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Anterior uveitis and Sjögren's syndrome in a patient with primary biliary cirrhosis
CASE REPORTS
Anterior uveitis and Sjogren's syndrome in a patient with primary biliary cirrhosis Oya Tekeli, MD; Ozden Ozdemir, MD
P
rimary biliary cirrhosis (PBC) is a chronic, progressive disease whose pathogenesis is unclear. Histologic evidence suggests an immune mechanism. Autoimmune disease may be found in up to 80% of patients with PBC, and keratoconjunctivitis sicca syndrome has been reported to occur in up to 80%.1 We are aware of two reports concerning the association between PBC and uveitis. 2•3 We describe a patient with PBC, Sjogren's syndrome and anterior uveitis. CASE REPORT
A 63-year-old woman was admitted to hospital with a 3-day history of blurred vision and hyperemia in the right eye. Eleven years earlier she had received a diagnosis of PBC, for which she had been treated with ursodeoxycholic acid. She had a past history of dry mouth and decreased salivary secretion. On ophthalmologic examination the best corrected visual acuity in her right eye was 0.8. The visual acuity in her left eye was 0.6 owing to amblyopia. The Schirmer 1 test (without anesthesia) showed 1 mm of wetting of the test strip in the right eye and 2 mm of wetting in the left eye. Anterior segment examination revealed conjunctival hyperemia, medium keratic precipitates, 2+ cells in the anterior chamber and posterior synechiae in the right eye (Fig. 1) and bilateral superficial punctate keratopathy. There was no aqueous flare. The fundi were normal. The intraocular pressure was 12 mm Hg in both eyes.
Laboratory investigations showed elevated levels of alkaline phosphatase (468 U/L [normally 37 to 147 U/L]), serum aspartate aminotransferase (61 U/L [normally 0 to 37 U/L]), alanine aminotransferase (64 U/L [normally 0 to 40 U/L]), -y-glutamyltransferase (211 U/L [normally 0 to 50 UIL]) and cholesterol (6.13 mmol/L [normally 3.10 to 5.17 mmol/L]). Testing for antinuclear antibody (ANA) (nuclear dots) gave a positive result. The immunofluorescence technique gave positive results for anticentromere antibody (95.3 lUlL [normally 0 to 251U/L]) and antimitochondrial antibody (AMA) (titre 1:40 [normally less than 1:40]). The levels of anti-SS-A antibody, anti-SS-B antibody, anti-n-RNP/ Sm antibodies and anti-double stranded DNA were within normal limits. Testing for anti-smooth muscle antibody and liver-kidney microsomal autoantibodies type 1 (by the immunofluorescence technique) gave negative results. The serum levels of IgG, IgA, IgM, C3, C4, bilirubin, albumin, a 1-globulin, a 2-globulin, 13globulin and-y-globulin were within normal limits. Testing for antistreptolysin-a, C-reactive protein, rheumatoid factor and cryoglobulin gave negative results, as did pathergy testing. The parotid flow rate after stimulation
From the Department of Ophthalmology, Faculty of Medicine, Ankara University, Ankara, Turkey Originally received Mar. 27, 2002 Accepted for publication July 19, 2002 Correspondence to: Dr. Oya Tekeli, Ankara Dniversitesi, T1p Fakiiltesi Goz Hastahklan, Ana Bilim Dah, Mamak, Ankara, Turkey; tekeli@ dialup.ankara.edu.tr This article has been peer-reviewed.
Can J Ophthafmof 2002;37:359-60
Primary biliary cirrhosis and uveitis-Tekeli et al
Fig. !-Posterior synechiae in right eye of patient with primary biliary cirrhosis.
359
Primary biliary cirrhosis and uveitis-Tekeli et al with lemon juice was 1.0 mL/5 min. The patient did not consent to biopsy of the labial minor salivary gland. The complete blood count and erythrocyte sedimentation rate were within normal limits. Sarcoidosis and tuberculosis were not suggested by the pulmonologist. The amount of induration on tuberculin skin testing with purified protein derivative was 3 mm. High-resolution computed tomography of the chest did not disclose any abnormalities. Skin biopsy did not show limited cutaneous sclerosis. After admission, topical therapy with a corticosteroid, a cycloplegic and artificial tears was started. Prednisolone acetate (1%) was administered topically every hour for 5 days and was then tapered slowly over 1 month. The patient's visual acuity returned to normal within I 0 days, and the other findings resolved within 3 weeks. The anterior uveitis recurred twice, 2 months and 4 months after the first episode. Both episodes resolved with topical steroid therapy. The attacks did not correlate with the systemic findings of PBC.
