Thymoma, myasthenia gravis, erythroblastopenic anemia and systemic lupus erythematosus in one patient H. L. N. MacKechnie, m.d., A. H. Squires, m.d., f.r.c.p.[c], M. W. Pruzanski, m.d., f.r.c.p.[c], f.a.c.p., Toronto
Summary: A 50-year-old woman who initially had myasthenia gravis subsequently presented with thymoma, erythroblastopenic anemia and systemic lupus erythematosus during 17 years of follow-up. In a review of the literature cases were were
no
similar documented
found, although 14 patients
reported with three of the above two also having positive LE
diseases,
cell tests. An association of several autoimmune disorders in one patient may be more frequent than was previously believed.
Resume: Thymome, myasthenie grave, Srythroblastope'nie et lupus eryth6mateux
dissSmine observes chez une malade Une femme de 50 ans qui avait anterieurement souffert d'une myasthenie grave presenta subsequemment un
thymone, une erythroblastopenie et un lupus erythemateux dissemine pendant les 17 ans ou elle a ete suivie. Une
de la litterature sur le pas permis de decouvrir un seul cas identique, bien qu'on ait signale trois des pathologies susmentionnees chez 14 malades, dont deux avaient egalement des cellules LE. Nous concluons que la coexistence de plusieurs maladies par auto-immunisation peut se rencontrer chez un meme malade plus souvent qu'on ne le croyait revue
sujet n'a
auparavant. The coexistence of thymoma with var¬ ious autoimmune disorders has frequent¬ ly been reported. For 17 years we have kept under our surveillance a patient in whom were associated thymoma,
myasthenia gravis, erythroblastopenic anemia and systemic lupus erythema¬
tosus. The occurrence of these four con¬ ditions in the same person, to our knowledge, has never been well docu-
From the Immunoproteins Research Laboratory of the University of Toronto Rheumatic Disease Unit, Departments of Medicine and Pathology of The Wellesley Hospital, Toronto Supported by Grant-in-aid of the Canadian Arthritis and Rheumatism Society W. Pruzanski, Reprint requests to: Dr. 160 The Wellesley Hospital, Wellesley St. E., Toronto 5, Ont.
Platts,
m.d.,
f.r.c.p.[c] and
ptosis of the right eyelid were Siguir et al1 in 1969 and Zou- facies andBlood pressure was 125/85 mm. Saegesser and Schneider2 in 1970 evident. each reported a patient with thymoma, Hg; pulse was 100 and regular. A freely thyroid nodule, 3 cm. in diameter, myasthenia gravis and erythrocyte mobile was found. There was no hepato- or both expatients aplasia. Although splenomegaly or lymphadenopathy. On hibited the LE cell phenomenon, no examination the skin appeared normal. definite clinical or pathological evid¬ Full extraocular movements were present. ence of systemic lupus erythematosus The uvula was directed to the right. There was weakness of the muscles of the neck was provided. and arms, more prominent proximally than distally, especially on the right side. Case report Sensation and reflexes were normal. mented.
panos,
J. M. was admitted to hospital for the first time in January 1954 when she was aged 33. She had not been feeling well for approximately three months and was mentally depressed. Since childhood she had developed urticaria during the strawberry season; otherwise she had enjoyed good health. Her family history was noncontributory. Results of the physical ex¬ amination were negative. She was treated with insulin shock and psychotherapy, and was able to return to her job. In March 1955 she was referred to the Ontario Department of Health with a five-month history of muscular weakness, mainly of proximal type, ptosis of the right upper lid and mild dysphagia, the onset of which followed an upper respira¬ tory illness. The diagnosis of myasthenia gravis was made and the patient was treated with prostigmine. The weakness progressed, however, and she developed mild shortness of breath on walking one block. A chest radiograph showed the presence of a shadow 5 cm. in diameter
Hemoglobin was 8.9 g./100 ml., reticulocytes 0.05%. The leukocyte count was 8100/c. mm. with a normal differential count, and the platelet count was 457,000/ c. mm. ESR was 113 mm. in the first hour. Bone marrow was hypocellular with complete absence of erythrocyte precursors. Albumin was 4.06 g./lOO ml., gamma globulin 1.76 g./lOO ml. Antinuclear factor test was positive. LE cell test was strongly positive on three occa¬
sions. Latex test was non-reactive. BUN was normal. PBI and radioactive iodine uptake were normal. A thyroid scan showed a functioning nodule in the left lobe.
