|Year : 1974 | Volume
| Issue : 4 | Page : 10-15
Clinical and immunological aspects of keratoconjunctivitis sicca
Ramesh K Singla, IS Jain, Shobha Sehgal, SD Gupta
Postgraduate Institute of Medical Education and Research, Chandigarh, India
Ramesh K Singla
Department of Ophthalmology and Pathology, Postgraduate Institute of Medical Education and Research, Chandigarh
Source of Support: None, Conflict of Interest: None
|How to cite this article:|
Singla RK, Jain I S, Sehgal S, Gupta S D. Clinical and immunological aspects of keratoconjunctivitis sicca. Indian J Ophthalmol 1974;22:10-5
|How to cite this URL:|
Singla RK, Jain I S, Sehgal S, Gupta S D. Clinical and immunological aspects of keratoconjunctivitis sicca. Indian J Ophthalmol [serial online] 1974 [cited 2020 Feb 27];22:10-5. Available from: http://www.ijo.in/text.asp?1974/22/4/10/31350
Keratoconjunctivitis sicca is a definite clinical entity which is caused by deficient lacrimal secretion. Although Duke Elder (1930)  described two cases of keratitis sicca due to the congenital absence of lacrimal gland but the term Keratoconjunctivitis sicca was introduced into general use by Sjogren  .
Sjogren's syndrome comprises of keratoconjunctivitis sicca, xerostomia and rheumatoid arthritis. In majority of the cases of keratoconjunctivitis sicca the aetiological factor is unknown, though there is trend to implicate auto-immunity in its aetiopathogenesis.
The present study was, undertaken to observe any clinical link between idiopathic keratoconjunctivitis sicca and Sjogren's syndrome and to study if there is any immunological background.
| Material and Methods|| |
Nearly 800 patients attending eye outpatients department of Nehru Hospital, Postgraduate Institute of Medical Education and Research, Chandigarh, were screened for the presence of keratoconjunctivitis sicca. 90 cases referred from rheumatology clinic were also studied for the presence of keratoconjunctivitis sicca.
The following tests were done to detect the presence of keratoconjunctivitis sicca
1. Schirmer's test No. I
Cases showing wetting of strip less than 1.5mm were subjected to Schirmer test No. II.
2. Schirmer's test No. II
Wetting of strip less than 5 mm was taken to be a positive test.
3. Rose Bengal dye test
The test was labelled as positive when both conjunctiva and cornea showed spots of pink staining.
Cases showing positive Schirmer test No. II and positive Rose Bengal dye test were labelled as having keratoconjunctivitis sicca.
These cases were subjected to full eye examination and positive general physical examination. Blood was taken and following immunological studies were done
1. Total and differential proteins. 2. Paper electrophoresis. 3. Immunoglobulin estimation. 4. Rheumatoid factor (latex fixation). 5. Antinuclear factor. 6. Anibodies against lacrimal gland. 7. Antibodies against thyroid gland by precipitation and fluorescence method. 8. L.E. Cell phenomenon.
| Observations|| |
Out of 800 cases attending eye outpatient department 16 case were diagnosed to have evidence of keratoconjuctivitis sicca.
Out of 93 cases of rheumatoid arthritis, 17 cases were diagnosed to have keratoconjunctivitis sicca giving an incidence of 18.2%
Thus in all 30 cases of keratoconjunctivitis were seen. These were divided into 3 groups
Group A : Keratoconjunctivitivis sicca only : 11 cases
Group B : Keratoconjunctivitis sicca and rheumatiod arthritis. : 17 cases
Group C : Keratoconjunctivitis sicca and xerostomia : 2 cases
Age and sex. Out of 30 cases 7 were male and 23 were females. The age varied from 19 years to 60 years with an average of 40.4 years.
Group A : There were 7 female and 4 male patients. Average age of this group was 39 years. 6 had healed trachoma while in rest of the cases no other local pathology was seen. Almost same incidence was seen in 800 cases screened for the present study. Two females out of 7 were having menopause at the time of study while rest five were in menopause age group.
