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Year : 1982  |  Volume : 30  |  Issue : 5  |  Page : 485-488

Type I V hypersensitivity reactions in orbit

A.M.U. Institute of Ophthalmology, Aligarh, India

Correspondence Address:
R Gogi
A.M.U. Institute of Ophthalmology, Aligarh
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How to cite this article:
Gogi R, Nath K, Gulabani N. Type I V hypersensitivity reactions in orbit. Indian J Ophthalmol 1982;30:485-8

How to cite this URL:
Gogi R, Nath K, Gulabani N. Type I V hypersensitivity reactions in orbit. Indian J Ophthalmol [serial online] 1982 [cited 2023 Dec 2];30:485-8. Available from: https://journals.lww.com/ijo/pages/default.aspx/text.asp?1982/30/5/485/29237

A pseudotumour is considered to be an inflammatory lesion of orbital tissue of unknown aetiology, clinically simulating a tumour. The term 'pseudotumour' was coined by Birch-Hirschfeld in 1905 and is still in use. However, this term is misleading. The condition present as an orbital tumour, whereas it is an inflammatory mass and not a neoplastic one.[2] On the basis of aetiology and microscopic pathology, the pseudotumours have been classified in different ways by a number of workers[3],[4],[5],[6] but it was Zimmer­man (1967) and Garner (1973)[7],[8] who classified this wild-looking subject in a proper way. Accordingly, there are two groups of pseudotumours. In one, the pathogenesis is known, while the other includes the idiopathic inflammatory swellings of the orbit. The first group includes a variety of bacterial, viral, fungal and, parasitic inflammations[9] and amyloidosis of the orbit etc. The knowledge of the pathogenesis of "idiopathic inflammatory pseudotumours" is still a challenge. In the majority of such cases inflammatory cellular infiltration is diffuse and consists mainly of mature lymphocytes, with smaller numbers of plasma cells, macrophages, eosinophils and plymorphonu­clear leucocytes.l° Why should there be such a lymphoproliferative lesion in a non­lymphatic space like the orbit?

It is a common clinical experience that such lesions do respond to systemic corticos­teroid therapy. We feel that some immunolo­gical mechanism may be operative in the pathogenesis of these lesions. The present work was undertaken to explore this possibility. This paper presents type IV hypersensitivity reactions produced in the orbital tissues of rabbits and the various microscopic changes so produced. An attempt shall also be made to find how far these changes can explain the genesis of lympho­proliferative lesions (lymphoid pseudotumours) of orbit. Type IV hypersensitivity was produced in the orbital tissues with the help of a hapten, 2, 4- dinitrochlorobenzene (DNCB). This chemical is known to give rise to a comparatively pure T-lymphocyte stimulation as compared to the conventionally employed tuberculoproteins which stimulates B-lymphocytes as well.[11]

  Materials and methods Top

Animals : 20 adult rabbits (average weight 1 Kg.) were used for this study.

H. pten : DNCB was supplied by BDH , England. It is a yellow coloured chemical, insoluble in water and highly soluble in acetone. Its molecular weight is 203.

Procedure : The animals were divided into the following groups :­

Group A (14 rabbits)

Sensitization : The animals were sensitized systemically by applying 10 pl of a 20% solution of DNCB in acetone (i.e., 2 mg of DNCB) on each of the four areas of skin on the animal's back, each circular area being about 10 mm in diameter from which fur had been removed. Acetone evaporated, leaving behind a thin layer of DNCB on the skin surface.

Challenge : Three weeks after the sensi­tization the animals were challenged as follows

After infiltration of the skin with 4% xylocaine without adrenaline, a stab incision was made through the skin and subcutaneous tissues near the inferior obital margin and an opening about 1 cm wide and 1.5 cm deep was made into the orbit with the help of sinus forceps. Through this opening 10 µl of 2% DNCB (containing 0.2 mg of DNCB) was applied deep into the orbital tissues with the help of an iris repositor. The skin wound was closed with sutures.

The stab wound in the skin was opened in 2 animals each time, 1, 2, 3, 4, 5, 6 and 7 days after the challenge and orbital tissue biopsies were obtained from the site of applica- of DNCB. The tissues were pro­cessed for 4-6 microns thick sections.

Group B : (6 animals)

This control group served as the case line for group A. The tissue biopsies were taken 48 hours the experimental procedure in the following subgroups :­

B-1: In two animals sensitization was carried out as usual and biopsies were taken from the corresponding orbital tissues without the challenge dose. This was to rule out orbital inflammation as a result of systemic application of DNCB.

B-2: In the next two animals the sen­sitizing sitizing dose of DNCB was not applied. To these virgin animals only a challenge dose of DNCB (0.2 mg) was applied into the orbit. This was necessary to rule out the direct phlogistic effect of the low dose of DNCB.

B-3: That the inflammatory response may not merely be due to the metal component of the iris repositor plus acetone, two animals were sensitized as usual and for the purppse of challenge the iris repositor plus acetone (which had been allowed to evaporate as usual) was swept in the orbital tissues. No DNCB was applied for challenge.

