Episcleritis, Conjunctivitis, and I(eratitis as Ocular Manifestations of Lyme Disease ALLAN J. FLACH, MD,t PAUL E. LAVOIE, MD2
Abstract: A 35-year-old woman presented with a bilateral palpebral follicular conjunctivitis. Subsequently, she developed a bilateral keratitis and, on a separate occasion, an episcleritis that was associated with a recrudescence of Lyme disease and poor compliance with the antibiotic regimen. Both the keratitis and episcleritis cleared completely after topical corticosteroid therapy and reinstitution of appropriate antibiotic treatment. This report emphasizes the importance of collaboration between internal medicine and ophthalmologic specialists during the long-term management of Lyme disease. Ophthalmology 1990; 97:973-975
Lyme disease is the most common tick-transmitted illness in the United States.! Ophthalmologists are familiar with the manifestations of Lyme disease because of the following ocular complications that have been reported: blepharitis, 2 conjunctivitis,3 keratitis,4 iritis, 5 choroiditis, 6 macular and disc edema/ and pseudotumor cerebri syndrome. 8 Recently, an overview of Lyme disease emphasized its historical background, stages, diagnosis, and medical treatment with specific reference to the ophthalmologist. 9 This report provides the first description of episcleritis in a patient with Lyme disease and the first detailed description of the follicular conjunctivitis that can coexist with Lyme disease. Furthermore, the potential importance of collaboration between internal medicine and ophthalmologic specialists during long-term management of the disease is emphasized.
Originally received: November 15, 1989. Revision accepted: April 2, 1990. Department of Ophthalmology, University of Califomia School of Medicine, and Veterans Administration, San Francisco. 2 Department of Intemal Medicine, Presbyterian Medical Center, San Francisco. 1
Supported by a Veterans Administration Merit Review grant (Dr. Flach). Reprint requests to Allan J. Flach, MD, Ophthalmology Service, VA Hospital and Medical Center, Mailstop 112A, 4150 Clement Street, San Francisco, CA94121.
CASE REPORT A 35-year-old Japanese-American woman presented in July 1985 with a 2-month history of bilateral photophobia and a history of many months of intermittent bilateral ocular irritation that she related to a camera flash. Past medical history included emotional problems and osteoarthritis of the knees, hands, and shoulders. An ovarian cyst resection had been done 6 years previously. She was not taking medications. Her best-corrected visual acuity was 20/20 in each eye. She demonstrated a bilateral follicular conjunctivitis without preauricular adenopathy. The follicular conjunctivitis was limited to the palpebral conjunctivae and was not associated with any significant ocular discharge. There was no associated blepharitis and no vasodilation of bulbar conjunctival vessels. Her corneas were clear and showed no staining with fluorescein. The balance of her eye examination was unremarkable. Because her history indicated she was getting better without treatment, she was reassured. She was asymptomatic 2 weeks later, but the bilateral and palpebral conjunctival follicular reaction remained. The following year the patient returned for a routine examination with several months of increasing intermittent bilateral ocular burning and irritation associated with mild photophobia. Visual acuity remained 20/20 in each eye, and slit-lamp examination continued to show a bilateral follicular conjunctivitis present within the palpebral conjunctivae. No follicles were observed on the bulbar conjunctiva. A Schirmer test without topical anesthesia showed 2-mm wetting at 5 minutes in each eye. There was no evidence of corneal staining with rose bengal solution. Her tear menisci were decreased. Tear film breakup times were
973
OPHTHALMOLOGY
•
AUGUST 1990
