Prevention of congenital rubella J. PHILIP WELCH, MB, CH B, PH D, FCCMG
The vaccine of choice for rubella vaccination is considered to be RA 27/3, based on frequency of side effects. duration of immunity, antigenic potential and rate of reinfection by wild virus. The most appropriate individuals to be vaccinated are prepubertal schoolgirls and susceptible members of other high-risk groups, and a nationwide immunization program is suggested. Premarital determination of rubella-immune status should be mandatory for all women of childbearing age. A favourable cost/benefit ratio for rubella vaccination seems highly probable. The use of a rubella "fact sheet" to provide education and information for those at risk is strongly recommended. Le vaccin de choix pour Ia vaccination contre Ia rubeole est considers Atre le RA 27/3 du point de vue de la frequence des effets secondaires, de Ia duree de l'immunit6, du potentiel antigenique et du taux de reinfection par le virus sauvage. Les meilleurs sujets pour Ia vaccination sont les ecolieres d'Age pr6pubertaire et les membres susceptibles d'autres groupes A risque 61ev6; un programme national d'immunisation est suggere. La determination avant le manage de l'etat d'immunit6 contre Ia rubeole devrait Otre obligatoire pour toutes les femmes en Age d'enfanter. Pour Ia vaccination contre Ia rubeole un rapport favorable des coOts et des benefices semble tres probable. On recommande fortement l'emploi d'un feuillet presentant les faits sur Ia rubeole, pour l'education et l'information des personnes expos6es.
The occurrence of rubella in women in early pregnancy is associated with a high incidence of congenital anomalies and mental retardation among the resultant offspring.1 Epidemics of rubella commonly occur at 7- to 9-year intervals, and about 1 % of infants born of women who were pregnant during an epidemic will have congenital rubella.1'1 At a conservative estimate 30000 children had rubella-associated birth defects in the United States after the 1964 epidemic.1 Roughly 20% of adults are susceptible to rubella, the proportion varying with age and chroFrom the Atlantic Research Centre for Mental Retardation and the department of pediatrics, Daihousie University, Halifax Reprint requests to: Dr. JP. Welch, Rm. C-RI, Clinical Research Centre, 5849 University Ave., Dalhousie University, Halifax, NS B3H 4H7
nologic proximity to a previous epidemic, and generally being highest among young adults. A "hidden" effect of rubella infection in pregnancy is the production of congenital deafness in the infant, as shown in the study by Gumpel, Hayes and Dudgeon:3 61.2% of a group of congenitally deaf children (85 of 139) showed evidence of previous rubella infection, in contrast to 7.1 % of a comparable control group. Further analysis suggested that about one quarter of all cases of congenital deafness of "unknown etiology" are due to rubella infection in pregnancy. Reduced incidence of rubella infection in pregnancy would thus be expected to decrease the number of children with congenital deafness of unknown etiology. Since many children with rubella infection in utero continue to shed the virus for a considerable time after birth, susceptible women working with young deaf children, and also those employed as schoolteachers or nurses in pediatric and obstetric hospitals, may be at high risk of infection. Several rubella vaccines of proven efficacy licensed for use in Canada4 make rubella embryopathy a theoretically preventable condition. They appear to produce serologic immunity for some years,5 but probably for a shorter period than does natural infection. Choice of vaccine A disturbing trait of the rubella vaccines currently available in Canada is their inability to protect against wild virus infection for any appreciable length of time.6 A newer vaccine, RA 27/3, prepared in human WI-38 cells, appears to be antigenically more complete than either HPV-77 or Cendehill strain vaccines.79 RA 27/3 also results in a higher rate of conversion to seropositive than either HPV-77 or Cendehill strain vaccines10 and is associated with a relatively low rate of reinfection by wild virus.11 The reinfection rate for other commonly used attenuated vaccine strains has been found to be significantly higher; for the Cendehill strain it was over 50% only 2 years after vaccination, and for RA 27/3 it was 9% (comparable to the reinfection rate following natural immunization).12 The immunity induced by RA 27/3 appears to be similar to natural immunity.13 The overall advantages have been extensively reviewed by Plotkin, Farquhar and Ogra.11 The side effects associated
with this vaccine appear to be no greater than those associated with other vaccine strains11 and RA 27/3 therefore appears to be overwhelmingly the vaccine of choice. At the time of writing it has been licensed for use in the US; although it is not yet licensed for use in Canada, licensing is anticipated in the near future. Lack of immediate availability of this vaccine, however, should not be considered a valid reason for postponing a national program of rubella immunization. Choice of vaccinee Women The effects of rubella vaccine on the fetus of a current pregnancy or one that shortly follows a vaccination are not fully established; however, it appears that the risks are less than those associated with similar wild virus infection.14 Since there has been documented recovery of the virus from various fetal sites after such maternal inoculation, pregnancy is contraindicated for at least 2 months after rubella vaccination.1416 Young children Evidence suggests that rubella vaccination of young children to produce herd immunity is not effective;6'17. in addition, young children may not be the major source of infection in pregnant women.23 Since rubella vaccines give immunity of relatively limited duration, a substantial percentage of a population artificially immunized in early childhood could become susceptible to rubella by childbearing age, as shown in a serologic follow-up study of early childhood immunization.1' The risk of early vaccination may also be concealed, since waning immunity may prevent overt clinical signs and symptoms but not infection, viremia and teratogenesis. Although the possibility of "booster" immunization in preadolescence has been considered,re evidence suggests that this does not significantly increase the antibody titre in those previously vaccinated26 unless RA 27/3 (intranasally) is used for the booster.11 Wild-type infection can occur as soon as 6 to 9 months after rubella immunization, though the potential for teratogenesis in these circumstances has not been fully determined.27 The possibility of teratogenesis must be taken very seriously, however, because embryopathy after reinfection of some naturally immune women has been documented.2
CMA JOURNAL/JULY 23, 1977/VOL. 117 151
Some workers28 have speculated that incomplete or "spotty" immunization programs could create pockets of Unimmunized children who would become totally susceptible adults among whom a rubella epidemic could be devastating. Although the numbers of cases of rubella and congenital rubella syndrome reported in the US have diminished since the licensing of attenuated rubella virus in 1969,14 the decline is not necessarily attributable to the current vaccination programs.29 Mass rubella immunization of all children also raises an ethical problem not present in similar programs for other diseases. Rubella immunization of young boys is based on the premise that immunity in this group will help prevent infection in a different group (pregnant women), which in turn will prevent rubella embryopathy in a third group (fetuses). This introduces a new and potentially dangerous concept in medical care: the immunization of a group of individuals (together with the attendant risks, though small) for little or no direct benefit to the group, so that a future generation may be protected from specific congenital abnormalities. Directive vaccination It has been recommended that vaccination be given to those at risk.23'.'283' Attention has been focused especially on immunizing young girls and instituting premarital testing for rubella susceptibility. Susceptibility is greatest in younger age groups. A study at the Hospital for Sick Children, Toronto, showed that more than 25% of teenagers attending the teen clinic (over half of whom were pregnant) were susceptible to rubella; determination of rubella immunity status by previous history of natural rubella or of immunization was shown to be totally unreliable.32'33 A directive vaccination scheme introduced in the United Kingdom advocates rubella vaccination of prepubertal girls and groups of women at high risk, including schoolteachers, nursery staff, female staff of pediatric hospitals, obstetric and gynecologic units and antenatal clinics, and women seeking premarital guidance.. With this scheme immune status of prepubertal girls is not determined. In studying the effects of the scheme Hambling. found that the proportion of seronegative (antibody titre K 1 / 8) girls in the age group 15 to 19 years decreased by over one third from 1971-72 to 1974. Since vaccination has been offered only since 1970, further reduction in the proportion of susceptible individuals is anticipated. Testing for rubella susceptibility at
