Home

Current Issue

Archives

Guidelines for Authors

Classified Ads

Links

Search PubMed

Subscriptions

Subscriber Registration

Guidelines for Website Users

JRheum Update Service

Contact Info

Correspondence

Not For Sale, Not Even For Rent: Just Say No. Thoughts About the American College of Rheumatology Adopting a Code of Ethics

To the Editor:

I enjoyed the article and the wonderfully erudite writing of Dr. Richard Panush¹. I learned from his comments and they were highly germane to our current relationship with the pharmaceutical industry. However, I don't think that we can "just say no" to drug company interactions. Doctors live in two worlds, one that is business and the other that is patient care. The income paying for the business endeavors (such as our salary and overhead) is based upon our medical knowledge that is delivered to patients, performance of laboratory and clinical research, writing of textbooks, teaching rheumatology, and being consultants to drug companies and the business world. Problems arise when patient care intersects with any of the business activities, but especially with pharmaceutical contacts, although that juxtaposition is impossible to avoid or ban. For example, how do I read this esteemed journal and not be influenced by the drug company advertisements? Do I pay someone to rip the glossy pictures out for me? Without the advertisements, it is likely that the journals would be very expensive, and truthfully I learn from many of them. How do I keep up with the introduction of the astoundingly effective new treatments for diseases without allowing the drug companies to tell me about them? My delivery of patient care is influenced by many factors including information from drug companies, journals, word of mouth, and professional meetings, just to name a few, all of which need to be kept in proper perspective. After all, if I only read journals, and wasn't up to date, I would still consider peptic ulcer to be caused by stress. I may become subconsciously beholden to the sponsor of an educational meeting that I attend, as Dr. Panush points out, but I believe that will be counterbalanced by the knowledge that I gained by attending the meeting.

We do need a code of ethics. We all believe in them. We can't allow ourselves to be captives of commercialism. Stop the excesses. Monitor the meetings for inappropriate or wrong information. Don't allow talks or seminars with commercial messages. Continue with educational meetings. Keep them modest. Have drug representatives meet with us only when something is new or needs explanation. Stop the free lunches at the workplace, they are not necessary for us and are demeaning to the drug representatives who bring them. Use these guidelines as the norm for the pharmaceutical industry and their encounters with us, but at the same time realize that the pharmaceutical companies and the doctors need to work together for the advancement of rheumatology.

MICHAEL H. ELLMAN, MD, University of Chicago Hospitals, Division of Rheumatology, 5841 South Maryland Avenue, Chicago, Illinois 60637, USA. E-mail: mellman@medicine.bsd.uchicago.edu

REFERENCE

1. Panush RS. Viewpoint: Not for sale, not even for rent: Just say no. Thoughts about the American College of Rheumatology adopting a code of ethics. J Rheumatol 2002;29:1049-57.

Dr. Panush replies

To the Editor:

As I know, like, and respect Dr. Ellman, I appreciate his kind and thoughtful comments. My article reflected on the ethics appropriate for American College of Rheumatology (ACR) leadership, and indeed the ACR as an organization regarding relationships with industry. I thought that the highest standards of ethical behavior would be met by eschewing such relationships. I still think so, and believe this applies to physicians generally. There are compelling professional and ethical reasons to reject industry gifts and relationships. I presented these. They include the obligations incurred, the clearly documented and sometimes pernicious influence they have, the unjust spending practice involved, the threat to the physician-patient relationship, and the erosion of the physician's fiduciary role as trustee of patients' welfare. I also acknowledged that individuals and organizations confront imperatives other than ethics and that some will judge there to be circumstances when these trump ethics.

