Final diagnosis
Gaucher's disease with bone crisis
Differential diagnosis
None.
Discussion
Gaucher disease is the most common lysosomal storage disorder
Gaucher disease is due to a deficiency in the enzyme glucocerebrosidase. It is an inborn error of glycosphingolipid metabolism. Enzymatic deficiency leads to an accumulation of glucocerebroside within the lysosomes of macrophages, giving the cytoplasm an appearance of wrinkled tissue paper.
The accumulation of Gauchers cells produces a multisystemic disease characterized by involvement of the liver, spleen and bone marrow.
The changes in the bone marrow in Gaucher Disease, are a combination of infiltration, edema and ischemia.
When bone marrow is infiltrated by Gaucher cells, they cause reduction of signal intensity on both T1 and T2-weighted. Gaucher cells- infiltrate contains glucocerebrosides and also protein and other components contributing to decrease signal intensity. In this case the total fat content in bone marrow is reduced.
Typically, there is a major infiltration of the lumbar spine but less involvement of the lower extremities. With disease progression, gaucher cells infiltration extends distally and signal intensity becomes more attenuated. Marrow replacement proceeds centrifugally from the axial to the appendicular parts of the skeleton. The infiltration tend to involve the metaphysis first and the epiphysis last. In the majority of cases, the epiphysis are preserved, and the extension of affected marrow, correlates with the severity of disease. We can see epiphyseal involvement correlated with severe disease The bone marrow in Gaucher Disease may present an homogeneous or a non-homogeneous pattern of infiltration, or the signal intensity may be homogeneously o non homogeneous decreased.
The increased signal on T2 is due to increased water within the marrow cavity, corresponding to the bone marrow edema pattern while bone crisis. Bone crisis are presumably due to ischemic necrosis causing acute infarction of a large segment of bone.
Bone crisis are acute episodes of skeletal pain and fever, localised in long bones, most often in distal femur, proximal tibia and humerus. Bone crises are common in the first two decades of life although patients of all ages may be affected. The incidence varies from 23 to 40% in tipe 1 patients.
They are called pseudo-osteomyelitis or aseptic osteomyelitis because of the non-infectious nature. Bone crisis are presumably due to ischemic necrosis causing acute infarction of a large segment of bone.
At 4-6 weeks, plain films can demonstrate in some cases a fine periosteal elevation because of fluid accumulation. Sometimes plain film is normal and MRI is the best method for early diagnosis.
Enzyme replacement theraphy (using the placental-derived (alglucerase) or recombinant (imiglucerase) preparation), produces an hematopoietic reconstution and resolution of hepatosplenomegaly.
Skeletal regeneration has been reported, as a increased mineralization on diaphysis, resolution of cortical and periostium infiltrations, and improvements of bone crisis.
Subjective bone pain and bone crises may be the firt to show improvement, and have been reported to be decreased or absent at 3-4 months.
Some authors (Rosenthal, Barton ) relate a marked improvement in marrow composition (increase of fat fraction), with increased cortical thickness and trabecular bone density after 42 months of high dose treatment. Barton have reported a gradual return to normal histological appearance of marrow, by bone biopsies after two years of treatment.
The response to theraphy appears to be more rapid in children, probably due to the faster turnover of the developing skeleton.
The skeletal responses to enzyme therapy are slower than the hematological and visceral changes, and may be dependent on the degree of bone involvement at the time theraphy is initiated. The marrow infiltration, may be reversible with enzyme therapy prior to the developpment of ischemic severe changes and necrosis. The effect may be limited when the administration is delayed and there are irreversible bone changes.
Gaucher disease is classified into three types. Type 1 (non neuronopatic), type 2 (acute neuronopatic), and type 3 (subacute neuronopatic. Initial presentation may be from early childhood to eight decade, along 10 to 40 years. First symptoms may be anemia, thrombocytopenia and hepatosplenomegaly.
Skeletal involvement is a major cause of morbidity in patiens with Gaucher Disease. Approximately 80% of patiens have some degree of bone involvement.