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| ORIGINAL ARTICLE |
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| Year : 2003 | Volume
: 51
| Issue : 4 | Page : 309-313 |
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Ocular manifestations of behcet's disease in Indian patients
J Rohatgi, A Singal
Department of Ophthalmology, University College of Medical Sciences and GTB Hospital, Delhi, India
Correspondence Address:
J Rohatgi
Department of Ophthalmology, University College of Medical Sciences and GTB Hospital, Delhi
India
 Source of Support: None, Conflict of Interest: None  | Check |
PMID: 14750618 
Purpose: To study the prevalence, manifestations and severity of ocular involvement in Indian patients with Behcet's disease.
Method: Prospective analysis of all patients of suspected Behcet's disease between 1997 and 2001.
Results: A total of 19 patients were diagnosed to have Behcet's disease. Ocular manifestations were seen in 36% patients. The commonest manifestation was conjunctival ulcer (26.3%), followed by iridocyclitis (10.5%). None of the patients had posterior segment involvement or visual loss. Response to topical corticosteroids was good.
Conclusion: The prevalence and severity of ocular lesions in Behcet's disease is relatively low in Indian patients. Conjunctival ulcers was a common finding, which is rarely reported in the world literature. Keywords: Behcet′s disease, India, ocular manifestation
How to cite this article:
Rohatgi J, Singal A. Ocular manifestations of behcet's disease in Indian patients. Indian J Ophthalmol 2003;51:309-13 |
Behcet's disease is a chronic, recurrent, multi-systemic inflammatory disorder of unknown aetiology, characterised by the triad of oral ulcers, genital ulcers, and ocular lesions. This association was probably first recognised by Hippocrates,[1] but bears the name of Behcet after his detailed description of this illness in 1937.[2] The disease is now recognised to be a multi-systemic disorder[3] involving mucocutaneous, ocular, intestinal, articular, vascular, urogenital and neurologic systems. The diagnosis of Behcet's disease is based on identification of its typical clinical features, and diagnostic criteria have been laid down by the International Study Group (ISG).[4] It has a worldwide distribution, being more common among populations with a higher prevalence of HLA B5 and its split, HLA B 51, in the Mediterranean basin, the Middle East and Far East.[5] Even though the prevalence of HLA B5 in north Indians (30%)[6] is comparable to the Mediterranean (27%)[7] and the Japanese (36.9%) populations,[8] there are very few reports of Behcet's disease from India. [9],[10],[11] It appears that either the disease is uncommon, under-diagnosed or under-reported in India. Our study aimed to identify the various manifestations and severity of ocular lesions in Indian patients of Behcet's disease.
| Materials and Methods | |  |
A prospective study was conducted on all consecutive patients of suspected Behcet's disease referred from the Department of Dermatology, University College of Medical Sciences, New Delhi, between 1997 and 2001. Details of clinical symptoms at the time of presentation and in the past, if any, were prospectively collected. Complete haemogram including ESR, urine microscopy, liver function test (LFT), kidney function test (KFT), VDRL, Montoux test, chest skiagram, biopsy from the muco-cutaneous lesion and Pathergy test was performed in all cases. Tuberculosis, sarcoidosis and syphilis were excluded based on clinical examination and investigations. All patients were subjected to a detailed ocular history and examination including assessment of visual acuity, external ocular examination, slitlamp biomicroscopy for anterior segment and a detailed fundus examination including indirect ophthalmoscopy. The intraocular pressure (IOP) was measured using an applanation tonometer.
The diagnosis was based on clinical features and histopathology of the skin lesions. A total of 19 patients fitted into the diagnosis of Behcet's disease. Of these, 15 patients fulfilled the diagnostic criteria laid down by the International Study Group,[4] [Table - 1] while the remaining 4 patients fitted into O'Duffy's[12] criteria [Table - 2] for diagnosis of Behcet's disease. All the patients were subjected to ocular examination during the phase of active oral ulceration. Appropriate treatment and follow-up was done for patients with ocular lesions. All patients were re-examined at the time of subsequent orogenital recurrences.
| Results | | |
Fifteen of 19 patients were females. The mean age at onset of disease was 25.7(range 15 - 46) years and at diagnosis was 27.6(range 16 - 48) years. The mean duration of disease at diagnosis was 20.28 months (range 1 week to 6years). A history of multiple recurrences was present in 17 (89.5%) patients.
