- Email: [email protected]
Gaucher's disease
GAUCHER'S DISEASE ]JEWIS ]-I.
SPIEGEL, D . D . S . , ~ CEDARtlURST, N . W.
Review of the Literature 1 reported a disease which he called "epithelimna de la r a t e . " I Nlie1882wasGaucher under the impression that it was a neoplasm. It was subsequently found to be a rare familial disorder of the lipoid metabolism, characterized by the deposition of kerasin, a eerebroside identified by Lieb, 2 in the reticulum cells of the retieuloendothelial system. These ceils take oll a typical appearance and are called Gaueher's cells. Thoma 3 states: " T h e y occur in bundles and are elongated and spindle shaped, and reveal sharp striations. They may measure twenty to eighty microns and are polymorphous with single or multiple nuclei placed near the border. The cytoplasm appears wrinkled rather than foamy due to an irregular network visible under high power. It stains light blue with Mallory's stain." This disease is found mostly in Jewish patients of all ages, with a ratio of two to one favoring females. 4 Any part of the reticuloendothelial system may be involved, but the spleen, liver, deep lymph nodes, and bone marrow are nlost commonly involved, as shown by Pick '~ in 1933. Because ot' the infiltration of Gaueher's cells. first the spleen and then the liver enlarges; this may begin in childhood and is progressive. The spleen becomes palpable and has a characteristic rounded edge on the border. The superficial lymph nodes remain normal in size. There are characteristic changes in the blood due to the invasion of Gaueher's cells in the bone marrow. There may be a leukopenia followed by a hypoehromic anemia. If there is a thromboeytopenia present, it is a secondary manifestation, and, if present, there may be spontaneous bleeding from the nose and gingiva. Bleeding, clotting, and coagulation times are usually normal. Two eases have been reported without leukopenia; one is described in this case report and the other was reported in 1954 by I)eVries and Izaih 6 in Jerusalem. Because of the ehronicity of the disease, patients may go along for years without any major symptoms. 7 However, SOlne develop pains in the femur and tibia which, upon x-ray, show areas of radiolucency which is sometimes mistaken for osteomyelitis as reported by Welt, Rosenthal, and Oppenheimer. s In many cases pinguecualae of the conjunetiva and cornea are present but this is not constant, as Hoffman and Makler 9 found only fourteen cases out of eighty-nine in which this was evident. Reported before the New York I n s t i t u t e of Clinical Oral P a t h o l o g y , Nov. 21. 1955. * A t t e n d i n g Oral Surgeon, St. Joseph's Hospital, F a r 1Roekaway, New York, and Mid Is]and General Hospital, Bethpage, New York. 15S
Volumel0 Number 2
GAUCHER'S DISEASE
159
Hemorrhagic petechiae are sometimes noted in the conjunctiva. Bronzing of the skin and brown spots may be present, according to Comroe, Collins, and Crane. 1~ The bone changes were first described by Pick, 5 who stated that the bone seemed to be less opaqued in the radiogram because of the generalized atrophy and calcium deficiency. They appear coarse-grained and wormeaten because of the extreme porosity. The cancellous bone may show large defects, together with a thinning of the cortex. Collapse and deformity of the head of the femur arc visible in the x-ray picture; clublike appearance of the lower femur is often a characteristic finding. 11 It was Bender, 12 a dentist, who first reported radiographic bone changes in the jaws in 1935. In the mandible there is a generalized porosity with areas of radiolucence which are eystlike in appearance, especially in the premolar and molar regions. These are m)t uniform on both sides as in a normal mandible, and that is the point of differentiation between normal and abnormal. In the maxilla there may be osteolytie areas seen mostly in the premolar region. It is interesting to note that Shira, la in 1947, took specimens from the mandible of Bender's first reported ease and demonstrated the presence of Gauehcr's cells, which confirmed tl~e original a priori evidence on her humerus24 In 1953 Moth 1~ reported the second case with Gaucher's cells shown in a specimen from the mandible. These are the only two cases ever reported with direct evidence shown microscopically from specimens from the mandible. Cahn? ~ in commenting on Moeh's ease, stated: " T h e roentgenograms, while most interesting, were not specific for any definite entity. I have seen a simila,' picture in a ease of agenesis and infantilism. Large bilateral radiolucent areas in the mandible may represent deposits of hematopoietie m a r r o w . " Because of the lack of clinical symptoms in the early stages of the disease and because bone changes take place very early, the dentist may be the first to detect Gaucher's disease during routine x-ray examination. ~7 There is no specific cure for Gaueher's disease. Santee ~s has reported favorable results with splenectomy in sixteen cases out of t h i r t y ; however, he also reported an operative mortality rate of 20 per cent. Sehein and Arkin ~ have reported that there are periods of remission during which the patient is quite free from all symptoms and that during acute symptoms their treatment of the disease consists primarily of bed rest. In 1952 Elliot 1'~ described a ease complicated by pregnancy. There was a normal full-term delivery; however, the mother almost lost her life due to hemorrhage. This is the only reported successful fuil-term delivery of a child from a mother with Gaucher's disease. This disease is one of the xanthomatosis group which includes Gaueher's disease, Sehiiller-Christian disease, Niemann-Piek disease, Tay-Saehs disease, and xanthomatoses of the skin. Epstein and Lorenzo ~~ established that each of the above was caused by a disturbance of the lipoid metabolism, which represents an inborn error of the general metabolism of the system.
