. Abdominal CT scan after contrast injection in axial view with maximum intensity projection (MIP) reconstruction showing bilateral renal artery ostial stenosis. (black arrow).

Fig 2:

Chest CT scan showed circumferential and regular bilateral pleural thickening with pericardial thickening (Fig. 3), cardiomegaly, pulmonary interstitial involvement with smooth and regular bilateral septal thickening, bilateral subpleural reticulations, bilateral ground-glass nodules and micronodules with centrolobular distribution and associated subcentimeter air-filled formations (Fig. 4)”.Fig. 3 A 53-year-old male patient with Erdheim Chester disease. CT scan of the chest in the mediastinal window showing bilateral pleural thickening, more pronounced on the right (black arrow), associated with pericardial thickening (white arrow) and thickening of the right atrial myocardium (yellow arrow).

Fig 3:

Fig. 4 A 53-year-old male patient with Erdheim Chester disease. Thoracic CT scan in parenchymal window showing: (A) smooth and regular septal thickening (yellow arrow). (B) Centrolobular micronodules (black arrow) and small air-filled cystic formations (yellow arrow).

Fig 4:

A brain CT scan showed sinus osteosclerosis with diffuse thickening of the diploë (Fig. 5).Fig. 5 A 53-year-old male patient with Erdheim Chester disease. CT scan of the brain in the bone window showing sinus osteosclerosis (yellow arrow).

Fig 5:

Lower limb radiographs showed bilateral symmetric metaphyseal-diaphyseal osteosclerosis with localized periosteal thickening (Fig. 6).Fig. 6 A53-year-old male patient with Erdheim Chester disease. Frontal radiographs of both femurs (A) and both humeri (B) show bilateral and symmetrical metaphyseal-diaphyseal patchy medullary sclerosis (white arrow) with resultant mild loss of corticomedullary differentiation. There is cortical thickening of the femur (yellow arrow) and an osteocondensing lesion at the neck of the right femur and humerus (red arrow).

Fig 6:

A mesenteric lymph node biopsy confirmed the diagnosis of Erdheim-Chester disease.

The diagnosis of Erdheim-Chester disease was supported by integrating clinical, radiologic, and histopathologic findings.

Discussion

Erdheim-Chester disease (ECD) is a sporadic form of non-Langerhans histiocytosis first described in 1930 by William Chester and Jakob Erdheim as “lipidic granulomatosis” [[1], [2], [3], [4]]. It includes xanthogranulomatous infiltration involving multiple systems, including the skin, heart, breast, bone marrow, kidneys, lungs, abdomen, eyes, brain, pituitary, and bones. [4,5].

ECD typically manifests between the fifth and seventh decade of life, mainly in males [1,6]. The diagnosis relies on clinical, laboratory, radiological, and histopathological findings [6]. Although nonmalignant, ECD can lead to life-threatening organ dysfunction [6].

According to the 2016 classification of histiocytoses by the Histiocyte Society, ECD falls into group L, which includes Langerhans cell histiocytosis (LCH) [7,8].

Patients may present with a variety of symptoms ranging from focal neurological deficits to multiple organ failure, with bone pain being the most common symptom. Diagnosis is often delayed [8].

Cardiovascular, pulmonary, and central nervous system involvement significantly affect the prognosis of this disease.

Imaging modalities such as CT scan, PET-CT, brain MRI, and cardiac MRI show different manifestations that aid the diagnosis. These modalities are usually sufficient to confirm the disease [9].

Bone manifestations

Bone involvement occurs in 96% of cases [1,10]. It presents with a typical imaging appearance characterized by bilateral and symmetric diaphyseal-metaphyseal involvement primarily of the long bones of the lower limbs around the knee, known as the “hot knees sign” [2].

Upper limb involvement is also possible. In contrast to Langerhans cell histiocytosis, there is no involvement of the mandible or axial skeleton [1,6].

Radiologic features may include heterogeneous osteosclerosis of cancellous bone, lytic or mixed lesions, endosteal cortical thickening, or loss of corticomedullary differentiation [7]. Bone infarcts may also be present.

These abnormalities are seen on standard radiographs or CT, which allow a more detailed analysis of cortical bone changes, including periosteal and endosteal bone apposition and trabecular changes (thickened trabeculae contributing to bone condensation in diaphyseal-metaphyseal regions) [7,10].

Although not essential, bone MRI can sometimes show bone marrow replacement with hypointensity on T1-weighted images and hyperintensity on T2-weighted images, heterogeneous enhancement depending on fibrous or edematous areas, clear boundaries between healthy and pathological zones, and subchondral sparing. Periostitis may also appear as hyperintense T2-weighted images or linear pericortical enhancement.