normal (greater than 15 seconds in each eye). She was not using medications that could have decreased tear production. She was treated with artificial tears and felt more comfortable. Several months later she presented with a painful, red right eye and epiphora. Results of slit-lamp examination showed a bilateral keratitis associated with fine, white keratic precipitates present only in the right eye. There was no evidence of cells or flare in the anterior chamber of the right eye. The bilateral keratitis consisted of moderate punctate staining associated with multiple, hazy stromal infiltrates with indiscrete borders located both superficially and deep within the stroma. There was no evidence of stromal blood vessels or stromal edema. The keratic precipitates and keratitis disappeared within 2 weeks on a regimen of topical prednisolone acetate 1% given four times daily. The second week following initiation of treatment, she was noted to have a 4 X 6-cm, annular, purplish area of discoloration over her left medial malleolus where she remembered receiving a spider bite in 1978. The skin changes looked similar to acrodermatitis chronica atrophicans, a dermatologic manifestation of Lyme disease; therefore, she was questioned further about her past medical history and general activities. During her youth, she had hiked in the Lake Tahoe area of California and Nevada, but she denied tick bites or a diagnosis of Lyme disease. However, she thought her rheumatologist (PEL) had recently performed a new laboratory test with positive results. He recently had initiated treatment with minocycline (200 mg each day) that bothered her stomach. It was confirmed that her polyclonal indirect fluorescent antibody test was positive for Borrelia burgdOl:feri at a 1 to 128 dilution. Her fluorescent treponemal antibodyabsorption test for syphilis was negative. Tests for rheumatoid factor, antinuclear antibody, and cryoglobulins were negative. Her erythrocyte sedimentation rate was normal. Several weeks later she returned with an acutely red and painful right eye. She had no evidence of corneal staining, keratitis, or iritis but had an episcleritis in the right eye. Because she had not tolerated the minocycline, she had complied poorly with the treatment regimen. The episcleritis responded to treatment with topical prednisolone acetate (1 % given four times daily over a 2- to 3-week period). She was also treated with amoxicillin (3 g twice daily) and probenecid (500 mg twice daily) for 3 months. Her most recent polyclonal indirect fluorescent antibody titer was positive for B. burgdorferi at a I to 256 dilution. Her ocular signs disappeared except for bilateral, scattered, inferior, palpebral conjunctival follicles.
DISCUSSION The patient had an elevated B. burgdorferi antibody level and evidence of dermatologic, neurologic, musculoskeletal, and ocular disease. Although she did not recall a tick bite, her frequent hiking trips in the Lake Tahoe area provided opportunity for exposure to Ixodes pacificus, a well-recognized tick vector for the spirochete B. burgdorferi. 1O Therefore, the diagnostic criteria for Lyme disease in this patient is fulfilled. II This patient is unusual because she showed several different ocular complications during the course of the disease: bilateral palpebral follicular conjunctivitis, bilateral keratitis, and right eye episcleritis. Conjunctivitis is the most commonly reported ocular complication of Lyme disease 3.5; however, there is no careful description of the characteristics of the conjunctivitis as it exists in Lyme
974
•
VOLUME 97
•
NUMBER 8
disease in the literature. Our patient had follicular conjunctivitis that mayor may not be characteristic of the early and later conjunctivitis present in Lyme disease. The bilateral keratitis that developed in this patient was similar to cases described previously.4,12,13 All reported cases showed superficial and deep, hazy stromal infiltrates that mayor may not affect vision. This case lacked evidence of associated stromal vessels4 but demonstrated fine, white keratic precipitates on the corneal endothelial layer in one eye. 12 The corneal changes responded dramatically to topical corticosteroid treatment as described; however, this patient also received antibiotic therapy at the same time. This is the first report of episcleritis as an ocular complication in Lyme disease. It is of particular interest that the episcleritis was associated with poor compliance to the chosen antibiotic regimen. Others have suggested the possibility that ocular manifestations might occasionally indicate a recrudescence of the disease because of inadequate treatment of the infection. 