All patients had oral ulcers. Other common manifestations were genital ulcers (18/19 patients, 94.7%), arthralgia / arthritis (17/19 patients, 89.5%), fever ( 10/19 patients, 52.6%). Erythema nodosum was seen in 11 (57.9%) patients while other skin lesions were observed in 5 of 19 patients (26.3%). ESR of >40mm 1st hour was found in 11 (57.9%) patients. Though the pathergy test was positive in only 4 (21%) patients, it was more common in males (2/4 males, 50%) than females (2/15 females, 13.3%).
Overall, ocular manifestations were seen in 7 of 19 (36.8%) patients. The clinical profile of patients with ocular involvement is given in [Table - 3]. The most common ocular manifestation was conjunctival ulcer (5/19 patients, 26.3%), followed by iridocyclitis (2/19 patients, 10.5%). None of the patients had posterior segment involvement.
Conjunctival ulcers
The mean age of patients with conjunctival ulcers was 24.6 years while the mean age of onset of disease symptoms was 22.8 years. The frequency of conjunctival ulcers was much higher in males (2/4 patients, 50%,) compared to females (3/15 patients, 20%). Oro-genital ulcers and arthritis were present in all while erythema nodosum was observed in three patients. Pathergy test was positive in one male patient.All conjunctival ulcers were unilateral, present on the bulbar conjunctiva (2 patients) or limbus (3 patients) with none on the palpebral conjunctiva. Only one patient had multiple ulcers (3 in number), while the rest had a single ulcer. The size of the ulcer was <2mm in diameter in all except one case with a large (4mm x 5mm) limbal ulcer. The ulcers were covered with dirty white slough, the base was slightly raised and erythematous, surrounding conjunctiva showed localised congestion. All ulcers stained positive with 2% fluorescein dye. Symptoms of mild irritation were present in all except two patients with limbal ulcers, who had definite symptoms of redness, pain and lacrimation. Visual acuity was normal in all the patients. Keratitis was absent and there was no evidence of anterior or posterior uveitis, retinal vasculitis, vascular occlusions or retinal infiltration in any of these patients. Conjunctival ulceration was the presenting feature of Behcet's disease in one patient.
All patients with conjunctival ulcers were treated with full-strength topical corticosteroids (dexamethasone 0.1% with neomycin 0.5%) 4-6 times a day, along with systemic colchicine. The conjunctival ulcers usually disappeared by day 7 of treatment, while the congestion and erythema took another week to clear. The patient with the large limbal ulcer took 4 weeks to recover. The ulcers healed without scarring in all the patients. Recurrence of conjunctival ulcer was seen in only one patient (2 episodes) along with a fresh crop of orogenital ulcers.
Iridocyclitis
Unilateral, active iridocyclitis was seen in one patient with severe arthritis, multiple recurrences and disease duration of 9 months. The patient recovered completely with topical atropine and corticosteroids for 6 weeks. Another patient had evidence of bilateral, healed iridocyclitis with normal visual acuity. There was a history of treatment for bilateral iridocyclitis, with topical corticosteroids and atropine, in the previous year. At that time, the diagnosis of Behcet's disease was missed. No recurrence of iridocyclitis was seen in these two patients on follow up.
| Discussion | | |
Behcet's disease is reported worldwide though it is more frequent between the northern latitudes of 30° and 45o, in the Asian and the European populations.[13] The highest incidence is reported from Japan, with an overall prevalence of 7-8.5 per 100,000 population.[14] According to the published literature, [9],[10],[11]Behcet's disease appears to be rare in India. The only major study from North India documented 58 cases over a period of 16 years.[11] We diagnosed 19 cases in our hospital in 5 years, which is quite comparable to the above study. Most studies[11],[15] have found a male preponderance, while a recent study from Korea[16] had a higher percentage of females with Behcet's disease. In our cohort too, the frequency of female involvement was much higher. Orogenital ulceration and arthiritis are usually early manifestations of the disease while intraocular inflammation, vasculitis and CNS features are late manifestations. Early diagnosis may be difficult due to sequential manifestations appearing over many years.