Case Report On J u n e 21, 1955, a 19-year-old J e w i s h girl, well developed, well nourished, and in a p p a r e n t l y excellent health: was r e f e r r e d for removal of the tissue flap over the p a r t i a l l y
]60
SPIEGEL
o. s,, o. M., & O. P.
February, 19r,7
erupted, normally positioned lower right third molar (Fig. 1). She had been treated by her dentist f o r a pericoronitis the week before. During t h a t time he had referred her to her family physician for parenteral penicillin therapy as an adjunct to his local treatment. She responded well to his treatinent. [ntraoral examination revealed a full complement of teeth, with the excel)lion of the erupting third molar~. Mouth hygietle was excellent; teeth were in good repair, with uo mobility; a].u('eas membranes wt,re II()rllllkl in appearant'e; and gingival tissues were firm and pink. There was some evidence of irritation in the h)wer right lhird molar area. P a s t hist()ry was essentially negative. She had had the usual childhoo,l diseases. Approximately m~e year before, during a routine medical examination, sbe was tohl that: she w'ts sliffhtl/ attemic and was ~iven liver and iron tal)lets. No I)lood stml 3- w,ts done.
Fig. 1.--Normally positioned lower right third molar, from which small ocelusal tissue flap was removed. Also note porosity and loss of trabeeulae of body of mandible,
Family history was essentialiy negative. The patie~Jt's mother, father~ and brother were living atnt all were in apparent good health. Her habits and environment are those of a normal 19-year-ohl girl of a well-to-do family. She was engaged and planned to be married in two months. Site was somewhat tired because of the constant rm,nd of social activities a t t e n d i n g the forthcoming marriage. She had not lost any weiffht and had no complaints except fur the pericoronitis the week before. Under 0.25 c.c. Xylocaine 1:50,000 epinephrine infiltration anesthesia, a small piece of tissue (at)out 1/25 inch in diameter) was removed with a scalpel, exposing the crown of the lower third molar; there was very little bleeding at this time. Probably, had this tissue been removed by electric e a u t e r / , there wouhl have been no subsequent blee, ling and this disease would not have been diagnosed at this time. The patient appeared for postoperative Ireatment the following day art(1 reported no disconffort or swelling, bt~t a constant oozing of blood. L o c a l application of Adrenalin chloride 1:1,000 stopped tile bleeding. The following day site reported t h a t within two hours a f t e r leaving the office on the previous day the bleeding started and that, while not copious, it was constant. Again topical application of Adrenalin chloride 1:1~000 stopped the oozing, but only temporarily. She was put (m Adrenosem Satieylatej 5 rag. tablets every two hours. '/?his was ineffective. There was a great deal of ecchymosis into the surrounding soft tissues. She was referred to her physician for a complete blood work-up, l i e did only a bleeding time, coagulating tim% clot, retraction time, and hemoglobin determination, and stated t h a t all were within normal limits, l i e considered the
Volume Number
10 .~
GAUCHER'S
DISEASE
]6]
O
o
o
a k0 o
1 62
SPIEGEL
o, s.. o. M., &O. P. February, 1957
10.5 grams per 100 c.c. hemoglobin normal for this patient. Ke was again requested to do a complete blood work-up with specific reference to the platelct count, as he was told t h a t a hemorrhagic disease was suspected because of the constant oozing which was not norula] a f t e r such minor surgery. He protested vehemently and stated that, as f a r as he was concerned, the p a t i e n t was perfectly normal and t h a t ~'it is not uncommon to bleed ~fter dental surgery. '~ The patient was then referred to a helaatologist. On the fourth post:operative (lay the bleeding stopped completely. Com]plete radiographic examinatiotJ of the maxilla and mandible revealed an abnormal radiolucency in the mandible, showing a loss of trabeculae, especially in the premolar and molar regions on both sides (Fig. 2). In the maxilla there was osteo]ysis in the left premolar region (Fig. 3).
