Prepared By: Moath A. Nassar

• Systemic diseases are diseases that involve many organs or the whole body.

• Many of these diseases also affect the eyes.

• In fact, an eye exam sometimes leads to the first diagnosis of a systemic disease

Why is the eye so important in systemic disease? The eye is composed of many different types of tissues. This unique feature makes the eye susceptible to a wide variety of diseases as well as provides insights into many body systems.

Systemic diseases to be discussed :

Collagen vascular disease

Spondyloarthropathies

Sarcoidosis

Systemic vasculitis

Blood disorders

Demyelinating disorders

Hypertention and vascular diseases

Thyroid disorders

• General signs & symptoms • Diagnostic tests • General management

• Ocular involvement

Signs & symptoms

Treatment and prognosis

1.Collagen vascular disease problems with the immune system affect collagen wide category of diseases Symptoms of collagen vascular disease vary from disease to disease, but may include:

Back pain Chest pain and shortness of breath Fatigue and weakness Fever Painful, swollen joints Rashes

Diagnosis Hx & physical examination, Blood tests can check level of autoantibodies, RF, urinalysis ,LFT , KFT , ESR, C- XR

Treatment

Some may go into remission spontaneously Depends on the extent of the disease Steroids or anti-inflammatory medications to ease discomfort In advanced cases, immunosuppressant drugs may help

a. Behçet's disease Recurrent multisystemic disease presented during third to fourh decade

Major diagnostic criteria :

• Recurrent oral aphthous stomatitis • Skin lesions ( erythema nodosum,…) • Recurrent genital ulceration • Uveitis : both anterior and posterior

Minor diagnostic criteria Arthritis , epididymitis, intestinal ulceration , neurological and vascular complications Four major criteria simultaneously or at different times is diagnostic

Hypopyon which can be seen in anterior uveitis in a patient with Behcet's disease.

Acute anterior uveitis generally responds to corticosteroid eye drops.

Inflammation involving the back of the eye requires treatment that is more aggressive with corticosteroids given by injection and/or pill (systemic therapy).

may lead to blindness in 20% of those affected

b. Sjögren's syndrome

Autoimmune inflammation and destruction of lacrimal and salivary glands Primary or secondary F>M Presented in adult life with gritteness( sandiness) of eyes and dryness of the mouth Signs

• Large salivary glands with diminished salivary flow • Dry nasal passages • Raynaud’s phenomenon

Diagnosed by serum autoantibodies and biopsies

Ophthalmic features • Common :Keratoconjunctivitis sicca • Rare : adie pupil

Treatment

• If mild tear substitutes would help • Avoiding low humidity environment • Occluding the punctum in severe cases

keratoconjunctivitis sicca

Complete cure could never be achieved but fowolloing a strict treatment guidelines may improve the outcome

c. Systemic Lupus Erythematosus

Autoimmune non-organ specific connective tissue disease F>M Presented during third to fifth decade with fatiguabilty without specific organ involvement Signs Mucocutaneous, musculoskeletal, renal, cardiovascular, pulmonary, haemopoitic, reticuloendothelial, neurological. Diagnosis: ESR is raised, C- ractive protein is normal, serology. Treated by steriods and cytotoxic agents

Ophthalmic complications • Common: Madarosis and keratoconjunctivitis sicca • Uncommon: peripheral ulcerative keratitis • Rare: scleritis, retinal vasculitis and optic neuropathy

Madarosis is the absence or loss of the eyelashes (and sometimes the eyebrows)

Discoid lesions is the cause in this case

d. Rheumatoid arthritis Autoimmune systemic disease characterized by symmetrical, destructive, deformating, inflammatory, polyarthropathy F>m Presented during the fourth decade and occasionally during the childhood Signs

• Arthritis ( symmetrical involvement of small joints of hands and feet, ulnar deviation ,…) • Skin ( raynaud’s phenomenon, vasculitis , …)

Treated by NSAIDs, cytotoxic drugs ,…

Ophthalmic features • Common: keratoconjunctivitis sicca ( secondary ) • Uncommon: scleritis and peripheral ulcerative keratitis • Rare: acquired superior oblique tendon sheath syndrome

Scleromalacia ; potential perforation

tumour necrosis factor (TNF) blockers (infliximab) are effective therapeutic agents in ocular complications of rheumatoid arthritis

e. Systemic scleroderma

Chronic connective tissue disease affecting the skin and internal organs

F>M

May be limited , diffuse and overlapping with other autoimmune diseases Presented in the fourth to sixth decade with raynaud phenomenon

Signs:

• Skin: tightening and thickening on hands , feet , face and trunk. Subcutaneous fibrosis, typical facial appearance( fixed expression, restrictive movements of lips and “ beaking of nose) • Organs: esophageal dysmotility, heart , lung and kidney disease, mild arthritis

Diagnosis: serology

Treatment: Immunosuppressive agents, Antifibrotic agents, Anti-infammatory agents,…..

