eMedicine Specialties > Emergency Medicine > Rheumatology

Scleritis

Theodore J Gaeta, DO, MPH, FACEP, Clinical Associate Professor, Department of Emergency Medicine, Joan and Sanford Weill Medical College at Cornell University; Vice Chairman and Program Director of Emergency Medicine Residency Program, Department of Emergency Medicine, New York Methodist Hospital; Academic Chair, Adjunct Professor, Department of Emergency Medicine, St George's University School of Medicine
Diana Valcich, MD, Staff Physician, Department of Emergency Medicine, New York Methodist Hospital

Updated: Apr 14, 2008

Introduction

Background

Scleritis is an inflammatory disease that affects the sclera; it may be localized, nodular, or diffuse. It may involve the anterior (visible segment) and/or posterior segments of the eye and manifests with redness of the eye and severe eye pain. Isolated posterior scleritis will not present with redness of the visible portion of the eye and may or may not present with pain. 

The 4 types of anterior scleritis are as follows:

1. Diffuse anterior scleritis: This is characterized by widespread inflammation of the anterior portion of the sclera. This is the most common form of anterior scleritis as well as the most benign.
2. Nodular anterior scleritis: This type is characterized by one or more erythematous, immovable, tender inflamed nodules on the anterior sclera. Approximately 20% of cases progress to necrotizing scleritis.
3. Necrotizing anterior scleritis with inflammation: This form frequently accompanies serious systemic collagen vascular disorders including rheumatoid arthritis. Pain with this condition is usually extreme, and damage to the sclera is often marked. Necrotizing anterior scleritis with corneal inflammation is also known as sclerokeratitis.
4. Necrotizing anterior scleritis without inflammation: This type most frequently occurs in patients with long-standing rheumatoid arthritis; it is due to the formation of a rheumatoid nodule in the sclera and is notable for its absence of symptoms. Necrotizing anterior scleritis without inflammation is also known as scleromalacia perforans.

Pathophysiology

The sclera, which consists of collagen and elastic connective tissue, provides a tough protective casing around the eye. Enzymatic degradation of collagen fibrils and invasion of inflammatory cells, including T cells and macrophages, appear to play an important role. 

The thickness of the sclera varies from 0.3-1.2 mm. Healthy sclera is consistently white. Inflammation, the principal pathology affecting the sclera, is frequently part of a general inflammatory reaction associated with a systemic immune-mediated collagen vascular disease.

Inflammation of the sclera can progress to ischemia and necrosis, eventually leading to scleral thinning and perforation of the globe. Necrotizing anterior scleritis represents a particularly destructive form of scleritis.

Frequency

United States

Scleritis is an uncommon disease. Well-defined incidence rates are hard to find. The prevalence is estimated to be 6 cases per 10,000 population. Of patients diagnosed with scleritis, anterior scleritis is demonstrated in 94% of patients, as opposed to posterior scleritis, which is diagnosed only 6% of the time.

An increased incidence of scleritis has been reported in patients taking bisphosphonates, which are commonly used in the management of osteoporosis.

International

No particular geographic distribution has been noted.

Mortality/Morbidity

• Morbidity arises from primary scleritis and associated systemic disease.
• Giant pigment epithelial tear and retinal detachment has been reported in a patient with scleritis.
• A significant percentage of patients with concurrent scleritis and collagen vascular disease die within 5 years.
• In 15% of cases, scleritis is the presenting manifestation of collagen vascular disorder and may precede additional symptoms by one to several months.

Race

No published information is available on racial differences.

Sex

The female-to-male ratio is approximately 1.6:1.

Age

• Cases have been reported in patients ranging from 11-87 years of age. Mean age for all types of scleritis is 52 years.
• Episcleritis tends to affect younger patients.

Clinical

History

• Pain 
  • Severe, constant, deep, boring, or pulsating pain is noted.
  • Pain worsens with movement of the eye.
  • Pain is worse at night and may awaken the patient.
  • Pain may be referred to the eyebrow, temple, or jaw. Occasionally, the configuration of the pain pattern corresponds to the course of the trigeminal nerve.
• Onset: Scleritis is subacute, a more gradual onset occurs than is seen in episcleritis.
• Duration of symptoms: Scleritis generally persists from months to years, whereas episcleritis usually resolves within weeks.
• Associated symptoms  
  • Erythema of the eye is a defining symptom with anterior scleritis.
  • Lacrimation
  • Photophobia
  • Discharge is ordinarily not part of the clinical picture of scleritis.
  • Less prevalent symptoms 
    • Fever
    • Nausea/vomiting
    • Headache
• Unilateral or bilateral: Both eyes are affected in slightly more than one half of cases.
• Similar previous episodes
• Prior history  
  • Underlying systemic disease
  • Trauma
  • Ocular surgery
  • Glaucoma
  • Exposure to irritants/chemicals
  • Previous use of eye drops
  • Medications