the time of marriage is an additional method of identifying a high-risk population. Several states in the US, including California, Rhode Island, Colorado and Montana, have passed legislation requiring premarital testing for rubella susceptibility in women of childbearing age. Studies indicate that a large proportion of women so identified are subsequently vaccinated.36 Prevention of rubella embryopathy in Canada A recent analysis. showed that the lifetime cost of congenital rubella in an unvaccinated population was more than $35 per female, whereas the cost of vaccination was estimated at $3. The same authors estimated that vaccination at age 12 yields benefits 80% greater than those of vaccination in early childhood. Clearly the cost of provision of rubella vaccine, vaccination when appropriate, and the necessary promotional campaign is far outweighed by the savings resulting from the prevention of rubella embryopathy and the reduced incidence of congenital deafness. The problem of rubella is substantially greater than that posed, for example, by phenylketonuria, which occurs in about 1 infant in 10000. Despite the fact that only about one new case of phenylketonuria occurs yearly in Nova Scotia, that province, like most others, has an excellent screening program financed by the provincial health service. Comparable attention to the prevention of rubella embryopathy is just beginning. Yet in Nova Scotia the 1973-74 rubella epidemic is expected to have affected 100 babies, or 1% of infants born of women who were pregnant during the epidemic.2 No exhaustive survey has been done but there are at least 25 infants with documented embryopathy, 19 of whom were born of Nova Scotians pregnant during that epidemic37 (and R.S. Faulkner: personal communication, 1976). The estimated cost of caring for these 25 infants is $1.5 to $2 million.38 It is apparent that there is a greater need for provincial health services to finance prevention of rubella embryopathy in Canada than to screen for phenylketonuria, despite the obvious benefit of the latter. I have several proposals for constructive future action. Some of the activities are already in effect in some provinces but the general level of concern in most provinces is too low. I have also prepared a rubella "fact sheet" (Appendix A) outlining the hazards of rubella and the benefits of vaccination and advocating specific policies, that I believe to be a most useful tool in fulfilling the critically important need to inform susceptible females of
152 CMA JOURNAL/JULY 23 1977/VOL. 117
the importance of rubella immunity. It is presently in use at both the Izaak Walton Killam Hospital for Children and the Grace Maternity Hospital in Halifax. Both hospitals test all female employees for rubella hemagglutination-inhibition (HI) antibodies at the beginning of their employment. Those found to be susceptible to rubella are given the fact sheet and offered vaccination. Proposals 1. Provincial departments of health should initiate a high-intensity publicity program aimed toward rubella vaccination of all schoolgirls during their 12th year. I suggest that this be done through a month-long, intensive promotion through the schools, along with the use of all news media. Vaccination should be done through the school health authorities by public health nurses. Appropriate notation of vaccination should be entered on the school health record of each child. The records should be checked shortly before the end of the school year to identify all 11- and 12-year-old girls who have not been vaccinated, then vaccination should be offered to each individual by the school health nurse after consultation with the parents. Further encouragement for vaccination may be provided by distribution of a rubella fact sheet, such as that in Appendix A, to these families. School health records should accompany children who transfer between schools. 2. HI testing should be introduced as a legal requirement for all women prior to marriage unless they are over 50 years of age or have had surgical sterilization. Those identified as susceptible to rubella should be given a rubella fact sheet and, if not then pregnant, offered rubella vaccination together with advice on and assistance in maintaining a pregnancy-free state for at least 3 months. 3. Provincial health departments should promote the free testing of rubella susceptibility (HI testing) for all women at their first prenatal visit to a physician or other appropriate health care professional. 4. All women should have HI testing at delivery to identify those still susceptible to rubella; those found susceptible should be provided with a rubella fact sheet. Rubella vaccination should be offered to all susceptible women. 5. The cost of rubella vaccine should be borne by the provincial governments and the cost of vaccination should be covered by provincial medical insurance. 6. After reviewing available rubella vaccines, data on side effects, likely duration of immunity and antigenic
potential, I recommend the use of RA 27/3 vaccine as soon as it is officially licensed in Canada.
31. JONCAS JH: Rubella immunization (C). Can Med Assoc J 111: 907, 1974 32. STOFFMAN SM, WOLFISH MG: The susceptibility of adolescent girls to rubella. Clin
The advice of Dr. K.R. Rozee, department of microbiology, Daihousie University, in the preparation of this manuscript is gratefully acknowledged.
girls. Med Post 10 (17): 19, 1974 34. DUDGEON JA: The control of diphtheria,
tetanus, poliomyelitis, measles, rubella and mumps. Practitioner 215: 299, 1975
35. HAMSLING MH: Effect of a vaccination programme on the distribution of rubella antibodies in women of childbearing age. Lancet
1: 1130, 1975 36. JUDSON EN, Sitaw BS, VERNON TM: Mandatory premarital rubella serologic testing in
References 1. COOPER LZ: Birth Defects. Orig Artic Ser 4: 23, 1968 2. COOPER LZ, KItUOMAN S: Clinical mamfestations of postnatal and congenital rubella. Arch Ophthalmol 77: 434 1967 3. GUMPEL SM, HAYEs K, bUDGEON JA: Congenital perceptive deafness: role of intrauterine rubella. Br Med 1 2: 300, 1971 4. MCLEAN DM: The rubella situation in Canada - 1972. Can I Public Health 63: 385, 1972
5. KRUGMAN 5, KATZ SL: Rubella immunization: a five-year progress report. N Engl .1 Med
290: 1375, 1974 6. HORSTMANN DM, LIESHABER H, La Bouvsrnt GL, et al: Rubella reinfection of vaccinated and naturally immune persons exposed in an epidemic. N Engl J Med 283: 771, 1970 7. LE BouvIER G, PLOTKJN SA: Precipitin responses to rubella vac.ine BA 27/3. 1 Infect Dis 123: 220, 1971 8. WALLACE RB, 15AC50N P: Comparative trial of HPV-77, DE-5 and RA 27/3 llve-attenuated rubella vaccines. Am I Dis Child 124: 536, 1972 9. HORSTMANN DM: Need for monitoring vaccinated populations for immunity levels. Frog
Med Virol 16: 215, 1973 10. FREESTONE DS, REYNOLDS GM, MCKINNON JA, et al: Vaccination of schoolgirls against rubella: assessment of serological status and a comparative trial of Wistar RA 27/3 and Cendehill strain llve attenuated rubella vaccines in 13-year-old schoolgirls in Dudley.