Ophthalmic features • Common: eyelid tightening and telangectasia • Uncommon: keratoconjunctivitis sicca

Skin tightening on the face ( including the eyelids)

Telangiectasia

2.Spondyloarthropathies Group of inflammatory joint diseases including:

• Ankylosing spondylitis • Reactive arthritis( reiter’s syndrome ) • Psoriatic arthropathy • Arthritis associated with inflammatory bowel disease(enteropathic spondylitis ) • Isolated acute anterior uveitis

An association with HLA –B27 occurs in all of them but in particularly strong for ankylosing sponndylitis ( > 95%) and reiter’s disease ( 90 %) They share common clinical features: Asymmetrical inflammatory oligoarthritis, Sacroiliitis and inflammatory spondylitis Diagnosis: Hx , exam ,radiographs, HLA B- 27, serology

Ophthalmic features: • Thay all cause acute anterior uveitis • conjunctivitis, keratitis, keratoconjunctivitis sicca, scleritis

Recurrent Iritis caused Synechiae(adhesions between the lens and iris) in ankylosing spondylitis

• Conjunctivitis (figure) is a common ophthalmic feature of Reiter's syndrome along with acute anterior uveitis • corneal infiltrate is Uncommon feature

Conjunctivitis is not very painful, does not affect vision, and is not serious and goes without treatment

Scleritis in Crohn disease

Also we may have conjunctivitis , peripheral corneal infiltrate & retinal periphlebitis in Crohn disease

If mild, could be treated by NSAIDs but if severe , systemic steriods may be introduced

3.Sarcoidosis Multi- systemic granulumatous inflammatory disorder Presentaion:

• Acute onset sarcoidosis typically occurs during the third decade • Insidious onset sarcoidosis occurs during the fifth decade

Signs • Pulmonary : in 90 % of patients, ranges from asymptomatic bilateral hilar lymphadenopathy to progressive pulmonary fibrosis and bronchectasis • Skin : erythema nodosum, granuloma • Neurological : cranial nerve palsies ( particularly facial) , intra cranial granuloma

Diagnosis: • Chest radiographs • Biopsy :

o Lungs , gives the greatest yield o Conjunctiva , positive in about 70 % o Lacrimal glands, positve in 25 % of unenlarged and 75 % of enlarged

• Calcium assay

Treatment options include NSAIDs steroids and low dose cytotoxic agents

Ophthalmic features

• Common : conjunctival granulomas, anterior uveitis, posterior uveitis and retinal periphlebitis • Uncommon : keratoconjunctivitis sicca and intermediate uveitis • Rare: fundus granulomas, retinal and disc neovascularization, and papilloedema

Mild symptoms are treated by topical steroids and cycloplegics. Systemic steroids are indicated in cases not responding to topical steroids

Anterior segment granulomatous involvement in a case of ocular sarcoidosis

Conjunctival granulomas in ocular sarcoidosis

A: Scattered peripheral multifocal lesions characteristic of ocular sarcoidosis. B: The macula of the same patient demonstrating a choroidal neovascular membrane.

