VALUE OF ESR IN ASSESSMENT OF RHEUMATOID ARTHRITIS

1531 evidence of CSF infection. infection rate was low we did not feel that such was indicated in our population.

progressive hydrocephaly and/or Because

our

investigation

Liverpool Maternity Hospital, Liverpool L7 7BN; Department of Medical Microbiology, Royal Liverpool Hospital; and Liverpool Maternity Hospital

N. J. SHAW B. C. PRATT A. M. WEINDLING

1. Waiter KB, Rudd PT, Crouse DT, et al. Chronic Ureaplasma urealyticum and Mycoplasma hominis infections of central nervous system in preterm infants. Lancet 1988; i: 17-21. 2. Taylor-Robinson D, McCormack WM. The genital mycoplasmas. N Engl J Med

1980; 302: 1003-19, 1063-67.

BALLOON VALVULOPLASTY IN PULMONARY ATRESIA AND INTACT VENTRICULAR SEPTUM

SiR,—Percutaneous balloon valvuloplasty (PBV) has been increasingly accepted as a non-surgical technique in congenital

pulmonary valve stenosis. Even in newborn babies with critical pulmonary valve stenosis PBV is sometimes effective for relieving cyanosis and pressure gradient.1-3 However, PBV has not been applied to newborn babies with atretic pulmonary valve. We report a baby with pulmonary atresia and intact ventricular septum in whom PBV was done. A 1-day-old male infant was referred to us because of cyanosis. On admission he was active and became cyanotic when he cried. He had an ejection systolic murmur at the upper left sternal border. Arterial blood gas analysis showed severe metabolic acidosis with hypoxaemia (pH 723, POz 23, HC03 12, BE,-24). Twodimensional echocardiography revealed a membranous atresia of pulmonary valve with a small right ventricular cavity. The annulus diameters of the tricuspid and mitral valves were 6-5 mm and 10-6 mm, respectively. An abnormal turbulent flow from patent ductus arteriosus was shown by colour doppler echocardiography. Alprostadil (prostaglandin E), initial dose 0-05 pg/kg per minute, was given. P02 then rose to about 40 mm Hg. At age 6 days cardiac catheterisation and angiography were done. The peak right ventricular and systemic pressures were 95 mm Hg and 56 mm Hg, respectively. The right ventricle was hypoplastic but tripartite with mild tricuspid regurgitation. Sinusoidal communication between the right ventricle and left anterior descending artery was seen. He was operated on 12 days later. A left modified Blalock-Taussig shunt was interposed and the atretic pulmonary valve was punctured with a 21-gauge needle from the pulmonary arterial wall. The hole was then dilated with an 8 F dilator. At age 34 days he was catheterised for PBV. The peak right ventricular and systemic pressures were 80 mm Hg and 65 mm Hg, respectively, before the procedure. A 5 F end-hole catheter was passed into the pulmonary trunk from the femoral artery through the patent ductus arteriosus. A long exchange guide wire was threaded through the catheter into the hole of the atretic valve, and then into the femoral vein through the tricuspid valve in a retrograde fashion. The wire was easily passed through the venous sheath. The dilatation catheter (Meditech, Watertown, Massachusetts, USA) with a 5 mm diameter balloon, was then positioned across the atretic valve. The balloon was inflated by hand with dilute contrast medium until the waist disappeared. The inflation/deflation cycle took 5 s. This procedure was repeated four times, after which the peak right ventricular and systemic pressures were 50 mm Hg and 60 mm Hg, respectively, and the pulmonary arterial pressure was 40 mm Hg. The right ventriculograph showed the opening of two valves with a jet of contrast medium across the pulmonary valve. 1 month later there was a 15 mm Hg pressure gradient across the pulmonary valve. Palliative surgery for pulmonary atresia and intact septum remains controversial.4,s The procedure selected is dependent mainly on the size and morphology of the right ventricle or the presence of ventriculocoronary communication. In patients with hypoplastic right ventricle, closed valvotomy with or without concomitant systemic pulmonary shunt is usually done.6 Closed valvotomy can be hazardous and requires arteriotomy. Our strategy

surgical valvotomy and may have the potential advantage of application to intraoperative balloon valvotomy. In addition, if the atretic valve can be non-surgically punctured with a new long dilator-needle system, PBV may be an alternative to surgical valvotomy for patients with pulmonary may carry fewer risks than

atresia and an intact ventricular septum. Departments of Paediatrics and Thoracic Surgery, Juntendo University School of Medicine, 2-1-1 Hongo, Bunkyo-ku, Tokyo, 113, Japan

