systmic disease

The Eye and Systemic Disorders

A---Rheumatoid arthritis
Rheumatoid arthritis (RA) is an autoimmune systemic disease characterized by a symmetrical, destructive, deforming, inflammatory polyarthropathy, in association with a spectrum of extra-articular manifestations and circulating antiglobulin antibodies, termed rheumatoid factor. It is much more common in females than males.

1 Presentation is often in the 3rd decade with joint swelling, usually of the hands.

2 Signs
• Symmetrical arthritis of the small joints of the hands typically involving the proximal interphalangeal and spares the distal interphalangeal joints.
• Joint instability may result in subluxation and deformities ,such as ulnar deviation of the metacarpophalangeal joints.
• Less frequent involvement of the feet, shoulders, elbows, hips and cervical spine.
• Skin involvement includes subcutaneous nodules over bony prominences, and vasculitis which may cause ulceration.
3 Complications include pulmonary nodules and fibrosis, multifocal neuropathy, septic arthritis, secondary amyloidosis and carpal tunnel syndrome.
4 Scleritis. RA is by far the most common systemic association of scleritis. Patients with non-necrotizing scleritis usually have mild joint disease whereas necrotizing disease tends to affect patients with severe long-standing rheumatoid disease with extra-articular manifestations, most notably rheumatoid nodules.
5 Other ocular manifestations include KCS (secondary Sjögren syndrome), ulcerative keratitis and acquired superior oblique tendon sheath syndrome (very rare).

Vaso-occlusive Scleritis is often associated with rheumatoid arthritis.

• Isolated patches of scleral oedema with overlying non-perfused episclera and conjunctiva.
• The patches coalesce, and if unchecked rapidly proceed to progressive scleral necrosis

Vaso-occlusive necrotizing scleritis with inflammation

Complications
1 Acute infiltrative stromal keratitis ..
2 Sclerosing keratitis.
3 Peripheral ulcerative keratitis .
4 Uveitis.
5 Glaucoma .
6 Hypotony.
7 Perforation .

B---Scleromalacia perforans

Scleromalacia perforans is a specific type of necrotizing scleritis without inflammation that typically affects elderly women with longstanding rheumatoid arthritis.
The use of the word ‘perforans’ is unfortunate because perforation of the globe is extremely rare as the integrity of the globe is maintained by a thin, but complete, layer of fibrous tissue.
Peripheral ulcerative keratitis secondary to necrotizing scleritis

C---Peripheral ulcerative keratitis

associated with systemic autoimmune disease Pathogenesis
Peripheral ulcerative keratitis (PUK) may precede or follow the onset of systemic disease.
Severe peripheral corneal infiltration, ulceration or thinning unexplained by evident ocular disease should prompt a search for an associated systemic collagen vascular disorder
In patients with an underlying autoimmune disease there is immune complex deposition in peripheral cornea. Diseased epithelium, keratocytes and recruited inflammatory cells may result in the release of matrix metalloproteinases that degrade collagen and the extracellular matrix. Autoantibodies may target sites in the corneal epithelium.

Clinical features

• Crescentic ulceration and stromal infiltration at the limbus
• Limbitis, episcleritis or scleritis are usually present.
• Circumferentially and occasionally central spread; in contrast to Mooren ulcer the process may also extend into the sclera.
• End-stage disease may result in a ‘contact lens’ cornea.


Associated systemic disease
1 Rheumatoid arthritis is the commonest systemic association. PUK involves both eyes in 30% of cases and tends to affect patients during the late and advanced vasculitic phase. Patients with rheumatoid arthritis may also develop the following non-ulcerative types of keratitis:
a - Peripheral stromal thinning is characterized by gradual resorption of peripheral stroma leaving the epithelium intact. Perforation may occur in advanced cases .

b - Sclerosing keratitis is characterized by gradual thickening and opacification of the corneal stroma adjacent to a site of scleriti. c Acute central corneal melting may occur in association with inflammation or severe dry eye .
2 Wegener granulomatosis .
3 Relapsing polychondritis .
4 Systemic lupus erythematosus .

Treatment .

