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Gaucher's disease
Gaucher’sdisease Report
of a case
Andrew E. Michanowicx, B.S., D.D.S.,* John P. Michanowicz, and Gary M. Stein, B.A., D.D.S.,*++ Pittsburgh, Pa., and New York, N. Y.
D.D.S.,+*
I
n 1882 Gauche? first described a disease that he considered to be malignant and gave it the name epithelioma de la rate (primary epithelioma of the spleen). He noted splenohepatomegaly and found the splenic pulp entirely replaced by large, pale cells. During the years that followed, several other investigators found these cells in the retroperitoneal lymph nodes and the skeleton. In 1913 Mandelbaum and Downey2 founded the modern concept of this disease as a fault in metabolism, and in 1924 Lieb3 succeeded in finding the metabolic disturbance. According to his findings, this condition is inborn and is due to the faulty storage of a lipoid substance called kerasin, a cerebroside, which is stored in the foam cells of the reticuloendothelial system. These foam cells have been given the name of Gauche& cells. Epstein and Lorenz’ established that all diseases of the xanthomatosis group (Gaucher’s disease, Schiiller-Christia,n disease, Neimann-Pick disease, Tay-Sachs disease, and xanthomatosis of the skin) are caused by a disturbance of the lipoid metabolism. Gauche& disease is generally found in white persons, although a few cases have been reported in Negroes5 This disease has been reported in children as young as 1 week6 and in adults as old as ‘79 years,’ which is contrary to the thinking that the primary occurrence is generally in children aad young adults. Jewish people seem to be most susceptible to this disease. Reich and associatesX and Groeng report a predominance of this disease in female patients.lO, I1 Groeng suggests that Ga.ucher’s disease is a mutation which is transmitted as a “simple dominant hereditary trait.” Gaucher’s disease is recognized as a progressive weakness with minor hcmorrhagic diathesis associated with spleno- or hepatomegaly. Most patients are gen*Assistant Professor, Department of Dental Medicine and Endodontics, University Pittsburgh School of Dentistry. *“Attending Endodontist, Montefiore Hospital, Pittsburgh, Pa. ***Graduate Student in Periodontics, New York University, New York, N. Y.
36
of
Volume 23 Number
Gaucher’s
disease
37
1
erally asymptomatic, despite the progressive disturbances of their metabolism. Actually, little evidence of the disease may be found through physical diagnosis. Often all that is present is a generalized weakness, a distended abdomen associated with splenomegaly, an uneven brownish pigmentation of the skin (especially in exposed areas), and vague joint or bone pain with an associated swelling and tenderness over the involved areas. Certain blood changes are generally seen in patients with Gaucher’s disease. PicklO reports these changes to be, first, leukopenia due to a reduction in polymorphonuclear leukocytes or lymphocytes and, second, hypochromic a.nemia. Often thrombocytopenia is present ea.rly in the disease and is related to hemorrhagic diathesis found in the late stages of the disease. Gaucher’s cells are not found in the bloodstream but may be demonstrated by a splenic or bone-marrow biopsy, and they may also invade the lymph nodes aad liver. Bleeding of the nose and gingiva may be recognized, and sometimes there is hematemesis, uterine bleeding, and hemorrhage into connective tissue, muscle, or skin upon the slightest trauma. PicklO reports that, roentgenographically, bones affected by this disease appear less opaque because of the generalized atrophy and deficiency of calcium. These bones .have a coarse-grained and worm-eaten appearaace because of their extreme porosity. Cancellous bone shows large defects, together with a marked thinning of the cortex. Pick cites the most common roentgenographic changes as collapse and deformity of the head of the femur, the Erlenmeyer-flask appearance of the shaft of the femur, the compression of the lower vertebrae, and generalized osteoporosis. The Erlenmeyer-flask appearance of the shaft of the femur is considered to be pathognomonic. Benderlll I2 cites several cases involving generalized porosity in the mental region of the mandible, pseudocystic areas of radiolucency in the premolar and molar region of the mandible, and areas of osteolysis in the maxillary premo1a.r region. The areas of radiolucency on both sides are not uniform