associated immune disorder, occurring in 70% to 100% of patients. 7 In patients with PBC who have Sjogren's syndrome, elevated titres of anti-SS-A and anti-SS-B antibodies are infrequent. 8 In our patient liver tests gave abnormal results, circulating AMA was present, and the titres of ANA and anticentromere antibody were elevated. The Schirmer 1 test gave abnormal results. The patient had conjunctival hyperemia, medium keratic precipitates, 2+ cells in the anterior chamber and posterior synechiae in the right eye and bilateral superficial punctate keratopathy. PBC preceded the development of uveitis. Santos and colleagues2 reported reduced basal tear production, mutton fat keratic precipitates, and flare and cells in the vitreous of both eyes and CREST syndrome (calcinosis cutis, Raynaud's phenomenon, esophageal dysfunction, sclerodactyly and telangiectasia) in a patient with PBC. In conclusion, acute anterior uveitis may be one of the presenting features of PBC. PBC is suggested by the presence of pruritus, jaundice, hepatosplenomegaly, right upper-quadrant pain, cutaneous findings of chronic liver disease, ascites and variceal hemorrhage.
COMMENTS REFERENCES
The uveal tract represents the lymphovascular organ of the eye and is involved in some forms of inflammation within the eye regardless of which tissue is affected.4 Although the causes of uveitis are multiple, most cases are idiopathic and are considered to have an endogenous, possibly autoimmune, pathogenesis. Chronic idiopathic uveitis may occur in isolation or with various systemic diseases. PBC complicated by uveitis is rare. PBC is an autoimmune disease and is characterized by immunemediated destruction of the biliary epithelial cells. Although there is a genetic predisposition for PBC, additional triggering factors are required. The triggers responsible for inducing PBC are unknown, but interest has focused on the potential role of infection, particularly recurrent urinary tract infections, and infection with atypical mycobacteria. 5 The link between PBC and uveitis has not been clearly demonstrated, but human chronic uveitis Mycoplasma-like microorganisms have been shown to cause inflammatory liver disease in a mouse model. 6 The initial manifestation of PBC is the development of AMA, which is found in 96% of affected patients. 1 Elevated titres of ANA, antiplatelet antibody, antithyroid antibody, anti-SS-A antibody, anti-SS-B antibody and anticentromere antibody are also seen in patients with PBC. 5 The sicca syndrome is the most commonly
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CAN J OPHTHALMOL-VOL. 37, NO.6, 2002
1. Neuberger J. Primary biliary cirrhosis. Lancet 1997;350: 875-9. 2. Santos PS, Oliveira L, Moraes MF, Da Gra~a JP, Monteiro E, Abecasis P, et al. Granulomatous uveitis, CREST syndrome, and primary biliary cirrhosis. Br J Ophthalmol 2000;84(5):548-9. 3. Nakajima K, Komatsu M, Hoshino T, Ishida S, Goto M, Masamune 0, et al. [A case of primary biliary cirrhosis accompanied by uveitis.] Nippon Shokakibyo Gakkai Zasshi 1991 ;88(10):2686-90. 4. Forrester JV, McMenamin PG. Immunopathogenic mechanisms in intraocular inflammation. In: Streilein JW, editor. Immune response and the eye. Vol 73 of Chemical immunology (Adorini L, Arai K, Berek C, Schmitt-Verhulst AM, series editors). Basel: Karger; 1999. p. 159-85. 5. Jones DEJ, Bassendine MF. Primary biliary cirrhosis. J Intern Med 1997;241:345-8. 6. Johnson LA, Wirostko E, Wirostko BM. Experimental murine chronic hepatitis: results following intrahepatic inoculation of human uveitis Mycoplasma-like organisms. Int J Exp Patholl993;74(4):325-3l. 7. Powell FC, Schroeter AL, Dickson ER. Primary biliary cirrhosis and the CREST syndrome: a report of 22 cases. Q J Med 1987;62:75-82. 8. Tsianos EV, Hoofnagle JH, Fox PC, Alspaugh M, Jones EA, Schafer DF, et al. Sjogren's syndrome in patients with primary biliary cirrhosis. Hepatology 1990; 11 :730-4. Key words: primary biliary cirrhosis, anterior uveitis, keratoconjunctivitis sicca, Schirmer 1 test, antimitochondrial antibody
Anterior uveitis and Sjogren's syndrome in a patient with primary biliary cirrhosis Oya Tekeli, MD; Ozden Ozdemir, MD
P