Dr. Ellman raises some specific issues which I did not address in my essay. I am grateful for the opportunity to comment on these. I do not disrespect the contributions of industry or advocate ignoring their advances, information, or representatives; I do suggest recognizing that their agendas are not always ours and that we not accept their "gifts." I do not urge that we avoid attending meetings but rather that educational sponsorship of meetings, when necessary, at least meet the expectations set by governing bodies (i.e., the Accreditation Council for Continuing Medical Education, the American Medical Association, and the American College of Rheumatology). We certainly ought to pay for our attendance at educational meetings and we are certainly able to do so (there should be no expectation that someone else do this for us). We certainly ought to buy our own pens, notepads, coffee mugs, and books, and can surely afford these; accepting such "gifts" is really silly, unnecessary, inappropriate, and morally offensive. Dr. Ellman and I agree that "there is no free lunch" and that these are demeaning to all. I don't defend print/journal advertising (and didn't discuss this in my paper) and would prefer reading the literature without it; but this may be a somewhat special case (e.g., see the correspondence and reply regarding "pharmaceutical advertising in the Journal," New England Journal of Medicine 1992;327:1688-9). I understand that many physicians have become dependent on professional and personal income from relationships with industry. I would hope that these relationships are contractually explicit (which is different than a gift), are fully disclosed when appropriate, and that these individuals recuse themselves in situations where conflicts of interest might arise or be perceived to arise (or avoid such situations entirely). I don't think it is enough to "stop the excesses" or "keep them modest." I don't think merely trying to set limits or "draw lines" (Whose line? Where? Under what circumstances?) works well enough. We generally have adapted to the pervasiveness of industry influence and struggled, variably, to tolerate the attendant discomfort. I worry greatly that there is something profoundly wrong with our professional world when/if we lose perspective about values and relationships, when we expect and accept entitlements for various personal and professional perquisites, and, yes, when/if we let financial incentives cloud our judgment or affect our behavior.

A paradigmatic change in attitude is needed. It's not easy to say "no" to gifts and the relationships they engender. But neither it is inordinately difficult. And, I respectfully suggest, it is the most rigorously ethical approach.

"A people that values its privileges above its principles soon loses both." — Dwight D. Eisenhower, Inaugural Address, January 20, 1953

RICHARD S. PANUSH, MD, Department of Medicine, Saint Barnabas Medical Center, 94 Old Short Hills Road, Livingston, NJ 07039, USA. E-mail: rspanush@sbhcs.com

Do Gastroprotective Drugs Prevent NSAID Toxicity?

To the Editor:

We read with interest the recent article by Wolfe and colleagues regarding gastrointestinal ulcers and nonsteroidal antiinflammatory drugs (NSAID)¹. Their description of channeling bias is very informative and may indeed, explain their results. However, we would like to offer another hypothesis.

Wolfe and colleagues found that patients who are prescribed anti-ulcer treatment (H2 receptor antagonists, proton pump inhibitors, sucralfate, or misoprostol) with a nonselective NSAID or selective cyclooxygenase-2 (COX-2) inhibitor are at a higher risk of future gastrointestinal (GI) ulceration than NSAID users who do not receive concomitant anti-ulcer treatment. The authors suggest that this demonstrates channeling bias — that is, the tendency for physicians to preferentially prescribe anti-ulcer treatment to patients at high risk of GI ulceration. Such patients, despite anti-ulcer treatment, are still prone to GI outcomes; thus, anti-ulcer treatments would paradoxically appear not to confer any safety advantage. They argue that the use of such agents acts as a marker for worse GI morbidity, and that this property can be used to demonstrate the added safety advantage of the selective COX-2 inhibitors.

We agree that this source of bias probably explains part of Wolfe and colleagues' results, but would suggest that another important common pharmacoepidemiologic bias may underlie their results — depletion of susceptibles. This refers to the loss to followup (depletion) of patients with dyspeptic symptoms who are prone to have GI ulceration (susceptibles) and therefore do not complete the full period of observation while taking an NSAID or selective COX-2 inhibitor². One would expect that discontinuation of antiinflammatory treatment would occur less often in patients taking anti-ulcer treatments that limit dyspepsia. These patients are likely to experience fewer GI symptoms and will be able to take an NSAID or selective COX-2 agent at higher dosages and/or for longer periods. Such greater use would put them at a higher risk of GI ulceration. Depletion of susceptibles has been suggested to explain part of the higher rates of complicated ulcers seen at the completion of the CLASS trial in patients randomized to selective COX-2 inhibitors versus traditional NSAID³.