1 Systemic high dose steroids are used to control acute disease and cytotoxic therapy .
2 Topical lubricants (preservative-free).
3 Topical antibiotics .
4 Oral tetracycline has an anticollagenase effect.
5 Topical steroids are generally avoided as they may worsen thinning.
6 Conjunctival excision
7 Corneal gluing or amniotic membrane patching for perforation.
8 Keratoplasty. Emergency keratoplasty .

D---Juvenile idiopathic arthritis (JIA)

is an inflammatory arthritis of at least 6 weeks' duration occurring before the age of 16 years when all other causes, such as infection, metabolic disorders or neoplasms have been excluded.
Females are affected more commonly by a ratio of 3 : 2.


JIA is by far the most common disease associated with childhood anterior uveitis. It should be emphasized that JIA is not the same as juvenile rheumatoid arthritis (JRA); the former is negative for rheumatoid factor whereas the latter is positive; JRA is the same disease as rheumatoid arthritis except that it occurs before the age of 16 years.

Arthritis

1 Presentation is based on the onset and the extent of joint involvement during the first 6 months; three types of presentation are recognized.
a Pauciarticular onset JIA involves four or fewer joints and accounts for about 60% of cases.
• Girls are affected five times as often as boys, with a peak age of onset around 2 years.
• The arthritis involves the knees most commonly , although the
ankles and wrists may also be affected.
• Some patients in this subgroup remain pauciarticular, others subsequently develop a polyarthritis.
• About 75% of children are antinuclear antibody (ANA) positive.
• Uveitis is common in this group and affects about 20% of children.
• Risk factors for uveitis are early onset of JIA and ANA positivity.
b Polyarticular onset JIA affects five or more joints = 20%
c Systemic onset . = 20%

Anterior uveitis

1 Presentation is invariably asymptomatic; the uveitis is frequently detected on routine slit-lamp examination. Even during acute exacerbations with +4 aqueous cells, it is rare for patients to complain, although a few report an increase in vitreous floaters. In the greater majority of patients, arthritis antedates the diagnosis of uveitis although rarely ocular involvement may precede joint disease by several years. Often uveitis may not be suspected until the parents recognize complications such as strabismus, or an abnormal appearance of the eye due to band keratopathy or cataract.

2 Signs

• Inflammation is chronic and non-granulomatous.
• Both eyes are affected in 70%; it is unusual for unilateral uveitis to become bilateral after more than a year.
• When bilateral, the severity of inflammation is usually symmetrical.
• The eye is usually white even in the presence of severe uveitis.
• During acute exacerbations, the entire endothelium shows ‘dusting’ by many hundreds of cells, but hypopyon is absent.
• Posterior synechiae are common in long-standing undetected cases.


3 Prognosis
• In about 10% of cases the uveitis is mild, with never more than +1 aqueous cells, and persists for less than 12 months.
• About 15% of patients have one attack lasting less than 4 months, the severity of inflammation varying from +2 to +4 aqueous cells.
• In 50% of cases, the uveitis is moderate to severe and persists for more than 4 months.
• In 25% of cases, the uveitis is very severe, lasts for several years and responds poorly to treatment. In this subgroup, band keratopathy occurs in 40% of patients, cataract in 30% and secondary glaucoma in 15%.
• Other serious complications include phthisis and amblyopia.
• The presence of complications at initial examination appears to be an
important risk factor for the development of subsequent complications, regardless of therapy.

4 Treatment with topical steroids is usually effective; acute exacerbations require very frequent instillation. Poor responders to topical administration may benefit from periocular injections. Low-dose methotrexate is useful for steroid resistance.

5 Screening. Because the onset of intraocular inflammation is invariably asymptomatic, it is extremely important to regularly screen children at risk for at least 7 years from the onset of arthritis or until the age of 12 years. The frequency of slit-lamp examination is governed by the following risk factors.
• Systemic onset = not required.
• Polyarticular onset = every 9 months.
• Polyarticular onset + ANA = every 6 months.
• Pauciarticular onset = every 3 months.
• Pauciarticular onset + ANA = every 2 months.

Differential diagnosis

1 Idiopathic juvenile chronic iridocyclitis. Whilst JIA is the most common systemic association of CAU in children, many patients with juvenile CAU are otherwise healthy. The majority of patients are also girls. small number of cases the uveitis is detected by chance.