Fig. 3.--Osteolysis in left upper premolar region.
Hematologist's R e p o r t . - - P h y s i c a l examination ou dtme 30, 1[~55, revealed a welldeveloped, well-nourished white gir]~ aged 19 years~ who did not appear acutely or chronically ill She had noted easy f a t i g a b i l i t y from time to time. F a s y bruisability ham been noted throughout the p a t i e n t ' s early childhood and adolescence. There have been no menstrual (lifflctilties and no prolonged bleeding. The fml,li were normal. The conjunctivae revealed I)ilateral pinguecalae. A small hemorrhagic petechia was noted in the right lower eon junetiva. The nose was externally clear. The right lower giugiva, posteriorly, had been incised aml a slight amotmt of bteedlng ooze was ~wted. The breasts were natural; the axillae were clear. The heart was nonttal. Tile neck was flaccid. There were no masses. The liver was palpable at the costal margin. The abdomen was soft. The spleen was palpable tit the costal margin and presented a reran(l, firm et]ge. Resolving ecchylnoses were noted between the knees and the ankles along the pretibial aspects of both lees. The following hematologic data were ol)tainc~]: Hemoglobin Red blood cells White blood cells Nonsegmented Segmented Eosinophils Basophils Lymphocytes Monoeytes Reticulocytes
10.7 (~rnl, per cent 3.7 million 7,200 3
57 9
I 26 4 2.3 per cent
(There was slight anise- and poikilocytosis of the red blood cells. mature cells were noted on the smear.)
No at)normal o1' im-
VoIume 10 Number 2
GAUCI-IE~r
163
DISEASE
Platelets 87,000--Normal 250~000 to 500,000 Sedimentation rate (Wintrobe 20 corrected) Hematocrit 33 M e a n corpuscular volume 89 (82-92) 1~ean corpuscular hemoglobin 32.5 (32-36) concentration ~fean corpuscular hemoglobin 29 (28-32) Blood type time.
' ' O ' ' Rh n e g a t i v e
I h a v e examined the p a t i e n t ' s serum and find no Rh antibodies to be present at this The following coagulation profile was obtained: Bleeding time (Duke-Earlobe) 5' 30" (1-4) Recalcification 300" (60-120) Rumpel-Leede +Clot r e t r a c t i o n - - b e g u n 30' ( w i t h i n 1 hour) complete in 2 hours ( w i t h i n 24 hours) Clot quality Pair (A moderate s e d i m e n t a t i o n of red cells is noted at the b o t t o m of the test tube.) Prothrombin 15 (control 15) Lee-White coagulation 12' (8-18) P r o t h r o m b i n consumption 28" ( g r e a t e r t h a n 45") (3 hours) (From the above data, it is evident t h a t a thrombocytopenic purpura is present.)
Bone m a r r o w aspiration was performed a t the level of the t h i r d sternal segment. The outer t a b l e was normal in consistency. The marrow c a v i t y was entered easily, l~[arrow was readily a s p i r a t e d and spread on slides. A review of the aspirated m a r r o w revealed G a u c h e r ' s cells, singly and in groups, s c a t t e r e d t h r o u g h o u t the smear. The over-all cellularity of the bone m a r r o w smear was good. M e g a k a r y o c y t e s were present, some of which showed p l a t e l e t formation. The following differential p a t t e r n was noted: Blasts Neutro-myeloeytes Nonsegmented Segmented Eosin-myelocytes Nonsegmented Segmented Lymphocytes P l a s m a cells Reticulum cells Reticulo-endothelial cells G a u e h e r ' s cells Proerythroblasts Erythroblasts lqormoblasts
1.2 714.8 24.0 13.6 3.2 1.2 0.8 710.4 1.6 0.4 1.~ 0.4 2.(] 4.0 20.5
(The above bone marrow is diagnostic of Gaucher's disease. p u r p u r a is also present.)
A secondary thrombocytopenic
The patient was admitted to the Long Island Jewish Hospital where f u r t h e r work-up was obtained: Blood, urea, nitrogen Bromsulphalein sodium Total protein Albumin Globulin
17 rag. per cent 6 per cent r e t e n t i o n a f t e r 45 rain. 7.1 Gin. per cent 3.6 3.5
(Eleetrophoresis of the serum is being performed but the results are not yet available.)
] 64
SPIEGEL
o . s . . o. M., a o. l ). Fcbrt~ar~', I~)$7
Fig. 4 . - - T y p i c a l h,~ion of C a u c h e r ' s d i s e a s e i~l d i s t a l t h i r d of r i g h t f e m u r .
