|Year : 1968 | Volume
| Issue : 1 | Page : 19-23
Sjogren's Syndrome - A Clinicopathological Study
Department of Ophthalmology, Jawaharlal Institute of Post-graduate Medical Education and Research, Pondicherry, India
|Date of Web Publication||22-Dec-2007|
N N Sood
Department of Ophthalmology, Jawaharlal Institute of Post-graduate Medical Education and Research, Pondicherry
Source of Support: None, Conflict of Interest: None
|How to cite this article:|
Sood N N. Sjogren's Syndrome - A Clinicopathological Study. Indian J Ophthalmol 1968;16:19-23
Sjogren's syndrome is a chronic systemic disorder of idiopathic origin characterized by three major components keratoconjunctivitis sicca, xerostomia and polyarthritis of rheumatoid origin occurring predominantly in women over forty years. The first person to associate dryness of mouth and conjunctiva due to diminution of salivary and lacrimal gland secretion was FUCHS  . The syndrome in its present form was established by SJOGREN  in 1933.
The terms Sjogren's syndrome and keratoconjunctivitis sicca are often used interchangebly, so that diagnostic criteria suggested by BUNIM, BUCHNAN, WERTLAKE, SOKOLOFF, BLOCK, BEEK AND ALEPPA  were employed. If two out of the three major components viz. keratoconjunctivitis sicca, xerostomia and rheumatoid arthritis are present a diagnosis of Sjogren's syndrome can be made. For each one of these there is an objective and a reliable diagnostic criterion.
| Materials and methods|| |
During the years 1964 - 1966 at the General Hospital, Pondicherry and at JIPMER Hospital, fifteen cases in whom a diagnosis of Sjogren's syndrome and keratoconjunctivitis sicca was made, were selected for study. A detailed ocular and general examination was carried out for each case.
The diagnosis of rheumatoid arthritis was made, based on the diagnostic criteria of the AMERICAN REUMATIC ASSOCIATION. 
Schirmer's test was done in each case before examination with light and repeated at a second sitting. A presence of punctate corneal stains on the slit lamp with fluorescein or rose bengal was required for the diagnosis of keratoconjunctivitis Sicca.
Sialogram was attempted in three cases. A present or a past history of swelling of parotids and submaxillary glands was enquired and so was the history of dryness of mouth but subjective history of dryness of mouth was not considered to be a reliable major criterion for diagnosis. Objective evidence of swelling or atrophy of parotid or submaxillary glands was taken as evidence of salivary gland involvement.
Blood was examined for blood counts, E.S.R., serum proteins (Total and A/G Ratio) and sheep cell agglutination. In three cases gastric function test for achylia gastrica were done.
Lacrimal gland biopsy was done in seven cases.
| Presentation of data and discussion|| |
Bunim  et al (1964) suggested that cases of Sjogren's syndrome may fall into 5 groups.
Group A:- includes those cases with classical rheumatoid arthritis.
Group B:- Consists of patients with probable rheumatoid arthritis.
Group C:- Cases associated with connective tissue disorders like scleroderma, disseminated lupus erythematosus and polyarteritis nodosa.
Group D:- Cases associated with polymyositis.
Group E:- Cases of keratoconjunctivitis sicca and xerostomia unassociated with rheumatoid arthritis or any connective tissue or muscle disorder. The patients in Group E have a higher concentration of serum gamma globulins and a greater frequency of a number of diverse circulating antibodies to tissue and subcellular components.
Out of the fifteen cases, 3 fell in Group A, five in Group B and seven in Group E. It is the latter group which is the centre of controversy. VANSELOW, DODSON, ANGELL AND DUFF  reviewing the charts of cases of keratoconjunctivitis sicca at Michigan Medical Centre found the majority of cases to be without any symptoms or signs of salivary glands involvement, rheumatoid arthritis or connective tissue disease. Further the keratoconjunctivitis sicca is the end result of a variety of local ocular and general diseases like trachoma, radiation to the eyes and sarcoidosis etc. So this sign may not be the hall mark of Sjogren's syndrome alone. No evidence of serological studies on these cases with keratoconjunctivitis sicca is presented by these authors.
BUNIM  et al (1964) on the other hand showed that cases with keratoconjunctivitis sicca and xerostomia show a higher concentration of gamma globulin (usually greater than 2.0 G/100 ml. Analytical ultracentrifugation showed that the major increase in protein concentration of these sera was found in the 7S fraction. Some sera disclosed, in addition, a modest increase in 19S fraction. Further Bentovite flocculation test (which detects the rheumatoid factor capable of reacting with human gamma globulins) was positive in 74%. The sheep cell agglutination test which detects the rheumatoid factor capable of reacting with rabbit gamma globulin was positive in 96%. of the 23 cases with sicca complex alone (Group E). These findings compared with the 100% and 72% respectively for the Bentonite flocculation test and sheep cell agglutination test for cases with Group A Sjogren's syndrome. This evidence lends considerable support to the fact that in cases of rheumatoid arthritis and in the sicca complex, similar alterations occur in the gamma globulin molecule making them antigenic within the host and leading to the production of rheumatoid or antigamma globulin factors.