Physical

• As with any eye complaint (except chemical injury), begin with vision testing.  
  • Visual acuity may be normal or decreased with all forms of scleritis.
  • Visual impairment is most pronounced with posterior scleritis.
• Additionally, a complete physical examination, particularly of the skin, joints, heart, and lungs, may be obligatory when an underlying complicating illness is suspected.
• External examination 
  • Ensure that the eye examined is supported by satisfactory lighting, inspecting for breadth and degree of injection, as well as the presence of bluish hue signifying attenuation of the sclera.
  • Prominent findings may include photophobia, tearing without discharge, tenderness of the eye, and purplish red, edematous, engorged blood vessels.
  • Deeper sclera blood vessels appear darker, follow a radial pattern, and do not move when manipulated with a cotton swab.
  • Administration of topical phenylephrine 2.5-10% causes blanching of the more superficial episcleral vessels but does not change the engorgement of deeper sclera vessels and can help differentiate between scleritis and episcleritis.
• Perform a slit lamp/biomicroscopic examination to judge the depth and breadth of involvement.  
  • Determine whether there is diffuse or segmental involvement. Widespread injection of the conjunctival and deep scleral vessels is characteristic of diffuse anterior scleritis.
  • Localized elevation of the sclera is representative of nodular anterior scleritis.
  • Nodules in anterior scleritis are immobile, differing from the non-mobile nodules that can be seen in episcleritis.
  • Scleral thinning is suggested when the choroid pigment becomes a blue-violet hue best seen in natural lighting.
  • Global perforation typically results in an abnormal shape of the pupil and/or uveal or vitreous prolapse.
  • Use of a red-free filter (green light) helps identify avascular areas of the sclera. Corneal changes are present in up to 50% of cases.
  • Examination of the eyelids for possible blepharitis or conjunctivitis should be performed.
• Assessment of the anterior chamber for possible narrowing, hyphema, or hypopyon. Angle narrowing can be seen in acute angle-closure glaucoma. Hyphema can be seen with trauma and/or bleeding disorders. Hypopyon may be seen in uveitis/iritis.
• Posterior scleritis  
  • External findings associated with posterior scleritis include restriction of eye movements, sensitivity to palpation, and proptosis.
  • Dilation of the fundus may be necessary to identify posterior scleritis. Posterior scleritis may simulate amelanotic choroidal.
  • Funduscopic examination of the patient with posterior scleritis may also reveal papilledema, choroidal folds, and retinal hemorrhage or detachment.

Causes

Scleritis coexists with a serious systemic disease in almost one half of cases; the underlying problem is frequently a connective tissue disorder.

• Rheumatoid arthritis is the underlying disease for approximately one sixth of patients suffering from scleritis, and approximately 1% of patients with rheumatoid arthritis will develop scleritis at some point in the course of the disease. Scleritis associated with RA is due to the development of a rheumatoid nodule on the sclera and is associated with an increased risk of mortality.
• Other connective tissue and autoimmune diseases seen with scleritis include the following:
  • Systemic lupus erythematosus (SLE)
  • Polyarteritis nodosa
  • Seronegative spondyloarthropathies
    • Ankylosing spondylitis
    • Psoriatic arthritis
    • Reactive arthritis
  • Wegener granulomatosis
  • Relapsing polychondritis
  • Sarcoidosis
  • Inflammatory bowel disease
  • Sjörgen syndrome  
• Additional maladies that may accompany scleritis include the following:
  • Syphilis
  • Post herpes zoster ophthalmicus
  • Tuberculosis
  • Gout
  • Lyme disease
  • Foreign body
  • Hypertension

Differential Diagnoses

Other Problems to Be Considered

Cerebral tumor
Chronic lymphocytic leukemia
Immunosuppression
Collagen vascular disease

Workup

Laboratory Studies

• Depending on the clinical suspicion, laboratory studies may be warranted. Laboratory tests include, but are not limited to, the following:
  • Complete blood count (CBC) and electrolytes
  • Erythrocyte sedimentation rate (ESR)
  • FTA-ABS (RPR)
  • Uric acid
  • Rheumatoid factor
  • Antinuclear antibody (ANA)
• The ED is the ideal location to initiate evaluation for collagen vascular disease, infection (conjunctival cultures), and immunocompetency. If scleritis is suspected, the emergency physician will contact an ophthalmologist. This would be a good opportunity to establish an evaluation and intervention plan. Getting the laboratory studies in the ED will save time for the patient and practitioners.