Fig'. 5 . - - J , o s s o f t r a b e c u l a e an(] p o r o s i t y of r i g L t mandiblc~
Volume l0 Number 2
GAUCHER'S DISEASE
165
Chest x-ray was negative. Skeletal x-rays of skull and long bones were t a k e n and have not been completely reported as yet. However, a lesion typical of G a u c h e r ' s disease was found in the distal t h i r d of the r i g h t f e m u r (Fig. 4).
Diagnosis: Gaucher's disease with secondary thromboeytopenic purpura and moderate normocytic normoehromie anemia. Prognosis: As to life, the prognosis is excellent for ten to thirty years. Gradual continuing enlargement of liver and spleen are expected. Secondary hypersplenism may necessitate splenectomy at some future date. Therapy: Expectant and supportive. X-radiatlon is of no value at this time. ued observation and re-evaluation will be r~ecessary.
Contin-
Comments and Discussion This case is important for three reasons: 1. The final diagnosis of Gauehcr's disease was made only because of the insistence of the oral surgeon, over the objections of the family physician, that a complete work-up be done. 2. Because the disease was discovered in a comparatively early stage of this girl's life, if she now becomes pregnant her physician, knowing that she has Gaueher's disease, can attempt to maintain her health with supportive therapy and t r y to effect a full-time delivery. 3. Gaucher's disease is rare; only 250 cases have been reported in the literature, as estimate'd by Croen. ~
Summary A case of Gaueher's disease in a 19-year-old Jewish girl has been described. The diagnosis was made only because of the oral surgeon's insistence that a complete examination be done, despite the lack of clinical symptoms. It is apropos to repeat Shira's is conclusions in his article entitled "Manifestations of Systemic Disorders in t:he Facial Bones"" " M a n y systemic disorders may cause changes in the facial bones. Although the diagnosis and treatment of many of these disturbances are definitely out of their province, the dentist and oral surgeon should be aware of the possibility of these abnormal conditions and be able to recognize the more common forms. They should be able to decide whether or not the disturbance is of odontogenic or of local origin and should have a knowledge of the proper procedures to follow in arriving at a correct diagnosis."
References 1. Gaucher, P. C . E . : De l ' e p i t h e l i o m a p r i m i t i f de la rate, hypertrophic idiopathique de la rate sans leucemie, These de Paris, 1882. 2. Lieb, H.: Ztschr. f. physiol. Chem. 115: 305, 1924. 3. Thoma, K. H.: Oral Pathology, ed. 3, St. Louis, 1950, The C. V. Mosby Company, p. 819. 4. Geschickter, C. F., and Copeland, 1~[./~[.: Tumors of Bone, Philadelphia, 1949, J. B. Lippincott Company, p. 566. 5. Pick, L.: Am. J. M. Sc. 185: 453, 1933. 6. DeVries, A., and Izaih, G.: Blood 10: 291, 1955. 7. Schein, A. J., a n d Arkin, A . M . : J-. Bone & J o i n t Surg. 9.4: 396, 1942.
] 66
SPIEGEL
o.s., o. M., & O. I"
February. 1957
8. Welt, S., Rosenthal, N., and Oppenheimer~ B . S . : Gaucher's Splenomegaly With Special Reference to Skeletal Changes, J. A. M. A. 99.: 637, 1929. 9. Hoffman, S. S., and Makler, M . I . : Am. J. Dis. Child. 38: 775, 1929. 10. Comroe, B. L., Collins, L. I-I., and Crane, M . P . : Internal Medicine ill Dental Practice, Philadelphia, ]938, Lea & Febiger, p. ]8]. ]1. Prinz, H., and Greenbaum, S. S.: Diseases of the Month and Their Treatment, c,t. 2~ Philadelphia, ]942, Lea & Febiger, p. 301. 12. Bender, I. B.: Dental Observations in Gaueher's Disease, 3. ]). Res. 17: 5, 193~. ]3. Shira, R . B . : J. Oral Surg. 11: 291, 1953. 14. Bender, I . B . : Personal Communication, December, 1955. 15. Moch, W . S . : ORAL SURG.,ORALMED., AND ORALPATI{. 6: 1250, 1953. 16. Cahn, L . R . : ORAL SURG., ORAL MED., AND ORALPATH. 6: 1253, 1953. ]7. Tassman, G. C., and Bender, I . B . : J. Am. Dent. A. 27: 1270, 1940. 18. Santee, H . E . : J. New York Surg. Soc., May, 1927, p. 20i. ]9. Elliot, Y.F.: Canad. %f. A. J. 66: 166, 1952. 20. Epstein, E , and Lorenz, K.: Ztschr. f. physiol. Chem. 192: 145~ 1930. 21. Groen, J.: Blood 3: ]238, ]948. 650 CENTRAl, AVI<.
