вход по аккаунту


The diagnosis of polymyalgia rheumatica in patients with a low erythrocyte sedimentation rateComment on the article by Helfgott and Kieval.

код для вставкиСкачать
artery). Laboratory test results, such as levels of hemoglobin,
rheumatoid factor, and antinuclear antibodies, and serum
protein electrophoresis findings were recorded as available.
Over an 8-year period, 39 patients with PMR were
seen and treated. Thirty-six patients (92%) had an elevated
ESR (average ESR 68 mmihour, range 32-120) and 3 patients
continued to have a normal ESR (average ESR 16 mmihour,
range 10-22) during followup of the disease. All of the latter
patients were female, compared with 25 of the 36 patients with
an elevated ESR (Pnot significant). The mean age (73 versus
69 years) did not differ significantly between groups. Shoulder
and pelvic girdle involvement, peripheral arthritis (oligoarticular involvement), fever, and weight loss showed no differences
of statistical significance. One patient in each group had
symptoms of GCA. One patient with an elevated ESR was
found to have GCA on temporal artery biopsy. All patients
were treated with low-dose corticosteroids (prednisone 5 10
mgiday). The response was prompt and striking. There was an
improvement in all patients. None of our followup patients
developed the peripheral polydrthritis of RA.
Based on the findings of several reports, the incidence
of PMR in patients with an initial pretreatment ESR considered to be normal was -22% (4,s). We think this frequency is
very high. In our study, we found that 8% of patients with
PMR had a normal ESR, which was maintained during the
followup. The clinical features of our patients with a normal
versus elevated ESR were similar.
Some authors have noted a normal ESR early in the
course of the disease, with subsequent elevation over time. We
believe that these patients should not be included in the
normal ESR group. Taking into account this observation,
further investigation is needed to establish what is dcemed a
normal ESR in PMR. We suggest that, to be considered a
normal ESR in PMR, the designated range should be maintained throughout the evolution of the illness.
A normal ESR in patients with otherwise classic PMR
has tended to mislead physicians, resulting in a serious delay in
diagnosis. Thus, if there is good clinical evidence for PMR, a
normal ESR should be ignored, and the patient should undergo an empirical trial of corticosteroid treatment.
L. Caliani, MD
Sergio 0. Paira, MD
Hospital Jose! M. Cullen
Santa Fe, Argentina
1. Helfgott S, l e v a 1 RI: Polymyalgia rheumatica in patients with a
normal erythrocyte sedimentation rate. Arthritis Rheum 30:304307, 1996
2. Jones JG, Hazleman BL: The prognosis and management of
polymyalgia rheumatica. Ann Rheum Dis 40:l-5, 1981
3. Bottiger LE, Suedberg CA: Normal erythrocyte sedimentation rate
and age. BMJ 2:85-87, 1967
4. Ellis ME, Ralston S: The ESR in the diagnosis and management of
the polymyalgia rheumatica/giant cell arteritis syndrome. Ann
Rheum Dis 42:168-170, 1983
5. Sueiro JLF, Armona J, Rodriguez-Valverde V, Blanco R, Taboada
MM: Polymyalgia rheumatica without clinically significant increased ESR (abstract). Arthritis Rheum 37 (suppl 9):S410, 1994
The diagnosis of polymyalgia rheumatica in patients
with a low erythrocyte sedimentation rate: comment
on the article by Helfgott and Kieval
To the Editor:
The issue of PMR with a low or normal ESR has
revived the interest of rheumatologists. Between 10% and 20%
of PMR patients show an ESR below 30 mmihour (1-3). In
these cases, the diagnosis is often delayed and the risk of visual
disturbanccs increased. Different strategies have been proposed for the diagnosis of PMR in patients with a low ESR.
including an evaluation of C-reactive protein levels (l), plasma
viscosity (4), symptoms and signs alone (2), concentration of
CD8+ T cells (S), or the effect of steroid treatment (6).