in the normal mandible, and this is the point of differentiation between the normal and pathologic states. Bender also noted that bone regeneration occurs after curettement of bones and extractions. In the maxilla osteolytic areas were observed primarily in the premolar region. Shira,13 in 1947, took specimens from the mandible of Bender’s first reported case and demonstrated the presence of Gaucher’s cells in the osteolytic areas. In 1953 Moch14 examined a biopsy specimen of a, mandibular lesion and reported Gauche& cells. As far as can be determined, these are the only two cases on record in which Gaucher ‘s cells have been isolated in the mandible by direct examination. Levine and Solis-CohenI” report generalized vacuolation and osteoporosis of the mandible. These numerous unilocular vacuolated spaces are due to the replacement of bone by Gauche& cells. The areas of rarefa,ction are sharply delineated by trabeculae and are diffusely distributed throughout the mandible. Levine and So&-Cohen believe that when diffuse areas of osteolysis are noticed on a roentgenogram, the possibility of Gaucher’s disease should be considered. We concur with Tassmer and BenderI that, because of the lack of early clinical symptoms and because the bone changes take place early and rapidly, the dentist
may be the first to detect Gancher’s disease during ;I routine roeut.genographic examination. CASE REPORT A 21-year-old white male Jewish college student was admitted to the hospital on Dec. 7, 1963, complaining of pain, tenderness, and swelling over the left maxilla of 3 days’ duration. Since the time of onset, the swelling ha,d become progressively more severe. There was evidence of periorbital edema and swelling of the eyelid, but there was no palpable adenopathy and the patient had no direct pain suggestive of orbital involvement. Upon questioning of the patient’s mother, it was learned that the patient had a welldocumented17 case of Gaucher’s disease. He had been admitted to the hospital at the age of 6 years when his mother noticed that his abdomen was increasing in size and becoming progressively harder and that the boy was complaining of transient joint pains. A splenectomy was performed and a diagnosis of Gaucher’s disease was made. The patient had made subsequent visits to the hospital for treatment of pain and swelling of the joint,s of the extremities. Physical
examination
The patient a.ppeared to be alert but small in stature and poorly nourished for his adult age. He reported easy fatigability, a tendency to bruise easily, difficulty in gaining weight despite a good appetite, and difficulty in moving the left lower extremity. The patient was generally depressed over the limitations of his disease. There was no family history of Gaucher’s disease, chronic infection, or blood dyscrasia. A staff hematologist17 reported that the patient exhibited myopia and a palpable liver 3 to 4 cm. below the costal margin, but hc found no rashes, abnormal sweating patterns, chest pains, or evidence of pingueculae, pigmentation, hemoptysis. Laboratory
and roentgenographic
data
The laboratory findings were as follows: Hemoglobin-15 Hematocrit-45 Urine-Negative White blood count-22,650 Pobymorphonuclear leukocytes-49 Lymphocytes-21 Monocytes-9 Basophil-1 Bleeding time-2 minutes Clotting time-6 minutes Platelet count-299,000 Prothrombin time-lZ”C/15”P Uric scid-4.4 Acid phosphatase-1.7 A blood smear revealed a mncrocytic anemia with anisocytosis and pleomorphism plus many target cells and basket cells. A bone-marrow specimen of the left iliac crest was found to contain Gaucher’s cells. Roentgenographically, the bones of the skull and pelvis appeared normal. There were aseptic necrosis of the left femoral head (Fig. 1) and borderline changes on the right femoral neck and shaft. The acetabulum on the left side showed evidence of irregularities along its medial and inferior portions. There was a severe bilateral coxa vara deformity. The distal end of the left femur exhibited the Erlenmeyer-flask deformity consistent with Gaucher’s disease (Fig. 2). Dental
examination
A full-mouth periapical roentgenographic examination (Fig. 3) lesions in the maxillary right first and second premolars, the maxillary
revealed large carious left second molar, the
Gaucher’s disease 39
Volume 23 Number 1
showing irregular and radiolucent areas Fig. I, Roentgenogram portion of lead on left side of femur. Right side appears normal.