rimary biliary cirrhosis (PBC) is a chronic, progressive disease whose pathogenesis is unclear. Histologic evidence suggests an immune mechanism. Autoimmune disease may be found in up to 80% of patients with PBC, and keratoconjunctivitis sicca syndrome has been reported to occur in up to 80%.1 We are aware of two reports concerning the association between PBC and uveitis. 2•3 We describe a patient with PBC, Sjogren's syndrome and anterior uveitis. CASE REPORT
A 63-year-old woman was admitted to hospital with a 3-day history of blurred vision and hyperemia in the right eye. Eleven years earlier she had received a diagnosis of PBC, for which she had been treated with ursodeoxycholic acid. She had a past history of dry mouth and decreased salivary secretion. On ophthalmologic examination the best corrected visual acuity in her right eye was 0.8. The visual acuity in her left eye was 0.6 owing to amblyopia. The Schirmer 1 test (without anesthesia) showed 1 mm of wetting of the test strip in the right eye and 2 mm of wetting in the left eye. Anterior segment examination revealed conjunctival hyperemia, medium keratic precipitates, 2+ cells in the anterior chamber and posterior synechiae in the right eye (Fig. 1) and bilateral superficial punctate keratopathy. There was no aqueous flare. The fundi were normal. The intraocular pressure was 12 mm Hg in both eyes.
Laboratory investigations showed elevated levels of alkaline phosphatase (468 U/L [normally 37 to 147 U/L]), serum aspartate aminotransferase (61 U/L [normally 0 to 37 U/L]), alanine aminotransferase (64 U/L [normally 0 to 40 U/L]), -y-glutamyltransferase (211 U/L [normally 0 to 50 UIL]) and cholesterol (6.13 mmol/L [normally 3.10 to 5.17 mmol/L]). Testing for antinuclear antibody (ANA) (nuclear dots) gave a positive result. The immunofluorescence technique gave positive results for anticentromere antibody (95.3 lUlL [normally 0 to 251U/L]) and antimitochondrial antibody (AMA) (titre 1:40 [normally less than 1:40]). The levels of anti-SS-A antibody, anti-SS-B antibody, anti-n-RNP/ Sm antibodies and anti-double stranded DNA were within normal limits. Testing for anti-smooth muscle antibody and liver-kidney microsomal autoantibodies type 1 (by the immunofluorescence technique) gave negative results. The serum levels of IgG, IgA, IgM, C3, C4, bilirubin, albumin, a 1-globulin, a 2-globulin, 13globulin and-y-globulin were within normal limits. Testing for antistreptolysin-a, C-reactive protein, rheumatoid factor and cryoglobulin gave negative results, as did pathergy testing. The parotid flow rate after stimulation
From the Department of Ophthalmology, Faculty of Medicine, Ankara University, Ankara, Turkey Originally received Mar. 27, 2002 Accepted for publication July 19, 2002 Correspondence to: Dr. Oya Tekeli, Ankara Dniversitesi, T1p Fakiiltesi Goz Hastahklan, Ana Bilim Dah, Mamak, Ankara, Turkey; tekeli@ dialup.ankara.edu.tr This article has been peer-reviewed.
Can J Ophthafmof 2002;37:359-60
Primary biliary cirrhosis and uveitis-Tekeli et al
Fig. !-Posterior synechiae in right eye of patient with primary biliary cirrhosis.
359
Primary biliary cirrhosis and uveitis-Tekeli et al with lemon juice was 1.0 mL/5 min. The patient did not consent to biopsy of the labial minor salivary gland. The complete blood count and erythrocyte sedimentation rate were within normal limits. Sarcoidosis and tuberculosis were not suggested by the pulmonologist. The amount of induration on tuberculin skin testing with purified protein derivative was 3 mm. High-resolution computed tomography of the chest did not disclose any abnormalities. Skin biopsy did not show limited cutaneous sclerosis. After admission, topical therapy with a corticosteroid, a cycloplegic and artificial tears was started. Prednisolone acetate (1%) was administered topically every hour for 5 days and was then tapered slowly over 1 month. The patient's visual acuity returned to normal within I 0 days, and the other findings resolved within 3 weeks. The anterior uveitis recurred twice, 2 months and 4 months after the first episode. Both episodes resolved with topical steroid therapy. The attacks did not correlate with the systemic findings of PBC.