Br I Prey Soc Med 29: 258, 1975
11. PLOTKIN SA, FARQiJHAR JD, OGRA PL: Immunologic properties of RA 27/3 rubella virus vaccine: a comparison with strains presently llcensed in tbe United States. JAMA 225: 585, 1973 12. GRILLNER L: Immunity to intranasal challenge with rubella virus two years after vaccination: comparison of three vaccines. I Infect Dis 133: 637, 1976 13. LIEBHABER H, INGALLS TH, La Bouvxazt GL, et al: Vaccination with RA 27/3 rubella vaccine. Am I Dir Child 123: 133, 1972 14. MODLIN JF, HERRMANN K, BRANDLINGBENNETF AD, et al: Risk of congenital abnormality after inadvertent rubella vaccination of pregnant women. N Engl I Med 294: 972, 1976 15. Rubella vaccination and pregnancy (E). Lancet 2: 769, 1973
16. LEVINE MM: Live-virus vaccines in pregnancy: risks and recommendations. Lancet 2: 234, 1974 17. HOR5TMANN DM, PAJOT TG, LIEBHABER H: Epidemiology of rubella: subclinical infection and occurrence of reinfection. Am I Dis
Child 118: 133, 1969 18. LEHANE DE, Nawauao NR, BEAM WE JR: Evaluation of rubella herd immunity during an epidemic. JAMA 213: 2236, 1970 19. RACHELEF5KY GS, HERRMANN KL: Congenital rubella surveillance following epidemic rubella in a partially vaccinated community. I Pedtatr 84: 474, 1974 20. WEINsTZrn L, CHANG TW: Prevention of
rubella. Pediatrics 55: 5, 1975 21. CHANG TW, DasRosiaas 5, Wamsmrn L: Clinical and serologic studies of an outbreak of rubella in a vaccinated population. N Engl I Med 283: 246, 1970 22. WILKINs 3, LEEDOM JM, PORTNOY B, et al: Reinfection with rubella virus despite live vaccine induced immunity. Trials of HPV-77 and HPV-80 live rubella virus vaccines and subsequent artificial and natural challenge
studies. Am I Dis Child 118: 275, 1969 23. SCHOENBAUM SC, BIANo 5, MACK T: Epidemiology of congenital rubella syndrome. JAMA 223: 151, 1975 24. HOR5TMANN DM: Controlling rubella: problems and perspectives. Ann Intern Med 83: 412, 1975 25. SCHOENDAUM SC, HYDE JN JR, BARTOsHESKY L, et al: Benefit-cost analysis of rubella vaccination policy. N EngI I Med 294: 806, 1976 26. WYLL SA, HERRMANN KL, AB1WTYN E, et al: Rubella booster immunization: serologic response to a second dose of vaccine. JAMA 216: 1451, 1971 27. Rubella reinfection and the foetus (E). Lancet 1: 978, 1973 28. Nasr 3M, CARVER DH:
Pediatr 15: 625, 1976 33. WILLS M: Rubella tests urged for all young
Rubella immuniza-
tion: reconsideration of our present policy. Am I Epidemiol 92: 162, 1970 29. SCHOENBAUM SC, BIANO 5, MAcic T: Rubella immunization. JAMA 235: 248, 1976 30. KATz M: Rubella va.ine. I Pedlatr 84: 615, 1974
Colorado. A preliminary report. JAMA 229:
1200, 1974
37. FAULKNER RS, GOUGH DA: Rubella 1974 and its aftermath, congenital rubella syndrome.
Can Med Assoc 1 114: 115, 1976 Epidemic: Estimated Health and Economic Costs, Atlanta, GA, 1965
38. Center for Disease Control: 1964-65 Rubella
Appendix A: Rubella fact sheet
1. What is rubella? Rubella, also known as German measles, is a mild infectious disease, usually occurring in childhood. It usually begins with a short period of mild symptoms of inflammation of the nose and air passages and slight fever, followed by a rash usually lasting 2 to 3 days. Such natural infection usually results in lifelong immunity. 2. Why is rubella so dangerous? Women who contract the disease while pregnant, especially during the 1st 3 months, have a high risk of miscarriage or of giving birth to children with heart defects, blindness, deafness, bone abnormalities, brain damage and other serious problems. The percentage of abnormal births ranges from very high among women who have rubella early in pregnancy, to relatively low in women who have the disease later in pregnancy. Those who contract rubella during the 1st month of pregnancy face a 90% risk of giving birth to an abnormal child. Infection during the 2nd month carries a 50% risk, and infection in the 3rd month, a 10% risk. 3. Are babies often affected and damaged by rubella? Yes. There are always rubelladamaged babies being born, and in the year following an epidemic there may be up to 10 affected babies in every 1000 pregnancies. 4. If a woman is pregnant and comes in Contact with a person who has rubella, can she get an injection that will protect her future baby? No. Antibody shots (gamma globulin) can be given; however, these probably only help prevent the mother from showing signs of rubella and probably do not protect the fetus. In this circumstance it is most important for the woman to visit her doctor right away so that he may test her susceptibility to rubella. If she is susceptible a repeated test will enable the doctor to determine whether she has been infected by rubella and thus whether the fetus is at risk.