Majority of patients complained of foreign body sensations and irritation of eyes and had chronic redness of the eye associated with frothy and sticky discharge. These cases were being treated as cases of non specific chronic conjunctivitis without much relief. Two cases came with severe keratitis and superficial ulceration.
Group B : It comprised of 17 cases having rheumatoid arthritis and keratoconjunctivitis sicca. Out of this 15 were females and 2 were males.
8 females had menopause at the time of study while rest seven were in premenopause age group.
13 cases had definite rheumatoid arthritis while 4 had probable rheumatoid arthritis. In all these cases joint trouble preceded the eye symptoms and the interval between the appearence of joint and eye trouble varied from 1-16 years.
One case showed secondary amyloidosis and right parotid absess. One male patient had hypogonadism. In one case there was hepatosplenomegaly while another showed only hepatomegaly. In one case purpuric spots were observed all over the body.
However, presentation of local symptoms was almost similar as in group A.
Out of a total of 30 cases only 4 cases showed all the three components of Sjogren syndrome.
Group C : It had only 2 cases. Both were young and were having keratoconjunctivitis sicca associated with subjective xerostomia.
| Immunological reactions|| |
Values ranged between 6.29gms% to 8.89gms%, however, figures of more than 8gms% were seen in only 6 cases. 2 cases were in group A, 3 cases in group B and one case in group C.
Values for albumin varied from 2.62 gms% to 5.35gms% while globulin level varied from 2.09 gms% to 5.46 gms%. Values more than 3gms% were seen in 21 (70%) cases. Out of this 6 cases were in group A, 14 cases group B and one case in group C.
On electrophoresis, 21 (70% cases showed hypergammaglobulinaemia, 5 cases were in group A, 15 cases in group B and one case in group C.
Rise in gammaglobulin was much more marked in group B as compared to group A and the difference is statistically significant (p 0.05).
Rheumatoid factor was positive in 13 cases (43.7%), 2 cases were in group A, 10 cases it group B and only one case in group C. Difference between group A and group B is statistically significant. Titre was also high in group B as compared to other groups.
Antinuclear factor was positive in only 5 cases (16.6%), 4 cases were in group B and one case in group A. Difference between group A and B is not significant.
By precipitation technique, no case showed positive results while by fluorescence method 4 cases out of 26 showed positive results. One case was in group A and 3 cases in group B and the difference between two groups is not significant statistically.
In no case antibodies against lacrimal gland could be demonstrated. In no case LE cell phenomenon was observed.
There was polydonal rise in immunologlobulins more marked in IgG followed by IgM and IgA.
Mean value of IgG for whole group was 1953mgs% SL):t-726 as compared to 1145mgs% SD ± 239 of mean normal value. Mean value for group A was 1362 mgs% SD±250, for group B 2234 mgs% SD ± 720 and for group C 2261 mgs%. Mean value of IgG for whole group and group B is significantly high as compared to normal. Mean value for group B is also high from mean value of group A statistically.
Mean value of IgA for whole group was 366 mgs SD ± 101 as campared to 273 mgs%SD + 119 of mean normal value. In group A, it was 349mgs% SD = 110 and for group B 387 mg SD = 98 and for group C 278mgs%. Mean value of IgA for whole group and group B is high from mean normal value statistically. No difference was seen between group B and group A.
Mean value for IgM was 221 mgs% SD f 87 as compared to 144 mgs% SD ± 6o of mean normal value. Values for group A, group B and C were 180 mgs% SD ± 83, 235 mgs% SD + 88 and 231 mgs% respectively.
Again mean value of IgM for whole group was high as compared to mean normal value. Group B showed high values as compared to normal but no differance was seen between group B and group A.
No statistically significant difference was seen in cases having trachoma and cases without trachoma.
Positive immunological reactions in various groups are given in [Table 2].
| Discussion|| |
The average age in this series was 40.4 years which is on the lower side as compared to the figures reported in the literature. 17% of our cases were below the age of 30 years, while Anderson' reported an incidence of 4% only.