12 Although the decrease in ocular pain and redness with topical corticosteroid treatment was impressive, the episcleritis signaled the need to prescribe a different antibiotic. This occurrence underscores the importance of internist-ophthalmologist collaboration in the long-term management of Lyme disease. This patient gave a history ofa spider bite on her ankle. Although suggestions that tabanid flies and mosquitoes may serve as vectors for borrelial infection exist,13,14 spiders have not been considered as potential vectors. It is conceivable that a spider could feed upon a spirocheteinfected deer fly or mosquito and, in turn, bite a human. However, experts feel this is very unlikely (personal communication, Dr. R. S. Lane, Department of Entomology, University of California, Berkeley, CA). It is much more probable that she was infected during one of her many hikes in the Lake Tahoe area of California. The patient had a purplish, atrophic area on her ankle that appeared to be consistent with acrodermatitis chronica atrophicans, and this observation suggested the diagnosis of Lyme disease to the patient's ophthalmologis (AlF). A definite diagnosis of acrodermatitis chronic~ atrophicans can only be made with histopathology showing telangiectases, lymphocytic infiltration, plasma cell~ in the dermis, and thin, hyperkeratotic epidermis. 15 Th( patient refused to have a biopsy done; therefore, a specific diagnosis was not made. It is important, however, fo ophthalmologists to recognize that acrodermatitis chronica atrophicans is a nonspecific dermatologic manifestation of Lyme disease. Although erythema chromicum migrans has been wellrecognized since the beginning of this century as an earl: cutaneous clinical hallmark following the bite of an Ixo· didae tick,16 the late cutaneous manifestation of acroder matitis chronica atrophicans is frequently overlooked 0 misinterpreted and has been largely ignored by th ophthalmic literature. This condition may be the first in dication of borrelial infection or it may follow erytheml chromicum migrans. It is observed more often in olde patients and in women. The onset is a gradual and insid
FLACH AND LAVOIE
•
OCULAR MANIFESTATIONS OF LYME DISEASE
ious appearance of a bluish-red discoloration and doughy swollen skin that starts in one extremity (most commonly in the hand or foot). It does not resolve spontaneously like erythema chromicum migrans but may persist for many years. It is therefore important to recognize acrodermatitis chronica atrophicans as a manifestation of Lyme disease because it may provide a persistent dermatologic clue to help make the diagnosis of this variable, multisystem disease. IS
REFERENCES 1. Falco RC, Fish D. Prevalence of Ixodes dammini near the homes of Lyme disease patients in Westchester County, New York. Am J Epidemiol 1988; 127:826-30. 2. Damrow T, Freedman H, Lane R, et al. Is Ixodes (Ixodiopsis) angustus a vector of Lyme disease in Washington State? West J Med 1989; 150:580-2. 3. Bruhn FW. Lyme disease. Am J Dis Child 1984; 138:467-70. 4. Baum J, Barza M, Weinstein P, et al. Bilateral keratitis as a manifestation of Lyme disease. Am J Ophthalmol 1988; 105:75-7. 5. Steere AC, Malawista SE, Bartenhagen NH, et al. The clinical spectrum and treatment of Lyme disease. Yale J Bioi Med 1984; 57:453-64.
6. Bialasiewicz AA, Ruprecht KW, Naumann GOH, Blenk H. Bilateral diffuse choroiditis and exudative retinal detachments with evidence of Lyme disease [Letter). Am J Ophthalmol1988; 105:419-20. 7. Wu G, Lincoff H, Ellsworth RM, Haik BG. Optic disc edema and Lyme disease. Ann Ophthalmol1986; 18:252-5. 8. Jacobson OM, Frens DB. Pseudotumor cerebri syndrome associated with Lyme disease [Letter). Am J Ophthalmol1989; 107:81-2. 9. Aaberg TM. The expanding ophthalmologic spectrum of Lyme disease. Am J Ophthalmol1989; 107:77-80. 10. Steere AC, Malawista SE. Cases of Lyme disease in the United States: locations correlated with distribution of Ixodes dammini. Ann Intem Med 1979; 91 :730-3. 11. Duffy J. Lyme disease. Infect Dis Clin North Am 1987; 1:511-6. 12. Orlin SE, Lauffer JL. Lyme disease keratitis [Letter). Am J Ophthalmol 1989; 107:678-80. 13. Bertuch AW, Rocco E, Schwartz EG, et al. Lyme disease: ocular manifestations. Ann Ophthalmol 1988; 20:376-8. 14. Spielman A. Prospects for suppressing transmission of Lyme disease. Ann NY Acad Sci 1988; 539:212-20. 15. Asbrink E, Hovmark A. Early and late cutaneous manifestations in Ixodes-bome borreliosis (erythema migrans borreliosis). Ann NY Acad Sci 1988; 539:4-15. 16. Afzelius A. Verhandlungen der dermatologischen Gesellschaft zu Stockholm. Arch Dermatol Syph 1910; 101:403-6.
