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BRIEF REPORT

BONE CRISIS OF GAUCHER’S DISEASE DUE TO BONE ISCHEMIA: A CASE REPORT

ANNE DAVIDSON, VICTOR KALFF, and PETER F. J

Adult-onset, or type 1, Gaucher’s disease is an autosomal disorder, characterized by deficiency of a lysosomal enzyme, p-glucocerebrosidase. This results in the accumulation of a glycolipid, glucosylceramide, in distinctive “foam” cells which are seen in the bone marrow, reticuloendothelial tissue, and other organs (1). Infiltration of the bone marrow with resulting bone resorption and destruction has been well described previously (2,3); however, the pathogenesis of bone crisis in this disease still remains a subject of conjec- ture. The use of bone scanning may aid in elucidating this problem. We present a case of bone crisis in Gaucher’s disease involving the pelvis, in which an extensive cold area became hot on serial bone scan- ning, suggesting that the lesion was due to ischemia. We also comment on the possible mechanism of this complication.

Case report. A previously well, 19-year-old white man was found to have Gaucher’s disease when his bone marrow was examined in August 1981 follow- ing presentation with recurrent epistaxis and thrombo- cytopenia. Leukocyte p-glucocerebrosidase levels were less than 10% of normal, and screening of the family resulted in the diagnosis of Gaucher’s disease in an asymptomatic brother aged 2 1.

Because of persistent thrombocytopenia (plate-

- From the Departments of Rheumatology and Nuclear Medi-

cine, Alfred Hospital, Prahran, Victoria, Australia. Anne Davidson, MBBS: Fellow in Rheumatology; Victor

Kalff, MBBS, FRACP: Nuclear Medicine Department; Peter F. J. Ryan, MBBS, FRACP: Head, Rheumatology Unit.

Address reprint requests to Dr. P. F. J . Ryan, Department of Medicine, Monash Medical School, Alfred Hospital, Prahran, 3181, Victoria, Australia.

Submitted for publication March 12, 1984; accepted in revised form August 13, 1984.

RYAN

lets 36 x 109/liter), splenectomy was performed in December 1981. The spleen weight was 4,700 gm and tissues from the liver, spleen, and a splenic hilar node biopsy revealed infiltration with Gaucher cells.

He remained well until April 1982 when he presented with a 3-week history of pain in the right hip, associated with fever and anorexia. On admission he looked unwell, was febrile (temperature 38.5”C), and walked with a pronounced right-sided limp.

Examination revealed right hip irritability with pain on passive movement in all directions. Labora- tory investigations revealed leukocytosis of 14.4 X lOY/liter, thrombocytosis of 672 x 109/liter, and an erythrocyte sedimentation rate (ESR) of 47 mm/hour (Westergren). Results of a hip radiograph were normal, and bone scan results using 9 y m T ~ phosphate were normal. Four days following admission, an arth- rotomy was performed at which time a large right hip “honey-like’ ’ effusion was found. The effusion con- tained no inflammatory cells and no organisms were cultured. Synovial biopsy showed no inflammation and no evidence of infiltration by Gaucher cells, and synovial vessels appeared normal on light microscopy. He was started on flucloxacillin therapy, 500 mg every 6 hours, was discharged after 9 days, but was readmit- ted 8 days later with persistent fever. A repeat bone scan showed an area of increased uptake in the right hip, which was attributed to his recent surgery. His temperature returned to normal in 2 days with con- servative measures.