Another evidence for this is from the passive cutaneous anaphylaxis test. If the diluted serum is injected intradermally into the skin of guinea pigs and after a latent period of several hours, the animal is challenged intravenously with Evans blue followed by a suspension of tissue extract (calf thymus extract) at sites of antigen antibody interaction, there is increased capillary permeability leading to extravasation of dye. Such a test was positive in 14% of Group A patients and 67% of Group E patients in Bunim's series.
In our series there were seven cases with keratoconjunctivitis sicca. The details of the physical and laboratory findings are shown in [Table - 1].
The cases of sicca complex showed the presence of other symptoms like dryness of mouth, swelling of salivary glands, together with an increase of serum globulin (over 2.OG/1000 ml.) and a positive sheep cell agglutination test (Rose Waaler Test).
Taking all the evidence together, these seven cases of sicca complex would fit in with the broader concept of Sjogren's syndrome as suggested by Bunim.
It would be of interest to note as a parallel that eye signs (Band Keratopathy, Iridocyclitis, complicated cataracts) may occur in Still's disease without any rheumatoid arthritis. Such cases show again the changes in the blood, in the form of raised serum proteins, changed albumin globulin ratio and a positive sheep cell agglutination (SOOD AND AGARWAL.  )
How can the occurrence of rheumatoid factor in Group E patients be explained? Presence of rheumatoid factor may herald the future development of rheumatoid arthritis or possibly the sicca complex may be an alternate expression of rheumatoid disease without joint involvement, or in the rheumatoid arthritis and in the sicca complex, similar alterations occur in gamma globulin molecules, making them antigenic within the host and leading to the production of rheumatoid or antigamma globulin factors.
The typical ocular changes in Sjogren's syndrome consist of filamentary keratitis. In fact many of these patients may be treated for months for chronic conjunctivitis without realizing the true significance of the ocular changes.
In one of the cases belonging to Group A - the ocular changes persisted for nearly two years before the polyarthritis of classical rheumatoid type set in (Sood)  The significance of ocular changes was not recognized until a few months after the onset of rheumatoid arthritis.
Filaments are visible in the lower fornix and punctate corneal stains are visible on the cornea. Recurrent ulceration of the cornea may occur in some cases (l0% of cases VANSE-LOW  et al,). Two of the cases in the present series showed corneal ulceration. Serious corneal complications are rare. Serious complications like pannus (DUKE ELDER AND GOLDSMITH,  ), and pannus and leukomatous corneal opacities (SOOD  ) have, however, been described.
Histopathological examination of the lacrimal gland shows infiltration by lymphocytes, plasma cells and later characterized by acinar atrophy and dilatation of ducts.
Lacrimal gland biopsy was done in seven cases, one in Group A Sjogren's syndrome and six in Group E. In one of the latter cases the lacrimal gland was essentially normal [Figure - 1] but all the other cases showed dense infiltration by lymphocytes and plasma cells [Figure - 2]. Acinar atrophy was noticeable in three cases.
| Summary|| |
1) Fifteen cases of Sjogren's syndrome are described.
2) Seven of these cases presenting only with keratoconjunctivitis sicca showed an increase of serum globulin. Rose Waaler test was positive in a titre of 1 : 32 or more in six cases.
3) It is suggested that serum studies should be carried out on patients presenting with keratoconjunetivitis sicca where no local ocular cause is discernible.
| Acknowledgment|| |
I am grateful to Dr. A. Lesigneur, M. D., Medical Superintendent, General Hospital, Pondicherry and Dr. D. J. Reddy, M. D., Principal, Jawaharlal Institute of Postgraduate Medical Education and Research. Pondicherry for facilities provided to use the Hospital Records.
| References|| |
AMERICAN RHFUMATIC ASSOCIATION) (1958) Revision of Diagnostic Criteria for Rheumatoid Arthritis. Arthritis Rheum. 2: 16, 1959.
BUNIM, J. J., BUCHMAN, W. W., WERTLAKE, P. T., SOKOLOFF, L., BLOCK, K. J., BECK, J. S., ALEPPA, F. B.: Ann. Int. Med. 61:
DUKE ELDER, W. S., GOLDSMITH, A. J. B.: (1951) Recent Advances in Ophthalmology, J & A Churchill, London.
FUCHS: Cited by Duke Elder, S: System of Ophthalmology. Disease of the Outer Eye, Vol. VIII, Part I, p. 131. Henry Kimpton, London, 1965.
SJOGREN, II.; (1933) Acta Ophthal. Suppl. 2, cited by Duke Elder.
SOOD, N. N., AGARWAL, T. P.: (1966) Orient. Arch. Ophthal. 4, 300.
SOOD, N. N.: - Personal observations - Under publication.
VANSELOW, N. A., DODSON, V. N., ANGELL, D. C., DUFF, I. F.: (1963) Ann. Int. Med. 58: 124.
[Figure - 1], [Figure - 2]
[Table - 1]