Download MBBS Ophthalmology PPT 5 Thyroid Ophthalmopathy Lecture Notes

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Acknowledgement

? UptoDate: Graves' orbitopathy: Diagnosis and Treatment.

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? Cummings Otolaryngology. Girod, Douglas A.; Wemer, Richard D.;

Larsen, Christopher G. Published January 1, 2015. ? 2015.

? Endocrinology : Adult and Paediatric. Burch, Henry B.; Bahn, Rebecca

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S.. Published January 1, 2016. ? 2016.

? Some of the images used were taken from eyetext.net

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Learning Objectives

? At the end of this class the students shal be able to :

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? Understand the pathogenesis and clinical features of thyroid eye disease.

? Enumerate and elicit the common eye signs of thyroid ophthalmopathy.

? Have a basic understanding of principles of management of the disease.

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Introduction

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? Thyroid eye disease is an autoimmune disease producing symptoms
related to inflammation, accumulation of fluid in the orbit and also to
adipogenesis raising intra-orbital pressure.
? Synonyms
? Graves' ophthalmopathy/orbitopathy (GO)

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? Thyroid eye disease (TED)
? Thyroid associated ophthalmopathy (TAO)
? Dysthyroid ophthalmopathy

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Epidemiology

? Prevalence of thyroid ophthalmopathy = 0.4%
Women > Men
? But severity greater in men

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? Bimodal age distribution ? Peak incidence in fourth and sixth decades

of life

? May be exacerbated by stress and smoking

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? Most common cause of exophthalmos
? >50% of cases with Graves' disease have eye involvement

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Etiology

? Graves' hyperthyroidism (90%)

? Hypothyroid Hashimoto's thyroiditis

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? Euthyroid subjects with no current or past evidence of thyroid hyper

or hypofunction (so called euthyroid Graves' disease).

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? In patients with Grave's disease, eye signs may precede, coincide with

or follow the hyperthyroidism

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Risk factors

? Smoking (strongest modifiable risk factor)

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? Family history

? Monozygotic twins

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Pathogenesis

? Autoimmune process manifesting as:

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? Extraocular muscle myositis

? T-cel inflammatory infiltrate

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? Fibroblast proliferation

? Glycosaminoglycan overproduction

? Increase in soft tissue mass within

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bony orbit due to extraocular muscle

enlargement, increased orbital fat and

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connective tissue

? Later in disease, inflammatory

infiltrate replaced by widespread

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fibrosis

? "Inactive" phase occurs after 8months

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to 3years

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pathogenesis

Pleomorphic cel ular infiltrate

Increased secretion of GAG's

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Osmotic imbibition of water

Muscular swel ing upto 8 times

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Subsequent degeneration leading to

fibrosis

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Histology

Fluid and inflammatory cells separate the muscle bundles of the
extraocular muscles

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Histology

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Lymphocytes, plasma

cells, macrophages

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and mast cells

infiltrate extraocular

muscles, fat and

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connective tissue

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Histology

Degeneration

of muscle fibres

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Leads to fibrosis

of the involved

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muscle

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Natural History of Thyroid Eye Disease

? Progressive phase lasting for up to 18 months
? Stable (inactive) phase

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Course of disease

? Inflammatory/active phase Fibrotic/inactive phase

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Clinical course of orbital disease proceeds independently of thyroid gland

dysfunction and treatment

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Symptoms

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? Foreign body sensation
? Epiphora (tearing)
? Photophobia
? Bulging of eyes
? Puffiness of eye lids

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? Diplopia
? Visual loss

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Signs

? Eyelid Retraction

? Proptosis

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? Restrictive Myopathy

? Soft Tissue Involvement

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--- Conjunctival hyperaemia, lid oedema and chemosis

? Optic Neuropathy

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Clinical signs in TED

? Facial signs

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? Joffroy's sign-absent creases

in the forehead on superior

gaze

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Clinical eye lid signs in TED

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? Kocher's sign- staring appearance
? Rosenbach's sign- tremors of eyelids
? Von graefe's sign- lid lag on downgaze
? Dalrymple's sign- lid retraction
? Stellwag's sign- incomplete & infrequent blinking

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? Gifford's sign- difficulty in everting the upper lid
? Enroth 's sign- edema of lower lid
? Griffith's sign- lower lid lag on upgaze

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Soft Tissue Inflammation

? Often the earliest sign.