Thus, the higher rates of GI ulceration reported by Wolfe and colleagues in patients prescribed gastroprotective drugs may not be solely the result of higher baseline patient risk (channeling bias). It may also be caused by depletion of susceptibles: patients taking gastroprotective drugs would be less likely to develop GI symptoms and would therefore continue their antiinflammatory treatments and remain at risk of ulceration. By contrast, those not taking gastroprotective drugs would be more likely to develop GI symptoms, which in turn would cause them to stop their NSAID or selective COX-2 inhibitor. This discontinuation of antiinflammatory treatment seen in patients without a gastroprotective treatment may in fact protect them against future GI ulceration. Consequently, the lower rate of ulceration observed by the authors may also be a result of this differential discontinuation of anti-ulcer drugs by patients, rather than solely the result of differential prescribing by physicians.

DANIEL H. SOLOMON, MD, MPH; JERRY AVORN, MD, Division of Pharmacoepidemiology and Pharmacoeconomics, Brigham and Women's Hospital, Boston, MA, USA.

REFERENCES

1. Wolfe F, Anderson J, Burke TA, Arguelles LM, Pettitt D. Gastroprotective therapy and risk of gastrointestinal ulcers: risk reduction by COX-2 therapy. J Rheumatol 2002;29:467-73.

2. Yola M. Lucien A. Evidence of the depletion of susceptibles effect in non-experimental pharmacoepidemiologic research. J Clin Epidemiol 1994;47:731-7.

3. Goldkind L. Gastrointestinal review highlights of the CLASS Study. [Cited August 9, 2002]. Available at: http://www.fda.gov/ohrms/dockets/ac/01/slides/3677s1_03_goldkind/tsld001.htm

Dr. Wolfe replies

To the Editor:

We appreciate the thoughtful letter of Solomon and Avorn in response to our article¹, in which we suggested that the positive association of proton pump inhibitors (PPI) and gastrointestinal (GI) ulceration was the result of (in the words of Solomon and Avorn) "channeling bias - that is, the tendency of physicians to preferentially prescribe anti-ulcer treatment to patients at high risk of GI ulceration." Solomon and Avorn suggest another "important, common bias may underlie [our] results — depletion of susceptibles." Specifically they suggest that there should be an increased rate of dropouts in our data bank among persons with dyspeptic symptoms. It would follow that data bank dropouts would be decreased among persons who receive PPI, as such drugs would decrease dyspeptic symptoms. The consequence of these effects would be to increase exposure to nonsteroidal antiinflammatory drugs (NSAID) and lead, therefore, to the observed increased rate of GI ulceration among PPI users.

The Solomon/Avorn hypothesis is testable. We performed Cox regression analysis using 16,058 patients with rheumatoid arthritis (RA) in the National Data Bank for Rheumatic Diseases (NDB). Failure was defined as terminating participation in the NDB surveys for any cause. Dyspeptic symptoms were defined as one or more of the following: nausea, vomiting, heartburn, epigastric pain, lower abdominal pain, constipation, or diarrhea. In addition, a count of GI dyspeptic symptoms was calculated. PPI use included any of the following drugs: lansoprazole, omeprazole, pantoprazole, esomeprazole, or rabeprazole.

Of the 54,174 observations, PPI use was noted in 18.3%. Dyspeptic symptoms were noted in 25.2% of observations, and the total dyspeptic symptom score was 1.0 (range 0-7). As shown in Table 1 (univariate analyses), dyspeptic symptoms have a protective effect as a dichotomous variable, but no effect as a continuous variable on the hazard of dropping out. PPI have a non-significant effect on the hazard of dropping out in the univariate analyses.