We have postulated that even a normal ESR may be an
indicator of inflammation. To substantiate this hypothesis, we
havc evaluated the changes in ESR after steroid treatment,
with a view to differentiating between patients with PMR and
healthy controls. The ESR was measured in 53 consecutive
patients with classic PMR and in 6 patients with PMR and a
normal ESR. The ESR was measured at diagnosis and after a
median of 24 days of treatment with a mean daily dosage of 1.5
mg of prednisone. PMR was diagnosed according to a modification of the criteria proposed by Jones and Hazleman (7), in
which only patients over SO years of age were included and the
ESR was not considered in the diagnosis. As controls, 2 young,
healthy individuals volunteered to receive prednisone (20 mg
daily) after giving their informed consent. ESRs of the 2
controls were measured at baseline and after 10 days of
The ESR significantly declined after treatment, both in
patients with a raised baseline ESR and in those with a normal
baseline ESR. The percentage differences were similar in both
groups (P < 0.00001 and P = 0.0029, respectively. by paired
t-test) (Table l), with a ratio between pre- and posttreatment
ESRs of 5.7 in patients with a raised ESR at baseline and a
ratio of 5.4 in patients with a normal ESR. The controls also
showed a decrease in ESR after steroid treatment; however,
this decrease was much lower than that observed in PMR
patients. The pre- and posttreatment ESR ratio for controls
was 1.4. The control subjects were considerably younger than
Table 1. Demographic and clinical characteristics of the study
Age, years
Ma1e:female ratio
Baseline ESR, mmihour
Posttreatment ESR, mm/hour
Baseline ESR:posttrcatment
ESR ratio
with high
(n = 53)
(n = 6)
(n = 2)
70.0 ? 9.6
76.4 t- 20.4
23.3 2 15.8
68.8 ? 9.2
25.8 5 3.7
7.5 ? 6.4
26 -t 2.8
10 -t 2.8
7 -t 1.4
* Except where otherwise indicated, values are the mean i- SD.
ESR = erythrocyte sedimentation rate.
the 2 patient groups, because we believe it is unethical to
administer steroids to healthy older people.
In 5 of the PMR patients, we were also able to evaluate
an ESR that was measured a few months before the onset of
PMR for reasons unrelated to the disease. This rate was
slightly lower than that observed after treatment (mean ? SD
11 i 8.8 mmihour versus 16.2 i 9.8 mmihour). One of these
patients, who belonged to the normal ESR group at baseline,
showed ii 1S-fold increase in the ESR, from 2 mmihour to 30
mmihour, in conjunction with the onset of PMR. This increase
was similar to the mean increase in ESR of 11.5 times,
observed in the remaining 4 patients with an elevated baseline
Our data suggest that measuring the ESR before and
after treatment with steroids, and calculating the ratio of
change, can help distinguish the diagnosis of PMR in patients,
even if their baseline ESR is normal. The same percentage of
decrease in the ESR was seen in patients with either a high or
normal baseline ESR. In contrast, normal subjects showed only
a small decrease in the ESR after steroid treatment. Therefore,
it seems that the absolute ESR value is not as clinically
significant in diagnosing PMR as is the increase in ESR from
the predisease value and its trend toward normalization after
therapy, as has been recently suggested by others (8).
Marco A. Cimmino, M D
Silvano Accardo, M D
Marco Scudeletti, M D
Francesco Indiveri, M D
Univecsity of Genoa
Genoa, Italy
1. Ellis ME, Ralston S: Thc ESR in the diagnosis and management of
the polymyalgia rheumaticaigiant cell arteritis syndrome. Ann
Rhcum Dis 42:168-170, 1983
2. Hclfgott SM, Kieval RI: Polymyalgia rheumatica in patients with a
normal erythrocyte sedimentation rate. Arthritis Rheum 39304307, 1996
3. Salvarani C, Boiardi C, Macchioni G, Olivieri I, Portioli I: Polymyalgia rheurnatica (letter). Lancet 348550-551, 1996
4. Murphy PT, Wood JK: Polymyalgia rheumatica (letter). Lancet
348550, 1996
5. Olsson AT, Elling H, Elling P: Frequency of a normal erythrocyte
sedimentation rate in patients with active, untreated arteritis temporalis and polymyalgia rheumatica: comment on the article by
Helfgott and Kicval (letter). Arthritis Rheum 40:191-192. 1997
6. Hopayian K: Diagnosing polymyalgia rheumatica (letter). Lancet
348:899, 1996
7. Jones JG, Hazleman B L The prognosis and management of
polymyalgia rhcuniatica. Ann Rheum Dis 4O:l-5, 1981
8. Caplan HI: Dcfining polymyalgia rheumatica: comment on thc
article by Helfgott and Kieval (letter). Arthritis Rheum 40:191, 1997
To the Editor:
Dry. Caliani and Paira confirm the main point of our
article, namely, that a normal ESR can bc found in patients
with the “classic” features of PMR. They point out that. in
some patients, the ESR may be normal initially, only to rise
over time. In fact, Jones and Hazleman noted this phenomenon in 5% of their patients (1).
In our study, the elevation of a previously normal ESR
was observed in only 3 patients. Thus, our higher incidence of
PMR in patients with a normal ESR cannot be explained on
this basis alone. Unfortunately, Drs. Caliani and Paira do not
quantify how frequently they observed this phenomenon in
their patient population. We would suggest that it remains an
unusual occurrence. The initiation of corticosteroid therapy
will almost always reduce the ESR toward normal levels. The
ability to study the course of a patient’s ESR over the long
term is usually precluded by the need to initiate corticosteroid
treatment for symptomatic relief.
