Granulomatous uveitis, CREST syndrome, and primary biliary cirrhosis

CASE REPORT

A 48 year old woman with a longstanding history of Raynaud's phenomenon complained of blurred vision in the right eye over the past 3 months for which she had not sought medical attention. Ophthalmological examination revealed diminished visual acuity (VA) in the right eye to counting fingers. VA in the left eye was normal. Pupillary light reflexes were normal. A 5 minute basal tear production test was 5 mm in the right eye and 12 mm in the left. Slit lamp examination showed mutton fat keratic precipitates, flare, and cells (1+) in the anterior chamber and vitreous (anterior and posterior) of both eyes, and a right eye posterior subcapsular cataract accounting for the visual loss. The fundi were normal without any signs of vasculitis or pars planitis. General clinical examination revealed microstomia, facial telangiectasias, sclerodactyly, and multiple finger pulp cutaneous infarcts.

Laboratory investigations showed raised serum aspartate aminotransferase (131 U/l, normal 0–40 U/l), alanine aminotransferase (154 U/l, normal 7–56 U/l), γ glutamyltransferase (274 U/l, normal 8–78 U/l), and alkaline phosphatase (471 U/l, normal 38–126 U/l). Serum bilirubin, calcium, and angiotensin converting enzyme levels were normal. The serum albumin was also normal (38.6 g/l) as was the prothrombin time (12.4 seconds). The serum IgM was 3.66 g/l (normal 0.60–2.63 g/l) whereas IgG and IgA levels were normal. RA test was 46.2 U/ml (normal 0–20 U/ml), Waaler-Rose was negative, and circulating immune complexes were detected at a level of 2.80 mg/l (normal <1.5 mg/l). Complement levels were normal. Antinuclear antibodies were positive (>1:1280) with a speckled pattern. Anticentromere, antimitochondrial (>1:100), and anti-M2 antibodies were also positive. There was no evidence of past or present hepatitis C or hepatitis B infection. The VDRL was non-reactive and Lyme, toxoplasma, CMV, and HIV serologies were negative. The HLA phenotype was A1, A9, B17, Bw4, Cw4, Cw6, DR5, DR52, DR8, DQ4, DQ7.

A chest x ray was normal and a radiograph of the hands revealed subcutaneous calcinosis. The Mantoux test (2 units) was anergic. There was no evidence of pathergy. The liver biopsy showed stage III PBC.

This patient was treated with ursodeoxycholic acid, calcium, vitamin A and D supplements. Topical corticosteroids and oral prednisolone 60 mg/day were also started. Systemic steroids were tapered to 10 mg/day after 2 months, and then slowly tapered over the next 4 months until they were discontinued. There was a temporary increase in liver enzymes (AST, 167 U/l; ALT, 313 U/l; GGT, 774 U/l) which returned to baseline values soon after steroids were stopped. The uveitis resolved and 5 months later, on no eye medication, she underwent cataract surgery successfully, significantly regaining vision in that eye (best corrected visual acuity = 1.0).

COMMENT

In PBC, CREST, and uveitis abnormalities of the humoral and cellular immune systems are common. These include increased levels of serum immunoglobulins, the presence of circulating autoantibodies, increased turnover of complement, the presence of activated T and B cells in the peripheral blood and impaired T cell regulation.1 4Despite the high frequency of these immunological abnormalities, a definite immunopathogenetic mechanism has not yet been clearly established for any of these disorders. Furthermore, no single mechanism seems to provide a link between these clinical entities. A mouse model for the development of liver damage through the intrahepatic inoculation of mycoplasma-like organisms, which cause human chronic uveitis, has recently been developed,5 but it remains a hypothetical concept. Our case report illustrates an association between ocular and hepatic diseases, which may be entirely coincidental but could, nevertheless, encourage further investigation for a common immunological pathway.