Table 1. Analysis of discontinuations of data bank surveys among 16,058 patients with RA in the National Data Bank for Rheumatic Diseases.

In multivariate analyses, controlling for demographic and severity factors, dyspeptic symptoms have a modest protective effect on the hazard of dropping out of the study when measured as a continuous variable. PPI have a modest but significant protective effect on this risk, and this protective effect is greatest among patients with dyspeptic symptoms. We also performed these analyses using various sensitivity analyses for the individual component of the dyspeptic variable/count, and noted no meaningful differences from the results presented in Table 1.

The results of these analyses do not confirm the Solomon/Avorn conjecture that dyspeptic symptoms are associated with increased risk of study dropouts in this data set. They do suggest that use of PPI has a small protective effect on study termination. The magnitude of this protective effect is small in comparison to the large effect of PPI on the risk of GI ulceration that we have reported¹. We conclude, therefore, that depletions of susceptibles did not play an important role in the results of our study of PPI and GI ulceration¹.

FREDERICK WOLFE, MD, National Data Bank for Rheumatic Diseases, Wichita, KS; THOMAS A. BURKE, PharmD, Pharmacia Global Health Outcomes, Peapack, NJ; DAN PETTITT, DVM MSc, Pfizer Outcomes Research, New York, NY, USA.

REFERENCES

1. Wolfe F, Anderson J, Burke TA, Arguelles LM, Pettitt D. Gastroprotective therapy and risk of gastrointestinal ulcers: risk reduction by COX-2 therapy. J Rheumatol 2002;29:467-73.

2. Fransen J, Hauselmann H, Michel BA, Caravatti M, Stucki G. Responsiveness of the self-assessed rheumatoid arthritis disease activity index to a flare of disease activity. Arthritis Rheum 2001;44:53-60.

3. Meenan RF, Gertman PM, Mason JH, Dunaif R. The arthritis impact measurement scales. Arthritis Rheum 1982;25:1048-53.

Treatment Resistant Ankylosing Spondylitis with Peripheral Joint Involvement — A Case for Infliximab?

To the Editor:

Inhibitors of tumor necrosis factor-a (TNF-a) have been successfully introduced to the treatment of rheumatoid arthritis (RA), juvenile chronic polyarthritis, and Crohn's disease^1-3. Recently, studies have confirmed their efficacy in other rheumatic conditions, especially in seronegative spondyloarthropathies^4-6. We read with interest the recent report by Maksymowych, et al⁷. In a prospective observational study, they investigated the efficacy and the side effect profile of infliximab in patients with nonsteroidal antiinflammatory drug (NSAID) refractory ankylosing spondylitis (AS). In 17 of 21 patients who completed the study, a significant improvement was seen with respect to all Bath AS indexes, erythrocyte sedimentation rate (ESR), and C-reactive protein. Notably, in 5 of 11 patients with peripheral joint involvement, complete resolution of peripheral arthritis was seen at the 14th week. This matches well with our own experience of the efficacy of infliximab in AS.

We started infliximab therapy in a 55-year-old woman with disabling, treatment resistant AS. Her disease started in 1978 with severe pain in the lumbar spine and peripheral arthritis involving wrist, proximal interphalangeal (PIP), and knee joints. She was initially diagnosed as having RA and treated with NSAID and prednisone (15 mg/day). Although some initial improvement was achieved, her disease progressed rapidly. We saw her first in May 1993; she presented with polyarthritis involving most peripheral joints (wrists, PIP joints, elbows, knees, ankles, and hip joints; Figure 1) and severe spinal deformities highly suggestive of AS (Figure 2).

Figure 1. Swelling of some PIP joints and enlargement of the right wrist (left). Enlargement of the suprapatellar recess of the left knee joint due to effusion (right).

Figure 2. Severe deformity of the spine (left) and complete ankylosis of the thoracic spine on the lateral chest radiograph (right). Note Cushingoid appearance (obesity with typical fat deposition pattern, striae on the lateral aspect of the chest).

