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Ocular Inflammatory Pseudotumor Associated with Propranolol Therapy
Ocular Inflammatory Pseudotumor Associated with Propranolol Therapy SUSAN M. YEOMANS, MS,*t DAVID L. KNOX, MD,* W. RICHARD GREEN, MD,*t GEORGE W. MURGATROYD, MDt
Abstract: A 60-year-old man presented with a unilateral mass involving the iris and ciliary body associated with iridocyclitis, which was refractive to both topical and systemic corticosteroid therapy. After a systemic work-up was negative, anterior chamber paracentesis and transcorneal biopsy were performed to rule out malignant melanoma and other tumors. The lesion proved to be an inflammatory lymphoid process, which resolved when systemic propranolol administration was withdrawn. Evidence for the possible role of propranolol in the induction of an intraocular inflammatory pseudotumor is presented. [Key words: ciliary body biopsy, cytopathology, inflammatory pseudotumor, ocular inflammatory pseudotumor, propranolol.] Ophthalmology 90:14221425, 1983
Inflammatory pseudotumors have been known to arise from the orbit, conjunctiva, and elsewhere. The more rare lymphoid proliferations of the uveal tract present a considerable diagnostic dilemma, as such intraocular masses are often indistinguishable from malignant melanoma. In the past, such lesions have been treated by enucleation before a histopathologic diagnosis could be made. In 1967 Gass' detailed the clinical presentation and histopathologic features of reactive lymphoid hyperplasia of the uvea. Ryan, Zimmerman, and King2 reported 19 such cases in 1972. In addition, bilateral lesions of the ciliary body,3 a localized tumor of the iris,4 and diffuse uveal involvement have been described. Earlier cases were diagnosed only after enucleation because of suspicion of metastatic carcinoma. ',2 In some instances the original histopathologic diagnosis was lymphosarcoma,6,7 but further studies reclassified the lesions as inflammatory.8,9 More recent cases have been diagnosed by ciliary body biopsy,3 iridocyclectomy,4 or on the basis of clinical, ultrasonographic, and computed tomographic From the Wilmer Ophthalmologicallnstitute,* Department of Pathology,t and Department of Medicine,:j: the Johns Hopkins Medical Institutions, Baltimore, Maryland. Reprint requests to W. Richard Green, MD, Eye Pathology Laboratory, Johns Hopkins Hospital, 600 N. Wolfe Street, Baltimore, MD 21205.
1422
studies. 5 These inflammatory lesions are quite sensitive to corticosteroid administration.'-3 In this report a case of an inflammatory pseudotumor of the iris and ciliary body unresponsive to steroid therapy but which virtually disappeared when systemic propranolol was withdrawn is presented, with a discussion of the clinical, ultrasonographic, and histopathologic findings.
CASE REPORT This 60-year-old man was in good ocular health until January 1980, when he first noted blurred vision in his left eye. Visual acuity was 20/20 in both eyes at that time, but slit-lamp examination revealed keratic precipitates and aqueous cells and flare in the left eye. He was treated with topical steroids for 2 weeks with resolution of his symptoms and clinical findings. Five months later, he had a second episode with left eye irritation and foreign body sensation. Keratic precipitates and aqueous flare were observed. Despite reinstatement of topical steroids and cycloplegics, symptoms and inflammation persisted. A limited systemic evaluation revealed a normal chest x-ray, blood count, and urinalysis, but an erythrocyte sedimentation rate elevated to 40 mm/hr. In September 1980, he was started on a course of oral prednisone, 25 mg every other day, which was tapered offby February 1981. Ocular findings were unchanged except for the development of a posterior subcapsular cataract in the left eye which reduced visual acuity to 20/30. Topical
