MULTISYSTEM AUTOIMMUNE DISEASES

SYSTEMIC LUPUS ERYTHEMATOSUS

Systemic or disseminated lupus erythematosus is a multisystem disease manifested by facial "butterfly skin lesions," pericarditis, Raynaud's phenomenon, renal involvement, arthritis, anemia, and central nervous system signs. Ocular findings include episcleritis and scleritis and keratoconjunctivitis sicca (in 25% of cases). Uveitis rarely occurs, and retinal involvement produces signs of arteriolar occlusion as a result of immune complex deposition with associated choroidal vasculitis. The fundus picture may be complicated by a hypertensive retinopathy, which in severe cases can cause capillary occlusion or even proliferative retinopathy.

Pathogenesis & Diagnosis

The disease is an immunologic disorder marked by the presence of circulating immune complexes. Diagnostic tests include anti-deoxyribonucleic acid (DNA) antibodies and mitochondrial type V antibodies. Active disease is associated with raised circulating immune complexes and reduced fractions of complement.

Treatment

Systemic steroids and pulsed intravenous cyclophosphamide are most effective. Hydroxychloroquine, methotrexate, and azathioprine may be useful.

ANTI-PHOSPHOLIPID ANTIBODY SYNDROME

This diagnosis should be considered in patients with recurrent thromboembolism, recurrent fetal loss, livedo reticularis, thrombocytopenia, and neurologic disease. Visual loss may be due to retinal vein or ar-terial occlusion or ischemic optic neuropathy. Choroidal infarcts may also occur (Figure 15-3). The diagnosis is confirmed by the presence of lupus anticoagulant and high-titer IgG and IgM anticardiolipin antibodies.

DERMATOMYOSITIS

In this rare disease, there is characteristically a degenerative subacute inflammation of the muscles, sometimes including the extraocular muscles. The lids are commonly a part of the generalized dermal involvement and may show marked swelling and erythema. Retinopathy with cotton-wool spots and hemorrhages may occur. High doses of systemic corticosteroids will frequently effect a remission that continues even after cessation of therapy. The ultimate prognosis is poor, however.

SCLERODERMA

This rare chronic disease is characterized by widespread alterations in the collagenous tissues of the mucosa, bones, muscles, skin, and internal organs. Individuals of both sexes between 15 and 45 years of age are affected. The skin in local areas becomes tense and leathery, and the process may spread to involve large areas of the limbs, rendering them virtually immobile. The skin of the eyelids is often involved. Iritis and cataract occur less frequently. Retinopathy similar to that which occurs in lupus erythematosus and dermatomyositis may be present. Systemic corticosteroid treatment improves the prognosis.

POLYARTERITIS NODOSA

This collagen disease affects the medium-sized arteries, most commonly in men. There is intense inflammation of all the muscle layers of the arteries, with fibrinoid necrosis and a peripheral eosinophilia. The main clinical features include nephritis, hypertension, asthma, peripheral neuropathy, muscle pain with wasting, and peripheral eosinophilia. Cardiac involvement is common, though death is usually caused by renal dysfunction.

Ocular changes are seen in 20% of cases and consist of episcleritis and scleritis, which is often painless (see Chapter 7). When the limbal vessels are involved, guttering of the peripheral cornea may occur. A retinal microvasculopathy is common. Sudden dramatic visual loss may be due to ischemic optic neuropathy reflecting the severity of the vasculitis in the ciliary vessels or to a central retinal artery occlusion. Ophthalmoplegia may result from arteritis of the vasa nervorum (Figure 15-31). Systemic corticosteroids and cyclophosphamide are of some value. A few patients have a monophasic disease that resolves completely, but in the remainder the long-term prognosis is uniformly bad.

WEGENER'S GRANULOMATOSIS

This granulomatous process shares certain clinical features with polyarteritis nodosa. The three diagnostic criteria are (1) necrotizing granulomatous lesions of the respiratory tract, (2) generalized necrotizing arteritis, and (3) renal involvement with necrotizing glomerulitis.

Ocular complications occur in 50% of cases, and proptosis resulting from orbital granulomatous formation occurs with associated ocular muscle or optic nerve involvement (Figure 15-32). If the vasculitis affects the eye, conjunctivitis, peripheral corneal ulceration, episcleritis, scleritis, uveitis, and retinal vasculitis may occur. Nasolacrimal duct obstruction is a rare complication.

Antineutrophil cytoplasmic antibodies are present in most cases and have both diagnostic and prognostic value. Combined corticosteroids and immunosuppressives (particularly cyclophosphamide) often produce a satisfactory response.

RHEUMATOID ARTHRITIS

Rheumatoid arthritis, a disease that is more common in women than in men, rarely presents with uveitis, but scleritis and episcleritis are comparatively common. The scleritis may herald exacerbation of the systemic disease, tends to occur with widespread vasculitis and may lead to scleromalacia perforans (see Chapter 7).

Corticosteroid drops are helpful in episcleritis or anterior uveitis, but systemic treatment (nonsteroidal anti-inflammatory agents and corticosteroids) is necessary for scleritis. Keratoconjunctivitis sicca is present in 15% of cases (see Chapter 4). Peripheral corneal melting may occur in more severe cases.