Fig. d. Characteristic
Erlenmeyer-flask
deformity
of distal
throughout
end of left
femur
is apparent.
OS, 0.x & 02. .January,
Fig. 3. Roentgenograms taken in February, molar, maxillary left second molar, mandibular premolar. Osteoporosis of mandible is evident.
1967
1964, disclose lesions on mandibular lci’t first right third molar., and maxillary right srtotltl
Fig.
Figs. 4 and 5. Periapical roentgenograms area disclosing osteoporosis and generalized
of right side of mandible vacuolation.
in premolar
and molar
mandibular right third molar, and the mandibular left first molar. In addition, there were numerous smaller carious lesions involving many of the remaining maxillary and mandibular teeth. There wore radiolucent areas circumscribing the apices of the mandibular right third molar and the mesial root of the mandibular left first molar, and an area of condensing osteitis circumscribed the distal root of the mandibular left first molar. Generalized vacuolation and osteoporosis were evident in the mandible (Figs. 3, 1, and 5).
Surgical treatment in patients with Gaucher’s disease may lead to hemorrhagic complications, especially in cases in which splenectomy has not been performed.12 Consultation with a hematologist prior to surgical intervention is advised. The clinical and roentgenographie examination findings were reviewed by the general
Volume 23 Number 1
Gaucher’s
disease
41
Fig. 6. Periapical roentgenograms taken 16 months postoperatively show complete healing following endodontic treatment of maxillary right second premolar and extraction of maxillary right second molar, mandibular left first molar, and mandibular left third molar. practitioner, endodontist, oral surgeon, and hematologist. It was concluded that, in view of the possible hemorrhagic complications that might arise, endodontic treatment rather than extraction should be considered wherever possible. The maxillary right second premolar was treated endodontically following control of the buccal swelling. Extraction of the mandibular right third molar, the mandibular left first molar, and the maxillary left second molar was advised, since asepsis was not feasible because of extensive coronal root caries. The extractions were performed under a local anesthetic, without complications. Healing was apparent in full-mouth roentgenograms taken 16 months after the endodontic treatment and extractions (Fig. 6). At this time it was observed that movement of the lower left extremities was more restricted; the patient dragged his left leg more than he had the previous year, indicating possible progressive degeneration of the acetabulum.
SUMMARY
A ease of Gaucher’s disease in a 21-year-old patient has been reported. The pathognomonic Erlenmeyer-flask a*ppearance of the shaft of the femur was observed, and generalized osteoporosis was apparent roentgenographically in the mandible. The patient was treated endodontically and surgically, without complications, aad roentgenographic examination 16 months postoperatively revealed apparent healing. It is noted that this patient had undergone a splenectomy at an early age ; thus, the chances of hemorrhagic complications were reduced. REFERENCES
1. Gaucher, P. C. E.: Del’epithelioma primitiff de la rate, Hypertrophie Idiopathique de la rate sari leucemie, These de Paris, 1882. 2. Mandelbaum, F. S., and Downey, H.: The Histopathology and Biology of Gaucher’s Disease (Large Cell Splenomegalia), Folia haemat. 20: 139, 1916. 3. Lieb, H.: Cerebrosidspeicherung bei Splenomeglie Typus Gaucher, Ztschr. physiol. Chem. 140: 305, 1924. 4. Epstein, E., and Lorenz, K. : Die Phosphatidzellverfettung der Milz bei Neimann-Pickscher Krankheit verglichen mit der Lipoidchemie des Morbus Gaucher und der Schiiller-Christianschen Krankheit, Ztschr. physiol. Chem. 192: 145., 1930. 5. Choisser, R. M., and Montgomery, R. R.: Gaucher’s Dmease in a Negro, Am. J. Clin. Path. 19: 570, 1949. 6. Hoffman, 5. J., and Makler, M. I.: Gaucher’s Disease; Review of the Literature and Report of a Case Diagnosed From a Section of an Inguinal Lymph Gland, Am. J. Clin. Path. 13: 260. 1943.