TOSHIHIRO INO KEIJIRO YABUTA ATSUSHI TANAKA

1. Rey C, Marache P, Francart C, Dupuis C. Percutaneous transluminal balloon valvuloplasty of congenital pulmonary valve stenosis, with a special report on infants and neonates. J Am Coll Cardiol 1988; 11: 815-20. 2. Tynan M, Baker EJ, Rohmer J, et al. Percutaneous balloon pulmonary valvuloplasty. Br Heart J 1985; 53: 520-24. 3. Beekman RH, Rocchini AP. Transcatheter treatment of congenital heart disease. Prog Cardiovasc Dis 1989; 32: 1-30. 4. Forker JE, Braunlin EA, St Cyr JA, et al. Management of pulmonary atresia with intact ventricular septum. J Thorac Cardiovasc Surg 1986; 92: 706-15. 5. Albolias ET, Julsrud PR, Danielson GK, et al. Definitive operation for pulmonary atresia with intact ventricular septum: results in twenty patients. J Thorac Cardiovasc Surg 1987; 93: 454-64. 6. Coles JG, Freedom RM, Lightfoot NE, et al. Long-term results in neonates with pulmonary atresia and intact ventricular septum. Ann Thorac Surg 1989; 47: 213-17.

VALUE OF ESR IN ASSESSMENT OF RHEUMATOID ARTHRITIS

SiR,—Dr Bull and colleagues (Oct 21,

p

965)

use consensus

analysis examine the efficacy of laboratory and clinical measures to monitor rheumatoid arthritis (RA). They suggest the erythrocyte sedimentation rate (ESR) is the best guide to disease severity, and that clinical tests perform poorly unless combined with laboratory data in a numerical index. We think they overestimate the clinical value of ESR measurement. Others have agreed that the ESR is probably the most useful of the conventional laboratory tests, but that it performs similarly to joint tenderness counts, a form of articular index. The ESR does not give the same information in all RA patients. In some it is high while joint disease is mild, whereas in others the converse is true. To examine this point we have reviewed the results of 137 RA patients treated continuously for six months with slow-acting anti-rheumatic drugs such as injectable gold. After six months’ therapy 15 had a persistently raised ESR (over 50 mm/h) and 35 had a low ESR (under 10 mm/h). The Ritchie articular index in these patients (figure) shows that some with a high ESR had a low articular index, whereas in others the opposite was true. The ESR was a poor predictor of the articular index. The articular index is by no means an ideal test, but it is a measure of the amount of joint to

Articular index

Articular indices in RA patients after 6 months’ therapy with a slow acting anti-rheumatic drug. 0 ESR

>

50 mm/h

(n - 15), Q ESR

<

10

mm/h (n 35). =

1532 disease. Many RA patients starting on a slow-acting anti-rheumatic drug have a high ESR, but clinical measures of disease activity show 2 a similar improvement with treatment whatever the previous ESR. More important is the failure of the ESR as a predictor of disease outcome. Long-term outcome and prognosis are the most relevant factors in a chronic disease such as RA. The table shows ESRs measured on the first attendance at a rheumatology unit in 50 consecutive RA patients who had become completely disabled (housebound) by their disease and were in functional class IV by the Steinbroker classification3: Initial ESR

< 30 mm/h 30-60 mm/h > 60 mm/h

No

of patients 13 23 14

under the curve) to obtain the final measurement. The upper normal limit is 60 mm at under age 50 years, and 85 mm at over 50. In 30 patients with inflammatory rheumatic diseases untreated by anti-inflammatory drugs, the haematocrit, sigma ESR, and Westergren ESR were measured at 0700, 0900, 1000, and 1200. Haematocrit and sigma ESR morning variations were characterised by significant increases at 0900-1200 (table). No circadian variation was detected by the Westergren ESR. The morning sigma ESR increase reached 23% and is probably explained by the morning increase of several acute-phase proteins. Therefore such an increase of the biological inflammatory process can be missed by the Westergren method if the haematocrit increases by 1 3% (from 37I to

We could find no direct relation between ESR level and the severity of synovitis. The initial ESR is thus of no use as a determinant of long-term outcome. This has also been recorded by others.4 We agree with Bull et al that too many laboratory variables are measured in RA patients. The balance of opinion undoubtedly favours measurement of ESR to help assess short-term disease activity in RA.5.6But it is misleading to regard the ESR as the ideal test in RA or that it is better than clinical or functional measures, especially over longer periods which have more relevance to the

384%).

