THE BONE MARROW AS A DIAGNOSTIC AID IN ACUTE DISSEMINATED LUPUS ERYTHEMATOSUS*
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1 THE BONE MARROW AS A DIAGNOSTIC AID IN ACUTE DISSEMINATED LUPUS ERYTHEMATOSUS REPORT ON THE HARGRAVES' "L. E." CELL JOHN R. HASERICK, M.D., AND R. DOROTHY SUNDBERG, PH.D. In 1946 Hrgrves observed phgocytic phenomenon in bone mrrow preprtions of ptients suffering from cute disseminted lupus erythemtosus. His findings were reported originlly in thesis by Morton (1), nd lter in preliminry report by Hrgrves, Richmond, nd Morton (2). It is the purpose of this pper to record s corrobortive evidence similr observtions in four cses of cute disseminted lupus erythemtosus nd filure to detect the phenomenon in other forms of lupus erythemtosus, in dermtomyositis, nd in other leukopenic conditions. Since the erly descriptions of the disese, nemi nd leukopeni hve been recognized s n integrl prt of the clinicl picture of cute disseminted lupus erythemtosus. It is, therefore, somewht surprising to find few investigtions of the bone mrrow reported in the literture. While mny cse reports hve included bone mrrow exmintions, few hve been complete, nd, until Morton's thesis, none hd given thorough description of the findings. Reltively mcroscopic studies were reported by Schumnn nd Introzzi (3) in In cses of cute disseminted lupus erythemtosus, they demonstrted dense perivsculr groups of lymphocytes nd few scttered fibroblsts in the heds of the mettrsls, but otherwise did not report the bone mrrow exmintion in detil. In 1939, Bunim (4) found hyperplsi of the cells of the grnulocytic series on post-mortem exmintion of the vertebrl bodies. In 1943, Cluxton nd Kruse (5) reported cse in which the femorl bone mrrow ws lrgely ftty with definite geltinous chnge. Morton's thesis, prepred under the guidnce of Hrgrves, hs presented thorough investigtion of the bone mrrow in eleven cses of disseminted lupus erythemtosus. Using Schleicher's technic (6), the myeloid-erythroid lyer ws found to be "norml" in five cses, less thn six volumes per cent in four cses, nd somewht elevted in two cses. In generl, the cellulrity ws decresed s though there were n "inhibition" of the mrrow. In differentil counts of the unconcentrted nucleted cells, the myeloid-erythroid rtio ws found to be higher thn the generlly considered norml of 2.7/1. A tendency to shift to the left ws noted in both the myeloid nd erythroid lines, nd, on touch preprtions, only few ft cells were present. Of prticulr interest in Morton's studies ws the presence of the Hrgrves "L. E." Cell in seven of the eleven cses. In its most chrcteristic form, the cell ws polymorphonucler leukocyte which hd engulfed round, bsophiic, Fromthe Division of Dermtology, Clevelnd Clinic, Clevelnd, Ohio, nd from the Deprtment of Antomy, University of Minnesot. Received for publiction My 27,
2 210 THE JOURNAL OF INVESTIGATIVE DERMATOLOGY homogenous mss of seemingly lymphocytic origin. The inclusion body stined with Feulgen's stin for thymonucleic cid, supporting the hypothesis tht the mss originted from nucler mteril. Hrgrves, Richmond, nd Morton (2) described two bone mrrow cells in which the phenomenon of phgocytosis ws prominent feture, the "L. E." Cell nd the "trt" cell, so-clled from common usge in their lbortory. The "trt" cell ws occsionlly found in norml mrrows, nd ws present in incresed numbers in the bone mrrow preprtions of ptients suffering from number of different illnesses such s lymphoblstom, multiple myelom, pulmonry infection, nd metsttic crcinom. The distinguishing feture between the "L. E." Cell nd the "trt" cell ws the difference in the structure of the engulfed mteril. In the "L. E." Cell, the mss, chrcterized by lck of chromtin structure, ws lmost homogeneous nd hd "smoky" ppernce. In contrst, the chromtin structure of the engulfed mteril in the "trt" cell ws distinct; the mteril resembled the nucleus of lymphocyte. Our interest in the vlue of bone mrrow studies in the dignosis of cute disseminted lupus erythemtosus ws stimulted when one of us (R. D. S.) hd the opportunity of exmining Morton's thesis (1). It ws reclled tht in series of pproximtely one thousnd cses in which the bone mrrow hd been exmined, the peculir phgocytosed mteril hd been observed in only two. In these cses, the bone mrrow reports hd clled ttention to the phenomenon of phgocytosis; the nture of the process ws considered to be unique. The dermtologic