Symmetrical metaphyseal-diaphyseal uptake on nuclear scintigraphy is specific to this pathology. However, PET-CT is increasingly replacing bone scintigraphy [6].

The differential diagnosis of bone involvement includes other osteosclerotic diseases such as Paget's disease, lymphoma, metastasis, and chronic osteomyelitis [1,10].

Retroperitoneal involvement

Retroperitoneal involvement, including the kidneys, is observed in 68% of cases [1]. Renal involvement in Erdheim-Chester disease presents with a typical and pathognomonic imaging appearance characterized by bilateral, symmetric, and irregular infiltration of the renal fascia and peri-renal fat, resulting in the “hairy kidney sign” with the risk of bilateral hydronephrosis [2,6,9,11].

The infiltration may also involve the adrenal gland, rarely leading to adrenal insufficiency [9].

This presentation may mimic retroperitoneal fibrosis; however, retroperitoneal fibrosis typically originates from the proximal aorta and progresses upward, whereas Erdheim-Chester disease primarily involves the renal hilum [1]. In addition, Erdheim-Chester disease does not extend to the inferior vena cava [6].

It is also important to note that hematologic pathologies such as lymphoma and extramedullary plasmacytoma may infiltrate perirenal fat [12].

Cardiovascular involvement

The vascular involvement in Erdheim-Chester disease predominantly involves the aorta and presents as the 'coated aorta sign', this manifestation appears circumferential, homogeneous, and regular. It primarily includes the periadventitial layer rather than the vessel wall itself. It typically does not result in arterial diameter abnormalities [1].

Any vascular structure may be affected [11].

Ostial stenoses may develop, particularly in the renal arteries, leading to a risk of renovascular hypertension [6].

Affection of arteries supplying the brain may lead to ischemic strokes [1].

The differential diagnosis for vascular involvement includes Takayasu's arteritis, characterized by transmural vascular inflammation, unlike the predominantly periadventitial involvement in Erdheim-Chester disease.

Cardiac involvement in Erdheim-Chester disease manifests as pericardial infiltration, myocardial and endocardial infiltration [6], myocardial infarction due to coronary infiltration, valvular disease, presence of effusion, cardiomegaly and right atrioventricular groove involvement which should be systematically assessed.

Pericardial infiltration is the most common cardiac manifestation. It occurs in 42% of cases [4,6].

Pulmonary involvement

Lung parenchymal involvement is seen in 25% to 50% of cases [11]. Manifestations include interstitial, alveolar, or combined involvement characterized by smooth septal and fissural thickening, ground-glass and centrolobular nodules or micronodular infiltrates, ground-glass opacities, and cysts. Pleural involvement with effusion or thickening may also occur. Consolidations have also been reported [13,14].

Pulmonary involvement may progress to fibrosis [15].

Isolated pulmonary parenchymal involvement is difficult to differentiate from other pathologies with similar features. Therefore, combining with other pathognomonic features is essential to help make the diagnosis [1].

Neurological involvement

Central nervous system manifestations are seen in 50% of cases [2]. MRI is more sensitive than CT in detecting lesions [8].

Craniocerebral manifestations may include:- Involvement of the hypothalamus-hypophysis axis, often with loss of spontaneous T1 hypersignal in the posterior pituitary due to vasopressin depletion or presence of enhanced infundibular nodules, single or multiple, with thickening of the pituitary stalk after gadolinium injection.

- Meningeal involvement is characterized by multiple focal thickenings and diffuse thickening of the falx, which enhances contrast and may mimic meningiomas.

- Parenchymal involvement often occurs in the subtentorial region, with frequent T2 hyperintensities in the dentate and peri-dentate nuclei and middle cerebellar peduncles [1], with variable enhancement, sometimes accompanied by atrophy of the affected organs [8]. Supratentorial structures and spinal lesions may also be involved [11,15].

- Orbital involvement presents as intraconal or extraconal masses due to histiocyte accumulation, which may cause exophthalmos [1,2].

- Osseous involvement manifests as sclerosing lesions in the sinus walls and cranial vault without osteolysis, in contrast to Wegener's disease [1,2].

Other sites

Skin involvement occurs in 27% of cases [4] and manifests as xanthelasma on the eyelids or periorbital regions. Other less common sites include the visceral organs, thyroid, breast, testes, lymph nodes, and pancreas [1,6,16,17].

Histologic confirmation is essential for the diagnosis, based on a biopsy of peri-renal fat or other relevant site.