The sigma ESR is a longer but probably more precise technique than the zeta sedimentation ratio (ZSR). The ZSR, as well as the sigma ESR, probably follows the circadian rhythm of the blood acute-phase proteins. Bull and colleagues did not take account of these factors in their consensus analysis. The ESR remains the best measure of the inflammatory syndrome, but there is certainly nothing to be gained from the use of such techniques when the results are affected by other factors, as is the case with the Westergren ESR. Y. PAWLOTSKY

patient.

G. CHALES Department of Rheumatology, St Bartholomew’s Hospital, London EC1A 7BE

DAVID L. SCOTT TIM D. SPECTOR

Therapeutics Clinic, Service of Rheumatology, and Haematology Laboratory, Hôpital Sud, 35056 Rennes, France

Silman AJ, Kirwan JR, Currey HLF. Articular indices of joint inflammation in rheumatoid arthritis; correlation with the acute phase response. Arthritis Rheum 1987; 30: 618-23. 2. Pullar T, Capell HA. Selection of suitable patients for second line therapy. Br J Rheumatol 1986; 25: 276-81. 3. Steinbroker O, Traeger CH. Battman RC. Therapeutic criteria in rheumatoid arthritis. JAMA 1949; 140: 659-62. 4. Sherrer YS, Bloch DA, Mitchell DM, Young DY, Fries JF. The development of disability in rheumatoid arthritis. Arthritis Rheum 1986; 29: 494-500. 5. Anderson JJ, Felson DJ, Meenan RF, Williams HJ. Which traditional measures should be used in rheumatoid arthritis clinical trials? Arthritis Rheum 1989; 32: 1093-99. 6. Scott DL, Spector TD, Pullar T, McConkey B. Viewpoint: what should we hope to achieve when treating rheumatoid arthritis? Ann Rheum Dis 1989; 48: 256-61. 1.

Thompson PW,

SIR,-We would like to draw attention to a particular point in Dr Bull and colleagues’ study. They assessed all their patients between 0900 and 1200 to reduce any circadian effect, but they did not take into account the circadian variations of laboratory measurements in the same period. Most acute-phase proteins and haematocrit have their peaks at about 0900 or between 0900 and 1200-and a reduction in erythrocyte sodimentation rate (ESR) due to an increase in haematocrit is more important when the blood concentration of these proteins is high than when it is low. We have measured ESR by the sigma method. 1-3 The sigma ESR is characterised by a preliminary correction of the haematocrit level which is reset to a constant (35%) by addition or removal of some plasma according to the actual haematocrit level, followed by addition of sodium citrate solution (0-1ml/ml blood). The four sedimentation rates at 20, 30, 40, and 50 min are then added (area MORNING VARIATION IN HAEMATOCRIT AND ESR

J. MEADEB A. PERDRIGER E. LEGRAND J. GOASGUEN

Y. Bourel M, Lenoir P, Kerbaol M. Syndrome inflammatoire et sédimentation globulaire, un nouveau mode de mesure: la Sigma VS. "R" Rhum

1. Pawlotsky

1972; 45: 69-75.

Pawlotsky Y, Chalès G, Grosbois B, Louboutin JY, Lenoir P, Bourel M. Sigma ESR, a new method of measuring erythrocyte sedimentation rate its value in studying the action and interactions of non steroidal anti-inflammatory agents, Curr Med Res Opin 1978; 5: 412-17. 3. Pawlotsky Y, Chalès G, Coutard J. et al. Etude des variations matinales de la Sigma VS, de la vitesse de sédimentation (Westergren) et de la proteine réactive. C Rev Rhum 1985; 52: 35-40. 2.

