- Author: Manolette R Roque, MD, MBA, FPAO; Chief Editor: John D Sheppard, Jr, MD, MMSc more...
The goals of pharmacotherapy are to reduce morbidity and to prevent complications.
Have anti-inflammatory properties and cause profound and varied metabolic effects. Corticosteroids modify the body's immune response to diverse stimuli.
Inhibits phospholipase A and Fc receptor expression, activates the glucocorticoid receptor, reduces cytokine production, suppresses lymphocyte function, and redistributes circulating leukocytes. Also potent inhibitors of angiogenesis and potent stabilizer of cell membranes.
Corticosteroids act as potent inhibitors of inflammation. They may cause profound and varied metabolic effects, particularly in relation to salt, water, and glucose tolerance, in addition to their modification of the immune response of the body. Alternative corticosteroids may be used in equivalent dosage.
Inhibit specific immune system pathways.
Inhibits DHFR, causing a block in the reduction of dihydrofolate to tetrahydrofolate. This inhibits the formation of thymidylate and purines; arrests DNA, RNA, and protein synthesis. Patients should take adjunctive folic acid therapy up to 1000 mg per day to avoid hematopoietic complications.
Interferes with DNA synthesis and inhibits lymphocyte proliferation.
Chemically related to nitrogen mustards. As an alkylating agent, the mechanism of action of the active metabolites may involve cross linking of DNA, which may interfere with growth of normal and neoplastic cells. Drug of choice for granulomatosis with polyangiitis or polyarteritis nodosa.
Cyclic polypeptide that suppresses some humoral immunity and, to a greater extent, cell-mediated immune reactions, such as delayed hypersensitivity. For children and adults, base dosing on ideal body weight.
Inhibits purine synthesis and proliferation of human lymphocytes. Promising published case report of 3 patients with resistant disease treated with mycophenolate mofetil. Reduced toxicity makes this regimen an attractive alternative.
Selective immunomodulators that affect specific aspects of the inflammatory pathways.
Subcutaneous recombinant human IgG1 monoclonal antibody specific for human TNF. Indicated to reduce inflammation and inhibit progression of structural damage in moderate-to-severe rheumatoid arthritis. Reserved for those who experience inadequate response to one or more DMARDs. Can be used alone or in combination with MTX or other DMARDs. Binds specifically to TNF-alpha and blocks interaction with p55 and p75 cell-surface TNF receptors.
Intravenous chimeric IgG1k monoclonal antibody that neutralizes cytokine TNF-alpha and inhibits its binding to TNF-alpha receptor. Reduces infiltration of inflammatory cells and TNF-alpha production in inflamed areas. Used with MTX in patients who have had inadequate response to MTX monotherapy.
Indicated to reduce signs and symptoms for moderately-to-severely active rheumatoid arthritis in combination with MTX. For use in adults who have experienced an inadequate response to one or more TNF antagonist therapies. Antibody genetically engineered. Chimeric murine/human monoclonal antibody directed against the CD20 antigen found on surface of B lymphocytes. Focal leukoencephalopathy is a lethal rare side effect that must be considered.
Nonsteroidal anti-inflammatory drugs
Have analgesic, anti-inflammatory, and antipyretic activities. Their mechanism of action is not known but may inhibit cyclooxygenase activity and prostaglandin synthesis. Other mechanisms may exist, such as inhibition of leukotriene synthesis, lysosomal enzyme release, lipoxygenase activity, neutrophil aggregation, and various cell membrane functions. Systemic therapy with NSAIDs, corticosteroids, and immunosuppressive agents, alone or in combination, may be effective in patients with noninfectious scleritis.
DOC for patients with mild to moderate pain. Inhibits inflammatory reactions and pain by decreasing prostaglandin synthesis.
Rapidly absorbed. Metabolism occurs in liver by demethylation, deacetylation, and glucuronide conjugation. Inhibits prostaglandin synthesis.
For relief of mild to moderate pain; inhibits inflammatory reactions and pain by decreasing activity of cyclooxygenase, which results in a decrease of prostaglandin synthesis.