2 Other types of juvenile arthritis and uveitis
a Juvenile AS .
b Juvenile Reiter syndrome .
c Juvenile psoriatic arthritis.
d Juvenile bowel-associated arthritis.
3 Juvenile sarcoidosis .
4 Lyme disease ..
5 Intermediate uveitis accounts for 20% of all cases of paediatric uveitis and is frequently bilateral. The inflammation primarily involves the vitreous and anterior uveitis is usually insignificant.
6 Neonatal-onset multisystem inflammatory disease .
7 Masquerade syndromes.

Rheumatoid arthritis : Also related to :

A – age related cataract.
B - Retinal occlusive diseases .
C – Duane Syndrome : failure of innervation of the lateral rectus by the 6th nerve, with anomalous innervation of the lateral rectus by fibres from the 3rd nerve.

E----Sjögren syndrome

Sjögren syndrome is characterized by autoimmune inflammation and destruction of lacrimal and salivary glands

The condition is classified as primary when it exists in isolation, and secondary when associated with other diseases such as rheumatoid arthritis, SLE, systemic sclerosis, mixed connective tissue disease, primary biliary cirrhosis, chronic active hepatitis and myasthenia gravis.


Primary Sjögren syndrome affects females more commonly than males and is characterized by the following:

Presentation is in adult life with grittiness of the eyes and dryness of the mouth.

Signs
• Enlargement of salivary glands and occasionally lacrimal glands, with secondary diminished salivary flow rate and a dry fissured tongue
• Dry nasal passages, diminished vaginal secretions and resultant dyspareunia.
• Raynaud phenomenon and cutaneous vasculitis.
• Arthralgia, myalgia and fatigue may be present.

Complications

• Dental caries in severe untreated cases.
• Reflux oesophagitis and gastritis.
• Malabsorption due to pancreatic failure.
• Pulmonary disease, renal disease and polyneuropathy.
• Lymphoma.

Diagnostic tests include serum autoantibodies, Schirmer test and biopsy of minor salivary glands.

Treatment options include a range of symptomatic treatments, salivary stimulants and immunosuppression with systemic steroids and cytotoxic agents.


F----Marfan syndrome

1 Pathogenesis. There is mutation of the fibrillin-1 gene (FBN1) on chromosome 15q21.

2 Inheritance is AD with variable expressivity; a minority of patients manifest only ocular signs.

3 Musculoskeletal features

• Tall, thin stature with disproportionately long limbs compared with the trunk (arm span > height )
• Kyphoscoliosis, sternal prominence (pectus carinatum) or depression
(pectus excavatum).
• Long spider-like fingers and toes (arachnodactyly – and mild joint laxity.
• A narrow high-arched (‘gothic’) palate .
• A long-shaped head, malar hypoplasia, enophthalmos and downslanting palpebral fissures.
• Flat feet, cutaneous striae and easy bruising.
• Muscular underdevelopment and predisposition to hernias.

4 Cardiovascular lesions include dilatation of the aortic root, mitral valve prolapse and aortic aneurysm formation.

5 Ectopia lentis which is bilateral and symmetrical is present in 80% of cases. Subluxation is most frequently supero-temporal, but may be in any meridian. Because the zonule is frequently intact , accommodation is retained, although rarely the lens may dislocate into the anterior chamber or vitreous . The lens may also be microspherophakic.

6 Other ocular features include angle anomaly which may result in glaucoma, retinal detachment associated with lattice degeneration, hypoplasia of the dilator pupillae, peripheral iris transillumination defects, cornea plana and strabismus.


G----Weill–Marchesani syndrome
Weill–Marchesani syndrome is a rare systemic connective tissue disease, conceptually the converse of Marfan syndrome.

1 Inheritance is AR or AD; the former maps to 19p13.3-p13.2 and the latter to FBN1, the same as Marfan syndrome.
2 Systemic features include short stature, brachydactyly characterized by short, stubby fingers and toes, stiff joints and mental handicap.
3 Ectopia lentis which is inferior occurs in 50% of cases during late childhood or early adult life. Microspherophakia is common so that subluxation occurs anteriorly to cause pupil block or occasionally into the anterior chamber .
4 Other ocular features include angle anomalies, asymmetrical axial lengths and presenile vitreous liquefaction.