JUVENILE RHEUMATOID ARTHRITIS (Still's Disease)

Ocular complications of Still's disease occur three times more frequently in girls with pauciarticular disease. The systemic disease appears to be disproportionately mild in children with severe visual loss, and diagnosis and treatment may therefore be delayed. Ocular involvement may occur before joint involvement. A chronic insidious uveitis with a high incidence of anterior segment complications develops (eg, posterior synechiae, cataract, secondary glaucoma, band-shaped keratopathy). Antinuclear antibodies are positive in 88% of patients with juvenile rheumatoid arthritis who develop uveitis, whereas they are positive in only 30% of the group as a whole.

SJöGREN'S SYNDROME

Sjögren's syndrome is a systemic disorder with diverse features. The disease is characterized by the clinical triad of keratoconjunctivitis sicca, xerostomia (dryness of the mouth), and a connective tissue disease, usually rheumatoid arthritis. It is more common in females. The onset of ocular symptoms occurs most frequently during the fourth, fifth, and sixth decades. Lymphoid proliferation is a prominent feature of Sjögren's syndrome and may involve the kidneys, the lungs, or the liver, causing renal tubular acidosis, pulmonary fibrosis, or cirrhosis. Lymphoreticular malignant disease such as reticulum cell sarcoma may complicate the benign course of Sjögren's syndrome many years after its onset.

The histopathologic changes in the lacrimal gland consist of infiltration of lymphocytes, histiocytes, and occasional plasma cells leading to atrophy and destruction of the glandular structures. These changes are part of the generalized polyglandular involvement in Sjögren's syndrome, which results in dryness of the eyes, mouth, skin, and mucous membranes.

Because of the relative inaccessibility of the lacrimal gland, the labial salivary gland biopsy serves as an important diagnostic procedure in patients with suspected Sjögren's syndrome.

Tear lysozyme and lactoferrin levels are absent or reduced in over 90% of patients, and very high titers of nuclear antibodies are present.

GIANT CELL ARTERITIS (Including Temporal or Cranial Arteritis)

This is a disease of elderly patients (mostly women over age 60). Medium-sized arteries are involved, particularly the intima of the vessels. Branches of the external carotid system are frequently involved, though pathologic studies have shown more diffuse arterial involvement. Polymyalgia rheumatica may precede or accompany the disease. Patients feel ill and have excruciating pain over the temporal or occipital arteries. Visual loss due to an ischemic optic neuropathy is frequent, and a few cases have a central retinal artery occlusion. Visual loss may also be due to cortical blindness. Other central nervous system signs include cranial nerve palsies and signs referable to brain stem lesions. The diagnosis is confirmed by a high erythrocyte sedimentation rate (ESR) and a positive temporal artery biopsy. In early stages of the disease, the ESR may be normal, but usually it is 80-100 mm in the first hour. It is important to make the diagnosis early, because immediate systemic corticosteroid administration produces dramatic relief of pain and prevents further ischemic episodes. The disease activity is monitored by the erythrocyte sedimentation rate and the clinical state. The cortico-steroid dose may have to be maintained for several years and should be kept below 5 mg prednisolone daily if possible, since with higher doses toxic effects develop.

IDIOPATHIC ARTERITIS OF TAKAYASU (Pulseless Disease)

This disease, found most frequently in young women and occasionally in children, is a polyarteritis of unknown cause with increased predilection for the aorta and its branches. Manifestations may include evidence of cerebrovascular insufficiency, syncope, absence of pulsations in the upper extremities, and ophthalmologic changes compatible with chronic hypoxia of the ocular structures. Ophthalmodynamometry may be of value by demonstrating decreased carotid blood flow on one or both sides.

Thromboendarterectomy, prosthetic graft, and systemic corticosteroid therapy have been reported to be successful.

ANKYLOSING SPONDYLITIS

Ankylosing spondylitis occurs mainly in males 16-40 years of age. In most cases, an intermittent anterior uveitis is seen, but in a minority anterior and posterior uveitis exists with glaucoma and cataracts developing in the long term. In a few cases, aortic valve disease is also seen (see Chapter 7). There is a strong association with HLA-B27. Antigenic cross-reactivity is present between HLA-B27 and Klebsiella pneumoniae, but the etiology remains poorly understood.

REITER'S DISEASE

The diagnosis of Reiter's disease is based on a triad of signs that includes urethritis, conjunctivitis, and arthritis (see Chapter 16). Scleritis, keratitis, and uveitis may also be seen in addition to conjunctivitis.

BEHÇET'S DISEASE

Behçet's disease consists of the clinical triad of relapsing uveitis and aphthous and genital ulceration (  Figure 15-33). Ocular signs occur in 75% of cases; the uveitis is severe, occasionally associated with hypopyon. Visual loss is due to inflammatory changes in the retinal vessels and retina, and there is a propensity to microvascular venous occlusions and retinal infiltrates. Treatment often involves multiple immunosuppression (eg, steroids, cyclosporine, azathioprine), but despite manipulation with these drugs the visual outcome is bad in 25% of cases. Ocular involvement is associated with the HLA-B5 haplotype.

10.1036/1535-8860.ch15

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