He remained well until February 1983 when he was readmitted with pain in the left iliac crest and the left hip, fever, and anorexia. His temperature was 37.8”C. In addition, new findings of 2 finger-breadths of hepatomegaly and several spider nevi over the chest

Arthritis and Rheumatism, Vol. 28, No. 2 (February 1985)

BRIEF REPORTS 219

were documented. Hemoglobin level was 13.3 gm/dl, white cell count 15.8 x lO’fliter, platelet count 370 X IO’lliter, and ESR 29 mm/hour. Results of a pelvic radiograph were again normal. A bone scan revealed multiple cold areas in the left wing of the ileum, left superior pubic ramus, and superior aspect of the left sacroiliac joint. He was treated with traction and antiinflammatory agents and his condition normalized after 5 days. A repeat bone scan 17 days later showed markedly increased uptake of tracer which corre- sponded to the cold areas on the previous scan (Fig- ures 1 and 2). Three months after discharge, hemostat- ic and platelet function tests were performed on the patient and his affected nonsplenectomized sibling. These test results were normal except that in the splenectomized patient, circulating platelet aggregates were demonstrated to be present by comparing the platelet counts of platelet-rich plasma of blood collect-

ed simultaneously in buffered EDTA and buffered EDTA formalin (circulating platelet aggregate ratio = 0.40; normal range 0.8-1.1).

Discussion. The main clinical manifestations of type 1 Gaucher’s disease are related to infiltration of the liver, spleen, and bone marrow by lipid-laden cells. Hypersplenism and thrombocytopenia are common, and mild anemia and leukopenia may occur (1). Bone marrow infiltration may lead to vertebral compression fractures, pathologic fracture of long bones, or aseptic necrosis, particularly of the femoral heads (2,3).

The sites involved have invariably been at the metaphyseal plate of long bones of children or growing adolescents and reports have noted involvement of femur, tibia, ribs, and clavicle (2-4). The metaphyseal plate in children and adolescents, which is also charac- teristically the site of acute hematogenous osteomyeli- tis (3, has a unique blood supply consisting of non-

Figure 1. 99mTc diphosphonate scans showing views of pelvis. On presentation, the bone scans of the pelvis shown in the anterior (Al) and posterior (Bl) projections demonstrate multiple subtle, but definite, areas of decreased uptake over the sacroiliac crest, acetabulum, and superior pubic ramus of the left hemi-pelvis. Corresponding views taken 17 days later (A2, B2) demonstrate that these abnormal regions now show markedly increased uptake.

220 BRIEF REPORTS

Figure 2. The bone scans of the left and right lateral projections at presentation (Al , B1) and 17 days later (A2, B2).

anastomosing arteriolar loops enclosed by rigid bony walls, which drain into a pool of venous sinusoids with a sluggish blood flow. The epiphyseal bone is also supplied by vascular loops but in contradistinction to the metaphyseal vessels, these anastamose freely with each other. In growing bone, there is no communica- tion between the epiphyseal and metaphyseal blood supply ( 6 ) . Thus, the metaphyseal bone is particularly prone to infarction if the nonanastomosing arcades of vessels are compromised by increased intraosseous tension resulting from infiltrating Gaucher cells, local edema, or subperiosteal hemorrhage. Although bone crisis involving the pelvis has not previously been reported, flat and irregular bones such as the pelvis also have metaphyseal equivalent locations with com- parable vascular arcades bordering epiphyseal growth plates or articular cartilage (6,7) (Figure 3).

Clinically, bone crisis of Gaucher’s disease resembles that of sickle cell disease, which is thought to be related to focal areas of bone ischemia or infarction secondary to thrombosis of small vessels by

Figure 3. Left hemi-pelvis. The metaphyseal-equivalent sites are indicated by broken lines (adapted from Nixon, ref. 7 and descrip- tions by Brookes, ref. 6). Note the excellent correspondence between these sites and the observed scan abnormalities.

BRIEF REPORTS 22 1

sickled cells (8). However, unlike sickle cell disease, bone marrow scintigraphy , using 99mTc-labeled sulfur colloid, appears to have little utility in Gaucher’s disease. In sickle cell disease, there is active bone marrow expansion, and thus, increased uptake of the radiopharmaceutical. Bone marrow infarction can therefore be readily diagnosed by the appearance of areas of diminished uptake in the regions of expanded bone marrow. However, in Gaucher’s disease, there is marrow replacement with characteristic cells which do not take up sulfur colloid and, therefore, there is little or no uptake of the radiopharmaceutical (9). This would therefore make b m e marrow infarction difficult or impossible to discern using this method.