O.S.!O.M. &I0.1’. January, 1967 7. Petit, J. V., and Sehleicher, E. M. : “Atypical” Gauc*her’s I)isewe, .
of a case
Andrew E. Michanowicx, B.S., D.D.S.,* John P. Michanowicz, and Gary M. Stein, B.A., D.D.S.,*++ Pittsburgh, Pa., and New York, N. Y.
D.D.S.,+*
I
n 1882 Gauche? first described a disease that he considered to be malignant and gave it the name epithelioma de la rate (primary epithelioma of the spleen). He noted splenohepatomegaly and found the splenic pulp entirely replaced by large, pale cells. During the years that followed, several other investigators found these cells in the retroperitoneal lymph nodes and the skeleton. In 1913 Mandelbaum and Downey2 founded the modern concept of this disease as a fault in metabolism, and in 1924 Lieb3 succeeded in finding the metabolic disturbance. According to his findings, this condition is inborn and is due to the faulty storage of a lipoid substance called kerasin, a cerebroside, which is stored in the foam cells of the reticuloendothelial system. These foam cells have been given the name of Gauche& cells. Epstein and Lorenz’ established that all diseases of the xanthomatosis group (Gaucher’s disease, Schiiller-Christia,n disease, Neimann-Pick disease, Tay-Sachs disease, and xanthomatosis of the skin) are caused by a disturbance of the lipoid metabolism. Gauche& disease is generally found in white persons, although a few cases have been reported in Negroes5 This disease has been reported in children as young as 1 week6 and in adults as old as ‘79 years,’ which is contrary to the thinking that the primary occurrence is generally in children aad young adults. Jewish people seem to be most susceptible to this disease. Reich and associatesX and Groeng report a predominance of this disease in female patients.lO, I1 Groeng suggests that Ga.ucher’s disease is a mutation which is transmitted as a “simple dominant hereditary trait.” Gaucher’s disease is recognized as a progressive weakness with minor hcmorrhagic diathesis associated with spleno- or hepatomegaly. Most patients are gen*Assistant Professor, Department of Dental Medicine and Endodontics, University Pittsburgh School of Dentistry. *“Attending Endodontist, Montefiore Hospital, Pittsburgh, Pa. ***Graduate Student in Periodontics, New York University, New York, N. Y.
36
of
Volume 23 Number
Gaucher’s
disease
37
1
erally asymptomatic, despite the progressive disturbances of their metabolism. Actually, little evidence of the disease may be found through physical diagnosis. Often all that is present is a generalized weakness, a distended abdomen associated with splenomegaly, an uneven brownish pigmentation of the skin (especially in exposed areas), and vague joint or bone pain with an associated swelling and tenderness over the involved areas. Certain blood changes are generally seen in patients with Gaucher’s disease. PicklO reports these changes to be, first, leukopenia due to a reduction in polymorphonuclear leukocytes or lymphocytes and, second, hypochromic a.nemia. Often thrombocytopenia is present ea.rly in the disease and is related to hemorrhagic diathesis found in the late stages of the disease. Gaucher’s cells are not found in the bloodstream but may be demonstrated by a splenic or bone-marrow biopsy, and they may also invade the lymph nodes aad liver. Bleeding of the nose and gingiva may be recognized, and sometimes there is hematemesis, uterine bleeding, and hemorrhage into connective tissue, muscle, or skin upon the slightest trauma. PicklO reports that, roentgenographically, bones affected by this disease appear less opaque because of the generalized atrophy and deficiency of calcium. These bones .have a coarse-grained and worm-eaten appearaace because of their extreme porosity. Cancellous bone shows large defects, together with a marked thinning of the cortex. Pick cites the most common roentgenographic changes as collapse and deformity of the head of the femur, the Erlenmeyer-flask appearance of the shaft of the femur, the compression of the lower vertebrae, and generalized osteoporosis. The Erlenmeyer-flask appearance of the shaft of the femur is considered to be pathognomonic. Benderlll I2 cites several cases involving generalized porosity in the mental region of the mandible, pseudocystic areas of radiolucency in the premolar and molar region of the mandible, and areas of osteolysis in the maxillary premo1a.r region. The areas of radiolucency on both sides are not