H----Ankylosing spondylitis

Definition. Ankylosing spondylitis (AS) is characterized by inflammation, calcification and finally ossification of ligaments and capsules of joints with resultant bony ankylosis of the axial skeleton. It typically affects males, of whom 90% are HLA-B27 positive; some patients also have inflammatory bowel disease (enteropathic arthritis).

AAU ( acute anterior uveitis) occurs in about 25% of patients with AS; conversely, 25% of males with AAU will have AS. Either eye is frequently affected at different times but bilateral simultaneous involvement is rare. There is often no correlation between the severity and activity of eye and joint involvement. In a few patients with many recurrent attacks the inflammation may become chronic.

J----Reiter syndrome

Definition. Reiter syndrome (RS), also referred to as reactive arthritis, is characterized by the triad of (a) non-specific (non-gonococcal) urethritis, (b) conjunctivitis and (c) arthritis. About 85% of patients are positive for HLA-B27.

AAU occurs in up to 12% patients but is higher in carriers of HLA-B27.

Conjunctivitis is very common and usually follows the urethritis by about 2 weeks and precedes the arthritis. The inflammation is usually mild, bilateral and mucopurulent with a papillary or follicular reaction. Spontaneous resolution occurs within 7–10 days and treatment is not required. Some patients develop peripheral corneal infiltrates.


Psoriatic arthritis
Definition. About 7% of patients with psoriasis develop arthritis. Psoriatic arthritis affects both sexes equally and is associated with an increased prevalence of HLA- B27 and HLA-B17.
AAU occurs in approximately 7% of arthritis patients.
Other ocular manifestations which are uncommon include conjunctivitis, marginal corneal infiltrates and secondary Sjögren syndrome.

I-----Sarcoidosis

Sarcoidosis is a T-lymphocyte-mediated non-caseating granulomatous inflammatory disorder of unknown cause. It is most common in colder climates, although it more frequently affects patients of African descent than Caucasians. The clinical spectrum of disease varies from mild single-organ involvement to potentially fatal multisystem disease which can affect almost any tissue. The tissues most commonly involved are the mediastinal and superficial lymph nodes, lungs, liver, spleen, skin, parotid glands, phalangeal bones and the eye.

Ocular features

Uveitis is the most common and may be in the form of anterior, posterior or intermediate. Other manifestations include KCS, conjunctival nodules, and rarely, orbital and scleral lesions.
1 AAU typically affects patients with acute-onset sarcoid.
2 CAU
3 Intermediate uveitis with snowballs
4 Periphlebitis
5 Choroidal infiltrates
6 Multifocal choroiditis
7 Retinal granulomas are small discrete yellow-white lesions.
8 Peripheral retinal neovascularization.
9 Optic nerve involvement may take the following forms:
• Focal granulomas, which do not usually affect vision.
• Papilloedema due to CNS involvement .
• Persistent disc oedema .
10 Treatment of anterior uveitis is with topical and/or periocular steroids. Posterior uveitis often requires systemic steroids and occasionally immunosuppressive agents .


K----Behçet syndrome

Behçet syndrome (BS) is an idiopathic, multisystem disease characterized by recurrent episodes of orogenital ulceration and vasculitis which may involve small, medium and large veins and arteries. The disease typically affects patients from the eastern Mediterranean region and Japan and is strongly associated with human leucocyte antigen (HLA) B51 in different ethnic groups; it is not clear whether the HLA-B51 itself is the pathogenic gene related to BS or some other gene is in linkage disequilibrium. The peak age of onset of BS is in the 3rd decade, although rarely it presents in childhood or old age; males are affected more frequently than females.

Diagnostic criteria

1 Recurrent oral ulceration characterized by painful minor or major aphthous , or herpetiform ulcerative lesions that have recurred at least three times in a 12-month period.
2 Plus at least two of the following:
• Recurrent genital ulceration .
• Ocular inflammation.
• Skin lesions include erythema nodosum, folliculitis, acneiform nodules or papulopustular lesions.
• Positive pathergy test, which is characterized by the formation of a pustule after 24–48 hours at the site of a sterile needle prick.