Imaging Studies

• B-scan ultrasonography may assist in detecting posterior scleritis. MRI or CT scans may play a role, but they should be ordered in consultation with an ophthalmologist.
• Chest radiography may be indicated to look for underlying pulmonary involvement arising from systemic disease.
• Imaging of sacroiliac joints is prudent when ankylosing spondylitis is suspected.

Other Tests

• Instillation of phenylephrine, a mydriatic vasoconstrictor, helps differentiate deep scleral episcleral blood vessel involvement from superficial involvement; superficial vessels blanch following application of phenylephrine, while deeper vessels remain unaffected.
• Seidel test helps detect possible global perforation. Apply a moistened fluorescein strip over the potential site of perforation while viewing under a slit lamp. If perforation exists, the fluorescein dye becomes diluted by the aqueous humor, appearing as a green dilute stream within the dark, concentrated, orange dye.

Procedures

• Apply an eye shield when scleral thinning or global perforation is suspected.  
  • Ensure that the eye guard does not contact the eyelid or globe.
  • Apply tape from the forehead to zygoma.
  • In the absence of an eye shield, use a paper or polystyrene cup, provided it is large enough to cover the eye without placing undue pressure on the globe.

Treatment

Prehospital Care

• Primary complaint of atraumatic eye pain rarely necessitates prehospital care, other than expedient transport to the ED.
• Take care not to overlook serious comorbidity.
• If global perforation is suspected, shield the eye and avoid palpation.

Emergency Department Care

• Recognition of the problem and timely ophthalmology referral are cornerstones of ED management.
• Pain medications may be prescribed in order to provide comfort for the patient.
• Detection of scleral thinning mandates shielding of the involved eye to decrease risk of perforation.
• Scleritis treatment will require immunomodulator therapy once the definitive diagnosis is made.
• The emergency practitioner can discuss using a topical steroid agent with the ophthalmologist. The caveat being that topical steroid therapy typically fails. However, it could be considered as first-line treatment for nonnecrotizing anterior scleritis, especially in cases in which the likelihood of complications from systemic steroid or nonsteroidal anti-inflammatory drug (NSAID) therapy is high.

Consultations

• Severity of scleritis and depth of involvement determine the urgency of ophthalmology consultation.
• Serious systemic illness may require consultation with a qualified internist and/or rheumatologist.

Medication

Therapeutic goals for scleritis are familiar to any emergency practitioner: relieve the patient’s pain and initiate therapy that will positively alter the course of the disease.

From the patient's perspective, pain cessation may be the most important action taken by the emergency practitioner. Outcome will depend on the patient's response to immunosuppressive therapy.

Narcotics and systemic NSAIDs may render temporary pain relief and can be started in the ED.

NSAIDs are generally found to be effective in approximately one third of patients with diffuse anterior scleritis and two thirds of patients with nodular anterior scleritis. NSAIDs have also been found to be helpful in patients with idiopathic posterior scleritis.
   
Initiation of immunosuppressive therapy may require coordination with an internist and/or rheumatologist.

Topical steroids have a high failure rate but should be discussed with the practitioner who will provide follow-up care.

Subconjunctival steroid injections for non-necrotizing scleritis remain controversial. Localized steroid injections may lead to increased intraocular pressure, scleral melting, or globe perforation/scleral rupture.

Surgical management is generally not required except in rare cases of necrotizing scleritis.

Nonsteroidal anti-inflammatory drugs

These agents are used to decrease pain and inflammation. NSAIDs are thought to act by inhibiting prostaglandin synthesis, interfering with migration of leukocytes, and inhibiting phosphodiesterase.

Indomethacin (Indocin)

Often considered the DOC. Indomethacin is rapidly absorbed. Metabolism occurs in the liver by demethylation, deacetylation, and glucuronide conjugation.