uniform in the normal mandible, and this is the point of differentiation between the normal and pathologic states. Bender also noted that bone regeneration occurs after curettement of bones and extractions. In the maxilla osteolytic areas were observed primarily in the premolar region. Shira,13 in 1947, took specimens from the mandible of Bender’s first reported case and demonstrated the presence of Gaucher’s cells in the osteolytic areas. In 1953 Moch14 examined a biopsy specimen of a, mandibular lesion and reported Gauche& cells. As far as can be determined, these are the only two cases on record in which Gaucher ‘s cells have been isolated in the mandible by direct examination. Levine and Solis-CohenI” report generalized vacuolation and osteoporosis of the mandible. These numerous unilocular vacuolated spaces are due to the replacement of bone by Gauche& cells. The areas of rarefa,ction are sharply delineated by trabeculae and are diffusely distributed throughout the mandible. Levine and So&-Cohen believe that when diffuse areas of osteolysis are noticed on a roentgenogram, the possibility of Gaucher’s disease should be considered. We concur with Tassmer and BenderI that, because of the lack of early clinical symptoms and because the bone changes take place early and rapidly, the dentist
may be the first to detect Gancher’s disease during ;I routine roeut.genographic examination. CASE REPORT A 21-year-old white male Jewish college student was admitted to the hospital on Dec. 7, 1963, complaining of pain, tenderness, and swelling over the left maxilla of 3 days’ duration. Since the time of onset, the swelling ha,d become progressively more severe. There was evidence of periorbital edema and swelling of the eyelid, but there was no palpable adenopathy and the patient had no direct pain suggestive of orbital involvement. Upon questioning of the patient’s mother, it was learned that the patient had a welldocumented17 case of Gaucher’s disease. He had been admitted to the hospital at the age of 6 years when his mother noticed that his abdomen was increasing in size and becoming progressively harder and that the boy was complaining of transient joint pains. A splenectomy was performed and a diagnosis of Gaucher’s disease was made. The patient had made subsequent visits to the hospital for treatment of pain and swelling of the joint,s of the extremities. Physical
examination
The patient a.ppeared to be alert but small in stature and poorly nourished for his adult age. He reported easy fatigability, a tendency to bruise easily, difficulty in gaining weight despite a good appetite, and difficulty in moving the left lower extremity. The patient was generally depressed over the limitations of his disease. There was no family history of Gaucher’s disease, chronic infection, or blood dyscrasia. A staff hematologist17 reported that the patient exhibited myopia and a palpable liver 3 to 4 cm. below the costal margin, but hc found no rashes, abnormal sweating patterns, chest pains, or evidence of pingueculae, pigmentation, hemoptysis. Laboratory
and roentgenographic
data
The laboratory findings were as follows: Hemoglobin-15 Hematocrit-45 Urine-Negative White blood count-22,650 Pobymorphonuclear leukocytes-49 Lymphocytes-21 Monocytes-9 Basophil-1 Bleeding time-2 minutes Clotting time-6 minutes Platelet count-299,000 Prothrombin time-lZ”C/15”P Uric scid-4.4 Acid phosphatase-1.7 A blood smear revealed a mncrocytic anemia with anisocytosis and pleomorphism plus many target cells and basket cells. A bone-marrow specimen of the left iliac crest was found to contain Gaucher’s cells. Roentgenographically, the bones of the skull and pelvis appeared normal. There were aseptic necrosis of the left femoral head (Fig. 1) and borderline changes on the right femoral neck and shaft. The acetabulum on the left side showed evidence of irregularities along its medial and inferior portions. There was a severe bilateral coxa vara deformity. The distal end of the left femur exhibited the Erlenmeyer-flask deformity consistent with Gaucher’s disease (Fig. 2). Dental
examination
A full-mouth periapical roentgenographic examination (Fig. 3) lesions in the maxillary right first and second premolars, the maxillary
revealed large carious left second molar, the
Gaucher’s disease 39
Volume 23 Number 1
showing irregular and radiolucent areas Fig. I, Roentgenogram portion of lead on left side of femur. Right side appears normal.
