Throwing a spotlight on under-recognized manifestations of Gaucher disease: Pulmonary involvement, lymphadenopathy and Gaucheroma

Abstract

Background: Gaucher disease (GD) is a rare lysosomal storage disorder classically subdivided into type 1 (non-neuronopathic) GD, and types 2 and 3 (neuronopathic) GD. It is typically characterized by clinical manifestations including anemia, thrombocytopenia, hepatosplenomegaly, bone lesions, and (in more severe forms) neurological impairment. However, less-commonly reported and often under-recognized manifestations exist, which potentially have a significant impact on patient outcomes. Greater efforts are needed to understand, recognize, and manage these manifestations.

Objectives: This review provides a synthesis of published information about three under-recognized GD manifestations (pulmonary involvement, lymphadenopathy, and Gaucheroma) and recommends diagnostic, management, and treatment strategies based on the available literature and author experience. The authors aim to raise awareness about these serious, progressive, and sometimes life-threatening conditions, which are often diagnosed late in life.

Conclusions: Little is known about the incidence, pathophysiology, prognostic factors, and optimal management of pulmonary involvement, lymphadenopathy, and Gaucheroma in patients with GD. Enzyme replacement therapy (ERT) has shown limited efficacy for the prevention and treatment of these manifestations. More research is needed to evaluate the potential effect of substrate reduction therapy (SRT) with glucosylceramide synthase (GCS) inhibitors, and to develop additional approaches to treat these GD manifestations. Improvements in data collection registries and international data-sharing are required to better understand the impact of these manifestations on GD patients, help develop effective management strategies, and, ultimately, improve patient outcomes.

Keywords: Gaucher disease; Gaucheroma; Lymphadenopathy; Protein-losing enteropathy; Pulmonary hypertension; Pulmonary involvement.