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Consists of
? periorbital edema
? conjunctival hyperemia
? chemosis
? superior limbic keratoconjunctivitis

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Eyelid retraction

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? Also cal ed Dalrymple's sign.

? Normal y, upper eyelid- 2mm below limbus

? Lower eyelid-inferior limbus

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? When retraction occurs, the sclera (white) can

be seen

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Occurs due to :

? Increased sympathetic stimulation of M?ller's

muscle by thyroid hormone

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? Overaction of the levator muscle contracting

against a tight inferior rectus

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Proptosis

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? Usually (90%) bilateral
? Thyroid eye disease is the most common

cause of unilateral

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and bilateral proptosis in adults
? Axial
? Resulting from enlargement of the

extraocular muscles and adipose

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tissue, as well as orbital fat
? Deposits and the infiltration of orbital

tissues by GAGs and leukocytes

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Proptosis

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? It does not respond to hyperthyroidism

treatment

? Is permanent in 70% of cases.

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? Severe proptosis prevents adequate lid

closure

? May lead to severe exposure

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keratopathy and corneal ulceration.

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Restrictive Myopathy

? Eye movements are restricted due to oedema in extraocular muscles
during infiltrative stage and subsequent fibrosis.

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? Despite expansion of the extraocular muscles , the muscle fibres
themselves are normal.
? IR>MR>SR>LR
? Pressure exerted by a fibrotic inferior rectus muscle on the
globe may cause a spike in intraocular pressure during upgaze.

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Dysthyroid Optic Neuropathy

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(DON)

Optic neuropathy as result of optic nerve compression

from enlargement of extraocular muscles

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WERNER?S CLASSIFICATION - NOSPECS

? Class 0: No signs or symptoms

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? Class 1: Only signs (lid retraction, stare ? lid lag)
? Class 2: Soft tissue involvement
? Class 3: Proptosis
? Class 4: Extraocular muscle involvement
? Class 5: Corneal involvement

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? Class 6: Sight loss (optic nerve involvement)

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EUGOGO classification

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? Mild : eyelid swelling , lid retraction, proptosis

? Moderate-Severe : Active disease (EOM dysfunction, diplopia ,

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proptosis >25 mm)

? Very severe : Compressive Optic Neuropathy , Corneal exposure

(needs emergent surgery)

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VISA classification

? V (Vision) , I (inflammation), S (Strabismus) , A (Appearance)

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? Vision/CON
? Inflammation/Congestion : based on documented change of

inflammation rather than absolute value

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? Strabismus/Motility : measuring ductions and alignments
? Appearance/Exposure
? Score of 5 or more --> Active disease or progression (Consider

Steroids)

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Differential Diagnosis

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? Orbital tumors (primary or metastatic)
? Orbital pseudotumor
? Wegener's granulomatosis
? Orbital infection
? Carotid-cavernous sinus fistula

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Diagnosis

? Characteristic eye findings

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? Thyroid dysfunction
? Imaging

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Blood investigations

? Highly sensitive & specific -- T4(thyroxine) + TSH or serum TSH

? If eye findings associates with euthyroid Graves' disease ?

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? Thyroid peroxidase antibody

? Antibody to thyroglobulin

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? Others

? Free T4 index

? Thyroid-stimulating immunoglobulin

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? Antithyroid antibodies

? Serum T3

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Radiological Evaluation

? Usually employed if cause of exophthalmos is unclear (ie. normal

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thyroid lab studies, or history/physical examination inconsistent with

thyroid disease)

? Also to determine optic nerve involvement if not obvious by

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fundoscopic examination.

? Distinct sparing of muscle tendons in thyroid ophthalmopathy.

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Radiological Evaluation

? CT scan is currently the imaging study of choice.

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? MRI is sensitive for showing compression of the optic nerve.

? Neuroimaging usually reveals
? Thick muscle belly with tendon sparing
? Usually IR & MR

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? Bilateral muscle enlargement is the norm
? Unilateral cases usually represent asymmetric involvement rather

than normality of the less involved side

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Axial and coronal C.T. scan in Thyroid eye disease

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? Non-contrast enhanced coronal orbital CT scan most helpful to assess

size of extraocular muscles.