SIR,-In Dr Bull and colleagues’ report there are, in our view, several methodological and conceptual flaws that might mislead the non-specialist reader. Firstly, the grouping of tests in the families, members of which were not scored against each other, seems to have been both arbitrary and illogical. We know of no reason why the various forms of articular index should be grouped in the same family as a visual analogue scale for stiffness whereas the various forms of erythrocyte sedimentation rate (ESR), the plasma viscosity with or without haematocrit, the fibrinogen level, and haemoglobin were grouped separately. Since ESR is dependent on the fibrinogen level, plasma viscosity, and haemoglobin, and plasma viscosity is determined by the fibrinogen concentration, this grouping obviously produced a bias in favour of these laboratory tests. Of greater importance, however, is the assumption that a single test result or compound value can, or indeed should, describe the various aspects of disease activity in rheumatoid arthritis. Until there is better evidence that the pharmacological improvement of laboratory indices of inflammation improves disease outcome,l the major aim of second-line therapy (a term we also prefer to "disease modifying") should be the improvement of the features of the disease, especially pain and subjective stiffness. Such improvement occurs even in patients whose initial Westergren ESR is low. Thus, improvement in symptoms is attainable with drugs in the absence of a significant laboratory response. The attainment of this important benefit might not be attempted if laboratory tests alone or a compound score involving both laboratory and clinical indices was used as sole indicator of active disease.3 Furthermore, some drugs produce improvement in laboratory indices out of keeping with the clinical improvementor reduce the ESR by a mechanism likely to be different from that which produces the anti-inflammatory and

symptomatic response.5** Statistical comparisons made with 0700. NS =not sigmficant.

We believe that the search for a single test or compound value of disease activity, and thus drug response, is a retrograde step in the investigation and use of second-line agents in RA. This is even more

1533 the case if, because of inadequacies in the methods appears that Eldorado has been attained.

applied,

it

University Department Medicine, General Infirmary, Leeds LS1 3EX

THOMAS PULLAR

Centre for Rheumatic Diseases,

Glasgow Royal Infirmary,

HILARY A. CAPELL

Glasgow

1. Pullar T, Capell HA. Can treatment really influence the radiological progression of rheumatoid arthritis? Br J Rheumatol 1986; 25: 2-6. 2. Pullar T, Capell HA. Selection of suitable patients for second-line therapy m rheumatoid arthritis. Br Rheumatol 1986; 25: 276-81. J 3. Scott DL, Spector TD, Pullar T, McConkey B. What should we hope to achieve when treating rheumatoid arthritis? Ann Rheum Dhs 1989; 48: 256-61. 4. Richards IM1, Fraser SM, Hunter JA, Capell HA. Comparison of phenytoin and gold as second line drugs m rheumatoid arthritis. Ann Rheum Dis 1987; 46: 667-69. 5. Belch JJF, Madhok R, McArdle B, et al. The effect of increasing fibrinolysis in patients with rheumatoid arthritis: a double blind study of stanozolol. Q J Med 1986; 225: 19-27.

COVERAGE OF MMR VACCINE

SiR,—Combined measles, mumps, and rubella (MMR) vaccine was

introduced into the UK childhood immunisation schedule in

October, 1988.1 The Cover of Vaccination Evaluated Rapidly (COVER) schemewhich is run by the Communicable Disease Surveillance Centre of the Public Health Laboratory Service, has provided timely statistics of coverage for diphtheria, pertussis, and measles in England and Wales since 1987. MMR was included in the scheme in October, 1988, and preliminary results are now available. MMR coverage by 15 months of age was assessed in nineteen health districts in England and Wales from November, 1988. The data were obtained with a standard programme from the statistical package of the child health system.3 MMR coverage was evaluated is six consecutive monthly cohorts of children bom between July 1 and Dec 31, 1987. Each monthly cohort was studied shortly after the youngest member had reached 15 months of age. For example, children bom in July, 1987, were evaluated in November, 1988. Evaluations of subsequent cohorts were conducted between December, 1988, and April, 1989. For comparison, measles coverage by age 15 months was evaluated in six consecutive monthly cohorts of children born in 1986 in the same period and in the same district. With the exception of children born in July, 1987, MMR coverage in each monthly cohort exceeded measles coverage in the previous year by 1-5% (figure). The measles (but not the MMR) data include immunisations done by 15 months of age but not reported until later; this has the effect of underestimating coverage for MMR but not for measles. Neither the MMR nor the measles data included immunisations done after 15 months. Subsequent evaluations of MMR coverage in the cohort of children born in July, 1987, showed that by February, 1989 (ie, by 18 months), it had risen from 26% (at 15 months) to 59%, and by August, 1989 (ie, by 2 years), it was 74%. Coverage by 2 years of age will increase further when late reported immunisations have been included.

