Why complete diagnostic imaging for Gaucher disease?

To assess the disease severity of Gaucher disease, a comprehensive evaluation including blood tests and diagnostic imaging should be performed. Diagnostic imaging should include magnetic resonance imaging (MRI) or ultrasound measurement of the liver and spleen volume, and assessment of trabecular and compact bone disease, including radiographs, bone densitometry by dual-energy X-ray absorptiometry (DXA) and MRI to evaluate the severity of bone marrow infiltration.1

Liver and spleen imaging

It is recommended that imaging of the liver and spleen is performed to confirm and extend clinical findings associated with a diagnosis of Gaucher disease. Imaging can also be used to detect parenchymatous lesions (e.g. nodules or sequelae of infarction) and gallstones, which may occur in patients with Gaucher disease.2,3 In general, hepatomegaly is defined as liver mass >1.25-times the estimated normal volume, which is 2.5% of total body weight, and splenomegaly as >0.2% of total body weight in kilograms.4 In patients with intact spleens, hepatomegaly is almost always present but is often not massive unless massive splenomegaly is also present.5 Liver function may be normal in patients, although excess blood bilirubin may be observed in patients of Ashkenazi Jewish ethnicity due to Gilbert syndrome: mild jaundice due to increased amounts of unconjugated bilirubin in the plasma without evidence of liver damage.1,6 Moreover, Gaucher disease has also been linked to hypergammaglobulinaemia and hyperferritinaemia.7

Bone manifestations of Gaucher disease

Bone involvement in Gaucher disease is heterogeneous and, in general, is caused by infiltration of Gaucher cells to bone marrow, extending from the axial to the appendicular skeleton. In Gaucher disease, it is often the lower extremities and proximal sites that are affected, whereas the epiphyses are usually spared, except in patients with advanced disease.8 In most patients with Gaucher disease, bone disease is progressively develops over many years and is considered one of the most debilitating aspects of the disease, affecting quality of life.9


There are at least three different disease processes that contribute to the skeletal manifestations of Gaucher disease10:

  • Focal disease: avascular necrosis and osteosclerosis characterised by infarctions caused by Gaucher cells, thrombosis and possibly inflammatory processes.
  • Local disease: cortical thinning and long bone deformity in areas adjacent to bone marrow infiltration.
  • Generalised osteopaenia: believed to be a result of abnormally high rates of bone resorption and reduced rates of bone formation, which progresses with age and correlates with the overall severity of the disease.

The severity of bone pain can vary between patients with Gaucher disease and may be acute or chronic in nature, and may not always correlate with radiological findings.10 Bone crises are acute episodes of severe skeletal pain associated with fever and oedema, accompanied by leukocytosis and elevated erythrocyte sedimentation rates.10,11 Bone crises can be immobilising and may require bed rest and opiate analgesia.11 The signs and symptoms of a bone crisis may mimic those of osteomyelitis (localised or generalised inflammation due to infection)12; however, toxaemia is not present and blood cultures are negative.13 Consequently, bone crises have also been referred to as pseudo-osteomyelitis and aseptic osteomyelitis.10,13,14 Nevertheless, osteomyelitis has been reported in patients with Gaucher disease and it is important for physicians to distinguish between bone crises and osteomyelitis because the latter is life-threatening.10,15 In general, MRI and radionuclide bone and bone marrow scintigraphy can provide information to separate bone crises from osteomyelitis 1‒3 days after pain onset.11

Patients with Gaucher disease may experience Erlenmeyer flask deformity (Figure 1); however, this is not necessarily a symptom of the disease and is not specific to Gaucher disease. This deformity is caused by an impairment of remodelling of the metaphyseal and tubular bones and manifests as flaring of the distal lateral aspects of the femur and proximal tibia causing a flask-like appearance.10,11 Erlenmeyer flask deformity is typically asymptomatic but can be observed in many of the tubular or long bones of the skeleton, and even in the phalanges of some patients with Gaucher disease. However, Erlenmeyer flask deformity does not affect bones of the skull.11