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Axial CT of orbits

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demonstrating

medial rectus

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enlargement

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Management

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? T ? Tobacco abstinence
? E ? Euthyroidism
? A ? Artificial tears
? R ? Referral

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? S ? Self help groups

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Medical Management of Hyperthyroidism

? Anti-thyroid drugs : thinoamides (PTU) , carbimazole , methimazole.

? Thionamides inhibit synthesis of thyroid hormones.

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? Need 6-8 weeks to achieve euthyroid state

? Side effects of anti-thyroid drugs
Skin rash , urticarial , arthralgia , fever

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Treatment of mild Thyroid eye disease

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Symptomatic treatment

? Artificial tears

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? Eye shades

? Raise head of bed at night

? Diplopia can be managed with prism glasses

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? Eventually may require strabismus surgery

? Conserve useful vision

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? Minimize amount of exposed cornea

? May require lid surgery

? Treat optic neuropathy

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Selenium

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? 200 microgram/day for 6 months
? For Mild disease

? Antioxidant effect
? Immunomodulatory effect : reduce thyroid autoantibodies

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? Reduces severity of disease and improve quality of life

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Corticosteroids

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? Intravenous , Oral
? IV pulses are more effective and have less side effects
? IV dose (max 8 grams) : 500 mg weekly for 6 weeks and then 250 mg
weekly for 6 weeks
? Relapse is common (20%)

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? Steroid response is evident usually 2-4 weeks later
? Moderate to severe TED : 71% respond to IV steroid vs 51% with oral
? IV steroids for compressive Optic Neuropathy

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Rituximab

? Chimeric mono-clonal antibody targets CD20
? CD20 is expressed on more than 95% of B cells and plasma cells

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? RTX removes B cells and short-lived plasma cells
? RTX depletes 95% of mature B cells , blocks Ab production , and
decreases inflammatory cytokine release
? For steroid-refractory disease
? Side effects : Allergic reaction (mild) PML (severe)

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Orbital Radiation

? Mechanism : lymphocyte sterilization, destruction of tissue

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monocytes
? 20 Gy in 10 divided sessions over 2 weeks
? May have a role in patients with TED who have restricted ocular
motility or active disease
? Some studies have shown benefit (controversial)

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? More suited for patients > 35 years of age
? Contra-indicated in pre-existing retinopathy (diabetes , hypertensive)

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Botulinum Toxin

? Neurotoxin , inhibits acetylcholine release
? For upper lid retraction (transconjunctival , transcutaneous route)
? Effect on Muller's muscle and LPS

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? Side effects of Botox : bruising , ptosis and diplopia

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Orbital Decompression for TED

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? Decompression usual y in stable phase of disease.

? Indications

? compressive optic neuropathy

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? severe exposure keratopathy

? Need to discuss goals of surgery with patients.

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? Post-operative complications (diplopia, vision loss)

? Outcome is variable : degree of fibrosis , fat expansion , bone

available, duration of optic neuropathy.

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? Decompression --> Muscle Surgery --> Lid surgery

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Strabismus Surgery for TED

? In the stable phase with stable alignments for 6 months
? Aim is single binocular vision in primary and reading position
? Typically involves release of the restricted muscle by recession rather

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than resection

? Conjunctival dissection is challenging
? Use of adjustable sutures is strongly recommended due to the

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variability in fibrosis, resulting in unpredictable results.

? Oblique surgery can increase area of single binocular vision

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Eye lid surgery

? The most common indication for lid surgery is upper lid retraction.

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? Graded Muller's and levator aponeurosis weakening.

? Lower lid lengthening is indicated in lower lid retraction.

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Psychological Impact of TED

? Disfigurement/altered facial appearance
? Misinterpretation as hostile or angry

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? Almost 50% of TED suffer depression and/or anxiety
? 90% of TED have appearance concerns (young females)
? 44% have self-confidence issues
? Quality of life measures and questionnaires
? Multidisciplinary approach (psychiatric included)

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? Support groups

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Psychological Disturbances in TED

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Conclusion

? Activation of thyrotropin receptor on orbital fibroblast by circulating
autoantibodies plays a primary role in development of thyroid
ophthalmopathy.

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? Management is based on accurate assessment of both severity and
activity of disease.
? Immunosuppressive therapy is reserved for patients with clinically
active moderate to severe disease

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Thank You

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