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Goodpasture’s syndrome is an autoimmune disease caused by IgG directed against the alpha-3 chain of type IV collagen found in basement membrane. It causes pulmonary haemorrhage and renal failure. The antibody has been demonstrated in the basement membranes in the eye. However, ophthalmological complications in Goodpasture’s syndrome are rare. As with other autoimmune diseases, Goodpasture’s syndrome patients have a strong susceptibility based on a genetic background.1 Much evidence supports the concept that cross reactivity with exogenous epitopes or insult to the basement membrane can initiate the process of autoimmunity resulting in Goodpasture’s syndrome.1 We present a case of a Chinese man in whom we believe uveitis precipitated the autoimmune reaction causing Goodpasture’s syndrome
A 77 year old Chinese man from Hong Kong presented to the eye casualty department with a 1 month history of a black patch in the centre of his visual field in the left eye. Before this he noticed floaters and a “black cloud” in the left eye. He did not complain of pain or photophobia.
Three months earlier he had an episode of acute anterior uveitis, which resolved with dexamethasone and cyclopentolate drops. His vision at that episode was 6/24 in the right eye and 6/12 in the left eye. Six months earlier he had developed septicaemia secondary to a urinary tract infection treated with a course of intravenous flucloxacillin and fusidic acid and he made a good recovery.
He came to the United Kingdom 30 years ago and returned to Hong Kong for holidays every few years. There was no family history of note.
He looked well on examination and he was apyrexial. Systemic examination was unremarkable apart from an itchy rash on both his legs and his blood pressure was 104/60.
His visual acuity was 6/9, N6 in the right eye and CF, N36 in the left eye. His right eye was white and quiet with evidence of old keratitic precipitates (KPs) only. His left eye had mutton fat KPs with ++ cells in the anterior chamber. The right fundus had a healthy disc and retinal vessels, but there were tiny white lesions at the level of the retinal pigment epithelium (RPE) which could represent drusen. In the left eye he had ++ cells in the vitreous, and similar white lesions in the fundus. There were no haemorrhages or cotton wool spots.
The fluorescein angiogram of the right eye (Fig 1) showed multiple dots of hyperfluorescence under the neuroretina at the level of the RPE, which looked more like inactive disease of the RPE and choroid rather than drusen. There was no leakage from the disc, vessels, or macula. The left eye had a similar picture with a few dilated capillaries at the disc but no leakage at the disc or the vessels. Late pictures of the left macular reveal minimal cystoid macular oedema which was confirmed by OCT. The clinical differential diagnosis was sarcoid or tuberculosis.
Investigations revealed a raised erythrocyte sedimentation rate (ESR) of 64 in the first hour and C reactive protein (CRP) of 14, but all other blood tests were normal including his full blood count, liver function tests, urea and electrolytes, serum ACE, VDRL/TPHA, ANA, ANCA, ENA, and complement C3 and C4. The lumbar puncture results were also normal with no growth and three early morning urine samples were also clear. The chest x ray was normal and a magnetic resonance imaging (MRI) of the orbits and head showed generalised ischaemia only. The Mantoux test was negative.
Investigations were unhelpful so he was treated symptomatically with dexamethasone 0.1% and cyclopentolate drops and an orbital floor injection of 40 mg of Kenalog (triamcinolone) in 1 ml.
The following week he was reviewed in clinic. His left eye had improved to 6/12, N8. However, he complained of generally feeling unwell with dizziness and nausea. There was no temperature or vomiting.
A blood test revealed that he was in acute renal failure with sodium of 125, potassium 6.9, urea 56.9, and creatinine 1681. ESR was 120, FBC 8.0, WCC 10.2, and platelets of 610. Liver function tests were normal apart from albumin of 21. He underwent haemodialysis and a renal biopsy showed Goodpasture’s disease (Fig 2). His glomerular basement membrane antibodies (ELISA confirmed by western blot) were also positive with a level of 77% (0–15 reference range), as were his PEG immune complexes. ANA, ANCA, and anti-DNA were all negative. He was given high dose steroids and had a course of plasma exchange (three 3 litre volume exchanges with FFP/PPF replacement).