It has been reported that when Behcet's disease presented with iridocyclitis or erythema nodosum, the diagnosis was made within 1.5 and 15 months, respectively.[17] Ocular manifestations are considered among the major criteria for the diagnosis of Behcet's disease.[4],[12] The frequency of ocular lesions in patients with Behcet's disease, however, could vary from 50 to 85%.[16],[17],[18],[19]The eyes get involved on an average, 2 to 3 years after the first evidence of systemic Behcet's disease,[14] but can range up to 14 years.[20] A low incidence of ocular involvement is a possibility with early diagnosis and early colchicine therapy. Our incidence of ocular involvement at 36% was similar to that recorded by Gurler et al from Turkey (28.9%).[21]
Both eyes may be affected simultaneously, but usually one eye is affected before the other, with a delay of up to 2 years, though 38% of the cases may become bilateral within a month.[20] The burden of diagnostic recognition of Behcet's disease often lies with the ophthalmologist, as many patients first present to them with ocular symptoms. The presenting feature of Behcet's disease was conjunctival ulcer in one of our cases; a similar presentation has been reported from France.[22]
Behcet's disease is not a common cause of uveitis. The highest incidence is reported from Japan,[14] where it constitutes about 25% of endogenous uveitis, but it is much rarer in other countries - 2% in Brazil[20] and 1% in India.[23] The classical feature of Behcet's disease is recurrent, acute anterior uveitis associated with hypopyon. However, hypopyon is a very transient sign, seen in a third of patients only.[20]
Ocular manifestations also include necrotizing vascular lesions involving the retina and the optic nerve. The reported frequency varies between 40-100%.[14],[20] These are often obscured by the severity of the anterior segment reaction and commonly include macular oedema, retinal periphlebitis and periarteritis, thrombosis of the vessels, and retinal or vitreous haemorrhages. These lesions are often described in male patients.[24],[25] Patients in our study group did not have posterior segment pathology. We are not sure if it was because a majority (15 of 19) were female in our group and additionally, they were diagnosed relatively early.
Mucosal ulcers are important features of Behcet's disease, and recurrent oral ulcers are very characteristic.[4] Ulcers similar to oral ulcers have been seen on the larynx, pharnyx[26] and all parts of the gastrointestinal tract.[27] They are also commonly seen on the skin and the mucosa of the genital tract including the vulva, vagina and cervix.[8] Conjunctival ulcers are rarely reported in the world literature.[22], [28],[29],[30],[31],[32],[33] Pazarli et al[28] reported 5 cases of conjunctival ulcers in 540 cases (0.9%) of Behcet's disease in Turkey, while one case was reported by Olivieri et al[29] from Italy. In a recent, retrospective analysis of 152 cases in Japan, conjunctival ulcers were present in only 4 cases (2.6%).[30] There are no reports of conjunctival ulcers in Behcet's disease from India. Surprisingly, we found a high frequency of conjunctival ulcers in our study (5/19 patients, 26.3%). This is much higher than in any reported series.
That the conjunctival ulcers are a manifestation of Behcet's disease was proved by the biopsy from the ulcer in one case by Matsuo et al.[30] In another case, histopathology of the eye on autopsy of a patient of Behcet's disease, clearly demonstrated the presence of a conjunctival ulcer.[31] A unique hyperactivity response of the conjunctiva to surgical trauma has been demonstrated[33] in Behcet's disease, similar to the skin hyperactivity (pathergy test) which is specific to this disease. This shows active involvement of the conjunctiva in the disease process. All our patients had exacerbation of systemic features of Behcet's disease along with the conjunctival ulcers including oral/genital ulcers, erythema nodosum, arthritis, and fever.
