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Overview of Overview of EpiscleritisEpiscleritisand and ScleritisScleritis

Thomas F. Freddo, O.D., Ph.D.Thomas F. Freddo, O.D., Ph.D.P f d F Di tP f d F Di tProfessor and Former DirectorProfessor and Former DirectorSchool of OptometrySchool of OptometryUniversity of WaterlooUniversity of Waterloo

Conjunctivitis vs Episcleritis

Conjunctivitis is common. Conjunctivitis is common. EpiscleritisEpiscleritis and and ScleritisScleritis are not.are not.

Apply topical anesthetic. Then use a cotton Apply topical anesthetic. Then use a cotton b t thb t th j ti lj ti l f hilf hilswab to move the swab to move the conjunctivalconjunctival surface while surface while

observing through slitobserving through slit--lamp. If the dilated and lamp. If the dilated and congested vessels move with the swab, its congested vessels move with the swab, its conjunctivitis.conjunctivitis.

Advice on holding lid Advice on holding lid open open -- rollroll--up awningup awning

Episcleritis

A relatively benign, A relatively benign, recurrentrecurrent disease rarely disease rarely associated with associated with systemic disease.systemic disease.

Visual acuity is normalVisual acuity is normal Visual acuity is normalVisual acuity is normalMild, occasional painMild, occasional painMore often in women More often in women

than men, as is than men, as is generally true for most generally true for most autoimmuneautoimmune--type type diseasesdiseases

Two varieties: simple & Two varieties: simple & nodularnodular

Simple Episcleritis

DDX Sectorial Redness

Staph marginal Staph marginal ulcerulcer

LimbalLimbalhl t lhl t lphlyctenulephlyctenule

LimbalLimbalmalignancymalignancy

PterygiumPterygium

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EPISCLERITIS

Most cases are idiopathic occurring more often Most cases are idiopathic occurring more often in women than men and usually in their 30’s or in women than men and usually in their 30’s or yy40’s.40’s.

A preliminary workA preliminary work--up is worth considering only up is worth considering only if your directed case history leads to suspicion if your directed case history leads to suspicion of an underlying systemic association.of an underlying systemic association.

Systemic associations found primarily through Systemic associations found primarily through history in 1/3 of patients. Labs are to confirm.history in 1/3 of patients. Labs are to confirm.

No correlation between type, laterality or No correlation between type, laterality or recurrences and presence of associated recurrences and presence of associated systemic diseasesystemic disease

Simple Episcleritis

Often recur at 1- to 3-month intervals.

Episodes appear acutely and usually last 7-10 days

Most resolve after 2-3 kweeks.

Prolonged episodes may be more common in patients with associated systemic conditions.

Some patients note that episodes are more common in the spring or fall.

Precipitating factor is rarely found.

Nodular Episcleritis

Takes longer to resolve (4-6 weeks)

EPISCLERITISDifferential DiagnosisDifferential Diagnosis

Virtually any infectious disease can be Virtually any infectious disease can be associated with associated with episcleritisepiscleritis –– CBCCBC with with differential , looking for differential , looking for leukocytosisleukocytosis//eosinophiliaeosinophilia

Bacteria, Bacteria, including including tuberculosistuberculosis, , Lyme diseaseLyme disease, and , and syphilissyphilis Viruses including herpesViruses including herpes Viruses, including herpesViruses, including herpes FungiFungi ParasitesParasites

Other more common causes Other more common causes –– AtopyAtopy -- rule out by history and skin appearancerule out by history and skin appearance

Foreign BodyForeign Body –– rule out by history and examrule out by history and exam

ChemicalsChemicals –– rule out by history, rule out by history, measuring tear pH measuring tear pH and examand exam

Gout Adult Rheumatoid Arthritis Seronegative spondyloparthropathies

Normal tears = 7.1

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If the patient is unresponsive to treatment a referral to an cornea/external disease specialist is prudent in order to explore the more rare causes including:

Other rare causes/associationsOther rare causes/associations Systemic Lupus Systemic Lupus erythematosuserythematosus PolyarteritisPolyarteritis nodosanodosa TT--cell leukemiacell leukemia ParaproteinemiaParaproteinemia ParaproteinemiaParaproteinemia ParaneoplasticParaneoplastic syndromes syndromes -- Sweet syndrome, Sweet syndrome, dermatomyositisdermatomyositis WiskottWiskott--Aldrich syndromeAldrich syndrome Adrenal cortical insufficiencyAdrenal cortical insufficiency NecrobioticNecrobiotic xanthogranulomaxanthogranuloma Progressive Progressive hemifacialhemifacial atrophyatrophy Following Following transscleraltransscleral fixation of posterior chamber intraocular fixation of posterior chamber intraocular

lenslens Insect bite Insect bite granulomagranuloma MalpositionedMalpositioned Jones tubeJones tube