dignosis in one of the two cses ws cute disseminted lupus erythemtosus. The other cse, the history of which will be presented in detil, w one in which there hd been persistent leukopeni of unknown etiology. RESULTS OF STUDY Bone mrrow exmintions were mde in ten cses of lupus erythemtosus, three cses of dermtomyositis, nd numerous cses in which leukopeni ws prominent feture. The Hrgrves "L. E." Cell ws found in four out of five cses of cute disseminted lupus erythemtosus (Fig. 1, A, B, C). Two cses of sub-cute nd three cses of chronic discoid lupus erythemtosus did not revel the "L. E." Cells, nor did ny of the other conditions. The "trt" cell, reltively common finding in bone mrrow smers, (Fig. 1, D) ws distinguished from the "L. E." Cell by its dult type of nucler pttern. It ws noted tht the "L. E." Cell ws more prominent in the severe cses of cute disseminted lupus erythemtosus. Three to four of the phgocytosed bodies were found in ech oil immersion field in two ptients during moribund stge, but other bone mrrow studies on the sme two ptients during prtil remissions reveled only one "L. E." Cell in severl fields. Congenitl hemolytic nemi complicted the one cse of cute disseminted lupus erythemtosus in which the Hrgrves' phenomenon ws not found. Trnfusions produced cute hemolytic crises in this ptient which brought the hemoglobin to between 3 nd 4 grms, nd the possibility exists tht the bone
3 BONE MARROW AS DIAGNOSTIC AID 211 V t 1... w.t % 'I,. j p 1. A p 'flr 4 S :;-ø' '4 U I E t't o 1 d.sp p FIG. 1. THE PHENOMENON OF PHAG0CYrosls A. The "L. E." Cell from ese of cute disseminted lupus erythemtosns. Engulfed body homogenized nd "foggy". B. Two "L. B." Cells, top one ttrcting three polymorphonucler leukocytes. From the cse reported in the rticle. C. The "L. B." Cell from cse of cute disseminted lupus erythemtosus in remission. D. Two "Trt" cells in pposition, showing more mture nucler pttern of engulfed body. mrrow phgocytosis my hve been ltered by the severe demnds on the mrrow. The dignostic vlue of the "L. E." Cell is demonstrted in the following cse report: D
4 212 THE JOURNAL OF INVESTIGATIVE DERMATOLOGY REPORT OF A CASE History Mrs. C. P., ged 61, noted the ooset of pin nd swelling of the hnds nd nkles ssocited with mlise, wekness, nd esy ftigubility in July On November 20, 1944, she becme cutely ill with high temperture, prostrtion, nd bilterl chest pin. A dignosis of pneumoni nd pericrditis ws mde, nd she ws dmitted to Ancker Hospitl, St. Pul. The hemoglobin ws found to be 9 grms, nd the leukocytc count vried between 2,000 3,000. Under penicillin therpy she grdully improved, leving the hospitl Februry 14, She ws followed in the out-ptient deprtment where it ws found tht the nemi did not respond to lrge doses of liver or iron. During tho next yer she suffered from repeted ttcks of rthritis. Wekness, norexi, restlessness, nd non-productive congh developed, nd she ws redmitted April 11, Physicl Positive findings on this dmission were s follows: The temperture ws 100.2, the pulse rte 112 per minute, nd the respirtions 24 per minute. The blood pressure ws 148/88. Brething ws lbored, nd inspirtory wheezes were herd in both upper lobes. A to nd fro pericrdil friction rub ws herd. The skin ws cler. Lbortory dt The hemoglobin vried between 9.4 nd 11 grms per cent. The white blood cell count ws 1,750 per cubic centimeter on dmission with 85 per cent polymorphonucler cells. A trce of lbumen ws found on repeted urinlyses. The urinry sediment ws negtive. The sedimenttion rte ws 53 millimeters per minute by the Westergren method. Totl plsm proteins were 6.7 grms per cent, lbumen 3.18 grms per cent, globulin 3.4 grms per cent. Course The ptient remined cutely ill for severl weeks. The temperture occsionlly rose to 103 degrees, nd she ws often disoriented nd confused. One month fter dmission the spleen ws plpted. Becuse of persistent nemi nd leukopeni, sternl bone mrrow ws spirted on June 20, This ws referrcd to one of us (R. D. S.) The report ws s follows: "Bone Mrrow Biopsy Ft 1%, plsm 57%, myeloid-erythroid 2%, erythrocytes 40%. The mrrow is modertely hypoplstic, but there is reltively little ltertion in the percentge of immture cells. Erythropoiesis is reltively norml. There is no pprent reduction in bnd form nd mture neutrophils. Neutrophil promyelocytes nd myclocytes re reltively decresed. All neutrophils show toxic ltertions; degenerting neutrophils re present but not