Nodular scleritis as a presenting feature of Takayasu's arteritis.

Takayasu, a Japanese ophthalmologist, was the first to describe the disease in 1908.[1] Takayasu's disease has an incidence of 2.6/million/year with a female to male ratio of 9:1.[2] Takayasu's retinopathy (TR) is the most common ophthalmic manifestation. It reflects ocular hypoperfusion and is manifested by microaneuryms, arteriovenous anastomosis, and neovascular complications. Hypertensive retinopathy is less frequently encountered. Retinal arterial occlusion was recently reported as well.[3] Smith and Rosenbaum suggested a real association between Takayasu's arteritis (TA) and scleritis because of the strong temporal relationship between the two conditions in their patient. Jain et al.[4] have published a report that describes a case of TA occurring in association with scleritis.

Case Report

A 44-year-old, (Indian) female was referred to our rheumatology clinic by an ophthalmologist with a history of fluctuating redness in both eyes with ocular pain. She was diagnosed as nodular scleritis and referred for systemic evaluation. On inquiry, she also gave a history of polyarthritis, lasting for 2-3 weeks, 10 years back, it had responded to symptomatic treatment. She also gave a history of intermittent claudication in the right arm, especially during activities such as washing clothes or utensils, for the past 10 years. She was a nonsmoker and had taken oral nonsteroidal anti-inflammatory drugs for arm pain from her general practitioner (GP) without much relief. On inquiry, she also gave a history of recurrent headaches. She did not have any sinusitis, nasal discharge, hemoptysis, skin rash, and fever or weight loss.

On ocular examination, her visual acuity was 20/20 oculus uterque and there was evidence of nonnecrotizing nodular scleritis in her right eye [Fig. 1] without any evidence of thinning bilaterally. There was no evidence of retinal vasculitis on dilated fundoscopy.

Figure 1

Right eye nodular scleritis

On examination, her right radial pulse was absent without any subclavian bruit. The blood pressure in the right upper limb was not recordable, whereas in the left upper limb it was 140/80 mmHg, and both lower limbs 150/90 mmHg. Her investigations revealed hemoglobin 12 g/dl, white cells – 5600/cu mm, erythrocyte sedimentation rate (ESR) of 90 mmHg, and C-reactive protein (CRP) was 6.3 mg/l (normal <6). Rheumatoid factor, anti-cyclic citrullinated peptide, antineutrophil cytoplasmic antibody (ANCA), and antinuclear antibody were negative, urine examination and biochemistry were normal. Serum venereal disease research laboratory was also negative. These reports add further evidence, in addition to the history and examination, to the lack of any other collagen vascular disease whatsoever.

In view of the above findings, a working diagnosis of Takayasu's disease was made, which was further confirmed on a computed tomography (CT) aortogram [Fig. 2]. It showed thickening of the right brachiocephalic artery, with complete occlusion of the right subclavian artery, origin of the right vertebral artery was not seen.

Figure 2

Computed tomography aortogram showing thickening of the right brachiocephalic artery, with complete occlusion of the right subclavian artery (yellow arrows)

The patient was started on oral prednisolone 1 mg/kg body weight along with injection methotrexate 25 mg/week, with folate supplements. Prednisolone was tapered by 5 mg/week after a month till 20 mg/day, then 2.5 mg/week till 7.5 mg daily, calcium supplements and alendronate 35 mg/week. Her attacks of recurrent scleritis subsided [Fig. 3], but right arm claudication persisted for which she underwent right subclavian artery stenting, with moderate symptomatic improvement.

Figure 3

Right eye follow-up clinical photo, 6 months after starting immunosuppressive therapy

Discussion

TA is a rare chronic obliterative vasculitis affecting the aorta and its major branches. It is more commonly seen in females of reproductive age and is more prevalent in Asian and Latin American countries. Although the pathogenesis has not been entirely elucidated, TA is considered to be a T-cell-mediated granulomatous vasculitis.[5]

Our patient satisfied 5 out of 6 American College of Rheumatology (ACR) criteria for TA, and she also had associated constitutional symptoms such as headache and malaise.[6] As per ACR 1990 criteria,[7] a patient is diagnosed as TA if she satisfies 3 out of 6 of the following criteria:

Age at disease onset <40 years

Claudication of extremities

Decreased brachial artery pulse

BP difference >10 mmHg between arms

Bruit over subclavian arteries or aorta

Arteriogram abnormality, arteriographic narrowing, or occlusion of the entire aorta, its primary branches or large arteries in the proximal upper or lower extremities, not due to arteriosclerosis, fibromuscular dysplasia, or similar causes; changes usually focal or segmental.

Ocular features of TA are a manifestation of the vasculitis and can affect anterior segment as in necrotizing scleritis, or the posterior segment as retinal vasculitis, with features of neovascularization and its associated complications. A study by Chun et al.[8] concluded that in patients with TA, no retinopathy was found in 87 (55.8%) eyes, hypertensive retinopathy was found in 48 (30.8%) eyes, and TR was found in 21 (13.5%) eyes. Patients with TR had carotid artery or aortic arch involvement. Arteritis involving the aortic arch and its branches favors the development of ischemic ocular complications.[9]

TR is a specific entity and it has been classified into four stages.[10]

Stage 1: TR is characterized by distension of veins

Stage 2: By microaneurysm formation

Stage 3: By the formation of arteriovenous anastomoses and

Stage 4: By the presence of ocular complications such as cataract, rubeosis iridis, retinal ischemia, neovascularization, and vitreous hemorrhage.

Management of TA involves systemic immunosuppression, stenting/angioplasty for relieving vascular occlusion, and surgical management of scleral thinning and/or proliferative retinopathy.

Takayasu's disease presenting as scleritis is very rare and likely to be overlooked by the general ophthalmologist. The 5 years mortality of TA being 35%,[11] it is an important diagnosis which may often be apparent after thorough history and examination. Other systemic diseases associated with scleritis, such as Wegener's granulomatosis, have a specific serological test like ANCA to support the diagnosis. While scleritis in rheumatoid arthritis or systemic lupus erythematosus occurs in already established disease, thus is easy to treat. As opposed to that TA is suspected on clinical evaluation and confirmed on aortogram.

Hence, it is important for ophthalmologists, especially those practicing in Asian countries to be aware of the life-threatening implications of an undiagnosed and untreated episode of scleritis, especially in middle-aged Asian female population. Certain laboratory investigations such as ESR, CRP, and appropriate vascular imaging can quickly lead to an obvious diagnosis.

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Conflicts of interest

There are no conflicts of interest.