According to the clinical picture, typical radiographic abnormalities (symmetric ankylosis of the sacroiliac joints, syndesmophytes of the spine), positive HLA-B27, and negative rheumatoid factor, the diagnosis of RA was revised and AS was diagnosed. Unfortunately, continuous use of glucocorticoids led to the Cushing-like appearance of the patient (Figure 2), hypertension, osteoporosis, and secondary diabetes. The dose of prednisone was tapered to 5 mg/day, but all attempts to discontinue the drug failed due to severe exacerbations of disease activity. NSAID therapy was continued and she received sulfasalazine (1.0 g twice daily) over several months, with no noticeable effect. As the peripheral arthritis worsened, arthrocenteses of the knee, wrist, and/or elbow joints with intraarticular glucocorticoid injections were required every 3-4 weeks. After a failure of cyclophosphamide pulse therapy, methotrexate was introduced (20 mg intramuscularly weekly) and then sulfasalazine (1.0 g twice daily) was added. This treatment provided some benefit and was continued over the next few years. In January 1994, she underwent synovectomy of the knee joints with only partial improvement. From 1994 to 2002, several hospitalizations were required due to the exacerbations of disease activity. She continuously suffered severe spinal pain and peripheral arthritis; recently, effusions of the knee joints had to be evacuated every 2nd week. As no improvement could be obtained with a standard approach, we decided to introduce infliximab (5 mg/kg intravenously). An impressive reduction of symptoms was seen 2 weeks after the infusion: duration of morning stiffness fell from 3 h to 1 h, tender joint count decreased from 12 to 1, swollen joint count fell from 10 to 2. ESR decreased from 100 to 17 mm (both values after 1 h). Changes in Bath AS Disease Activity Index (8.2 pre- and 7.3 post-treatment) and Bath AS Functional Activity Index (9.2 pre- and 9.0 post-treatment) were less impressive, most probably due to advanced ankylosis and structural damage of the spine.

We decided not to start the typical induction scheme of infliximab as we feared the increased infection risk due to diabetes and the longterm prednisone treatment. However, we are going to continue the infliximab infusions at longer intervals (5 mg/kg every 12th week). During the 8 weeks of post-infusion observation, no further arthrocenteses nor intraarticular glucocorticoid injections were needed, despite the reduction of the NSAID and oral prednisone intake (now the patient takes 5 mg prednisone every second day). No adverse events occurred during the observation.

The patient's excellent response to a single infliximab dose suggests that introduction of TNF-a inhibitors should always be considered as a therapeutic option in patients with the most severe, refractory AS, especially in those with peripheral polyarthritis. Early introduction of biologic therapies may reduce the need for oral and intraarticular glucocorticoids and prevent serious prednisone related complications in the most severe cases of AS, and the future use of TNF-a inhibitors will greatly improve the outcome of AS.

PAWEL HRYCAJ, MD; JAN K. LACKI, MD, PhD, Department of Rheumatology and Clinical Immunology, University School of Medical Sciences, Winogrady 144, 61-626 Poznan, Poland. E-mail phrycaj@icpnet.pl

REFERENCES

1. Taylor PC, Williams RO, Maini RN. Immunotherapy for rheumatoid arthritis. Curr Opin Immunol 2001;13:611-6.

2. Bloom BJ. New drug therapies for the pediatric rheumatic diseases. Curr Opin Rheumatol 2001;13:410-4.

3. Sandborn WJ, Targan SR. Biologic therapy of inflammatory bowel disease. Gastroenterology 2002;122:1592-608.

4. Sieper J, Braun J. New treatment options in ankylosing spondylitis: a role for anti-TNF-a therapy. Ann Rheum Dis 2001;60 Suppl 3:58-61.

5. Van den Bosch F, Baeten D, Kruithof E, De Keyser F, Mielants H, Veys EM. Treatment of active spondyloarthropathy with infliximab, the chimeric monoclonal antibody to tumour necrosis factor alpha. Ann Rheum Dis 2001;60 Suppl 3:33-6.

