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The consensus report also suggests that renal dysfunction and hypertension are contraindications for CSA.
We initially excluded patients who had renal dysfunction
defined by the presence of a >2-fold rise in serum creatinine
levels and those who had hypertension that was resistant to
conventional therapy. Furthermore, it should be emphasized
that side effects observed during the study period were
tolerable and did not warrant discontinuation of CSA.
Another question seems focused on the mildness or
severity (or activity) of our patients’ diseases. Patients who
had central nervous system or vascular system manifestations or serositis were excluded from our study. However,
most rheumatologists may consider these manifestations to
be life-threatening, necessitating prompt establishment of
high-dose corticosteroid treatment. Some of our patients
(patients 2, 3, and 7) did indeed have only immunologic
abnormalities which had failed to respond to conventional
immunosuppressive therapies. However, it is well known
that immunologic abnormalities, including hypocomplementemia and a rise in anti-double-stranded DNA antibody
levels, might reflect the disease activity of SLE and often
precede disease exacerbations (2-4).
This work is important since low-dose CSA combined with low-dose corticosteroids can effect both clinical
and immunologic improvement, with probable safety when
possible side effects are carefully monitored. We hope that a
randomized trial will be undertaken with the objective of
determining whether criteria could be established for the
selection of patients most likely to derive benefit from
low-dose CSA treatment. Studies to examine the possibility
of establishing these criteria are in progress.
Michiaki Tokuda, MD
Noriyuki Kurata, MD
Akihito Mizoguchi, MD
Masayuki Inoh, MD
Kunio Seto, MD
Makoto Kinashi, MD
Jiro Takahara, MD
Kagawa Medical School
Kagawa, Japan
1. Panayi GS, Tugwell P: An international consensus report: the use
of cyclosporin A in rheumatoid arthritis. Br J Rheumatol32(suppl
1):1-3, 1993
2. Laitman RS, Glicklich D, Sablay LB, Grayzel AI, Barland P,
Bank N: Effect of long-term normalization of serum complement
levels on the course of lupus nephritis. Am J Med 87(2):132-138,
3. Rauch J, Hazeltine M, Tannenbaum H , Danoff D, Isenberg DA,
Wild J, Sampalis J, Esdaile JM: Association of anti-DNA idiotype markers with clinical and serological manifestations in
patients with systemic lupus erythematosus. 3 Rheumatol 17(2):
178-185, 1990
4. Ter Borg EJ, Horst G, Hummel EJ, Limburg PC, Kallenberg
CGM: Measurement of increases in anti-double-stranded DNA
antibody levels as a predictor of disease exacerbation in systemic
lupus erythematosus: a long-term, prospective study. Arthritis
Rheum 33:634-643, 1990
Limitations in the usefulness of the 28-joint count:
comment on the article by Fuchs and Pincus and the
editorial by the American College of Rheumatology
To the Editor:
Fuchs and Pincus (1) and the accompanying editorial
(2) in a recent issue of Arthritis and Rheumatism demonstrate evidence to support a major advance in rheumatoid
arthritis (RA) assessment methodology. Its use should expedite controlled studies of RA, and it should facilitate international drug development strategies. I would add to the
clinical caveats mentioned (the importance, clinically, of
foot pathology in RA, including its use as an early radiographic marker, and the continued necessity for individualization of RA treatment in practice) another important
methodologic point which may, I think, have potentially
broad ramifications: guarding against allowing our vision of
future therapeutics in RA to be overguided by “datadriven,” rather than “disease-driven,’’ methodologic innovations. The 28-joint count proposal is purely data-driven,
its raison d’&trederived exclusively from the performance of
treatments that have already been in use. Succumbing to the
temptation to use this rather than the 66-joint count in all
situations is tantamount to allowing research to be driven by
methodology, rather than methodology driven by research.
The 28-joint count can have a use in supporting
claims of similarity among existing disease-modifying antirheumatic or nonsteroidal antiinflammatory drugs. However, the 28-joint count is clearly inappropriate for assessing
claims of superiority. In fact, the rationale for the 28-joint
count is itself diametrically opposed to the rational pursuit of
superior, nonstandard therapies. For these pursuits, fully
inclusive measures, reflecting the breadth of disease pathology, are needed.
Kent Johnson, MD
Bethesda. MD
1. Fuchs HA, Pincus T: Reducedjoint counts in controlled clinical
trials in rheumatoid arthritis. Arthritis Rheum 37:47W75, 1994
2. American College of Rheumatology Committee on Outcome
Measures in Rheumatoid Arthritis Clinical Trials: Reduced joint
counts in rheumatoid arthritis clinical trials (editorial). Arthritis
Rheum 37:463464, 1994
To the Editor:
We share Dr. Johnson’s concerns regarding possible
inappropriate use of reduced joint counts. However, isn’t a
joint count that is “data-driven,” whether the 28-joint count
(1) or any other carefully analyzed joint count (2), more
“disease-driven” than one that is simply empirically derived? The joints included in the 28-joint count were selected
because they are likely to be involved in disease, responsive
to therapeutic interventions, and reproducibly assessed (1).
