SARCOIDOSIS

SIGNS AND SYMPTOMS
Sarcoidosis is a systemic granulomatous disease of unknown etiology. Clinical findings may include a debilitating, febrile illness with cough and dyspnea, fatigue, bilateral hilar lymphadenopathy (visible upon plain film radiograph), erythema nodosum, alveolitis, acute polymyositis, arthritis, musculoskeletal anomalies, lacrimal or salivary gland infiltration or sarcoid nodules of the skin. It occurs most frequently in young adults (20 to 40 years), has a predilection for women and for races of color.

Patients diagnosed with systemic sarcoidosis have nearly 20 percent incidence of ocular involvement. The most prevalent ocular sign is unilateral, anterior, granulomatous uveitis. Less common presentations include unilateral nongranulomatous uveitis, bilateral intermediate uveitis, and bilateral chronically smoldering low-grade granulomatous ocular inflammation (Lofgren's syndrome).

The common clinical ocular findings associated with sarcoid uveitis include decreased or hazy vision, pain, photophobia, lacrimation, conjunctival injection, cells and flare in the anterior chamber, granulomatous iritis with large "mutton fat" keratic precipitates scattered over the back surface of the corneal endothelium, iritis spill over leading to anterior vitritis, true vitritis with white exudative debris in the region of the ora serrata (snowball or snowbank retinopathy) with retinal vasculitis (candle wax drippings) and phlebitis (venous sheathing).

Nodules of the iris stroma (Busacca nodules), nodules of the pupillary border (Koeppe nodules), conjunctival granulomas, band keratopathy, posterior synechiae, cataract formation, secondary glaucoma, retinal hemorrhage, retinal neovascularization, cystoid macular edema, venous occlusion, optic disc swelling, optic nerve infiltration, compressive optic neuropathy, proptosis and extra ocular muscle palsy are all documented findings.

PATHOPHYSIOLOGY
Studies underscore that lymphocytes interact with macrophages. Some postulate that CD4+ T-helper 1 cells, in concert with macrophages, produce a cascade of cytokines and chemotactic factors which result in tissue changes and granulomatous lesions that affect many tissues and allow for the multi-system, multi-symptom nature of this disease. The clinical features of sarcoidosis mimic those of rheumatologic diseases, with increasing reports of coexistent autoimmune disease; however, no one has decisively determined an association.

MANAGEMENT
Manage the ocular signs and symptoms of sarcoidosis by the findings. Manage uveitis aggressively with topical cycloplegics (e.g. homatropine 5%, scopolamine 0.25%, or atropine 1%, BID), topical steroids such as Vexol (rimexolone 1%) and Pred Forte (prednisolone acetate 1%), Q1H to QID if necessary, oral steroidal or nonsteroidal anti-inflammatories. In recalcitrant cases, you may attempt periocular subtenon steroid injections of Kenalog 40 (triamcinolone) every three to four weeks. Antimetabolites such as methotrexate and cyclosporin-A have been used effectively in patients intolerant to steroids. Add topical aqueous suppressants if intraocular pressure control is required. Topical nonsteroidal anti-inflammatory agents such as Acular (Ketorolac tromethamine) and Voltaren (diclofenac sodium), QID, may be attempted if you detect cystoid macular edema. Allow the retinologist to manage peripheral retinal neovascularization and pars planitis with panretinal photocoagulation and oral or injected steroids respectively.

The primary care physician can lead systemic management. Referral for laboratory testing across the autoimmunologic, rheumatologic, infectious and inflammatory spectrum is essential, especially for atypical uveitis or optic neuropathy. Obtain or suggest to the PCP testing for anemia, leukemia, syphilis, HIV, lupus, Lyme disease, tuberculosis, arthritis, ankylosing spondylitis and hypertension. The initial battery could include complete blood count (CBC with differential), fluorescent treponemal antibody absorption test (FTA-Abs), reactive plasma reagin (RPR), purified protein derivative with anergy panel (PPD with anergy panel), anti-nuclear antibody (ANA), angiotensin converting enzyme (ACE), Lyme titre, rheumatoid factor (RF), sickle prep, chest x-ray (CXR) and sacroiliac joint films. Tests that indicate sarcoidosis most specifically are the chest x-ray, ACE and gallium scan.

CLINICAL PEARLS

Diagnose sarcoidosis through clinical (laboratory tests and biopsy) and radiologic evidence. Up to 90 percent of patients with ocular sarcoid have abnormal chest radiographs. Lung biopsy by tracheobronchial fiber optic techniques is 90 percent accurate. Biopsy of an enlarged, potentially infiltrated lacrimal gland or conjunctival granuloma is an acceptable alternative and can be handled by most general ophthalmologists.

A simple but effective practice management tool: a dictated letter to the primary care physician explaining the ocular problem, the management, the request for lab studies and the progress reports.

Vitritis without retinitis, vasculitis or phlebitis should be considered large reticulum cell sarcoma until proven otherwise. The minimum initial work up for this form of intermediate uveitis includes, but is not limited to, CBC with differential, FTA-Abs, RPR, PPD, ANA, ACE, Lyme titre, RF and CXR.