6. Mease PJ. Tumour necrosis factor (TNF) in psoriatic arthritis: pathophysiology and treatment with TNF inhibitors. Ann Rheum Dis 2002;61:298-304.

7. Maksymowych WP, Jhangri GS, Lambert RG, et al. Infliximab in ankylosing spondylitis: a prospective observational inception cohort analysis of efficacy and safety. J Rheumatol 2002;29:959-65.

Drs. Maksymowych and Russell reply

To the Editor:

We thank Drs. Hrycaj and Lacki for their interest in our report. The response of their patient with treatment refractory AS to a single infusion of infliximab is consistent with our own experience and highlights several issues. First, disease modifying agents traditionally used in RA lack efficacy in AS. Second, systemic steroids are similarly of limited value. Third, although anti-TNF-a therapies are costly, many such patients with NSAID refractory AS would not only be spared the toxicities associated with currently available therapies but also experience substantial symptomatic and functional improvement. The ultimate cost-utility benefits could therefore be significant. Fourth, the apparent lack of change in the BASDAI score despite significant clinical improvement suggests that there is further room for improvement in the development of clinically meaningful outcome measures, especially in late disease.

WALTER P. MAKSYMOWYCH, FRCPC; ANTHONY S. RUSSELL, FRCPC, Department of Medicine, University of Alberta, Edmonton, Alberta, Canada.

Clinical and Immunological Factors Associated with Low Lacrimal and Salivary Flow Rate in Patients with Primary Sjögren's Syndrome

To the Editor:

Salivary gland dysfunction is one of the key manifestations in Sjögren's syndrome (SS), and determining salivary flow rates is of diagnostic and prognostic importance. Collection of unstimulated whole saliva (UWS) is currently used as a sialometrical investigation in the diagnosis of SS¹. Particularly at the time SS develops, not all salivary glands may manifest dysfunction, rendering whole saliva less valuable as a diagnostic fluid. The collection of glandular saliva, however, reveals sequential involvement of different glands, reflecting the autoimmune process in individual salivary glands. Haga² evaluated the association between various clinical and immunological measures and reduced salivary flow. He concluded that only immunological factors (antinuclear antibodies and anti-Ro/SSA) were associated with salivary flow in primary SS, while he did not observe a correlation between UWS and duration of disease. This conclusion may be partly due to his experimental method, as the number of patients with a long duration of symptoms (mean 13.5 years) in his study is rather high. Surprisingly, in spite of this long disease duration, almost half the patients (34/72) have an UWS rate > 1.5 ml/15 min.

We recently defined reference values of several salivary variables, for diagnosing SS³. Our study indicated that gland-specific saliva collection and analysis are much more accurate diagnostics than the collection of UWS. Moreover, different sialometrical and sialochemical profiles can be observed, characteristic for either early or late salivary manifestations⁴. Patients with short duration of oral symptoms (less than one year) showed either normal flow rates with changed salivary composition, or reduced stimulated flow rate from the submandibular/sublingual (SM/SL) glands accompanied by (sub)normal flow rate from the parotid glands. It seems that the parotid gland is the last salivary gland to manifest hyposalivation, which has been confirmed in other studies^5,6.

Recent data from a longitudinal study indicate that loss of salivary gland function is mainly prominent in early SS, and that the (diminished) function stays relatively stable during the subsequent disease course (Figure 1). Since Haga predominantly evaluated patients with a rather late salivary manifestation, i.e., after long disease duration, the initial normal or selective hypofunction characteristically associated with disease onset will be absent. Further, the use of UWS may lead to underdiagnosing patients with SS of early onset, because a persisting normal function of parotid glands may mask an acquired dysfunction of SM/SL glands. Determination of glandular flow rates is therefore not only important in the diagnosis of SS, but also in identifying patients early after disease onset. These patients in particular, who manifest substantial residual exocrine gland function, may benefit more from (systemic) therapy. A longterm prospective study to clarify the prognosis of salivary gland function is currently in progress.