5. Do measles shots protect against rubella also? No, not unless the shots are a combination vaccine against both diseases. Measles (rubeola) and German measles (rubella) are different diseases. Protection against one does not offer protection against the other. 6. Does rubella occur in epidemics? Yes. Rubella epidemics usually occur at 7- to 9-year intervals. (See question 3.) 7. What is the disease's history? Rubella was regarded as relatively harmless until 1941, when an Australian eye specialist, Sir Norman McAlister Gregg, noted an unusually high number of birth defects following an outbreak of the disease. Fetal abnormalities that occurred included congenital blindness, heart disease, deafness and mental retardation. His observation led to the discovery that rubella, when contracted by expectant mothers, can damage their unborn children. Scientists isolated the virus that causes rubella in 1962 and immediately began work on developing live vaccines to protect against it. The first vaccine became available in Switzerland in 1969. 8. Are there any side effects of the vaccine? The vaccine causes no side effects in most children and only mild side effects in a few, such as slight fever, or a minor rash that subsides after 1 or 2 days. (Sometimes the latter reaction occurs a week or 2 after vaccination.) Some women have experienced a similar reaction, or slight discomfort in the joints for 1 to 2 days. 9. Who should get rubella vaccine? The vaccine should be given to all girls between their 11th and 12th birthdays. It should also be given to any women who are not immune to rubella and are of childbearing age; these women should not become pregnant for at least 3 months after vaccination. (See questions 12 to 14.) 10. Should boys be vaccinated against rubella? If all girls and nonimmune young women are vaccinated it is not really necessary to vaccinate boys. However, it is not harmful, and their vaccination may help control the spread of rubella in a community in which a substantial number of girls and young women are not vaccinated or naturally immune. 11. Where can one get a rubella vaccination and how much does it cost? Rubella vaccination may be obtained from either one's family doctor or any of the provincial public health clinics. Both vaccine and vaccination are provided free of charge at the public health clinics. In some provinces fain-
CMA JOURNAL/JULY. 23, 1977/VOL. 117 153
ily doctors must pay for their supplies of rubella vaccine; hence there is likely to be a small charge incurred for both 4'accine and vaccination obtained from them. If blood tests are necessary to determine possible susceptibility to rubella (see questions 12 and 14) these can be arranged through one's family doctor. There is usually no charge for the laboratory test, the cost of which, in most cases, is borne by the provincial departments of health. 12. Are there any who have an especially high risk? Yes. It is particularly important that young women who may become pregnant and who have a particularly high possibility of exposure to rubella be tested for immunity and vaccinated if susceptible. This includes all such female staff in any children's hospital, obstetric and gynecologic unit, nursery and school (see below).
13. Is there anyone who should not receive rubella vaccine? Yes. Pregnant women or those likely to become pregnant within 3 months after vaccination, patients who have a high fever, those who have leukemia or other malignant disease, those whose resistance to infection has been lowered by radiation therapy and those known to be allergic to any ingredients in the vaccine. 14. What if a woman of childbearing age requests vaccination against rubella? Her doctor should decide whether vaccination is necessary. It is not necessary if she has natural immunity, but studies indicate that one in every five women of childbearing age is not immune. Immunity can be determined by a laboratory test. If she is not immune - and is not pregnant - her doctor may vaccinate her if she agrees to avoid
pregnancy by a medically approved method for at least 3 months after she has been vaccinated. 15. Is it possible to terminate the pregnancy (therapeutic abortion) if the fetus is known to be likely to have rubella damage? It is not presently legal to terminate a pregnancy in Canada because of known rubella damage. If such a state of pregnancy has a significant effect on the mother's health, termination can be considered. 16. How can the pregnant woman and her child be protected? The best way is for expectant mothers to avoid exposure to rubella, and to ensure that those at risk are immune to this disease. The best way to do this is by mass immunization of young girls.E
Pericarditis as a manifestation of essential thrombocythemia P. AVERBACK, MD; M. MOINUDDIN, MD
A 58-year-old woman presented with pericarditis and pericardial effusion. Investigation revealed that she was suffering from a thrombocythemic myeloproliferative disorder; she died of massive pulmonary embolism 10 days after admission. Histologic study verified epicardial and pericardial trilineage hematopoiesis. Pericarditis is an unusual feature of essential thrombocythemia and it may occur in direct relation to the abnormal cellular proliferation. Une femme de 58 ans a presente une p6rlcardite avec epanchement pericardique. L'etude du cas a revel6 que Ia patiente souffralt d'une proliferation my6loude thrombocytop6nique; elle est decedee d'embolie pulmonaire massive 10 jours apres son hospitalisation. Une etude histologique a confirm6 Ia presence d'une hematopolese 6picardique et pericardique touchant trois lignees cellulaires. La pericardite est une manifestation inhabituelle de Ia thrombocytopenie essentielle et elle peut survenir en relation directe avec une prolif6ration cellulaire anormale.
This report describes a patient with essential thrombocythemia who presented with pericarditis, and in whom Prom the Pathology Institute and Royal Victoria Hospital, Montreal Reprint requests to: Dr. P. Averback, 3775 University St., Montreal, PQ H3A 2B4
autopsy study revealed histologic evidence of hematopoiesis (erythrocyte and leukocyte series and megakaryocytes) in the epicardium and pericardium. While the chief cause of death in patients with agnogenic myeloid metaplasia is cardiac (due to arteriosclerosis and other factors1) we were unable to find other reports of pericarditis as a presenting feature in thrombocythemia or in association with proven pencardial and epicardial trilineage hematopoiesis.
Case report Clinical course and findings A 58-year-old woman was admitted to hospital with chief complaints of fatigue and anterior chest pain. She had noted blood-tinged stools intermittently for 2 years and had lost 6 kg in that time, but had not seen a physician. She described generalized fatigue of 5 months' duration. For 2 weeks prior to admission there had been low-grade fever, episodes of fainting and anterior chest pain; acetylsalicylic acid provided some relief. Physical examination revealed pulsus paradoxus (rate, 100 beats/mm), jugular venous distension, scattered basal rhonchi, and enlargement of the spleen (to 11 cm below the left costal margin) and the liver (to 16 cm below the right costal margin) with slight tenderness of the liver. Admission chest radiograph showed a large cardiac silhouette, with clear lung fields and small bilateral pleural effusions. Echocardiography confirmed a large
154 CMA JOURNAL/JULY 23, 1977/VOL. 117
anterior and posterior pericardial effusion. Electrocardiography revealed minimal STsegment elevation in leads II, III, aVF, V5 and V6, but was otherwise normal. The hemoglobin value was 8.3 g/dL; hematocrit, 29%; leukocyte count, 32.2 x 109/L with 3% blast forms, 3% promyelocytes, 5% myelocytes, 2% metamyelocytes, 5% band forms, 60% mature neutrophils, 13% lymphocytes and 9% basophils; platelet count, 2200 x 109/L; and reticulocyte count, 1.8%. Blood smear showed microcytic hypochromic erythrocytes with occasional tear-drop forms. Mean corpuscular volume was 60 .3; mean corpuscular hemoglobin, 17.3 pg; and mean corpuscular hemoglobin concentration, 28.4%. The erythrocyte count was 4.95 x 1012/L. The leukocyte alkaline phosphatase score was 122. Prothrombin time was 16.2 s (control, 11.8 s) and partial thromboplastin time, 62.8 s (control, 32.9 s). The value for the platelet glass-bead retention test was 9% (normal, 27 to 48%). One of three stool specimens was positive for occult blood. Serum alkaline phosphatase value was 272 lU/L and serum lactate dehydrogenase value, 628 lU/L. Results of other initial tests, including lupus erythematosus cell preparations and tests for Philadelphia chromosome, antinuclear antibodies and rheumatoid factor were negative. A bone marrow aspirate and biopsy taken from the posterior iliac crest showed hypercellular particles without fat spaces, no stainable iron and a striking increase in number of megakaryocytes (Fig. 1). Therapy was started with busulfan, hydroxyurea, transfusions of packed erythrocytes, and ferrous sulfate. A lung scan on the 3rd day showed a segmental right
The vaccine of choice for rubella vaccination is considered to be RA 27/3, based on frequency of side effects. duration of immunity, antigenic potential and rate of reinfection by wild virus. The most appropriate individuals to be vaccinated are prepubertal schoolgirls and susceptible members of other high-risk groups, and a nationwide immunization program is suggested. Premarital determination of rubella-immune status should be mandatory for all women of childbearing age. A favourable cost/benefit ratio for rubella vaccination seems highly probable. The use of a rubella "fact sheet" to provide education and information for those at risk is strongly recommended. Le vaccin de choix pour Ia vaccination contre Ia rubeole est considers Atre le RA 27/3 du point de vue de la frequence des effets secondaires, de Ia duree de l'immunit6, du potentiel antigenique et du taux de reinfection par le virus sauvage. Les meilleurs sujets pour Ia vaccination sont les ecolieres d'Age pr6pubertaire et les membres susceptibles d'autres groupes A risque 61ev6; un programme national d'immunisation est suggere. La determination avant le manage de l'etat d'immunit6 contre Ia rubeole devrait Otre obligatoire pour toutes les femmes en Age d'enfanter. Pour Ia vaccination contre Ia rubeole un rapport favorable des coOts et des benefices semble tres probable. On recommande fortement l'emploi d'un feuillet presentant les faits sur Ia rubeole, pour l'education et l'information des personnes expos6es.