The use of bone scanning in bone crisis of Gaucher’s disease has only been reported on 2 previ- ous occasions. In 1 patient, an area of decreased uptake corresponded to the site of bone pain but no followup scans were performed (9). In the second patient, scans revealed a persistent cold area in the tibia1 plateau corresponding to the site of symptoms. This patient also had a hemorrhagic bursitis of the knee, suggestive of subperiosteal hemorrhage. There was no change in the cold area over a period of 16 months (9). In our patient, serial bone scanning sug- gested local ischemia involving pelvic metaphyseal equivalent sites followed by reactive bone formation 17 days later.

The first episode of bone crisis described in our patient occurred 4 months following splenectomy. The effect of splenectomy on the onset or progression of bone lesions in Gaucher’s disease has been a subject of considerable discussion in the literature, with some authors suggesting an increased incidence of bone lesions in splenectomized patients (2,3,4,10). Silver- stein and Kelly (3) postulate that removal of the spleen could divert large numbers of Gaucher cells to the bone marrow and other reticuloendothelial tissue. In this context, rapidly advancing hepatomegaly has been reported following splenectomy (1 l ) , a finding also noted in our patient. The effect of postsplenectomy thrombocytosis and the presence of increased num- bers of platelet aggregates, as seen in our patient, has not been investigated.

We have reported a case of bone crisis in Gaucher’s disease that involved metaphyseal-equiva-

lent sites of the pelvis in which bone scanning was suggestive of an ischemic lesion. We postulated that the unique blood supply of the growing metaphysis made this area susceptible to ischemic insult and accounted for the age distribution of this complication. Differentiation of bone crisis from osteomyelitis, which also occurs in these patients, is difficult but may be aided by the use of serial bone marrow scanning as in sickle cell disease. Whether bone involvement is accelerated by splenectomy is still a subject of conjec- ture, but it may be possible to delay bony complica- tions in Gaucher’s disease with the use of anti-platelet agents. Further investigation of this area is warranted.

REFERENCES

1. Brady RO, Barranger JA: Glucosyl ceramide lipidosis, Gaucher’s Disease, The Metabolic Basis of Inherited Disease. Fifth edition. Edited by JB Stahbury, JB Wyn- gaarden, DS Fredrickson. New York, McGraw-Hill,

2. Amstutz HC, Carey EJ: Skeletal manifestations and treatment of Gaucher’s disease: review of twenty cases. J Bone Joint Surg 48A:670-701, 1966

3. Silverstein MN, Kelly PJ: Osteoarticular manifesta- tions of Gaucher’s disease. Am J Med Sci 253569-576, 1967

4. Yossipovitch ZH, Herman G, Makin M: Aseptic osteo- myelitis in Gaucher’s disease. Isr J Med Sci 1531-536, 1965

5. Welt S, Rosenthal N, Oppenheimer BS: Gaucher’s splenomegaly with reference to skeletal changes. JAMA

6. Brookes M: Blood Vessels in Bone Marrow, Vascular Patterns: The Blood Supply of Bone, An Approach to Bone Biology. London, Butterworths, 1971, pp 74-81

7. Nixon GW: Hematogenous osteomyelitis of metaphy- seal-equivalent locations. AJR 130: 123-1 29, 1978

8. Espinosa LR, Spilberg I , Osterland CK: Joint manifesta- tions of sickle cell disease. Medicine (Baltimore) 53:295- 305, 1974

9. Cheng TH, Holrnan BL: Radionuclide assessment of Gaucher’s disease. J Nucl Med 19:1333-1336, 1978

10. Gelford G, Bienenstock H: Hemorrhagic bursitis and bone crises in chronic adult Gaucher’s disease. Arthritis Rheum 25:1369-1373, 1982

1 I . Matoth Y, Fried K: Chronic Gaucher’s disease: clinical observations on 34 patients. Isr J Med Sci 1:521-530, 1965

1983, pp 842-856

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