extremely numerous. Mny of the neutrophils re pprently pbgocytosing lymphocytes. Since this phenomenon hs not been previously encountered it is, in ll probbility, peculir to this mrrow. It could be prtil explntion of the persistent leukopeni. Megkryocytes pper to be decresed, but since mrrow nd blood pltelets re numerous, the decrese is probbly not significnt. Lymphocytes re slightly decresed. There is slight increse in plsm cells. "Peripherol Blood Erythrocytes show slight nisocytosis nd hypochromsi. Blood plt-elets do not pper to be decresed. There is slight leukopeni with mrked decrese in lymphocytes (12%). Neutrophils comprise 86% of the circulting leukocytes nd show mrked toxic ltertions. There is no evidence of primry blood disese. "Conclusion. Hypoplstic mrrow with mrked toxic ltertions. Phgocytosis of lymphocytes by neutrophils in the mrrow." The ptient grdully improved, nd she ws dischrged November 4, No dignosis hd been mde though Felty's syndrome, rheumtoid rthritis, cute disseminted lupus erythemtosus, nd rheumtic fever were suggested. The ptient ws redmitted for study Februry 2, She stted tht she hd felt well since 1946, nd hd suffered only occsionlly from rthritic pins. Exmintion ws negtive except for moderte, diffuse erythem noted bove the V of the neck. A biopsy from this re did not revel the chnges ssocited with lupus erythemtosus. The hemoglobin ws 14 grms per cent. The totl white blood count ws 7,200 with 79 per cent polymorphonucler cells, 18 per cent lymphocytes, nd 3 per cent monocytes. No lbumen ws found in the urine. A bone mrrow exmintion ws reported by Dr. J. F. Noble s follows: "Erythrocytes 50%, myeloid-erythroid 2%, plsm 48%. On exmintion of
5 BONE MARROW AS DIAGNOSTIC AID 213 numerous stined smers only one "L. E." Cell ws encountered. This is comptible with dignosis of lupus erythemtosus in remission." COMMENT Evidence for the dignosis of cute disseminted lupus erythemtosus in this ptient is s follows: repeted ttcks of rthritis, polyserositis (pneumoni nd pericrditis), fever, nemi, leukopeni, lbuminuri, incresed sedimenttion rte, reversed lbumen-globulin rtio, nd splenomegly in n cutely ill ptient whose illness ws chrcterized by relpses nd remissions over severl yers. It is felt tht the dditionl finding of the "L. E." Cells in the bone mrrow in 1946 nd 1948 permits the dignosis of cute disseminted lupus erythemtosus in retrospect. The inbility to demonstrte the phgocytic phenomenon in the cses of dermtomyositis my hve been due to the fct tht the two cses were chronic, though severe exmples of the disese. It is not within the scope of this pper to discuss the underlying mechnism of the phgocytosis. This intriguing spect of the problem merits considerble investigtion, nd will be delt with in future reports. SUMMARY Bone mrrow preprtions were studied in 10 cses of lupus erythemtosus, in 3 cses of dermtomyositis, nd in numerous cses in which leukopeni ws prominent. The Hrgrves' "L. E." Cell ws demonstrted in four out of five cses of cute disseminted lupus erythemtosus, but it ws not found in ny of the other conditions. From these studies it is felt tht the following conclusions my be drwn: 1. The Hrgrves' "L. E." Cell is vluble dignostic id in cute disseminted lupus erythemtosus. 2. The "L. E." Cell is found in the lrgest numbers during the severe stges of the disese, nd with difficulty during remissions. 3. The "L. E." Cell is not found in the sub-cute nd chronic forms of lupus erythemtosus. 4. The gretest vlue of the "L. E." Cell lies in its possible presence in suspected cses of cute disseminted lupus erythemtosus in which the clssic dermtologic mnifesttions re lcking. REFERENCES 1. MoRToN, R. J.: A study of the blood nd bone mrrow in cses of disseminted lupus erythemtosus. Thesis. University of Minnesot. Februry, HARORAVES, M. M., RICHMOND, HELEN, AND MoRToN, R. J.: Presenttion of two bone mrrow elements: The "Trt" cell nd the "L. E." cell. Proc. Stff Meet., Myo Clinic, 23: 25 28, (Jn. 21) SCHAUMANN, J., AND INTEOZZI, P.: Sulle eziologic sull lterzioni sistemtico degli orgni emtopoietici del lupus eritemtos cut. Hemtologic, 12: , BUNIM, J.: Lupus erythemtosus dissemint. Ann. mt. Med., 13: , CLUXPON, H., AND KRAUSE, L.: Acute lupus erythemtosus. Ann. mt. Med., 19: (Dec.) SCITLEICHER, E. M., AND SHARP, E. A.: Rpid methods for prepring nd stining bone mrrow. J. Lb. & Clin. Med., 22: 949, 1937.
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