The clinical spectrum of Erdheim-Chester disease: an observational cohort study

Juvianee I. Estrada-Veras, Kevin J. O’Brien, Louisa C. Boyd, Rahul H. Dave, Benjamin H. Durham, Liqiang Xi, Ashkan A. Malayeri, Marcus Y. Chen, Pamela J. Gardner, Jhonell R. Alvarado Enriquez, Nikeith Shah, Omar Abdel-Wahab, Bernadette R. Gochuico, Mark Raffeld, Elaine S. Jaffe and William A. Gahl

Data supplements

Article Figures & Data


  • Figure 1.

    Bone lesions in ECD. The red arrows show: (A) Whole-body bone scan with technetium-99 showing avid uptake in the knees and left hip of an ECD patient. Less intense uptake occurs bilaterally in the humeri and distal tibias. (B) FDG PET-CT scan showing increased FDG uptake in the knees and proximal and distal tibias. (C) Bone radiograph showing cortical osteosclerosis in the right humeri. (D) Bone radiograph showing cortical osteosclerosis in the distal right radius. (E) CT scan of the right knee of an ECD patient showing cortical osteosclerosis and mottled appearance of the bone. (F) MRI scan of the right knee of an ECD patient showing serpiginous areas of T1 signal hypointensity, indicative of osteosclerosis. (G) Panoramic radiograph showing bilateral osteosclerosis of the mandible and maxillary sinus disease.

  • Figure 2.

    Cardiovascular, retroperitoneal, and lung images of ECD patients. (A) Sagittal reconstruction postcontrast CT demonstrates encasement of the thoracic aorta down to the bifurcation. (B) Coronal FDG PET-CT scan showing increased FDG uptake in the thoracic and abdominal aorta. Symmetrically encased kidneys “hairy kidney” showing increased FDG uptake. (C) Axial CT with contrast demonstrates mass-like enhancement encasing the kidneys symmetrically (“hairy kidney”). In addition, there is circumferential encasement and narrowing of the abdominal aorta (arrow). (D) Cardiac CT showing partial encasement of the right coronary artery. (E) Cardiac CT showing partial encasement of the right coronary artery. (F) Axial postcontrast CT image of the upper abdomen demonstrating mass-like perinephric stranding surrounding the kidneys with bilateral hydronephrosis. Hyperdense material within the right collecting system is a ureteral stent. (G) Postcontrast coronal MRI image of the kidneys demonstrating extension of the perinephric mass into the adrenal bed and encasement of the adrenals (arrows). (H) High-resolution CT of the chest showing interstitial fibrosis.

  • Figure 3.

    Brain images in ECD. (A) Axial post contrast brain MRI showing suprasellar and cerebellar involvement in a patient with ECD. (B) Sagittal post contrast brain MRI (from panel A) showing suprasellar and cerebellar tumors in a patient with ECD. (C) Axial fluid attenuated inversion recovery brain MRI showing ECD tumors in cerebral hemispheres. (D) Axial fluid attenuated inversion recovery brain MRI showing ECD tumors in cerebral hemisphere. (E) Sagittal post contrast brain MRI showing an ECD tumor with cystic components in the midbrain-pons of a patient with ECD. (F) T2 fluid attenuated inversion recovery MRI image showing increased symmetrical signal intensity in the cerebellum. (G) Neurodegeneration and atrophy of the cerebellum in a patient with ECD seen on brain MRI. (H) Orbital involvement with tissue accumulation in the intraconal space secondary to histiocytes accumulation in ECD. (I) Orbital involvement showing increased thickening of the lateral rectus muscle. (J) Pituitary stalk is thickened secondary to macrophage accumulation in ECD and deviated to the right. (K) Hematoxylin and eosin stain for brain lesion showing foamy macrophages and inflammation in brain mass biopsy specimen (original magnification ×40). (L) CD68 KP-1 stain of panel K highlighting the foamy macrophages (original magnification ×40).

  • Figure 4.