975
Abstract: A 35-year-old woman presented with a bilateral palpebral follicular conjunctivitis. Subsequently, she developed a bilateral keratitis and, on a separate occasion, an episcleritis that was associated with a recrudescence of Lyme disease and poor compliance with the antibiotic regimen. Both the keratitis and episcleritis cleared completely after topical corticosteroid therapy and reinstitution of appropriate antibiotic treatment. This report emphasizes the importance of collaboration between internal medicine and ophthalmologic specialists during the long-term management of Lyme disease. Ophthalmology 1990; 97:973-975
Lyme disease is the most common tick-transmitted illness in the United States.! Ophthalmologists are familiar with the manifestations of Lyme disease because of the following ocular complications that have been reported: blepharitis, 2 conjunctivitis,3 keratitis,4 iritis, 5 choroiditis, 6 macular and disc edema/ and pseudotumor cerebri syndrome. 8 Recently, an overview of Lyme disease emphasized its historical background, stages, diagnosis, and medical treatment with specific reference to the ophthalmologist. 9 This report provides the first description of episcleritis in a patient with Lyme disease and the first detailed description of the follicular conjunctivitis that can coexist with Lyme disease. Furthermore, the potential importance of collaboration between internal medicine and ophthalmologic specialists during long-term management of the disease is emphasized.
Originally received: November 15, 1989. Revision accepted: April 2, 1990. Department of Ophthalmology, University of Califomia School of Medicine, and Veterans Administration, San Francisco. 2 Department of Intemal Medicine, Presbyterian Medical Center, San Francisco. 1
Supported by a Veterans Administration Merit Review grant (Dr. Flach). Reprint requests to Allan J. Flach, MD, Ophthalmology Service, VA Hospital and Medical Center, Mailstop 112A, 4150 Clement Street, San Francisco, CA94121.
CASE REPORT A 35-year-old Japanese-American woman presented in July 1985 with a 2-month history of bilateral photophobia and a history of many months of intermittent bilateral ocular irritation that she related to a camera flash. Past medical history included emotional problems and osteoarthritis of the knees, hands, and shoulders. An ovarian cyst resection had been done 6 years previously. She was not taking medications. Her best-corrected visual acuity was 20/20 in each eye. She demonstrated a bilateral follicular conjunctivitis without preauricular adenopathy. The follicular conjunctivitis was limited to the palpebral conjunctivae and was not associated with any significant ocular discharge. There was no associated blepharitis and no vasodilation of bulbar conjunctival vessels. Her corneas were clear and showed no staining with fluorescein. The balance of her eye examination was unremarkable. Because her history indicated she was getting better without treatment, she was reassured. She was asymptomatic 2 weeks later, but the bilateral and palpebral conjunctival follicular reaction remained. The following year the patient returned for a routine examination with several months of increasing intermittent bilateral ocular burning and irritation associated with mild photophobia. Visual acuity remained 20/20 in each eye, and slit-lamp examination continued to show a bilateral follicular conjunctivitis present within the palpebral conjunctivae. No follicles were observed on the bulbar conjunctiva. A Schirmer test without topical anesthesia showed 2-mm wetting at 5 minutes in each eye. There was no evidence of corneal staining with rose bengal solution. Her tear menisci were decreased. Tear film breakup times were
973
OPHTHALMOLOGY
•
AUGUST 1990
