Hospital for Sick Children's, The: Atlas of Pediatric Ophthalmology & Strabismus, 1st Edition

Ocular Manifestations of Systemic Disease



Alex V. Levin

Thomas W. Wilson

David Rootman

Rheumatologic diseases include the collagen vascular disorder, systemic vasculitides, and other related disorders. These diseases often have an immunologic pathophysiology. Arthritis may or may not be a key feature. The most commonly involved ocular tissue in rheumatologic diseases is the uvea: the iris, ciliary body, and choroid. Manifestations include any combination of anterior uveitis, posterior uveitis, vitreitis, paras planitis (intermediate uveitis), papillitis, or panuveitis. Complications from chronic uveitis include glaucoma, cataract, band keratopathy, and cystoid macular edema. Significant visual loss and amblyopia are common in undertreated patients and those with chronic ocular involvement. Treatments of systemic rheumatoid diseases will often have toxic effects on the ocular tissues. Systemic steroids may cause posterior subcapsular cataracts and steroid-induced glaucoma. Hydroxychloroquine may cause retinal toxicity with long-term use.

The ophthalmologist plays several roles in the care of children with rheumatologic disease. Some disorders, such as juvenile idiopathic arthritis, require periodic screening to detect the first signs of ocular involvement. Other patients with chronic rheumatologic disease will present to their rheumatologist or pediatrician with an ocular complaint that prompts referral to the ophthalmologist. Lastly, the ophthalmologist may make a diagnosis of an ocular manifestation of an underlying rheumatologic disorder that has not yet been diagnosed. The classic example is the onset of iritis prior to the development of the joint manifestations of juvenile idiopathic arthritis, a sequence that occurs in approximately 10% of affected patients.

Collaboration between the pediatrician or rheumatologist and the ophthalmologist is essential for the management of ocular manifestations of rheumatologic disease. In addition to the diagnostic collaboration, the nonophthalmologist is often the key physician in the management of systemic medications such as prednisone, methotrexate, antitumor necrosis factor agents, or other immunosuppressants. Likewise, the ophthalmologist often provides the screening that is required to ensure that patients do not develop systemic side effects of these medications.



Figure 27.1 Juvenile Idiopathic Arthritis—Papillitis

Juvenile idiopathic arthritis (also known as juvenile rheumatoid arthritis or juvenile chronic arthritis) is the most common rheumatologic disease of childhood and the most common identifiable cause of iritis. The iritis is usually granulomatous and the response to steroids may be variable. The iritis may be a single acute event, recurrent, or chronic. Pauciarticular and polyarticular forms occur with some patients starting as the former and evolving into the latter. At younger ages, antinuclear antibody–positive, rheumatoid factor–negative, pauciarticular girls are more commonly affected. There is no correlation between severity or activity of the joint and eye disease. Although an uncommon manifestation, this photograph shows papillitis with hyperemia and swelling of the optic nerve, which portends a poor visual outcome.


Figure 27.2 Juvenile Idiopathic Arthritis—Granulomatous Uveitis

Approximately 20% of patients with juvenile rheumatoid arthritis will develop anterior uveitis. The severity of uveitis can range from mild anterior chamber reaction to severe chronic uveitis. Granulomatous uveitis with “mutton fat” keratoprecipitates is an uncommon presentation. Even hypopyon may rarely be seen as well as vitritis, pars planitis (Fig. 27.17), or panuveitis. Initial treatment would include high-dose topical prednisolone and a mydriatic agent. Following the resolution of the uveitis, the steroids should be tapered slowly over several weeks or months as tolerated. Adjunct interventions may be required including sub-Tenon depot steroid injections, methotrexate, antitissue necrosis factor agents, or, less commonly, immunosuppressive agents such as cyclosporine or azathioprine.


Figure 27.3 Juvenile Idiopathic Arthritis—Serous Retinal Detachment

The serious retinal detachment in this photograph is an uncommon manifestation of juvenile rheumatoid arthritis. It is usually confined to those cases with severe chronic uveitis and often optic nerve involvement as well. There is often an overlying vitritis. With aggressive treatment of the uveitis and vitritis, the detachment may settle although the visual prognosis is very guarded, particularly if cystoid macular edema has occurred.