YEOMANS,
et al •
INFLAMMATORY PSEUDOTUMOR
corticosteroid therapy was continued. Cataractous changes progressed, with reduction of visual acuity to 20/100 in April 1981 and 20/400 in May 1981, at which time the fundus could no longer be visualized. In addition, a pinkish fleshy mass was noted in the inferior iris of the left eye. The patient was referred to the Wilmer Institute in June 1981. Visual acuity in the normal right eye was 20/20. Visual acuity in the left eye was hand motions at 10ft. The left conjunctiva was injected and slit-lamp examination showed many fine keratic precipitates centrally and inferiorly. There was a mild aqueous flare and cellular reaction. A pinkish tissue was seen behind the limbus in the iris peripherally from 2:30 to 9:30 o'clock (Fig 1), with posterior displacement of the lens temporally. Posterior synechiae extended from the 5- to I-o'clock position. Ultrasonography revealed a large, low-density mass in the temporal ciliary body. The patient underwent an extensive systemic evaluation that revealed only antinuclear antibodies at a titre of 1:40, a sedimentation rate of 17, and complement fractions C3 and C4 within normal limits. Chest and sinus x-rays were normal. Dental and ear, nose and throat consultations were noncontributory. A review of the patient's past medical history revealed that he had taken propranolol (Inderal®), 40 mg orally four times daily, since an episode of chest pain and shortness of breath 3 years previously. Systemic physical examination was notable for bilateral gynecomastia and nipple tenderness. The patient also complained of back pain. On July 1, 1981, an aqueous paracentesis was performed to obtain cells that might help in determination of the nature of the lesion. The specimen, prepared using a membrane filter and modified Papanicolaou staining technique, showed mature lymphocytes and occasional pigment-containing macrophages (Fig 2). There were no giant cells or cells demonstrating atypical features. The following day a transcorneal biopsy of the peripheral iris and ciliary body was performed under local anesthesia in the 4- to 5-0'clock meridian. A Bard-Parker blade was used to incise the cornea concentrically at the limbus. Dissection into the deeper tissue displayed dilated blood vessels and pinkish tissue identical to that seen through the cornea. The tip of a Smith-Green corneal knife was used to excise a 3 X 1 X 0.5 mm strip of the pink tissue. Microscopic examination showed an infiltrate consisting of mostly normal-appearing lymphocytes and rare plasma cells (Fig 3). The impression was inflammatory pseudotumor of the iris and ciliary body. After the ciliary body biopsy, the patient's propranolol therapy was stopped, because a physician-patient had observed that he had experienced gynecomastia and nipple tenderness while taking propranolol, which ceased when he stopped taking the drug. Within 24 hours of discontinuing propranolol, our patient reported that he no longer had back pain, and the nipple pain and tenderness were gone in 2 days. Five days after discontinuing the propranolol, a distinct diminution in the size of the pink inflammatory mass was seen (Fig 4). Three weeks after biopsy, the lesion (Fig 5) was seen to be slightly larger in the area ofthe corneal incision where it persisted long after the other areas had disappeared. By November 1981, 5 months after biopsy, the mass was not evident externally (Fig 6) and visible only by gonioscopy as a tiny rim of pink tissue. Since that time, the patient has had a persistent mild aqueous flare and cellular reaction, for which topical steroid therapy has been continued. The lens is no longer displaced. No evidence of systemic disease has been found. The patient has been unwilling to use oral or topical propranolol (Timoptic®) to provide a putative antigenic challenge to the inflammatory disease in his eye.