as a thymic mass. The patient received cobalt irradiation of 3000 rads and a remarkable shrinkage of the mass took place. Over the next three years her state remained unchanged. In 1958 the patient's condition deteri¬ orated. The complaints mentioned were persistent but there was no diplopia, dysarthria or leg weakness. Slight exacerbations of myasthenia followed one to three respiratory infections per year, and were treated with Mytelase chloride® (ambenonium chloride) 12.5 mg. four times
interpreted
daily. In 1960 the patient first noticed blanching and numbness of the fingertips on exposure to cold. In 1963 she began noticing increasing fatiguability, shortness of breath and postural vertigo, and was ad¬ mitted to hospital. On admission she re¬ lated a history of arthralgia and inter¬ FIG. 1.Lymphorrhage in right deltoid mittent swelling of the proximal inter- muscle biopsy. Lymphocytes in connective phalangeal joints. She looked chronically tissue between striated muscle fibres. ili and her speech was slurred. Myopathic x 200 CMA JOURNAL/OCTOBER 20, 1973/VOL. 109 733
She was given 1500 ml. of whole blood. The reticulocyte count was unaffected by the discontinuation df Mytelase chloride or the later administration of Mestinon® (pyridostigmine bromide). Methandrostenolone was begun but no response oc¬ curred.
negative and osmotic fragility was normal. Calcium was 8.9 mg., phosphate 4.0 mg., bilirubin 0.7 mg., BUN 24 mg. and crea¬ tinine 0.65 mg./100 ml. Urinalysis yielded normal findings. Two 24-hour urine collections showed protein values up to 168 mg./24 hours. Creatinine clearance varied from 44.9 to 55.4 ml./min. ECG showed nonspecific abnormalities. Thyroid scan showed slightly decreased uptake at the periphery of the right lobe, but the 24hour value for total uptake was normal,
29%, and the T4 level was 6 Mg./100 ml. Bone marrow showed severe erythroid hypoplasia with myeloid:erythroid ratio of 100:1 (Fig. 3). A further course of prednisone, 100 mg. per day, was given in an attempt to induce a remission in the erythroblaatopenia. However, there was no reticulocytic response and the hemoglobin continued to fall (Fig. 2). An aortic systolic and diastolic murmur were heard, the latter for the first time. In October 1971 the patient developed
Over the next year her hemoglobin was kept at a normal level with transfusions of packed cells, two units being given every two to three months. In May 1964 the patient was readmitted. The physical findings were un¬ PREDNISONE MG/DAY changed. Hemoglobin was 10.1 g./lOO ml., ESR 72 mm. in the first hour. Serum protein electrophoresis was normal. LE cell test was strongly positive. Both Kell and thyroid antibodies were found. Uri¬ nalysis yielded normal findings. Electromyography showed a typical myasthenie pattern. A biopsy of the right deltoid muscle showed minimal myopathic changes with lymphorrhages (Fig. 1). Repeat bone marrow aspiration showed marked erythroid hypoplasia. A course of prednisone 60 mg. per day resulted in reticulocytosis, rise in hemoglobin (Fig. 2) and prominent increase in erythroid eleS ments in the bone marrow. The LE cell test became negative. However, the myas¬ 09 \ thenia relapsed and the patient developed 12 polydypsia with glycosuria. Prednisone 10 was gradually reduced to 5 to 10 mg./ day, and instead of Mytelase chloride, 8 Mestinon timespan® was given with ex¬ cellent results. The LE cell test remained 6 negative until September 1965. In 1967 her serum test was negative 4 for anti-DNA, weakly positive for antiSS DNA and strongly positive for free I- 2 DNA. Hemoglobin fluctuated from 8 to 12 g./lOO ml. without blood transfusions 3 4 SEPT 2 3 until April 1970 when the patient devel¬ 16 WEEKS WEEKS intermittent of oped arthralgia hands and 1971 wrists and a pericardial friction rub. Hemoglobin was 10.4 g./lOO ml. and the FIG. 2.Graph showing response of reticulocytes and hemoglobin to prednisone LE cell test became strongly positive. administration. Arrow denotes blood transfusion. Prednisone was increased to 20 mg./day and by August 1970 the friction rub was gone. Prednisone was then reduced to 10 mg./day. In August 1971 she was hospitalized for the last time, with complaints of
\h
.
