Portuguese Version

Year:  2002  Vol. 68   Ed. 3 - (11º)

Artigo Original

Pages: 363 to 367

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Diagnostic aspects in Sjogrën's Syndrome

Author(s): Bianca M. Liquidato(1),
Ivo Bussoloti Filho(2),
Ana Cristina K. Camargo(3),
Rita de Cássia Soler(1)

Keywords: Sjogrën's syndrome, salivary glands, sialometry

Abstract:
Introduction: Sjogrën's syndrome is an autoimmune disease that primarily affects the salivary and lachrymal glands, causing only xerostomia and decreased lachrymal flow or also other systemic manifestations. Many papers tried to establish a set of diagnostic criteria as far as there is not a single diagnostic criterion. Aim: Our work's objective was to evaluate the diagnostic methods utilized. Study design: Clinical prospective. Material and Method: 15 patients with Sjogrën's syndrome's symptoms were evaluated at the Ambulatório de Estomatologia do Depto. de Otorrinolaringologia da Santa Casa de São Paulo. Results: Only 6 out of 15 patients had their diagnosis confirmed. Conclusions: It is a very difficult disease to establish the diagnosis, this way, new non-invasive techniques must be developed with participation of the otolaryngologist.

Introduction

Sjogrën's syndrome is an autoimmune exocrine gland disease that involves mainly salivary and lachrymal glands. Its clinical spectrum is wide and it may range from reduction of lachrymation and xerostomia to articular, pulmonary or renal compromise. Sjogrën's syndrome may manifest alone, also called primary Sjogrën's syndrome, or together with other autoimmune diseases, especially lupus and rheumatoid arthritis, called secondary Sjogrën's syndrome.

The disease affects mainly females, with a prevalence of 9 women to one man, and onset of symptoms is at about 40 to 45 years, being a rare disease in children1. The mean age at diagnosis is 50 years2. Its real prevalence is not precisely defined because of the difficult diagnosis, but it is estimated to be about 1 to 3% of the population16.

Most of the cells that form the tissue infiltrate (60 to 70%) are made of TCD4, together with a minority of B-lymphocytes. However, there is hyperactivity of B cells, producing mono and polyclonal IgM or IgG immunoglobulins. Epithelial cells of minor salivary glands express cytokines such as interleukin 1b, interleukin-6 and TNF a. Autoimmune response is directed to rhibonucleoprotein Ro/SS-A, with two protein chains of 52 and 60kDa (cytoplasm) and La/SS-B (nuclear) of 48kDa. The mechanism that may be responsible for the autoimmune process is epithelial cell apoptosis 13.

More than one third of the patients present systemic manifestations that can include vasculitis, cryoglobulinemia, autoimmune hepatitis, pulmonary fibrosis, involvement of the central nervous system, renal tubular acidosis, B-cell lymphoma and multiple myeloma 1, 13, 16. Therefore, the appropriate diagnosis of the picture is important not only to alleviate the symptoms of the patients2, but also to provide the clinical follow-up of possible complications, since they are normally late events in the progression of the disease11.

A number of studies tried to define diagnostic criteria for Sjogrën's syndrome, since there is no single test that confirms the presence of the pathology. Such criteria were employed by different centers and it became difficult to interpret the data provided by the international literature. Some, for example, classified the clinical picture as "possible Sjogrën's syndrome" or "defined Sjogrën's syndrome", taking into account the positive results of rheumatic tests3.

A multicenter study conducted in 12 countries, guided by the European Community Study Group On Diagnostic Criteria For Sjögren's Syndrome, tried to define the criteria and test their specificity and sensitivity in order to have reliable criteria that could standardize diagnosis16, 17, 18.

The criteria defined by this multicenter study were:

1. Ocular symptoms of reduced lachrymation;

2. Oral symptoms of reduced salivation;

3. Signs of ocular compromise:

· Schirmer Test I (< or = 5 mm in 5 min).

· Rose Bengal (> or = 4).

4. Hystopathology: one or more foci (agglomerate of 50 or more inflammatory cells) in the biopsy of a minor salivary gland.

5. Salivary gland involvement:

· Salivary scintigraphy;

· Parotid sialography;

· Sialometry with non-stimulated salivary flow < or = 1.5ml in 15 min.

6. Anti Ro/SSA or Anti-La/SSB antibodies.

In patients without other associated diseases, the presence of 4 of the 6 items is indication of primary Sjogrën's syndrome. For secondary Sjogrën's syndrome, the presence of items 1 or 2 plus 2 of items 3, 4 or 5 is enough.

The technique of sialometry used in the studies of the European Community Study Group is simple collection of saliva during 15 minutes for non-stimulated modality and 5-minute collection after paraffin chewing for the stimulated modality. Non-stimulated sialometry was preferred because it is less influenced by age of subjects16, 17.

The positive results of autoantibodies varies a lot, and it is about 70% for anti-Ro/SSA and 60% for anti-La/SSB and some authors stated that this range of positive results may vary according to age of patients and methods used to detect them4, 5, 6, 9, 10.

Minor salivary gland biopsy is the most accurate test18, but it is not a sine qua non criterion for the diagnosis of Sjogrën's syndrome but, together with autoantibodies, they are considered the most specific tests available.