DISCUSSION The case reported herein represents another example of the unusual and rare occurrence of an inflammatory tumor of the iris and ciliary body. The clinical and pathologic features are reported because of the rarity of the lesion, establishment of the diagnosis by intraocular biopsy and the high probability that propranolol (Inderal®) was the causative factor. The inflammatory mass reduced in size during a 6-month period after cessation of propranolol, but persisted in a small area at the biopsy incision site. Only 23 cases of intraocular inflammatory pseudotumors have been described. I - 5 Diagnosis has been on the basis of enucleation in 21 eyes, excisional biopsy of an iris mass in one case,4 and by clinical criteria based on appearance, ultrasound and computerized tomography in one case. 5 Previously diagnosed cases ranged from 30 to 94 years of age, with men twice as often as women. Duration of symptoms has ranged from months to 35 years.2 The case reported here is characteristic of intraocular inflammatory pseudotumor. With such a mass presenting in the anterior segment, the initial clinical differential diagnosis would include primary and metastatic neoplasms, granulomata both infectious (syphilis or tuberculosis) and noninfectious (sarcoidosis) in origin, and serum dysproteinemic conditions such as Waldenstrom's macroglobulinemia. These disease entities were effectively ruled out in our patient by appropriate clinical and laboratory evaluation. Malignant melanoma, leukemia, lymphoma, and metastatic carcinoma were excluded first by aqueous cytopathology, which found no malignant cells, and secondly by transcorneal ciliary body biopsy. The histopathologic features of the ciliary body biopsy are similar to those seen in other cases. Ryan, Zimmerman, and King2 noted that the infiltrate may include mature lymphocytes, plasma cells, reticular lymphoblasts, Russell bodies, and Dutcher bodies. Systemic and topical corticosteroid use, which was thought to be responsible for improvement of the inflammatory mass in two patients,3,5 improved the picture in our patient only in the early phase of his iridocyclitis. Later in his course, iridocyclitis persisted, and the inflammatory mass developed despite continued corticosteroid use. In our experience, progression of intraocular inflammation refractive to corticosteroids indicates the continued presence of causative factors such as intraocular microorganisms, remote foci of infection, drug and food allergies, ischemia, or neoplasm. We are intrigued by the possibility that the oral use of propranolol (Inderal®) was responsible for the induction of this patient's intraocular inflammatory pseudotumor. A review of the literature concerning adverse reactions to propranolol administration reveals a variety of complications in virtually all organ systems, including watery nasal secretions,1O dermatologic eruptions of a psoriasiform, lichenoid and eczematous nature,lI-14 polyarthri1423
OPHTHALMOLOGY •
DECEMBER 1983 •
VOLUME 90 •
NUMBER 12
Fig l. Top left. appearance of iris lesion at presentation. Fig 2. Top right. aqueous specimen with normal-appearing lymphocyte (membrane filter; modified Papanicolaou stain. X640). Fig 3. Center left. biopsy of lesion showing infiltrate oflymphocytes (hematoxylin-eosin, X 160). Fig 4. Center right. appearance of lesion 5 days after biopsy and discontinuation of propranolol. Fig 5. Bottom left. appearance of enlargement of lesion in area of corneal incision 25 days after biopsy and discontinuance of propranolol. Fig 6. Bottom right. appearance of lesion 5 months after discontinuance of propranolol.
tis, IS acute interstitial nephritis, 16 retroperitoneal fibrosis, 17 and sclerosing peritonitis. 18,19 Central nervous system side effects have included acute and organic brain syndromes, with visual and sensory hallucinations, vivid dreams, and insomnia. 20 - 22 Documented ocular effects include a myasthenic-type diplopia, decreased tear production with or without associated dry mouth, and hyperemic conjunctivae. 23- 25 We found no previous cases of intraocular 1424
inflammation in our review ofthe literature. Challenging patients with a second use of propranolol has been reported twice with recurrence of symptoms, an eczematous eruption in one,l1 and diplopia in the other. 23 The observation by one of us (GM) of the association of nipple pain and gynecomastia with propranolol therapy led to the decision to halt administration of the drug in our patient. Resolution of his back and nipple pain began
YEOMANS, et al
•
INFLAMMATORY PSEUDOTUMOR
within 1 day, and the eye lesion subsided over a period of weeks to months. Evidence for the potential role of propranolol in the ocular process is further substantiated by the fact that drug administration preceded the development of ocular inflammation by 2 years; the failure of the anterior segment mass to respond to both topical and systemic steroids as an indication of persistent activity and continuing antigenic challenge; and the time course of improvement following withdrawal of propranolol (back and nipple symptoms within days, and the eye lesion over several months, with persistent, although nonworsening, mild iridocyclitis). The slow resolution of the pink mass parallels the 5to 14-month time course for recovery seen after removal of gluten from the diet of many patients with dermatitis herpetiformis. 26 Relative persistence of the pink inflammatory mass in the area of the transcorneal ciliary body biopsy is demonstrated in Figure 5. The tissue in the 3- to 5-0'clock meridian was slightly enlarged and persisted longer than in other areas of the iris and ciliary body. It is possible to speculate that the trauma of the biopsy and reaction to sutures stimulated vascularization and promoted factors responsible for maintenance of inflammation. Unfortunately, our patient is reluctant to participate in a rechallenge through the use of oral or topical propranolol (Timolol®), to test our hypothesis concerning the role of propranolol in the induction of this inflammatory uveal process.