.
generalized muscle weakness and shortness on exertion. She had some difficulty with chewing and occasional regurgitation. There was no history of paroxysmal nocturnal dyspnea and only occasional swelling of the ankles at the end of the day. She appeared chronically ili. On ex¬ amination, the chest was clear; a left parasternal ejection murmur was heard, maximal at the second to fourth interspace. There was no hepato- or splenomegaly or lymphadenopathy. Neurological examination revealed easily fatigued eye muscles with slight ptosis of both upper eyelids, and the neck and arm weakness previously noted. The thyroid nodule was unchanged. Hemoglobin was 6.2 g./lOO ml., ESR 92 mm./hr., Coombs' test, direct and indirect, was negative. No antibodies were found against DNA or single stranded DNA. No free circulating DNA was detected. The total hemolytic complement was 178 CHU50 (normal range 180-260 FIG. 3.Bone CHU50). Ham's test for hemolysis was series. x250 734 CMA JOURNAL/OCTOBER 20, 1973/VOL. 109 of breath
marrow
showing a marked decrease in number
of cells of the erythroid
fever, tachycardia and tachypnea. Right lower lobe pneumonia was diagnosed, and she was given antibiotics; some improve¬ ment followed. However, on the evening of October 24, 1971, 20 minutes after receiving an oral dose of 12.5 mg. of Mytelase chloride, the patient was found dead. At autopsy the immediate cause of death was found to be bronchopneumonia. Situated in the anterosuperior mediastinum was a
white, hard, cystic
mass
measuring
2x2x1 cm. Its wall was composed of dense collagenous connective tissue with foci of calcification (Fig. 4A). A few nests of epithelioid cells and lymphocytes were present in the wall and occasional HassaFs corpuscles were noted in immediately adjacent fat (Fig. 4B). Because of the anatomical situation of this mass and the presence of both epithelioid cells and Hassall's corpuscles, it was thought that it represented the thymoma noted radiologically and subsequently destroyed by irradiation. Muscles showed scattered atrophic fibres but frankly necrotic fibres and lymphorrhages were not seen. The bone marrow showed a marked decrease in cells of the erythroid series as well as marked hemosiderosis. Hemosiderosis was also present in the liver and spleen. There was no evidence of extramedullary
hematopoiesis. The right kidney weighed 120 g. and the left 150 g. Both had moderately granular cortical surfaces. Basement membrane thickening was evident in many glomeruli. This was mild in degree in most, but in a few, "wire-loop" formations typical of lupus erythematosus were
noted (Fig. 5). Capsular thickening had occurred in some glomeruli while others were totally sclerotic. A few tubules con¬ tained hyaline casts. The heart was increased in weight to 350 g. owing to left ventricular hypertrophy. The aortic valve showed large fibrinous vegetations adherent to the lateral ventricular surfaces and the commissure of two cusps as well as to their inner surface (Fig. 6). The valve was normal other¬ wise. Microorganisms were not seen in these vegetations. Although they did not present the classical appearance of Libman-Sacks endocarditis, it was thought that these organizing aortic vegetations were related to the presence of lupus erythematosus. Fibrous pericardial adhe¬ sions were noted as well as fibrous pleural adhesions. Other findings were a microfollicular adenoma of the left lobe of the thyroid gland with fibrosis and atrophy of the rest of the thyroid parenchyma, adrenal cortical atrophy, and a small superficial ulcer of the duodenum.