Dosing

Adult

25-50 mg/dose IR PO bid/tid
75 mg SR PO bid; not to exceed 200 mg/d

Pediatric

1-2 mg/kg/d PO divided bid/qid; not to exceed 4 mg/kg/d or 150-200 mg/d

Interactions

Coadministration with aspirin increases risk of inducing serious NSAID-related adverse effects; probenecid may increase concentrations and, possibly, toxicity of NSAIDs; may decrease effect of hydralazine, captopril, and beta-blockers; may decrease diuretic effects of furosemide and thiazides; monitor PT closely (instruct patients to watch for signs of bleeding); may increase risk of methotrexate toxicity; phenytoin levels may be increased when administered concurrently

Contraindications

Documented hypersensitivity; because of potential cross-sensitivity to other NSAIDs, do not give these agents to patients with hypersensitivity to aspirin, iodides, or other NSAIDs; avoid in GI bleeding; renal insufficiency

Precautions

Pregnancy

B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals

D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus

Precautions

Acute renal insufficiency, hyperkalemia, hyponatremia, interstitial nephritis, and renal papillary necrosis may occur; increases risk of acute renal failure in patients with preexisting renal disease or compromised renal perfusion; reversible leukopenia may occur, (discontinue if leukopenia, granulocytopenia, or thrombocytopenia persists); perform ophthalmologic studies in patients who develop eye complaints during therapy, and discontinue therapy if changes (eg, blurred or diminished vision, corneal deposits and retinal disturbances, scotomata, changes in color vision, macula degeneration) noted

Diflunisal (Dolobid)

Nonsteroidal salicylic acid derivative that acts peripherally as an analgesic. Has antipyretic and anti-inflammatory effects; however, differs chemically from aspirin and is not metabolized to salicylic acid. It is a prostaglandin-synthetase inhibitor.

Dosing

Adult

Initial: 500-1000 mg PO
Maintenance: 250-500 mg PO divided bid; not to exceed 1.5 g/d

Pediatric

Not established

Interactions

Antacids may decrease effects; acetaminophen plasma levels may increase when taken with diflunisal; acetaminophen does not affect plasma levels of diflunisal; oral coadministration of diflunisal may increase hypoprothrombinemic effects of anticoagulants; diflunisal competitively displaces coumarin from their protein-binding sites; monitor prothrombin time during coadministration with anticoagulants and adjust dose as needed; coadministration with hydrochlorothiazide can significantly increase hydrochlorothiazide plasma levels; administration of diflunisal with indomethacin can decrease indomethacin renal clearance and significantly increase plasma levels (their combined use has also been associated with fatal GI hemorrhages); coadministration of diflunisal with sulindac may result in significantly lower plasma levels of active sulindac sulfide metabolite

Contraindications

Documented hypersensitivity; active GI bleeding

Precautions

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus

Precautions

At high doses, diflunisal inhibits platelet function and bleeding time; ophthalmologic examinations should be performed in patients who develop eye complaints during treatment; peripheral edema has been reported with diflunisal use; caution when in cardiovascular conditions that predispose patient to fluid retention; because diflunisal is a salicylic acid derivative, may potentially cause Reye syndrome

Naproxen (Naprelan, Anaprox, Aleve, Naprosyn)

Used for relief of mild-to-moderate pain. It inhibits inflammatory reactions and pain by decreasing the activity of the enzyme cyclooxygenase, resulting in a decrease of prostaglandin synthesis.
Naproxen is rapidly absorbed and has a half-life of 12-15 h. It is highly protein bound.

Dosing

Adult

375-500 mg PO bid

Pediatric

<2 years: Not established
>2 years: 2.5 mg/kg/dose PO; not to exceed 10 mg/kg/d

Interactions

Coadministration with aspirin increases risk of inducing serious NSAID-related adverse effects; probenecid may increase concentrations and, possibly, toxicity of NSAIDs; may decrease effect of hydralazine, captopril, and beta-blockers; may decrease diuretic effects of furosemide and thiazides; monitor PT closely (instruct patients to watch for signs of bleeding); may increase risk of methotrexate toxicity; phenytoin levels may be increased when administered concurrently

Contraindications

Documented hypersensitivity; peptic ulcer disease; recent GI bleeding or perforation; renal insufficiency

Precautions

Pregnancy

B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals

D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus

Precautions

Acute renal insufficiency, interstitial nephritis, hyperkalemia, hyponatremia, and renal papillary necrosis may occur; patients with preexisting renal disease or compromised renal perfusion risk acute renal failure; leukopenia occurs rarely, is transient, and usually returns to normal during therapy; persistent leukopenia, granulocytopenia, or thrombocytopenia warrants further evaluation and may require discontinuation of drug

Ibuprofen (Motrin, Ibuprin, Advil)

Usually the DOC for treatment of mild- to- moderate pain, if no contraindications exist. Inhibits inflammatory reactions and pain, probably by decreasing activity of the enzyme cyclooxygenase, which results in prostaglandin synthesis.
Highly protein-bound drug that is readily absorbed orally. The half-life is short (1.8-2.6 h).