SPIEGEL, D . D . S . , ~ CEDARtlURST, N . W.
Review of the Literature 1 reported a disease which he called "epithelimna de la r a t e . " I Nlie1882wasGaucher under the impression that it was a neoplasm. It was subsequently found to be a rare familial disorder of the lipoid metabolism, characterized by the deposition of kerasin, a eerebroside identified by Lieb, 2 in the reticulum cells of the retieuloendothelial system. These ceils take oll a typical appearance and are called Gaueher's cells. Thoma 3 states: " T h e y occur in bundles and are elongated and spindle shaped, and reveal sharp striations. They may measure twenty to eighty microns and are polymorphous with single or multiple nuclei placed near the border. The cytoplasm appears wrinkled rather than foamy due to an irregular network visible under high power. It stains light blue with Mallory's stain." This disease is found mostly in Jewish patients of all ages, with a ratio of two to one favoring females. 4 Any part of the reticuloendothelial system may be involved, but the spleen, liver, deep lymph nodes, and bone marrow are nlost commonly involved, as shown by Pick '~ in 1933. Because ot' the infiltration of Gaueher's cells. first the spleen and then the liver enlarges; this may begin in childhood and is progressive. The spleen becomes palpable and has a characteristic rounded edge on the border. The superficial lymph nodes remain normal in size. There are characteristic changes in the blood due to the invasion of Gaueher's cells in the bone marrow. There may be a leukopenia followed by a hypoehromic anemia. If there is a thromboeytopenia present, it is a secondary manifestation, and, if present, there may be spontaneous bleeding from the nose and gingiva. Bleeding, clotting, and coagulation times are usually normal. Two eases have been reported without leukopenia; one is described in this case report and the other was reported in 1954 by I)eVries and Izaih 6 in Jerusalem. Because of the ehronicity of the disease, patients may go along for years without any major symptoms. 7 However, SOlne develop pains in the femur and tibia which, upon x-ray, show areas of radiolucency which is sometimes mistaken for osteomyelitis as reported by Welt, Rosenthal, and Oppenheimer. s In many cases pinguecualae of the conjunetiva and cornea are present but this is not constant, as Hoffman and Makler 9 found only fourteen cases out of eighty-nine in which this was evident. Reported before the New York I n s t i t u t e of Clinical Oral P a t h o l o g y , Nov. 21. 1955. * A t t e n d i n g Oral Surgeon, St. Joseph's Hospital, F a r 1Roekaway, New York, and Mid Is]and General Hospital, Bethpage, New York. 15S
Volumel0 Number 2
GAUCHER'S DISEASE
159
Hemorrhagic petechiae are sometimes noted in the conjunctiva. Bronzing of the skin and brown spots may be present, according to Comroe, Collins, and Crane. 1~ The bone changes were first described by Pick, 5 who stated that the bone seemed to be less opaqued in the radiogram because of the generalized atrophy and calcium deficiency. They appear coarse-grained and wormeaten because of the extreme porosity. The cancellous bone may show large defects, together with a thinning of the cortex. Collapse and deformity of the head of the femur arc visible in the x-ray picture; clublike appearance of the lower femur is often a characteristic finding. 11 It was Bender, 12 a dentist, who first reported radiographic bone changes in the jaws in 1935. In the mandible there is a generalized porosity with areas of radiolucence which are eystlike in appearance, especially in the premolar and molar regions. These are m)t uniform on both sides as in a normal mandible, and that is the point of differentiation between normal and abnormal. In the maxilla there may be osteolytie areas seen mostly in the premolar region. It is interesting to note that Shira, la in 1947, took specimens from the mandible of Bender's first reported ease and demonstrated the presence of Gauehcr's cells, which confirmed tl~e original a priori evidence on her humerus24 In 1953 Moth 1~ reported the second case with Gaucher's cells shown in a specimen from the mandible. These are the only two cases ever reported with direct evidence shown microscopically from specimens from the mandible. Cahn? ~ in commenting on Moeh's ease, stated: " T h e roentgenograms, while most interesting, were not specific for any definite entity. I have seen a simila,' picture in a ease of agenesis and infantilism. Large bilateral radiolucent areas in the mandible may represent deposits of hematopoietie m a r r o w . " Because of the lack of clinical symptoms in the early stages of the disease and because bone changes take place very early, the dentist may be the first to detect Gaucher's disease during routine x-ray examination. ~7 There is no specific cure for Gaueher's disease. Santee ~s has reported favorable results with splenectomy in sixteen cases out of t h i r t y ; however, he also reported an operative mortality rate of 20 per cent. Sehein and Arkin ~ have reported that there are periods of remission during which the patient is quite free from all symptoms and that during acute symptoms their treatment of the disease consists primarily of bed rest. In 1952 Elliot 1'~ described a ease complicated by pregnancy. There was a normal full-term delivery; however, the mother almost lost her life due to hemorrhage. This is the only reported successful fuil-term delivery of a child from a mother with Gaucher's disease. This disease is one of the xanthomatosis group which includes Gaueher's disease, Sehiiller-Christian disease, Niemann-Piek disease, Tay-Saehs disease, and xanthomatoses of the skin. Epstein and Lorenzo ~~ established that each of the above was caused by a disturbance of the lipoid metabolism, which represents an inborn error of the general metabolism of the system.
