A patient with systemic lupus erythematosus developed severe abdominal pain and tender hepatomegaly associated with progressive pancytopenia and elevated serum levels of circulating immune complexes. Liver scintigram demonstrated extreme hepatomegaly with poor colloid uptake and splenomegaly with increased colloid uptake. An unusual accumulation of colloid in the lungs was also noted. Subsequent clinical and laboratory studies raised the possibility of saturation of the reticuloendothelial system in the liver by circulating immune complexes and blood cells, a condition demonstrated in experimental animals, but not hitherto well documented in the human immune complex disorder

Fukuda, Kiyoshi

Kabashima, Teizo

Kashiwagi, Heihachiro

Kono, Ichiro

Sakurai, Tetsushi

Yamane, Kazuhide

English

Henry Ford Health System Scholarly Commons

Henry Ford Hospital Medical Journal Volume 32 Number 2 Article 11 6-1984 Rapidly Progressive Pancytopenia, Hepatomegaly, and Abnormal Lung Uptake of Colloid in Systemic Lupus Erythematosus: Possible Saturation of Reticuloendothelial System with Blood Elements Tetsushi Sakurai Kiyoshi Fukuda Ichiro Kono Teizo Kabashima Kazuhide Yamane See next page for additional authors Follow this and additional works at: https://scholarlycommons.henryford.com/hfhmedjournal  Part of the Life Sciences Commons, Medical Specialties Commons, and the Public Health Commons Recommended Citation Sakurai, Tetsushi; Fukuda, Kiyoshi; Kono, Ichiro; Kabashima, Teizo; Yamane, Kazuhide; and Kashiwagi, Heihachiro (1984) "Rapidly Progressive Pancytopenia, Hepatomegaly, and Abnormal Lung Uptake of Colloid in Systemic Lupus Erythematosus: Possible Saturation of Reticuloendothelial System with Blood Elements," Henry Ford Hospital Medical Journal : Vol. 32 : No. 2 , 142-145. Available at: https://scholarlycommons.henryford.com/hfhmedjournal/vol32/iss2/11 This Article is brought to you for free and open access by Henry Ford Health System Scholarly Commons. It has been accepted for inclusion in Henry Ford Hospital Medical Journal by an authorized editor of Henry Ford Health System Scholarly Commons. Rapidly Progressive Pancytopenia, Hepatomegaly, and Abnormal Lung Uptake of Colloid in Systemic Lupus Erythematosus: Possible Saturation of Reticuloendothelial System with Blood Elements Authors Tetsushi Sakurai, Kiyoshi Fukuda, Ichiro Kono, Teizo Kabashima, Kazuhide Yamane, and Heihachiro Kashiwagi This article is available in Henry Ford Hospital Medical Journal: https://scholarlycommons.henryford.com/hfhmedjournal/vol32/iss2/11 Henry Ford Hospital Med J Vol . 32, No. 2, 1984 Rapidly Progressive Pancytopenia, Hepatomegaly, and Abnormal Lung Uptake of Colloid in Systemic Lupus Erythematosus: Possible Saturation of Reticuloendothelial System with Blood Elements Tetsushi Sakurai, MD,* Kiyoshi Fukuda, MD,* Ichiro Kono, MD,* Teizo Kabashima, MD,* Kazuhide Yamane, MD,* and Heihachiro Kashiwagi, MD** A patient with systemic lupus erythematosus developed severe abdominal pain and tender hepatomegaly asso-ciated with progressive pancytopenia and elevated serum levels of circulating immune complexes. Liver scintigram demonstrated extreme hepatomegaly with poor colloid uptake and splenomegaly with increased colloid uptake. An unusual accumulation of colloid in the lungs was also noted. Subsequent clinical and laboratory studies raised the possibility of saturation of the reticuloendothelial sys-tem in the liver by circulating immune complexes and blood cells, a condition demonstrated in experimental animals, but not hitherto well documented in the hu-man immune complex disorder. Systemic lupus erythematosus (SLE) is a typical immune complex disease. In experimental animals, circulating immune complexes (IC) have been shown to be re-moved by the reticuloendothelial system (RES), espe-cially by the liver (1 -3). The saturation of hepatic uptake, however, has not been well documented in the human disorder, but has been experimentally documented in mice (2,3). In this paper, we present an interesting case of SLE which manifested pancytopenia associated wi th a rapidly enlarging