normal (greater than 15 seconds in each eye). She was not using medications that could have decreased tear production. She was treated with artificial tears and felt more comfortable. Several months later she presented with a painful, red right eye and epiphora. Results of slit-lamp examination showed a bilateral keratitis associated with fine, white keratic precipitates present only in the right eye. There was no evidence of cells or flare in the anterior chamber of the right eye. The bilateral keratitis consisted of moderate punctate staining associated with multiple, hazy stromal infiltrates with indiscrete borders located both superficially and deep within the stroma. There was no evidence of stromal blood vessels or stromal edema. The keratic precipitates and keratitis disappeared within 2 weeks on a regimen of topical prednisolone acetate 1% given four times daily. The second week following initiation of treatment, she was noted to have a 4 X 6-cm, annular, purplish area of discoloration over her left medial malleolus where she remembered receiving a spider bite in 1978. The skin changes looked similar to acrodermatitis chronica atrophicans, a dermatologic manifestation of Lyme disease; therefore, she was questioned further about her past medical history and general activities. During her youth, she had hiked in the Lake Tahoe area of California and Nevada, but she denied tick bites or a diagnosis of Lyme disease. However, she thought her rheumatologist (PEL) had recently performed a new laboratory test with positive results. He recently had initiated treatment with minocycline (200 mg each day) that bothered her stomach. It was confirmed that her polyclonal indirect fluorescent antibody test was positive for Borrelia burgdOl:feri at a 1 to 128 dilution. Her fluorescent treponemal antibodyabsorption test for syphilis was negative. Tests for rheumatoid factor, antinuclear antibody, and cryoglobulins were negative. Her erythrocyte sedimentation rate was normal. Several weeks later she returned with an acutely red and painful right eye. She had no evidence of corneal staining, keratitis, or iritis but had an episcleritis in the right eye. Because she had not tolerated the minocycline, she had complied poorly with the treatment regimen. The episcleritis responded to treatment with topical prednisolone acetate (1 % given four times daily over a 2- to 3-week period). She was also treated with amoxicillin (3 g twice daily) and probenecid (500 mg twice daily) for 3 months. Her most recent polyclonal indirect fluorescent antibody titer was positive for B. burgdorferi at a I to 256 dilution. Her ocular signs disappeared except for bilateral, scattered, inferior, palpebral conjunctival follicles.
DISCUSSION The patient had an elevated B. burgdorferi antibody level and evidence of dermatologic, neurologic, musculoskeletal, and ocular disease. Although she did not recall a tick bite, her frequent hiking trips in the Lake Tahoe area provided opportunity for exposure to Ixodes pacificus, a well-recognized tick vector for the spirochete B. burgdorferi. 1O Therefore, the diagnostic criteria for Lyme disease in this patient is fulfilled. II This patient is unusual because she showed several different ocular complications during the course of the disease: bilateral palpebral follicular conjunctivitis, bilateral keratitis, and right eye episcleritis. Conjunctivitis is the most commonly reported ocular complication of Lyme disease 3.5; however, there is no careful description of the characteristics of the conjunctivitis as it exists in Lyme
974
•
VOLUME 97
•
NUMBER 8
disease in the literature. Our patient had follicular conjunctivitis that mayor may not be characteristic of the early and later conjunctivitis present in Lyme disease. The bilateral keratitis that developed in this patient was similar to cases described previously.4,12,13 All reported cases showed superficial and deep, hazy stromal infiltrates that mayor may not affect vision. This case lacked evidence of associated stromal vessels4 but demonstrated fine, white keratic precipitates on the corneal endothelial layer in one eye. 12 The corneal changes responded dramatically to topical corticosteroid treatment as described; however, this patient also received antibiotic therapy at the same time. This is the first report of episcleritis as an ocular complication in Lyme disease. It is of particular interest that the episcleritis was associated with poor compliance to the chosen antibiotic regimen. Others have suggested the possibility that ocular manifestations might occasionally indicate a recrudescence of the disease because of inadequate treatment of the infection. 