Decreases activity of cyclooxygenase, which, in turn, inhibits prostaglandin synthesis. These effects decrease formation of inflammatory mediators.
Primarily inhibits COX-2. COX-2 is considered an inducible isoenzyme, induced by pain and inflammatory stimuli. Inhibition of COX-1 may contribute to NSAID GI toxicity. At therapeutic concentrations, COX-1 isoenzyme is not inhibited, thus incidence of GI toxicity, such as endoscopic peptic ulcers, bleeding ulcers, perforations, and obstructions, may be decreased when compared to nonselective NSAIDs. Seek lowest dose for each patient.
Neutralizes circulating myelin antibodies through anti-idiotypic antibodies; down-regulates proinflammatory cytokines, including INF-gamma; blocks Fc receptors on macrophages; suppresses inducer T and B cells and augments suppressor T cells; blocks complement cascade; promotes remyelination; may increase CSF IgG (10%).
Has a sulfonamide chain and is primarily dependent upon cytochrome P450 enzymes (a hepatic enzyme) for metabolism.
González-López JJ, Lavric A, Dutta Majumder P, Bansal N, Biswas J, Pavesio C, et al. Bilateral Posterior Scleritis: Analysis of 18 Cases from a Large Cohort of Posterior Scleritis. Ocul Immunol Inflamm. 2015 Oct 16. 1-8. [Medline].
Sims J. Scleritis: presentations, disease associations and management. Postgrad Med J. 2012 Sep 12. [Medline].
Sainz de la Maza M, Foster CS, Jabbur NS. Scleritis associated with rheumatoid arthritis and with other systemic immune-mediated diseases. Ophthalmology. 1994 Jul. 101(7):1281-6; discussion 1287-8. [Medline].
Sainz de la Maza M, Foster CS, Jabbur NS. Scleritis associated with systemic vasculitic diseases. Ophthalmology. 1995 Apr. 102(4):687-92. [Medline].
French DD, Margo CE. Postmarketing surveillance rates of uveitis and scleritis with bisphosphonates among a national veteran cohort. Retina. 2008 Jun. 28(6):889-93. [Medline].
Agrawal R, Lavric A, Restori M, Pavesio C, Sagoo MS. NODULAR POSTERIOR SCLERITIS: Clinico-Sonographic Characteristics and Proposed Diagnostic Criteria. Retina. 2015 Aug 19. [Medline].
Axmann S, Ebneter A, Zinkernagel MS. Imaging of the Sclera in Patients with Scleritis and Episcleritis using Anterior Segment Optical Coherence Tomography. Ocul Immunol Inflamm. 2015 Aug 10. 1-6. [Medline].
[Guideline] Zimmerman RD, Seidenwurm DJ, Davis PC, et al. ACR Appropriateness Criteria. Orbits, vision, and visual loss. National Guideline Clearinghouse. 2006.
Nieuwenhuizen J, Watson PG, Emmanouilidis-van der Spek K, Keunen JE, Jager MJ. The value of combining anterior segment fluorescein angiography with indocyanine green angiography in scleral inflammation. Ophthalmology. 2003 Aug. 110(8):1653-66. [Medline].
Sainz de la Maza M, Molina N, Gonzalez-Gonzalez LA, Doctor PP, Tauber J, Foster CS. Clinical characteristics of a large cohort of patients with scleritis and episcleritis. Ophthalmology. 2012 Jan. 119(1):43-50. [Medline].
Hakin KN, Ham J, Lightman SL. Use of orbital floor steroids in the management of patients with uniocular non-necrotising scleritis. Br J Ophthalmol. 1991 Jun. 75(6):337-9. [Medline].
Galor A, Jabs DA, Leder HA, Kedhar SR, Dunn JP, Peters GB 3rd. Comparison of antimetabolite drugs as corticosteroid-sparing therapy for noninfectious ocular inflammation. Ophthalmology. 2008 Oct. 115(10):1826-32. [Medline].