In both children and adults with Gaucher disease, a reduction in bone mass or osteopaenia is common and is associated with an increased risk of bone fractures.10,16 Patients with severe osteopaenia may develop pathological fractures of the ribs and weight-bearing bones, as well as vertebral compression fractures, which can lead to rounding of the spine and restrictive lung problems and neurological deficits as a result of nerve compression.8 The pathophysiology of osteopaenia in Gaucher disease is not clearly understood, as most patients exhibit normal serum concentrations of calcium, phosphorus, γ-carboxy-glutamic acid-protein (bone-GLA protein) and immunoreactive parathyroid hormone; urinary calcium and hydroxyproline excretions are also typically normal.17 These findings suggest that increased, localised bone resorption, rather than a generalised derangement of bone turnover, may have a greater effect on inducing osteopaenia.8 Evidence of osteopaenia is apparent at sites adjacent to bone marrow infiltration by Gaucher cells, but is not limited to these areas as it can also affect trabecular and cortical bone in either a localised or diffuse manner.10

Avascular necrosis (or osteonecrosis) is believed to be secondary to ischaemia due to chronic infarction (Figure 1). It is bone death, which mainly affects the femoral head, proximal humerus and vertebral bodies. Once the necrotic process of avascular necrosis begins, the process is irreversible and can cause fracture and joint collapse in patients with Gaucher disease.10

As a result of aberrant remodelling of the bone following bone infarction, deposition of calcium into the bone can occur and cause osteosclerosis. These infarctions are often very painful and can occur in patients with both mild and severe bone disease.10,17

Gaucher disease should be considered in the differential diagnosis of a patient with bone manifestations, such as bone pain, osteopaenia, osteoporosis, osteolytic lesions, bone infarcts, avascular necrosis and fractures; although, rarely patients with acute osteomyelitis.9

Figure 1.
Examples of Erlenmeyer flask deformity and avascular necrosis in patients with Gaucher disease. Reproduced with permission from Simpson WL et al. World J Radiol 2014; 6: 657-668.18

Bone imaging

For newly diagnosed patients, a thorough assessment of the skeleton is important as patients may have bone complications, even in the absence of visceral disease or skeletal symptoms.10 In general, regular assessment of bone mineral density (BMD), bone marrow infiltration and the axial skeleton and searching for potential malignancy is recommended for patients with Gaucher disease. Use of MRI is recommended to monitor skeletal involvement in Gaucher disease as it can provide semi-quantitative assessment of bone marrow infiltration, in addition to the degree of bone infarction. Monitoring of painful acute bone crises and avascular necrosis using plain X-ray is considered of limited value. Therefore, if MRI is not available, DXA of the lumbar spine and left and right hips is recommended in patients with Gaucher disease, with careful protocols designed to exclude focal disease. Serial follow-ups using the same standardised instrument are also recommended.11

Histologically, the appearance of infiltrated bone marrow in Gaucher disease is heterogeneous.11 Pathological examination of the femoral head shows areas of vital bone adjacent to bone marrow that has been infiltrated by Gaucher cells. In addition, the femoral head also reveals areas of non-specific chronic inflammation and fibrosis, areas of necrosis in osteocyte-free regions of bone and areas of normal haematopoietic marrow.19 The extent of bone marrow infiltration by Gaucher cells can be evaluated semi-quantitatively from MRI data of the spine, pelvis and lower limbs by using the BMB score.11

In Gaucher disease, the predominant MRI characteristic of infiltrated bone marrow is low signal intensity on T1-, T2- and T2*-weighted images. T2*-weighted images are determined in relation to signal intensity of subcutaneous fat.20 An increase in signal intensity may be observed on T2-weighted images, which is thought to reflect active bone marrow disease.20,21 For both the lumbar spine and femoral head, higher BMB scores indicate more severe bone involvement.20

In Gaucher disease, low mineral bone mass can be detected by DXA as reduction in BMD.11,22 In adults, DXA should be performed at the lumbar spine (L1 to L4) and hip (total hip or femoral neck). In children aged ≥5 years, DXA should be performed at the lumbar spine and total body (minus head), considering methodological precision and least significant change detectable by individual equipment. DXA measurements include bone mineral content (g), area (cm2) and BMD (g/cm2). Z-scores should be used to interpret DXA: this is the difference between the individual’s measured value of BMD and the mean general population score in younger individuals. Z-scores below ‒2 indicate reduced BMD. In post-menopausal women and in men aged >50 years, BMD is expressed as T-scores, which are calculated in relation to young adults of the same gender. This is interpreted using the World Health Organization classification of osteopaenia (T-score between ‒1 and ‒2.5) and osteoporosis (T-score less than ‒2.5). A scan of total body (minus head) is mandatory in children with Gaucher disease, although measurement of femoral BMD is unreliable because of the high variability in skeletal maturity, bone size and pubertal stage.11

C-ANPROM/INT//7567; Date of preparation: September 2020