A scale for patient-reported symptom assessment for patients with Erdheim-Chester disease

Abstract

Erdheim-Chester disease (ECD) is an ultra-rare hematologic neoplasm characterized by somatic mutations of the MAPK pathway and by accumulation of lesional histiocytes within tissues. Clinical phenotypes and sites of disease involvement are heterogenous in ECD, and no tool exists for systematic and comprehensive assessment of ECD symptomatology. We describe a collaborative effort among ECD specialists, patient-reported outcome (PRO) methodologists, and ECD patients to develop the Erdheim-Chester Disease Symptom Scale (ECD-SS): a symptom inventory for clinical ECD care and evaluation of ECD therapies. Methodologically rigorous focus groups led to the identification of 63 ECD symptoms in 6 categories, incorporated into the ECD-SS with respect to both severity and frequency. Among 50 ECD patients participating in a prospective registry study completing the ECD-SS, 46 (92%) reported neurological/psychological symptoms, 29 (58%) reported pain, and at least one-half reported mood symptoms, memory problems, or fatigue. Symptoms were highly frequent or almost constant regardless of their severity. The ECD-SS is a rigorously developed, patient-centered tool that demonstrates the wide and previously unappreciated burden of symptomatology experienced by ECD patients. Further studies will refine the symptom inventory and define its psychometric properties and role in clinical care and investigation in the context of ECD.

Cerebellar ataxia and exercise intolerance in Erdheim-Chester disease

“…The presence of cognitive impairment has been reported in one third of neuro-ECD patients [2], but the pathogenesis is still poorly understood. In a recent analysis of patient-reported outcomes of 50 prospectively enrolled ECD patients, attention and memory appeared impaired in 52% of the cohort [22]. A retrospective volumetric neuroimaging study of 11 ECD patients without recognizable supratentorial CNS lesions demonstrated a substantial reduction of cerebral gray matter volumes in ECD patients as compared to matched controls [23].…”

An Unusual Case of Myasthenia-Like Presentation in Erdheim-Chester Disease

“…The presence of cognitive impairment has been reported in one third of neuro-ECD patients (2), but the pathogenesis is still poorly understood. In a recent analysis of patient-reported outcomes of 50 prospectively enrolled ECD patients, attention and memory appeared impaired in 52% of the cohort (12). A retrospective volumetric neuroimaging study of 11 ECD patients without recognizable supratentorial CNS lesions demonstrated a substantial reduction of cerebral gray matter volumes in ECD patients as compared to matched controls (13).…”

Highlights of the Management of Adult Histiocytic Disorders: Langerhans Cell Histiocytosis, Erdheim-Chester Disease, Rosai-Dorfman Disease, and Hemophagocytic Lymphohistiocytosis

“…Constitutional symptoms in the form of fever, weight loss, fatigability, and sweating were found in 28% of patients with ECD. 13 We reported a case of ECD with a 50-kg weight loss and no skeletal bone involvement. 14 …”

“…Cobimetinib is used at dose of 20 to 60 mg daily for 21 days as part of a 28-day cycle. 13 Patients on MEK inhibitors can suffer from cardiac and retinal toxicities, therefore echocardiogram and retinal exam are recommended. Some cases may have rare ALK, NTRK, RET fusions or CSF1R mutations, and specific kinase inhibitors may be considered for those situations as available.…”