EPISCLERITISDifferential DiagnosisDifferential Diagnosis

GoutGout

Adult RheumatoidAdult Rheumatoid arthritisarthritisAdult Rheumatoid Adult Rheumatoid arthritisarthritis

SeronegativeSeronegative spondyloarthropathiesspondyloarthropathies

EPISCLERITIS

Differential Differential DiagnosisDiagnosis

GoutGout–– acute attacks of foot or lower joint pain especially in great toe but acute attacks of foot or lower joint pain especially in great toe but any synovial joint can be involved. Elevated uric acid level as a result of a any synovial joint can be involved. Elevated uric acid level as a result of a defect in defect in purinepurine metabolism. Results in deposition of crystallized uric acid metabolism. Results in deposition of crystallized uric acid as “as “tophitophi” R/O in history or exam Get urine sample for uric acid level In” R/O in history or exam Get urine sample for uric acid level Inas as tophitophi . R/O in history or exam. Get urine sample for uric acid level. In . R/O in history or exam. Get urine sample for uric acid level. In acute attacks white count elevated with acute attacks white count elevated with left shift left shift and and sedsed rate (ESR) may be rate (ESR) may be elevated. Diet. Medication of choice elevated. Diet. Medication of choice allopurinolallopurinol..

Removal of tophi

Differential Diagnosis

AUTOIMMUNE DISEASESAUTOIMMUNE DISEASES

Adult rheumatoid arthritisAdult rheumatoid arthritis

SeronegativeSeronegative spondyloarthropathiesspondyloarthropathiesSeronegativeSeronegative spondyloarthropathiesspondyloarthropathies AnkylosingAnkylosing spondylitisspondylitis

Inflammatory bowel diseaseInflammatory bowel disease

Psoriatic arthritisPsoriatic arthritis

Reactive arthritis (Reiter’s syndrome)Reactive arthritis (Reiter’s syndrome)

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Episcleritis/Scleritis and relationship with the seronegative spondyloarthropathies

Read and review:

www.arc.org.uk/about_arth/med_reports/series4/tr/6604/6604 htms/series4/tr/6604/6604.htm

www.orthop.washington.edu/uw/tabID_3376/print_full/ItemID_130/mid_0/Articles/Default.aspx

If the patient is unresponsive to treatment a referral to an cornea/external disease specialist is prudent in order to explore the more rare causes including:

Other rare causes/associationsOther rare causes/associations Systemic Lupus Systemic Lupus erythematosuserythematosus PolyarteritisPolyarteritis nodosanodosa TT--cell leukemiacell leukemia ParaproteinemiaParaproteinemia ParaproteinemiaParaproteinemia ParaneoplasticParaneoplastic syndromes syndromes -- Sweet syndrome, Sweet syndrome, dermatomyositisdermatomyositis WiskottWiskott--Aldrich syndromeAldrich syndrome Adrenal cortical insufficiencyAdrenal cortical insufficiency NecrobioticNecrobiotic xanthogranulomaxanthogranuloma Progressive Progressive hemifacialhemifacial atrophyatrophy Following Following transscleraltransscleral fixation of posterior chamber intraocular lensfixation of posterior chamber intraocular lens Insect bite Insect bite granulomagranuloma MalpositionedMalpositioned Jones tubeJones tube

Episcleritis – Work-up

Useful laboratory studies in this group of patients include:

serum uric acid - Gout

complete blood count with differentialdifferential

rheumatoid factor

erythrocyte sedimentation rate

Venereal Disease Research Laboratory (VDRL) test

fluorescent treponemal antibody absorption (FTA-ABS)

chest x-ray

Treatment Ocular therapy

Simple episcleritis often requires no treatment. Cold compresses and iced artificial tears are useful for patients with mild-to-moderate symptoms. Patients with severe or prolonged episodes may require topical corticosteroids but steroids have been shown to worsen recurrences.

Nodular episcleritis is more indolent and may require local corticosteroid drops or anti-inflammatory agents.

Topical pred phosphate penetrates the eye less well and thus may be preferred over acetate in these cases to mitigate against steroid response.

Systemic therapy

If nodular episcleritis is unresponsive to topical therapy, systemic anti-inflammatory agents may be useful.

Flurbiprofen (100 mg tid) is usually effective until inflammation is suppressed.

If there is no response to flurbiprofen, indomethacin should be used; 100 mg daily and decreased to 75 mg when there is a response.

Many patients who do not respond to one nonsteroidal anti-inflammatory agent (NSAID) may respond to another NSAID.

Activity Sunglasses may be useful for patients with sensitivity to light.

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Episcleritis vs. Scleritis

View patient in daylight and/or red-free.