Discussion
The association of thymic hyper¬ or thymoma with various mani¬ festations now thought to be of auto¬ immune origin has long been known. A classical example is the association of thymoma and myasthenia gravis.8'4
plasia
FIG. 4A.Wall of mediastinal cystic showing dense connective tissue with calcification. This represents the residuum of the irradiated thymoma. x 12.5 mass
FIG. 5.Renal glomerulus with basement membrane thickening, showing "wire-loop" lesion typical of lupus erythematosus. x 125
CM
1
Similarly, thymoma complicated by erythroblastopenic anemia has been frequently reported.5*6 Cases of thy¬ moma and systemic lupus erythema¬ tosus7 and others of myasthenia gravis and systemic lupus erythematosus8 have also been reported. Of the four above-mentioned dis¬ eases, thymoma, myasthenia gravis, systemic lupus erythematosus and erythroblastopenia, a combination of three has been recorded in only 14 instances (Table I).1-2-9-20 The existence of all four conditions in one patient, to the best of our knowledge, has never
2
3
«¦ «-h , in adipose d 4B.Hassall, s corpuscle FIG. tissue in the cyst wall shown in Fig. 4A. FIG. 6.Organizing fibrinous endocarditis of aortic valve cusps, consistent with x 250 Libman-Sacks endocarditis (vertical marks indicate centimetre measurements). 736 CMA JOURNAL/OCTOBER 20, 1973/VOL. 109
been well documented, although a posi¬ tive LE cell test was recorded in two patients who had the other three con¬ ditions.1'2 In several of the above-mentioned cases various circulating anti¬ bodies have been found. These in¬
volvement of the peripheral vessels, joints and pericardium. LE cell test was
repeatedly positive except during
thematosus with two specific histocompatibility antigens, HL-A-8 and W15, incidences of 33 and 40%, as com¬ pared to control population levels of 16 and 10% respectively.23 According to others, some autoim¬ mune diseases may have a viral etio¬ logy. For example, the SLE-like dis¬ ease of NZ black mice is now thought to be due to immune complexes with
16 months of clinical remission. Al¬ though no definite evidence for renal involvement was present during the clude antinuclear factor,1418,20 anti- course of the disease, at autopsy typical DNA antibodies,15'16'19 anti-thyroid wire-loop lesions were seen in the antibodies15 and skeletal muscle anti¬ glomeruli. Other findings included bodies.14'19 No rheumatoid factor was pericardial and pleural adhesions and Libman-Sacks-like vegetations on the viral particles as antigen.24 detected in the sera tested.1516'19 Whatever the etiology, there is clearOur patient first presented clinically aortic valve. The pathogenesis of the association cut evidence that some conditions fre¬ with myasthenia gravis confirmed by electromyography, muscle biopsy and of thymic disorders and autoimmune quently found in association may have diseases is not yet completely under- an immunological background. It was a remarkable response to anticholinesterase agents. Five months later an stood. A central role for the thymus in shown that intraperitoneal injections of anterior mediastinal mass was detected immune surveillance has now been sug¬ autologous or heterologous striated and irradiated. At autopsy, remnants gested. Fudenberg21 has postulated that muscle or thymus cells into guinea of thymic tissue wth cystic formation production of physiologic autoanti- pigs results in the release of an agent bodies is normally under the control which can produce a neuromuscular were seen in that area. The erythrocyte hypoplasia was do¬ of "T cells". If these thymus-derived block similar to that found in myas¬ cumented by several bone marrow as- cells are defective then there would be thenia gravis.25'26 This experimental pirations. It is of interest that at the an increase in production of autoanti- model can be further supported by the onset of the disease the administration bodies with eventual development of finding of anti-skeletal-muscle anti¬ of steroids induced proliferation of autoimmune diseases. A similar point bodies in 30% of patients with myas¬ erythrocyte precursors in the bone mar¬ of view was expressed by Osoba22 who thenia gravis.25 Half of the patients with pure ery¬ row and disappearance of the anemia. postulated that autoimmune phenoNo such effect was observed in the late mena may result from genetically de¬ throcyte hypoplasia (or erythroblasto¬ termined immunologic disease. For ex¬ penic anemia) have also a thymoma.*7 stage of the disease. Systemic lupus erythematosus was ample, recent reports have shown a Conversely, 5 to 6% of patients with clinically manifested mainly by in¬ high incidence of systemic lupus ery¬ thymoma eventually develop this form Table I.Immunological abnormalities in patients with thymoma, myasthenia gravis and/or erythrocyte aplasia and
systemic lupus erythematosus
Ref.
Age (yrs.) T /sex 48/M
no.