Characteristic findings include histiocytic infiltration, fibrosis, and multinucleated Touton giant cells. Immunohistochemistry shows positivity for CD163, CD68, and factor XIIIa and negativity for CD1a and langerin, essential for differentiation from Langerhans cell histiocytosis. The S100 protein is absent in 80% of cases [6,8]. In addition, detection of the BRAF V600 mutation is critical for tailoring treatment.

Approximately 20% of Erdheim-Chester disease cases are associated with Langerhans cell histiocytosis.

Treatment strategies vary according to disease extent and often include interferon-alpha as initial therapy, supplemented by corticosteroids and BRAF inhibitors [6]. Despite therapeutic advances, the prognosis remains poor, with a high mortality rate due primarily to extra-skeletal manifestations. Overall survival rates are 96% at 1 year and 68% at 5 years [1,4,10].

Conclusion

Erdheim-Chester disease is a rare disorder characterized by several pathognomonic signs. Recognition of these signs and increased awareness of the condition are essential to prevent diagnostic delays and improve patient management and prognosis.

Patient consent

Written informed consent was obtained from the patient for publication of his case.

Competing Interests: There are no conflicts of interest declared by any of the authors.
==== Refs
References

1 Kumar P Singh A Gamanagatti S Kumar S Chandrashekhara SH Imaging findings in Erdheim-Chester disease: what every radiologist needs to know Pol J Radiol 83 2018 e54 e62 30038679
2 Benson JC Vaubel R Ebne BA Mark IT Peris Celda M Hook CC Erdheim-Chester disease AJNR Am J Neuroradiol 44 5 2023 505 510 36997288
3 Haroch J. Erdheim-Chester disease La Revue de Médecine Interne 35 11 2014 715 722 24878295
4 Oliveira M Monteiro S Dos Santos J Morais Ferreira R Erdheim-Chester disease: a rare clinical entity Eur J Case Rep Intern Med 7 2020 001630 32908822
5 Alduraibi S.K. A case of Erdheim-Chester disease initially mistaken for retroperitoneal lymphoma Radiol Case Rep 15 5 2020 570 575 32211088
6 Chiocchi M Luciano A De Stasio V Pugliese L Di Donna C Cerocchi M Radiological findings in Erdheim Chester disease: a very rare multisistemic disease Radiol Case Rep 18 5 2023 Mar 26 2047 2054 37006835
7 Pegoraro F Papo M Maniscalco V Charlotte F Haroche J Vaglio A Erdheim-Chester disease: a rapidly evolving disease model Leukemia 34 2020 2840 2857 32591646
8 Emile J-F Abla O Fraitag S Horne A Haroche J Donadieu J Revised classification of histiocytoses and neoplasms of the macrophage-dendritic cell lineages Blood 127 2016 2672 2681 26966089
9 Liu J. Gao L. Pu H. He W. Peng L Erdheim-Chester disease with multisystem involvement evaluated by multimodal imaging: a case report Radiol Case Rep. 17 3 2022 784 789 10.1016/j.radcr.2021.11.076 35024076
10 Mazor R.D. Manevich-Mazor M. Shoenfeld Y. Erdheim-Chester Disease: a comprehensive review of the literature Orphanet J Rare Dis 8 2013 137 24011030
11 Cives M Simone V Rizzo FM Dicuonzo F Cristallo Lacalamita M Ingravallo G Erdheim–Chester disease: a systematic review Crit Rev Oncol Hematol 95 2015 1 11 25744785
12 Purysko AS Westphalen AC Remer EM Coppa CP Leão Filho HM Herts BR Imaging manifestations of hematologic diseases with renal and perinephric involvement Radiographics 36 2016 1038 1054 27257766
13 Haroutunian SG O'Brien KJ Estrada-Veras JI Yao J Boyd LC Mathur K Clinical and histopathologic features of interstitial lung disease in Erdheim–Chester disease J Clin Med 7 2018 243 30154360
14 Mirmomen SM Sirajuddin A Nikpanah M Symons R Paschall AK Papageorgiou I Thoracic involvement in Erdheim–Chester disease: computed tomography imaging findings and their association with the BRAFV600E mutation Eur Radio 28 2018 4635 4642
15 Jeon I. Choi J.H. Isolated thoracic intramedullary Erdheim-Chester disease presenting with paraplegia: a case report and literature review BMC Musculoskelet Disord 22 2021 270 33711983
16 Shah MV Call TG Hook CC Johnston PB Letendre L Colgan JP Clinical presentation, diagnosis, treatment, and outcome of patients with Erdheim–Chester disease: the mayo clinic experience Blood 124 2014 1405
17 Goyal G Ravindran A Liu Y He R Shah MV Bennani NN Bone marrow findings in Erdheim–Chester disease: increased prevalence of chronic myeloid neoplasms Haematologica 105 2020 e84 e86 31624111