The disease predominantly affects females, but 23% of our cases were males, while Gifford  reported a 14% incidence in males. Pure keratoconjunctivitis sicca involved males more commonly, a 36% incidence in our series as compared to 20% reported by Henderson. 
69% our females were in premenopausal age group which is significantly high as compared to 36% reported by Henderson. 
IgM 1145 mgs% SD-339
IgA 273 mgs% SD-119
IgM 144 mgs% SDf60
The commonest presenting symptoms of these patients were foreign body sensation and frothy discharge at the canthi and chronic redness. Only 43% of the cases were aware of the diminished tear production in their eyes.
Although, healed trachoma was seen in nearly 50% of cases of keratoconjunctivitis sicca but it did not appear to have any etiological significance as a similar incidence of trachoma was found in the 800 cases screened for Schirmer tests and no significant difference was noted in the values in trachoma versus non trachoma cases.
Pure keratoconjunctivitis sicca was present in 37% of cases.
Xerostomia as an associated finding was present in only 20% of our cases as compared to higher incidence varying from 42% to 70% reported by other workers. ,,
Rheumatoid arthritis was seen in 57% o, our cases, this figure is almost the same as reported by various workers ,,
In all cases, the eye symptoms followed after the onset of rehumatoid arthritis. The interval period varied between 1-l0 years.
| Immunological abnormalities|| |
Total serum proteins values varied between 6.29 gms% to 8.89 gms%. However, only 20% of the cases had figures above 8gms% which are significantly high as compared to 5% reported by Stoltze. Similarly, hyperglobulinaemia was present in 70% of our cases as compared to an incidence of 6% reported by Stoltze.
In our series pure keratoconjunctivitis sicca as well as those having rheumatoid arthritis showed elevated serum protiens levels, while Stoltze reported a rise in Sjogren's syndrome cases only.
On electrophoresis 70% of cases showed hypergammaglobulinaemia. The incidence is much higher as compared to 37% reported by Crews  . However, Venselow  and Bloch  reported an incidence of 61% and 69% respectively.
The elevation of gammaglobulin was more marked in group B as compared to group A cases.
Rise in alpha 2 globulin was seen in 30% of cases only.
Antinuclear factor was positive in only 5 cases (16.6%). This incidence is very low. Venselow  reported an incidence of 40% while Bloch  and Feltkamp  observed positive results in 68% and 77% respectively.
Rheumatoid factor studied by latex fixation technique was positive in 43.3% of the whole group, 18% in group A and 59% in group B. Again this incidence is low as compared to 75% reported by Vanselow  , 85% by Crews  , while 100% positives results were seen by Bunim  and Feltkamp  .
Thyroid antibodies when studied by fluorescence technique were seen in 16% of the cases while no case showed positive results by precipitin technique. This incidence is very low as compared to 33% reported by Anderson  and 35% by Bloch  . This can be explained due to lack of any clinical thyroid disease in our patients.
In no case, antibodies were seen against lacrimal gland.
Again positive LE cell phenomenon was not seen in any case. This is significant as Heaton  reported an incidence of 35%. Vanselow  observed an incidence of 9% and Bloch 3 observed 10% positive results.
Immunoglobulin studies have shown a polydonal rise but more marked in group B of our cases. Mean values of IgG, IgA and IgM were significantly higher than the mean normal values. More marked rise was seen in IgG followed by IgM and IgA. Almost same pattern was observed by Gumpel and Hobbs  . In our series, group B showed the maximum rise and the difference between group B and mean normal is significant statistically. Although mean values of IgG, IgA, and IgM were high in group A but the difference between group A and mean normal is not significant.