With regard to the true incidence of PMR with a
normal ESR, it should be noted that the frequency observed in
our study (22%) closely resembles that observed by Ellis and
Ralston (2) (22.5%), Gonzalez-Gay et a1 (3) (20.4%), and
Olsson et a1 (4) (18%). Regardless of the true incidence of
PMR with a normal ESR, the diverse published descriptions of
this entity in patients from 3 different continents supports the
authenticity of this phenomenon as a clinical disorder.
Cimmino et a1 propose that measuring the ratio of the
decline in the ESR pre- and post-corticosteroid therapy may
provide a more accurate means of confirming the diagnosis of
PMR in patients with a normal ESR. Although statistical
significance was reached when comparing the normal ESR
with the elevated ESR groups, their small sample size of
normal ESR patients and the lack of age-matched controls
raises some concern. We doubt that this type of analysis would
be helpful in determining clinical relapses in patients being
treated with corticosteroids. Kyle et a1 (5) found the ESR to be
<30 mmihour in 48% of their patients. The inherent difficulty
with such a ratio lies in the fact that low values will greatly
enhance the ratio. In order to achieve the ratios noted by
Cimmino et al, these patients’ baseline ESR values would need
to be 5 mmihour or less. For example, a pretreatment ESR of
30 mmihour that drops to 2 mmihour post-corticosteroid
therapy (ratio 15) appears far more striking than an ESR of 75
mmihour pretreatment falling to 25 mmihour posttherapy
(ratio 3). Yet, is the first scenario more clinically significant
than the second?
Other disease states have been measured by the ESR.
Recently, Spector et a1 (6) reported that low-level increases in
the serum C-reactive protein level occur in early osteoarthritis
of the knee and can predict progressive disease. Ridker et a1
(7) and others (8,Y) have shown that the baseline plasma
concentration of C-reactive protein predicts the risk of future
myocardial infarction and stroke. It seems likely that these
results could be extrapolated to the role of the ESR measurement as well.
Based on these observations, we can conclude that the
currently used laboratory markers for inflammation may also
be influenced by disorders previously not thought to be
mediated by inflammation. Despite this concern, measurement
of the ESR in the evaluation of suspected PMR remains a
useful tool in the majority of patients with an elevated ESR.
However, as the recent profusion of published reports
(3,4,10) as well as our own study suggest, the finding of a
normal ESR in PMR is not uncommon. Although the calculation of the ratio of pretreatment to posttreatment ESR may
carry some clinical value, we would interpret the ratio obtained
with caution. When facing the diagnostic dilemma of PMR
with a normal ESR, the response to corticosteroids may hold
greater clinical utility in determining the diagnosis of PMR.
Simon M. Helfgott, MD
Haward Medical School
Boston, M A
Raphael I. Kieval, MD
Brockton Hospital
Brockton, M A
1. Jones JG, Hazleman BL: ESR in polymyalgia rheumaticd and
giant cell arteritis. Ann Rheum Dis 42:702-703, 1983
2. Ellis ME, Ralston S: The ESR in the diagnosis and management of
the polymyalgiaigiant cell arteritis syndrome. Ann Rheum Dis
421168-170, 1983
3. Gonzalez-Gay MA, Rodriguez-Valvarde V, Bianco R, FernandezSueiro JL, Armona J, Figueroa M, Martinez-Taboada VM: Polymyalgia rheumatica without significantly increased erythrocyte
sedimentation rate. Arch Intern Med 157:317-320, 1997
4. Olsson AT, Elling H, Elling P: Frequency of a normal erythrocyte
sedimentation rate in patients with active, untreated arteritis
temporalis and polymyalgia rheumatica: comment on the article by
Helfgott and Kieval (letter). Arthritis Rheum 40:191-192, 1997
5. Kyle V, Cawston TE, Hazleman BL: Erythrocyte sedimentation
rate and C-reactive protein in the assessment of polymyalgia
rheumatica giant cell arteritis presentation and during follow-up.