Sobrin L, Christen W, Foster CS. Mycophenolate mofetil after methotrexate failure or intolerance in the treatment of scleritis and uveitis. Ophthalmology. 2008 Aug. 115(8):1416-21, 1421.e1. [Medline].
Wakefield D, McCluskey P. Cyclosporin therapy for severe scleritis. Br J Ophthalmol. 1989 Sep. 73(9):743-6. [Medline].
Huynh N, Cervantes-Castaneda RA, Bhat P, Gallagher MJ, Foster CS. Biologic response modifier therapy for psoriatic ocular inflammatory disease. Ocul Immunol Inflamm. 2008 May-Jun. 16(3):89-93. [Medline].
Murphy CC, Ayliffe WH, Booth A, Makanjuola D, Andrews PA, Jayne D. Tumor necrosis factor alpha blockade with infliximab for refractory uveitis and scleritis. Ophthalmology. 2004 Feb. 111(2):352-6. [Medline].
Ahmadi-Simab K, Lamprecht P, Nolle B, Ai M, Gross WL. Successful treatment of refractory anterior scleritis in primary Sjogren's syndrome with rituximab. Ann Rheum Dis. 2005 Jul. 64(7):1087-8. [Medline].
Cheung CM, Murray PI, Savage CO. Successful treatment of Wegener's granulomatosis associated scleritis with rituximab. Br J Ophthalmol. 2005 Nov. 89(11):1542. [Medline].
Taylor SR, Salama AD, Joshi L, Pusey CD, Lightman SL. Rituximab is effective in the treatment of refractory ophthalmic Wegener's granulomatosis. Arthritis Rheum. 2009 May. 60(5):1540-7. [Medline].
Recillas-Gispert C, Serna-Ojeda JC, Flores-Suárez LF. Rituximab in the treatment of refractory scleritis in patients with granulomatosis with polyangiitis (Wegener's). Graefes Arch Clin Exp Ophthalmol. 2015 Oct 27. [Medline].
Tuft SJ, Watson PG. Progression of scleral disease. Ophthalmology. 1991 Apr. 98(4):467-71. [Medline].
Sainz de la Maza M, Jabbur NS, Foster CS. Severity of scleritis and episcleritis. Ophthalmology. 1994 Feb. 101(2):389-96. [Medline].
Sobrin L, Kim EC, Christen W, Papadaki T, Letko E, Foster CS. Infliximab therapy for the treatment of refractory ocular inflammatory disease. Arch Ophthalmol. 2007 Jul. 125(7):895-900. [Medline].
Fong LP, Sainz de la Maza M, Rice BA, Kupferman AE, Foster CS. Immunopathology of scleritis. Ophthalmology. 1991 Apr. 98(4):472-9. [Medline].
Heinz C, Bograd N, Koch J, Heiligenhaus A. Ocular hypertension and glaucoma incidence in patients with scleritis. Graefes Arch Clin Exp Ophthalmol. 2012 Jul 22. [Medline].
Onal S, Kazokoglu H, Koc A, Yavuz S. Rituximab for remission induction in a patient with relapsing necrotizing scleritis associated with limited Wegener´s granulomatosis. Ocul Immunol Inflamm. Sep-Oct 2008. 16(5):230-232.
Sainz de la Maza M, Jabbur NS, Foster CS. An analysis of therapeutic decision for scleritis. Ophthalmology. 1993 Sep. 100(9):1372-6. [Medline].
Sainz de la Maza M, Tauber J, Foster CS. Scleral grafting for necrotizing scleritis. Ophthalmology. 1989 Mar. 96(3):306-10. [Medline].
Watson PG, Hayreh SS. Scleritis and episcleritis. Br J Ophthalmol. 1976 Mar. 60(3):163-91. [Medline].
de Fidelix TS, Vieira LA, de Freitas D, Trevisani VF. Biologic therapy for refractory scleritis: a new treatment perspective. Int Ophthalmol. 2015 Aug 29. [Medline].