MG
ND not done ANF= antinuclear factor ?Circulating antibodies T thymoma, MG myasthenia gravis, EA
EA
SLE
LE cell test
ANF
+
Antimuscle ab*
AntiDNA Latex ab* ab* test ND ND NDND ND ND Anti-
thyroid
Comments Transient reticulocytosis after thymectomy and after splenectomy, sustained response with ACTH
=
=
=
=
erythrocyte aplasia, SLE systemic lupus erythematosus =
CMA JOURNAL/OCTOBER 20, 1973/VOL. 109 737
of anemia."8 The immunological background of this association has been suggested by showing that plasma from a patient with a thymoma and erythrocyte hypoplasia could inhibit the effect of exogenous erythropoietin in polycythemic mice.'9 Further studies showed that this plasma fraction was an IgG."O Field e.t aP1 and Krantz and Kao" suggested that this antibody is not directed specifically against erythropoietin, but that it exerts its activity at the stem cell level. Our case supports the concept of an immune basis of the erythrocyte aplasia since the administration of prednisone restored the erythroblastic activity of the bone marrow, at least on one occasion. The lack of response on the second occasion could be explained by irreversible atrophy of bone marrow elements in the advanced stage of the disease. The favourable influence of steroids on bone marrow changes in erythrocyte aplasia was seen by others, and recently immunosuppressive agents were suggested as treatment of this condition;'", also, splenectomy was found to be of value in some patients.1' Recently the response of bone marrow in culture to erythropoietin has been found to be helpful in determining response to treatment.'3 The link between systemic lupus erythematosus and other autoimmune disorders has been repeatedly stressed. Development of hyperplastic changes in the thymus similar to those in myasthenia gravis and even thymomas have been reported in systemic lupus
erythematosus.i'3" The similar age of onset, female predilection and clinical pattern of myasthenia gravis and systemic lupus erythematosus have led several authors to suggest an association between these two entities. As well, family studies of patients with myasthenia gravis have shown a higher incidence of systemic lupus erythematosus than is found in a normal population.36 It is likely, furthermore, that the thymic disorders common to both have pathogenetic significance."7,3" On review of the literature no evidence could be found to implicate anticholinesterase agents - the only medication the patient received other than prednisone - in either the drug-induced systemic lupus erythematosus syndrome or erythroblastopenic anemia. Whatever the etiological factors(s), it seems that an association of two or more autoimmune disorders in one patient (Table I) may be more frequent than was previously believed. A preexisting "central" immunological deficiency may be the common denominator. Our thanks are expressed to Dr. D. Osoba for his critical comments and discussion
of the case, to Mrs. R. Hajdinjak for performance of immunological tests, to Miss M. Bliss for excellent photographic assistance, and to Mrs. Christine Onofrey for her diligent preparation of the manuscript. References 1. SIGUIR F, MATHE G, GODEAU P, et al: Erythroblastopenie, myasthenie, cellules de Hargraves, tumeur thymique. Etude d'une observation d'evolution favorable. Ann Med Interne (Paris) 120: 561, 1969 2. ZOUPANOS G, SEAusuR F, SCHNEIDEt G: Association de thymome, myasthenie, anemie par erythroblastop6nie et presence de cellules LE dans le sang chez le xneme malade. Schweiz Med Wochenschr 100: 1885, 1970 8. OPPENHEIM H: Weiterer Beitrag zur Lehre von der acuten, nichst eltrigen Encephalitis und der Polioencephalo-myelitis. Dtsch Z Nervenheilkd 15: 1, 1899 4. WFJGEaT K: Pathologisch-anatomischen Beitrag zur Erbschen Krankheit. Neurol Clin 20: 597, 1901 5. MATRAs A, PRISEL A: Uber einige gew&chse des Thymus. Beitr Pathol Anat 80: 270, 1928 6. HIRST E, ROBERTSON T: The syndrome of thymoma and erythroblastopenic anemia. A review of 56 cases Including 8 case reports. Medicine (Baltimore) 46: 225, 1967 7. LARBsON 0: Thymoma and systemic lupus erythematosus in the same patient. Lancet II: 665, 1968 8. HARVEY AM, SCHULMAN LE, TUMULTY PA, et al: Systemic lupus erythematosus: review of the literature and analysis of 188 cases. Medicine (Baltimore) 88: 291, 1954 9. CHALMERS JNM, BOHEIMER K: Pure red cell anemia in patients with thymic tumours. Br Med J II: 1514, 1954 BAKHER PM: Enkele opmenkinger by twee 10. gezwellen van der thymus. Med T Geneesk 98: 386, 1954 11. WEINBAUM JG, THOMSON RF: Erythroblas-