Figure 27.4 Juvenile Idiopathic Arthritis—Vitritis

Decreased vision in juvenile rheumatoid arthritis can be secondary to amblyopia, cataract, vitreitis, band keratopathy, cystoid macular edema, and glaucoma. This photograph shows significant vitreous involvement (arrow), an uncommon but significant ocular complication indicating the need for medical interventions beyond topical therapy. Cystoid macular edema and posterior subcapsular cataract are likely to form in this setting. Note also the posterior synechiae and early cataract, which characterize this disorder.


Figure 27.5 Juvenile Idiopathic Arthritis—Cataract

This image is the most common appearance of chronic complicated anterior uveitis due to juvenile idiopathic uveitis. Note the severe posterior synechia and total white cataract. Significant synechia formation can lead to iris bombe (Fig. 27.6) with secondary glaucoma. The cataract may have started as the typical posterior subcapsular cataract, which then progresses to a total white cataract, often acutely, and sometimes with intumescence of the lens and shallowing of the anterior chamber. Phacomorphic and phacolytic glaucoma can occasionally occur. When possible, cataract surgery should be deferred until there is iritis control and a decline in visual function.


Figure 27.6 Juvenile Idiopathic Arthritis—Iris Bombe

Multiple 360-degree posterior synechia can lead to iris bombe. In addition to the synechia seen at the pupil edge, there are often broad-based synechia involving the posterior surface of the mid-iris. Aggressive mydriasis is rarely successful in breaking the synechia and laser iridotomy may also be difficult as well as proinflammatory with a high incidence of hyphema. Therefore, surgical intervention may be required and would include breaking of the synechia, cataract surgery if needed, and a surgical iridectomy.




Figure 27.7 Dermatomyositis—Heliotrope

Dermatomyositis is an idiopathic inflammatory myopathy characterized by proximal muscle weakness. This child demonstrates two of the oculofacial manifestations: A malar erythematous rash and a %variant of a heliotrope rash involving the upper eyelids. The clinical features of dermatomyositis include proximal muscle weakness and cutaneous abnormalities. Intraocular involvement is very rare. The external involvement requires no intervention, although it may be associated with increased systemic disease activity.


Figure 27.8 Dermatomyositis—Heliotrope

Note the purplish supraciliary discoloration that on high power may be associated with small vessel telangiectasia. This is an often-missed sign of the disease. Other ocular involvement may be from the ocular side effects of steroids, in particular subcapsular cataracts, and these are more common than the intraocular effects of the disease. The heliotrope is not painful or pruritic and is rarely associated with edema or fever, thus differentiating it from periorbital cellulitis (Chapter 11: Orbit, Fig. 11.8) or allergy.


Figure 27.9 Dermatomyositis—Gottron Sign

Gottron papules and Gottron sign are pathognomonic cutaneous manifestations of dermatomyositis. Gottron papules are erythematous papules on the dorsal surface of the metacarpophalangeal and proximal interphalangeal joints. Gottron sign is demonstrated in this photograph, which consists of scaly, erythematous plaques on the dorsal metacarpophalangeal and interphalangeal joints. Similar patches may occur on the elbows, knees, or medial malleoli. Although there is no correlation between these signs and the absence or presence of ocular involvement, they do denote that the child likely has dermatomyositis.




Figure 27.10 Dermatomyositis—Lid Lesion

This excavated “pox” lesion (arrow) is characteristic of dermatomyositis and is noted after a period of disease activity with or without heliotrope. It is similar to the excavated scar of primary varicella infection (Chapter 19: Infectious Diseases, Fig. 19.7) but is distinguished by its solitary nature and location. Similar lesions may occur elsewhere but the lid is a common site. This child has a typical excavated lesion on the medial aspect of his left upper lid.


Figure 27.11 Systemic Lupus Erythematosus

Systemic lupus erythematosus is a chronic inflammatory disease that affects the skin and may have associated synovitis, pericarditis, pleuritis, nephritis, vasculitis, and cerebral involvement. The most common cutaneous manifestation is a malar butterfly rash, shown here. The skin is erythematous, edematous, and often indurated. Typically, the rash extends from the malar region across the bridge of the nose. The facial rash is not necessarily correlated with particular systemic manifestations or ocular involvement.