tender liver and avid col loid uptake by the lungs. The combination of these abnormalities must be rare in SLE because a similar case could not be found in the literature. Based on studies of liver scintigram, liver enzymes, serum IC, and hemogram, saturation of hepatic uptake was considered to be responsible for these abnormalit ies. Case Report A 22-year-old woman was admitted to the University Hospital in September, 1980 because of severe right upper quadrant pain associated wi th enlarging liver and rapidly progressive pancytopenia of four weeks' dur-ation (Fig. 1). The patient also had arthralgia and spiking fever. Past history and family history were not contr ibutory. On physical examination, the patient was grossly pale. Funduscopy revealed cotton wool spots and hemor-rhages. The liver was palpable 7 cm below the right costal margin with a rounded edge and severe ten-derness. Splenomegaly could not be conf i rmed by physical examina t ion because of abdomina l t en -derness. Laboratory tests revealed a leukocyte count of 1600/|xl wi th48% neutrophils, 44% lymphocytes, and 8% monocytes; hemoglobin, 5.9 g/dl; hematocrit, 18.6%; reticulocyte count, 4.8x10*/ p.1. Liver enzymes were nor-mal at this t ime. The fo l lowing studies were normal: ur inalys is, s tool guaiac tests, d i rec t and ind i rec t Coombs' tests, serological tests for syphyllis, and latex fixation test. Serum levels of haptoglobin, folate and Bi2 were normal. Lupus erythematosus (LE) cell pre-parations and tests for the antinuclear factor (ANF) were positive; CH50 level was 12 units (normal 30-40). Ant i-RNP and anti-Sm antibodies were negative. Levels of IC [Clq deviat ion test (4)] and anti-ds DNA ant ibody [Mil l ipore-f i l ter assay (5)] were 70% (normal <30) and 56.9% (normal <5) , respectively. Bone marrow aspira-t ion was normal wi th a megakaryocyte count of 105/|ji,l. The diagnosis of SLE was considered to be established on the basis of arthralgias, hematological abnormalit ies, positive LE-cell preparations, positive ANF, and positive anti-ds DNA antibody. Therapy was initiated with 60 mg Submitted for publication: March 20, 1984 Accepted for publication: July 19, 1984 •Rheumatology and Collagen Disease Division of the Department of Medicine, institute of Clinical Medicine, University of Tsukuba ••Formerly a resident in the Department of Internal Medicine, Henry Ford Hospital; presently in the Department of Internal Medicine, University of Tsukuba, Ibaraki, Japan Address reprint requests to Tetsushi Sakurai, MD, Institute of Clinical Medicine, University of Tsukuba, Ibaraki - 305, Japan, 142 Pancytopenia, Hepatomegaly, and Abnormal Lung Uptake in SLE WBC Hb I S PSL ::;;:::|:::::::::::;:::i::::^ ^^  i;!;: PLT x i o V x i 30 2 0 1980 July Aug Sep Oct Dec 1981 Jan Abdofninal pain Hapatomegalv — + 4+ # t+ ++ +t + 4- -h LAP 170 20OI 1 9 2 2 1 7 3 7 1 4 8 1 6 3 9 5 1 2 4 3 0 2 5 7 2 7 6 r G T P 10-671 1 7 26 58 67 1 11 8 6 73 4 8 4 6 S G O T I 8 - 4 0 I 1 8 9 7 1 0 1 4 11 8 10 1 1 Fig. 1 Changes of the levels of hemocytes, IC, and liver enzymes during treatment. Abdominal pain and hepatomegaly became prominent with high IC level and pancytopenia. LAP and 7-CTP elevated following hepatomegaly. Hb: Hemoglobin (12-16 g/dl); WBC: White blood cell (4000-9000/ (xl); Pit: Platelet (15-35x1 OV |xl); IC: Immune complexes (0-30%); LAP: Leucine aminopeptidase (70-200 G.R. unit); 7-GTP: 7-G-lutamyltransferase (0-57 lU/l); ( ) indicates normal ranges daily of prednisolone. As shown in Fig. 1, the patient responded well to the treatment wi th improvement of anemia, leukopenia, and abdominal pain. However, the platelet count remained around 10,000/ |xl. After two months of treatment, a "pulse therapy" was given for persistent th rombocy topen ia w i th subsequent im-provement. From the first visit in July, the IC level rose gradually and peaked in mid-September, 1980. The level rapidly decreased after prednisolone treatment was given. On September 26, liver scan was performed using 7 mCi of '*"Tc-phytate. Twenty minutes after the colloid was injected intravenously, camera studies were