REFERENCES 1. Gass JDM. Retinal detachment and narrow-angle glaucoma secondary to inflammatory pseudotumor of the uveal tract. Am J Ophthalmol 1967; 64:612-21. 2. Ryan SJ, Zimmerman LE, King FM. Reactive lymphoid hyperplasia: an unusual form of intraocular pseudotumor. Trans Am Acad OphthalmolOtolaryngol 1972; 76:652-71. 3. Ryan SJ Jr, Frank RN, Green WR. Bilateral inflammatory pseudotumors of the ciliary body. Am J Ophthalmol 1971; 72:586-91. 4. Shields JA, Augsburger JJ, Gonder JR, MacLeod D. Localized benign lymphoid tumor of the iris. Arch Ophthalmol 1981; 99:2147-8.
5. Desroches G, Abrams GW, Gass JDM. Reactive lymphoid hyperplasia of the uvea; a case with ultrasonographic and computed tomographic studies. Arch Ophthalmol 1983; 101 :725-8. 6. Cook C. Uveal lymphosarcoma. Br J OphthalmoI1954; 38:182-5. 7. Beasley H. Lymphosarcoma of the choroid. Am J Ophthalmol1961; 51:1294-6. 8. Zimmerman LE. Lymphoid tumors. In: Boniuk M, ed. Ocular and Adnexal Tumors; New and Controversial Aspects. St Louis: CV Mosby, 1964; 438. 9. Crookes GP, Mullaney J. Lymphoid hyperplasia of the uveal tract simulating malignant melanoma. Am J Ophthalmol1967; 63:962-7. 10. Malm L. Propranolol as cause of watery nasal secretion. Lancet 1981; 1:1006. 11. van Joost T, Smitt JHS. Skin reactions to propranolol and cross sensitivity to beta-adrenoreceptor blocking agents. Arch Dermatol 1981; 117:600-1. 12. Felix RH, Ive FA, Dahl MGC. Skin reactions to beta-blockers. Br Med J 1975; 1:626. 13. Cochran REI, Thomson J, McQueen A, Beevers DG. Skin reactions associated with propranolol. Arch Dermatol 1976; 112: 1173-4. 14. Halevy S, Feuerman EJ. Psoriasiform eruption induced by propranolol. Cutis 1979; 24:95-8. 15. Machtey I. PolyarthritiS following propranolol. Arthritis Rheum 1981; 24:568-9. 16. Bailey RR. Propranolol-induced acute interstitial nephritis. N Z Med J 1981; 94:397-8. 17. Pierce JR Jr, Trostle DC, Warner JJ. Propranolol and retroperitoneal fibrosis. Ann Intem Med 1981; 95:244. 18. Ahmad S. Sclerosing peritonitis and propranolol. Chest 1981; 79:361-
2. 19. Nicholls JT, Rutty DA. Sclerosing peritonitis with short-term propranolol therapy. Arch Intem Med 1980; 140:1124-5. 20. Tikare SK, Bandisode MS. Central nervous system side effects of propranolol. J Med Assoc Ga 1982; 71:777-8. 21. Kurland ML. Organic brain syndrome with propranolol. N Engl J Med 1979; 300:366. 22. Helson L, Duque L. Acute brain syndrome after propranolol. Lancet 1978; 1:98. 23. Weber JCP. Beta-adrenoreceptor antagonists and diplopia. Lancet 1982; 2:826-7. 24. Cubey RB, Taylor SH. Ocular reaction to propranolol and resolution on continued treatment with a different beta-blocking drug. Br Med J 1975; 4:327-8. 25. Skegg DCG, Doll R. Frequency of eye complaints and rashes among patients receiving practolol and propranolol. Lancet 1977; 2:475-8. 26. Leonard J, Haffenden G, Tucker W, et aI. Gluten challenge in dermatitis herpetiformis. N Engl J Med 1983; 308:816-9.