Dosing

Adult

400-600 mg PO qid

Pediatric

<6 months: Not established
6 months to 12 years: 10-70 mg/kg/d PO divided tid/qid; start at lower end of dosing range and titrate to maximum of 2.4 g/d
>12 years: Administer as in adults

Interactions

Coadministration with aspirin increases risk of inducing serious NSAID-related adverse effects; probenecid may increase concentrations and, possibly, toxicity of NSAIDs; may decrease effect of hydralazine, captopril, and beta-blockers; may decrease diuretic effects of furosemide and thiazides; monitor PT closely (instruct patients to watch for signs of bleeding); may increase risk of methotrexate toxicity; phenytoin levels may be increased when administered concurrently

Contraindications

Documented hypersensitivity; hypersensitivity to other NSAIDs, aspirin, iodides; peptic ulcer disease; recent GI bleeding or perforation; renal insufficiency; high risk of bleeding

Precautions

Pregnancy

B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals

D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus

Precautions

Caution in congestive heart failure, hypertension, and decreased renal and hepatic function; caution in anticoagulation abnormalities or during anticoagulant therapy

Sulindac (Clinoril)

Decreases activity of cyclooxygenase and, in turn, inhibits prostaglandin synthesis. Results in a decreased formation of inflammatory mediators.

Dosing

Adult

150-200 mg PO bid or 300-400 PO qd; not to exceed 400 mg/d

Pediatric

Not established

Interactions

Coadministration with aspirin increases risk of inducing serious NSAID-related adverse effects; probenecid may increase concentrations and, possibly, toxicity of NSAIDs; may decrease effect of hydralazine, captopril, and beta-blockers; may decrease diuretic effects of furosemide and thiazides; monitor PT closely (instruct patients to watch for signs of bleeding); may increase risk of methotrexate toxicity; phenytoin levels may be increased when administered concurrently

Contraindications

Documented hypersensitivity; hypersensitivity to other NSAIDs, aspirin, iodides; GI bleeding; renal insufficiency

Precautions

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus

Precautions

Acute renal insufficiency, hyperkalemia, hyponatremia, interstitial nephritis, and renal papillary necrosis may occur; increases risk of acute renal failure in preexisting renal disease or compromised renal perfusion; low white blood cell counts occur rarely, and usually return to normal in ongoing therapy; discontinuation of therapy may be necessary if leukopenia, granulocytopenia, or thrombocytopenia persists; caution in anticoagulation defects or in those who are receiving anticoagulant therapy

Piroxicam (Feldene)

Chemically different from other NSAIDs. Extensively bound to plasma proteins. Decreases activity of cyclooxygenase and, in turn, inhibits prostaglandin synthesis. These effects decrease formation of inflammatory mediators.

Dosing

Adult

10-20 mg/d PO qd

Pediatric

0.2-0.3 mg/kg/d PO qd; not to exceed 15 mg/d

Interactions

Coadministration with aspirin increases risk of inducing serious NSAID-related adverse effects; probenecid may increase concentrations and, possibly, toxicity of NSAIDs; may decrease effect of hydralazine, captopril, and beta-blockers; may decrease diuretic effects of furosemide and thiazides; monitor PT closely (instruct patients to watch for signs of bleeding); may increase risk of methotrexate toxicity; phenytoin levels may be increased when administered concurrently

Contraindications

Documented hypersensitivity; active GI bleeding

Precautions

Pregnancy

B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals

D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus

Precautions

Acute renal insufficiency, hyperkalemia, hyponatremia, interstitial nephritis, and renal papillary necrosis may occur; increases risk of acute renal failure in patients with preexisting renal disease or compromised renal perfusion; reversible leukopenia may occur, (discontinue if leukopenia, granulocytopenia, or thrombocytopenia persists)

Immunosuppressive agents

These agents are used in severe (necrotizing scleritis) and resistant forms of the disease. Only an ophthalmologist experienced with the medication should prescribe these drugs.

Methotrexate (Folex, Rheumatex)

Mechanism of action in treatment of inflammatory reactions is unknown. May affect immune function and usually ameliorates symptoms of inflammation (eg, pain, swelling, stiffness).