Figure 1. Relation between disease duration, i.e., the time from first complaints induced by or related to oral dryness until referral, and mean salivary flow rates. UWS: unstimulated whole saliva, SM/SL: submandibular/sublingual glands.

JUSTIN PIJPE, MD; WOUTER W.I. KALK, MD, DDS, PhD; ARJAN VISSINK, MD, DDS, PhD, Department of Oral and Maxillofacial Surgery, University Hospital Groningen, Groningen, The Netherlands.

REFERENCES

1. Vitali C, Bombardieri S, Jonsson R, et al. Classification criteria for Sjögren's syndrome: a revised version of the European criteria proposed by the American-European Consensus Group. Ann Rheum Dis 2002;61:554-8.

2. Haga HJ. Clinical and immunological factors associated with low lacrimal and salivary flow rate in patients with primary Sjögren's syndrome. J Rheumatol 2002;29:305-8.

3. Kalk WWI, Vissink A, Spijkervet FKL, Bootsma H, Kallenberg CGM, Nieuw Amerongen AV. Sialometry and sialochemistry: diagnostic tools for Sjögren's syndrome. Ann Rheum Dis 2001;60:1110-6.

4. Kalk WWI, Vissink A, Stegenga B, Bootsma H, Nieuw Amerongen AV, Kallenberg CGM. Sialometry and sialochemistry: a non-invasive approach for diagnosing Sjögren's syndrome. Ann Rheum Dis 2002;61:137-44.

5. Carpenter GH, Proctor GB, Pankhurst CL, O'Donohue J, Scott D, Hunnable MP. Sialochemical markers of salivary gland involvement with Sjögren's syndrome secondary to rheumatoid arthritis and primary biliary cirrhosis. J Oral Pathol Med 2000;29:452-9.

6. Fox PC, Sarras AK, Bowers MR, Drosos AA, Moutsopoulos HM. Oral and sialochemical findings in patients with autoimmune rheumatic disease. Clin Exp Rheumatol 1987;5:123-6.

Dr. Haga replies

To the Editor:

I enjoyed the comments to our report¹ from Dr. Pijpe and colleagues. They question the use of unstimulated whole saliva collection as a diagnostic tool in primary Sjögren's syndrome. They have demonstrated that gland-specific saliva collection and chemical analysis of saliva are much more accurate diagnostic tools than collection of UWS².

Different sialometrical and sialochemical profiles can be observed, characteristic for either early or late salivary manifestations³. UWS collection is a crude diagnostic tool that is more practical to perform in a clinical setting than gland-specific saliva collection, which I also believe is of more diagnostic value. Another point is that patients who really "want" the diagnosis of primary SS may swallow the saliva to achieve low saliva volume during the collection time. This is uncommon, but in my clinical practice I have experienced this phenomenon. Dr. Pijpe, et al also demonstrated that UWS collection is of less value early in the disease, thereby underdiagnosing patients with primary SS at early onset. Therefore I will look forward to the results of their longterm prospective study to clarify the prognosis of salivary gland function.

HANS-JACOB HAGA, MD, The National Hospital, N-0027 Oslo, Norway.

REFERENCES

1. Haga H-J. Clinical and immunological factors associated with low lacrimal and salivary flow rate in patients with primary Sjögren's syndrome. J Rheumatol 2002;29:305-8.

2. Kalk WWI, Vissink A, Spijkervet FKL, Bootsma H, Kallenberg CGM, Nieuw Amerongen AV. Sialometry and sialochemistry: diagnostic tools for Sjögren's syndrome. Ann Rheum Dis 2001;60:1110-6.

3. Kalk WWI, Vissink A, Stegenga B, Bootsma H, Nieuw Amerongen AV, Kallenberg CGM. Sialometry and sialochemistry: a non-invasive approach for diagnosing Sjögren's syndrome. Ann Rheum Dis 2002;61:137-44.