Figure 27.12 Lupus Retinitis

Ocular manifestations of lupus include dry eye, eyelid lesions, and retinal vascular lesions. The most common retinal manifestation of systemic lupus erythematosus includes characteristic large amorphous cotton-wool spots, which represent infarctions of the nerve fiber layer. The presence of cotton-wool spots often correlates well with the activity of the systemic illness. Severe ischemia and vascular congestion can also occur, often with exudates and retinal hemorrhage. The visual acuity in both patients was significantly reduced. The retinopathy will often respond to systemic treatment for the lupus. Visual recovery can occur.




Figure 27.13 Kawasaki Disease— Conjunctivitis

Kawasaki disease (mucocutaneous lymphadenopathy syndrome) is an autoimmune vasculitis that presents with high fever, cervical lymphadenopathy, desquamation of the extremities, mucous membrane inflammation, and an erythematous exanthem. Ocular manifestations are one of the cardinal features, in particular a bilateral nonpurulent bulbar conjunctivitis. Anterior uveitis can also be associated with this disease, but the course is usually mild and self-limited, and may not require pharmacologic treatment. Retinal involvement is very rare.


Figure 27.14 Kawasaki Disease— Rash

Although the desquamating skin disorder in Kawasaki disease more typically involves the hands and feet, involvement of the groin, as seen in this older child, may also occur. Treatment of Kawasaki disease initially involves immunoglobulins and aspirin. The role of corticosteroids is unclear and there is some concern that they may increase the risk for coronary aneurysm, the major cause of outcome morbidity and mortality. There is no known correlation between ocular and cardiac involvement.


Figure 27.15 Behçet Disease

Behçet disease is an autoimmune disorder that has a higher incidence in patients of Far Eastern or Mediterranean descent. The major features are aphthous ulcers of the gastrointestinal tract, genital ulcers, and erythema nodosum. Ocular manifestations include severe bilateral anterior uveitis with hypopyon. The uveitis is nongranulomatous and is typically associated with posterior synechiae and cataract. Posterior uveitis presents as a vaso-occlusive retinitis with vitreous inflammation. Aphthous ulcers occur in most patients with Behçet disease. The ulcers shown here are typically located on the gums and the soft palate. The lesions are painful and recurring, and can last weeks.




Figure 27.16 Scleroderma

Scleroderma is a systemic disease of connective tissue that is characterized by inflammation and subsequent degeneration and fibrosis. The skin and skeletal muscle are most commonly affected, but the gastrointestinal tract, respiratory system, heart, and kidneys can be affected. Ocular manifestations include keratoconjunctivitis sicca and conjunctival fibrosis with shortening of the inferior fornix. Linear scleroderma, also known as morphea, is a localized form of scleroderma that can involve the forehead or one side of the face, as shown here. It may begin as a localized yellow or hypopigmented patch of hard taught skin. A depression in the affected area leads to progressive deformation that has also been given the name “coup de sabre.” Ipsilateral or, rarely, bilateral uveitis may occur.


Figure 27.17 Pars Planitis

Pars planitis or intermediate uveitis is an ocular inflammatory disorder of the uveal tissues in the ciliary body and anterior choroid that affect young adults and children. Patients present with significant anterior vitreous involvement (Fig. 27.4), which can be complicated by cataract and macular edema. Although pars planitis may be an isolated idiopathic disorder, associated systemic diseases include Lyme, sarcoidosis (Chapter 25: Pulmonary, Figs. 25.1 and 25.2), and multiple sclerosis (Chapter 21: Neurologic, Fig. 21.11). Patients will often complain of decreased vision with floaters due to vitritis aggregates of inflammatory debris, as shown here. Some patients will have the classic snow banking on the pars plana. Differential diagnosis would include other infectious causes of uveitis and vitritis. Treatment is periocular and/or systemic.


Figure 27.18 Sjögren Syndrome— Raynaud Phenomena

Sjögren syndrome is an autoimmune disorder characterized by chronic inflammation of the salivary glands, lacrimal glands, and connective tissues. Patients typically present with xerostomia (dry mouth), xerophthalmia (dry eye), and arthritis. This patient demonstrates severe Raynaud phenomenon: Vascular occlusion secondary to cold environment, which initially appears as blanching followed by reflex erythema, but in this case ultimately led to necrosis. Diagnosis is made on clinical findings and by the presence of Ro/SSA and La/SSB antibodies. Artificial tears and immunosuppressive therapy are the mainstays of treatment.