Additional features

1 Major vascular complications
• Aneurysms of the pulmonary and/or systemic arterial system.
• Coronary artery disease, cardiomyopathy and valvular disease.
• Venous thrombosis which may involve superficial or deep veins, the vena cava, portohepatic vein and cerebral sinuses.
2 Arthritis typically mild and involves a few large joints, particularly the knees.
3 Skin hypersensitivity demonstrated by the formation of erythematous lines following stroking of the skin (dermatographia)
4 Gastrointestinal ulceration .
5 Neurological manifestations occur in 5% of patients and mainly involve the brainstem although meningoencephalitis and spinal cord disease may also occur.
6 Other uncommon manifestations include glomerulonephritis and epididymitis.


Ocular features
Ocular complications occur in up to 95% of men and 70% of women. Eye disease typically occurs within 2 years of oral ulceration, but rarely the delay may be as long as 14 years. Conversely, ocular inflammation is the presenting manifestation in about 10% of cases. Ocular disease is usually bilateral and typically presents during the 3rd–4th decades.

1 AAU, which may be simultaneously bilateral and frequently associated with a transient mobile hypopyon in a relatively white eye (‘cold hypopyon) It usually responds well to topical steroids.
2 Retinitis may take the following forms:
• Transient, white, superficial infiltrates , that heal without scarring may be seen during the acute stage of the systemic disease.
• Diffuse retinitis similar in appearance to a virus-induced lesion.
3 Retinal vasculitis may involve both veins and arteries and result in occlusion Vascular leakage may give rise to diffuse retinal oedema, CMO and disc oedema.
4 Vitritis, which may be severe and persistent, is universal in eyes with active disease.
5 End-stage disease is characterized by optic atrophy, vascular occlusion and gliotic sheathing , but the vitreous is remarkably clear by this stage.
6 Other manifestations, which are uncommon, include conjunctivitis, conjunctival ulcers, episcleritis, scleritis and ophthalmoplegia from neurological involvement.

Treatment of posterior uveitis

1 Systemic steroids may shorten the duration of an inflammatory episode but an additional agent is usually required.
2 Azathioprine .
3 Ciclosporin .
4 Subcutaneous interferon alfa.
5 Biological blockers such as infliximab show promise in treating retinal vasculitis.

Differential diagnosis

Differential diagnosis in patients with suggestive ocular findings but lack of classical systemic manifestations should include the following:
1 Recurrent anterior uveitis with hypopyon may occur in spondyloarthropathies. However, the uveitis is not usually simultaneously bilateral and the hypopyon is not mobile because it is frequently associated with a fibrinous exudate. In BS uveitis is frequently simultaneously bilateral and the hypopyon shifts with gravity as the patient changes head position.
2 Retinal vasculitis may be associated with sarcoidosis. However, sarcoid vasculitis involves only veins in a segmental manner and is rarely occlusive. In contrast, BS usually affects both arteries and veins, is diffuse, frequently occlusive and is associated with vitritis, which is uncommon in sarcoid-related vasculitis.
3 Retinal infiltrates similar to those in BS may be seen in viral retinitis such as acute retinal necrosis. However, in viral retinitis the infiltrates eventually coalesce. Multiple retinal infiltrates also occur in idiopathic acute multifocal retinitis in which the clinical course is more favourable.


L----Toxoplasmosis
Toxoplasmosis is caused by Toxoplasma gondii, an obligate intracellular protozoan. It is estimated to infest at least 10% of adults in northern temperate countries and more than half of adults in Mediterranean and tropical countries. The cat is the definitive host and intermediate hosts include mice, livestock and humans

The parasite exists in the following forms:

1 Sporozoites are contained within an oocyst (sporocyst) and result from sexual reproduction of the organisms with the intestinal mucosa of the cat. They are excreted in the faeces and spread to intermediate hosts.
2 Bradyzoites are relatively inactive and are contained within tissue cysts that most commonly develop in the brain, eye, heart, skeletal muscles and lymph nodes. They may lie dormant for many years without provoking an inflammatory reaction.
3 Tachyzoites (trophozoites) are the proliferating active form responsible for tissue destruction and inflammation following rupture of the wall of a cell containing bradyzoites .
Life cycle of Toxoplasma gondii