1425
Abstract: A 60-year-old man presented with a unilateral mass involving the iris and ciliary body associated with iridocyclitis, which was refractive to both topical and systemic corticosteroid therapy. After a systemic work-up was negative, anterior chamber paracentesis and transcorneal biopsy were performed to rule out malignant melanoma and other tumors. The lesion proved to be an inflammatory lymphoid process, which resolved when systemic propranolol administration was withdrawn. Evidence for the possible role of propranolol in the induction of an intraocular inflammatory pseudotumor is presented. [Key words: ciliary body biopsy, cytopathology, inflammatory pseudotumor, ocular inflammatory pseudotumor, propranolol.] Ophthalmology 90:14221425, 1983
Inflammatory pseudotumors have been known to arise from the orbit, conjunctiva, and elsewhere. The more rare lymphoid proliferations of the uveal tract present a considerable diagnostic dilemma, as such intraocular masses are often indistinguishable from malignant melanoma. In the past, such lesions have been treated by enucleation before a histopathologic diagnosis could be made. In 1967 Gass' detailed the clinical presentation and histopathologic features of reactive lymphoid hyperplasia of the uvea. Ryan, Zimmerman, and King2 reported 19 such cases in 1972. In addition, bilateral lesions of the ciliary body,3 a localized tumor of the iris,4 and diffuse uveal involvement have been described. Earlier cases were diagnosed only after enucleation because of suspicion of metastatic carcinoma. ',2 In some instances the original histopathologic diagnosis was lymphosarcoma,6,7 but further studies reclassified the lesions as inflammatory.8,9 More recent cases have been diagnosed by ciliary body biopsy,3 iridocyclectomy,4 or on the basis of clinical, ultrasonographic, and computed tomographic From the Wilmer Ophthalmologicallnstitute,* Department of Pathology,t and Department of Medicine,:j: the Johns Hopkins Medical Institutions, Baltimore, Maryland. Reprint requests to W. Richard Green, MD, Eye Pathology Laboratory, Johns Hopkins Hospital, 600 N. Wolfe Street, Baltimore, MD 21205.
1422
studies. 5 These inflammatory lesions are quite sensitive to corticosteroid administration.'-3 In this report a case of an inflammatory pseudotumor of the iris and ciliary body unresponsive to steroid therapy but which virtually disappeared when systemic propranolol was withdrawn is presented, with a discussion of the clinical, ultrasonographic, and histopathologic findings.
CASE REPORT This 60-year-old man was in good ocular health until January 1980, when he first noted blurred vision in his left eye. Visual acuity was 20/20 in both eyes at that time, but slit-lamp examination revealed keratic precipitates and aqueous cells and flare in the left eye. He was treated with topical steroids for 2 weeks with resolution of his symptoms and clinical findings. Five months later, he had a second episode with left eye irritation and foreign body sensation. Keratic precipitates and aqueous flare were observed. Despite reinstatement of topical steroids and cycloplegics, symptoms and inflammation persisted. A limited systemic evaluation revealed a normal chest x-ray, blood count, and urinalysis, but an erythrocyte sedimentation rate elevated to 40 mm/hr. In September 1980, he was started on a course of oral prednisone, 25 mg every other day, which was tapered offby February 1981. Ocular findings were unchanged except for the development of a posterior subcapsular cataract in the left eye which reduced visual acuity to 20/30. Topical
YEOMANS,
et al •
INFLAMMATORY PSEUDOTUMOR