In children, the disease is normally manifested by recurrent parotiditis, rather than symptoms of the pure syndrome, and diagnosis is based on amylase increase and other laboratory abnormalities1, 12.

In recent years, many studies have concentrated on non-invasive methods to diagnose Sjogrën's syndrome, especially through dosage of substances present in the inflammatory process of the saliva and tears, such as interleukin-6 and hyaluronic acid14, 15. However, there are still no definite studies that validate their use as diagnostic criteria. Other imaging techniques such as magnetic resonance sialography have been studied as non-invasive alternatives to traditional sialography, trying to avoid possible complications such as duct trauma, pain upon the injection of the contrast, infection and allergic reaction8.

The participation of the Otorhinolaryngologist is essential to diagnosis, not only to perform minor salivary gland biopsy, but also to assess gland involvement, always trying to perform little invasive techniques. Sialometry with the cotton weighing method, which has been used in our center, has proven to be easy and simple to perform compared to the others and less invasive than parotid sialography.

The purpose of the present study was to assess the methods used to diagnose the pathology, based on the criteria defined by the European Community Study Group.

Material AND METHOD

We assessed clinically 15 patients who had suspicion of Sjogrën's syndrome, submitted to different diagnostic methods and cotton weighing sialometry technique.

Results

In the past three years, 15 female patients with suspicion of Sjogrën's syndrome were assessed at the Ambulatory of Stomatology, Department of Otorhinolaryngology, Santa Casa de São Paulo. Ages ranged from 35 to 76 years, mean age of 55 years. Out of the 15 patients, Sjogrën's syndrome diagnosis was confirmed based on the criteria mentioned above in 6 cases, and there were two cases of Sjogrën's syndrome secondary to rheumatoid arthritis. Ocular compromise, through the detection of keratitis points, was detected by staining; we did not use Rose Bengal nor non-stimulated sialometry, but rather cotton weighing, as described above.

Oral symptoms of dry mouth were present in 13 patients (86%) and ocular symptoms of dry eyes in 8 patients (53%). The ocular compromise investigation was conducted in 8 patients, but there was no direct correlation with the presence of ocular symptoms. We confirmed the diagnosis of ocular compromise by Schirmer test, Rose Bengal or both in 7 cases (46% of the total and 87% of the tested subjects). Schirmer test was performed in only 3 patients (20%), and out of them, 2 were positive.

Pathology of minor salivary gland biopsy with detection of inflammatory infiltrate foci was positive in 8 cases (53%). In the other cases, biopsy was not performed or it was non-conclusive owing to lack of salivary gland in the collected material (3 cases).

The involvement of salivary gland was investigated with at least one test in 7 cases (46%) and out of them, 6 were confirmed: 2 by scintigraphy, 1 by parotid sialography, and 3 by sialometry.

Anti-SSA and anti-SSB antibodies were tested in 8 cases (53%). Positive responses to anti-SSA or Anti-SSB antibodies were detected in 4 cases (50% of the tested cases).

Chart 1 shows the diagnostic criteria results for the studied cases.

Discussion

The main aspect we could observe in the present study was the difficulty to define the diagnosis of Sjogrën's syndrome. Since in many situations a multidisciplinary assessment, involving rheumatologist, otorhinolaryngologist and ophthalmologist is necessary, professionals form different areas should be integrated and use the same criteria to define the diagnosis, because the most appropriate diagnostic investigation is not always performed in many cases. The predominance of female subjects described in the literature was also confirmed by our results. However, the mean age range of our patients was different from the age described for onset of symptoms2, which may be explained by the fact that in many occasions both patients and physicians tend to disregard symptoms.

We could observe that the positive results for anti-SSA and anti-SSB antibodies were lower than those described by the literature16, 17, 18, a fact that may be explained by the examination technique or the reduced size of the sample.

Among the tests that assess ocular compromise, we noticed that Schirmer test was little performed, although it is an easy test, even for otorhinolaryngologists, who are familiarized with the technique owing to its use for topodiagnosis of peripheral facial palsy.

The analysis of cases showed that assessment methods involving the salivary glands were not frequently made, both invasive ones, such as parotid sialography, and less invasive ones, such as sialometry. It shows the reduced role of the Otorhinolaryngologist. Similarly, minor salivary gland biopsy was not appropriately performed in 3 cases, in which the material sent for biopsy did not show glands, which is a technical failure that has to be corrected.

Conclusion

In the present study, we observed that it is very difficult to define the diagnosis of Sjogrën's syndrome. The improvement of less invasive diagnostic techniques, such as sialometry, is extremely important. Since most of the tests involved in the diagnosis of this pathology belong to the Otorhinolaryngology arena, the participation of Otorhinolaryngologists is expected to be more active and integrated with the other specialties aiming at coming to a precise diagnosis of the disease.

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[1] Doctorate studies under course in Otorhinolaryngology, Medical School, Santa Casa de São Paulo.
[2] Assistant Professor, Discipline of Otorhinolaryngology, Medical School, Santa Casa de São Paulo.
[3] Master studies under course in Otorhinolaryngology, Medical School, Santa Casa de São Paulo.

Study conducted as the Department of Otorhinolaryngology, Santa Casa de São Paulo.

Address correspondence to: Rua Ministro Godoy, 928 apto. 102 - Perdizes CEP 05015-000 - São Paulo - SP.

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