Episcleritis will look pred, scleritis will have a deeper, purple-red coloration not well seen by slit-lamp.

Note deep purple-red background

Pain in the Differential

MOST Important - judge the pain. If it is deep penetrating pain, radiating all around the

DDx: Severe ocular pain:Corneal surface

problemshead and/or awakens the patient from sleep, think scleritis. OTC analgesics will not lessen pain.

If pain worsens with eye movement, think scleritis.

problems

Angle closure glaucoma

Scleritis, especially with anterior uveitis.

EPISCLERITIS VS SCLERITIS: EPISCLERITIS VS SCLERITIS: Use 2.5% Use 2.5% phenylephrinephenylephrine. Generally, it will whiten . Generally, it will whiten an an episcleritisepiscleritis, not a deep , not a deep scleritisscleritis

EpiscleritisEpiscleritis

ScleritisScleritis

ScleritisMost common Most common

4th4th--6th decade6th decade

In 15% of cases, In 15% of cases, scleritisscleritis is the is the presenting sign of presenting sign of collagen vascular collagen vascular disease.disease.

More in females More in females 1.6:11.6:1

OneOne--third are third are recurrentrecurrent

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Scleritis Rheumatoid arthritis is the underlying disease for Rheumatoid arthritis is the underlying disease for

approximately one sixth of patients suffering from approximately one sixth of patients suffering from scleritisscleritis

Other connective tissue and autoimmune diseases seen with Other connective tissue and autoimmune diseases seen with scleritisscleritis include the following:include the following:Systemic lupus Systemic lupus erythematosuserythematosus (SLE)(SLE)

PolyarteritisPolyarteritis nodosanodosaPolyarteritisPolyarteritis nodosanodosa

SeronegativeSeronegative spondyloarthropathiesspondyloarthropathies

AnkylosingAnkylosing spondylitisspondylitis

Psoriatic arthritisPsoriatic arthritis

Reactive arthritisReactive arthritis

Inflammatory bowel diseaseInflammatory bowel disease

SarcoidosisSarcoidosis

TuberculosisTuberculosis

SyphilisSyphilis

LymeLyme*List is almost identical to anterior uveitis

Anterior Scleritis

AnteriorDiffuse - most

common

Nodular

Necrotizing

Most cases stay as same type as at original presentation, but some advance

Treatable Masquerades

Infectious scleritis is a possibility that should be evaluated.

Herpes scleritis can present as a masquerade of Herpes scleritis can present as a masquerade of scleritis and should always be considered if the patient has unilateral scleritis.

Syphilis is another important masquerader that needs to be ruled out, as it is treatable. (Lueticserology)

Conditions such as severe rosacea or severe atopy or allergy can also induce scleritis, so a thorough patient history is essential.

Diffuse Anterior Scleritis

Most common form

Insidious onset over 5-10 days

Easily misdiagnosed as Easily misdiagnosed as episcleritis

Increased scleral translucency when healed

Least associated with systemic disease

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Nodular Scleritis

Nodule firm and immobile

Onset insidious

Necrotizing Anterior Scleritis

May occur with or without

i fl tiinflammation

Necrotizing Scleritis

Most severe and destructive form

29% di ithi 5 f

Scleromalacia perforans

Painless melting of sclera

INFLAMMATORY NON-INFLAMMATORY

29% die within 5 yrs of onset

50-90% have underlying disease, usually rheumatoid arthritis, Wegener’s, relapsing polychondritis

gleaving choroid exposed to conjunctiva

Spontaneous perforation rare

Most often with rheumatoid arthritis

Wegener’s GranulomatosisUsually begins with respiratory symptomsUsually begins with respiratory symptoms Runny nose, with pusRunny nose, with pus--filled discharge Nosebleeds filled discharge Nosebleeds

Sinus pain and inflammation (sinusitis) Sinus pain and inflammation (sinusitis)

Hoarse voice Hoarse voice

Inflammation of the gumsInflammation of the gums Inflammation of the gums Inflammation of the gums

Ear infections Ear infections

Cough Cough

Chest pain Chest pain

Coughing up blood (Coughing up blood (hemoptysishemoptysis) )

Shortness of breath Shortness of breath

Wheezing Wheezing

General ill feeling (malaise)General ill feeling (malaise)

But can present with But can present with scleritisscleritis or or granulomatousgranulomatous anterior anterior uveitisuveitis

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Work up of Wegener’s

AntiAnti--neutrophilneutrophil cytoplasmiccytoplasmic antibodies (ANCAs) are a antibodies (ANCAs) are a group of group of autoantibodiesautoantibodies, mainly of the , mainly of the IgGIgG type, against type, against antigens in the cytoplasm of antigens in the cytoplasm of neutrophilsneutrophils and and monocytesmonocytes. .