The occurrence of rubella in women in early pregnancy is associated with a high incidence of congenital anomalies and mental retardation among the resultant offspring.1 Epidemics of rubella commonly occur at 7- to 9-year intervals, and about 1 % of infants born of women who were pregnant during an epidemic will have congenital rubella.1'1 At a conservative estimate 30000 children had rubella-associated birth defects in the United States after the 1964 epidemic.1 Roughly 20% of adults are susceptible to rubella, the proportion varying with age and chroFrom the Atlantic Research Centre for Mental Retardation and the department of pediatrics, Daihousie University, Halifax Reprint requests to: Dr. JP. Welch, Rm. C-RI, Clinical Research Centre, 5849 University Ave., Dalhousie University, Halifax, NS B3H 4H7
nologic proximity to a previous epidemic, and generally being highest among young adults. A "hidden" effect of rubella infection in pregnancy is the production of congenital deafness in the infant, as shown in the study by Gumpel, Hayes and Dudgeon:3 61.2% of a group of congenitally deaf children (85 of 139) showed evidence of previous rubella infection, in contrast to 7.1 % of a comparable control group. Further analysis suggested that about one quarter of all cases of congenital deafness of "unknown etiology" are due to rubella infection in pregnancy. Reduced incidence of rubella infection in pregnancy would thus be expected to decrease the number of children with congenital deafness of unknown etiology. Since many children with rubella infection in utero continue to shed the virus for a considerable time after birth, susceptible women working with young deaf children, and also those employed as schoolteachers or nurses in pediatric and obstetric hospitals, may be at high risk of infection. Several rubella vaccines of proven efficacy licensed for use in Canada4 make rubella embryopathy a theoretically preventable condition. They appear to produce serologic immunity for some years,5 but probably for a shorter period than does natural infection. Choice of vaccine A disturbing trait of the rubella vaccines currently available in Canada is their inability to protect against wild virus infection for any appreciable length of time.6 A newer vaccine, RA 27/3, prepared in human WI-38 cells, appears to be antigenically more complete than either HPV-77 or Cendehill strain vaccines.79 RA 27/3 also results in a higher rate of conversion to seropositive than either HPV-77 or Cendehill strain vaccines10 and is associated with a relatively low rate of reinfection by wild virus.11 The reinfection rate for other commonly used attenuated vaccine strains has been found to be significantly higher; for the Cendehill strain it was over 50% only 2 years after vaccination, and for RA 27/3 it was 9% (comparable to the reinfection rate following natural immunization).12 The immunity induced by RA 27/3 appears to be similar to natural immunity.13 The overall advantages have been extensively reviewed by Plotkin, Farquhar and Ogra.11 The side effects associated
with this vaccine appear to be no greater than those associated with other vaccine strains11 and RA 27/3 therefore appears to be overwhelmingly the vaccine of choice. At the time of writing it has been licensed for use in the US; although it is not yet licensed for use in Canada, licensing is anticipated in the near future. Lack of immediate availability of this vaccine, however, should not be considered a valid reason for postponing a national program of rubella immunization. Choice of vaccinee Women The effects of rubella vaccine on the fetus of a current pregnancy or one that shortly follows a vaccination are not fully established; however, it appears that the risks are less than those associated with similar wild virus infection.14 Since there has been documented recovery of the virus from various fetal sites after such maternal inoculation, pregnancy is contraindicated for at least 2 months after rubella vaccination.1416 Young children Evidence suggests that rubella vaccination of young children to produce herd immunity is not effective;6'17. in addition, young children may not be the major source of infection in pregnant women.23 Since rubella vaccines give immunity of relatively limited duration, a substantial percentage of a population artificially immunized in early childhood could become susceptible to rubella by childbearing age, as shown in a serologic follow-up study of early childhood immunization.1' The risk of early vaccination may also be concealed, since waning immunity may prevent overt clinical signs and symptoms but not infection, viremia and teratogenesis. Although the possibility of "booster" immunization in preadolescence has been considered,re evidence suggests that this does not significantly increase the antibody titre in those previously vaccinated26 unless RA 27/3 (intranasally) is used for the booster.11 Wild-type infection can occur as soon as 6 to 9 months after rubella immunization, though the potential for teratogenesis in these circumstances has not been fully determined.27 The possibility of teratogenesis must be taken very seriously, however, because embryopathy after reinfection of some naturally immune women has been documented.2
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Some workers28 have speculated that incomplete or "spotty" immunization programs could create pockets of Unimmunized children who would become totally susceptible adults among whom a rubella epidemic could be devastating. Although the numbers of cases of rubella and congenital rubella syndrome reported in the US have diminished since the licensing of attenuated rubella virus in 1969,14 the decline is not necessarily attributable to the current vaccination programs.29 Mass rubella immunization of all children also raises an ethical problem not present in similar programs for other diseases. Rubella immunization of young boys is based on the premise that immunity in this group will help prevent infection in a different group (pregnant women), which in turn will prevent rubella embryopathy in a third group (fetuses). This introduces a new and potentially dangerous concept in medical care: the immunization of a group of individuals (together with the attendant risks, though small) for little or no direct benefit to the group, so that a future generation may be protected from specific congenital abnormalities. Directive vaccination It has been recommended that vaccination be given to those at risk.23'.'283' Attention has been focused especially on immunizing young girls and instituting premarital testing for rubella susceptibility. Susceptibility is greatest in younger age groups. A study at the Hospital for Sick Children, Toronto, showed that more than 25% of teenagers attending the teen clinic (over half of whom were pregnant) were susceptible to rubella; determination of rubella immunity status by previous history of natural rubella or of immunization was shown to be totally unreliable.32'33 A directive vaccination scheme introduced in the United Kingdom advocates rubella vaccination of prepubertal girls and groups of women at high risk, including schoolteachers, nursery staff, female staff of pediatric hospitals, obstetric and gynecologic units and antenatal clinics, and women seeking premarital guidance.. With this scheme immune status of prepubertal girls is not determined. In studying the effects of the scheme Hambling. found that the proportion of seronegative (antibody titre K 1 / 8) girls in the age group 15 to 19 years decreased by over one third from 1971-72 to 1974. Since vaccination has been offered only since 1970, further reduction in the proportion of susceptible individuals is anticipated. Testing for rubella susceptibility at