These results suggest that the introduction of MMR has been associated with some improvement in immunisation coverage. This improvement has also been seen in other countries.4,s Measles coverage in the UK has, however, been increasing steadily for several years and it is not clear whether the introduction of MMR has accelerated this process. More comprehensive information on MMR coverage will become available in 1990 from both the COVER scheme and Department of Health statistics. Although these results are encouraging, further improvements are needed if measles, mumps, rubella, and congenital rubella syndrome are to be eliminated. A greater commitment to immunisation is needed by all professionals involved in the delivery of preventive child health services. PHLS Communicable Disease Surveillance Centre, 61 Colindale Avenue, London NW9 5EQ

NORMAN BEGG SARAH HANDFORD

1. Badenoch J. Big bang for vaccination. Br Med J 1988; 297: 750-51. 2. Begg NT, Gill ON, White JM. COVER (Cover of Vaccination Evaluated Rapidly): description of the England and Wales scheme Publ Hlth 1989; 103: 81-89. 3. Child Health Computing Committee, 1987. The child health system a statistical guide. Cardiff. Welsh Health Common Services Authority, 1987. 4. Bottiger M, Chnstenson B, Romanus V, Taranger J, Strandell A. Swedish experience of two dose vaccination programme aiming at eliminating measles, mumps and rubella. Br Med J 1987; 295: 1264-67. 5. Peltola H, Karanko V, Kurki T, et al. Rapid effect on endemic measles, mumps, and rubella of nationwide vaccination programme m Finland. Lancet 1986; 1: 137-39.

EFFECT OF RACE AND BLOOD GROUP ON THE IMMUNE RESPONSE TO BACTERIAL POLYSACCHARIDE AND CONJUGATE VACCINES

SiR,—The ability of an individual to produce an antibody following vaccination is regulated by many factors. Non-responsiveness to hepatitis B vaccine has been attributed to the response

absence of a dominant immune-response gene in the major histocompatibility complex.! The presence of Km(l) immunoglobulin allotype in black, but not white, children has been associated with an increased concentration of serum antibody following immunisation with Haemophilus influenzae type b polysaccharide vaccine.2 Expression of the G2m(n) allotype of IgG2 results in a significantly greater immune response to H influenzae type b polysaccharide and 8 of 11pneumococcal polysaccharides after vaccination compared with subjects who were G2m(n) negative.3 Furthermore, the increased susceptibility of certain ethnic populations to invasive disease caused by encapsulated bacteria suggests that race may also play a part in the immune response to polysaccharide antigens. 3,4 We have described the safety and immunogenicity of a polyvalent Klebsiella capsular polysaccharide vaccine and a Pseudomonas aeruginosa 0-polysaccharide-toxin A vaccine in man. 5,6 We have used these two vaccines to immunise simultaneously 62 healthy volunteers, about two-thirds of whom were of hispanic origin, the remainder being white. This presented a unique opportunity to evaluate the immune response to conjugated and non-conjugated polysaccharide antigens as determined by age, race, and blood group.

too-,

Age did not seem to affect the ability of vaccinees to mount a antibody response (response is defined as a 4-fold rise to

serum

EFFECT OF BLOOD GROUP AND RACE ON ANTIBODY RESPONSE TO PS AERUGINOSA VACCINES 1-

I

Jul

Aug

Sep

Study

Oct

Nov

Dec

cohort birth month

Coverage of

MMR and measles by age 15 months in nineteen health districts of England and Wales.

No of children evaluated in each month ranged from 5461

to

6358.

*p < 0-05 (hispanic vs white; group 0 vs group A), by both Fisher’s exact test and X2 analysis with Yates’ correction for continuity. NC = not considered

as a

variable.