Consensus guidelines for the diagnosis and clinical management of Erdheim-Chester disease

Abstract

Erdheim-Chester disease (ECD) is a rare, non-Langerhans histiocytosis. Recent findings suggest that ECD is a clonal disorder, marked by recurrent BRAFV600E mutations in >50% of patients, in which chronic uncontrolled inflammation is an important mediator of disease pathogenesis. Although ∼500 to 550 cases have been described in the literature to date, increased physician awareness has driven a dramatic increase in ECD diagnoses over the last decade. ECD frequently involves multiple organ systems and has historically lacked effective therapies. Given the protean clinical manifestations and the lack of a consensus-derived approach for the management of ECD, we provide here the first multidisciplinary consensus guidelines for the clinical management of ECD. These recommendations were outlined at the First International Medical Symposium for ECD, comprised of a comprehensive group of international academicians with expertise in the pathophysiology and therapy of ECD. Detailed recommendations on the initial clinical, laboratory, and radiographic assessment of ECD patients are presented in addition to treatment recommendations based on critical appraisal of the literature and clinical experience. These formalized consensus descriptions will hopefully facilitate ongoing and future research efforts in this disorder. (Blood. 2014;124(4):483-492)

Tocilizumab in patients with multisystem Erdheim–Chester disease

“…Changes in target lesions were evaluated by comparing baseline and post-treatment PET/ CT images, by means of a side-by-side image analysis to evaluate dimensional as well as FDG uptake changes. 7,16 Similarly, follow-up cardiac and cerebral MRIs were compared to baseline images, and lesion size was measured before treatment and during follow-up evaluations. Coated aorta, pericardial effusion, and pseudotumoral atrial infiltration were measured at the first and last visits.…”

“…1,4,5 Interferon (IFN)-a is the first-line treatment for ECD, but efficacy is limited against severe manifestations, specifically CNS and cardiovascular involvement. 6,7 Recent evidence indicates that deregulated activation of the mitogen-activated protein kinase (MAPK) pathway due to oncogenic mutations in the BRAF, NRAS, PIK3CA, and MAP2K1 genes is central to the pathogenesis of ECD. [8][9][10] Following these discoveries, treatment with small-molecule inhibitors of BRAF V600E (vemurafenib) or MEK (cobimetinib, trametinib) came to fruition (reviewed in 11 ).…”

Tratamiento con sirolimus y prednisona en enfermedad de Erdheim-Chester con compromiso cardiaco: Caso clínico

“…Frecuentemente existe compromiso cardiovascular, que puede ser asintomático y detectarse en RM y/o scanner [2][3][4] . Las anormalidades más frecuentes son: a) recubrimiento de la aorta por un manguito de tejido-pudiendo comprometer sus ramas; b) infiltración pericárdica, que puede manifestarse por pericarditis, derrame pericárdico, taponamiento cardiaco o pericarditis constrictiva.…”

“…Las anormalidades más frecuentes son: a) recubrimiento de la aorta por un manguito de tejido-pudiendo comprometer sus ramas; b) infiltración pericárdica, que puede manifestarse por pericarditis, derrame pericárdico, taponamiento cardiaco o pericarditis constrictiva. Menos frecuentemente se observa: c) infiltración miocár-dica-pudiendo originar insuficiencia cardiaca; d) infiltración de la aurícula derecha semejando un tumor cardiaco; e) infiltración de los sulcus aurículo-ventriculares, septum interauricular y lecho peri-coronario-pudiendo originar infartos; f) valvulopatías aórtica y mitral-produciendo regurgitación; g) anormalidades de la conducción o arritmias [3][4][5][6] . La falla cardiaca inducida por la fibrosis miocárdica y/o el compromiso pericárdico son las principales causas de muerte 7 .…”

“…En ellos se han ensayado drogas antineoplásicas, biológicas e inmunosupresoras 3,7,[10][11][12][13][14][15][16][17][18][19][20][21] .…”