None of the patients with conjunctival ulcers in this study had associated intraocular inflammation or retinal vasculitis. This has been observed in other studies too.[30] It seems that conjunctival ulcers are related to mucocutaneous ulcers rather than the intraocular inflammation. They tend to occur along with the orogenital ulcers in the early stages of the disease. Hence, they should be considered a separate entity and included as a major criteria for the diagnosis of Behcet's disease, like oral and genital ulcers. In our study too only 4 of 5 patients with conjunctival ulcers met the ISG criteria.[4] Since conjunctival ulcers are not considered a major manifestation of Behcet's disease, the remaining patient could satisfy only O'Duffy's criteria for diagnosis.[12]
The clinical picture of Behcet's disease is known to vary in different regions. Geographic and genetic factors are important in the pathogenesis of the disease.[34] Our findings corroborate the findings of Pande et al[11] that the disease occurs in a much milder form in India and is primarily mucocutaneous and arthritic; other features are less frequent. We also suggest that routine examination of the conjunctiva be done in patients with Behcet's disease, and the disease should be included in the list of differential diagnosis, for patients with conjunctival ulcerations.
| References | | |
| 1. | Feigenbaum A. Description of Behcet's Syndrome in the Hippocratic Third book of Endemic Diseases. Br J Ophthalmol 1956;40:355-57.  [ PUBMED] |
| 2. | Behcet H. (1937), as quoted by Duke Elders, Perkin ES. Inflammation of the uveal tract: Uveitis. In: Duke-Elders, editor. System of Ophthalmology. London: S Henry Hampton, 1966. Vol. IX. pp 358-73. |
| 3. | Behcet's Disease Research Committee of Japan : Behcet's Disease, guide to diagnosis of Behcet's Disease. Jpn J Ophthalmol 1974;18:291-94. |
| 4. | International Study Group for Behcet's Disease. Criteria for Diagnosis of Behcet's Disease. Lancet 1990;335:1078-80. |
| 5. | Ohno S, Ohguchi M, Hirosa S, Matsuda S, Wakisaka A, Aizawa M. Close association of HLA Bw51 with Behcet's Disease. Arch Ophthalmol. 1982;100:1455-58. |
| 6. | Mehra NK, Taneja V, Kailash S, Vaidya MC. Distribution of HLA Antigens in a sample of North Indian Hindu Population. Tissue Antigens 1986;27:64-74. |
| 7. | Yazici H, Akokan G, Yalein B, Mufatuoglu A. The high prevalence of HLA B5 in Behcet's Disease . Clin Exp Immunol 1977;30:259-61. |
| 8. | Shimuzu T, Erlich GE, Inaba G, Mayashi K. Behcet's Disease (Behcet's Syndrome). Semin Arthritis Rheum 1979;8:223-60. |
| 9. | Kunjuraman G, Joseph PP, Philip J. Behcet's Syndrome : A report of 3 cases with review of literature. J Assoc Physicians India 1980;28:195-98. |
| 10. | Singh RR, Malaviya AN. Behcet's Syndrome in North India. J Assoc Physicians India 1988;36:238. |
| 11. | Pande I, Uppal SS, Kailash S, Kumar A, Malaviya AN. Behcet's Disease in India: A Clinical, Immunological, immunogenetic and outcome study. Br J Rheum 1995;34:825-30. |
| 12. | O'Duffy JD, Goldstein NP. Neurologic Involvement in seven patients with Behcet's Disease. Am J Med 1976;61:170-78. |
| 13. | Ohno S. Behcet's Disease in the World. In: Lehner T and Barnes CG, editors. Recent Advances in Behcet's Disease . Royal Society Of Medicine Services, London.1986;p181-186. |