associated immune disorder, occurring in 70% to 100% of patients. 7 In patients with PBC who have Sjogren's syndrome, elevated titres of anti-SS-A and anti-SS-B antibodies are infrequent. 8 In our patient liver tests gave abnormal results, circulating AMA was present, and the titres of ANA and anticentromere antibody were elevated. The Schirmer 1 test gave abnormal results. The patient had conjunctival hyperemia, medium keratic precipitates, 2+ cells in the anterior chamber and posterior synechiae in the right eye and bilateral superficial punctate keratopathy. PBC preceded the development of uveitis. Santos and colleagues2 reported reduced basal tear production, mutton fat keratic precipitates, and flare and cells in the vitreous of both eyes and CREST syndrome (calcinosis cutis, Raynaud's phenomenon, esophageal dysfunction, sclerodactyly and telangiectasia) in a patient with PBC. In conclusion, acute anterior uveitis may be one of the presenting features of PBC. PBC is suggested by the presence of pruritus, jaundice, hepatosplenomegaly, right upper-quadrant pain, cutaneous findings of chronic liver disease, ascites and variceal hemorrhage.
COMMENTS REFERENCES
The uveal tract represents the lymphovascular organ of the eye and is involved in some forms of inflammation within the eye regardless of which tissue is affected.4 Although the causes of uveitis are multiple, most cases are idiopathic and are considered to have an endogenous, possibly autoimmune, pathogenesis. Chronic idiopathic uveitis may occur in isolation or with various systemic diseases. PBC complicated by uveitis is rare. PBC is an autoimmune disease and is characterized by immunemediated destruction of the biliary epithelial cells. Although there is a genetic predisposition for PBC, additional triggering factors are required. The triggers responsible for inducing PBC are unknown, but interest has focused on the potential role of infection, particularly recurrent urinary tract infections, and infection with atypical mycobacteria. 5 The link between PBC and uveitis has not been clearly demonstrated, but human chronic uveitis Mycoplasma-like microorganisms have been shown to cause inflammatory liver disease in a mouse model. 6 The initial manifestation of PBC is the development of AMA, which is found in 96% of affected patients. 1 Elevated titres of ANA, antiplatelet antibody, antithyroid antibody, anti-SS-A antibody, anti-SS-B antibody and anticentromere antibody are also seen in patients with PBC. 5 The sicca syndrome is the most commonly
360
CAN J OPHTHALMOL-VOL. 37, NO.6, 2002
1. Neuberger J. Primary biliary cirrhosis. Lancet 1997;350: 875-9. 2. Santos PS, Oliveira L, Moraes MF, Da Gra~a JP, Monteiro E, Abecasis P, et al. Granulomatous uveitis, CREST syndrome, and primary biliary cirrhosis. Br J Ophthalmol 2000;84(5):548-9. 3. Nakajima K, Komatsu M, Hoshino T, Ishida S, Goto M, Masamune 0, et al. [A case of primary biliary cirrhosis accompanied by uveitis.] Nippon Shokakibyo Gakkai Zasshi 1991 ;88(10):2686-90. 4. Forrester JV, McMenamin PG. Immunopathogenic mechanisms in intraocular inflammation. In: Streilein JW, editor. Immune response and the eye. Vol 73 of Chemical immunology (Adorini L, Arai K, Berek C, Schmitt-Verhulst AM, series editors). Basel: Karger; 1999. p. 159-85. 5. Jones DEJ, Bassendine MF. Primary biliary cirrhosis. J Intern Med 1997;241:345-8. 6. Johnson LA, Wirostko E, Wirostko BM. Experimental murine chronic hepatitis: results following intrahepatic inoculation of human uveitis Mycoplasma-like organisms. Int J Exp Patholl993;74(4):325-3l. 7. Powell FC, Schroeter AL, Dickson ER. Primary biliary cirrhosis and the CREST syndrome: a report of 22 cases. Q J Med 1987;62:75-82. 8. Tsianos EV, Hoofnagle JH, Fox PC, Alspaugh M, Jones EA, Schafer DF, et al. Sjogren's syndrome in patients with primary biliary cirrhosis. Hepatology 1990; 11 :730-4. Key words: primary biliary cirrhosis, anterior uveitis, keratoconjunctivitis sicca, Schirmer 1 test, antimitochondrial antibody