  Observations Top

At the site of challenge in the orbit there was mild redness of the skin near the incision. Conjunctiva showed mild super­ficial congestion and chemosis in the lower bulbar conjunctiva corresponding to the site of application of the orbital challenge. It appeared 12-24 hours after the challenge, increased in intensity during the next 48 hours andsubsided gradually afterwards. Rest of the eye did not show any observable change.

  Microscopic pathology Top

Group : A

In the biopsies taken 24 hours after chall­enge, an inflammatory response was observed in the various orbital tissues. There was voso­dilatation, prominence of endothelial cells, varying degree of extracellular oedema and perivascular infiltration by polymorphonuclear cells and a few lymphocytes. During the next 24 hours the histopathological picture was more pleomorphic, being dominated by lymphocytes and eosinophils, and even showing a few plasma cells. The presence of epitheloid cells was also noted occasion­ally in the biopsies taken 72 hours after challenge. In four days the inflammatory reaction had become better organized and lymphocytes were present in different areas in aggregated form, contributing the nodular appearance [Figure l]. Such lymphocytic collections were present in the orbital tissues and in the extraocular muscles. There was pericanalicular [Figure - 2] and interacinar lymphocytic infiltration in the lacrimal gland. Serial sections cut at different levels of the tissue failed to show any evidence of giant-cell formation or necrosis.

The intracellular oedma was more marked during the first two days. Variable amount of fibrin outpouring was also detected by picro-Mallory stain.

Group B

In subgroup B-1 there was no evidence of inflammation, whereas in subgroup B-2 when virgin rabbits were exposed to the weaker dose of DNCB (i.e., the challenging dose). there was a mild polymorphonuelear response. In subgroup B-3 also there was no inflammation.

  Comments Top

Systemically sensitized animals, when challenged through the orbit, developed a lymphocyte-dominated lesion. There was involvement of all the orbital tissues includ­ing the lacrimal gland. Such a lesion had become better organized 96 hours after the challenge. This was a typical delayed hyper­sitivity, response. and not a phlogistic effect of the challenging dose as proved by the study of the animals of the control group.

The lesion so produced resembles the lymphoproliferative nature of the orbital pseudotumours as seen in human beings. We feel inclined to say that the individuals suffering from lymphoid pseudotu­mours develop a delayed hyperse­nsitivity reaction in the orbital tissues, in response to some antigen or hapten. The source of this complete or incomplete antigen could be upper respiratory tract infections, especially sinusitis, or an environmental pollu­tant. The same antigen on inhalation may reach the nasal sinuses, especially the ethmoid sinus, which is in communication with the orbit due to an incomplete medical orbital wall. Once the orbital tissue, a lymphopro­liferative reaction (T-cell mediated) sets in. This, however, does not explain the much lower incidence of pseudotumours as com­pared to the almost universal inci­dence of exposure to these inhalants and microbial agents. This could be due to indi­vidual variations in the immunological res­ponse, i.e., persons suffering from lymphoid pseudotumours may be particularly prone to respond to these antigens and haptens.

  Summary Top

Delayed hypersensitivity response in orbi­tal tissues of the rabbit has been studied. The lesion so produced is similar to the lympho­proliferative lesions of the human rabit. may be that such lymphoid pseudotumours are manifestations of a T-lymphocyte media­ted reaction.

  References Top

Birch -Hirschfeld, A., 1905,. Ber. Dtsch. Oph­thalmol, 32: 127.  Back to cited text no. 1
Blodi, F. C. and Gass, J. D. M., 1967, Trans. Amer. Acad. Ophthalmol, Otolaryng. 71 : 303.  Back to cited text no. 2
Dunnington, J. H. and Berke, R. N., 1943, Arch. Ophthalmol, 30 :446,  Back to cited text no. 3
Hogan, M.J. and Zimmerman, L. E., 1962, "Oph­thalmic Pathology-An Atlas and Text Book", P. 763, W. B. Saunders Company, Philadelphia and London.  Back to cited text no. 4
Reese, A. B., 1963, "Tumours of the Eye" 2nd edn., P. 538, Hoeber, New York.  Back to cited text no. 5
Agarwal, P. K., Dayal, Y. and Agarwal, L. P., 1967, Orient. Arch. Ophthalmol, 5 : 263.  Back to cited text no. 6
Zimmerman, L. E., 1967, Arch. Ophthalmol, 78 : 166.  Back to cited text no. 7
Garner, A, 1973, J. Clin. Path. 26 : 639.  Back to cited text no. 8
Malik, S. R. K.. Gupta, A. K. and Choudhry, S., 1968, Amer. J. Ophthalmol, 66 ; 1168.  Back to cited text no. 9
Zimmerman, L. E., 1964, Lymphoid Tumours. In "Ocular and Adnexal Tumours: New and Controversial Aspects", PP. 429-426. Kimpton, London; Mosby, St. Louis.  Back to cited text no. 10
Turk, J. L., Parker, D. and Poulter, L. W., 1972, lmmunol. 23 :439.  Back to cited text no. 11


  [Figure - 1], [Figure - 2]


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