Mode of human infection

Ingestion of undercooked meat (lamb, pork, beef) containing bradyzoites of an intermediate host.
Ingestion of sporocysts following inadvertent contamination of hands when disposing of cat litter trays and then subsequent transfer on to food. Infants may also become infected by eating dirt (pica) containing sporocysts. It is likely that water contamination plays an important role in the transmission of the disease in rural areas.
Transplacental spread of the parasite (tachyzoite) can occur if a pregnant woman becomes infected.

Congenital toxoplasmosis

Toxoplasmosis is transmitted to the fetus through the placenta when a pregnant woman becomes infected. If the mother is infected before pregnancy, the fetus will be unscathed.
1 Severity of involvement of the fetus is dependent on the duration of gestation at the time of maternal infection. For example, infection during early pregnancy may result in stillbirth, whereas if it occurs during late pregnancy it may result
in convulsions, paralysis, hydrocephalus , and visceral involvement.
2 Manifestations
• Intracranial calcification seen on CT .
• However, just as in the acquired form, most cases of congenital systemic toxoplasmosis are subclinical. In these children, bilateral healed chorioretinal scars may be discovered later in life, either by chance or when the child is found to have defective vision.
• Infections occurring towards the end of the second trimester usually result in disease that can be detected at birth such as macular scars , while those occurring later in the third trimester may result in normal examination at birth, but the appearance of ocular or neurological symptoms in the future.
• The risk of disease later in life can be modified by early recognition of the transmission and long-term therapy.
3 Serological tests .


Toxoplasma retinitis Pathogenesis
Toxoplasmosis is the most frequent cause of infectious retinitis in immunocompetent individuals. Reactivation at previously inactive cyst-containing scars is the rule in the immunocompetent, although a small minority may represent new infection. Most quiescent lesions will have been acquired postnatally. Recurrent episodes of inflammation are common and occur when the cysts rupture and release hundreds of tachyzoites into normal retinal cells. Recurrences usually take place between the ages of 10 and 35 years (average age 25 years).

Clinical features

The diagnosis of toxoplasma retinitis is based on a compatible fundus lesion and positive serology for toxoplasma antibodies (see ‘Investigations’). Any antibody titre is significant because in recurrent ocular toxoplasmosis, no correlation exists between the titre and the activity of retinitis.

1 Presentation is with unilateral sudden onset of floaters, visual loss and photophobia.

2 Signs
• ‘Spill-over’ anterior uveitis, which may be granulomatous and resemble Fuchs syndrome, is common.
• Solitary inflammatory focus near an old pigmented scar (‘satellite lesion’)
• Multiple foci are uncommon.
• Severe vitritis may greatly impair visualization of the fundus, although the inflammatory focus may still be discernible (‘headlight in the fog’ appearance.

Complications

Nearly 25% of eyes develop visual loss as a result of the following:
1 Common • Direct involvement of the macula . • Secondary optic nerve head involvement due to a juxtapapillary lesion .
2 Uncommon • Primary optic nerve head involvement may mimic anterior ischaemic optic neuropathy. • Occlusion of a major blood vessel by the inflammatory focus . • Choroidal neovascularization . • Serous retinal detachment . • Tractional retinal detachment secondary to organization of severe vitreous opacification. • Macular oedema.

Treatment

1 Aims
• To reduce the duration and severity of acute inflammation.
• To lessen the risk of permanent visual loss by reducing the size of the eventual retinochoroidal scar.
• To reduce the risk of recurrences.


2 Indications.
• A sight-threatening lesion involving the macula, papillomacular bundle, optic nerve head or a major blood vessel.
• Very severe vitritis, because of the risk of vitreous fibrosis and tractional retinal detachment. • In immunocompromised patients all lesions should be treated irrespective of location or severity.
3 Regimen. immunocompromised.

a Pyrimethamine (Daraprim) .

b Sulfadiazine .
c Other systemic options include clindamycin, spiramycin, tetracyclines, atovaquone, azithromycin and clarithromycin.
d Topical steroids may be given for anterior uveitis but periocular depot injections are contraindicated as they may lead to uncontrolled progression.