corticosteroid therapy was continued. Cataractous changes progressed, with reduction of visual acuity to 20/100 in April 1981 and 20/400 in May 1981, at which time the fundus could no longer be visualized. In addition, a pinkish fleshy mass was noted in the inferior iris of the left eye. The patient was referred to the Wilmer Institute in June 1981. Visual acuity in the normal right eye was 20/20. Visual acuity in the left eye was hand motions at 10ft. The left conjunctiva was injected and slit-lamp examination showed many fine keratic precipitates centrally and inferiorly. There was a mild aqueous flare and cellular reaction. A pinkish tissue was seen behind the limbus in the iris peripherally from 2:30 to 9:30 o'clock (Fig 1), with posterior displacement of the lens temporally. Posterior synechiae extended from the 5- to I-o'clock position. Ultrasonography revealed a large, low-density mass in the temporal ciliary body. The patient underwent an extensive systemic evaluation that revealed only antinuclear antibodies at a titre of 1:40, a sedimentation rate of 17, and complement fractions C3 and C4 within normal limits. Chest and sinus x-rays were normal. Dental and ear, nose and throat consultations were noncontributory. A review of the patient's past medical history revealed that he had taken propranolol (Inderal®), 40 mg orally four times daily, since an episode of chest pain and shortness of breath 3 years previously. Systemic physical examination was notable for bilateral gynecomastia and nipple tenderness. The patient also complained of back pain. On July 1, 1981, an aqueous paracentesis was performed to obtain cells that might help in determination of the nature of the lesion. The specimen, prepared using a membrane filter and modified Papanicolaou staining technique, showed mature lymphocytes and occasional pigment-containing macrophages (Fig 2). There were no giant cells or cells demonstrating atypical features. The following day a transcorneal biopsy of the peripheral iris and ciliary body was performed under local anesthesia in the 4- to 5-0'clock meridian. A Bard-Parker blade was used to incise the cornea concentrically at the limbus. Dissection into the deeper tissue displayed dilated blood vessels and pinkish tissue identical to that seen through the cornea. The tip of a Smith-Green corneal knife was used to excise a 3 X 1 X 0.5 mm strip of the pink tissue. Microscopic examination showed an infiltrate consisting of mostly normal-appearing lymphocytes and rare plasma cells (Fig 3). The impression was inflammatory pseudotumor of the iris and ciliary body. After the ciliary body biopsy, the patient's propranolol therapy was stopped, because a physician-patient had observed that he had experienced gynecomastia and nipple tenderness while taking propranolol, which ceased when he stopped taking the drug. Within 24 hours of discontinuing propranolol, our patient reported that he no longer had back pain, and the nipple pain and tenderness were gone in 2 days. Five days after discontinuing the propranolol, a distinct diminution in the size of the pink inflammatory mass was seen (Fig 4). Three weeks after biopsy, the lesion (Fig 5) was seen to be slightly larger in the area ofthe corneal incision where it persisted long after the other areas had disappeared. By November 1981, 5 months after biopsy, the mass was not evident externally (Fig 6) and visible only by gonioscopy as a tiny rim of pink tissue. Since that time, the patient has had a persistent mild aqueous flare and cellular reaction, for which topical steroid therapy has been continued. The lens is no longer displaced. No evidence of systemic disease has been found. The patient has been unwilling to use oral or topical propranolol (Timoptic®) to provide a putative antigenic challenge to the inflammatory disease in his eye.
