Scleritis—Infectious Versus Inflammatory

US Ophthalmic Review, 2016;9(2):92–6 DOI: https://doi.org/10.17925/USOR.2016.09.02.92

Abstract:

Scleritis refers to a heterogeneous group of diseases characterized by a severe painful inflammatory process of the sclera, that may also involve the cornea, adjacent episclera, and underlying uveal tract. It is associated with significant ophthalmic and systemic morbidity. Scleritis sometimes occurs in an isolated fashion, without evidence of inflammation in other organs. However, in up to 50% of patients, scleritis is associated with an underlying systemic illness such as rheumatoid arthritis or granulomatosis with polyangiitis. Infection is an important but rare cause of scleritis, occurring in about 5–10% of all cases. Due to the similarity of its presentation, infectious scleritis is often initially managed as autoimmune, potentially worsening its outcome. Careful clinical history taking (including history of ocular surgery), detailed ocular examination, appropriate investigation for ocular disease with or without underlying systemic disease, and timely intervention has improved the long-term outcome for patients with this disease.
Keywords: Scleritis, infectious, autoimmune, vasculitides, pterygium, immunomodulatory therapy
Disclosure: Felipe A Valenzuela and Victor L Perez have nothing to disclose in relation to this article. No funding was received in the publication of this article. This study involves a review of the literature and did not involve any studies with human or animal subjects. performed by any of the authors.
Received: July 04, 2016 Accepted August 26, 2016
Correspondence: Victor L Perez, University of Miami Miller School of Medicine (UM), William McKnight Research Building, 1638 NW 10th Avenue, #613 Miami – Florida 33136, US. E: vperez4@med.miami.edu
Open Access: This article is published under the Creative Commons Attribution Noncommercial License, which permits any noncommercial use, distribution, adaptation, and reproduction provided the original author(s) and source are given appropriate credit.

Scleritis refers to a heterogeneous group of diseases characterized by inflammation of the sclera, which may also involve the cornea, adjacent episclera, and underlying uveal tract.1 In contrast to episcleritis, scleritis is associated with significant ophthalmic and systemic morbidity.2 Patients who are not appropriately diagnosed and treated are at high risk of vision loss owing to the progressive destruction of the eye and other associated ophthalmic complications. Moreover, the presence of scleritis can be the initial manifestation of a potentially lethal systemic vasculitis or can be the sole sign of active systemic disease of an already diagnosed inflammatory disorder.3 Therefore, the recognition and prompt treatment of scleritis could not only protect the eye, but also prolong the life of the patient.

Specific etiologies of scleritis, varying from idiopathic to autoimmune to infectious, portend variable disease severity and outcome. Scleritis sometimes occurs in an isolated fashion, without evidence of inflammation in other organs. However, in up to 50% of patients, scleritis is associated with an underlying systemic illness such as rheumatoid arthritis (RA) or granulomatosis with polyangiitis (Wegener’s).1 Infection is an important but rare cause of the scleritis, occurring in about 5–10% of all cases.4 Geographical location should be considered, as infectious scleritis is more commonly seen in the southern area of the United States.5 However, owing to the similarity of its presentation, infectious scleritis is often initially managed as autoimmune, potentially worsening its outcome.

Clinical features
Scleritis can occur in any age group, but most commonly presents between the fourth and sixth decades of life; women are affected approximately twice as often as men.6,7 The primary clinical sign of scleritis is redness associated with severe pain. The redness has a bluish red appearance, tends to progress with time and can be sectorial or involve the whole eye. The pain is described as dull, aching, or boring and it may be severe and constant; it often awakens patients from sleep and is poorly responsive to analgesics. Patients complain of deep pain that radiates from the eye to the forehead, orbit and even the sinuses in some instances. It is exacerbated by touching the eye or by pressing the periocular area. Other complaints may include tearing, photophobia, and decreased vision (especially in posterior scleritis).2,7

Slit lamp examination shows edema of the episcleral and scleral tissue, with congestion of the deep episcleral plexus. The use of topical vasoconstrictors has minimal effect on these vessels and in contrast to episcleritis, the redness of scleritis will not be resolved with the instillation of 10% phenylephrine or 1:1000 epinephrine.

Scleritis is associated with a number of ophthalmic complications that can lead to loss of vision. These include keratitis, uveitis, glaucoma, exudative retinal detachment, and macular edema.2,7

Scleritis can be further classified into anterior and posterior forms using the Watson and Hayreh classification.2 This classification is useful in determining the severity of the inflammation and as a guide for treatment. Anterior scleritis is much more frequent and can be further divided into diffuse, nodular, necrotizing and necrotizing without inflammation (scleromalacia perforans).8

Scleritis subtypes
Anterior sclertitis

Diffuse anterior scleritis (see Figure 1)—the inflammation of diffuse scleritis is generalized, has an insidious onset and, if untreated, can last up to several months. Upon resolution the sclera may look bluish due to a rearrangement of the collagen fibrils, with no loss of tissue or thinning. About 45% of patients with anterior diffuse scleritis will have an associated disease, RA been the most common.7–9

Nodular anterior scleritis (Figure 2)—this type of anterior scleritis is localized to a scleral nodule that is immobile, elevated, and firm. The nodule has a violaceous color with a congested vascular network. 40–50% of patients with nodular scleritis have an associated disease and RA is the most common. Patients with nodular scleritis may progress to anterior necrotizing scleritis and this needs to be carefully monitored.7,8

Necrotizing anterior scleritis (Figure 3)—necrotizing scleritis is the most severe form of scleritis and causes a significant amount of ocular morbidity. This form of scleritis is also a sign of the onset of a potential lethal systemic vasculitis.