M----Bacterial uveitis

Tuberculosis .
Anterior segment involvement
• Eyelid involvement may manifest as reddish-brown nodules (lupus vulgaris) or a ‘cold abscess’.
• Tuberculous conjunctivitis is uncommon and may be associated with lymphadenopathy as in Parinaud syndrome.
• Corneal involvement most commonly manifests as phlyctenular keratoconjunctivitis or interstitial keratitis.
• Scleritis is rare.

Tuberculous uveitis

Tuberculous uveitis may be difficult to diagnose because it may occur in patients without systemic manifestations of TB. The diagnosis is therefore often presumptive, based on indirect evidence such as intractable uveitis unresponsive to steroid therapy, a positive history of contact, a positive skin test and negative findings for other causes of uveitis.


Anterior uveitis, usually granulomatous, is the most frequent feature.
Choroiditis is caused by direct infection.
• Unilateral focal or (less frequently) multifocal.
• Extensive diffuse choroiditis may occur in patients with AIDS .
• Large solitary choroidal granulomas , are uncommon.
• Choroiditis may occasionally resemble serpiginous choroidopathy.
Periphlebitis is often bilateral and represents a manifestation of hypersensitivity to the bacillus.
Treatment is initially with at least three drugs (isoniazid, rifampicin and pyrazinamide) and then with isoniazid and rifampicin. Quadruple therapy with the addition of ethambutol is necessary in pulmonary TB and in resistant cases. Concomitant systemic steroid therapy is also frequently necessary. The steroid dose needs to be adjusted when given with rifampicin.

P----Syphilis

Syphilis is caused by the spirochaete bacterium Treponema pallidum.
Stages
1 Primary syphilis occurs after an incubation period commonly lasting 2–4 weeks and is characterized by a painless ulcer (chancre) at the site of infection. The most common site in males is the penis and in females the vulva. In homosexual men the anus is a major site. The chancre is associated with discrete, mobile, rubbery enlargement of inguinal lymph nodes. Without treatment the chancre
resolves within 2–6 weeks leaving an atrophic scar.
2 Secondary syphilis usually develops 6–8 weeks after the chancre and is characterized by:
• Generalized lymphadenopathy with mild or absent constitutional symptoms.
• Symmetrical maculopapular rash on the trunk , palms and soles.
• Condylomata lata on the vulva, scrotum or the anal region.
• Mucous patches in the mouth, pharynx and genitalia consisting of painless greyish-white circular erosions (‘snail-track ulcers’).
• Meningitis, nephritis and hepatitis may occur.
3 Latent syphilis follows resolution of secondary syphilis, may last for years and can be detected only by serological tests.
4 Tertiary syphilis occurs in about 40% of untreated cases and is characterized by the following.
• Cardiovascular manifestations: aortitis with aneurysm formation and aortic regurgitation.
• Neurosyphilis is characterized by tabes dorsalis, Charcot joints and general paresis of the insane.
• Gummatous infiltration of bone and viscera. Gummatous infiltration of the tongue , may lead to leukoplakia and an increased risk of carcinoma.


Syphilitic uveitis
AAU occurs in about 4% of patients with secondary syphilis and is bilateral in 50%. In some cases, iritis is first associated with dilated iris capillaries (roseolae) which may develop into more localized papules and subsequently into larger yellowish nodules. Various types of post-inflammatory iris atrophy may ensue.
Posterior uveitis
• Chorioretinitis is often multifocal , and bilateral.
• Acute posterior placoid chorioretinitis is characterized by bilateral, large, solitary, placoid, pale-yellowish subretinal lesions .
• Untreated neuroretinitis gives rise to secondary optic atrophy and replacement of retinal vessels by white strands .
• Retinal vasculitis may be occlusive and involves both arteries and veins.
Treatment is the same as for neurosyphilis (which should be ruled out by lumbar puncture). One of the following regimens may be used: a Intravenous aqueous penicillin G 12–24 million units daily for 10–15 days. b Intramuscular procaine penicillin 2.4 million units daily, supplemented with oral probenecid (2 g daily), for 10–15 days.