DISCUSSION The case reported herein represents another example of the unusual and rare occurrence of an inflammatory tumor of the iris and ciliary body. The clinical and pathologic features are reported because of the rarity of the lesion, establishment of the diagnosis by intraocular biopsy and the high probability that propranolol (Inderal®) was the causative factor. The inflammatory mass reduced in size during a 6-month period after cessation of propranolol, but persisted in a small area at the biopsy incision site. Only 23 cases of intraocular inflammatory pseudotumors have been described. I - 5 Diagnosis has been on the basis of enucleation in 21 eyes, excisional biopsy of an iris mass in one case,4 and by clinical criteria based on appearance, ultrasound and computerized tomography in one case. 5 Previously diagnosed cases ranged from 30 to 94 years of age, with men twice as often as women. Duration of symptoms has ranged from months to 35 years.2 The case reported here is characteristic of intraocular inflammatory pseudotumor. With such a mass presenting in the anterior segment, the initial clinical differential diagnosis would include primary and metastatic neoplasms, granulomata both infectious (syphilis or tuberculosis) and noninfectious (sarcoidosis) in origin, and serum dysproteinemic conditions such as Waldenstrom's macroglobulinemia. These disease entities were effectively ruled out in our patient by appropriate clinical and laboratory evaluation. Malignant melanoma, leukemia, lymphoma, and metastatic carcinoma were excluded first by aqueous cytopathology, which found no malignant cells, and secondly by transcorneal ciliary body biopsy. The histopathologic features of the ciliary body biopsy are similar to those seen in other cases. Ryan, Zimmerman, and King2 noted that the infiltrate may include mature lymphocytes, plasma cells, reticular lymphoblasts, Russell bodies, and Dutcher bodies. Systemic and topical corticosteroid use, which was thought to be responsible for improvement of the inflammatory mass in two patients,3,5 improved the picture in our patient only in the early phase of his iridocyclitis. Later in his course, iridocyclitis persisted, and the inflammatory mass developed despite continued corticosteroid use. In our experience, progression of intraocular inflammation refractive to corticosteroids indicates the continued presence of causative factors such as intraocular microorganisms, remote foci of infection, drug and food allergies, ischemia, or neoplasm. We are intrigued by the possibility that the oral use of propranolol (Inderal®) was responsible for the induction of this patient's intraocular inflammatory pseudotumor. A review of the literature concerning adverse reactions to propranolol administration reveals a variety of complications in virtually all organ systems, including watery nasal secretions,1O dermatologic eruptions of a psoriasiform, lichenoid and eczematous nature,lI-14 polyarthri1423
OPHTHALMOLOGY •
DECEMBER 1983 •
VOLUME 90 •
NUMBER 12
Fig l. Top left. appearance of iris lesion at presentation. Fig 2. Top right. aqueous specimen with normal-appearing lymphocyte (membrane filter; modified Papanicolaou stain. X640). Fig 3. Center left. biopsy of lesion showing infiltrate oflymphocytes (hematoxylin-eosin, X 160). Fig 4. Center right. appearance of lesion 5 days after biopsy and discontinuation of propranolol. Fig 5. Bottom left. appearance of enlargement of lesion in area of corneal incision 25 days after biopsy and discontinuance of propranolol. Fig 6. Bottom right. appearance of lesion 5 months after discontinuance of propranolol.
tis, IS acute interstitial nephritis, 16 retroperitoneal fibrosis, 17 and sclerosing peritonitis. 18,19 Central nervous system side effects have included acute and organic brain syndromes, with visual and sensory hallucinations, vivid dreams, and insomnia. 20 - 22 Documented ocular effects include a myasthenic-type diplopia, decreased tear production with or without associated dry mouth, and hyperemic conjunctivae. 23- 25 We found no previous cases of intraocular 1424
inflammation in our review ofthe literature. Challenging patients with a second use of propranolol has been reported twice with recurrence of symptoms, an eczematous eruption in one,l1 and diplopia in the other. 23 The observation by one of us (GM) of the association of nipple pain and gynecomastia with propranolol therapy led to the decision to halt administration of the drug in our patient. Resolution of his back and nipple pain began
YEOMANS, et al
•
INFLAMMATORY PSEUDOTUMOR
within 1 day, and the eye lesion subsided over a period of weeks to months. Evidence for the potential role of propranolol in the ocular process is further substantiated by the fact that drug administration preceded the development of ocular inflammation by 2 years; the failure of the anterior segment mass to respond to both topical and systemic steroids as an indication of persistent activity and continuing antigenic challenge; and the time course of improvement following withdrawal of propranolol (back and nipple symptoms within days, and the eye lesion over several months, with persistent, although nonworsening, mild iridocyclitis). The slow resolution of the pink mass parallels the 5to 14-month time course for recovery seen after removal of gluten from the diet of many patients with dermatitis herpetiformis. 26 Relative persistence of the pink inflammatory mass in the area of the transcorneal ciliary body biopsy is demonstrated in Figure 5. The tissue in the 3- to 5-0'clock meridian was slightly enlarged and persisted longer than in other areas of the iris and ciliary body. It is possible to speculate that the trauma of the biopsy and reaction to sutures stimulated vascularization and promoted factors responsible for maintenance of inflammation. Unfortunately, our patient is reluctant to participate in a rechallenge through the use of oral or topical propranolol (Timolol®), to test our hypothesis concerning the role of propranolol in the induction of this inflammatory uveal process.