tic hypoplasia associated with thymic tumour and myasthenia gravis. Am J Clin Pathol 25: 761, 1955 12. CASTAIGNE P, LHERMITTE F, ESCOUROLLE R, et al: Myasthenia, thymic tumour and aplastic anemia. Rev Neurol (Paris) 105: 878, 1961 1 8. FUNKHOUSEt JW: Thymoma associated with myocarditis and the LE cell phenomenon. N Engl J Med 264: 84, 1961 14. HESS EV: Lupus erythematosus cells, antinuclear and antimuscle factors and thymic abnormalities in myasthenia patients, In l'he thymus in immunobiology edited by GOOD RA, GABRIELSEN AE, kew York, Harper and Row, 1962, p 668 15. GOLDiN H, ROBBINS WC: A patient with myasthenia gravis, thymoma and lupus nephritis. Arthritis Rheum 6: 272, 1963 16. MAKELA TE: Myasthenia gravis and systemic lupus erythematosus. Acta Med Scand 175: 777, 1964 17. ROLAND AS: The syndrome of benign thymoma and primary aregenerative anemia. Am J Med Sci 247: 719, 1964 18. HINRICHS VR, STEvENSON JD: Thymoma, myasthenia gravis and aplastic anemia. Ohio State Med J 61: 81, 1965 19. DELMAS-MARSELET Y, LEDuc M, LERCHE B, et al: Tuineur du thymus et lupus-6ryth& mateux-dissemine. Etude anatomoclinique et physio-pathologiques. considerations Presse Med 77: 821, 1969 20. SAFDAN SH, KRANTZ SB, BROWN EB: Successful inmmunosuppressive treatment of erythroid aplasia appearing after thymectomy. Br J Haematol 19: 485, 1970 21. FUDENBERG HH: Genetically determined immune deficiency as the predisposing cause of autoimmunity and lymphoid neoplasia. Am J Med 51: 295, 1971 22. OSORA D: Thymic function, immunologic deficiency and autoimmunity. Med Clin North Am 56: 819, 1972 28. ZiF- M: Viruses and the connective tissue diseases. Ann Intern Med 75: 951, 1971 24. TALAL N: Immunologic and viral factors in the pathogenesis of systemic lupus erytheinatosus. Arthritis Rheum 18: 887, 1970 2.5. GOLDSTEIN G: Myasthenia gravis and the tliymus. Annual Review of Medicine, vol 22, edited by DE GRA AC, CRESR WP, Palo Alto, Calif, Annual Reviews, 1971, p 119 26. GOLDSTEIN G, WHITNGHAM S Experimnental autoimmune thymitis: an animal model for myasthenia gravis. Lancet II: 815, 1966 27. DAMFSHEK W, BROWN SM, RUBIN AD: Pure red cell anemia (erythroblastic hypoplasia) and thymoma. Semin Hematol 4: 222, 1967 28. JAcoBs EM, Hu-rEs RVP, POOL JL, et al: Benign thymoma and selective erythroid aplasia. Cancer 12: 47, 1959
738 CMA JOURNAL/OCTOBER 20, 1973/VOL. 109
29. JEPSON JH, LOWENSTEIN L: Inhibition of erythropoiesis by a factor present in the plasma of patients with erythroblastopenia. Blood 27: 425, 1966 30. JEPsoN JH, GARDNER FH, DEGAN I, et al: A gamma globulin inhibitor of erythropoiesis in erythroblastopenic plasma from patlents with thymoma (abstract). Clin es 16: 586, 1968 31. FIELD EO, CAUGHI MN, BLACKETT NM, et al: Marrow suppressing factors in the blood in pure red cell aplasia, thymoma, and Hodgkin's disease. Br J Haematol 15: 101, 1968 32. KRANTZ SB, KAO V: Studies on red celi aplasia. II. Report of a second patient with an antibody to erythroblast nuclei and a remission after immunosuppressive therapy. Blood 84: 11, 1969 88. KRANTZ SB: Pure red cell aplasia: response of 8 patients treated with immunosuppressive drugs (abstract). Clin Res 20: 787, 1972 34. MACKAY IR, DE GAIL P: Thymic germinal centers and plasma cells in systemic lupus erythematosus. Lancet II: 667, 1968 35. KOUGH RH, BARNES WT: Thymoma associated with erythroid aplasia, bullous skin eruption and the lupus erythematosus cell phenomenon. Report of a case. Ann Intern Med 61: 308, 1964 36. PIEMME TE: Myasthenia gravis and autoimmune disease. Review of the literature including a case report of the coexistence of myasthenia and systemic lupus erythematosus. Ann Intern Med 60: 180 1964 87. HUND ER, DOWDLE W, CAsEy ii et al: Virus antibody levels in systemic lupus erythematosus. Arthritis Rheum 15: 267, 1972 88. KANTOR GL, GOLDBERG LS, JOHNSON BL: Immunologic abnormalities induced by post-perfusion cytomegalovirus infection Ann Intern Med 78: 558, 1970 89. HOLLINGER FB, ROTHFIELD NF, NiEDEamAN JC: Antibodies to viral antigens in systemic lupus erythematosus. Arthritis Rheum, 14: 1, 1971