This condition has an older age of onset and a higher proportion of patients (60–90%) have an underlying systemic disease, most commonly granulomatosis with polyangiitis and RA.9

The onset of necrotizing scleritis is gradual (3–4 days) and associated with severe pain. The affected avascular scleral tissue will look white and will be surrounded by intense swelling and redness of actively inflamed tissue. The inflammation starts in a demarcated area and will spread circumferentially and involve the whole anterior segment. The damaged sclera will become translucent due to tissue loss and thinning, leaving the choroid covered by conjunctiva or residual thinned scleral tissue. The protrusion of choroid can occur with trauma or increased intraocular pressure.7

It is important to keep in consideration that infections can also be a cause of necrotizing scleritis and need to be included in the differential diagnosis. Systemic immunosuppression is required for the treatment of anterior necrotizing scleritis associated with autoimmune diseases.

Scleromalacia perforans—This form of necrotizing scleritis without inflammation is almost always seen in patients with long-standing RA. It is characterized by the painless and slow disappearance of the overlying episcleral tissue, associated with attenuation of the conjunctival and episcleral vessels. The scleral tissue changes color from white to yellow and this becomes absorbed and disintegrated, leading to exposure of the underlying choroid. Although spontaneous perforation is rare, traumatic perforations can easily occur.7,8,10

References:
1. Okhravi N, Odufuwa B, McCluskey P, Lightman S, Scleritis, Surv Ophthalmol, 2005;50: 351–63.
2. Watson PG, Hayreh SS, Scleritis and episcleritis, Br J Ophthalmol, 1976;60:163–7.
3. Foster CS, Forstot SL, Wilson LA, Mortality rate in rheumatoid arthritis patients developing necrotizing scleritis or peripheral ulcerative keratitis, Ophthalmology, 1984;91:1253.
4. Jain V, Garg P, Sharma S, Microbial scleritis-experience from a developing country, Eye, 2009;23:255–61.
5. Hodson K, Galor A, Karp K, et al., Epidemiology and visual outcomes in patients with infectious scleritis, Cornea, 2013;32:466–72.
6. McCluskey PJ, Watson PG, Lightman S, et al., Posterior scleritis: clinical features, systemic associations, and outcome in a large series of patients, Ophthalmology, 1999; 106:2380–6.
7. Jabs DA, Mudun A, Dunn JP, Marsh MJ, Episcleritis and scleritis: clinical features and treatment results, Am J Ophthalmol, 2000;130:469–76.
8. Sainz M, Molina N, Gonzalez LA, et al., Clinical characteristics of a large cohort of patients with scleritis and episcleritis, Ophthalmology, 2012;119:43–50.
9. Hakin KN, Watson PG, Systemic associations of scleritis, Int Ophthalmol Clin, 1991;31:111–29.
10. Sainz de la Maza M, Tauber J, Foster CS, Clinical considerations of episcleritis and scleritis. In: Sainz de la Maza M, Tauber J, Foster CS, The Sclera, Second Edition, New York: Springer, 2012;102–32.
11. Wakefield D, Di Girolamo N, Thurau S, et al., Scleritis: Immunopathogenesis and molecular basis for therapy, Progress in Retinal and Eye Research, 2013;35:44–62.
12. Sainz de la Maza, Molina N, Gonzalez-Gonzalez LA, et al., Scleritis therapy, Ophthalmology, 2012;119:51–8
13. Cao J, Cocho L, Foster CS, Rituximab in the treatment of refractory noninfectious scleritis, Am J Ophthalmol, 2016;164:22–8.
14. Stone JH, Merkel PA, Spiera R, Seo P, et al., Rituximab versus cyclophosphamide for ANCA-associated vasculitis, N Engl J Med, 2010;363:221.
15. Ashok D, Ayliffe WH, Kiely PD, Necrotizing scleritis associated with rheumatoid arthritis: long-term remission with high-dose infliximab therapy, Rheumathology (Oxford), 2005;44:950.
16. El-Shabrawi Y, Hermann J, Anti-TNF alpha therapy in chronic necrotizing scleritis resistant to standard immunomodulatory therapy in a patient with Wegener’s granulomatosis, Eye, 2005;19:1017.
17. Doctor P, Sultan A, Syed S, et al., Infliximab for the treatment of refractory scleritis, Br J Ophtahlmol, 2010;94:579.
18. Murphy CC, Ayliffe WH, Booth A, et al., Tumor necrosis factor alpha blockade with infliximab for refractory uveitis and scleritis, Ophthalmology, 2004;111:352.
19. Sen HN, Suhler EB, Al-Khatib SQ, et al., Mycophenolate mofetil for the treatment of scleritis, Ophthalmology, 2003;110:1750.
20. Jachenes AW, Chu DS, Retrospective review of methrotrexate therapy in the treatment of chronic, noninfectious, noncretizing scleritis, Am J Opthalmol, 2008;145–487.
21. Bielefeld P, Muselier A, Devilliers H, et al., Cotrimoxazole as a treatment for recurrent idiopathic anterior scleritis: A single-center experience in 20 patients, Ocular Immunology & Inflammation, 2015;23:184–7.
22. Rameneden R, Raiji V, Clinical characteristics and visual outcomes in infectious scleritis: a review, Clinical Ophthalmology, 2013;7:2113–22.
23. McCluskey PJ, Watson PG, Lightman S, et al., Posterior scleritis: clinical features, systemic associations, and outcome in a large series of patients, Ophthalmology, 1999;106:2380–6.
24. Reynolds MG, Alfonso E, Treatment of infectious scleritis and keratoscleritis, Am J Ophthalmol, 1991;112:543–7.
25. Foster CS and de la Maza MS, The Sclera, New York: Springer, 1994.
Keywords: Scleritis, infectious, autoimmune, vasculitides, pterygium, immunomodulatory therapy