REFERENCES 1. Gass JDM. Retinal detachment and narrow-angle glaucoma secondary to inflammatory pseudotumor of the uveal tract. Am J Ophthalmol 1967; 64:612-21. 2. Ryan SJ, Zimmerman LE, King FM. Reactive lymphoid hyperplasia: an unusual form of intraocular pseudotumor. Trans Am Acad OphthalmolOtolaryngol 1972; 76:652-71. 3. Ryan SJ Jr, Frank RN, Green WR. Bilateral inflammatory pseudotumors of the ciliary body. Am J Ophthalmol 1971; 72:586-91. 4. Shields JA, Augsburger JJ, Gonder JR, MacLeod D. Localized benign lymphoid tumor of the iris. Arch Ophthalmol 1981; 99:2147-8.
5. Desroches G, Abrams GW, Gass JDM. Reactive lymphoid hyperplasia of the uvea; a case with ultrasonographic and computed tomographic studies. Arch Ophthalmol 1983; 101 :725-8. 6. Cook C. Uveal lymphosarcoma. Br J OphthalmoI1954; 38:182-5. 7. Beasley H. Lymphosarcoma of the choroid. Am J Ophthalmol1961; 51:1294-6. 8. Zimmerman LE. Lymphoid tumors. In: Boniuk M, ed. Ocular and Adnexal Tumors; New and Controversial Aspects. St Louis: CV Mosby, 1964; 438. 9. Crookes GP, Mullaney J. Lymphoid hyperplasia of the uveal tract simulating malignant melanoma. Am J Ophthalmol1967; 63:962-7. 10. Malm L. Propranolol as cause of watery nasal secretion. Lancet 1981; 1:1006. 11. van Joost T, Smitt JHS. Skin reactions to propranolol and cross sensitivity to beta-adrenoreceptor blocking agents. Arch Dermatol 1981; 117:600-1. 12. Felix RH, Ive FA, Dahl MGC. Skin reactions to beta-blockers. Br Med J 1975; 1:626. 13. Cochran REI, Thomson J, McQueen A, Beevers DG. Skin reactions associated with propranolol. Arch Dermatol 1976; 112: 1173-4. 14. Halevy S, Feuerman EJ. Psoriasiform eruption induced by propranolol. Cutis 1979; 24:95-8. 15. Machtey I. PolyarthritiS following propranolol. Arthritis Rheum 1981; 24:568-9. 16. Bailey RR. Propranolol-induced acute interstitial nephritis. N Z Med J 1981; 94:397-8. 17. Pierce JR Jr, Trostle DC, Warner JJ. Propranolol and retroperitoneal fibrosis. Ann Intem Med 1981; 95:244. 18. Ahmad S. Sclerosing peritonitis and propranolol. Chest 1981; 79:361-
2. 19. Nicholls JT, Rutty DA. Sclerosing peritonitis with short-term propranolol therapy. Arch Intem Med 1980; 140:1124-5. 20. Tikare SK, Bandisode MS. Central nervous system side effects of propranolol. J Med Assoc Ga 1982; 71:777-8. 21. Kurland ML. Organic brain syndrome with propranolol. N Engl J Med 1979; 300:366. 22. Helson L, Duque L. Acute brain syndrome after propranolol. Lancet 1978; 1:98. 23. Weber JCP. Beta-adrenoreceptor antagonists and diplopia. Lancet 1982; 2:826-7. 24. Cubey RB, Taylor SH. Ocular reaction to propranolol and resolution on continued treatment with a different beta-blocking drug. Br Med J 1975; 4:327-8. 25. Skegg DCG, Doll R. Frequency of eye complaints and rashes among patients receiving practolol and propranolol. Lancet 1977; 2:475-8. 26. Leonard J, Haffenden G, Tucker W, et aI. Gluten challenge in dermatitis herpetiformis. N Engl J Med 1983; 308:816-9.
1425