Dosing

Adult

7.5-15 mg PO qwk or 15 mg IM qwk

Pediatric

5-15 mg/m²/wk PO/IM as a single dose or as 3 divided doses given 12 h apart

Interactions

Oral aminoglycosides may decrease absorption and blood levels of concurrent oral methotrexate (MTX); charcoal lowers MTX levels; coadministration with etretinate may increase hepatotoxicity of MTX; folic acid or its derivatives contained in some vitamins may decrease response to MTX; coadministration with NSAIDs may be fatal; indomethacin and phenylbutazone can increase MTX plasma levels; may decrease phenytoin serum levels; probenecid, salicylates, procarbazine, and sulfonamides, including TMP-SMZ, may increase effects and toxicity of MTX; may increase plasma levels of thiopurines

Contraindications

Documented hypersensitivity; alcoholism; hepatic insufficiency; documented immunodeficiency syndromes; preexisting blood dyscrasias (eg, bone marrow hypoplasia, leukopenia, thrombocytopenia, significant anemia)

Precautions

Pregnancy

X - Contraindicated; benefit does not outweigh risk

Precautions

Monitor CBCs monthly, and liver and renal function q1-3mo during therapy (monitor more frequently during initial dosing, dose adjustments, or when risk of elevated MTX levels, eg, dehydration); MTX has toxic effects on hematologic, renal, GI, pulmonary, and neurologic systems; discontinue if significant drop in blood counts; aspirin, NSAIDs, or low-dose steroids may be administered concomitantly with MTX (possibility of increased toxicity with NSAIDs including salicylates has not been tested)

Cyclophosphamide (Cytoxan, Neosar)

Chemically related to nitrogen mustards. As it is an alkylating agent, mechanism of action of active metabolites may involve cross-linking of the DNA, which may interfere with growth of normal and neoplastic cells.

Dosing

Adult

1-2 mg/kg/d PO

Pediatric

Administer as in adults

Interactions

Allopurinol, may increase risk of bleeding or infection and enhance myelosuppressive effects; may potentiate doxorubicin-induced cardiotoxicity; may reduce digoxin serum levels and antimicrobial effects of quinolones; chloramphenicol may increase half-life while decreasing metabolite concentrations; may increase effect of anticoagulants; coadministration with high doses of phenobarbital may increase rate of metabolism and leukopenic activity; thiazide diuretics may prolong cyclophosphamide-induced leukopenia and neuromuscular blockade by inhibiting cholinesterase activity

Contraindications

Documented hypersensitivity; severely depressed bone marrow function

Precautions

Pregnancy

D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus

Precautions

Regularly examine hematologic profile (particularly neutrophils and platelets) to monitor for hematopoietic suppression; regularly examine urine for RBCs, which may precede hemorrhagic cystitis

Azathioprine (Imuran)

Inhibits mitosis and cellular metabolism by antagonizing purine metabolism and inhibiting synthesis of DNA, RNA, and proteins.

Dosing

Adult

1 mg/kg/d PO/IV for 6-8 wk; increase by 0.5 mg/kg q4wk until response or dose reaches 2.5 mg/kg/d

Pediatric

Initial: 2-5 mg/kg/d PO/IV
Maintenance: 1-2 mg/kg/d PO/IV

Interactions

Toxicity increases with allopurinol; concurrent use with ACE inhibitors may induce severe leukopenia; may increase levels of methotrexate metabolites and decrease effects of anticoagulants, neuromuscular blockers, and cyclosporine

Contraindications

Documented hypersensitivity

Precautions

Pregnancy

D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus

Precautions

Increases risk of neoplasia; caution with liver disease and renal impairment; hematologic toxicities may occur

Cyclosporine (Sandimmune, Neoral)

Cyclic polypeptide that suppresses some humoral immunity and, to a greater extent, cell-mediated immune reactions, such as delayed hypersensitivity, allograft rejection, experimental allergic encephalomyelitis, and graft versus host disease for a variety of organs.
For children and adults, dosing should be based on ideal body weight.