the time of marriage is an additional method of identifying a high-risk population. Several states in the US, including California, Rhode Island, Colorado and Montana, have passed legislation requiring premarital testing for rubella susceptibility in women of childbearing age. Studies indicate that a large proportion of women so identified are subsequently vaccinated.36 Prevention of rubella embryopathy in Canada A recent analysis. showed that the lifetime cost of congenital rubella in an unvaccinated population was more than $35 per female, whereas the cost of vaccination was estimated at $3. The same authors estimated that vaccination at age 12 yields benefits 80% greater than those of vaccination in early childhood. Clearly the cost of provision of rubella vaccine, vaccination when appropriate, and the necessary promotional campaign is far outweighed by the savings resulting from the prevention of rubella embryopathy and the reduced incidence of congenital deafness. The problem of rubella is substantially greater than that posed, for example, by phenylketonuria, which occurs in about 1 infant in 10000. Despite the fact that only about one new case of phenylketonuria occurs yearly in Nova Scotia, that province, like most others, has an excellent screening program financed by the provincial health service. Comparable attention to the prevention of rubella embryopathy is just beginning. Yet in Nova Scotia the 1973-74 rubella epidemic is expected to have affected 100 babies, or 1% of infants born of women who were pregnant during the epidemic.2 No exhaustive survey has been done but there are at least 25 infants with documented embryopathy, 19 of whom were born of Nova Scotians pregnant during that epidemic37 (and R.S. Faulkner: personal communication, 1976). The estimated cost of caring for these 25 infants is $1.5 to $2 million.38 It is apparent that there is a greater need for provincial health services to finance prevention of rubella embryopathy in Canada than to screen for phenylketonuria, despite the obvious benefit of the latter. I have several proposals for constructive future action. Some of the activities are already in effect in some provinces but the general level of concern in most provinces is too low. I have also prepared a rubella "fact sheet" (Appendix A) outlining the hazards of rubella and the benefits of vaccination and advocating specific policies, that I believe to be a most useful tool in fulfilling the critically important need to inform susceptible females of
152 CMA JOURNAL/JULY 23 1977/VOL. 117
the importance of rubella immunity. It is presently in use at both the Izaak Walton Killam Hospital for Children and the Grace Maternity Hospital in Halifax. Both hospitals test all female employees for rubella hemagglutination-inhibition (HI) antibodies at the beginning of their employment. Those found to be susceptible to rubella are given the fact sheet and offered vaccination. Proposals 1. Provincial departments of health should initiate a high-intensity publicity program aimed toward rubella vaccination of all schoolgirls during their 12th year. I suggest that this be done through a month-long, intensive promotion through the schools, along with the use of all news media. Vaccination should be done through the school health authorities by public health nurses. Appropriate notation of vaccination should be entered on the school health record of each child. The records should be checked shortly before the end of the school year to identify all 11- and 12-year-old girls who have not been vaccinated, then vaccination should be offered to each individual by the school health nurse after consultation with the parents. Further encouragement for vaccination may be provided by distribution of a rubella fact sheet, such as that in Appendix A, to these families. School health records should accompany children who transfer between schools. 2. HI testing should be introduced as a legal requirement for all women prior to marriage unless they are over 50 years of age or have had surgical sterilization. Those identified as susceptible to rubella should be given a rubella fact sheet and, if not then pregnant, offered rubella vaccination together with advice on and assistance in maintaining a pregnancy-free state for at least 3 months. 3. Provincial health departments should promote the free testing of rubella susceptibility (HI testing) for all women at their first prenatal visit to a physician or other appropriate health care professional. 4. All women should have HI testing at delivery to identify those still susceptible to rubella; those found susceptible should be provided with a rubella fact sheet. Rubella vaccination should be offered to all susceptible women. 5. The cost of rubella vaccine should be borne by the provincial governments and the cost of vaccination should be covered by provincial medical insurance. 6. After reviewing available rubella vaccines, data on side effects, likely duration of immunity and antigenic
potential, I recommend the use of RA 27/3 vaccine as soon as it is officially licensed in Canada.
31. JONCAS JH: Rubella immunization (C). Can Med Assoc J 111: 907, 1974 32. STOFFMAN SM, WOLFISH MG: The susceptibility of adolescent girls to rubella. Clin
The advice of Dr. K.R. Rozee, department of microbiology, Daihousie University, in the preparation of this manuscript is gratefully acknowledged.
girls. Med Post 10 (17): 19, 1974 34. DUDGEON JA: The control of diphtheria,
tetanus, poliomyelitis, measles, rubella and mumps. Practitioner 215: 299, 1975
35. HAMSLING MH: Effect of a vaccination programme on the distribution of rubella antibodies in women of childbearing age. Lancet
1: 1130, 1975 36. JUDSON EN, Sitaw BS, VERNON TM: Mandatory premarital rubella serologic testing in
References 1. COOPER LZ: Birth Defects. Orig Artic Ser 4: 23, 1968 2. COOPER LZ, KItUOMAN S: Clinical mamfestations of postnatal and congenital rubella. Arch Ophthalmol 77: 434 1967 3. GUMPEL SM, HAYEs K, bUDGEON JA: Congenital perceptive deafness: role of intrauterine rubella. Br Med 1 2: 300, 1971 4. MCLEAN DM: The rubella situation in Canada - 1972. Can I Public Health 63: 385, 1972
5. KRUGMAN 5, KATZ SL: Rubella immunization: a five-year progress report. N Engl .1 Med
290: 1375, 1974 6. HORSTMANN DM, LIESHABER H, La Bouvsrnt GL, et al: Rubella reinfection of vaccinated and naturally immune persons exposed in an epidemic. N Engl J Med 283: 771, 1970 7. LE BouvIER G, PLOTKJN SA: Precipitin responses to rubella vac.ine BA 27/3. 1 Infect Dis 123: 220, 1971 8. WALLACE RB, 15AC50N P: Comparative trial of HPV-77, DE-5 and RA 27/3 llve-attenuated rubella vaccines. Am I Dis Child 124: 536, 1972 9. HORSTMANN DM: Need for monitoring vaccinated populations for immunity levels. Frog
Med Virol 16: 215, 1973 10. FREESTONE DS, REYNOLDS GM, MCKINNON JA, et al: Vaccination of schoolgirls against rubella: assessment of serological status and a comparative trial of Wistar RA 27/3 and Cendehill strain llve attenuated rubella vaccines in 13-year-old schoolgirls in Dudley.