Fig. d. Characteristic
Erlenmeyer-flask
deformity
of distal
throughout
end of left
femur
is apparent.
OS, 0.x & 02. .January,
Fig. 3. Roentgenograms taken in February, molar, maxillary left second molar, mandibular premolar. Osteoporosis of mandible is evident.
1967
1964, disclose lesions on mandibular lci’t first right third molar., and maxillary right srtotltl
Fig.
Figs. 4 and 5. Periapical roentgenograms area disclosing osteoporosis and generalized
of right side of mandible vacuolation.
in premolar
and molar
mandibular right third molar, and the mandibular left first molar. In addition, there were numerous smaller carious lesions involving many of the remaining maxillary and mandibular teeth. There wore radiolucent areas circumscribing the apices of the mandibular right third molar and the mesial root of the mandibular left first molar, and an area of condensing osteitis circumscribed the distal root of the mandibular left first molar. Generalized vacuolation and osteoporosis were evident in the mandible (Figs. 3, 1, and 5).
Surgical treatment in patients with Gaucher’s disease may lead to hemorrhagic complications, especially in cases in which splenectomy has not been performed.12 Consultation with a hematologist prior to surgical intervention is advised. The clinical and roentgenographie examination findings were reviewed by the general
Volume 23 Number 1
Gaucher’s
disease
41
Fig. 6. Periapical roentgenograms taken 16 months postoperatively show complete healing following endodontic treatment of maxillary right second premolar and extraction of maxillary right second molar, mandibular left first molar, and mandibular left third molar. practitioner, endodontist, oral surgeon, and hematologist. It was concluded that, in view of the possible hemorrhagic complications that might arise, endodontic treatment rather than extraction should be considered wherever possible. The maxillary right second premolar was treated endodontically following control of the buccal swelling. Extraction of the mandibular right third molar, the mandibular left first molar, and the maxillary left second molar was advised, since asepsis was not feasible because of extensive coronal root caries. The extractions were performed under a local anesthetic, without complications. Healing was apparent in full-mouth roentgenograms taken 16 months after the endodontic treatment and extractions (Fig. 6). At this time it was observed that movement of the lower left extremities was more restricted; the patient dragged his left leg more than he had the previous year, indicating possible progressive degeneration of the acetabulum.
SUMMARY
A ease of Gaucher’s disease in a 21-year-old patient has been reported. The pathognomonic Erlenmeyer-flask a*ppearance of the shaft of the femur was observed, and generalized osteoporosis was apparent roentgenographically in the mandible. The patient was treated endodontically and surgically, without complications, aad roentgenographic examination 16 months postoperatively revealed apparent healing. It is noted that this patient had undergone a splenectomy at an early age ; thus, the chances of hemorrhagic complications were reduced. REFERENCES
1. Gaucher, P. C. E.: Del’epithelioma primitiff de la rate, Hypertrophie Idiopathique de la rate sari leucemie, These de Paris, 1882. 2. Mandelbaum, F. S., and Downey, H.: The Histopathology and Biology of Gaucher’s Disease (Large Cell Splenomegalia), Folia haemat. 20: 139, 1916. 3. Lieb, H.: Cerebrosidspeicherung bei Splenomeglie Typus Gaucher, Ztschr. physiol. Chem. 140: 305, 1924. 4. Epstein, E., and Lorenz, K. : Die Phosphatidzellverfettung der Milz bei Neimann-Pickscher Krankheit verglichen mit der Lipoidchemie des Morbus Gaucher und der Schiiller-Christianschen Krankheit, Ztschr. physiol. Chem. 192: 145., 1930. 5. Choisser, R. M., and Montgomery, R. R.: Gaucher’s Dmease in a Negro, Am. J. Clin. Path. 19: 570, 1949. 6. Hoffman, 5. J., and Makler, M. I.: Gaucher’s Disease; Review of the Literature and Report of a Case Diagnosed From a Section of an Inguinal Lymph Gland, Am. J. Clin. Path. 13: 260. 1943.
O.S.!O.M. &I0.1’. January, 1967 7. Petit, J. V., and Sehleicher, E. M. : “Atypical” Gauc*her’s I)isewe, .