Dosing

Adult

3-5 mg/kg PO qd

Pediatric

Administer as in adults

Interactions

Carbamazepine, phenytoin, isoniazid, rifampin, and phenobarbital may decrease cyclosporine concentrations; azithromycin, itraconazole, nicardipine, ketoconazole, fluconazole, erythromycin, verapamil, grapefruit juice, diltiazem, aminoglycosides, acyclovir, amphotericin B, and clarithromycin may increase cyclosporine toxicity; acute renal failure, rhabdomyolysis, myositis, and myalgias increase when taken concurrently with lovastatin

Contraindications

Documented hypersensitivity; uncontrolled hypertension or malignancies; do not administer concomitantly with PUVA or UVB radiation in psoriasis since it may increase risk of cancer

Precautions

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

Evaluate renal and liver functions often by measuring BUN, serum creatinine, serum bilirubin, and liver enzymes; may increase risk of infection and lymphoma; reserve IV use only for those who cannot take PO

Glucocorticoids

These agents have anti-inflammatory properties and cause profound and varied metabolic effects. Corticosteroids modify the body's immune response to diverse stimuli and are useful in the treatment of recurrent scleritis.

Methylprednisolone (Depo-Medrol, Solu-Medrol, Medrol)

Administered IM or IV. Usually used in addition with other immunosuppressive agents.

Dosing

Adult

1 g IV 3 times/wk

Pediatric

Not established

Interactions

Coadministration with digoxin may increase digitalis toxicity secondary to hypokalemia; estrogens may increase levels of methylprednisolone; phenobarbital, phenytoin, and rifampin may decrease levels of methylprednisolone (adjust dose); monitor patients for hypokalemia when taking medication concurrently with diuretics; grapefruit juice increases prednisolone concentrations; methylprednisolone and cyclosporine mutually inhibit one another resulting in increased plasma levels of each drug

Contraindications

Documented hypersensitivity; viral, fungal, or tubercular skin infections

Precautions

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

Hyperglycemia, edema, osteonecrosis, peptic ulcer disease, hypokalemia, osteoporosis, euphoria, psychosis, growth suppression, myopathy, and infections are possible complications of glucocorticoid use; Depo-Medrol contains benzyl alcohol, which is potentially toxic when administered locally to neural tissue
Administration of Depo-Medrol by other than indicated routes, including the epidural route, has been associated with reports of serious medical events including arachnoiditis, meningitis, paraparesis/paraplegia, sensory disturbances, bowel/bladder dysfunction, seizures, visual impairment including blindness, ocular, and periocular inflammation, and residue or slough at injection site

Prednisone (Deltasone, Orasone, Sterapred)

Used to treat inflammatory and allergic reactions. By reversing increased capillary permeability and suppressing PMN activity, may decrease inflammation.

Dosing

Adult

60-120 mg PO qd; following satisfactory response, taper over 2-3 wk to approximately 20 mg/d with gradual taper (2.5-mg increments) until discontinuation

Pediatric

2 mg/kg PO qd

Interactions

Coadministration with estrogens may decrease prednisone clearance; concurrent use with digoxin may cause digitalis toxicity secondary to hypokalemia; phenobarbital, phenytoin, and rifampin may increase metabolism of glucocorticoids (consider increasing maintenance dose); monitor for hypokalemia with coadministration of diuretics

Contraindications

Documented hypersensitivity; peptic ulcer disease; hepatic dysfunction; connective tissue infections; viral, fungal, or tubercular skin infections

Precautions

Pregnancy

B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals

Precautions

Abrupt discontinuation of glucocorticoids may cause adrenal crisis; hyperglycemia, edema, osteonecrosis, myopathy, peptic ulcer disease, hypokalemia, osteoporosis, euphoria, psychosis, myasthenia gravis, growth suppression, and infections may occur with glucocorticoid use

Follow-up

Further Inpatient Care

• Inpatient care rarely is indicated for scleritis, unless complicated by serious exacerbation of underlying disorder.

Further Outpatient Care

• Referral to an ophthalmologist is mandatory.

Inpatient & Outpatient Medications

• A variety of NSAIDs is available to choose from, including diflunisal, naproxen, indomethacin, piroxicam, sulindac, and ibuprofen. These are particularly effective in nodular and diffuse scleritis and ordinarily are prescribed for at least 1 week.
• High-dose oral prednisone is used primarily in necrotizing scleritis and severe nonnecrotizing scleritis.
• Immunosuppressives
  • These agents are used as an adjunct when steroids alone fail to control progression of the disease and include cyclosporine, azathioprine, cyclophosphamide, and methotrexate.
  • These drugs have serious side effects and contraindications and should be prescribed only by a physician who is well aware of their actions.

Transfer

• If global perforation is suspected, transfer to a center with a qualified ophthalmologist may be necessary.

Complications

• Scleral thinning leading to global perforation is the most devastating complication.
• Visual impairment is a possible complication.
• Cornea is affected more than 50% of time. Damage to the cornea may include the following: uveitis, keratitis, glaucoma, and cataracts.
• Posterior chamber derangements may include the following: optic neuritis, choroidal detachment, macular edema, retinal hemorrhage and/or detachment, and papilledema.