| 14. | Mishima S, Masuda K, Izawa Y, Mochizuki M, Namba K. Behcet's Disease in Japan : Ophthalmological aspects. Trans Am Ophthalmol Soc 1979;77:225-79. |
| 15. | Muhaya M, Lightman S, Ikeda E, Mochizuki M, Shaer B, McCluskey P, et al. Behcet's Disease in Japan and Great Britain: A comparative study. Ocular Immunol Inflamm 2000;8:141-48. |
| 16. | Bang D, Lee JH, Lee ES, Lee S, Choi JS, Kim YK, et al. Epidemiologic and Clinical Survey of Behcet's Disease in Korea: The first multicentric study. J Korean Med Sci 2001;16:615-18. |
| 17. | Zouboulis CC, Kotter I, Djawari D, Kirch W, Kohl PK, Ochsendorf FR, et al. Epidemiological features of Adamantiades-Behcet's disease in Germany and in Europe. Yonsei Med J 1997;38:411-22. |
| 18. | Nazzaro P: Cutaneous manifestations of Behcet's Disease. Clinical and histopathological findings. In: Monacelli M, Nazzaro P, editors. Int Symp on Behcet's disease , Rome, 1965 . Basel: S Karger, 1966. pp 15-41. |
| 19. | Oshima Y, Shimizu T, Yokohari R, Matsumoto T, Kano K, Kogami T, et al. Clinical studies on Behcet's syndrome. Ann Rheum Dis 1963;22:36-45. |
| 20. | Barra C, Belfort R, Abreu MT, Kim MK, Martins MC, Petrilli AMN, Behcet's Disease in Brazil: A review of 49 cases with emphasis on ophthalmic manifestation. Jpn J Ophthalmol 1991;35:339-46. |
| 21. | Gurler A, Boyvat A, Tursen U. Clinical manifestations of Behcet's disease: an analysis of 2147 patients. Yonsei Med J 1997;38:423-27. |
| 22. | Ouertani A, Lasram L, Mili I. Behcet's Disease disclosed by ocular conjunctival aphthous ulcer. Apropos of a case. J Fr Ophthalmol 1992;15:131-32. |
| 23. | Sen DK. Endogenous uveitis in Indian children: Analysis of 94 cases. J Pediatr Ophthalmol 1976;14:25-32. |
| 24. | Ames PR, Steuer A, Pap A, Denman AM. Thrombosis in Behcet's disease: A retrospective survey from a single UK centre. Rheumatology (Oxford) 2001;40:652-55. |
| 25. | Ermakova NA, Alekberova ZS. Retinal vasculitis in Behcet's disease. Vestn Oftalmol 2001;117:44-46.
|
| 26. | Lehner T. Progress Report: Oral Ulcerations and Behcet's Syndrome. Gut 1977;18:491-511. |
| 27. | Griffen JW, Harrison HB, Tedescor FJ, Mills LR. Behcet's Disease with multiple sites of gastrointestinal involvement. South Med J 1982;75:1405. |
| 28. | Pazarli H, Ozyagzan Y, Bahcecioglu H, Yazici H, Hattat N, Yurdakal S, et al. Ocular involvement in Behcet's Syndrome in Turkey. In : Lehner T, Barnes CG, editors. Recent Advances in Behcet's Disease. London, New York : Royal Society Of Medicine Services, 1986. pp 267-68.
|
| 29. | Olivieri I, Genovesi - Ebert F, Signorini G, Pasero G. Conjunctival Ulceration in Behcet's Syndrome. Ann Rheum Dis 1992;51:574-75. |
| 30. | Matsuo T, Itami M, Nakagawa H, Nagayama M. The Incidence and Pathology of Conjunctival Ulceration in Behcet's Syndrome. Br J Ophthalmol 2002;86:140-43. |
| 31. | Winter FC, Yukins RE. The Ocular Pathology of Behcet's Disease. Am J Ophthalmol 1966;62:257-62. |
| 32. | Otmani F, Brouri M, Brouri H, Abbes L, Berrah A. Conjunctival Aphthosis; an unusual site in Behcet's Disease . Presse Med 1995;25;24:1708. |
| 33. | Tugal-Tutkun I, Urgancioglu M, Foster CS. Immunopathologic Study of the Conjunctiva in Patients with Behcet Disease. Ophthalmology 1995;102:1660-68. |
| 34. | Chen YC, Chang HW. Clinical characteristics of Behcet's Disease in Southern Taiwan. J Microbiol Immunol Infect 2001;34:207-10. |
[Table - 1], [Table - 2], [Table - 3]
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