4.Systemic vasculitis The systemic vasculitides are characterized by inflammation of blood

vessel walls Vessels of any type, in any organ can be affected,

classified based on affected vessel size (large, medium, and small) Signs and symptoms

• Nonspecific complaints • Those should raise a strong suspicion:

Mononeuritis multiplex, palpaple purpura, pulmonary renal syndrome

Diagniosis : a compatible clinical presentation supported by specific laboratory or imaging tests and confirmatory histology

Glucocorticoids are the primary treatment for many forms of vasculitis , Additional immunosuppressive agents are sometimes required

a. Giant cell arteritis

A granulumatous necrotizing arteritis with predilection for large and medium

size arteries , particularly the superficial temporal , ophthalmic, posterior ciliary and proximal vertebral Presented during the seventh to eighth decade with the following: Scalp tenderness, headach, jaw claudication (pthognomonic) , polymyalgia

rheumatica , non specifc symptoms, blindness ( sudden with minimal systemic upset), superficial temporal arteritis ( thick , tender, inlammed, and nodular arteries which can’t be flattened against the skull), the pulsation later ceases which strongly suggestive of GCA Diagnostic tests

• High ESR , CRP • Temporal artery biopsy should be performed

Treatment : by administration of systemic steriods

Ophthalmic features Common: anterior ischemic optic neuropathy

Uncommon: cotton wool spots, central retinal artery occlusion , ocular motor nerve palsy ( commonly a pupil sparing third nerve palsy ) Rare: ocular ischemic syndrome

Typical findings of a patient with arteritic ischemic optic neuropathy. Note the pallid disk edema, associated hemorrhages, and adjacent cotton wool spot

Treatment for arteritic ischemic optic neuropathy is CORTICOSTEROID MEDICATIONS

b. Polyarteritis nodosa

Idoipathic , potentially lethal , collagen vascular disease affecting medium sized and small arteries

Presented during the sixth decade

Signs

• Skin: purpura and easy bruising , gangrene • Muscles: weakness and tenderness

Complications

• Renal involvement and hypertension • Coronary arteritis • GI bleeding • Stroke or multifocal neuropathy

Diagnosis: skin biopsy

Treatment: systemic steriods and immunosuppressive agents

Ophthalmic features Common: peripheral ulcerative keratitis and scleritis

Rare: orbital pseudo-tumour and occlusive retinal periarteritis

Peripheral ulcerative keratitis presents with a crescent shaped destructive lesion of the juxtalimbal corneal stroma

c. Wegener’s granulomatosis

Idiopathic , multisystem, granulomatous disorder characterized by generalized small-vessel vasculitis affecting predominantly the respiratory tract and the kidneys Presented in the fifth decade , often with pulmonary symptoms Signs

• Respiratory tract o Upper: perforation of the nasal septum o Lower: nodular lesions , infiltrates and cavitaions

• Organs o Necrotizing glomerulonephritis with renal failure o Affects heart , spleen and adrenals o Neurological: polyneuritis and meningoencephalitis

Diagnosis: Anti-neutrophil cytoplasm antibodies Treated with systemic steriods and cyclophosphamide

Ophthalmic features

Common : nasolacrimal obstruction and dacrycystitis

Uncommon: scleritis and peripheral ulcerative keratitis

Rare: orbital pseudo- tumour and occlusive retinal periarteritis

sclerokeratitis

Nasolacrimal duct involvement can result in epiphora, dacryocystitis and draining fistulas.

Dacrocystitis treated by surgey (Dacryocystorhinostomy ) . Good outcome

5.Hematologic disorders

Hematological diseases encompass a wide spectrum of disorders ranging from benign to malignant conditions that can present with ocular involvement Ocular findings related to anemia, hematological malignancies and platelet disorders are to be disscussed

a. Anemia Anemia is a common condition that occurs when the level of healthy RBCs or Hb is below normal Causes include: destruction, increased blood loss and inadequate production of RBCs by the bone marrow Additional causes related to poor nutrition or absorption defects in the GI tract include iron, vitamin B12or folic acid deficiencies general symptoms: pallor of the skin or nail beds, weakness, headaches, shortness of breath, GI disturbances, fever, and numbness or coldness of extremities Diagnosis: CBC is the most important, assess level of B12 and folic acid, bone marrow biopsy

Ocular changes

conjunctival pallor and hemorrhages

anemic retinopathy(intraretinal hemorrhages, Roth’s spot hemorrhages, cotton-wool spots, retinal exudates, venous dilation and optic nerve pallor) These changes generally occur in patients with severe anemia or when thrombocytopenia is present

Sickle cell anemia may also cause sickled conjunctival vessels, central retinal artery occlusion (CRAO), branch retinal artery occlusion (BRAO), sickling maculopathy

b.

c. Platelets disorders Ocular changes can include :

• Conjunctival petechial hemorrhages

• Amaurosis fugax

• Vascular occlusions • Retinal, vitreal and choroidal hemorrhages