Inclusion of additional joints adds “noise” and dilutes
effective measurement (more joints are not necessarily better). The 28-joint count, and counts with even fewer joints,
have been shown to be as predictive of long-term mortality
as more elaborate joint counts (3).
Clearly, all joints should be examined in a clinical
assessment, and we include hips and ankles in our own
studies of long-term outcomes of RA. We are concerned that
most rheumatologists do not incorporate any quantitative
joint assessment, despite evidence that these data are useful
for monitoring clinical status and predicting long-term outcomes, including mortality. A reduced joint count would
appear potentially helpful to remedy this situation, much as
simplified laboratory measures for rheumatoid factor and
acute-phase reactants have contributed to establishment of
the scientific base of rheumatology, despite the fact that
neither of these measures is as comprehensive as more
elaborate laboratory studies.
If a new laboratory test had the power of a joint
count in the prognosis of disability and mortality in RA or in
the monitoring of disease activity, it would undoubtedly be
incorporated into routine rheumatologic care. Hopefully,
reduced joint counts-not necessarily the 28-joint count
proposed, but counts that are equally pragmatic and validated-could not only be used in clinical trials but could be
standardized for general use by rheumatologists for all types
of clinical studies and clinical care. Standardized quantitative clinical measures would enhance the scientific basis of
clinical rheumatology .
Howard Fuchs, MD
Theodore Pincus, MD
Vanderbilt University School of Medicine
Nashville, TN
1. Fuchs HA, Brooks RH, Callahan LF, Pincus T: A simplified
twenty-eight-joint quantitative articular index in rheumatoid
arthritis. Arthritis Rheum 32531-537, 1989
2. Egger MJ, Huth DA, Ward JR, Reading JC, Williams HJ:
Reduced joint count indices in the evaluation of rheumatoid
arthritis. Arthritis Rheum 28513419, 1985
3. Pincus T, Brooks RH, Callahan LF: Prediction of long-term
mortality in patients with rheumatoid arthritis according to
simple questionnaire and joint count measures. Ann Intern Med
120:26-34, 1994
Cost-effectiveness of orally administered liquid
methotrexate: comment on the letters by McLaughlin
and by Wase
To the Editor:
The May 1994 issue of Arthritis and Rheumatism
contained 2 letters to the editor regarding the use of oral
versus parenteral methotrexate and the relative costs involved (1,2). It was pointed out that parenteral methotrexate
is much cheaper per mg than are the oral tablets. What was
not mentioned in either letter is that liquid methotrexate can
be given not only parenterally, but orally as well. In my
experience this has been very well accepted by patients,
requiring them only to do a simple measurement of dosage
and to dilute the drug in either water or Kool-Aid (the drug
is almost tasteless).
In our local pharmacy the following cost comparisons apply: Lederle methotrexate is $3.26 per 2.5-mg tablet.
Generic methotrexate is $2.22 per 2.5-mg tablet. Liquid
methotrexate costs $10.00 per 50 mg, which corresponds to
$0.50 per 2.5-mg dose.
I agree with Dr. McLaughlin that self-administered
subcutaneous methotrexate is an excellent way to give the
drug, especially in patients who have gut intolerance to oral
methotrexate. However, the parenteral form can also be
given orally, avoiding the need and expense for syringes and
David L. Hanson, MD, FACP, FACR
St. Cloud Clinic of internal Medicine
St. Cloud, MN
1. McLaughlin GE: Parenteral versus oral methotrexate: a cost
comparison (letter). Arthritis Rheum 37:779, 1994
2. Wase LC: Reply (letter). Arthritis Rheum 37:779, 1994
Rheumatology. Edited by John H . Klippel and Paul A .
Dieppe. London, Mosby- Year Book Europe Limited, 1994.
1,760 p p . Illustrated. indexed. $225.00.
In their preface to Rheumatology, Drs. Klippel and
Dieppe outline their reasons for developing an “entirely new
and different textbook,” stating that “lengthy tracts of dense
text are rarely read and of little value in the modem
world. . .” With an introduction like that, one might anticipate something long on glitz but short on substance. However, it doesn’t take long to discover that this textbook is as
solid as it is flashy.
That Rheumatology is truly a different textbook is
readily apparent. There is color galore-photographs by the
hundreds, very helpful drawings and cartoons (check the
section on the cellular immunology of lupus by Mary K.
Crow and Steven Friedman, for example), and the entire
book is even color-coded by chapter for easy access. Like
virtually all texts, it is multi-authored, but even here this
book is unique, with more than 250 authors from literally all
over the world.
Rheumatology is nicely edited. By that I mean that it
is not over-edited. No attempt is made to give this book the
feel of a single author, and the different personalities and
writing styles of the contributors are allowed to come
through. This is perhaps best exemplified by the witty
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