Ann Rheum Dis 48:667-671, 1989
6. Spector TD, Hart DJ, Nandra D, Doyle DV, Mackillop N,
Gallimore JR, Pepys MB: Low-level increases in serum C-reactive
protein are present in early osteoarthritis of the knee and predict
progressive disease. Arthritis Rheum 40:723-727, 1997
7 . Ridker PM, Cushman M, Stampfer MJ, Tracy RP, Hennekens
CH: Inflammation. aspirin, and the risk of cardiovascular disease
in apparently healthy men. N Engl J Med 336373-979, 1997
8. Kuller LH, Tracy RP, Shaten J, Mellahn EN: Relationship of
C-reactive protein and coronary heart disease in the MRFIT
nested case control study. Am J Epidemiol 144:537-547, 1996
9. Thompson SG, Kienast J, Pyke SDM, Haverkate F, van de Loo
JCW: Hemostatic factors and the risk of myocardial infarction or
sudden death in patients with angina pectoris. N Engl J Med
332:635-641, 1995
10. Salvarani C, Boiardi C, Macchioni G, Olivieri I, Portioli I:
Polymyalgia rheumatica (letter). Lancet 348:550-551, 1996
Penicillin in the treatment of Behget’s disease:
comment on the article by Calgiineri et al
To the Editor:
We read with great interest the article by Calgiineri et
a1 on penicillin treatment of BehEet’s disease (BD) (1). They
compared the efficacy of colchicine alone versus colchicine
plus penicillin in the prophylaxis of recurrent arthritis of BD.
The etiology of BD has not yet been definitely established (2). Although viruses, environmental factors, racial and
familial tendency, and autoimmunity have been implicated in
the pathogenesis of the disease, none of these factors has been
proven to be causative. It has been emphasized in recent years
that the manifestations of the disease are due to humoral and
cell-mediated immune reactions against streptococcal infections (3,4). We have made an interesting observation on the
interrelationship between streptococcal infections and BD
symptomatology (5). We observed 2 patients with BD who
developed chronic neutropenia. The manifestations of BD,
such as orogenital ulcers, erythema nodosum, papulopustular
skin lesions, and arthritis, had shown exacerbations following
attacks with these pathogens. We assumed that recurrent
streptococcal infections were the result of decreased immunity
caused by the neutropenic state. We treated these patients with
granulocyte colony-stimulating factor to increase absolute neutrophil counts. With this treatment, neutrophil counts returned
to normal and streptococcal infections did not recur. With the
disappearance of recurrent streptococcal infections, the attack
rates of BD decreased considerably. We believe that, rather
than being a direct etiologic factor, streptococcal infections
have a permissive action for the recurrence of the manifestations of BD.
The proposed relationship between BD and streptococcal infections is the rationale for the use of penicillin. We
wish to share our own experience with the use of penicillin in
BD. Since 1988, we have been prescribing benzathine penicillin
(1.2 million units intramuscularly every 3 weeks) alone or in
combination with colchicine (1.5 mgiday orally). We reported
our preliminary results at the Mediterranean Congress of
Rheumatology meeting held in Athens, Greece in 1994 (6).
Although penicillin was effective in the prevention of articular
attacks, its effect was more marked in the prophylaxis of oral
and genital ulcers.
Since no definite therapy is established in BD, new
agents are being evaluated. Interferon is gaining popularity for
its antiviral and immunomodulatory properties ( 7 ) . In another
study evaluating the role of interferon, we showed that this
agent was more effective than penicillin in the treatment and
prophylaxis of vascular and ocular complications (8).
Penicillin is a new agent for BD, and further studies are
required to definitely establish its role in the management of
the disease. The only convincing proof that streptococcal
infections are the cause of BD would be the documentation of
disappearance of all manifestations of the disease with antistreptococcal therapy alone. The cause-and-effect relationship
between streptococcal infections and BD is not as definite as in
the case of acute rheumatic fever and p-hemolytic streptococci.
In the latter interaction, penicillin prophylaxis will completely
prevent recurrent attacks. However, the effect of prophylactic
penicillin in the prevention of arthritis attacks in BD is not as
dramatic as that seen in acute rheumatic fever. Moreover, it
has no effect in the prevention of vascular and ocular disease
(6). Vascular involvement such as deep vein thrombosis and
ocular lesions seems to occur more commonly in patients who
are 5 3 0 years of age, have central nervous system disease, and
are within the first 2 years of disease onset (Y-11).
At present, we suggest that penicillin should especially
not be prescribed to patients who are at high risk for vascular
and ocular involvement. However, in patients with mucocutaneous lesions and articular manifestations dominating the
clinical picture, a trial with benzathine penicillin alone or in
combination with colchicine may be justified.
HalClk Demiroglu, MD
Semra Dundar, MD
Hacettepe University Medical School
Ankara, Turkey
1. Calguneri M, Kiraz S, Ertenli I, Benekli M, Karaarslan Y, Celik I:
The effect of prophylactic penicillin treatment on the course of
Без категории
Размер файла
383 Кб
articles, patients, low, kieval, rheumatic, sedimentation, erythrocytes, polymyalgia, ratecomment, helfgott, diagnosis
Пожаловаться на содержимое документа