Case Report On J u n e 21, 1955, a 19-year-old J e w i s h girl, well developed, well nourished, and in a p p a r e n t l y excellent health: was r e f e r r e d for removal of the tissue flap over the p a r t i a l l y
]60
SPIEGEL
o. s,, o. M., & O. P.
February, 19r,7
erupted, normally positioned lower right third molar (Fig. 1). She had been treated by her dentist f o r a pericoronitis the week before. During t h a t time he had referred her to her family physician for parenteral penicillin therapy as an adjunct to his local treatment. She responded well to his treatinent. [ntraoral examination revealed a full complement of teeth, with the excel)lion of the erupting third molar~. Mouth hygietle was excellent; teeth were in good repair, with uo mobility; a].u('eas membranes wt,re II()rllllkl in appearant'e; and gingival tissues were firm and pink. There was some evidence of irritation in the h)wer right lhird molar area. P a s t hist()ry was essentially negative. She had had the usual childhoo,l diseases. Approximately m~e year before, during a routine medical examination, sbe was tohl that: she w'ts sliffhtl/ attemic and was ~iven liver and iron tal)lets. No I)lood stml 3- w,ts done.
Fig. 1.--Normally positioned lower right third molar, from which small ocelusal tissue flap was removed. Also note porosity and loss of trabeeulae of body of mandible,
Family history was essentialiy negative. The patie~Jt's mother, father~ and brother were living atnt all were in apparent good health. Her habits and environment are those of a normal 19-year-ohl girl of a well-to-do family. She was engaged and planned to be married in two months. Site was somewhat tired because of the constant rm,nd of social activities a t t e n d i n g the forthcoming marriage. She had not lost any weiffht and had no complaints except fur the pericoronitis the week before. Under 0.25 c.c. Xylocaine 1:50,000 epinephrine infiltration anesthesia, a small piece of tissue (at)out 1/25 inch in diameter) was removed with a scalpel, exposing the crown of the lower third molar; there was very little bleeding at this time. Probably, had this tissue been removed by electric e a u t e r / , there wouhl have been no subsequent blee, ling and this disease would not have been diagnosed at this time. The patient appeared for postoperative Ireatment the following day art(1 reported no disconffort or swelling, bt~t a constant oozing of blood. L o c a l application of Adrenalin chloride 1:1,000 stopped tile bleeding. The following day site reported t h a t within two hours a f t e r leaving the office on the previous day the bleeding started and that, while not copious, it was constant. Again topical application of Adrenalin chloride 1:1~000 stopped the oozing, but only temporarily. She was put (m Adrenosem Satieylatej 5 rag. tablets every two hours. '/?his was ineffective. There was a great deal of ecchymosis into the surrounding soft tissues. She was referred to her physician for a complete blood work-up, l i e did only a bleeding time, coagulating tim% clot, retraction time, and hemoglobin determination, and stated t h a t all were within normal limits, l i e considered the
Volume Number
10 .~
GAUCHER'S
DISEASE
]6]
O
o
o
a k0 o
1 62
SPIEGEL
o, s.. o. M., &O. P. February, 1957
10.5 grams per 100 c.c. hemoglobin normal for this patient. Ke was again requested to do a complete blood work-up with specific reference to the platelct count, as he was told t h a t a hemorrhagic disease was suspected because of the constant oozing which was not norula] a f t e r such minor surgery. He protested vehemently and stated that, as f a r as he was concerned, the p a t i e n t was perfectly normal and t h a t ~'it is not uncommon to bleed ~fter dental surgery. '~ The patient was then referred to a helaatologist. On the fourth post:operative (lay the bleeding stopped completely. Com]plete radiographic examinatiotJ of the maxilla and mandible revealed an abnormal radiolucency in the mandible, showing a loss of trabeculae, especially in the premolar and molar regions on both sides (Fig. 2). In the maxilla there was osteo]ysis in the left premolar region (Fig. 3).
Fig. 3.--Osteolysis in left upper premolar region.