His eyes continued to improve during the following month and the inflammation settled. At last review his visual acuity was 6/9 right eye and 6/12 left eye. Unfortunately, he developed haemoptysis and overwhelming septicaemia and died 2 months later. A post mortem was declined.
In 1919 Ernest Goodpasture described a patient with haemoptysis, anaemia, and proteinuria and a post mortem showing pulmonary alveolar haemorrhage and proliferative glomerulonephritis. Goodpasture’s disease is a rare autoimmune organ specific disease in which IgG antibodies are directed against the NCl domain of the alpha-3 chain of type IV collagen2 leading to pulmonary haemorrhage, glomerulonephritis, and renal failure. Goodpasture’s syndrome, however, describes Goodpasture’s disease with either haemoptysis or crescentic glomerulonephritis, or both.1 Clearly, this patient had the complete syndrome. Thirty per cent of patients are ANCA positive1 and lung or kidney biopsy shows linear immunofluorescent staining for IgG along the basement membrane.3 The death rate has drastically improved from 75% to 25% with the advent of plasmapheresis combined with immunosuppressants.4 However, it is rare to escape irreversible dialysis dependency unless the disease is detected and anti-GBM antibody levels are reduced before oliguria has ensued.
Immunofluorescent and immunohistochemistry studies show that the deposition of the antibasement membrane antibodies can also occur in the eye in the basement membrane of the choroidal vessels, ciliary body, lens capsule, and Bruch’s membrane.3,5 The pathogenic significance of this is still unknown. Furthermore, there have not been any studies confirming the actual presence of type IV collagen or of the alpha-3 epitope in the eye, although it is widely assumed that they are both present.
Documented ophthalmological abnormalities in Goodpasture’s include retinal haemorrhages and exudates6 and serous retinal detachment.5,7 It is possible that these signs may reflect hypertension or ANCA positivity rather than direct damage from antiglomerular basement membrane antibodies possibly because of the small percentage of alpha-3 chain or its NCl domain in the eye. As the disease is so florid in the kidneys and the lung, one would expect a disease of similar severity in the eye if the antibasement membrane antibodies were pathogenic in the eye.
This man had a granulomatous panuveitis with choroidal infiltrates. These ophthalmic features have not previously been described in Goodpasture’s syndrome. The serum from his initial admission with uveitis in February, 2 months after his episode of septicaemia, was normal apart from raised ESR and CRP levels and his antiglomerular basement membrane antibodies were 9%, which is within normal limits. Four weeks later in March, the titre of antibodies had risen to a grossly abnormal level of 77%. The temporal relation of developing antiglomerular basement membrane antibodies and disease means it is likely that these complexes occurred in response to his septicaemia and produced a reactive uveitis. As type IV collagen is also found in the choroidal plexus, the uveitis may have exposed type IV collagen to the immune system causing antibody production which results in cross reactivity with the glomerular basement membrane in the kidney to produce Goodpasture’s syndrome. As with other autoimmune diseases, Goodpasture’s syndrome patients have a strong susceptibility based on a genetic background.1 Much evidence supports the concept that insult to the basement membrane or cross reactivity with exogenous epitopes can initiate the process of autoimmunity resulting in Goodpasture’s syndrome.1 Interestingly, uveitis and Goodpasture’s share some similar characteristics. The immunological profiles both involve the cytokines IL-6, IL-12, and TGFβ,8 and both are associated with HLA B7 (indicating a particularly poor prognosis in Goodpasture’s) and HLA DR 15.8
This case is extremely rare. Other events associated with the induction of anti-GBM disease in humans have included lung damage by infections such as influenza and toxin exposure with tobacco and hydrocarbons. Renal injury by ischaemia and membranous nephropathy can also induce disease. Other causes include lymphoma and adenoma.1 To our knowledge this is the first reported case where uveitis was the likely precipitating factor for the induction of Goodpasture’s disease.
Moreover, ophthalmologists should be aware of all blood test results and check the results of ordered tests. They should follow up the patient with repeated history and examination and repeat tests if the diagnosis is uncertain. Unsuspected fatal diseases as we have seen in this case, may occasionally present to ophthalmologists.