Prognosis

• Necrotizing scleritis, the most destructive type of scleritis, and scleritis with extensive scleral thinning or perforation convey less favorable prognoses than other types of scleritis.
• Prognosis of scleritis, when originating from systemic disorders, usually conforms to the course of the underlying disease.

Patient Education

• For excellent patient education resources, visit eMedicine's Eye and Vision Center. Also, see eMedicine's patient education article Eye Pain.

Miscellaneous

Medicolegal Pitfalls

• Failure to differentiate scleritis from the more benign, self-limited episcleritis. A quick bedside test to help distinguish the two entities involves instillation of 1-2 drops of 2.5% phenylephrine into the involved eye; episcleral vessels blanch upon application, while deeper scleral vessels remain unaffected.
• Failure to see discoloration representing scleral thinning because discoloration is overlooked easily in a darkened room
• Failure to document visual acuity before proceeding to any manipulation of the eye or instillation of medications
• Failure to shield the eye if global perforation or scleral thinning is present

References

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Keywords

scleritis, sclera, leucitis, anterior scleritis, posterior scleritis, necrotizing anterior scleritis, scleromalacia perforans, diffuse anterior scleritis, eye redness, eye pain, sclerokeratitis

Contributor Information and Disclosures

Author

Theodore J Gaeta, DO, MPH, FACEP, Clinical Associate Professor, Department of Emergency Medicine, Joan and Sanford Weill Medical College at Cornell University; Vice Chairman and Program Director of Emergency Medicine Residency Program, Department of Emergency Medicine, New York Methodist Hospital; Academic Chair, Adjunct Professor, Department of Emergency Medicine, St George's University School of Medicine
Theodore J Gaeta, DO, MPH, FACEP is a member of the following medical societies: American College of Emergency Physicians, Council of Emergency Medicine Residency Directors, New York Academy of Medicine, New York Academy of Medicine, and Society for Academic Emergency Medicine
Disclosure: Nothing to disclose.

Coauthor(s)

Diana Valcich, MD, Staff Physician, Department of Emergency Medicine, New York Methodist Hospital
Diana Valcich, MD is a member of the following medical societies: American College of Emergency Physicians
Disclosure: Nothing to disclose.

Medical Editor

Joseph A Salomone, III, MD, Associate Professor, Department of Emergency Medicine, Truman Medical Center, University of Missouri at Kansas City School of Medicine
Joseph A Salomone, III, MD is a member of the following medical societies: American Academy of Emergency Medicine, Society for Academic Emergency Medicine, and Southern Medical Association
Disclosure: Nothing to disclose.

Pharmacy Editor

Francisco Talavera, PharmD, PhD, Senior Pharmacy Editor, eMedicine
Disclosure: Nothing to disclose.

Managing Editor

Gino A Farina, MD, Program Director, Associate Professor of Clinical Emergency Medicine, Department of Emergency Medicine, Long Island Jewish Medical Center, Albert Einstein College of Medicine
Gino A Farina, MD is a member of the following medical societies: American Academy of Emergency Medicine, American College of Emergency Physicians, and Society for Academic Emergency Medicine
Disclosure: Nothing to disclose.

CME Editor

John D Halamka, MD, MS, Associate Professor of Medicine, Harvard Medical School, Beth Israel Deaconess Medical Center; Chief Information Officer, CareGroup Healthcare System and Harvard Medical School; Attending Physician, Division of Emergency Medicine, Beth Israel Deaconess Medical Center
John D Halamka, MD, MS is a member of the following medical societies: American College of Emergency Physicians, American Medical Informatics Association, Phi Beta Kappa, and Society for Academic Emergency Medicine
Disclosure: Nothing to disclose.

Chief Editor

Robert E O'Connor, MD, MPH, Professor and Chair, Department of Emergency Medicine, University of Virginia Health System
Robert E O'Connor, MD, MPH is a member of the following medical societies: American Academy of Emergency Medicine, American College of Emergency Physicians, American College of Physician Executives, American Heart Association, American Medical Association, Medical Society of Delaware, National Association of EMS Physicians, Society for Academic Emergency Medicine, and Wilderness Medical Society
Disclosure: Nothing to disclose.

The authors and editors of eMedicine gratefully acknowledge the contributions of previous authors, Jerome FX Naradzay, MD, Loice Swisher, MD, and Jonathan Adler, MD, to the development and writing of this article.

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