Hematologist's R e p o r t . - - P h y s i c a l examination ou dtme 30, 1[~55, revealed a welldeveloped, well-nourished white gir]~ aged 19 years~ who did not appear acutely or chronically ill She had noted easy f a t i g a b i l i t y from time to time. F a s y bruisability ham been noted throughout the p a t i e n t ' s early childhood and adolescence. There have been no menstrual (lifflctilties and no prolonged bleeding. The fml,li were normal. The conjunctivae revealed I)ilateral pinguecalae. A small hemorrhagic petechia was noted in the right lower eon junetiva. The nose was externally clear. The right lower giugiva, posteriorly, had been incised aml a slight amotmt of bteedlng ooze was ~wted. The breasts were natural; the axillae were clear. The heart was nonttal. Tile neck was flaccid. There were no masses. The liver was palpable at the costal margin. The abdomen was soft. The spleen was palpable tit the costal margin and presented a reran(l, firm et]ge. Resolving ecchylnoses were noted between the knees and the ankles along the pretibial aspects of both lees. The following hematologic data were ol)tainc~]: Hemoglobin Red blood cells White blood cells Nonsegmented Segmented Eosinophils Basophils Lymphocytes Monoeytes Reticulocytes
10.7 (~rnl, per cent 3.7 million 7,200 3
57 9
I 26 4 2.3 per cent
(There was slight anise- and poikilocytosis of the red blood cells. mature cells were noted on the smear.)
No at)normal o1' im-
VoIume 10 Number 2
GAUCI-IE~r
163
DISEASE
Platelets 87,000--Normal 250~000 to 500,000 Sedimentation rate (Wintrobe 20 corrected) Hematocrit 33 M e a n corpuscular volume 89 (82-92) 1~ean corpuscular hemoglobin 32.5 (32-36) concentration ~fean corpuscular hemoglobin 29 (28-32) Blood type time.
' ' O ' ' Rh n e g a t i v e
I h a v e examined the p a t i e n t ' s serum and find no Rh antibodies to be present at this The following coagulation profile was obtained: Bleeding time (Duke-Earlobe) 5' 30" (1-4) Recalcification 300" (60-120) Rumpel-Leede +Clot r e t r a c t i o n - - b e g u n 30' ( w i t h i n 1 hour) complete in 2 hours ( w i t h i n 24 hours) Clot quality Pair (A moderate s e d i m e n t a t i o n of red cells is noted at the b o t t o m of the test tube.) Prothrombin 15 (control 15) Lee-White coagulation 12' (8-18) P r o t h r o m b i n consumption 28" ( g r e a t e r t h a n 45") (3 hours) (From the above data, it is evident t h a t a thrombocytopenic purpura is present.)
Bone m a r r o w aspiration was performed a t the level of the t h i r d sternal segment. The outer t a b l e was normal in consistency. The marrow c a v i t y was entered easily, l~[arrow was readily a s p i r a t e d and spread on slides. A review of the aspirated m a r r o w revealed G a u c h e r ' s cells, singly and in groups, s c a t t e r e d t h r o u g h o u t the smear. The over-all cellularity of the bone m a r r o w smear was good. M e g a k a r y o c y t e s were present, some of which showed p l a t e l e t formation. The following differential p a t t e r n was noted: Blasts Neutro-myeloeytes Nonsegmented Segmented Eosin-myelocytes Nonsegmented Segmented Lymphocytes P l a s m a cells Reticulum cells Reticulo-endothelial cells G a u e h e r ' s cells Proerythroblasts Erythroblasts lqormoblasts
1.2 714.8 24.0 13.6 3.2 1.2 0.8 710.4 1.6 0.4 1.~ 0.4 2.(] 4.0 20.5
(The above bone marrow is diagnostic of Gaucher's disease. p u r p u r a is also present.)
A secondary thrombocytopenic
The patient was admitted to the Long Island Jewish Hospital where f u r t h e r work-up was obtained: Blood, urea, nitrogen Bromsulphalein sodium Total protein Albumin Globulin
17 rag. per cent 6 per cent r e t e n t i o n a f t e r 45 rain. 7.1 Gin. per cent 3.6 3.5
(Eleetrophoresis of the serum is being performed but the results are not yet available.)
] 64
SPIEGEL
o . s . . o. M., a o. l ). Fcbrt~ar~', I~)$7
Fig. 4 . - - T y p i c a l h,~ion of C a u c h e r ' s d i s e a s e i~l d i s t a l t h i r d of r i g h t f e m u r .