    Skin findings in ECD. (A) Periorbital xanthelasmas in a patient with ECD. Note mild exophthalmos secondary to retro-orbital mass. (B) Upper lid xanthelasmas are apparent when the patient’s eyes are closed. (C) Skin lesions containing foamy macrophages negative for S-100 protein but with activating ALK gene fusion. (D) Skin lesion positive for BRAF V600E mutation. (E) Foamy macrophages in skin lesion. Inset shows lipid-laden macrophages interspersed with inflammatory cells (original magnification ×20; hematoxylin and eosin stain).


  • Table 1.

    Clinical presentation and treatment of 60 NIH patients with Erdheim-Chester disease

    Case-sexAge (y) at:Presenting findingTreatment
    NIH visitFirst findingsDiagnosis
    1-F201618Knee pain, memory lossPEG-IFN
    2-F302528Scalp nodules, bone painCladribine
    3-F332628Ataxia, blindnessCladribine
    4-F332232Dizziness, weaknessPEG-IFN
    6-M383637Testicular painAnakinra
    8-M393739DI, hypogonadismIFN
    9-M422436DI, bone painIFN
    10-M423242DI, hypogonadismPEG-IFN
    12-M454244Bone painVemurafenib
    13-M454141Bone pain, Horner syndromeDasatinib
    14-M453543Pain, fatigue, depressionTocilizumab
    15-F462644DI, seizuresCladribine
    16-M464343Pain, fatigue, weaknessImatinib
    18-M474047PapilledemaDabrafenib, trametinib
    19-M474344Liver and respiratory failureIFN
    22-M493444DI, ataxiaPEG-IFN
    23-M504046DI, fatigue
    24-F505050Skin nodules, lymph nodes6-MP + Vincristine
    25-M504649Bone painPEG-IFN
    26-M504749Abdominal mass
    27-M514748DI, hypogonadism
    28-M514548Lung surgery, leg painIFN
    29-M515051Bone pain, fatigueIFN
    32-M545152Testicular and bone painIFN
    33-M564051Fatigue, painVemurafenib
    34-M565054Bone lesion, pain
    35-M574650Pain, fatigueIFN
    36-F575353Cardiac tamponade, skin rashCladribine
    37-F574444Periorbital swellingMethotrexate
    38-M585557Pain, fatigue
    39-M584857DI, hypogonadismCyclophosphamide
    40-F584758Skin lesions and rash
    44-F605559Renal artery stenosis, HTAnakinra
    45-M615960Skin nodulesLCH chemotherapy
    46-M615961Bone painIFN
    47-F646264Pericardial effusionCladribine
    50-F646161Abdominal massVemurafenib
    51-M655354Ataxia, proptosisAnakinra
    54-M666464Cerebellar syndrome
    56-M686465Blindness and right-sided weaknessCyclophosphamide
    57-M696868Pain, fatigue, ataxiaMethotrexate
    58-M696768Fatigue, kidney lesionMethotrexate
    60-M747374Incidental imaging findings
    • Of the 60 patients included, 51 were white, 4 were Hispanic, 3 were Middle Eastern, 1 was African American, and 1 was Asian.

    • DI, diabetes insipidus; F, female; IFN, interferon; M, male; PEG-IFN, pegylated interferon.

  • Table 2.

    ECD organ involvement in NIH patients and in the literature

    Organ system and clinical findingsNIH patients,* n (%)Veyssier-Belot et al (%)Haroche et al (%)
    Bone57 (95)NR96
    Kidney39 (65)2768
    Periaortic encasement37 (62)NR66
    Hypogonadism36 (60)NRNR
    Lung31 (52)1443
    Bone pain28 (47)4740
    Maxilla and mandible§24 (47)NRNR
    Diabetes insipidus28 (47)2925
    CNS disease infiltration23 (38)1751
    Retro-orbital area ± exophthalmos15 (27)2925
    Heart (pseudotumor in RA)22 (37)NR19
    Xanthelasma20 (33)1928
    Skin15 (25)10NR
    Pericardial disease5 (8)742
    • CNS, central nervous system; NR, not reported; RA, right atrioventricular groove.

    • * Number of patients out of the 60 patients prospectively investigated.

    • Data included 59 cases (1996).3

    • Data included 122 historical cases (2014).4

    • § Panoramic dental imaging was performed in 51 cases.