carried out in the anterior, posterior, right lateral, and right obl ique projections (Fig. 2). The images conf i rmed severe hep-atomegaly wi th poor col loid uptake and splenomegaly with increased col loid uptake. Of interest was an un-usual accumulation of colloid in the lungs, indicating increased lung uptake as defined by Keyes, et al (6). A second liver scintigram, performed after hematologic recovery in January, 1981, showed almost normal im-ages of the liver and spleen and disappearance of ab-normal col loid uptake by the lungs. Fig. 2 Left: Liver scintigrams (same magnification) performed on September 26, 1980. Marked hepatomegaly with poor colloid uptake. Note un-usual lung and prominent spleen uptake. Right: Performed on January 14, 1981. Liver size, uptake of colloid by liver and spleen are almost natural. Lung uptake is no longer demon-strated. 143 Sakurai, Fukuda, Kono, et al The levels of 7-glutamyltransferase (7-GTP) and leucine aminopeptidase (LAP), wh ich were elevated dur ing hepatomegaly, became normal as the size of the liver and hematological values improved (Fig. 1). The level of alkaline phosphatase (Al-P) was slightly abnormal in parallel wi th these enzymes. Levels of GOT and GPT remained w i th in the normal ranges. The HBAg re-mained negative. After four months of prednisolone therapy, all the hematologic and serologic abnormali-ties which were present on admission became normal, and the patient was discharged receiving a maintenance dose of prednisolone. Comment A striking feature in this case was that progressive pan-cytopenia and elevation of the levels of circulating IC developed concomitantly wi th acute hepatomegaly and that the scintigram taken at that t ime conf i rmed extreme hepatomegaly with poor col loid uptake associated wi th an abnormal pulmonary and splenic uptake. In ad-di t ion, levels of liver enzymes indicating biliary tract obstruction paralleled changes in the liver size. Mannik demonstrated that experimentally prepared immune complexes are preferentially removed by the liver (1). It is only after the liver is saturated that the lungs and the bone marrow funct ion like the reticuloendothelial sys-tem. In our case, we assume that the liver had been saturated by immune complexes and sensitized hemo-cytes, hence the col loid shift to the spleen, the lungs, and the bone marrow. The severe abdominal pain was attributed to rapid expansion of the liver capsule. The results of subsequent liver scintigram studies after cl ini-cal and hematologic recovery support this assumption. The cause of severe anemia in the absence of overt hemolytic anemia in this case is di f f icul t to explain. The negative Coombs' test and the normal level of serum haptoglobin do not support the possibil ity of auto-immune hemolytic anemia. In experimental animals, complement-bearing erythrocytes have been shown to be sequestered by the liver in the absence of antibody, then gradually return intact to the circulation (7,8). The fact that, in SLE, complement alone is frequently found as a surface protein of erythrocytes (9) is compatible with the hypothesis of red cell sequestration. Garratty and Petz reported that eight of ten commercial "b road-spectrum" antiglobulin sera failed to react wi th cells strongly sensitized wi th complement which were ob-tained f rom patients wi th hemolytic anemia (10). Se-questration rather than hemolysis may have been re-sponsible for the anemia in our case. The abnormally reduced hepatic col loid uptake may be explained by the presence of both IC and blood cells adherent to the surface of Kupffer cells through C3b receptors. Elevated levels of 7-GTP and LAP wi th normal levels of SGOT and SGPT dur ing the first months of hospitalization could be the result of saturated sinusoids obl i terating the biliary tracts. Diagnosis of acute and chronic hepatitis and malignant tumor can be excluded on the basis of the levels of GOT and GPT along wi th the hospital course. Steatosis o f t h e liver, reported as a common hepatic disorder in SLE (11), is also un l i ke l y ; the pat ient had deve loped hep-atomegaly