These investigations clearly demonstrate that immunological changes develop in all the three groups although group A having pure keratoconjunctivitis sicca showed the minimum changes mainly of raised gammaglobulins. Changes were, however more marked in group B and most marked in four cases who had all the three components of Sjogren syndrome i.e. keratoconjunctivitis, rheumatoid arthritis and xerostomia. This group of 4 cases can easily be labelled as definite Sjogren syndrome while cases showing keratoconjunctivitis sicca and rheumatoid arthritis can be placed under the label of possible Sjogren syndrome. Group C having pure keratoconjunctivitis sicca and xerostomia also showed immunological changes but as the group is very small, it is difficult to compare the results. According to Bloch  , it forms a separate group of Sjogren syndrome. We also feel that these cases should be regarded as Sjogren syndrome although a collagen disorder component is missing.
From minimum immunological changes seen in group A, it is difficult to postulate autoimmunity as an aetiological factor for pure keratoconjunctivitis sicca. Further sophisticated immunological parameters are required for further evaluation. Trachoma also does not seem to play any significant role in aetiology as almost same incidence was seen in normal control group and no difference was seen in immunological reactions between cases having trachoma and cases without trachoma. Again it is difficult to say whether pure keratoconjunctivitis sicca is a precursor of Sjogren syndrome. For this a long follow up is required. It is likely that a few cases of pure keratoconjunctivitis sicca who have some immunological abnormalities may develop Sjogren syndrome with the passage of time and more and more of immunological observations may appear. Only a prolonged follow up of such cases can settle this issue.
This study has highlighted the differing spectrum of this group of autoimmune disease as observed in this geographical area. Surprisingly only one case showed parotid swelling, evidence of xerostomia likewise was also much less and no case had overt thyroid disease. Associated other systemic abnormalities were also less.
Immunologically, positive antinuclear factor and antibodies against thyroid gland were also minimum while in no case LE cell phenomenon could be seen and no case had antibodies against lacrimal gland. This all could be due to different nature of the disease in our patients as mentioned earlier.
| Summary|| |
Thirty cases of keratoconjunctivitis sicca were studied-out of which 17 cases were associated with rheumatoid arthritis and 11 had keratoconjunctivitis sicca only while two cases had keratoconjunctivitis sicca alongwith xerostomia.
Immunological studies revealed hyperglobulinaemia in 70% of the cases, The elevation of gammaglobulin was more marked in cases associated with rheumatoid arthritis than in pure sicca cases. Mean values of IgG, IgA and IgM were significantly higher than the mean normal values. More marked rise was seen in IgG followed by IgM and IgA.
| References|| |
Anderson, J. R., Gouldie, R. B., Gray, K. G., and Buchanan, W. W., 1961, Scot. Med. J., 6, 449.
Anderson, J. R., Gray, K. G., Beck, J. S. and Kinnear, W. F., 1961, Lancet, 2, 456.
Bloch, K. J., Buchanan, W. W., Wohl, M. J., and Bunim, 1965, Medicine, 44, 187.
Bunim, J.J., 296, Ann. Rheu. Dis. 20, 1.
Duke Elder, W. S., 1941, Text Book of Ophthalmology.
St. Louis, Mosby.
Crews, S. J. and Whitfield, A. G. W., 1963, Postgraduate Med. J. 39, 324.
Feltkamp, T. E. W., Van Rossum, A. L., 1968, Clinical Exp. Immune. 3, 1.
R., Puntenney, I and Bellows, J. 1943, Arch. Ophthal 30, 207.
Gumpel, J. M. and Hobbs, J. R., 1970, Ann. Rheu. Dis. 29, 681.
Heaton, J. M., 1959, Brit. Med. J. 1, 466.
Henderson, J. W., 1950, Amer. J. Ophthal. 33, 197.
Mac Sween, R. N. M., Goudie, R. B., Anderson, J. R. Armstrong, E., Murray, M. A., Mason, D. K., Jasati, M. K., and Williamon, J., 1967, Ann. Rheu. Dis, 26, 402.
Sjogren, H., 1933, Acta Ophthal.
(kbh), 11, 1.
Sood, N. N., 1965,
J. All India Ophthal. Soc. 16, 19.
Vanselow, N. A., Dodson, V. N., Angell, D. C. and Duff, K. F., 1963, Ann. Int. Med. 58,124.
[Table - 1]