Fig'. 5 . - - J , o s s o f t r a b e c u l a e an(] p o r o s i t y of r i g L t mandiblc~
Volume l0 Number 2
GAUCHER'S DISEASE
165
Chest x-ray was negative. Skeletal x-rays of skull and long bones were t a k e n and have not been completely reported as yet. However, a lesion typical of G a u c h e r ' s disease was found in the distal t h i r d of the r i g h t f e m u r (Fig. 4).
Diagnosis: Gaucher's disease with secondary thromboeytopenic purpura and moderate normocytic normoehromie anemia. Prognosis: As to life, the prognosis is excellent for ten to thirty years. Gradual continuing enlargement of liver and spleen are expected. Secondary hypersplenism may necessitate splenectomy at some future date. Therapy: Expectant and supportive. X-radiatlon is of no value at this time. ued observation and re-evaluation will be r~ecessary.
Contin-
Comments and Discussion This case is important for three reasons: 1. The final diagnosis of Gauehcr's disease was made only because of the insistence of the oral surgeon, over the objections of the family physician, that a complete work-up be done. 2. Because the disease was discovered in a comparatively early stage of this girl's life, if she now becomes pregnant her physician, knowing that she has Gaueher's disease, can attempt to maintain her health with supportive therapy and t r y to effect a full-time delivery. 3. Gaucher's disease is rare; only 250 cases have been reported in the literature, as estimate'd by Croen. ~
Summary A case of Gaueher's disease in a 19-year-old Jewish girl has been described. The diagnosis was made only because of the oral surgeon's insistence that a complete examination be done, despite the lack of clinical symptoms. It is apropos to repeat Shira's is conclusions in his article entitled "Manifestations of Systemic Disorders in t:he Facial Bones"" " M a n y systemic disorders may cause changes in the facial bones. Although the diagnosis and treatment of many of these disturbances are definitely out of their province, the dentist and oral surgeon should be aware of the possibility of these abnormal conditions and be able to recognize the more common forms. They should be able to decide whether or not the disturbance is of odontogenic or of local origin and should have a knowledge of the proper procedures to follow in arriving at a correct diagnosis."
References 1. Gaucher, P. C . E . : De l ' e p i t h e l i o m a p r i m i t i f de la rate, hypertrophic idiopathique de la rate sans leucemie, These de Paris, 1882. 2. Lieb, H.: Ztschr. f. physiol. Chem. 115: 305, 1924. 3. Thoma, K. H.: Oral Pathology, ed. 3, St. Louis, 1950, The C. V. Mosby Company, p. 819. 4. Geschickter, C. F., and Copeland, 1~[./~[.: Tumors of Bone, Philadelphia, 1949, J. B. Lippincott Company, p. 566. 5. Pick, L.: Am. J. M. Sc. 185: 453, 1933. 6. DeVries, A., and Izaih, G.: Blood 10: 291, 1955. 7. Schein, A. J., a n d Arkin, A . M . : J-. Bone & J o i n t Surg. 9.4: 396, 1942.
] 66
SPIEGEL
o.s., o. M., & O. I"
February. 1957
8. Welt, S., Rosenthal, N., and Oppenheimer~ B . S . : Gaucher's Splenomegaly With Special Reference to Skeletal Changes, J. A. M. A. 99.: 637, 1929. 9. Hoffman, S. S., and Makler, M . I . : Am. J. Dis. Child. 38: 775, 1929. 10. Comroe, B. L., Collins, L. I-I., and Crane, M . P . : Internal Medicine ill Dental Practice, Philadelphia, ]938, Lea & Febiger, p. ]8]. ]1. Prinz, H., and Greenbaum, S. S.: Diseases of the Month and Their Treatment, c,t. 2~ Philadelphia, ]942, Lea & Febiger, p. 301. 12. Bender, I. B.: Dental Observations in Gaueher's Disease, 3. ]). Res. 17: 5, 193~. ]3. Shira, R . B . : J. Oral Surg. 11: 291, 1953. 14. Bender, I . B . : Personal Communication, December, 1955. 15. Moch, W . S . : ORAL SURG.,ORALMED., AND ORALPATI{. 6: 1250, 1953. 16. Cahn, L . R . : ORAL SURG., ORAL MED., AND ORALPATH. 6: 1253, 1953. ]7. Tassman, G. C., and Bender, I . B . : J. Am. Dent. A. 27: 1270, 1940. 18. Santee, H . E . : J. New York Surg. Soc., May, 1927, p. 20i. ]9. Elliot, Y.F.: Canad. %f. A. J. 66: 166, 1952. 20. Epstein, E , and Lorenz, K.: Ztschr. f. physiol. Chem. 192: 145~ 1930. 21. Groen, J.: Blood 3: ]238, ]948. 650 CENTRAl, AVI<.