They are detected in a number of conditions associatedThey are detected in a number of conditions associated They are detected in a number of conditions associated They are detected in a number of conditions associated with systemic with systemic vasculitisvasculitis, so called ANCE, so called ANCE--associated associated vasculiditiesvasculidities, including , including Wegener’s granulomatosis; microscopic polyangitis and Churg–Strauss syndrome.

ANCA were originally shown to divide into two main ANCA were originally shown to divide into two main classes, cclasses, c--ANCA and pANCA and p--ANCA, based on the pattern of ANCA, based on the pattern of staining on ethanolstaining on ethanol--fixed fixed neutrophilsneutrophils and the main target and the main target antigen. ANCA titers can also be measured using ELISA antigen. ANCA titers can also be measured using ELISA and indirect and indirect immunofluorescenceimmunofluorescence..

ANCA p-ANCA, or protoplasmic-

staining antineutrophilcytoplasmic antibodies, show a perinuclearstaining patternstaining pattern.

c-ANCA, or classical antineutrophil cytoplasmicantibodies, show a diffusely granular, cytoplasmic staining pattern.

It is cIt is c--ANCA that is primarily ANCA that is primarily associated with Wegener’sassociated with Wegener’s

Posterior ScleritisVascular congestion with hemorrhage, reduced Vascular congestion with hemorrhage, reduced vision with macular vision with macular striastria –– but with PAIN!but with PAIN!

B-scan: Flattening of posterior pole, Choroidal and scleral thickening with sub-Tenon’sfluid accumulation and “T-sign”

Summary of Work-up

Patients with scleritis need to be evaluated for potential systemic diseases. I would recommend that the scleritis work-up be done by a rheumatologist due to the wide range of conditions.

Laboratory studies are likely to include both serologic tests and urinalysisurinalysis.

Luetic serology – FTA-Abs and VDRL/RPR

CBC with diff

Anti-neutrophil cytoplasmic antibody (ANCA) studies will test for Wegener’s granulomatosis.

Various vasculidities can affect kidney and so urine protein should be measured.

R/o TB with CXR and PPD

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Based on the past history, review of systems, and physical examination, select appropriate diagnostic tests to confirm or reject the following suspected associated diseases:

Rheumatoid factor Rheumatoid factor -- Rheumatoid arthritisRheumatoid arthritis

Antinuclear antibodies Antinuclear antibodies -- Systemic lupus Systemic lupus erythematosuserythematosus, rheumatoid arthritis, , rheumatoid arthritis, polymyositispolymyositis, progressive systemic sclerosis, or mixed connective tissue , progressive systemic sclerosis, or mixed connective tissue

AntineutrophilAntineutrophil cytoplasmiccytoplasmic antibodies (ANCA) antibodies (ANCA) -- Wegener Wegener granulomatosisgranulomatosis, , polyarteritispolyarteritis nodosanodosa, or microscopic , or microscopic polyangiitispolyangiitis

Human leukocyte antigen (HLA) typingHuman leukocyte antigen (HLA) typing AnkylosingAnkylosing spondylitisspondylitis reactive arthritisreactive arthritis Human leukocyte antigen (HLA) typing Human leukocyte antigen (HLA) typing -- AnkylosingAnkylosing spondylitisspondylitis, reactive arthritis, , reactive arthritis, psoriatic arthritis, or arthritis associated with inflammatory bowel disease psoriatic arthritis, or arthritis associated with inflammatory bowel disease

EosinophilEosinophil count/immunoglobulin E (count/immunoglobulin E (IgEIgE) ) -- Allergic Allergic angiitisangiitis of of ChurgChurg--Strauss Strauss syndrome or syndrome or atopyatopy

Uric acid Uric acid -- GoutGout

Erythrocyte sedimentation rate (ESR) Erythrocyte sedimentation rate (ESR) -- Giant cell Giant cell arteritisarteritis

Hepatitis B surface antigen (Hepatitis B surface antigen (HBsAgHBsAg) ) -- PolyarteritisPolyarteritis nodosanodosa

SerologiesSerologies -- Infectious diseases, including syphilis and Lyme diseaseInfectious diseases, including syphilis and Lyme disease

PurifiedPurified--protein derivative (PPD) skin test protein derivative (PPD) skin test -- TuberculosisTuberculosis

AnergyAnergy skin test skin test -- SarcoidosisSarcoidosis

Prick test Prick test -- AtopyAtopy

Treatment of Scleritis

Oral NSAIDS first line, either COX-1 or more recent COX-2 such as Celebrex at 100-200 mg qd. More difficult cases may require oral steroids or immunosuppressants If NSAID usesteroids or immunosuppressants. If NSAID use chronic, protection of GI system may be required (omeprazole-Prilosec)

Treatment should be coordinated with rheumatologist of an ophtho with specialty training in ocular immune disease.