Sarcoidosis is an idiopathic, multisystem, granulomatous disease that often involves the eyes. Ocular involvement may be the presenting sign of this disease in children. Some of the more commonly cited ocular findings include: lacrimal gland swelling, orbital granulomas, conjunctival granulomas, anterior uveitis and its sequelae, vitritis, periphlebitis, chorioretinitis, optic disc edema, and optic nerve involvement.1·2 Often, multiple findings are present in the same eye.
Interstitial keratitis also is associated with sarcoidosis, although it was found to occur in only 1% of patients, in a large series of ocular findings of this disease.1 Multiple sites of ocular involvement have not been reported in association with interstitial keratitis.
This report describes an unusual case in a 13-year-old boy, whose initial ocular manifestation of sarcoidosis was pronounced interstitial keratitis, with subsequent development of multiple, more common, ocular findings.
A 13-year-old white male presented to the Eye Clinic at the University of Wisconsin in January 1987 with a 2-year history of corneal lesions and decreased vision in the right eye. His medical history includes erythema nodosum since 1981 of both lower extremities. He had a single episode of left ankle swelling in 1986.
Examination at the time of his presentation revealed vision of 20/20 OD and 20/25 OS. The slit-lamp microscopic examination showed multiple, nummular opacities both deep and superficial of both corneas with adjacent neovascularization. The lesions were round in appearance and 1 mm to 2 mm in diameter. There was no fluorescein staining of any of the lesions. Dilated funduscopic exam revealed discrete vitreous opacities and old chorioretinal lesions inferiorally in both eyes.
Laboratory investigation at that time revealed a normal complete blood count (CBC), antinuclear antibody, nonreactive FTA-ABS. Prednisolone acetate 1%, 1 drop to both eyes, four times daily was instituted and the patient was referred to the immunology service who treated his erythema nodosum with oral steroids.
Over the next 2 years, he was seen in the ophthalmology clinic every 2 months. He was treated with topical Pred Forte for varying degrees of anterior chamber inflammation.
In February 1989, he was again seen for routine exam without further eye complaints. His vision was 20/200 right eye and 20/20 left. His anterior segment examination was stable but his ophthalmoscopic examination revealed optic nerve swelling in the left eye greater than in the right, a single active chorioretinal lesion in the right eye, and 2 + vitreous cells in both eyes. Goldmann visual fields revealed slight constriction in both eyes, but no central scotoma. A magnetic resonance imaging was normal as was examination of his cerebral spinal fluid. Laboratory tests revealed elevated alkaline phosphatase 306 (normal: 50300), GGT 100 (normal: 0-30), AST 72 (normal: 0-50), and LDH total 366 (normal: 150-250). Normal lab values included CBC, sed rate, BUN, Cr, PO4, uric acid, albumin, ANA, antiparietal antibody, mitochondrial antibody, and smooth muscle antibody. No angiotensin converting enzyme was performed at this time as sarcoid was not suspected. The optic disc swelling was thought to be secondary to the intraocular inflammation and 40 mg of prednisone was instituted daily. From February 1989 through July 1989, the optic nerve swelling gradually diminished. His vision remained 20/200 in the right eye and 20/20 in the left eye with treatment.
FIGURE 1: The right cornea demonstrating 0.5- to 1.5-mm nebular corneal opacities. Vessels may be seen in each quadrant. There was no fluorescein staining over any of the lesions.
He was stable until May 1990 when he developed headaches for a 2-week period. A computed tomography (CT) scan performed at the local hospital was reported as normal. He complained of diplopia and was referred to the neurology service at the University of Wisconsin. History obtained at his presentation included dyspnea on exertion.
A chest radiograph revealed increased interstitial markings in the bases of both lung fields. All lab tests as listed above were repeated, finding only mild elevation of liver functions. At this point, the constellation of findings, including erythema nodosum, intersitial keratitis, optic nerve swelling, arthritis, and pulmonary changes, were felt to be consistent with a diagnosis of sarcoidosis. The patient was again treated with oral steroids, and his symptoms were brought under control. In July 1990, an angiotensin converting enzyme level was elevated at 80. Six months later, a transbronchial biopsy was performed with a finding of granulomatous inflammation with giant cells (Fig 2). GMS staining was negative for fungus and a Ziehl Neilsen stain was negative for tuberculous bacillus. He has continued to require oral steroids and additionally methotrexate to allow reduction in steroid dose.
Compliance has been, and continues to be a problem, as he intermittently finds the side effects of his medications intolerable. His vision has remained stable at 20/200 right eye and 20/20 left eye.
Sarcoidosis is a systemic granulomatous disorder of unknown etiology. Accurate assessment of its incidence has been difficult because many patients with sarcoidosis are asymptomatic or only mildly affected, and thus do not seek medical attention. In the United States, best estimates are that sarcoidosis occurs in 1 in 10 000 people per year,3 making for some 25 000 cases annually. It affects African Americans 10 times more frequently than Caucasians, and is more common among those of Northern European descent. Sarcoidosis primarily affects young adults, although people of all ages have been affected. The symptoms of sarcoidosis usually are secondary to local infiltration and tissue injury by noncaseating granulomas, and are thus dependent on the organs involved. While sarcoid granulomas have been reported in every organ of the body, the most commonly affected sites include the lungs, skin, and eyes.
FIGURE 2: Histologic section of tissue obtained from transbronchial biopsy. Note the Langhan's type giant cell (black arrows).
Typically, one third of patients with sarcoidosis are asymptomatic at the time of diagnosis, the initial abnormality being detected on a chest radiograph performed for other reasons. Of symptomatic patients, pulmonary symptoms are the most frequent presentation. Obenauf et al found ocular manifestations to be the second most frequent presentation in symptomatic patients.1
Pediatric presenting complaints differ by age group. Children age 5 years and younger are usually noted to have arthritis, rash, or uveitis.4 Despite a 77% incidence of uveitis, eye pain and photophobia are uncommon in the 5 and younger age group. 5In a series of patients age 8 to 15 years, the initial presentation is usually constitutional or respiratory.6·7 Uveitis is noted to occur in 32% of children age 8 to 15 years.6"8 The initial ophthalmic presentation in our patient was decreased vision due to intersititial keratitis although erythema nodosum and arthritis occurred previously. Ultimately, symptoms of diplopia led to his confimatory transbronchial biopsy.
Apart from band keratopathy, corneal involvement in sarcoidosis is rarely described. Obenauf et al, in their large series, listed interstitial keratitis as occurring in 1% of patients, but did not describe any specific cases.1 GifFord reported corneal involvement in 3 of 10 cases in his 1941 article.9 In only one of these cases are corneal lesions similar to our own described but without vascularization.
Interstitial keratitis refers to nonsuppurative infiltration and vascularization of the corneal stroma. It usually is associated with systemic disease, most commonly congenital or acquired syphilis, and rarely with sarcoidosis.10 Nummular keratitis, on the other hand, is a form of interstitial keratitis characterized by multiple, coinshaped opacities in the corneal stroma, with sarcoidosis listed as a rare cause. Other conditions associated with nummular keratitis include: tuberculosis, Padi keratitis, Dimmer's nummular keratitis, herpes zoster, herpes simplex, leprosy, syphilis, onchocerciasis, and epidemic keratoconjunctivitis. 11
This case demonstrates the rare occurrence of interstitial keratitis in sarcoidosis. The tissue diagnosis was obtained on transbronchial biopsy. As with many other ocular inflammatory disorders, interstitial keratitis should be evaluated in the context of other symptoms and signs and a diagnosis of sarcoidosis should be considered.
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