Rheumatology 2004; 43: 529-531
Rheumatology Vol. 43 No. 4 (c) British Society for Rheumatology 2004; all rights reserved
Letter to the Editor |
ANCA-associated giant cell arteritis presenting with mononeuritis multiplex and central retinal artery occlusion: a case report
Departments of Ophthalmology and Visual Sciences, and 1Medicine and Therapeutics, The Chinese University of Hong Kong, and 2Department of Anatomical and Cellular Pathology, Prince of Wales Hospital, The Chinese University of Hong Kong, Hong Kong
Correspondence to: W. M. Chan. E-mail: cwm6373{at}netvigator.com
SIR, We report a woman with temporal artery biopsy-proven giant cell arteritis coupled with high activity perinuclear-ANCA (p-ANCA) with specificity against myeloperoxidase (MPO) presenting with small and large vessel vasculitis as foot drop and central retinal artery occlusion, respectively. To the best of our knowledge, this combination of presentations has not been reported previously in the English literature. The initial clinical manifestations, high erythrocyte sedimentation rate (ESR) and high C-reactive protein (CRP), responded well to pulse methylprednisolone and pulse cyclophosphamide.
A 55-yr-old Chinese woman developed gradual weakness of her left foot followed by, 6 weeks later, an acute loss of her left eye vision. She denied jaw claudication, headache, girdle pain, fever or weight loss. Neurological examination showed left foot drop, weakness in the dorsiflexion of the left foot with power grade 1/5, and otherwise normal neurological findings. The visual acuity comprised hand movement in the left eye and 6/12 in the right. Fundoscopy revealed central retinal artery occlusion with generalized retinal and macular oedema, cherry red spot at macula, pale optic disc and sluggish blood flow in retinal arteries (Fig. 1A). Normochromic normocytic anaemia (haemoglobin 9.6 g/dl, mean cell volume 80 fl), creatinine 83 µmol/l, ESR of 130 mm/1 h and CRP of 202 mg/l were found. Indirect immunofluorescence (IIF)-documented p-ANCA positivity and enzyme-linked immunosorbent assay (ELISA)-based MPO antigen specificity were demonstrated with titres being 160 and >200, respectively. Other autoimmune markers including antinuclear antibody (ANA), anti-dsDNA and rheumatoid factor were negative. Chest radiography was normal. All neuroimaging was unremarkable. Biopsy of the left superficial temporal artery was normal. Subsequent right superficial temporal artery biopsy showed necrobiotic granuloma in the adventitia of the artery, intimal thickening with narrowing of the arterial lumen, accumulation of histiocytes and lymphocytes in the arterial wall and absence of diffuse fibrinoid necrosis as evidenced in panarteritis, strongly favouring giant cell arteritis (Fig. 1B). She was treated with pulse methylprednisolone 1 g intravenously for 3 days followed by oral prednisolone 60 mg daily. In addition, we started pulse cyclophosphamide 750 mg intravenously. Three weeks later, left foot dorsiflexion returned to full power while both titres of p-ANCA and anti-MPO showed marked decrement. Her left eye visual acuity reverted to 6/30. Inflammatory markers (ESR 15 mm/h and CRP 7.1 mg/l) were normalized.
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The association between giant cell arteritis and ANCA remains obscure despite several published studies [1–5]. Giant cell arteritis is a granulomatous necrotizing vasculitis of large arteries with predilection over cranial arteries, aorta and their branches [2], whereas ANCA is believed to play a key role in pathogenesis in a specific group of patients with small and medium-sized vessel vasculitis like Wegener's granulomatosis, polyarteritis nodosa and microscopic polyangiitis [1, 6]. Mononeuritis multiplex manifestation such as wrist drop or foot drop is extremely uncommon in giant cell arteritis and the combination of both small and large vessel vasculitic presentation may obfuscate the primary or coexisting diagnosis [3].
In the literature, there have been only a few reported cases of giant cell arteritis associated with small vessel vasculitis as mononeuritis multiplex and they have been attributed to arteritis of the vasa nervosum [5, 7]. The presentation of neuropathy preceding other giant cell arteritis symptoms was however extremely unusual [5, 7]. Among all these cases, ANCA status was either unreported or lacking. Cytoplasmic ANCA (c-ANCA) is considered to have high immunodiagnostic value in Wegener's granulomatosis whereas p-ANCA is generally believed to be less specific [3]. Central retinal artery occlusion as a complication of ANCA-associated vasculitis or Wegener's granulomatosis is extremely rare, and only a few cases have been reported [8]. The role of ANCA in giant cell arteritis, in contrast, is unclear and immunofluorescent studies addressing ANCA positivity in 153 patients have demonstrated nine (6%) with p-ANCA pattern. However, p-ANCA immunofluorescence may simulate positive results because of the presence of ANA and validation of ANCA positivity by other methods such as by ELISA is important [6].
Gross et al. [3] demonstrated p-ANCA pattern in 7 of 62 patients with giant cell arteritis. Baranger et al. [1] found no typical ANCA in 23 patients with giant cell arteritis when antigen-specific ELISA methods were used in addition to IIF. Nassberger and Andersson [4] showed p-ANCA in 2 out of 10 patients with biopsy-proven giant cell arteritis, but none of them had antibodies against MPO. All the reported cases had low incidence of ANCA in giant cell arteritis and no specific association was demonstrated upon further validation with more specific ELISA-based antibodies against MPO. ANCA cannot be used as a real marker for giant cell arteritis. In our case, the high activity of p-ANCA was confirmed with the ELISA method and it was unlikely to be an epiphenomenon related to age [4].
The temporal biopsy of our patient was highly suggestive of giant cell arteritis [9], although vasculitis of the temporal artery can also be involved in some other vasculitic syndromes such as Wegener's granulomatosis [8] and polyarteritis nodosa [10]. In such cases, the histology shows the presence of necrotizing vasculitis and absence of giant cells as the characteristic features.
In our patient, the mononeuritis multiplex with unilateral foot drop as small vessel vasculitis was seemingly in agreement with the presence of high serological titres of p-ANCA and anti-MPO. Clinical improvement correlates well with decline of the p-ANCA activity after initiation of immunosuppressants. The subsequent manifestations of central retinal artery occlusion and histology-proven giant cell arteritis are atypical and may signify the coexistence of both small and large vessel diseases.
As a result, in patients presenting with vague peripheral neuropathy and unexplained ANCA positivity, it is important to watch out actively for giant cell arteritis that carries significant ophthalmic and neurological morbidity if left untreated.
Informed consent was obtained from the patient for treatment and publication.
The authors have declared no conflicts of interest.
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