12 Although the decrease in ocular pain and redness with topical corticosteroid treatment was impressive, the episcleritis signaled the need to prescribe a different antibiotic. This occurrence underscores the importance of internist-ophthalmologist collaboration in the long-term management of Lyme disease. This patient gave a history ofa spider bite on her ankle. Although suggestions that tabanid flies and mosquitoes may serve as vectors for borrelial infection exist,13,14 spiders have not been considered as potential vectors. It is conceivable that a spider could feed upon a spirocheteinfected deer fly or mosquito and, in turn, bite a human. However, experts feel this is very unlikely (personal communication, Dr. R. S. Lane, Department of Entomology, University of California, Berkeley, CA). It is much more probable that she was infected during one of her many hikes in the Lake Tahoe area of California. The patient had a purplish, atrophic area on her ankle that appeared to be consistent with acrodermatitis chronica atrophicans, and this observation suggested the diagnosis of Lyme disease to the patient's ophthalmologis (AlF). A definite diagnosis of acrodermatitis chronic~ atrophicans can only be made with histopathology showing telangiectases, lymphocytic infiltration, plasma cell~ in the dermis, and thin, hyperkeratotic epidermis. 15 Th( patient refused to have a biopsy done; therefore, a specific diagnosis was not made. It is important, however, fo ophthalmologists to recognize that acrodermatitis chronica atrophicans is a nonspecific dermatologic manifestation of Lyme disease. Although erythema chromicum migrans has been wellrecognized since the beginning of this century as an earl: cutaneous clinical hallmark following the bite of an Ixo· didae tick,16 the late cutaneous manifestation of acroder matitis chronica atrophicans is frequently overlooked 0 misinterpreted and has been largely ignored by th ophthalmic literature. This condition may be the first in dication of borrelial infection or it may follow erytheml chromicum migrans. It is observed more often in olde patients and in women. The onset is a gradual and insid
FLACH AND LAVOIE
•
OCULAR MANIFESTATIONS OF LYME DISEASE
ious appearance of a bluish-red discoloration and doughy swollen skin that starts in one extremity (most commonly in the hand or foot). It does not resolve spontaneously like erythema chromicum migrans but may persist for many years. It is therefore important to recognize acrodermatitis chronica atrophicans as a manifestation of Lyme disease because it may provide a persistent dermatologic clue to help make the diagnosis of this variable, multisystem disease. IS
REFERENCES 1. Falco RC, Fish D. Prevalence of Ixodes dammini near the homes of Lyme disease patients in Westchester County, New York. Am J Epidemiol 1988; 127:826-30. 2. Damrow T, Freedman H, Lane R, et al. Is Ixodes (Ixodiopsis) angustus a vector of Lyme disease in Washington State? West J Med 1989; 150:580-2. 3. Bruhn FW. Lyme disease. Am J Dis Child 1984; 138:467-70. 4. Baum J, Barza M, Weinstein P, et al. Bilateral keratitis as a manifestation of Lyme disease. Am J Ophthalmol 1988; 105:75-7. 5. Steere AC, Malawista SE, Bartenhagen NH, et al. The clinical spectrum and treatment of Lyme disease. Yale J Bioi Med 1984; 57:453-64.
6. Bialasiewicz AA, Ruprecht KW, Naumann GOH, Blenk H. Bilateral diffuse choroiditis and exudative retinal detachments with evidence of Lyme disease [Letter). Am J Ophthalmol1988; 105:419-20. 7. Wu G, Lincoff H, Ellsworth RM, Haik BG. Optic disc edema and Lyme disease. Ann Ophthalmol1986; 18:252-5. 8. Jacobson OM, Frens DB. Pseudotumor cerebri syndrome associated with Lyme disease [Letter). Am J Ophthalmol1989; 107:81-2. 9. Aaberg TM. The expanding ophthalmologic spectrum of Lyme disease. Am J Ophthalmol1989; 107:77-80. 10. Steere AC, Malawista SE. Cases of Lyme disease in the United States: locations correlated with distribution of Ixodes dammini. Ann Intem Med 1979; 91 :730-3. 11. Duffy J. Lyme disease. Infect Dis Clin North Am 1987; 1:511-6. 12. Orlin SE, Lauffer JL. Lyme disease keratitis [Letter). Am J Ophthalmol 1989; 107:678-80. 13. Bertuch AW, Rocco E, Schwartz EG, et al. Lyme disease: ocular manifestations. Ann Ophthalmol 1988; 20:376-8. 14. Spielman A. Prospects for suppressing transmission of Lyme disease. Ann NY Acad Sci 1988; 539:212-20. 15. Asbrink E, Hovmark A. Early and late cutaneous manifestations in Ixodes-bome borreliosis (erythema migrans borreliosis). Ann NY Acad Sci 1988; 539:4-15. 16. Afzelius A. Verhandlungen der dermatologischen Gesellschaft zu Stockholm. Arch Dermatol Syph 1910; 101:403-6.
975