Br I Prey Soc Med 29: 258, 1975
11. PLOTKIN SA, FARQiJHAR JD, OGRA PL: Immunologic properties of RA 27/3 rubella virus vaccine: a comparison with strains presently llcensed in tbe United States. JAMA 225: 585, 1973 12. GRILLNER L: Immunity to intranasal challenge with rubella virus two years after vaccination: comparison of three vaccines. I Infect Dis 133: 637, 1976 13. LIEBHABER H, INGALLS TH, La Bouvxazt GL, et al: Vaccination with RA 27/3 rubella vaccine. Am I Dir Child 123: 133, 1972 14. MODLIN JF, HERRMANN K, BRANDLINGBENNETF AD, et al: Risk of congenital abnormality after inadvertent rubella vaccination of pregnant women. N Engl I Med 294: 972, 1976 15. Rubella vaccination and pregnancy (E). Lancet 2: 769, 1973
16. LEVINE MM: Live-virus vaccines in pregnancy: risks and recommendations. Lancet 2: 234, 1974 17. HOR5TMANN DM, PAJOT TG, LIEBHABER H: Epidemiology of rubella: subclinical infection and occurrence of reinfection. Am I Dis
Child 118: 133, 1969 18. LEHANE DE, Nawauao NR, BEAM WE JR: Evaluation of rubella herd immunity during an epidemic. JAMA 213: 2236, 1970 19. RACHELEF5KY GS, HERRMANN KL: Congenital rubella surveillance following epidemic rubella in a partially vaccinated community. I Pedtatr 84: 474, 1974 20. WEINsTZrn L, CHANG TW: Prevention of
rubella. Pediatrics 55: 5, 1975 21. CHANG TW, DasRosiaas 5, Wamsmrn L: Clinical and serologic studies of an outbreak of rubella in a vaccinated population. N Engl I Med 283: 246, 1970 22. WILKINs 3, LEEDOM JM, PORTNOY B, et al: Reinfection with rubella virus despite live vaccine induced immunity. Trials of HPV-77 and HPV-80 live rubella virus vaccines and subsequent artificial and natural challenge
studies. Am I Dis Child 118: 275, 1969 23. SCHOENBAUM SC, BIANo 5, MACK T: Epidemiology of congenital rubella syndrome. JAMA 223: 151, 1975 24. HOR5TMANN DM: Controlling rubella: problems and perspectives. Ann Intern Med 83: 412, 1975 25. SCHOENDAUM SC, HYDE JN JR, BARTOsHESKY L, et al: Benefit-cost analysis of rubella vaccination policy. N EngI I Med 294: 806, 1976 26. WYLL SA, HERRMANN KL, AB1WTYN E, et al: Rubella booster immunization: serologic response to a second dose of vaccine. JAMA 216: 1451, 1971 27. Rubella reinfection and the foetus (E). Lancet 1: 978, 1973 28. Nasr 3M, CARVER DH:
Pediatr 15: 625, 1976 33. WILLS M: Rubella tests urged for all young
Rubella immuniza-
tion: reconsideration of our present policy. Am I Epidemiol 92: 162, 1970 29. SCHOENBAUM SC, BIANO 5, MAcic T: Rubella immunization. JAMA 235: 248, 1976 30. KATz M: Rubella va.ine. I Pedlatr 84: 615, 1974
Colorado. A preliminary report. JAMA 229:
1200, 1974
37. FAULKNER RS, GOUGH DA: Rubella 1974 and its aftermath, congenital rubella syndrome.
Can Med Assoc 1 114: 115, 1976 Epidemic: Estimated Health and Economic Costs, Atlanta, GA, 1965
38. Center for Disease Control: 1964-65 Rubella
Appendix A: Rubella fact sheet
1. What is rubella? Rubella, also known as German measles, is a mild infectious disease, usually occurring in childhood. It usually begins with a short period of mild symptoms of inflammation of the nose and air passages and slight fever, followed by a rash usually lasting 2 to 3 days. Such natural infection usually results in lifelong immunity. 2. Why is rubella so dangerous? Women who contract the disease while pregnant, especially during the 1st 3 months, have a high risk of miscarriage or of giving birth to children with heart defects, blindness, deafness, bone abnormalities, brain damage and other serious problems. The percentage of abnormal births ranges from very high among women who have rubella early in pregnancy, to relatively low in women who have the disease later in pregnancy. Those who contract rubella during the 1st month of pregnancy face a 90% risk of giving birth to an abnormal child. Infection during the 2nd month carries a 50% risk, and infection in the 3rd month, a 10% risk. 3. Are babies often affected and damaged by rubella? Yes. There are always rubelladamaged babies being born, and in the year following an epidemic there may be up to 10 affected babies in every 1000 pregnancies. 4. If a woman is pregnant and comes in Contact with a person who has rubella, can she get an injection that will protect her future baby? No. Antibody shots (gamma globulin) can be given; however, these probably only help prevent the mother from showing signs of rubella and probably do not protect the fetus. In this circumstance it is most important for the woman to visit her doctor right away so that he may test her susceptibility to rubella. If she is susceptible a repeated test will enable the doctor to determine whether she has been infected by rubella and thus whether the fetus is at risk.