before prednisolone therapy, and the liver size returned to normal wi th the treatment. Thus, ac-cumulation of IC and sequestration of b lood cells seems the most reasonable explanation for the hepatomegaly. Hepatomegaly is present in 30-40% of SLE cases, and the incidence of cytopenia is significant in those patients (11). This correlation supports our concept that the liver is at least partly responsible for the sequestration of sensitized hemocytes in this disease. The presence of another independent b lood dyscrasia is excluded by the results of laboratory studies and the clinical course. Kl ingensmith, et al (12) described six patients wi th collagen-vascular diseases among 27 patients wi th in-creased lung uptake dur ing liver scintigram. To explain their f indings, they raised the possibility of diffuse liver disease and decreased hepatic clearance of col lo id. Our concept is compatible wi th their theory; the presence of diffuse liver abnormality is apparent f rom the abnor-mal liver image. It has been shown that clearance of particles mediated by these RES membrane receptors is independent of the clearance of aggregated a lbumin, which is not mediated by receptors (13). It seems probable, however, that the uptake of col loid by the liver may be impeded when the degree of saturation by IC and b lood cells is extreme. 144 Pancytopenia, Hepatomegaly, and Abnormal Lung Uptake in SLE References 1. Mannik M. Physicochemical and functional relationships of im-mune complexes. J Invest Dermatol 1980;74:333-8. 2. Haakenstad AO, Mannik M. Saturation of the reticuloendothelial system with soluble immune complexes, J Immunol 1974; 112:1939-48. 3. Finbloom DS, Plotz PH. Studies of reticuloendothelial function in the mouse with model immune complexes. II, Serum clearance, tissue uptake, and reticuloendothelial saturation in NZB/W mice, J Immunol 1979;123:1600-3. 4. Sobel AT, Bokisch VA, Meuller-Eberhard H). Clq deviation test for the detection of immune complexes, aggregates of IgG and bac-terial products in serum. J Exp Med 1975;142:139-50. 5. Kredich NM, Skyler JS, Foote LJ, etal. Antibodies to native DNA in systemic lupus erythematosus, A technique of rapid and quan-titative determination. Arch Intern Med 1973;131:639-44, 6. Keyes JW Jr, Wilson GA, Quinonest JD, An evaluation of lung uptake of colloid during liver imaging, J Nucl Med 1973;14:687-91, 7. Mantovani B, Rabinovitch M, Nussenzweig V, Phagocytosis of immune complexes by macrophages: Different roles of the macrophage receptor sites for complement (C3) and for immu-noglobulin (IgG). J Exp Med 1972;135:780-92, 8, Nussenzweig V, Role of complement in the clearance and pro-cessing of immune complexes. In: Fougereau M, Dausset J, eds. Immunology 80, Progress in immunology IV, New York: Aca-demic Press, 1980:1048-56, 9, Budman DR, Steinberg AD, Hematologic aspects of systemic lupus erythematosus: Current concepts. Ann Intern Med 1977; 86:220-9. 10. Garratty G, Petz LD. An evaluation of commercial antiglobulin sera with particular reference to their anticomplement proper-ties. Transfusion 1971;11:79-88. 11. Runyon BA, Labrecque DR, Anuras B. The spectrum of liver disease in systemic lupus erythematosus. Report of 33 his-tologically-proved cases and review of the literature. Am J Med 1980;69:187-94, 12. Klingensmith WC III, Yang SL, Weagner HN Jr, Lung uptake of Tc-99m sulfure colloid in liver and spleen imaging, J Nucl Med 1978;19:31-5, 13. Frank MM, Hamburger MI, Lawley TJ, Kimberly RP, Plotz PH. Defective reticuloendothelial system Fc-receptor function in sys-temic lupus erythematosus, N Engl J Med 1979;300:518-23. 145 

Rapidly Progressive Pancytopenia, Hepatomegaly, and Abnormal Lung Uptake of Colloid in Systemic Lupus Erythematosus: Possible Saturation of Reticuloendothelial System with Blood Elements

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Rapidly Progressive Pancytopenia, Hepatomegaly, and Abnormal Lung Uptake of Colloid in Systemic Lupus Erythematosus: Possible Saturation of Reticuloendothelial System with Blood Elements

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