5. Do measles shots protect against rubella also? No, not unless the shots are a combination vaccine against both diseases. Measles (rubeola) and German measles (rubella) are different diseases. Protection against one does not offer protection against the other. 6. Does rubella occur in epidemics? Yes. Rubella epidemics usually occur at 7- to 9-year intervals. (See question 3.) 7. What is the disease's history? Rubella was regarded as relatively harmless until 1941, when an Australian eye specialist, Sir Norman McAlister Gregg, noted an unusually high number of birth defects following an outbreak of the disease. Fetal abnormalities that occurred included congenital blindness, heart disease, deafness and mental retardation. His observation led to the discovery that rubella, when contracted by expectant mothers, can damage their unborn children. Scientists isolated the virus that causes rubella in 1962 and immediately began work on developing live vaccines to protect against it. The first vaccine became available in Switzerland in 1969. 8. Are there any side effects of the vaccine? The vaccine causes no side effects in most children and only mild side effects in a few, such as slight fever, or a minor rash that subsides after 1 or 2 days. (Sometimes the latter reaction occurs a week or 2 after vaccination.) Some women have experienced a similar reaction, or slight discomfort in the joints for 1 to 2 days. 9. Who should get rubella vaccine? The vaccine should be given to all girls between their 11th and 12th birthdays. It should also be given to any women who are not immune to rubella and are of childbearing age; these women should not become pregnant for at least 3 months after vaccination. (See questions 12 to 14.) 10. Should boys be vaccinated against rubella? If all girls and nonimmune young women are vaccinated it is not really necessary to vaccinate boys. However, it is not harmful, and their vaccination may help control the spread of rubella in a community in which a substantial number of girls and young women are not vaccinated or naturally immune. 11. Where can one get a rubella vaccination and how much does it cost? Rubella vaccination may be obtained from either one's family doctor or any of the provincial public health clinics. Both vaccine and vaccination are provided free of charge at the public health clinics. In some provinces fain-
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ily doctors must pay for their supplies of rubella vaccine; hence there is likely to be a small charge incurred for both 4'accine and vaccination obtained from them. If blood tests are necessary to determine possible susceptibility to rubella (see questions 12 and 14) these can be arranged through one's family doctor. There is usually no charge for the laboratory test, the cost of which, in most cases, is borne by the provincial departments of health. 12. Are there any who have an especially high risk? Yes. It is particularly important that young women who may become pregnant and who have a particularly high possibility of exposure to rubella be tested for immunity and vaccinated if susceptible. This includes all such female staff in any children's hospital, obstetric and gynecologic unit, nursery and school (see below).
13. Is there anyone who should not receive rubella vaccine? Yes. Pregnant women or those likely to become pregnant within 3 months after vaccination, patients who have a high fever, those who have leukemia or other malignant disease, those whose resistance to infection has been lowered by radiation therapy and those known to be allergic to any ingredients in the vaccine. 14. What if a woman of childbearing age requests vaccination against rubella? Her doctor should decide whether vaccination is necessary. It is not necessary if she has natural immunity, but studies indicate that one in every five women of childbearing age is not immune. Immunity can be determined by a laboratory test. If she is not immune - and is not pregnant - her doctor may vaccinate her if she agrees to avoid
pregnancy by a medically approved method for at least 3 months after she has been vaccinated. 15. Is it possible to terminate the pregnancy (therapeutic abortion) if the fetus is known to be likely to have rubella damage? It is not presently legal to terminate a pregnancy in Canada because of known rubella damage. If such a state of pregnancy has a significant effect on the mother's health, termination can be considered. 16. How can the pregnant woman and her child be protected? The best way is for expectant mothers to avoid exposure to rubella, and to ensure that those at risk are immune to this disease. The best way to do this is by mass immunization of young girls.E
Pericarditis as a manifestation of essential thrombocythemia P. AVERBACK, MD; M. MOINUDDIN, MD
A 58-year-old woman presented with pericarditis and pericardial effusion. Investigation revealed that she was suffering from a thrombocythemic myeloproliferative disorder; she died of massive pulmonary embolism 10 days after admission. Histologic study verified epicardial and pericardial trilineage hematopoiesis. Pericarditis is an unusual feature of essential thrombocythemia and it may occur in direct relation to the abnormal cellular proliferation. Une femme de 58 ans a presente une p6rlcardite avec epanchement pericardique. L'etude du cas a revel6 que Ia patiente souffralt d'une proliferation my6loude thrombocytop6nique; elle est decedee d'embolie pulmonaire massive 10 jours apres son hospitalisation. Une etude histologique a confirm6 Ia presence d'une hematopolese 6picardique et pericardique touchant trois lignees cellulaires. La pericardite est une manifestation inhabituelle de Ia thrombocytopenie essentielle et elle peut survenir en relation directe avec une prolif6ration cellulaire anormale.
This report describes a patient with essential thrombocythemia who presented with pericarditis, and in whom Prom the Pathology Institute and Royal Victoria Hospital, Montreal Reprint requests to: Dr. P. Averback, 3775 University St., Montreal, PQ H3A 2B4
autopsy study revealed histologic evidence of hematopoiesis (erythrocyte and leukocyte series and megakaryocytes) in the epicardium and pericardium. While the chief cause of death in patients with agnogenic myeloid metaplasia is cardiac (due to arteriosclerosis and other factors1) we were unable to find other reports of pericarditis as a presenting feature in thrombocythemia or in association with proven pencardial and epicardial trilineage hematopoiesis.
Case report Clinical course and findings A 58-year-old woman was admitted to hospital with chief complaints of fatigue and anterior chest pain. She had noted blood-tinged stools intermittently for 2 years and had lost 6 kg in that time, but had not seen a physician. She described generalized fatigue of 5 months' duration. For 2 weeks prior to admission there had been low-grade fever, episodes of fainting and anterior chest pain; acetylsalicylic acid provided some relief. Physical examination revealed pulsus paradoxus (rate, 100 beats/mm), jugular venous distension, scattered basal rhonchi, and enlargement of the spleen (to 11 cm below the left costal margin) and the liver (to 16 cm below the right costal margin) with slight tenderness of the liver. Admission chest radiograph showed a large cardiac silhouette, with clear lung fields and small bilateral pleural effusions. Echocardiography confirmed a large
154 CMA JOURNAL/JULY 23, 1977/VOL. 117
anterior and posterior pericardial effusion. Electrocardiography revealed minimal STsegment elevation in leads II, III, aVF, V5 and V6, but was otherwise normal. The hemoglobin value was 8.3 g/dL; hematocrit, 29%; leukocyte count, 32.2 x 109/L with 3% blast forms, 3% promyelocytes, 5% myelocytes, 2% metamyelocytes, 5% band forms, 60% mature neutrophils, 13% lymphocytes and 9% basophils; platelet count, 2200 x 109/L; and reticulocyte count, 1.8%. Blood smear showed microcytic hypochromic erythrocytes with occasional tear-drop forms. Mean corpuscular volume was 60 .3; mean corpuscular hemoglobin, 17.3 pg; and mean corpuscular hemoglobin concentration, 28.4%. The erythrocyte count was 4.95 x 1012/L. The leukocyte alkaline phosphatase score was 122. Prothrombin time was 16.2 s (control, 11.8 s) and partial thromboplastin time, 62.8 s (control, 32.9 s). The value for the platelet glass-bead retention test was 9% (normal, 27 to 48%). One of three stool specimens was positive for occult blood. Serum alkaline phosphatase value was 272 lU/L and serum lactate dehydrogenase value, 628 lU/L. Results of other initial tests, including lupus erythematosus cell preparations and tests for Philadelphia chromosome, antinuclear antibodies and rheumatoid factor were negative. A bone marrow aspirate and biopsy taken from the posterior iliac crest showed hypercellular particles without fat spaces, no stainable iron and a striking increase in number of megakaryocytes (Fig. 1). Therapy was started with busulfan, hydroxyurea, transfusions of packed erythrocytes, and ferrous sulfate. A lung scan on the 3rd day showed a segmental right
